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FREE PAPERS (ORAL) FP-1 Morbidity and Mortality in Cirrhotic Patients Undergoing Major Colorectal Resection Alaa Abduljabbar1, Nasser Ahmed Al-Sanea2, Luai Hassan Ashari2 1 Department of Surgery, King Faisal Specialist Hospital & Research Centrer, 2King Faishal Specialist Hospital and Research Centrer, Saudi Arabia Purpose This study was undertaken to determine the morbidity and mortality associated with major colorectal resection in cirrhotic patients at King Faisal Specialist Hospital and Research Centre. Material & Methods Between 2000-2002, the colorectal database was searched for all cirrhotic patients who underwent major colorectal resection. The review included: etiology of cirrhosis, Child-Pugh Classification, renal and hepatic function, anesthesia drug record and postoperative complications.ResultsThree men and two women were identified with age range between 49-77 years. According to ChildPugh Classification, 2 patients were grade A and 3 were grade B. All patients had normal renal function. Two patients underwent sigmoid colectomy one right hemicolectomy and one anterior resection. All with primary anastomosis. One patient had total colectomy with end ileostomy. Average length of surgery was 3 hours and 49 minutes (range: 2hrs 37min-4hrs 57 min). Average estimated blood loss was 450 ml (range: 50ml-1000ml). Four patients had significant morbidity and one patient who was graded as Child A died postoperatively. Average length of hospital stay was 35.2 days (range: 17-49 days). No patient required reoperation. Three patients were admitted to the intensive care unit. No anastomotic leak was encountered. Conclusion Cirrhotic patients carry a high risk of morbidity and mortality following major colorectal resection.
FP-2 Palliative Management of Colorectal Stricture using Colorectal Stents Alaa Abduljabbar1, Nasser Ahmed Al-Sanea2, Adel Abdulkader Tash2, Luai Hassan Ashari 2, Mohammed Al-Shammari 2, Hamad AlSuhaibani2 1 Department of Surgery, King Faisal Specialist Hospital & Research Centrer, 2King Faisal Specialist Hopital and Research Centrer, Saudi Arabia Purpose This study was undertaken to evaluate the effectiveness, feasibility, safety and outcome of using fluoroscopically inserted expandable metallic wall colorectal stents in palliation of colorectal obstruction and avoiding stoma creation. Method This study is a retrospective evaluation of all patients who underwent placement of fluoroscopically inserted colorectal stents throughout the period from June 2000 till December 2003. All the stents were inserted as a palliative measure to relief colorectal obstruction in patients with locally advanced irresectable and/or metastatic cancer or patients with significant comorbid conditions
rendering surgery a high risk option. Results 19 patients underwent placement of expandable metallic wall stents under fluoroscopic guidance. 4 patients underwent placement of the stent with both fluoroscopic and colonscopic guidance. There were 10 females and 9 males. 16 patients presented with incomplete obstruction. The stricture was rectosigmoid in 8 patients, sigmoid in 7 patients, descending colon in one, 1 patient had distal transverse colonic stricture, and hepatic flexure in 2 patients. 7 patients had metastatic colorectal cancer. 10 patients had a locally advanced metastatic colorectal cancer, 1 patient had advanced ovarian cancer and one patient had an ischemic colonic stricture. Stenting was successful, restoring bowel function within 24-72 hours in all patients. 2 patients had an early stent migration and the stent was removed in the Emergency Room. Both were not restenting. 1 patient had a late stent migration and was restented and still in place until now. 2 patients had a colonic perforation managed conservatively and did not require a surgical intervention. Conclusion Expandable wall stents may provide safe and effective palliation for patients with irresectable colorectal strictures avoiding stoma creation.
FP-3 Polycystic Liver Disease : Surgical Management R. Adam1, G. Pascal2, H. Bismuth2, D. Azoulay2, D. Samuel2, D. Castaing2 1 11, Hopital Paul Brousse, France, 2Hopital Paul Brousse Objectives: To evaluate the respective indications of deroofing, liver resection (LR) and liver transplantation (LT) for the treatment of Polycystic liver disease (PLD) Patients and methods: Beetween 1975 and 2001, 52 patients with PLD were managed at a single institution: 44 females (85%), mean age: 52 years. Half of them had an associated polycystic kidney disease. Operative mortality, morbidity and long-term results were analysed. Results: Surgery was performed in 47 patients (90%) with highly symptomatic PLD: laparoscopic deroofing (LD) in 18 patients (38%), open deroofing (OD) in 17 (37%), liver resection (LR) in 3 (6%), liver transplantation (LT) in 9 (19%), combined with kidney transplantation in 7 patients. There was no mortality in all patients. After LD, there was no conversion and no morbidity. After OD, a complication occured in 10 patients (59%) and beyond them, 6 (35%) developed ascites. After LR, there was no complications. After LT, morbidity was 78% : 4 patients (44%) had a surgical complication, requiring a reintervention for 3 of them. After deroofing, long-term results (2-15 years) were good in all patients with large cysts (75%) and poor in the remaining patients with small cysts. After LR and LT all patients recovered an excellent quality of life (2-9 years). Conclusion : LD must be the gold standard of PLD with large symptomatic cysts. When cyts are symptomatic, small and extensive LT should be considered as a safe option.
Abstract of 19th WC-ISDS
FP-4 Laparoscopic Large Volume, Single Insertion, Microwave Tissue Ablation (MTA) of Liver Tumours using a Novel Applicator Fateh Ahmad, Andrew Strickland, David Lloyd Department of Surgery, Leicester Royal Infirmary, UK Background: Tissue ablation is becoming an established modality for the treatment of solid tumours, particularly in the liver. Methods: A novel MTA applicator has been developed which is capable of producing large volume ablations. Three patients underwent laparoscopic MTA for the treatment of liver tumours. Cross-sectional imaging was used to identify these lesions preoperatively, and their size and location were confirmed using intraoperative ultrasound (IOUS). A 5mm laparoscopic MTA applicator was positioned centrally within the tumour under IOUS guidance and ablated until a margin of clearance was achieved. Treatment was monitored with real-time IOUS imaging. Treatment efficacy, tumour recurrence, complications and survival were recorded. Results: The mean age of patients was 42 years. Each patient had one tumour which was ablated (mean tumour size 3.8cm). MTA treatment time ranged from 60 seconds to 180 seconds (mean 120 seconds) and was carried out with a single insertion of the probe. No further MTA treatment was required in any of the patients. Mean follow-up time was 7 months. Post-operative imaging revealed complete tumour destruction with no evidence of recurrence, and all 3 patients remain asymptomatic and disease free. There were no immediate or long term complications arising from the MTA treatment. Mean hospital stay was 36 hours. Conclusions: Large volume MTA represents significant advancement in the treatment of benign and malignant liver tumours. Results from these patients suggest that the use of this novel microwave equipment laparoscopically combines the benefits of a minimally invasive approach without compromising the efficacy of the ablation.
FP-5 Competent Surgeons do not Require Specific Training in Laparoscopic Appendicectomy Fateh Ahmad, Prashant Reddy, David Lloyd, Gavin Robertson Department of Surgery, Leicester Royal Infirmary, UK Aims: Initially laparoscopic cholecystectomy led to an increase in complications due to inexperience. This paper examined the outcome when surgeons with laparoscopic experience in cholecystectomy and experience in open appendicectomy started to perform laparoscopic appendicectomies with no supervision or additional training. Methods: All laparoscopic appendicectomies in the three Teaching Hospitals in Leicester between 1993 and 2003 were retrospectively reviewed noting the most senior surgeon and the outcome. Results: A total of 36 men and 200 women with a median age of 25 years (range 8-81) underwent laparoscopic appendicectomy by 33 different surgeons. 25 of the surgeons were registrars (n=201, range 43-1) and 8 consultants (n=30, range 11-1) who were competent at performing laparoscopic cholecystectomies unsupervised. The median duration of surgery was 55 minutes (range 20-120). There were 7 conversions. Opiate analgesia was not required by 105 patients; only 20 patients required more than 4 doses. Histo-
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logically, 70 (30%) of the appendixes removed were normal. Postoperatively, 8 patients merited an abdominal ultrasound- a pelvic abscess was noted in 6 patients; 1 required percutaneous drainage and 2 patients required further laparoscopy. There was a single recorded wound infection and 1 portsite hernia. Median postoperative stay was 2 days (range 1-12). Conclusion: The results suggest laparoscopic appendicectomy can be safely performed by surgeons who are competent at laparoscopic cholecystectomy without the need for any additional training or supervision.
FP-6 An Algorithm for the Management of Bile Leak following Laparoscopic Cholecystectomy Fateh Ahmad, David Lloyd, Gavin Robertson Department of Surgery, Leicester Royal Infirmary, UK AIM: Bile leak is a well-documented complication of laparoscopic cholecystectomy. Recognition and treatment of this event varies. We have standardised the management of such bile leaks and an algorithm is presented. METHODS: Twenty-five patients with bile leaks following laparoscopic cholecystectomy between 1991 and 2003 were reviewed in two groups, before (pre-1998) and after standardising the management. RESULTS: There were no bile leaks due to CBD damage. Nine cases occurred pre-1998. Of these, 4 patients underwent open surgery to control cystic stump bile leak and 1 patient had relaparoscopy with washout and suturing of an accessory duct. Four patients were managed conservatively. Mean duration of hospital stay was 11.5 days (range 5-30). There was one mortality. Following establishment of our HPB unit in 1998, 16 patients were referred with a bile leak and managed according to a protocol involving establishment of drainage, insertion of endoscopic stent and laparoscopic lavage in cases with peritonitis. Seven patients underwent ultrasound, 4 who did not have a perioperative drain had drain insertion. Thirteen patients had postoperative ERCP, with stent insertion in 12. Five patients had re-laparoscopy to oversew a leak (n=2) or washout with drain insertion (n=3). There was no mortality and none required open surgery. Mean hospital stay was 9.89 days (range 5-11). DISCUSSION: Early referral of bile leaks and management on a specialised unit using ERCP and percutaneous drainage produces a good outcome for most patients minimising morbidity and maintaining patient satisfaction with a minimal access approach.
FP-7 Rapid Large Volume Microwave Tissue Ablation (MTA) of Unresectable Liver Tumours using a Novel Applicator Fateh Ahmad1, Andrew Strickland1, Moshier Elabassy1, Peter Clegg2, Nigel Cronin2, David Lloyd1 1 Department of Surgery, Leicester Royal Infirmary, 2Department of Physics, University of Bath,UK Objective: The efficacy of current in situ thermal ablation systems for the treatment of liver malignancies is limited by tumour size or associated complications. Methods: Eleven patients with unresectable liver tumours greater than 4cm in diameter were enrolled in this study. Pre-operative cross-sectional imaging and intra-operative ultrasound was used to
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identify the tumours. A total of 67 liver tumours were treated in this group of patients, 53 with MTA and 14 resected. Tumour types included metastases from colorectal cancer (n=6) and parathyroid carcinoma (n=1), hepatocellular carcinoma (n=2), adenoma (n=1) and carcinoid (n=1). The largest tumour was 6.5cm in diameter necessitating a single treatment of 4 minutes. Lesions 4 4.5cm in diameter were treated in less than 3 minutes. Most ablations were carried out with a single insertion of the applicator. Complications, tumour recurrence and survival were recorded. Results: Mean age was 61.4 years. Mean tumour size was 5.0cm and mean MTA treatment time was 4 minutes. Six patients were alive at mean follow-up of 10 months. There were no complications related to the MTA treatment. Successful ablation was achieved in all patients, and no obvious tumour recurrence was visible at 3 months on imaging. At 1 year, two patients had tumour recurrence distant from the original ablation site and one patient developed extra-hepatic disease at 27 months. Conclusions: Successful large volume ablation was achieved in all patients using this novel microwave equipment. This was accomplished using a rapid, single insertion technique comparing favourably with other currently available ablative modalities.
FP-8 Evaluation of Transanal Endoscopic Microsurgery (TEM) for the Resection of Rectal Tumors Kunihiko Amano, Shinpei Ogawa, Michio Itabashi, Shingo Kameoka Department of Surgery 2, Tokyo Women’s Medical University, Japan Purpose: In order to clarify the indication of TEM, we analyzed the patients who underwent transanal local excision. Method: We analyzed 31 patients who underwent TEM and compared with 84 patients who underwent conventional transanal local excision and minimum invasive transanal surgery (MITAS) using double stapling technique. We examined the distance from the anal verge to the tumors, tumor size, operation time, and the percentage of the tumor-positive lateral margin. Results: The mean distance from the anal verge to the tumor in the TEM group was 69.2mm, whereas conventional excision allowed mean distance of 40.2mm. The maximum distance from the anal verge to the tumor was 200mm in the TEM group. In the TEM group, maximum tumor size was 103mm, and the mean operation time was 88.2 minutes, whereas the MITAS group showed the maximum tumor size to be 80mm, and the minimum mean operation time of 38.7minutes. The percentage of the tumor-positive lateral margin were 7.1%, 12.1%, and 25.0% respectively for the TEM, conventional local excision, and MITAS groups. Discussion: TEM allowed distant rectal tumor to be resected compared with the conventional local excision, however mean operation time was longer compared with the other groups. Maximum tumor size resected with the MITAS was the smallest in the three groups, but the MITAS group had the shortest mean operation time. Conclusions: TEM was capable of resecting large tumor with the lowest tumor-positive rate of the margin, and enabled the resection of distant tumors, although longer operation time is required.
FP-9 The Unexpected Postoperative Finding of the Gallbladder Carcinoma after Laparoscopic Chelecyctectomy Takeshi Aoki, Takashi Kato, Masahiko Murakami, Yoshinori Shimizu, Noriyuki Murai, Mitsuo Kusano Syrgery II, Showa University, Japan The unexpected postoperative finding of the gallbladder carcinoma has become particularly problematic since the advent of laparoscopic cholecystectomy. Because the new pattern of recurrence, involving either the port site implantation or intraperitoneal implants, is unique to the laparoscopic procedure, which attributed to bile spillage during laparoscopic cholecystectomy. After several patients presenting with gallbladder stones were found to have gallbladder carcinoma, we performed the following study. Methods. Records of patients with an admitting diagnosis of gallbladder stones and performing laparoscopic cholecystectomy, were reviewed. Results. Carcinoma involving the gallbladder was found by postoperative pathologic examination in 10 patients (0.41%) aged 55 to 88 years (mean age, 69.8 years, 2 man and 8 women) after laparoscopic cholecystectomy. The preoperative diagnosis was gallbladder stones with chronic cholecystitis in 10 patients. 5 patients with pT3 disease were advised to undergo further surgery, and one patient with pT4 disease had found abdominal wall recurrence as an intraoperative finding in further surgery. 4 patients (66.7%) with pT3 had cancer recurrence. Conclusion. We demonstrated that not only patients with early stage of gallbladder carcinoma but also patients with pT3 or pT4 after laparoscopic cholecystectomy were found in this study. To minimize the likelihood of encountering unexpected gallbladder carcinoma at laparoscopic cholecystectomy, our results would seem to lend support to the opinion that it is imperative to identify the patient population at the greatest risk for gallbladder carcinoma after laparoscopic cholecystectomy and avoid the occasional seeding of bile spillage when laparoscopic cholecystectomy was performed.
FP-10 Analysis of Complications in Hepatic Right Lobe Living Donors Ayman Azzam, Kenji Uryuhara, Takashi Ito, Yasutsugu Takada, Hiroto Egawa, Koichi Tanaka Department of Transplantation and Immunology, Kyoto University, Japan Background Living donor liver transplantation (LDLT) has been expanding the territory to adult recipients by using right lobe grafts. However, the incidence of complications is more frequent than that involving left lobe graft. Objective Donor safety is always the top priority in LDLT, so we aimed to analyze the postoperative complications in right lobe liver donors as a step to improve the results of the donor side. Methods 311 right lobe donors between February 1998 and December 2003 were retrospectively subjected for the study. Results Median age of the donors was 44 years old (19-64 years). Body mass index was 22.1 (16.6-34.3). Duration of the operation was 6.58±1.25 hours, and blood loss was 289±254 ml. Estimated residual liver volume was 42.2% of the whole liver (20.6-60.3%). Hospital stay was 14.5 days (6-267 days). All but one donor are
Abstract of 19th WC-ISDS
alive and healthy, although 30% of the donors experienced one or more complications. The most common complication was biliary leakage then persistent abdominal fluid collection. Other complications include pleural effusion, wound infection, biliary stricture, small bowel obstruction, ascites, pulmonary embolism and portal vein thrombosis. One donor died of liver failure due to small remnant liver (26%) and concomitant non-alcoholic steatohepatitis, which was diagnosed postoperatively, in spite of rescue domino transplant. Conclusion Right lobe liver donation is an acceptable procedure which results in the expansion of the indication for LDLT to large-sized recipients. However, remnant liver size and anatomical variations in the biliary tree may represent important risk factors for the postoperative complications.
FP-11 Surgery and Adjuvant Chemotherapy for Advanced Gastric Cancer Hideo Baba1, Koujirou Mashino1, Eiji Oki1, Manabu Yamamoto1, Masahiko Ikebe1, Yoshihiro Kakeji2, Yoshihiko Maehara1 1 Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 2Center for the Integration of Advanced Medicine and Innovative Technology, Kyushu University Hospital, Japan Gastric cancer remains the 2nd most common cause of cancer death in Japan. Treatment outcome has been much improved during the past decades, mainly due to earlier diagnosis. However, prognosis of patients with advanced gastric cancer still remains poor. Surgical approach for advanced gastric cancer includes gastrectomy and D2 or D3 lymph node dissection with or without a combined resection of adjacent organs. The Interim analysis of JCOG study about D2 vs D3 showed a feasibility of D3 lymph node dissection in Japan, although randomized control trials in Western countries could not show superiority of D2 compared D1 dissection. At present, a standard lymph node dissection is D2 until the final report of JCOG study about D2 vs D3 will be published. For advanced gastric cancer, peritoneal dissemination often occurs even after curative surgery and may need chemotherapy. Recently, active anticancer agents effective to peritoneal dissemination have been developed, which includes TS-1 or Taxans. These new agents either alone or in combination have been used for the treatment of recurrent patients. Several clinical trials with new agents have been conducted with an attempt to improve survivals of patients. With regard to postoperative adjuvant chemotherapy, no standard regimen has been established,yet. A nation wide clinical trials of adjuvant chemotherapy using TS-1 has now been conducted and the enroll of it will be finish this year. In this presentation, I will review current surgical and chemotherapeutic approach and present our data.
FP-12 Recurring Colorectal Cancer with SM Invasion Yoshiko Bamba, Michio Itabashi, Shinpei Ogawa, Akiyoshi Seshimo, Noriyasu Shirotani, Shingo Kameoka Surgery 2, Tokyo Women’s Medical University, School of Medicine, Japan Purpose: We studied the clinical and pathological characteristics of
Journal of Gastrointestinal Surgery
colorectal adenocarcinoma with a submucosal (SM) invasion. Methods: We treated 223 patients with colorectal adenocarcinoma with SM invasion (1987-2003). Among these, 8 (3%) were recurrences. Clinicopathologic findings were compared with cases without recurrence. Results: The tumors were in the ascending colon (1), sigmoid colon (2), and rectum (5). Histological classification revealed highly and moderately differentiated adenocarcinomas in 6 and 2 cases, respectively. Lymphoid invasion was positive in 5. Vessel invasion was negative. Lymph-node metastasis was more frequent in cases of recurrence, 4 of 8 (50%), compared with no recurrence, 20 of 182 (11%). We performed 3 local resections per anus and 5 colon resections. The recurrence was local after local resections in all cases, and liver metastasis was also detected in 1 case. Vessel invasion was positive in 1 case after local resection, however, the depth of invasion was more than 1,500µm in all cases. In the recurrence type after colon resections, however, liver metastasis was seen in 4 of 5 cases (80%). Both lymphoid and vessel invasion were positive in 4 of 5 cases. D3 lymphoidectomy was performed in 1 case and D2 lymphoidectomies in the others. Conclusions: Careful follow-up is mandated in cases of recurring colorectal adenocarcinoma after local resections when invasion depth exceeds 1,500µm, and for cases of colon resection with lymphoid metastasis, surgical intervention with D2 lymphoidectomy is indicated.
FP-13 Intraoperative Endoscopy for Laparoscopic Antireflux Procedures: A Preliminary Report Guillermo Becerril-Martinez1, Cesar Oscar Decanini1, Alberto Farca2, Francisco Fournier2, Antonio Giovanni Spaventa1 1 Endoscopic Surgery, American British Cowdray Medical Center, I.A.P.,2Gastrointestinal Endoscopy, American British Cowdray Medical Center, I.A.P., Mexico Background: Laparoscopic antireflux procedures (LARP) are the standard treatment of patients with gastroesophageal reflux disorder (GERD) unresponsive to medical treatment. Adequate surgical technique is the most important factor for the outcome. There is no objective method to evaluate the procedure itself. We propose intraoperative endoscopy (IOE) during LARP to confirm adequate surgical technique. Materials: Patients undergoing LARP in a private hospital setting from July 1999 to June 2004, excluding open procedures and reoperations of previous failed LARP. IOE performed during the dissection and suturing of the procedure to determine if the technique needs correction. Functional outcome assesed during hospitalization and as outpatient. Results: 300 patients were operated with IOE during the study, 23 were excluded (14 reoperations of LARP and 9 conventional laparotomies). Of the 277 patients included, 178 (64.3%) were males and 99 (35.7%) females. Average age was 43 years (range 1285 years). There were 71(25.6%) Toupet and 206(74.4%) Nissen fundoplications. IOE determined correction of the technique in 115(41.5%) patients. 103(89.6%) rotated and/or angled fundoplication, 1(0.8%) rotation with distended stomach, 1(0.8%) redundant gastric fundus, and 10(8.7%) change in the type of fundoplication from Nissen to Toupet because of stenosis. There were up to 4 changes (average 1.68 times) in the positioning and/or suturing of the fundoplication to achieve adequate fundoplication. Conclusion: IOE can assist the surgeon during LARP to perform
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an adequate procedure. Further studies will determine if routine use of IOE during LARP can prevent postoperative complications and improve the outcome of surgical treatment of GERD.
FP-14 Effects of Ischemic Preconditioning on Regenerative Capacity of Hepatocyte in the Ischemically Damaged Liver Abdulkadir Bedirli 1, Mustafa Kerem 1, Hatice Pasaoglu 2, Ozlem Erdem3, Ebru Ofluoglu2, Omer Sakrak1, Gulen Akyol3 1 General Surgery, Gazi University, 2Biochemistry, Gazi University, 3Pathology, Gazi University, Turkey Objective. To evaluate the effects of ischemic preconditioning (IPC) on liver regeneration after partial hepatectomy under ischemia-reperfusion (IR) in rats. Methods. Male Wistar rats were subjected to 45 minutes of total hepatic ischemia, and 70% hepatectomy was performed just before reperfusion. Animals were pretreated with either IPC (10/15 minutes) (IPC group) or not (control group). The survival rate, serum transaminases, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels, hepatocyte proliferation and histologic change of the remnant liver were measured in both groups and compared with rats subjected to 70% hepatectomy alone (PH group). Results. The survival rate was significantly better in the IPC group than in the control group. Furthermore, IPC reduced liver injury determined by liver histology and serum transaminases. There was an early rise in serum TNF-α and IL-6 levels in the control group. Interestingly, IPC significantly decreased TNF-α, but not IL-6. Rats subjected to 70% hepatectomy and 45 minutes of hepatic ischemia showed significantly reduced hepatocyte proliferation (mitotic index, proliferating cell nuclear antigen, and relative liver weight) when compared with animals subjected to hepatectomy alone. However, hepatocyte proliferation was markedly increased in rats pretreatment with IPC when compared with controls. Conclusions. Ischemic preconditioning ameliorates the hepatic injury associated with ischemia-reperfusion and has a stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective modality. Il-6 appears to be key mediator in promoting regeneration following combined ischemia and hepatic resection.
FP-15 Management of Common Bile Duct Stone in a Rural Area of the United States: Results of a Survey Juliane Bingener1, George B. Kazantsev2, Wayne Homer Schwesinger1 1 Dept of Surgery, UTHSCSA, 2First Surgical Consultants, Oakland, CA, USA Purpose: Although laparoscopic common bile duct exploration (CBDE) has been reported to be highly successful and cost effective, it remains unknown to what extent the procedure is used in routine surgical practice. Methods: We conducted a survey of general surgeons practicing in a rural area of the United States. The type of practice, the timing of laparoscopic training, performance of intraoperative cholangiography (IOC), and preferred approach to choledocholithiasis were elicited. Results: Sixty-eight of 207 (33%) surveys were returned. The majority of surgeons (73%) obtained laparoscopic training after residency. Twenty-four surgeons (36%) performed IOC routinely
and 43 surgeons (64%) performed it selectively. Thirty respondents (45%) indicated that they perform laparoscopic CBDE. The transcystic approach was the most common method (22% of total). Choledochotomy was used by 5 surgeons (7%), and combination of both procedures was used by 10 (15%). The preferred approach to a patient with a CBD stone was ERCP (75%), followed by laparoscopic CBDE (21%) and open CBDE (4%). Reasons for not performing laparoscopic CBDE were: “too time-consuming” (58%), lack of equipment (24%), good GI backup (6%), poor reimbursement (3%), increased morbidity (1.5%), lack of skill (1.5%), other (9%). While 12% of surgeons gave more than one reason, 9% provided no reason. Conclusion: Although 45 % of practicing surgeons indicated that they perform laparoscopic CBDE, only half of this group (21%) practiced it as their preferred approach. Time constraints and lack of equipment are the main factors preventing the application of the laparoscopic technique towards CBD stones.
FP-16 Fluorescent Orthotopic Mouse Models of Pancreatic Cancer Michael Bouvet 1, Matthew H. Katz 1, Shinako Takimoto 1, A. R. Moossa1, Robert Hoffman1,2 1 Department of Surgery, University of California San Diego, 2 AntiCancer Inc., San Diego, CA, USA Here we describe our cumulative experience with the development and preclinical application of several highly fluorescent, clinicallyrelevant, orthotopic mouse models of pancreatic cancer. These models utilize the human pancreatic cancer cell lines BxPC-3, MIA-PaCa-2 and COLO-357 which have been genetically engineered to selectively express high levels of the bioluminescent green fluorescent (GFP) or red fluorescent (RFP) proteins. Fluorescent tumors are established subcutaneously in nude mice, and tumor fragments are then surgically transplanted onto the pancreas. Locoregional tumor growth and distant metastasis of these orthotopic implants occurs spontaneously and rapidly throughout the abdomen in a manner consistent with clinical human disease. Highly specific, high-resolution, real-time visualization of tumor growth and metastasis may be achieved in vivo without the need for contrast agents, invasive techniques, or expensive imaging equipment. Alternatively, transplantation of tumor fragments onto the pancreas of GFP-expressing transgenic mice may be used to facilitate visualization of tumor-host interaction between the pancreatic tumor fragments and host-derived stroma and vasculature. Such in vivo models have enabled us to serially visualize and acquire images of the progression of pancreatic cancer in the live animal, and to demonstrate the real-time antitumor and antimetastatic effects of several novel therapeutic strategies on pancreatic malignancy. These fluorescent models are therefore powerful and reliable tools with which to investigate human pancreatic cancer and therapeutic strategies directed against it.
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FP-17 Effects of a Restricted Intravenous Fluid Regimen versus a Standard Regimen on Haemodynamics, Renal Function and Metabolism: A Clinical Randomised Multi Centre Trial Birgitte Brandstrup1, Poul-Erik Svendsen2, Birgit Thage3, Henrik H. Rottensten4, Lene Iversen5 1 Surgical Department D., Glostrup University Hospital, 2Anaesthesiological Dept., Bispebjerg University Hospital, 3Anaesthesiological Dept., Gentofte University Hospital, 4Anaesthesiological Dept., Rigshospitalet, 5Surgical Dept. Vejle Sygehus, Denmaek Background. Large intravenous fluid volumes have been claimed necessary for prevention of hypotension, renal failure and tissue hypo-perfusion in major abdominal surgery. We have, however, recently introduced a restricted intravenous fluid regimen that significantly reduced complications following colorectal surgery (1). In this paper the effects of the restricted regimen on physiological changes was evaluated. Methods. A clinical randomised multi centre trial was performed. Patients undergoing colorectal resection were allocated to either a restricted (R) or a standard (S) intravenous fluid regimen. The Rregimen aimed at maintaining unchanged bodyweight throughout the time in hospital. The S-regimen followed current recommendations. Results. With 141 patients completing the trial, the trial’s power to determine a difference between groups was very high. We found, however, no significant differences in BP, HR, or administration of pressor substances during or after surgery between the groups. The R-group had significantly higher arterial pH, s-bicarbonate, base-excess, and improved oxygen tension following surgery (p<0.01). S-Cortisol was similar between groups, but S-Aldosteron was increased in the R-group on 1st, 3rd and 5th postoperative day (p<0.05). The R-group had smaller diuresis, higher s-creatinine, salbumin, and s-protein on the day of surgery (p<0.01) but not the following days. Analysed for the entire period of measurement screatinine and s-urea was similar between groups. Conclusions. No evidence was found that perioperative intravenous fluid restriction caused haemodynamic instability, compromised renal function, or poor tissue perfusion. S-Aldosteron was increased in the group with the best outcome.References. Brandstrup B. et al. Ann Surg. 2003;238:641-48
FP-18 Sentinel Node Detection and Lymphatic Mapping for Adenocarcinoma of the Gastroesophageal Junction Maria Burian1, Hubert Stein1, Andreas Sendler1, Morand Piert2, Joerg Naehrig3, Marcus Feith1, Joerg Ruediger Siewert1 1 Department of Surgery, 2Department of Nuclear Medicine, 3 Institute of Pathology, Klinikum rechts der Isar, Technical University Munich, Germany Introduction: The clinical value of lymphatic mapping and sentinel lymphadenectomy in gastrointestinal cancers is still discussed controversially. We prospectively evaluated the pattern of lymphatic spread in patients who underwent resectin for invasive adenocarcinoma of the esophagogastric junction and assessed the feasibility of radio-guided sentinel node identification. Patients and Methods: 54 patients with an adenocarcinoma of the esophagogastric junction (AEG type I-III) peroperatively staged T1-T3 were included into the study. 30 patients had an AEG I
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(Barrett’s carcinoma) and 15 patients an AEG II, 9 patients an AEG type III tumor. 2 ml 60mBq TC99m-nanocolloid was injected submucosally around the tumor 16-18h prior to surgery. After laparotomy the activity of all lymph node stations according to the JGCA was measured b a hand-held gamma probe. All sentinel nodes were removed from the resected specimen and asservated for intensified histopathologic assessment including serial sections and immunohistochemistry. Results: In 49 out of 54 (91%) patients one or more sentinel lymph node could be identified. The median range was between 1 and 8 lymph nodes. 9 patients were nodal positive. A correct prediction of the nodal status was possible in 43 out of 49 patients (88%). Conclusion: First experiences with sentinel node identification in AEG tumors was shown to be feasible. However the learning curve is quite long. Lymphatic spread of AEG tumors is not erratic but appears to follow certain rules. This may open the door to tailored lymphadenectomy-strategies based on the sentinel lymphadenectomy concept in AEG tumors.
FP-19 Management of Carcinoma of Gallbladder: A Single-Institution Experience in 16 Years Fion Siu-Yin Chan, Ronnie Tung-Ping Poon, Kelvin Kwok-Chai Ng, Chi-Ming Lam, Sheung-Tat Fan Department of Surgery, University of Hong Kong Medical Centre, Hong Kong, China Background: Radical surgery is the only curative treatment for carcinoma of gallbladder. However, the clinical outcome of most patients remains poor due to low resectability rate. Aim of Study: This study was to evaluate the outcome of patients with carcinoma of gallbladder managed in a single institution over 16 years. Patients and Methods: From April 1988 to November 2003, 86 patients (29 males, 57 females) (median age = 69.5 years) were diagnosed to have carcinoma of gallbladder. Tumor staging, treatment modalities and clinical outcome of patients were evaluated. Results: Thirty-two patients (37%) had early stage (TNM stage I or II) disease whereas 54 patients (63%) had advanced stage (TNM stage III or IV) disease. Curative surgery was performed in 23 patients (27%) and 21 patients (24%) received palliative surgery. Among patients with curative surgery, local and distant tumor recurrence occurred in 8 patients and 4 patients, respectively. Overall survival was significantly better in patients with curative surgery (1-year: 85%; 2-year: 63%; 3-year: 55%) than those with palliative treatment (1-year: 11%; 2-year: 0%; 3-year: 0%) (P < 0.001). By multivariate analysis, curative surgery was the only independent prognostic factors affecting overall survival. Conclusion: Favorable survival outcome can be achieved in patients with carcinoma of gallbladder after curative resection.
FP-20 Enhancement of Epirubicin-induced Apoptosis and Cytotoxicity Effect in Human Hepatoma Cells by Progesterone Wen-Tsan Chang, King-Teh Lee Department of Surgery, Kaohsiung Medical University Hospital, Taiwan Purpose: Testosterone and androgen receptor had been reported to participate in the development of HCC. In our preliminary clin-
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ical observation, administration of progesterone and epirubicin simultaneously may lowers the postoperative recurrence rate of HCC. Thus, we try to investigate the effect of combination of progesterone and epirubicin in preventing recurrence of HCC in vitro. Methods: The different concentrations (12.5 nM, 25 nM, and 50 nM) of testosterone, progesterone and epirubicin (0.5µg/ml, 1µg/ml, and 5µg/ml) were added to HepG2 cell lines. The effect of treatments were studied by (1) 3H-Thymidine incorporation (2) LDH leakage(3) MTT assay (4) measure the DNA fragmentation and (5) flow cytometry to assess the inhibition, proliferation, cytotoxicity, and apoptosis effect induced by different drugs. Results: The testosterone (12.5nM, 25 nM and 50 nM) can promote and the progesterone (12.5nM, 25 nM and 50 nM) can inhibit the proliferation of HepG2 cells analyzed by 3H-Thymidine incorporation and MTT assay. But there was no dose-dependent effect observed. Epirubicin-induced cytotoxicity and apoptosis effect were identified by LDH assay, DNA fragmentation, and flowcytometry. Besides, combination of 12.5 nM progesterone and 1µg/ml epirubicin can increase 1.7 times of LDH leakage compared to treat with 1µg/ml epirubicin alone at 48 hours. Conclusion: In vitro, testosterone can promote proliferation of HepG2 cells and progesterone had the adverse effect. And 12.5nM progesterone can increase the epirubicin-induced cytotoxicity and apoptosis effect on HepG2 cells. For lowering the postoperative recurrence rate of HCC, it maybe reasonable to combine progesterone with epirubicin as the postoperative adjuvant therapy.
FP-21 Serum Antioxidants and Malnutrition in Patients with Liver Cirrhosis Wen-Tsan Chang1, Meng-Chuan Huang2, King-Teh Lee1 1 Department of Surgery, 2Department of Nutrition, Kaohsiung Medical University Hospital, Taiwan Purpose. Reduced serum antioxidant concentrations and malnutrition have been characterized in patients with liver cirrhosis. However, very few studies examined the relationship between antioxidant status and malnutrition among cirrhotic patients. The purpose of the study is to examine antioxidant status and their relations to nutrition status indicators in different stages of liver cirrhotic patients. Methods. Nutritional assessment including anthropometric measurement and protein-energy malnutrition indicators, total protein, albumin, prealbumin and transferring, and serum antioxidants including retinol, lycopene, α-carotene, β-carotene, δ-tocopheral, γ-tocopheral and α-tocopheral were evaluated in 50 cirrhotic patients without HCC. Results. There were no differences in anthropometric indices including body mass index, mid arm circumference, mid muscle arm circumference and tricep skinfold in patients with different cirrhotic stages classified using Child-Pugh scores. Serum albumin, transferrin, and prealbumin decreased from the Child-Pugh A to Child-Pugh C stage in a dose response manner. Among all antioxidants investigated, retinol and α-tocopherol were significantly lower in patients of Child-Pugh B and C than those of Child-Pugh A and they were similar between B and C class. In multivariate regression model, prealbumin and albumin, but not transferrin, were independently associated with retinoids, upon adjustment of coufounders. However, there were no associations found between these nutritional indicators and α-tocopherol.
Conclusions. Nutritional indicators did not associate with serum α-tocopherol level in liver cirrhosis patients. However, prealbumin and albumin may serve as an important clinical indicator to predict serum retinol status.
FP-22 Tumor Down-Staging by Preoperative Chemoradiation of Rectal Cancer did not Predict the Prognosis Yeon-Soo Chang, Jae-Chang Lee, Kil- Yeon Lee, Suk- Hwan Lee, Soo-Myung Oh, Choong Yoon Dept. of Surgery, Kyunghee University College of Medicine, Korea Purpose: Very few studies have published so far in eastern countries regarding preoperative chemoradiation (XRT) therapy for advanced rectal cancer. The aims of this study were to determine whether the down-staging by preoperative XRT influences the outcome and to find the clinicopathologic factors influencing the response to preoperative XRT. Methods: The study reviewed 62 rectal cancer patients diagnosed as stage II, III and treated with preoperative XRT and total mesorectal excision (TME). Clinical staging was compare with the pathologic staging. Results: There were 48 male (77%) with the mean age of 56 years. Mean radiation dose was 4925cGY. All patients have undergone operation with the mean of 6 weeks after completion of XRT. Median follow-up period was 43(2~96) months. Thirty-four patients (55%) achieved down-staging including 8 patients (13%) of pathologic complete response. Recurrences were occurred in 14 patients (23%, 8% local and 15% systemic). The mean interval for local and systemic recurrence was 18 and 36 months, respectively. Down-staging achieved with preoperative XRT showed no statistically significant differences in 5-year disease free survival (65.1% vs.63.4%), however, complete response group showed no recurrence or death during the follow-up. There were no clinicopathological prognostic factors related with complete remission. Conclusions: Downstaging by preoperative XRT has no influence on the prognosis of patients. However, complete pathologic response group demonstrated a trend toward improved survival and decreased recurrence compared with non-complete response group. So we insist that continuous study is needed for selection of complete pathologic response group after preoperative XRT.
FP-23 Portal Hypertension in Post-cholecystectomy Biliary Stricture: Genesis, Management and Outcome Adarsh Chaudhary1, Sanjay Singh Negi1, Malhotra Veena2, Sakhuja Pooja 1 Department of Surgical Gastroenterology, Sir Ganga Ram Hospital, 2Department of Pathology, Gobind Ballabh Pant Hospital, India Background: Prolonged biliary obstruction initiates complex hepatic structural changes that can promote development of portal hypertension. Objective: To evaluate clinico-histological variables predictive of portal hypertension in patients with post-cholecystectomy biliary strictures and to study the outcome of such patients following single stage definitive biliary repair without initial portal decompression. Patients and Methods: Sixty four patients with post-cholecystectomy bile duct strictures undergoing definitive biliary repair.
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Prospectively collected information included demographic and disease related characteristics. The hepatic histological features (fibrosis, cholestasis, portal inflammation, ductular proliferation and hepatocyte hyperplasia) were independently graded by two pathologists who were unaware of the clinical data. Patients were dichotomized into groups based on presence (n=13) or absence (n=51) of portal hypertension. Results: Univariate analysis demonstrated duration of biliary obstruction (p<0.001), grade of hepatic fibrosis (p<0.001), degree of portal inflammation (p=0.001) and diffuse hepatocyte hyperplasia (p=0.013) to be significantly associated with presence of portal hypertension. Regression analysis revealed only grade of hepatic fibrosis (Odds Ratio 28.13; 95% Confidence Interval 3.76, 210.67; p=0.001) to be an independent predictor of portal hypertension. All the patients underwent single stage biliary repair. After a mean follow-up of 40.5 months none of the patients developed cholangitis, pruritus or gastrointestinal bleed. Conclusions: Hepatic fibrosis plays a central role in the genesis of portal hypertension associated with post-cholecystectomy bile duct strictures and a single stage definitive biliary repair without preliminary portosystemic shunt can safely and effectively be accomplished in a majority of such patients.
FP-24 CAPD Peritonitis Versus Surgical Peritonitis: How Do We Tell? Juliana Jia Chuan Chen, Wai Keong Wong General Surgery, Singapore General Hospital, Singapore Differentiating surgical peritonitis from routine CAPD peritonitis has always been a difficult surgical problem. Prior studies have suggested that multi-organ and gram negative CAPD fluid cultures correlate with an intra-abdominal pathology. However fluid cultures take a few days to return and certain surgical decision regarding laparotomy may have to be made before the cultures return. We looked at CAPD peritonitis patients who underwent emergency laparotomy for suspected surgical pathology. There were 20 patients who had an emergency laparotomy for suspected acute abdomen of which 13 had a positive pathology. These included acute appendicits, ischaemic colitis and small bowel, perforated duodenal ulcer and interloop abscess collection. Our mortality rate in both groups was 30% with a higher mortality rate in those who had undergone a negative laparotomy (42.9% vs 23%) Of these 13 patients, 10 (76.9%) had positive peritoneal fluid cultures for gram negative bacteria including pseudomonas, enterococcus and klebsiella. 9 patients (75%) had a positive findings on the CT scan such as appendicitis, intravascular and intramural air and fluid with inflammation. A negative finding was defined as reporting just fluid in the abdomen with enhancement of the peritoneum suggestive of CAPD peritonitis. We conclude that computerized tomogram is a fast and accurate method of screening for surgical pathology in patients with CAPD peritonitis. Screening laparoscopy may be used in the future in patients with CAPD peritonitis so that patients can return to peritoneal dialysis in the future.
Journal of Gastrointestinal Surgery
FP-25 Mycobacterium Avium Subspecies Paratuberculosis DNA in Inflamed Gut Tissues of Chinese Patients with Crohn’s Disease Jun Cheng1, Tim Bull2, Guojing Jennifer Zhu3, Peter Dalton2, Caroline Finlayson2, John Hermon-Taylor2 1 General Surgery, TC-2926D, University of Michigan Health System, USA, 2St. George’s Hospital Medical School, London, UK, 3 Life Science Institute, the University of Michigan, MI, USA PURPOSE: To determine whether Mycobacterium avium subspecies paratuberculosis (MAP) can be detected in archival paraffin-embedded full thickness samples of inflamed gut tissue from Chinese patients with CD. METHODS: Optimized recovery of tissue and access to MAP DNA. MAP-specific nested IS900 PCR is unique for MAP, together with stringent internal positive and negative controls. Amplification confirmed by Southern blotting and DNA sequencing. All samples were collected from patients having surgery for CD or in control subjects for bowel cancer, and tested blind. RESULTS: 13 CD patients (12 men, 1 woman, age 19-66) and 14 patients with cancer (8 men, 6 women, age 36-75). In the CD group, 6 pathologic blocks contained ileum only, 1 ileum/colon, and 6 colon only. In the ‘cancer’ group, 1 contained ileum only, 3 ileum/colon, and 10 colon only. 9/13 CD (69.2%), and 2/14 non-inflamed gut samples (14.3%) were IS900 PCR positive for MAP (p=0.0063). All internal PCR controls reported correctly. In 2 positive CD samples the DNA extraction with controls were repeated, and the DNA extract re-amplified in duplicate and sequenced. The IS900 sequences from Chinese CD tissues were 99.3% homologous to IS900 database sequence (GenBank X16293) with consistent base substitutions at 2 IS900 conserved sites 44/45 and 125, CG®GC and G®A, respectively. CONLUSION: MAP DNA is detectable in paraffin-embedded gut tissues from CD patients. The demonstration of MAP DNA in CD tissues further supports the association between MAP and CD in human. Larger sampling studies are required to elucidate the role of MAP in CD.
FP-26 Role of bFGF and HGF on Colon Adenocarcinoma Growth in Liver Jun Cheng1, Guojing Zhu2, Jennifer A. Gallagher3, Richard E. Slavin3, Lee L. Swanstrom3, Paul D. Hansen3 1 General Surgery, TC-2926D, University of Michigan Health System, 2Life Science Institute, the University of Michigan, 3Legacy Health System, Portland, OR, USA Purpose: To assess the effect of basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) infusion on tumor growth and metastases in a rat colon-adenocarcinoma tumor model. Methods: Liver tumors were established in each of 21 BDIX rats via surgical subcapsular implantation of a 1.0mm3 piece of DHD/K12/TRb tumor. Test groups were infused systemically with 5mg/day/rat bFGF or 0.5mg/day/rat HGF via osmotic pump; and controls received saline. At 28 days animals were killed and examined. Tumor size was calculated as p/6 [a2´b], where a is shorter length and b the longer length. Liver and lung specimens were processed for H&E staining and immunohistochemical study. Monoclonal mouse anti-VEGF and -flk-1 antibodies were used for immunostaining. Results: Tumor size (85.1±25.0 mm3) and lung
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metastases rate (5/7) in bFGF group were significantly increased in comparison with controls (48.8±17.6 mm3 and 0, P≤.05). The incidences of intrahepatic and peritoneal metastases were 3/7 in bFGF group although there were no statistical significances when compared with controls (0). There were no differences in tumor size and metastases rates between HGF and control groups (P>.05). On histologic examination, tumor cells were seen to grow along blood vessel branches after infusion bFGF and HGF. Both VEGF and flk-1 expression was strong cytoplasmic staining in cancer cells from hepatic, peritoneal and lung metastases. Conclusion: bFGF induced greater tumors, and more local/distant metastases than HGF did. These tumor cells expressed VEGF and its receptor flk1. Further studies are required to evaluate the mechanism of bFGF in tumor growth and metastasis.
FP-27 Improved Survival Rate for Patients with Esophageal Carcinoma who Undergo Lymphadenectomy Yu-Jen Cheng, Eing-Long Kao, Shah-Hwa Chou Thoracic Surgery, Kaohsiung Medical University Hospital, Taiwan Background: Esophageal carcinoma is known to metastasize to lymph nodes at a considerable frequency. The aim of this study is to retrospectively analyze the effect of two-field lymph node excision on the survival of patients with esophageal carcinoma. Methods: Between July 1995 and December 2001, 64 patients with esophageal squamous cell carcinoma were enrolled in this study. The tumors of 34 patients (group A) were resected. The other 30 patients (group B) received palliative treatment. Group A was further divided according to the metastatic status of resected regional lymph nodes. Fifteen patients (group C) had positive and 19 (group D) had negative findings. Results: Between groups A and B, the difference in survival time and difference in survival rate were statistically significant (P=0.0279 and 0.0138, respectively). Between sub-groups C and D, these differences were not statistically significant (P=0.7284 and 0.4674, respectively). Conclusion: Although regional lymph node metastasis indicates a poor prognosis, our data show that if these lymph nodes could be extensively removed, the patients could have outcomes similar to those without lymph node metastasis. This demonstrates that twofield extended lymphadenectomy has a beneficial effect on the survival of esophageal carcinoma patients by adequately eradicating the regional lymph nodes.
FP-28 Combination of Systemic Neoadjuvant Chemotherapy, Radical Surgery, and Intraperitoneal Mitomycin-C in Patients with Locally Advanced Gastric Carcinoma: 5-Year Follow-up of a Phase II Trial Frances Ka Yin Cheung1, Nancy Ng1, Simon Kh Wong1, Winnie Chu2, Wy Chan3, Enders Kw Ng1, Sydney Sc Chung1 1 Surgery, 2Department of Dignostic Radiology and Organ Imaging, 3Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Hong Kong, China Background: This study aims to investigate the tolerance and effectiveness of a combined treatment approach using systemic neoadjuvant chemotherapy, radical surgery and immediate
intraperitoneal chemotherapy to patients with locally adanved gastric cancer. Methods: Patients with T3/T4 gastric cancer confirmed by endoscopic ultrasonography and staging laparoscopy were recruited. With informed consent, 2 cycles of preoperative systemic chemotherapy as described by the Royal Marsden Hospital (Cisplatin, Epirubicin and 5-FU) were given to the patients. Chemo-response was determined by CT scan and EUS before and after the chemotherapy. All patients were subjected to laparotomy and, if possible, radical gastrectomy, and immediate intraperitoneal charcoal adsorbed mitomycin-C therapy before closure of the wound. Results: 38 patients with a median age of 60 (range: 38-72) were recruited. Severe complications developed in 2 patients during preoperative chemotherapy: 1 tumor perforation and 1 reactivation of hepatitis B leading to liver failure. Of the remaining patients, 34 had D2 gastrectomy performed. Complete or partial response was observed in 21 patients (62%). At 50 months of follow up, 5 patients in the responder group and 12 patients in the non-responder group died. Responders had a significant better cumulative survival than the non-responders(p<0.003). Conclusions: The tri-modality treatment is well tolerated by most patients and shows a response rate of 60%. Responders had a better prognosis than the non-responders.
FP-29 The Results of Using Warren-cattel Anastomosis in Soft Pancreatic Remnant after Pancreatic Resection for Malignant Diseases Fawaz Chikh Torab1, Hans Guenter Beger2 1 Surgery, Faculty of Medicine & Health Sciences, UAE, 2University Hospital of Ulm, Germany Pancreatic fistula is a dangerous complication after pancreatic resection, especially in a soft pancreatic stump. The optimal technique to reduce this complication is still controversial. The Warren-Cattel (WC) anastomosis is an end-to-side, duct to mucosa pancreatico-jejunostomosis (PJ). We performed a retrospective evaluation of two different types of PJ,WC and telescope (T) with regard to post-operative mortality, morbidity and the activity of pancreatic enzymes in drainage fluids. Patients and Methods: 70 patients with pancreatic resection were evaluated in a period of 17 months. 37 patients with a soft pancreatic stump (80 % Malignancy) underwent the WC and 33 patients with a hard pancreas (Chronic pancreatitis). All patients received octreotide therapy as an additional treatment until the 7th post-operative day. The clinical and labor-chemical courses were documented. Results: There was only one mortality in WC (1.4%). The postoperative intraabdominal morbidity was in both groups of patients: pancreatic fistula: 2 (5.4%) in WC, 1 (3%) in T, Biliary fistula: 0 in WC, 2(6%) in T, Periotnitis: 1(2.7%) in WC, 0 in T, cholangitis: 2 (5.4%) in WC, 1 (3%). The course of pancreatic enzyme activity in the drainage fluids was: Peak 700 U/l in WC, 500 U/l in T ont 2nd day in T, back to normal level on 4th day in WC and on 3rd day in T.Conclusion: The Warren-Cattel Anastomosis combined with octreotide therapy is a safe method to decrease morbidity after resection of the pancreas for malignant diseases.
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FP-30 The Role of an Anti-Obesity Surgery Centre in the United Arab Emirates Fawaz Chikh Torab1, Gabi Wazz2, Hakem El Taji2, Frank Branicki1 1 Surgery, Faculty of Medicine & Health Sciences, 2Tawam Hospital, UAE Introduction: The cardiovascular diseases are the leading cause of death in our country. Half of these cases are related to obesity and Diabetes. Patients and Methods: Since October 2001, 55 patients have been evaluated by the multidisciplinary team using the selection criteria as defined by the American Society of Bariatric Surgery. Laparoscopic gastric banding (LGB) was performed by 33 patients. Mean age was 32.5 (range: 21-48) years. 21 females and 9 males. Mean preoperative Body Weight and Body Mass Index were 133 (99.8-181) Kg and 49 (38-60) Kg/m2 accordingly. Hypertension was found in 9 patients, diabetes in 5 patients, infertility in 1 patient, a painful joint in 5 patients. Patients were followed up according to a protocol. Results: An LGB was inserted successfully in 32 patients (97%) with no perioperative mortality. Mean postoperative hospital stay was 2+1 days. Mean follow up for 25 patients was 10.8 months (range1-36 months). The mean weight loss was 19.18 Kg (3-43 Kg) and mean reduction of BMI was 6.9 Kg/m2 (0.4-17 Kg/m2). Complications occurred in 5 patients (20%), including pain at the port side in 1 patient, herniation of the stomach through the band in 1 patient, disconnection of the port in 1 patient, oesophageal dilatation in 1 patient and oesophagitis in 1 patient.Conclusion: The LGB in a specialized centre is a safe and effective method to reduce weight and morbidity in selected morbidly obese patients in countries with high prevalence of obesity and diabetes.
FP-31 Low Rectal Cancer: A Different Cancer Patrick Chiotasso, Yannick Selve, Franck Lazorthes Department of Digestive Surgery, Chu Purpan, France The aim of this study was to search for the specific characteristics of low rectal cancers. 236 charts of operated rectal adenocarcinomas, between June 86 and March 93, were reviewed. Patients were followed until november 03. 47 patients had a Miles procedure, 132 an anterior resection and 57 an abdomino-transphincteric approach. 79 patients had a preoperative pelvic radiotherapy. According to Dukes classification, there were 60 A, 81 B, 69 C and 26 with distant metastases. 2 groups of tumours were defined: group I was composed of tumours located between 2 and 4 cm from the anal verge (low rectal cancers - 65 cases), and group II was composed of tumours 4.5 and 15 cm distant (high rectal cancers - 171 cases). 3 parameters were compared as follow. The histologic stage of the tumour. In group I, there were 13 Dukes A, 19 B, 27 C and 6 with distant metastases. In Dukes C, the lymph nodes were involved in 6 cases while the tumour was still confined in the rectal wall. In group II, the figures were 47, 62, 42, 20 and 4. The risk of lymph nodes involvement was significantly higher in group I (41.5 % vs 24.5 % : chi2 = 6.561, df = 1, p < .02). The risk of having an early lymph node involvement, while the tumour is still confined in the bowel wall, was significantly higher in group I (6/19 cases vs 4/51 cases: 31.5 % vs 7.8 %, chi2c = 4.578, df = 1, p < .05). The distal intramural spread of the
Journal of Gastrointestinal Surgery
tumour. This was found in 14 cases in group I, and in 19 cases in group II. The risk was higher in group I (21.5 % vs 11.1 % : chi2 = 4.257, df = 1, p <.05). The risk was particularly high for Dukes B in group I (8/19 cases vs 6/62 cases: 42.1 % vs 9.6 %, chi2c = 8.549, df = 1, p < .01). The local recurrences. 12 patients presented a local recurrence in group I and 16 in group II. The risk of local recurrences while the tumour is still confined in the bowel wall, regardless of lymph node involvement, was 0/19 (0 %) in group I and 1/51(1.9 %) in group II. For tumours invading the perirectal tissues, regardless of lymph node involvement, local recurrences were found in 12/40 cases (30 %) in group I and 12/100 cases (12 %) in group II: the difference is significant (chi2 = 6.517, df = 1, p < .02). It is concluded that low rectal cancers have specific characteristics: they are more lymphophile. The distal spread is more common. The risk of local recurrences is major for Dukes B tumours (30 %), and zero for Dukes A tumours.
FP-32 Multicentered Randomized Trial Comparing Esophagectomy vs Primary Chemo-Irradiation for Squamous Esophageal Cancer : An Analysis on Early Outcomes and Quality of Life Philip Wai Yan Chiu1, Angus CW Chan2, Enders KW Ng1, Danny WH Lee2, SF Leung3, J Griffith4, Simon KH Wong 5, WT Siu5, Micheal KW Li5, Peter KH Kwong6, HT Leong2, Alex CM Au Yeung1, Candice CH Lam1, Sydney CS Chung1 1 Department of Surgery, Prince of Wales Hospital, 2Department of Surgery, Northern District Hospital, 3Department of Oncology, 4 Department of Radiology, Prince of Wales Hospital, 5Department of Surgery, Pamela Youde Nethersole Eastern Hospital, 6Department of Surgery, United Christian Hospital, Hong Kong, China Aim We conducted a prospective randomized trial to compare the efficacy, survival and quality of life achieved by primary chemoirradiation to that by esophagectomy. Method From July 2000 to 2003, 66 patients with potentially operable squamous cell carcinoma of mid or lower thoracic esophagus were randomized. Two or three-staged esophagectomy with 2-field dissection were performed. Patients treated with chemoirradiation received continuous 5-fluorouracil infusion (200mg/m2/day) from day 1 to 42 and cis-platin (60mg/m2) on day 1 and 22. The tumor and regional lymphatics were concomitantly irradiated with a total of 60 Gy. Tumor response was assessed by endoscopy, EUS and CT scan. Salvage esophagectomy was performed for incomplete response or recurrence. The quality of life were assessed by EORTC OES-24 before and 3 months after therapy. Results 36 patients received standard esophagectomy, while 30 were treated with primary chemoirradiation. Median followup was 19 months. The operative mortality was 8.3%. The rate of postoperative complication was 38.9%. There was no difference in the early cumulative survival between the two groups (Log rank test p = 0.26). There were a higher proportion of patients complaint of indigestion in the esophagectomy group (p = 0.001). Otherwise there is no different between the groups in other aspects of EORTC OES-24 before and 3 months after therapy. Conclusions Primary surgery and primary chemoirradiation offered similar early clinical outcome, quality of life and survival for patients with squamous cell carcinoma of the esophagus. The challenge lies in the detection of residue disease after primary chemoirradiation.
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FP-33 Proposal for a Reclassification of Liver Based Anatomy on Portal Ramifications Akihiro Cho 1, Shinichi Okazumi 2, Harufumi Makino 3, Kiyohiko Shutou2, Ryouyu Mochiduki2, Takayuki Tohma2, Katsuhiko Matsubara2, Hisashi Gunji2, Takumi Ohta2, Seiji Arita1, Naoto Koike1, Naohide Isaka 1, Kenichi Kusume1, Hidehiko Kashiwabara1, Hiroshi Yamamoto4, Munemasa Ryu5, Takenori Ochiai2 1 Surgery, Seirei Sakura Citizen Hospital, 2Department of Academic Surgery, Graduate School of Medicine, Chiba University, 3 Research Center for Frontier Medical Engineering, Chiba University, 4Department of Surgery, Chiba Cancer Center Hospital, 5 Department of Surgery, Chiba Prefectural Sawara Hospital, Japan Purpose: Portal branching patterns which differ from those previously described are occasionally encountered during liver surgery. Thus, we reevaluated the ramification patterns of the portal branches in the right hemiliver using computed tomography during arterial portography (CTAP). In addition, we propose a more practical classification of the liver. Methods: A total of 60 patients with normal intrahepatic venous anatomy underwent helical CTAP. Next, three dimensional portograms were reconstructed to verify the locations of the portal veins. Portal branching patterns in the right hemiliver were assessed. Results: In all 60 patients examined, the right anterior portal vein bifurcated into the ventral and dorsal branches. The anterior fissure vein was located between the ventral and dorsal branches. In 42 (70%) of 60 patients, the posterior portal vein did not bifurcated, but some superior and inferior branches arose from the right posterior portal trunk. Conclusions: We propose that the right liver should be divided longitudinally into three segments, which are designated as the anterior, middle, and posterior segments. The conventional anterior segment described by previous reports is divided into the anterior and middle segments by the anterior fissure. The introduction of our segmental anatomy and surgical procedure will allow more systematic and limited liver resections.
FP-34 Proposal for Anatomical Reclassification of the Dorsal Liver Baik-Hwan Cho, Doo Hyun Yang, Jung Hun Lee, Sang Koo Kang, Eun Jeong Jo Surgery, Chonbuk National University Hospital, Korea PURPOSE: The present study was designed to verify precise surgical planes anatomically in the dorsal liver. Currently most of liver surgeons underwent hepatectomy using anterior approach to mobilize liver minimally. After anterior dissection, surgeon should decide the final target plane in the dorsal liver. Frequently the complexity of dorsal liver put us to confuse to make the decision. The hanging maneuver itself may indicate the final target plane. But many surgeons cut short hepatic veins before the insertion of a forceps through avascular space between dorsal liver and inferior vena cava, which may deviates the target plane. METHODS: We dissected 44 formalin-fixed dorsal liver segments to define the territories of dorsal liver according to the short portal veins (b, c, d by Couinaud and i by Ishiyama). RESULTS: Couinaud’s segment IX was divided into 4 territories (b, c, d and caudate process) according to the supplying territories
of Couinaud’s b, c, d veins. Segment I was divided into two (i territory and Spiegle’s lobe) by the land mark of ventral margin of the lesser omentum. Total numbers of short portal veins in both segment I and IX is almost same (50:50), but their origins are slightly shifted to the left portal side (60:40). CONCLUSIONS: Clear delineation of the territories of dorsal liver according to the short portal veins appeared to be possible when the invisible dorsal liver was divided along a straight line around the IVC.
FP-35 The Effect of Combined Hepatic Resection for Hilar Cholangiocarcinoma: Comparison with Nonsurgical Metallic Stent Insertion Dongwook Choi, Kwangil Ha, Sangbeom Kim, Sunhoo Park, Byunghee Lee Department of Surgery, Korea Cancer Center Hospital, Korea Purpose: The range of the treatment option for hilar cholangiocarcinoma varies from a curative resection including hepatectomy to minimal therapy with percutaneously placed stent insertion. However, combined hepatic resection for hilar cholangiocarcinoma seems to be accepted as important procedure since the excellent results of professor Nimura in 1990. This study was conducted to evaluate the resectability including pathological curability and postoperative morbidity and mortality following combined hepatic resection for hilar cholangiocarcinoma and to assess the survival benefit compared with nonsurgical metallic stent insertion. Method: In Korea Cancer Center Hospital, 34 hilar cholangiocarcinoma patients (stent group) underwent nonsurgical metallic stent insertion from Sep-1991 through Sep-1994 due to both no information on surgery and reluctance to surgery. On the other hand, 57 patients (surgery group) were operated on for curative resection including hepatectomy from Mar-1994 to Oct-2003. Various combined hepatectomies with bile duct resection including 8 hepatopancreaticoduodenectomy were performed after biliary drainage. Results: Resectability was 86.0% (49/57) and pathologically curative resection rate was 77.3% (38/49). 34 patients developed postoperative complications (69.4%). Among them, 4 patients died without discharge, so in-hospital mortality was 8.1%. For the stent group, 1,3 YSR was 32.6% and 0%. For the surgery group including unresectable cases 1,3,5 YSR were 71.3%, 37%, 27.0% (p=0.0001), respectively. For pathologically curative group, 5 YSR was 41.2%. On univariate analysis, well differentiated carcinoma and polypoid tumor showed better survival rates. Conclusion: Surgical resection including combined hepatectomy for hilar cholangioncarcinoma should be performed, in case that evident contraindication for resection is absent.
FP-36 Two Stage Hepatectomy Using the New Method for Future Remnant Liver Volume Growing in the Patient with Initially Non- resectable Colon Cancer Liver Metastases Chong Woo Chu1, Hyung Cheol Kim2, Eung Jin Shin2, Cheol Wan Lim2, Gyu Seok Cho2, Ok Pyung Song2, Ki Won Yu2 1 Surgery, 2General Surgery, Soonchunhyang University Hospital, Korea Multiple bilobar liver metastases are the main cause of low resectability in the colon cancer liver metastases. The authors
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experienced one case of initially non-resectable colon cancer liver metastases. He was curatively and safely treated with a two-stage hepatectomy using the new method of future remnant liver volume growing. A 54-year-old man was referred to our department with the sigmoid colon cancer combined with MBLM, which were checked in two small metastatic lesions in the left lobe and five large sized lesions in the right lobe in the computed tomogram. A laparoscopic assisted anterior resection was primarily performed. We performed the 1st stage hepatectomy 3 weeks after the colon resection. Intra-operative Ultrasonogram found 9 small superficial metastatic lesions in the left lobe. All that lesions were completely removed by non-anatomical wedge resection. An occlusion balloon catheter was placed in the right portal vein through a small branch of the inferior mesenteric vein at that time. The future remnant liver volume was sufficiently increased 3 weeks after the 1st hepatectomy. A right hepatectomy was safely performed 22 days after the 1st hepatectomy. The patient had received a regional chemotherapy (IL2 based immuno-chemotherapy through hepatic artery) for 6 months, then has been receiving a systemic chemotherapy (biweekly Oxaliplatin, leucovorin, plus 5-fluorouracil) without any recurrence evidence.
FP-37 Loss of CEACAM1 Expression Indicates both Dedifferentiation and Aggressive Biology in Hepatocellular Carcinoma Pauldion Venzon Cruz, Toshifumi Wakai, Yoshio Shirai, Naoyuki Yokoyama, Katsuyoshi Hatakeyama Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Japan PURPOSE. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is expressed by normal hepatocytes and well differentiated hepatocellular carcinoma cells. We hypothesized that loss of CEACAM1 expression indicates poor differentiation in hepatocellular carcinoma and predicts poor outcome after resection. METHODS. A retrospective analysis was conducted of 139 patients who underwent a curative resection for hepatocellular carcinoma. Immunohistochemical examination of the resected specimen was conducted using monoclonal anti-CEACAM1. CEACAM1-positive tumor was defined immunohistochemically as a homogeneously stained tumor, whereas CEACAM1-negative tumor as a tumor having distinct unstained areas within the tumor. The median follow-up period was 83 months. RESULTS. One hundred and thirteen tumors were classified as CEACAM1-positive and 26 were classified as CEACAM1-negative. The area with loss of CEACAM1 expression was always noted in the areas of the tumor having the highest histologic grade. The incidences of CEACAM1-negative tumors were 0% in Edmondson-Steiner grade I, 5% in grade II, and 66% in grade III plus IV; loss of CEACAM1 expression was more frequent in poorly differentiated tumors (P < 0.001). CEACAM1-negative tumors showed a significantly higher incidence of portal vein invasion (16/26, 62%) than CEACAM1-positive tumors (22/113, 19%; P < 0.001). CEACAM1 expression was the strongest independent prognostic factor by univariate (P < 0.0001) and multivariate (relative risk, 7.38; P < 0.001) analyses. CONCLUSIONS. Loss of CEACAM1 expression represents dedifferentiation in hepatocellular carcinoma and emerges as a late event in hepatocellular carcinogenesis. CEACAM1-negative tumors are biologically aggressive and thus bear worse prognosis after resection.
Journal of Gastrointestinal Surgery
FP-38 Covering Ileostomy after Low Rectal Resection: Can We Give up the Habit? Raffaele De Luca, Fernando Prete, Paolo Nitti, Leonardo Vincenti, Francesco Paolo Prete “C. Righetti” General Surgery -Department of Emergency and Organ Transplant, Policlinico Hospital - Bari, Italy STATE THE PURPOSE: The protection ileostomy of coloanal and lower colorectal anastomosis is of use in many colorectal surgery unit; however, as the leakage rate in these cases is around 20%, 4 times out of 5 it would be useless. A modality defined “ghost ileostomy” is prospectively evaluated in this pilot study, with the aim to avoid unnecessary fecal diversions. METHODS: Completed the resection-anastomosis, the ileal tract for the possible stoma is searched and surrounded with a vessel-loop, and his afferent branch identified with a stitch; the vessel-loop is retracted outwards and fixed without traction to the overlooking skin. The clinical course of the patient is strictly followed: in absence of complication the loop is removed in the second week; otherwise at the first suspect of anastomotic leakage we proceed, in local anesthesia to enlarge the incision, by pulling the vessel-loop, thus completing the ileostomy. RESULTS: From January 2001 to May 2004 52 patients (29 M; 23 F, mean age 54) with low colorectal (29) and coloanal (23) anastomosis after resection for primary rectal cancer received this so-called “ghost ileostomy”. Only 7 of the 52 patients needed a postoperative diverting ileostomy: 6 in local anesthesia and 1 under general anesthesia for open peritoneal washing. No perioperative mortality (30 days). In the remaining patients the loop was removed after 8-12 days without consequences. CONCLUSIONS: Finally only 13% of the lower anastomoses required a diverting stoma, with consistent advantage in terms of compliance and cost saving, without worsening of the prognosis.
FP-39 Early Results of Exvivo Sentinel Lymph Node Mapping in the Patients with Early-Staged Colorectal Carcinoma Sezai Demirbas, Mehmet Ince, Huseyin Baloglu, Tuncay Celenk General Surgery, GATA Haydarpasa Teaching Hospital, Turkey Introduction; Correct determination of lymphatic nodal statement is necessary to stage accurately and to predict survival. As it is so critical to make an evaluation about the adjacent lymph node(s) this study was designed to make a sensitive detection on the sentinel lymph nodes (SLN) indicating tumoral lymphatic basin by using ultrastaging pathologic examination . Patients and Methods; From June 2002 to June 2003, this prospective study was performed in 46 patients undergoing standard resection for colorectal cancer. In this study we employed the exvivo SLN mapping technique. Results; At least one SLN in 37 of 41 patients was identified (90.2%). The lymph nodes (LN) from those patients were utilized by Hematoxilene and Eosin dye (H&E) and mutisectioning. Then 20/37 patients with trace of the metastasis were found. Remaining 17 patients without any metastatic LN by H&E were applied to clarify micrometastases (MM) by using immunohistochemical (IHC) staining technique. 2 patients (11.7%) had MM in the SLN(s). Then Upstaging was evaluated in those 2. The sensitivity of SLNs was obtained as 90%. In two patients with no metastatic
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SLN had metastasis in the non-sentinel LNs. Conclusion; MM in the SLN identified by IHC in the patients with CRC is still not obvious to display dreadful prognosis. But upstaging and the need for treatment alteration in those patients were obvious.
FP-40 Protective Effect of Affiliating Portosystemic Shunt on Smallfor-Size Liver Transplantation JH Dong1, JJ Leng2 1 Southwest Hospital & Institute of Hepatobiliary Surgery, 2Institute & Hospital of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, China Objectives To evaluate the protective effects of affiliating portosystemic shunt on small-for-size graft. Meterials and Methods Animal models were established with skeletonized and denervated anatomic dissection around the liver, hepatectomy and perfusion in situ. Chinese Bama miniature pigs were divided into three groups (n=5): (a) control group, small-for-size liver transplantation. (b) group A, distal splenorenal shunt + small-for-size liver transplantation. (c) group B, mesocaval H-shape shunt + small-forsize liver transplantation. Animals were followed for 7 days with survival, dynamical liver function biochemical parameters, liver biopsies, portal venous pressure (PVP) and portal blood flow (PBF). Results Animal survivals were as follows: control group, 1/5, group A, 3/5 and group B, 5/5. Control group resulted in abnormal liver function parameters that were significantly ameliorated in group A and B. The histological examination of graft in control group displayed severe pathologic changes including hepatocyte cacuolar change or necrosis, sinusoidal congestion, parenchymal hemorrhage. Affiliating portosystemic shunt significantly alleviated graft injuries in group A and B. PVP rose and peaked up to 28.6mmHg, PBF fluctuated after reperfusion in control group, but group A and B with affiliating protosystemic shunt showed significantly lower PVP and maintained rather stable PBF after reperfusion. There were also statistical differences in PVP or PBF between group A and B. Conclusions Affiliating portosystemic shunt effectively protect small-for-size graft from injuries after reperfusion.
FP-41 Superficial Cancer Spread is Frequently Observed in the Superficial Raised Type of Gallbladder Cancer Hidetoshi Eguchi1, Osamu Ishikawa1, Hiroaki Ohigashi1, Yo Sasaki1, Terumasa Yamada1, Yuichiro Doki1, Isao Miyashiro1, Kohei Murata1, Ko Takachi1, Shingo Noura1, Shigekazu Yokoyama2, Tsutomu Kasugai1, Shingi Imaoka1 1 Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 2Surgery, Suita Municipal Hospital, Japan (Background) A simple cholecystectomy for early gallbladder cancer should be carefully done not to leave cancer cells behind at the surgical margins, because it has been reported that considerable percentage of gallbladder cancers are accompanied with superficial cancer spread. (Patients and Methods) Thirty-two patients with gallbladder cancer invading no more than perimuscular connective tissue underwent surgical resection in our hospital, and resected specimens were investigated macroscopically and microscopically to determine the histopathological patterns of the superficial cancer spread and a high risk factor of this event. (Results) Sixty-six
percent of all cases were accompanied with superficial cancer spread. Univariate analyses revealed that the macroscopic morphology of the primary tumor and the depth of cancer invasion in the gallbladder wall (pT category) were the predictive factors for having superficial spread. Furthermore, multivariate analysis revealed that the macroscopic morphology of the primary tumor was the independent predictive factor. Gallbladder cancers invading perimuscular connective tissue were accompanied with more widely extended superficial spread than those invading only lamina propria or muscle layer. (Conclusions) Superficial raised type gallbladder cancers are frequently accompanied with superficial cancer spread, to which we need to confirm not to leave cancer cells behind at the cut margin of the cystic duct by using intraoperative frozen-section histology in performing the cholecystectomy.
FP-42 Surgical Management and Complex Treatment of Infected Pancreatic Necrosis: 18-Year Experience at a Single Centre Gyula Farkas1, Janos Marton1, Laszlo Leindler1, Edit Szederkenyi1, Yvette Mandi2 1 Department of Surgery, University of Szeged, Faculty of Medicine, 2University of Szeged, Faculty of Medicine, Institute of Microbiology, Hungary Introdation: Infected pancreatic necrosis (IPN), the most severe form of acute pancreatitis, is responsible for most cases of pancreatitis-related morbidity and mortality. In this study, we present 18year experience on 216 patients who underwent surgery for IPN. Methods: Since 1986, 216 patients with IPN have been treated. The mean APACHE II score was 17.5 (range 11-32). The surgical treatment was performed on average 18.5 days (range 8-25 days) after the onset of acute pancreatitis. The operative management consisted of wide-ranging necrosectomy in the total affected area, combined with wide-spread drainage and continuous lavage. In 106 of the 216 cases (49%), some other surgical intervention (distal pancreatic resection, splenectomy, total pancreatectomy, cholecystectomy, sphincteroplasty, gastric suture, or colon resection) was also performed. Following surgery, the supportive therapy consisted of immunonutrition (glutamine and arginine supplementation) and modification of cytokine production with pentoxifyllin and dexamethasone. Results: Following surgery, continuous widespread lavage was applied for an average of 44.5 days (range 21-95 days), with an average of 9.5 (range 5-20) litres of saline per day. The bacteriological findings revealed mainly enteral bacteria, but Candida infection was also frequently detected. The incidence of fungal infection was 21%. Forty-seven patients (22%) had to undergo reoperation. The overall hospital mortality was 7.8% (17 patients died). Conclusion: In our experience, infected pancreatic necrosis responds well to adequate surgical treatment, continuous, long-standing wide-spread drainage and lavage, together with supportive therapy consisting of immunonutrition and modification of cytokine production, combined with adequate antibiotic and antifungal medication.
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FP-43 The Impact of Technical Complications on Short Term Adverse Outcomes and Survival after Esophagectomy Lorenzo Edwin Ferri, Simon Law, Kam-Ho Wong, Ka-Fai Kwok, John Wong Department of Surgery, University of Hong Kong, Hong Kong, China Purpose: The dismal survival associated with esophagectomy for cancer has led to the search for potentially correctable factors responsible for this poor prognosis. Although there have been suggestions that technical complications are associated with shortterm adverse outcomes and operative mortality, the impact on long-term survival remains controversial. Methods: From 19902002, 434 patients underwent esophagectomy for intrathoracic squamous cell carcinoma. Prospectively collected data were reviewed for the presence of technical complications. Patient, tumor, and operative characteristics and short-term adverse outcomes and survival were compared between 98 patients with and 336 patients without technical complications. Fisher’s exact test or Mann-Whitney U-test determined significance (*p<0.05). Multivariate analysis defined predictors for long-term survival. Results: Technical complications occurred in 22.6% (most common technical complications: recurrent laryngeal nerve palsy-10.6%, hemorrhage-3.5%, leak-3%, chylothorax-2.5%). Technical complications resulted in increased pulmonary morbidity (37.8% vs. 10.7%)* and hospital mortality (9.2% vs. 3.3%)*, but no difference in 30-day mortality (2% vs. 1.2%). No significant difference was noted in median survival (14.4 vs. 18.8 months) and 5-year survival rates (20.9% vs. 22.4%). Reduced survival was predicted by male gender (Hazard Ratio=1.52:95% Confidence Interval=1.11-2.06)*, stage III/IV (1.97:1.52-2.54)*, cirrhosis (2.36:1.11-5.05)*, proximal tumors (1.48:1.07-2.06)*, and R1/R2 resection (2.53:1.94-3.32)*, but not technical complications. Conclusions: Although shortterm adverse outcomes and hospital mortality are increased, no lasting effect on long-term survival is seen in patients with technical complications after esophagectomy.
FP-44 Inguinal Hernia Management: The Rationale for Watchful Waiting Robert Fitzgibbons Dept. of Surgery, Creighton University, USA Modern inguinal herniorrhaphies have a low recurrence rate which makes them effective at preventing life threatening complications such as bowel obstruction or strangulation. They can be performed in an outpatient setting under local anesthesia and are associated with an uneventful recovery in most. For these reasons, surgeons are taught that all inguinal hernias should be repaired at diagnosis. In fact, the natural history of an untreated inguinal hernia is poorly understood with almost no modern data available. The most important question is the incidence of life threatening. Recent evidence suggests that the mortality and morbidity may be much less than has been historically stated. At the same, it is now realized that inguinal herniorrhaphy results in greater morbidity than has previously been appreciated. Now that the recurrence rate has been brought down to a minimum using modern hernioplasty techniques, chronic postoperative groin pain syndromes have emerged as the biggest issue facing inguinal hernia surgeons.
Journal of Gastrointestinal Surgery
Despite popular wisdom to the contrary, it may be that asymptomatic patients with inguinal hernias can safely delay surgical treatment in favor of careful watchful waiting (WW) as the method of management for their hernia. This information represents the background for the development of a randomized, prospective clinical trial with minimally symptomatic patients being randomized to Watchful Waiting vs. conventional Lichtenstein tensionfree herniorrhaphy ( RO 1 HS/AG 9860-01A1). Although results will not be available until March 2005, this background is the subject of this presentation.
FP-45 Liver Metastasis-Associated Genes Identified with High Density DNA Microarray in Highly Liver Metastatic Human Breast Cancer Model Rika Fukui 1, Hidefumi Nishimori 1, Fumitake Hata 1, Takahiro Yasoshima2, Keisuke Ohno1, Yoshiyuki Yanai1, Eiri Ezoe1, Kenjiro Kamiguchi3, Ryuichi Denno1, Noriyuki Sato3, Koichi Hirata1 1 Dept. of Surgery 1, Sapporo Medical University, 2Dept. of Surgery and Institute of Gastroenterology, Shin-Sapporo Keiaikai Hospital, 3Dept. of Pathology 1, Sapporo Medical University, Japan [Introduction] A variety of biological and molecular changes are implicated in multiple steps of cancer metastasis to the liver. To clarify the mechanism of liver metastasis in breast cancer, we established a highly liver metastasis mouse model, ZR-H4, derived from parental human breast cancer cell lines, ZR-75-1, and analyzed a differential gene expression using DNA microarray. [Materials and Methods] First, we established a highly liver metastatic mouse model, ZR-H4, by repeated intrasplenic injection method. Subsequently, using DNA microarray (U133 Gene Chip set, Affymetrix), representing roughly 33,000 genes, we analyzed a wide range of gene expression between ZR-H4 and ZR-75-1 cell lines. [Results] ZR-H4 showed highly liver metastatic rate compared with parental ZR-75-1. In ZR-H4 compared with ZR-75-1 cell line, seventy-one genes including TGF-α, LTBP3 and so on, were overexpressed and 99 including MMP-1, MAP3K10 and so on, were underexpressed showing 3-fold differences in expression levels. [Conclusions] Our established model might be very useful for investigating the mechanism of liver metastasis. Moreover, genes revealed by array analysis will be novel molecular markers to predict the development of liver metastasis after curative resection.
FP-46 Mechanisms of Intestinal Adaptation after Total Proctocolectomy (TPC): Lessons from Animal Models Kouhei Fukushima1, Shun Sato2, Kaori Koyama3, Sho Haneda1, Yuji Funayama 1, Chikashi Shibata1, Ken-Ichi Takahashi1, Munenori Nagao1, Kazuaki Watanabe1, Hiroo Naito4, Iwao Sasaki1 1 Surgery, Tohoku Univ. Graduate School of Med., 2Iwaki Kyoritu Hospital, 3Fukushima Rosai Hospital, 4Kennann Tyukaku Hospital, Japan Patients who had a total proctocolectomy (TPC) suffer from persistent diarrhea and frequent bowel movement, resulting in sodium deficit, dehydration and impaired quality of life. Analysis of the intestinal adaptation may lead to developing novel therapies for the post-operative diarrhea. To assess molecular and functional changes after TPC a rat TPC
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model was established. Dietary sodium-depleted and aldosteroneinfused rats were also used to evaluate effects of endogeneous or exogeneous aldosterone in phenotypic changes of epithelial cells. We investigated ileal expression of epithelial sodium channel (ENaC), 11b-hydroxysteroid dehydrogenase type 2 (11b-HSD2), Na/K ATPase, prostasin, sodium glucose transporter 1 (SGLT1) and mineralocorticoid receptors (MR), which determine sodium absorption from the apical side, aldosterone specificity, sodium extrusion from the basal side, activation of ENaC, glucose-coupled sodium transport or aldosterone signal, respectively. We used an Ussing chamber technique to evaluate active sodium absorption and aldosterone reactivity of ileal mucosae. Epithelial cells of the ileum exhibited induction of three subunits of ENaC, 11b-HSD2, prostasin and SGLT1 after TPC without marked morphological changes. The remnant ileum exhibited enhanced electrogenic and amiloride-sensitive sodium absorption and aldosterone-reactivity in a strictly site-dependent fashion. Aldosterone infusion could induce those molecules except for SGLT1, suggesting that aldosterone has major roles for ileal induction of sodium transport machinery originally equipped in the colon. In conclusion, aldosterone-mediated induction of those molecules appears to be essential for the functional adaptation after TPC. Local delivery of aldosterone into the ileal mucosa is a novel therapeutic approach to promote the intestinal adaptation.
FP-47 Postoperative Clinical Course in Crohn’s Disease Predicted from the Reoperative Findings Yuji Funayama, Kouhei Fukushima, Chikashi Shibata, Ken-Ichi Takahashi, Tatsuya Ueno, Munenori Nagao, Kazuhiro Watanabe, Sho Haneda, Katsumasa Kudo, Atsushi Kouyama, Iwao Sasaki Department of Surgery, Division of GI & Colorectal Surgery, Tohoku University, Japan [Aim] To clarify the mode of recurrence at the surgical sites after the initial operation, medical records of 107 cases of reoperation was analyzed. [Patients and Methods] Operative results of 107 reoperations were analyzed. The behavior and the disease location was classified with Vienna Classification. Statistical analysis was done using chi-square test and significant difference was determined by p<0.05. [Results] 1. Behavior: The comlications after the initial operation were similar as that before the initial operation. (p=0.0014) Perforating type was likely to show as the same type even in the reoperation. (p<0.004) 2. Location: Disease location at reoperation was similar as that of the initial operation. (p<0.0001) 3. Recurrence rates at the surgical sites: Cumulative risk of reoperation after intestinal resection and anastomosis was similar as that after strictureplasty per patient. Cumulative risk of reoperation in each anastomosis was also similar as that in each strictureplasty site. 4. Comlications in each surgical site: The risk of postoperative penetrating disease after strictureplasty was significantly lower than after anastomosis. (p<0.001) [Conclusion]Clinical course after surgery was seemed to be determined by the individual nature . The penetrating disease after strictureplasty was significantly infrequent. The clinical course and the mode of recurrence after surgery could be evaluated to some extent.
FP-48 Cystic Neoplasms of the Pancreas with Mucin-production: IPMT versus MCT Brian Kim-Poh Goh1, Yu-Meng Tan2, Peng-Chung Cheow3, Alexander YF Chung3, Pierce KH Chow3, Wai-Keong Wong3, London LPJ Ooi2 1 General Surgery, Singapore General Hospital, 2Department of Surgical Oncology, National Cancer Center, Singapore, 3Department of General Surgery, Singapore General Hospital, Singapore Aim: To compare the clinicopathological features of intraductal papillary mucinous cystic tumours (IPMT) and mucinous cystic tumours (MCT) of the pancreas and determine the similarities and differences between these 2 lesions. In addition, predictive factors of malignancy in IPMT and MCT were analyzed. Methods: Thirty-six patients with mucin-producing cystic neoplasms of the pancreas (18 IPMT and 18 MCT) who underwent surgical resection between 1990 to 2004 at the Department of General Surgery, Singapore General Hospital were retrospectively reviewed. The clinicopathological features between these 2 entities were compared using univariate analysis. Furthermore, statistical analysis of potential predictive factors of malignancy for each of these 2 groups were conducted. Results: Patients with IPMT were found to be older (64+/-10 years) than cases with MCT (43+/-18, p<0.001). There was a significantly higher male:female ratio in IPMTs (5:4) as compared to MCTs (1:17, p=0.003). The presence of a palpable mass was also significantly associated with MCT (p=0.003). IPMTs were usually located at the head (50%) whereas MCT were found in the body-tail region (100%) of the pancreas (p=0.001). Histopathologically, the IPMT was distinct from MCT in terms of size (3.8+/-3.2 vs 9.1+/-4.4, p=0.001), association with secondary pancreatitis (50% vs 0%, p=0.011), communication with the pancreatic duct (94% vs 0%, p<0.001), intraductal growth (100% vs 0%, p<0.001) and the presence of a dilated main pancreatic duct (61% vs 0%, p< 0.001). On the other hand, the presence of ovarian-type stroma (44% vs 0%, p=0.003) and a fibrous capsule (100% vs 6%, p<0.001) were associated with MCT. Larger cyst size and the presence of a dilated main pancreatic duct were found to be significant predictive factors of malignancy in IPMT. Predictors of malignancy in MCT were a larger cyst size and the presence of a mural nodule. The short-term survival was excellent in both groups with only 1 operative mortality in the IPMT group after a median follow-up of 15 months (range, 0-63). Conclusion: This study demonstrates significant clinicopathological differences between IPMT and MCT. These 2 cystic tumors should thus be regarded as distinct clinicopathological entities.
FP-49 Intra-abdominal Lymphangioma: A Comparison between Paediatric and Adult Patients Brian Kim-Poh Goh1, Yu-Meng Tan1, Hock-Soo Ong1, Chan-Hon Chui2, London Lucien Ooi1, Pierce K. H. Chow1, Carolyn E. L. Tan2, Wai-Keong Wong1 1 General Surgery, Singapore General Hospital, 2Dept of Pediatric Surgery, KK Women’s and Children’s Hospital, Singapore Purpose: Intra-abdominal lymphangiomas are rare, congenital malformations of the lymphatics which are found predominantly in children. The aim of this study is to evaluate the clinical features of this tumour, highlighting the differences in adults and paediatric
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patients. We also evaluate the preoperative diagnosis, radiological features, surgical treatment and outcome of this rare condition. Patients and methods: Between 1990 and 2004, 14 patients who underwent surgical resection of an intra-abdominal lymphangioma were reviewed retrospectively. Results: There were 5 paediatric patients aged 17 years or less and 9 adults aged between 31 to 62 years. Overall, females outnumbered males in the series with a male-to-female ratio of 3:4. However, males predominated in the paediatric age group with a male-to-female ratio of 1.5:1. The clinical presentation of children was more acute ranging from 3 days to 2 months. In adults, four patients were asymptomatic and the remaining five had symptom duration ranging from 2 weeks to a year. The lymphangiomas occurred in the mesentery (n=4), retroperitoneum (n=4), omentum (n=3), pancreas (n=2) and spleen (n=1). All the patients underwent total surgical resection with or without organ resection and there were no recurrences at a median follow-up of 2 years (range, 3 months to 13 years). Conclusion: This study suggests a difference in the biological characteristic and behaviour of intra-abdominal lymphangiomas presenting in paediatric patients compared to adults. Intra-abdominal lymphangiomas diagnosed in children tend to predominate in males, have a more aggressive behaviour and present more acutely as opposed to those diagnosed in adults.
FP-50 Synergistic Anti-tumor Effect Produced by Transfer of AntiAngiogenic Factor Genes on Colon Tumor Yoshio Gunji, Masaya Uesato, Shinichi Miyazaki, Hideaki Shimada, Hisahiro Matsubara, Yoshihiro Nabeya, Keiji Kouda, Harufumi Makino, Takenori Ochiai Academic Surgery (M9), Chiba University, Japan Anti-angiogenic factors are potent endothelial cell growth inhibitors that have been shown to inhibit angiogenesis in vitro and tumor growth in mice. We have demonstrated the synergistic anti-tumor effect of anti-angiogenic genes (mouse angiostatin: pBLAST-mAngio, and mouse endostatin: p-BLAST42-mEndo XV) delivered to tumors by low-voltage electroporation in mouse colon 26 models. A synergistic anti-tumor effect was strongly suggested by in vivo tumor growth kinetics, as well as in survival studies with the mice. RT-PCR confirmed the fragments of each gene were transferred by low-voltage electroporation in the tumor. Decreased microvessel density measurements in tumors also confirmed the efficacy of the synergistic anti-tumor effect of both genes. Significant growth inhibition was observed in mice treated with a 1:1-proportion of angiostatin and endostatin genes, and the order of the both genes transferred (first the endostatin-gene, followed one week later by the angiostatin-gene) had a profound inhibitory effect on tumor growth. These data suggest that in vivo delivery of anti-angiogenic genes with low-voltage electroporation could be a possible therapeutic strategy for established solid tumors when both genes were applied in combination.
Journal of Gastrointestinal Surgery
FP-51 Surgery for Advanced Gallbladder Carcinoma Rajesh Gupta1, Thakur Deen Yadav1, Sabareesh Kumar Natarajan1, Jai Dev Wig1, Naveen Kalra2, Niranjan Kumar Khandelwal2, Sudha Suri2 1 Dept. of General Surgery, 2Dept. of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, India Purpose: To assess resectability rate and morbidity and mortality after surgery for carcinoma of gall bladder Methods: Prospective ongoing study from May 2002. Patients with clinical, sonographic or CT suggestion of carcinoma gall bladder with or without pathological confirmation were included.Results: There were 48 patients during 2 years up to May 2004 with median age of 50 years (3375). The male to female ratio was 1: 2.7. There were 8 patients with Stage III, 19 with Stage IVa and 19 with Stage IVb according to TNM classification. 17/48 patients had metastatic disease on preoperative evaluation and were not explored. Out of the remaining 31 patients undergoing exploration, 16 underwent resection and 15 were unresectable. The surgery included wedge resection in 6, Segment IV b and V liver resection in 10 patients. N1 lymph nodal dissection was done in 4, N2 in 10 and M1 in 2 patients. CBD resection was performed in 11, segmental duodenal resection in 1 and colonic resection in 1patient. Mean oper tive time was 7.08 + 1.7 hours with average blood loss of 570ml. (200-1000ml). 5 patients did not require any transfusion. Median postoperative stay for the operated patients was 17days (6-37). 5/16 patients had morbidity (31.3%), which included superficial wound sepsis in 3, hypoalbuminemia in 1 and biliary leak in 2. Both the patients with biliary leak died with mortality of 12.5%. Conclusions: Resectability was 33% in this series despite the advanced stage of disease in all of our patients. Hepaticojejunostomy leak was major predisposing factor contributing to mortality in both our patients.
FP-52 Intraluminal Brachytherapy for Positive Surgical Margin after Resection of the Bile Duct Carcinoma: Does it Play a Role? Kenichi Hakamada, Kazunori Aoki, Yoshikazu Toyoki, Shunji Narumi, Mutsuo Sasaki Department of Surgery II, Hirosaki University, Japan [Background and Aims] Intraluminal brachytherapy and biliary stents have been widely used in the treatment of patients with unresectable bile duct carcinoma. But the efficacy of brachytherapy for the positive bile duct margin after palliative resection is not clarified yet. The purpose of this study was to evaluate the effect of intralumninal brachytherapy on survival and types of recurrence of patients with positive surgical margin after resection of the bile duct carcinoma. [Patients] Fifteen patients with positive margin after resection of the bile duct carcinoma between 1955 and 2003 were included. Seven patients underwent adjuvant brachytherapy (4 with biliary stenting) while seven was treated with surgery alone. One patient was treated with brachytherapy and biliary stenting for a recurrent disease. [Results] Patient survivals with brachythearpy alone, brachytherapy plus biliary stent , and surgery alone were 67%, 75%, 88% at 1 year, 67%, 38%, 50% at 2 years, and 67%, 0%, 33% at 3 years, which showed no statistical differences. Death related to local recurrence was 100% (5/5) in patients with brachytheapy and 57% (4/7) without brachytherapy. [Conclusion] Intraluminal brachytherapy for positive surgical margin after
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resection of the bile duct carcinoma did not prolong patient survival nor reduce death rates related to local recurrence.
FP-53 Predicting Factors for Operative Morbidity and Mortality of Gastric Cancer Surgery Dong-Seok Han1, Do Joong Park2, Hyuk-Joon Lee2, Han-Kwang Yang2, Kuhn Uk Lee1, Kuk Jin Choe1 1 Department of Surgery, 2Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Korea Purpose: This study aimed to find out predicting factors affecting the morbidity and mortality of gastric cancer surgery. Methods: A total of consecutive 719 patients who underwent operation for gastric cancer at Seoul National University Hospital from January 2002 to December 2002 were reviewed. Results: The overall morbidity rate was 17.4% (125/719 patients) and mortality rate was 0.5% (4/719 patients). The rate of surgical complications was 14.7% (106/719 patients) and that of non-surgical complications was 3.3% (24/719 patients). When patient’s age is older (odds ratio (OR)=1.036, 95% confidence interval (CI)=1.017~1.056), tumor was resected together with other organ (morbidity rate of combined resection vs. gastrectomy only=34.3% vs. 15.4%, OR=3.254, 95% CI=1.756~6.031), and type of reconstruction after subtotal gastrectomy was gastrojejunostomy (Billroth II vs. Billroth I=17.0% vs. 9.5%, OR=1.999, 95% CI=1.054~3.791), the morbidity rates were higher. Only 3 patients with surgical complication (2.8%, 2 patients of adhesive obstruction and 1 patient of intraabdominal bleeding) needed re-operation. Conclusion: Higher operative morbidity was observed in aged patient, combined resection, and Billroth II reconstruction after radical subtotal gastrectomy. Most surgical complications could be managed nonoperatively.
FP-54 Clinicopathologic Evaluation of Long-Term Survivors Treated for Pancreas Cancer Sung-Sik Han, Sun-Whe Kim, Jin-Young Jang, Min-Gew Choi, Kuhn-Uk Lee, Yong-Hyun Park Department of Surgery, Seoul National University Hospital, Korea Purpose: The objective of this study is to determine the long-term clinical results of patients with pancreatic cancer who underwent a resection with curative intent and to investigate clinicopathologic features of 5-year survivors to determine factors associated with favorable prognosis. Methods: Among 1275 patients who admitted into Seoul National University Hospital for pancreatic cancer between 1986 and 2003, we retrospectively reviewed the records of patients who underwent resection with curative intent. Clinicopathologic features of the patients are analyzed to determine prognostic factors. After reviewing pathologic slides, we re-evaluated the detailed characteristics of long-term survivors. Results: 207 patients underwent resection with curative intent(resection rate 16.2%). There was one case of operative mortality. The 5-year survival rate was 17.2% and the median survival was 18.0 months. T stage, lymph node status, tumor size, resection margin involvement, and adjuvant chemoradiation were significant prognostic factors. Actually, twelve patients survived 5 years or more. 10
patients underwent Whipple resection and 2 patients distal pancreatectomy. Among the long-term survivors, certain patients had poor prognostic factors like large tumor size, lymph node (+). Histologic review revealed 5 cases had variant types of ductal adenocarcinoma (anaplastic, undifferentiated, mucinous (2), mucinous noncystic). Conclusion: Although well known prognostic factors generally affected the survival after curative resection, there was diversity in the clinico-pathologic features of actual long-term survivors, which suggests the patients with poor prognostic factors have the chance for cure through surgical resection. Considering the low curability for pancreatic cancer, new effective adjuvant therapy and better modality for early diagnosis are needed.
FP-55 Novel Anti-Adhesive Agent with Antibiotic Activity Kazuyoshi Hanasawa1, Mitsuhiro Fujino1, Yoshihiro Tsutamoto1, Sumihiro Kamitani1, Tohru Tani1, Seijiro Uchiyama2, Noriaki Shirahama2, Akinori Sueoka2 1 Department of Surgery, Shiga University of Medical Science, Japan, 2Kawasumi Laboratories, INC., Ohita, Japan A sodium hyaluronate and carboxymethylcellulose bioresorbable membrane was developed to reduce formation of postoperative adhesions and has been used in operations widely. But there might be some problems in use of contaminated operations such as the colorectal resection. We develop new anti-adhesional agents with antibiotic activities. We report here to determine the efficacy of our newly invented polymer crosslinked with norfloxacin (NFLX) on intra-abdominal adhesion formation. (Material and Method) We incubated Pseudomonas aeruginose, Klebsiella pneumoniae, and Escherichia coli in the medium including the polymer based on polylactic acid, polyglicol acid, and polykapurolacton crosslinked with norfloxacin (NFLX) and counted the number of bacteria until 3 days. Next, rats underwent laparotomy and peritoneal resection and were randomly assigned to receive one of the three kinds of new anti-adhesional agents with antibiotic activities or only vehicule as a control group. At postoperative Day 1-7 day, the rats underwent relaparotomy and complete adhesiolysis. An investigator who was blinded to the group assignment scored the extent of adhesion formation and the difficulty of adhesiolysis using our scale that ranged from 0 to 9 (no adhesions). (Results) 1. The number of incubated bacteria was decreased significantly in the medium including the polymer crosslinked with norfloxacin (NFLX) in all kinds of bacteria, and there were no changes in the control groups. 2. Adhesion score was improved in the treated group with our new developed materials.
FP-56 Telomerase Induces Immortalization of Human Esophageal Epithelial Cells without p16INK4a Inactivation Hideki Harada 1, Hiroshi Nakagawa 2, Kenji Oyama 2, Munenori Takaoka2, Gregory H Enders2, Yutaka Shimada3, Oliver G. Opitz4, Anil K. Rustgi2 1 Surgery, Tango Central Hospital, Japan, 2University of Pennsylvania, USA, 3Kyoto University, Japan, 4University of Freiburg, Germany Purpose: Normal human somatic cells have a finite life span and undergo replicative senescence after a limited number of cell divisions. Erosion of telomeric DNA has emerged as a key factor in
Abstract of 19th WC-ISDS
senescence that is antagonized during cell immortalization and transformation. To clarify the involvement of telomerase in the immortalization of esophageal epithelial cells, hTERT expression was restored in normal human esophageal epithelial cells (EPC2). Methods: EPC2 were retrovirally infected with either pBABE vector expressing hygromycin resistance gene (EPC2-hyg) or hTERT (EPC2-hTERT) just prior to senescence. Senescence and immortalization were monitored by growth curves, morphology as well as senescence associated β-gal staining, and expression of cell cycle regulators by western blotting. p16 and p53 were extensively examined for genetic and epigenetic alterations, and function. Results: EPC2-hTERT overcame senescence and were immortalized without p16 alterations. p16 was expressed at moderate levels, inducible with UV treatment, and bound to Cdk4 and Cdk6. There were no mutations in the p53 gene, and p53 was functionally intact upon treatment with UV light or hydroxyurea. As a parallel consideration, senescence could be activated in EPC2-hTERT by overexpression of oncogenic Ha-ras or p16. EPC2-hTERT, when placed in organotypic culture, induced basal cell hyperplasia and hyperproliferation but were not transformed. In our prolonged observation of immortalized hTERT-expressing cells, a subpopulation of cells spontaneously acquired trisomy of chromosome 20 and demonstrated anchorage-independent growth. Conclusion: The expression of telomerase induces immortalization of normal human esophageal epithelial cells without inactivation of p16 or abrogation of p53.
FP-57 Indications of Laparoscopic Surgery for Crohn’s Disease using the Vienna Classification Hirotoshi Hasegawa, Hideki Nishibori, Yoshiyuki Ishii, Koji Okabayashi, Masaki Kitajima Department of Surgery, Keio University, Japan [Aim] The aim of this study was to clarify the indications of laparoscopic surgery using the Vienna Classification. [Methods] Between September 1994 and August 2003, 89 patients with Crohn’s disease underwent 102 operations. Of these, 75 laparoscopic operations formed the basis of this study. There were 54 primary cases and 21 recurrent cases. The Vienna Classification consisting of the location (L1: terminal ileum, L2: colon, L3: ileocolon, L4: upper GI) and the behaviour (B2: stricturing, B3: penetrating) was used to compare the conversion to open procedures, major postoperative complications (anastomotic leak, abscess, bowel obstruction and others requiring reoperation) and minor complications (wound infection, bowel obstruction and others not requiring reoperation). [Results] Conversion to open procedures occurred in 7 patients (9%). Major and minor complications developed in 5 (7%) and 13 (17%), respectively. The conversion and major complications occurred more frequently in L3/L4 group than L1/L2 group with statistical significance (conversion: 5/22 vs 2/53, P=0.0204, major: 4/22 vs 1/53, P=0.0240). The major complications in B3 group were more common than those in B2 group (5/39 vs 0/36, P=0.0552). The conversion and major complications in B3L3/L4 group were significantly more common than those in the other subgroups (conversion: 5/17 vs 2/58, P=0.0057, odds ratio: 11.7, major: 4/17 vs 1/57, P=0.0089, odds ratio: 17.5), however, there were no significant differences in the complications between the laparoscopic and open groups. [Conclusions] Laparoscopic surgery is feasible and justified in patients with B3L3/L4 Crohn’s disease, however, associated with a higher conversion rate.
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FP-58 Indicators for Surgical Resection of Locally Recurrent Rectal Cancer Yojiro Hashiguchi1, Hideki Ueno1, Hirotoshi Kobayashi1, Hajime Fujimoto1, Chikara Ueno1, Masayoshi Miyoshi1, Suminori Maeshima1, Kazuo Hase2, Hidetaka Mochizuki1 1 Surgery 1, National Defense Medical College, 2Self Defense Forces Central Hospital, Japan PURPOSE: We retrospectively analyzed prognostic factors for surgical resection of local recurrence of rectal cancer. METHODS: Thirty-nine consecutive patients with locally recurrent rectal cancer, who underwent potentially curative surgical resection from 1985 to 2002, were analyzed. Mean follow-up period was 3.2 years. Clinicopatholocigal factors including age, gender, primary tumor status (size, location, stage, pathological findings such as lymph node metastases, vessel invasion, tumor budding, etc.) and recurrent disease status (pathological findings, tumor markers, etc.) were analyzed univariately and multivariately by Cox’s proportional hazards model. Tumor budding was categorized into two categories: none or minimal and moderate or marked. RESULTS: Overall survival for all patients was 52% at 3 year. Prognostic factors which were significant on univariate and multivariate analysis were moderate to severe tumor budding at the primary site of rectal cancer (HR 2.56; CI 1.08-6.09, p=0.033 ) and elevated preoperative serum CEA (>10 ng/ml) (HR 3.30; CI 1.35-8.12, p=0.009). We divided the patients into three groups; Group A (n=17) had neither of these two parameters, Group B (n=14) contained one, and Group C (n=8) contained both of these factors. This classification was significantly related to overall survival after recurrence surgery (3-year, 5-year survival rate, 74%, 42% in Group A, 45%, 22 % in B, and 0%, 0%, in Group C, p=0.003). Conclusion: The three-ranked classification by tumor budding at the primary tumor and preoperative serum CEA level can provide useful prognostic information for the treatment of local recurrence. Surgical resection may not be useful for patients in Group C.
FP-59 Genistein Inhibits Angiogenesis, Increases Apoptosis, and Slows the Growth and Metastases of Pancreatic Cancer Oscar Joe Hines1, Peter Buchler2, Howard A. Reber1 1 Department of Surgery, UCLA, USA, 2Department of Surgery, Heidelberg, Germany Purpose: We sought to determine the effect of genistein, a tyrosine kinase inhibitor, on pancreatic cancer growth, apoptosis, and angiogenesis. Methods: Capan-1. Capan-2, AsPc-1, PANC-1 and MiaPaCa-2 cell lines were studied. VEGF protein was measured by ELISA, HIF DNA binding by EMSA and mRNA by Northern blot. Cell growth was assessed by cell count and MTT. Apoptosis was determined by DNA laddering and annexin-V. Caspase-3 and NF-kappa B activities were measured following treatment. Immunohistochemistry of 18 human tumors was performed for VEGF and HIF. Genistein was administered intraperitoneal in an orthotopic nude mouse model. Apoptosis in tumor specimens was determined by TUNEL. Angiogenesis was quantified by CD31 staining. Results: All cell lines increased VEGF production under hypoxic conditions by specific activation of HIF-1 alpha. Cell lines with high constitutive levels of HIF-1 alpha produced higher
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basal levels of VEGF. VEGF protein was dose-dependently suppressed with genistein. Genistein caused impaired activation of HIF-1 under hypoxic culture conditions. Treatment also resulted in apoptosis in all pancreatic cancer cell lines tested and this was mediated by activation of caspase-3. Studies of human pancreatic cancer tissue showed co-localization of VEGF in ductal cancer cells, and HIF-1 alpha protein in the cell nuclei of the same cells. HIF-1 alpha mRNA expression was dramatically upregulated 13 fold in these specimens as well. Genistein treatment significantly improved survival, almost completely inhibited metastasis, increased apoptosis, and decreased vessel count in an orthotopic model of pancreatic cancer. Conclusion: Genistein may be beneficial for patients suffering from pancreatic cancer.
FP-60 Surgical Anatomy of the Inferior Vena Cava Ligament Ichiro Hirai, Wataru Kimura, Akira Fuse, Koichi Suto, Masaomi Mizutani, Toshiyuki Moriya, Jinfeng Ma First Department of Surgery, Yamagata University, Japan The inferior vena cava ligament is a fibrous membrane located around the inferior vena cava (IVC). Few reports exist on the ligament’s location, attachment to the liver, or the IVC. We obtained 16 specimens of human liver and IVC from cadavers. Relationships among the ligament, IVC, and liver were examined macro- and microscopically. The numbers and diameters of veins, arteries, and lymph vessels were recorded. The cranial portion above the midportion of the Spiegel lobe was thicker than the caudal portion. The ligament was attached to the right and left hepatic veins. The mean length of the right side of the IVC ligament was 37.0 mm and the mean width 15.6 mm. The IVC ligament had a mean thickness of 0.8 mm (thin end) and 2.5 mm (thick end). Although the IVC ligament was usually tightly continuous with the liver capsule, microscopically the attachment between the ligament and the IVC was loose. The mean number and diameter of veins in the IVC ligament was 1.0 and 1.4 mm. The mean number and diameter of arteries was 0.2 and 2.4 mm. The mean number and diameter of lymphatic vessels was 2.8 and 1.7 mm. After dissection of the IVC ligament, major hepatic veins can be dissected extrahepatically. Because the ligament is wider caudally, the forceps should be inserted caudocranially during separation. Since both the number and diameters of lymphatic vessels in the ligament are large, the ligament should be ligated and cut.
FP-61 Surgical Strategy for Advanced Gallbladder Carcinoma According to the Mode and Degree of the Tumor Spread Satoshi Hirano1, Satoshi Kondo2, Takashi Hara2, Eiichi Tanaka2, Katsunori Saitoh2 1 Surgical Oncology, Hokkaido University Graduate School of Medicine, 2Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Japan PURPOSE: Surgical outcome was analysed to evaluate our operative strategy for advanced gallbladder carcinoma. METHODS: Between 1998 and 2003, 59 patients with gallbladder carcinoma underwent operation. Patients without peritoneal, hepatic, or paraaortic lymphnodes metastasis underwent radical resection. Pancreato-duodenectomy was performed exclusively in the cases with massive infiltration to the duodenum, or positive parapancrat-
ic lymph nodes. Direct invasion into the liver was treated with wedge hepatectomy with free hepatic margin over 1 cm. When the tumor progressed to the hepatic hilum, extended right hepatic and caudate lobectomy was employed. Portal vein or hepatic artery, invaded by the tumor was excised together with the tumor. Arterioportal shunting was made when micro surgical arteial anastomosis seemed infeasible. RESULTS: Radical resection was performed in 42 of 59 patients. Right hepatectomy, pancreatoduodenectomy and combination of them were performed in 12, 7 and 1 patients, respectively. In 8 patients, complete excision of the tumor was obtained using partial resection of the pancreas and/ or duodenum, not pancreatoduodenectomy. Resection of portal vein and hepatic artery was applied for 12 and 4 patients, respectively. Thirty-seven resections (88%) proved histologically to be curative. In-hospital death was encountered in one patient who suffered from postoperative hemorrhage. Cumulative 3-year survival rate for patients with p-TNM (2002) stage II (n=21) and III (n=7) were 49 and 43%, respectively. No patient with stage IV disease (n=4) survived over 3 years. CONCLUSIONS: According to the rate of curative resection and postoperative outcome, our strategy for advanced gallbladder carcinoma seems acceptable.
FP-62 A Phase I Study of Biweekly Paclitaxel and TS-1 Combined Chemotherapy in Patients with Advanced Gastric Cancer Shuichi Hokita, Sumiya Ishigami, Futoshi Miyazono, Kuniaki Aridome, Shigeho Maenoahara, Hiroshi Mure, Toyokuni Suenaga, Hiroshi Imamura, Tetsushi Saihara, Hidehiro Nomura, Yuuzo Kawasaki, Shoji Natsugoe, Sonshin Takao, Takashi Aikou Department of Oncology, Division of Surgical Oncology, Kagoshima University, Japan Background : Paclitaxel (PTX), S1 (TS1) are each active in gastric carcinoma, either as single agent or as part of a multidrug regimen. To the authors’ knowledge, the combination of these two agents in the treatment of patients with gastrointestinal carcinoma has been a few previously studied. Objectives : To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of a combination of TXL and TS1 in advanced gastric cancer patients. Methods. 15 patients with distant advanced or recurred carcinoma of the stomach were enrolled in this study until now. The dose of TS1 was fixed at 80 mg/m2/day (Day1_14), and escalating doses of TXL with a starting dose of 100 was mg/m2 given as in 1 hour infusion. The dose was escalated by 10 mg/m2 every 3 patients. Results : At 130 mg/m2 of paclitaxel, there were events including leukocytopenia and neutropenia with grade 4 and diarrhea with grade 3 in one patient of three patients. One patient in another 3 patients who were enrolled at level 3 had granulocytopenia with grade 4 and leukocytopenia with grade 3. Eight patients out of 15 achieved a partial response, resulting in 53 % as an objective response rate. Biweekly PTX/TS-1 combination chemotherapy may be safely used for the treatment of advanced gastric caner. The recommended doses for paclitaxel and TS-1 in phase II study are 120 mg/m2 and 80 mg/m2, respectively. Conclusin : Biweekly PTX/TS-1 combination chemotherapy may be safely used for the treatment of advanced gastric caner.
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FP-63 Living Donor Liver Transplantation for Fulminant Hepatic Failure in Children : Its Indication and Optimal Timing of Liver Transplantation Ken Hoshino, Yasuhide Morikawa, Motohide Shimazu, Go Wakabayashi, Minoru Tanabe, Shigeyuki Kawachi, Masashi Yoshida, Masaki Kitajima Department of Surgery, Keio University, School of Medicine, Japan Fulminant hepatic failure (FHF) is an indication for liver transplantation. However, together with unknown causes of FHF in children, it is difficult to determine an indication and optimal timing of liver transplantation. We have treated 10 children suffering from FHF. Living donor liver transplantation (LDLT) was performed in 7 patients. Five of them are alive.We evaluated these patients according to the guidelines which are defined by Japan acute liver failure study group in 1996, five patients fulfilled the criteria (one patient: no need of liver transplantation, 4 patients: need for liver transplantation). In theses group, 4 patients were performed LDLT. and all the five patients were alive. On the other hand, 5 patients which did not fulfill criteria. It means that all the five patients developed severe encephalopathy in day 2 or 3. Two patients were diagnosed immediately as systemic disease and died at day 4 and day 21 respectively. Three patients were performed LDLT. Only one patient survived after LDLT. One patient developed severe cerebral edema immediately after LDLT. Conclusion: 1. The survival rate of the patients with FHF patients who could keep the guideline would be very high (almost 100%). 2. Patients with FHF should be considered LDLT as soon as possible when hepatic encephalopathy develops. 3. However, the systemic disease which shows hepatic failure should be neglected immediately to evaluate the contra-indication of LDLT. 4. Construction of highly sophisticated medical organization as pediatric acute liver team is essential to supply an optimal treatment for FHF patients.
Journal of Gastrointestinal Surgery
retention than that in DGE (-) patients. All the patients had lower change in ratio per minute than that of healthy. In solid food, the DGE (+) patients had significantly lower proximal retention than that in DGE (-) patients. All the patients had significant lower change in ratio per minute than that in healthy. The DGE (+) patients had significant lower change in ratio per minute than that in DGE (-) patients. Conclusions: The data showed more solid food retained in the distal stomach and the emptying ability of the retained stomach was impaired after PPPD. The DGE depend on the extent of impairment in the emptying ability of the distal stomach.
FP-65 Short to Midterm Outcomes of Laparoscopic Incisional and Ventral Hernia Repair at a Medical Center in Taiwan Chi Cheng Huang, Heng Hui Lien, Ching Shui Huang Division of General Surgery, Department of Surgery, Cathay Medical Center, Taiwan Purpose: Laparoscopic incisional and ventral hernia repairs (LIVHR) are reported to have low recurrences, short hospital stays and rapid ambulation and have gained increasing popularity. Short to midterm outcomes of this procedure at Cathay Medical Center will be presented. Methods: Demographic, perioperative and follow up features of 58 incisional (33 were recurrent) and 11 ventral hernias undergoing laparoscopic underlay DualmeshR placement were collected for analysis. Three incarcerated hernias were operated as emergent procedures. Results: The conversion rate was 2.9% and minor complications were observed in 26% (n=18) of the patients. Late complications included 2.9% (n=2) of recurrences, 7.2% (n=5) of chronic pain and 4.3% (n=3) of eventrations. Conclusions: Short to midterm outcomes of LIVHR was satisfactory both in complications and recurrences. The efficacy of LIVHR was ascertained and reproducible for Taiwanese from current series. The concerns with chronic non-disabling pain and eventrations necessitate the long-term follow up of this technique.
Intragastric Distribution of Meal in Patients with or without Delayed Gastric Emptying after Pylorus-Preserving Pancreaticoduodenectomy Hui-Ping Hsu, Yan-Shen Shan, Yu-Hsiang Hsieh, Mei-Ling Tsai, Pin-Wen Lin Department of Surgery, National Cheng Kung University Hospital, Taiwan
Prolene Hernia System Compared with Mesh Plug Technique: A Prospective Study of Short to Mid-Term Outcomes in Primary Groin Hernia Repair Ching-Shui Huang, Chi-Chen Huang, Heng-Hui Lien Dept. of General Surgery, Cathay Medical Center, Taiwan
Background: Food distribution in the stomach depends on the emptying function of the stomach. This study is to investigate the food distribution in the stomach in patients with or without DGE after PPPD. Patients and Methods: Patients receiving PPPD between October 1998 and June 2002 were analyzed. Single phase gastric emptying scintigraphy was used to evaluate the food distribution in the stomach 14 days after operation. Twelve health volunteers received the similar test for data validation. The area of stomach was determined by summed pictures and divided into proximal and distal using mid-length separation. The ratio of proximal over distal counts was compared at all time intervals for both phases. Results: Twenty-one patients receiving PPPD were analyzed, 12 patients without DGE and 9 patients with DGE. In liquid food, the DGE (+) patients had significantly higher proximal
Two types of anterior tension-free hernioplasty, prolene hernia system (PHS) repair and mesh plug technique (MPT), were introduced to Taiwan since 2001. This study was to compare the short to mid-term outcomes following primary groin hernia repair with PHS and MPT. Since Jan 2001 to Dec 2003, 393 patients with 426 primary groin hernias were repaired with MPT (n=234) and PHS (n=192). Perioperative details and follow-up information were compared. Demographic characteristics were similar in both groups. The laterality, types of anesthesia, postoperative stay, postoperative wound pain scores, wound complications and days to return to activities were equally distributed. However, the distribution of Gilbert types in the PHS group was shifted to the right compared with the MPT. PHS repair had longer operative time (34>17 vs 25>9 minutes, p<0.01). No recurrence was noted in both groups during the 5 to 41 months follow-up. Chronic non-disabling groin pains were noted in 2.8% in the PHS group and 8.9%
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in the MPT group (p=0.01). Our results had shown that both repairs can be performed with short operation time, minor wound pain and quick return to activities without short to mid-term recurrences, but postoperatively the MPT group had higher incidence of chronic non-disabling groin pain. Although the MPT is less invasive, the additional protective patch in the pre-peritoneal space of the PHS may provide further safeguard against recurrences especially for those patients with attenuated inguinal floor.
FP-67 Individualized Surgery for Early Gastric Cancer using Sentinel Node Biopsy Takashi Ichikura1, Kentaro Chochi1, Hidekazu Sugasawa1, Susumu Saigusa1, Yoshihisa Yaguchi1, Naoko Sakamoto1, Satoshi Ono1, Shigeru Kosuda2, Hidetaka Mochizuki1 1 Department of Surgery I, 2Department of Radiology,National Defense Medical College, Japan Background: We have reported that lymphatic mapping using indocyanine green (ICG) can be a tool for identifying sentinel nodes (SNs) in gastric cancer. The purpose of this study was to clarify the validity of our clinical application of sentinel node concept. Methods: Since September, 2000, we have offered SN navigated strategy to gastric cancer patients with T1 tumor ; D1+α/β gastrectomy preserving vagus when SN biopsy (SNB) was negative, and D2 standard gastrectomy when SNB was positive. Another optional procedure has been added since July, 2003; segmental or wedge resection of the stomach with dissection of the station where SNs were located in when SNB was negative. SNs were identified by submucosal injection with ICG solution and/or 99mTc-labeled tin colloid. Results: Sixty-six patients were enrolled in this study. Six patients who were diagnosed as T2 or N positive after laparotomy and 7 patients with positive SNB underwent D2 gastrectomy. Among the 53 patients with negative SNB, 52 patients underwent D1+α/β gastrectomy (distal, 25; pylorus preserving, 17; proximal, 7; total, 3), and 1 patient underwent segmental gastrectomy with dissection of stations of SNs. Postoperative pathologic examination by H.E. staining of paraffin-embedded specimens revealed lymph node metastasis in 1 of the 53 patients with negative SNB by frozen section, in whom micrometastasis was observed only in one of the sentinel nodes. Conclusion: SN navigated surgery may be feasible in early gastric cancer, although false negative results by frozen section should be taken into account.
FP-68 Overcoming Multidrug Drug Resistance in P-glycoprotein/ MDR1-overexpressing Cell Lines by Ecteinascidin 743 Takehito Igarashi, Yuji Takebayashi, Tomoyuki Monma, Atsuko Kanzaki, Masashi Higashimoto, Seiichi Takenoshita Department of Surgery 2, Fukushima Medical University,School of Medicine, Japan Ecteinascidin 743 (Et-743) is a novel anticancer agent forming covalent guanine adducts at specific sites in the DNA minor groove. Et-743 has a unique mechanism of action because it kills cancer cells by poisoning transcription-coupled nucleotide excision repair. Recent studies suggested a complex relationship between Pglycoprotein (P-gp) /MDR1 and Et-743. On one hand, Et-743 was reported to down-regulate the MDR1 promoter in vitro. On the other hand, P-gp overexpression was hypothesized to contribute to
Et-743 resistance in an ovarian cell line. The present study was performed to further investigate the relationship between Pgp/MDR1 and the activity of Et-743. First, we found no Pgp/MDR1 overexpression (mRNA and protein levels) in two independently generated Et-743-resistant human colon carcinoma cell lines (HCT116/ER5 and SW480/ER0.5). Secondly, we found no cross-resistance to Et-743 in two well-characterized P-gp/MDR1overexpressing cell lines (KB-8-5 and KB-C-2). Third, Et-743 pretreatment enhanced the cytotoxicity and the cellular accumulation of doxorubicin and vincristine in P-gp/MDR1-overexpressing KB-8-5/KB-C-2 cell lines. Fourth, we observed P-gp/MDR1 down-regulation by Et-743 in KB-C-2 cells. These results indicate that Et-743 does not select for the emergence of a P-gp phenotype in all cell lines made resistant to Et-743 and that P-gp overexpression is not sufficient to confer resistance to Et-743. Furthermore, Et-743 is an effective agent in P-gp-overexpressing cells. Et-743 can potentiate the activity of other chemotherapeutic agents by down-regulating P-gp/MDR1, suggesting that the combination of Et-743 and chemotherapeutic agents that are substrates for Pgp/MDR1 may be valuable in the clinic.
FP-69 Surgical Simulation on Computed Fusion Images of 99mTcGSA SPECT and X-ray CT is Useful for Decision Making in HCC Treatment Yuji Iimuro 1, Junichi Yamanaka 1, Tadamichi Hirano 1, Shinichi Saito1, Toru Kashiwagi2, Hideaki Yoshimura2, Jiro Fujimoto1 1 First Department of Surgery, 2Department of Nuclear Medicine, Hyogo College of Medicine, Japan Preoperative estimation of remnant liver function is critically important for surgical decision in treatment of hepatocellular carcinoma (HCC). The AIM of the present study was to determine whether surgical simulation on computed fusion images obtained from 99mTc-GSA SPECT and X-ray CT could be useful for decision making in HCC treatment. Methods: Out of 110 HCC patients who received surgical resection during recent three years, 48 patients (male 39, female 10) underwent dynamic 99mTc-GSA SPECT preoperatively. The SPECT images were reconstructed according to nonuniform attenuation correction determined by a separate X-ray CT. Whole liver uptake ratio (LUR; % = total hepatic SPECT counts/total pre-injection SPECT counts) and functional liver volume (FLV; cm3) were calculated. Preoperative surgical simulation was performed on the computed fusion images of SPECT and X-ray CT, and post-operative remnant functional liver volume (RFLV) and remnant liver uptake ratio (RLUR) were estimated. Two weeks after surgery, these patients underwent 99mTc-GSA SPECT again, and actual RFLV (ARFLV) and actual RLUR (ARLUR) were calculated. Results: LUR, but not FLV, well correlated with ICGR15 and PT%. Significant correlation between ARLUR and PT% at 1 and 2 week after surgery was detected. RFLV and RLUR had good correlations with ARFLV and ARLUR, respectively. Correlations between RLUR and PT% at 1 week or peak s-T.Bil values were observed., suggesting usefulness of RLUR for the prediction of remnant liver function. Conclusions: Prediction of remnant liver function by calculating RLUR using X-ray CT-fused SPECT images could be useful for decision making in treatment of HCC.
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FP-70 A Strategy on Obstuructive Left-Sided Colorectal Cancer Takayuki Iino, Yuka Yoshimura, Tomoichiro Hirosawa, Shinpei Ogawa, Michio Itabashi, Shingo Kameoka Surgical Department 2, Tokyo Women’s Medical University, Japan In the treatment of colorectal cancer with intestinal obstruction, avoiding unnecessary stoma will ameliorate the quality of life of the patient. Preopertive peroral (using long tube) decompression frequently yields poor results in left-sided colorectal cancer, and demands emergency surgery, with unsatisfactory outcomes. Selecting adequate decompression method will result with successful one-stage operation. 59 patients undergone operations for obstructive colorectal cancer for the past 15 years, between 1989 to 2003. 25 cases were right-sided and 34 cases were left-sided. For left-sided obstructive colorectal cancer, we treated with preoperative peroral and/or transanal decompression by patient condition and the state of stenosis of the intestine. 5 cases undergone twostage operation or developed stoma. The rate of successful onestage operation was 85.3%. In conclusion, one-stage operation after transanal decompression is the ideal treatment of obstructive left-sided colorectal cancer. But temporary stoma should be also considered by patient conditions.
FP-71 Mid-to-Distal Esophagectomy and Reconstruction in Posterior Mediastinum as a Limited Operation Masahiko Ikebe, Hideo Baba, Motonori Futatsugi, Naoyuki Ueda, Eiji Oki, Manabu Yamamoto, Yoshihiro Kakeji, Yoshihiko Maehara Department of Surgery and Science, Graduate School of Medicine, Kyushu University, Japan Purpose: In our country, combined cervicothoracoabdominal resection with extended lymph-node dissection has been standard procedure for esophageal carcinoma. For selective patients with midto-distal esophageal carcinoma, we have performed mid-to-distal esophagectomy with regional lymph-node dissection as a limited operation. Clinical results were compared between two procedures. Methods: A total of 271 patients with carcinoma of the midto-distal esophagus were operated in our hospital either with subtotal esophagectomy or mid-to-distal esophagectomy. Subtotal esophagectomy included extended en bloc lymph-node dissection in the posterior mediastinum, upper abdomen and cervix. Esophagus is reconstructed in the cervical region. Mid-to-distal esophagectomy included lymph-node dissection in the peritumoral tissue, upper mediastinum and upper abdomen. Reconstruction is made in the posterior mediastinum. Overall survival and early morbidity were determined. Results: One hundred thirty-four patients were performed mid-to-distal esophagectomy and 137 patients underwent subtotal esophagectomy. Five year survival rate according to tumor stage was similar between Mid-to-distal esophagectomy and subtotal esophagectomy; 74% vs 63% for stage I, 45.8% vs 40.4% for stage II, 17.9% vs 16.7% for stage III, respectively. Post-operative complications were lower after midto-distal esophagectomy compared with subtotal esophagectomy. Anastomotic failure occurred in 8 vs 34, pulmonary complications; 5 vs 14, recurrent nerve palsy; 0 vs 5 patients, respectively. All the anastomotic failure after distal esophagectomy resolved with conservative management. Conclusions: Mid-to-distal esophagectomy
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was associated with lower morbidity than subtotal esophagectomy with extended en bloc lymphadenectomy. As overall survival rate did not differ statistically between the groups, this procedure is recommended for selective patients.
FP-72 Effects of Nutritional Therapy on Surgical Treatment in Crohn’s Disease Hiroki Ikeuchi, Hiroki Nakano, Motoi Uchino, Mitsuhiro Nakamura, Masafumi Noda, Hidenori Yanagi, Takehira Yamamura Second Department of Surgery, Hyogo College of Medicine, Japan Background/Aims: The effectiveness in Crohn’s disease of nutritional therapy with an elemental diet (ED) which produces almost no side effects. Enteral nutrition is the currently established primary therapy for Crohn’s disease in Japan. We examined the effects of postoperative nutritional therapy in patients with Crohn’s disease. Methodology: We retrospectively reviewed the records for 330 patients who underwent surgical interventions for Crohn’s disease in our hospital between January 1, 1974 and April 30, 2004. They were divided into four groups: 110 patients in the non-perforating type (NP type) + Elemental Diet (ED) group had received ED therapy and nutritional education, 59 patients in the NP type + NoED group had not received ED therapy or nutritional education, 100 patients in the perforating type (P type) + ED group and 61 patients in P type + NoED group. We evaluated the incidence of re-operation rate for each group. Results: Patients with a postoperative ED therapy demonstrated a significant decrease in the incidence of second resection. The incidence of second resection in the NP type + ED group was significantly lower than that of the other groups. The NP type + NoED group and the P type + ED group followed similar courses. Conclusion: In patients with Crohn’s disease postoperative ED therapy and nutritional education is effective for reducing the incidence of second resection. It appears that adequate instruction is necessary to alleviate the poor prognosis P type Crohn’s disease patients.
FP-73 Indication and Results of Repeated Hepatic Resection for Intrahepatic Recurrence of Hepatocellular Carcinoma Hiroshi Imamura, Keiji Sano, Yasuhiko Sugawara, Norihiro Kokudo, Masatoshi Makuuchi Department of Hepato-Biliary-Pancreatic Surgery, University of Tokyo, Graduate School of Medicine, Japan Purpose: Frequent intrahepatic recurrence is a drawback of surgical resection of hepatocellular carcinoma (HCC). We have been determining the indication for repeated hepatectomy in the same manner as for the initial hepatectomy and review our institutional experience. Methods: We have carried out 375 curative resections for HCC during the last 8 years. Recurrence was observed in 224 patients. In 198 patients, recurrence was solely to the liver. Repeated hepatectomy was possible in 59 patients. Other 23 patients undergoing hepatectomy in other hospitals underwent repeated hepatectomy. Thus, 82 patients become the subjects of this study. We have analyzed the patient profiles and prognostic factors. Results: Ratio of repeated hepatectomy was 30.0%. Until now, 52 of 82 patients experienced re-recurrences. Third hepatectomy was carried out in 13 of 49 patients in whom the recurrence
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was found exclusively to the liver. Likewise, fourth or fifth hepatectomies were performed in a total of 7 patients. In multivariate analyses, interval from the initial hepatectomy, presence of vascular invasion, and presence of intrahepatic metastases were the factors contributing to early recurrence; in addition to these variables, HCV, low albumin value were the factors to overall survival. There was no difference in the survivals between those who underwent initial hepatectomy and those undergoing repeated hepatectomy from the time of respective hepatectomies. Conclusions: Repeated hepatectomy to HCC intrahepatic recurrence can be performed based on the same indication criteria for the initial hepatectomy and similar survival benefit to the initial resection can be expected in a selected patient population.
FP-74 Effect of Postoperative Interferon+5FU+Cisplatin for Advanced Hepatocellular Carcinoma with Macroscopic Portal Invasion Satoru Imura, Hisamitsu Shinohara, Yuji Morine, Masahiko Fujii, Tsutomu Ando, Hidenori Miyake, Seiki Tashiro , Mitsuo Shimada Digestive and Pediatric Surgery, The University of School of Medicine, Japan Purpose: Despite of adequate hepatic resection the prognosis of the patients with hepatocellular carcinoma (HCC) having macroscopic tumor thrombus in the portal vein, especially Vp≥2 cases, are still poor. We investigated the prognosis of those patients and discussed the significance of postoperative adjuvant therapy. Methods: Out of 265 patients with HCC underwent hepatic resection at Tokushima University Hospital from February 1985 to March 2004, 28 patients had Vp≥2 portal invasion. Among 28 patients who had Vp≥2 portal invasion, 8 patients who had an operation after June 2000 underwent postoperative adjuvant systemic interferon+5FU+cisplatin (interferon alpha, 3 days a week / 5FU+cisplatin, 5 days a week) at least 4 weeks after operation (IFN+chemo group) and 16 patients underwent no adjuvant therapy (control group) were enrolled this study. 4 patients had other postoperative therapy. Results: Overall survival rate was significantly higher in systemic IFN+chemo group compared with control group (1 year: 100% vs 37.5%, 3 year: 100% vs 25.0%). There was not significant difference in two groups about disease free survival rate. Conclusions: Our results suggest that hepatic resection and postoperative adjuvant systemic therapy consisting of interferon+5FU+cisplatin could improve the prognosis of the patients with macroscopic portal invasion.
FP-75 Molecular Diagnosis of Gastric Cancer Determined by cDNA Microarray & Lazar Micro Dissection Hiroshi Inoue, Tohru Utsunomiya, Koshi Mimori, Fumiaki Tanaka, Masahiro Okamoto, Masaki Mori Surgery, Medical Institute of Bioregulation, Kyushu University, Japan Purpose: To estimate gastric cancer patients’ prognosis more comprehensively, we developed a prognostic scoring system using cDNA microarray. Experimental Design: (1) RNA was extracted from tumor/normal-paired samples of 43 patients with gastric cancer, and cDNA microarray was performed. (2) For 10 cases of gastric cancer, biopsy and multiple RNA samples were extracted from
different portions of the tumor (superficial and deep portion) and the gene expression profiling was compared. Results: (1) We selected 78 genes that were differentially expressed between aggressive and non-aggressive groups with respect to five conventional pathologic factors. Next, we determined a coefficient for each gene and a prognostic score was calculated. It ranged from 47 to 201 with a median of 114. Ten of 11 patients who were alive with no evidence of recurrence more than 5 years showed a score of less than 100 point, while all 19 patients who died of disease showed more than 100 point. In 13 patients who were alive but the follow-up time was less than 5 years, two of the 3 patients with more than 100 point revealed recurrent disease. (2) Gene expression profiles from superficial portion and biopsy material were well coordinated (p=0.88) in all cases. Gene expression profiles from deep portion and biopsy material were less coordinated, especially in cases with poorly differentiated tumor (p=0.66). Conclusions: These findings demonstrate that such a system with cDNA microarray can contribute to the comprehensive analysis of malignant behavior of the tumor and may provide accurate information on prognosis.
FP-76 A New Concept for Classification of Intrahepatic Cholangiocarcinoma Associated with Direct Infiltration into the Hepatic Hilum Kazuto Inoue, Tadatoshi Takayama, Tokio Higaki, Masamichi Moriguchi, Mitsugu Kochi, Osamu Aramaki, Yoshihiro Watanabe, Komei Kato Digestive Surgery, Nihon University School of Medicine, Japan [Background] Intrahepatic cholangiocarcinoma associated with direct infiltration into the hepatic hilum and hilar bile duct (extrahepatic bile duct) carcinoma has been defined as different clinical entities. Actually, the origin of intrahepatic bile duct and extrahepatic bile duct is different, however, there is no exact border between them and moreover, discriminate the origin of tumor that occupies both intra- and extra-hepatic area is sometimes impossible. [Aim] To over come this situation, we have suggested the new classification of the diseases according to the depth of cancer infiltration into bile duct layer. In this study, we confirmed the utility of our new classification. [Patients and method] Patients having intra- and extra- hepatic cholangiocarcinoma who were treated in our hospital were classified into four categories and the results of the treatment and the prognosis of the patients were investigated. The four categories are (1) cancer limited with in mucosa (m), (2) cancer with infiltration into bile duct wall (ss, fm), (3) cancer with infiltration into extra-bile duct organ including liver and hepatoduodenal ligament, and (4) mass-forming type peripheral cholangiocarcinoma. [Results] The category (1) resulted the best prognosis and the category (4) was the second. The worst prognosis was seen in category (3). Patients in category (3) were almost unresectable and chemotherapy and/or irradiation were performed, however, they had been not effective. [Conclusion] Our new classification for intrahepatic cholangiocarcinoma associated with direct infiltration into the hepatic hilum and hilar bile duct carcinoma is useful.
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promising in decreasing the incidence of local recurrence.
Molecular Detection of Circulating Tumor Cells by (CEA)Specific Real Time Quantitative PCR during Gastric Cancer Surgery Sumiya Ishigami1, Akihiro Sakamoto2, Shuichi Hokita2, Akihiro Nakajo2, Shoji Natsugoe2, Takashi Aikou2 1 Surigical Oncology, Digestive Surgery, Kagoshima University, Japan, 2Kagoshima University, Japan
AIM: To elucidate the relation between presence of cancer cells in blood according to the time course during a surgical procedure and recurrence in gastric cancer patients by real time PCR. METHODS: Blood samples from 67 patients with gastric cancer were obtained from the peripheral artery after tumor dissection. After total RNA was extracted from each blood sample, carcinoembryonic antigen (CEA)-specific real time quantitative PCR was performed. RESULTS: CEA-mRNA was detected in the blood of 32 of the 67 patients. CEA-mRNA was not detected in the blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate increased in proportion to the depth of tumor and lymph node metastasis. A significant relation was not found between the detection of CEA-mRNA and occurrence of tumor relapse. Higher CEA-mRNA level was, earlier tumor relapse occurred. CONCLUSIONS: A relatively high incidence of positive CEA-mRNA was found in the blood during gastric cancer surgery. CEA-mRNA level may reflect number of disseminated cancer cells in the blood. Earlier detection of recurrence of gastric cancer may be possible by intraoperative CEAmRNA level.
Background: Little is known as to whether severe pancreatitis due to gallstone depends upon stone impaction or stone passage into the duodenum, and the role of endoscopic sphincterotomy (ES) for patients with severe pancreatitis has remained controversial. Methods: This study reviewed our experience of 183 patients with gallstone pancreatitis, with special attention to the relationship between the severity of pancreatitis, complicated biliary pathology and outcome. Results: Based on the clinical Atlanta classification system, 16 patients (9%) had severe pancreatitis (SP) and the remaining 167 patients (91%) had mild pancreatitis (MP). Most SP patients (94%) had stones in the gallbladder alone, indicating stone passage into the duodenum. Of the 167 MP patients, on the other hand, 58 (35%) had stones impacted at the papilla of Vater or persistent stones and pus in the bile duct (severe cholangitis). Four patients (25%) with SP died of multiple organ failure. Four death in MP (2%) occured in patients complicated with severe cholangitis, 2 of whom were septic shock at the time of admission. Conclusion: No correlation between SP and severe cholangitis suggests that early ES is not advocated for patients with SP. The real danger in some patients with MP is the specific complication of lifethreatening severe cholangitis, and it is for these patients that emergency ES is necessary.
FP-78 Postoperative Cytology for the Drained Fluid from the Pancreatic Bed after Resection of T3-/T4-pancreatic Cancer—A Predictor of Local Cancer Relapse and Implication of Preoperative Chemoradiation Osamu Ishikawa, Hiroaki Ohigashi, Hidetoshi Eguchi, Terumasa Yamada, Yo Sasaki, Shingi Imaoka Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan Since the incidence of locoregional cancer relapse is high after a “curative” resection of the pancreatic cancer, this study is designed to know whether both cancer residual or following local recurrence is foreseeable by the postoperative cytodiagnosis of the drained fluid from the pancreatic bed. The effects by the preoperative chemoradiation is also studied. For 55 patients with T3-/T4pancreatic cancer, R0-resection was performed after negative result had been confirmed by the peritoneal washing cytology. Postoperatively, 16 (29%) patients revealed positive cytology and 39 (71%) showed negative cytology. In the positive group, local recurrence was significantly higher than other types of cancer recurrence such as liver metastasis or peritoneal implant. The 3-yr cumulative rate of local recurrence was 85% in positive group and 23% in negative group (p<0.05), and 3-yr survival rate was 14% and 55%, respectively (p<0.05). In other 20 patients who had received preoperative chemo-radiation plus following pancreatectomy for T3-/T4-cancer, cytology-positive rate was decreased to 15%. From these data, we are allowed to conclude that local recurrence is predicted by the postoperative cytology for drained fluid from the pancreatic bed and preoperative chemoradiation is
Gallstone Pancreatitis: Positive Correlation between Severe Pancreatitis and Passed Stone Masatoshi Isogai, Akihiro Yamaguchi, Tohru Harada, Yuji Kaneoka, Junji Washizu, Kiyoshi Aikawa Department of Surgery, Ogaki Municipal Hospital, Japan
FP-80 Indications of Partial Hepatectomy for Transplantable Hepatocellular Carcinoma with Compensated Cirrhosis Toshiyuki Itamoto, Hideki Nakahara, Hideki Ohdan, Hirotaka Tashiro, Toshimasa Asahara Division of Frontier Medical Science, Department of Surgery, Hiroshima University, Graduate School of Biomedical Science, Japan Purpose. To determine the appropriate treatment strategy for transplantable hepatocellular carcinoma (HCC) patients with compensated cirrhosis. Patients and Method. Surgical outcomes were reviewed in 136 cirrhotic patients with transplantable HCC who had undergone partial hepatectomy. Transplantable HCC was defined as that corresponding to Milan’s criteria. Results. The adverse prognostic factors for both survival and disease-free survival were histological surgical margin of 5 mm or less, ChildPugh B, and the presence of hepatitis C virus infection. Overall 5year survival and disease-free survival rates of patients with one of or without any adverse prognostic factors were 73% and 33%, respectively, whereas those of patients with two or three adverse prognostic factors were 36% and 17%, respectively. Conclusions. Transplantable HCC patients with two or three adverse prognostic factors should be considered as candidates for liver transplantation, whereas patients with only one of or without any adverse prognostic factors have a good indication of partial hepatectomy.
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FP-81 Long-term Outcomes Associated with Surgical Treatment for Lower Rectal Cancer Hiromichi Ito, Elizabeth L.. Breen, Stanley W. Ashley, Michael J. Zinner, Edward E. Whang, Ronald Bleday Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, USA Introduction: The aim was to analyze our experience of early low rectal cancers and evaluate the outcomes associated with surgical treatment. Methods: One hundred and sixty-one patients with T1/2 rectal cancer located within 15 cm of the anal verge were treated between 1994 through 2003. Patients undergoing neoadjuvant chemotherapy or with positive lymph node metastasis were excluded. Survival was analyzed using the Kaplan-Meier method, Log-Rank test and Cox regression. Mean follow-up period was 61 months. Results: 82 patients had low anterior resections (LAR), 23 abdominoperineal resections (APR) and 56 local excisions. Overall 5-year survival rate and disease-free survival rate of the entire cohort were 79% and 74%, respectively. The factors associated with higher local recurrence rates were local excision, T factor, and tumor size greater than 3cm. Local excision and tumor size were significant in multivariate analysis (p=0.021, p=0.012, respectively). Although the recurrence rate of the patients who underwent local excision was higher than that of patients who underwent APR (32% vs 13% at 5 years, p=0.027), there was no significant difference in the survival rates between these patient groups. 20% of patients who underwent local excisions had local recurrence and all patients but one underwent successful salvage surgery (APR). Conclusions: T1/2 adenocarcinoma at low rectum can be treated with local excision with excellent outcomes. Patients undergoing a local excision for a T2 tumor should have additional adjuvant therapy, and either radical resection or adjuvant therapy should be considered for tumors >3cm.
FP-82 Outcomes Associated with Surgical Therapy for Mucinous Colorectal Cancer Hiromichi Ito, Michael J. Zinner, Stanley W. Ashley, Edward E. Whang Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, USA Introduction: The prognostic significance of mucinous histology in colorectal adenocarcinoma is controversial. The aim of this study was to analyze our experience with mucinous colorectal cancers and to evaluate outcomes associated with surgical therapy. Methods: 774 consecutive patients with colorectal cancer who underwent resection with curative intent were studied. Survival was analyzed using the Kaplan-Meier method, log rank test and Cox regression. Mean follow-up period was 50 months. Results: Eighty patients (10%) were found to have mucinous denocarcinoma. Patients with mucinous adenocarcinoma were older than those with non-mucinous adenocarcinoma (68 years vs 64 years, p=0.02). Mucinous cancers were associated with higher T stage (T3 or higher: 86% vs 59%, p<0.0001) and higher grade (G3: 28% vs 11%, p<0.0001). The 5-year survival rates of patients with mucinous cancers and those with non-mucinous cancers were 55% and 71%, respectively (p=0.0086). On univariate analysis, T stage, N stage, tumor grade, the presence of lymphovascular invasion, M
stage, and mucinous histology emerged as factors associated with poorer prognosis. On multivariate analysis, only T stage and N stage (but not mucinous histology) were significant independent prognostic factors. Conclusions: Although the mucinous histology is associated with higher grade and T stage in colorectal cancer, it does not independently predict poor prognosis.
FP-83 Evaluation of Surgical Resection of Advanced Pancreatic Cancer Considering Postoperative Adjuvant Chemotherapy with Gemcitabine Hiroshi Ito, Fumio Kimura, Hiroyuki Shimizu, Satoshi Ambiru, Akira Togawa, Masayuki Ohtsuka, Hiroyuki Yoshidome, Atsushi Kato, Hideyuki Yoshitomi, Shigeaki Sawada, Masaru Miyazaki General Surgery, Graduate School of Medicine, Chiba University, Japan [Purpose] Prognosis of advanced pancreatic cancer is yet poor remarkably, even if complete resection was performed by enlarged abscission. Effective adjuvant therapy should be needed to improve survival after pancreatectomy. We have adopted postoperative adjuvant chemotherapy with Gemcitabine since 2002. We investigated the factors which influenced on postoperative outcome, and reviewed validity of pancreatectomy and postoperative adjuvant chemotherapy. [Patients and Methods] Seventy nine cases of advanced pancreatic carcinoma, stage III and IV according to general rules for the study of pancreatic cancer by Pancreas Society, were examined. Tumor extension factors, invasion to serosa (S), retroperitoneum (RP), portal vein (PV), and nerve plexus (PL) were analyzed. Lymph node metastasis status was classified as N0; no lymph node metastasis, N1; metastasis to adjacent pancreas tissue lymph node, N2; metastasis to extra-pancreatic lymph node. [Results] All of tumor extension factors (S, RP, PV, PL), lymph node metastasis (N0/1,2 or N0,1/2), and postoperative adjuvant chemotherapy with Gemcitabine (GEM) showed correlation with postoperative survival. Median survival of patients with GEM was 19.6 month, while that of patients without GEM was 12.1 month. Applying a multivariate analysis, presence of lymph node metastasis showed the strongest correlation with poor prognosis, and S and GEM also remained as an independent prognostic factor. [Conclusion] Evaluating surgical resection of advanced pancreatic cancer, aggressive surgical resection would be justified for the cancer without lymph node metastasis or with only positive in pancreatic neighboring lymph node, even if with major vascular involvement, and postoperative adjuvant chemotherapy with Gemcitabine would improve their prognosis.
FP-84 Treatment of Non-albumin Rats with Chronic Liver Failure Using Hepatocytes Transplantation Masahiro Ito1, Shuichi Miyakawa1, Ira J. Fox2, Akihiko Horiguchi1, Hideo Nagata1, Toshiyuki Yamamoto1 1 Surgery, Fujita Health University, Japan, 2Unversity of Nebraska Medical Center, USA INTRODUCTION: We already knew that Transplantation of hepatocytes into the spleen of Cirrhotic chronic rats and Gunn rats resulted in significant improvement of bilirubin levels and duration of survival. but we have no idea that the mechanisms of going down bilirubin levels.This time, we used chronic liver failure
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model for cleafiy about this mechanisms and how the relatively hepatocytes can ameliorate chronic liver failure secondary to common bile duct ligation warrants further investigation. MATERIALS AND METHODS: Liver Failure Models (Chronic liver failure; CLF); CLF was caused by common bile duct ligation using non-albumin rat (Nasage rats: NARs). The average survival time after this procedure, based on results obtained rats, was 12.8+3.6 days. Htx was performed 7 days after common bile duct ligation. Group A: intrasplenic transplantation of 3x107 primary hepatocytes (pHTx) with FK506 (n=4) Group B: intrasplenic transplantation of 0.5ml DMEM with FK506 (n=4;Sham) Group C: common bile duct ligation only (n=4;Negative Control) Group D: intrasplenic transplantation of 3x107 primary hepatocytes (pHTx) with FK506 for NARs (n=4; Positive Control) RESULT : All measures of billirubin level and albumin level were significantly different post-HTX. Survival of animals receiving intrasplenic HTX was significantly prolonged compared to non transplant control group from 12.1+/-4.9 d to 35+/-4.2 d (GA VS GB-C, P<0.01) Conclusion: We got some idea about mechanisms of going down bilirubin levels. Hepatocyte transplantation can survive and function chronic liver failure rats to improve signs of liver function and prolong survival.
FP-85 Role of Expression of Focal Adhesion Kinase and Growth Factor Receptor Bound Protein 7 in Hepatocellular Carcinoma Shinji Itoh1, Akinobu Taketomi1, Shinji Tanaka1, Takashi Maeda1, Ken Shirabe1, Tomonobu Gion1, Mitsuo Shimada2, Yoshihiko Maehara1 1 Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, 2Course of Diseased Organ and Repair Medicine, Department of Digestive and Pediatric Surgery, University of Tokushima School of Medicine, Japan Purpose: Although hepatocellular carcinoma (HCC) is one of the most common cancer, the mechanisms that regulate its development and progression remain unclear. The aim of this study was to investigate whether focal adhesion kinase (FAK) and growth factor receptor bound protein 7 (Grb7) is involved in the progression of human HCC. Methods: FAK and Grb7 expressions in HCC cell lines were analyzed using Western blot analysis. Immunohistochemistry (IHC) analysis for FAK and Grb7 was performed on paraffin embedded tissues in 64 HCC samples, respectively. We also investigated the correlation between the FAK and Grb7 expressions and the clinical outcome. Moreover, we established the transfectant of Grb7 small interfering RNA (siRNA) in Hep3B cell lines. Using this, we evaluated its participation in invasion potential. Results: Western blot analysis showed FAK and Grb7 expression in HCC cell lines. FAK expression in HCC was correlated with portal venous invasion (p<0.01) and poor prognosis (p<0.05). Grb7 overexpression was also correlated with portal venous invasion (p<0.01), intra-hepatic matastasis (p<0.01), and hepatic venous invasion (p<0.05), and tendency for a poor prognosis. Grb7 negative cells showed significantly lower level of invasion potential (p<0.05) than the control cells. Conclusions: The present study showed that FAK and Grb7 are strongly expressed in HCC cells and involved in the invasion potential of HCC. FAK and Grb7 would be a novel molecular target for HCC therapeutics.
Journal of Gastrointestinal Surgery
FP-86 Loss of Heterozygosity of Nucleotide Excision Repair Factors in Sporadic Ovarian, Colon and Lung Carcinomas: Implication for their Roles of Carcinogenesis in Human Solid Tumors Manabu Iwadate, Yuji Takebayashi, Tomoyuki Monma, Atsuko Kanzaki, Masashi Higashimoto, Seiichi Takenoshita Department of Surgery 2, Fukushima Medical University,School of Medicine, Japan The deficiencies of nucleotide excision repair (NER) factors are genetic diseases, xeroderma pigmentosum (XP) increasing risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NER factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (LOH) analysis for the XP, XPA, XPB, XPC, XPD, XPE, XPF, XPG and the transcription-coupled repair factor, Cockayne syndrome B (CSB) revealed that NER factors were abnormal in 62.1 % of ovarian tumors (18/29), 16.7% of colon (2/12) and 22.2% lung (2/9) carcinomas. Furthermore, 13.8% of ovarian, 8.3% of colon and 22% of lung carcinomas exhibited LOH for NER factors without LOH for tumor suppressor genes such as p53, FHIT, APC, BRCAI, BRCA2 and DCC. Although both microsatellite instability and LOH of NER factors were observed in some cases, there was no strong association between them in the present study. These observations raise the possibility that alterations of NER factors may be frequent in human sporadic carcinomas. Further study should be needed to find the direct evidence of NER gene abnormalities in human sporadic carcinoma tissues.
FP-87 Endoscopic Ultrasonography for Gastric Cancer: How has it Influenced Treatment? Shridhar Ganpathi Iyer1, So Bok Yan2, Lawrence Khek Yu Ho2 1 Surgery, National University Hospital, Singapore, 2National University Hospital, Singapore Introduction. This study was aimed to evaluate the utility and shortcomings of EUS (endoscopic ultrasound) in TNM staging of gastric cancer and its influence on treatment. Methods: The series included 126 gastric cancer patients underwent EUS from July 1997 to June 2003 at National University Hospital, Singapore. 109 patients were included in the final analysis. There were 65 male and 44 female patients with age range 29 to 97 years(mean 63.13). Results: EUS staging for primary: Specimen histology was available for 102/109 patients operated. The accuracy for T1, T2, T3 and T4 was 79%, 73.9%, 85.7% and 72.7% respectively (overall accuracy =80.4%). EUS staging for Nodes The sensitivity of EUS for detecting nodal disease was 74.2% for N0, 78% for N1, 53.8% for N2 and 50% for N3 respectively. Overall accuracy was 79%, sensitivity was 82.81%, and specificity was 70.2%. Radical gastrectomy was proposed in 95 patients based on the staging with EUS and CT scan and 87 patients underwent the same (91.6%). Preoperative staging accurately predicted the operative strategy in 89% of the patients. Performing a logistic regression analysis for the correct staging of T stage using EUS and adjusting for tumor location (middle part / distal third / whole stomach versus Proximal / Cardio-esophageal)(p=0.873), operator (p=0.546)and subject’s sequence (Initial 50 versus last 50 cases)(p=0.06), there was no significant predictor for accuracy. Conclusion EUS is the most accu-
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rate and reliable method for preoperative staging of gastric carcinomas and mandatory if tailored therapeutic approach is planned according to stage.
FP-88 Comparison of Open and Laparoscopic Approaches for Ventral Hernia - An Instituitional Experience Shridhar Ganpathi Iyer, Davide Lomanto, Wei Keat Cheah, Asim Shabbir Surgery, National University Hospital, Singapore OBJECTIVES: Open ventral hernia repair is associated with significant morbidity and high recurrence rates. Laparoscopic approach is increasingly becoming an attractive alternative. Our objective was to compare open with laparoscopic ventral hernia repairs. METHODS: 34 laparoscopic and 37 open ventral hernia mesh repairs were included in the study. There were 63 female and 8 male patients in the study. No significant difference between the two groups was noted regarding patient demographics except that the mean hernia size for laparoscopic group was larger (93.38 cm 2) as compared to open (54.89 cm2) (p=0.013). The mean follow up time was 12.51 months. RESULTS: We found no significant difference in the operative time between the two groups (laparoscopic 115.41 min vs open 95.74min). Pain score and analgesic requirement was not significantly different between the two groups for the first 48hours but a significantly less pain was noticed at 72 hours (p=0.017). Hospital stay was significantly less in the laparoscopic group (2.29 vs 3.81days, P < 0.02). There was no difference in overall complication rates (p= 0.072). There was one recurrence in laparoscopic goup and 4 in open group. CONCLUSIONS: Laparoscopic ventral hernia repair offers significant advantages and should be considered for repair of primary and incisional ventral hernias. In this series significantly larger ventral hernias hernias were repaired with better short term outcomes.
FP-89 Laparoscopic Exploration of the Left Main Intrahepatic Duct Young-Ju Jeong, Yong-Oon Yoo Department of Surgery, Daegu Catholic University Hospital, Korea Laparoscopic removal of the stones in the left main intrahepatic duct through choledochotomy at the level of common bile duct is very difficult, because of long tract and relatively narrow common hepatic duct. We report a patient in whom 1.5 cm sized stone(old blood clots in the prmanent biopsy) in the left main intrahepatic duct was removed through laparoscopic exploration of the left main intrahepatic duct. A 47 year old male was admitted to IM department because of cholelithiasis and stones in the common bile duct. Endoscopist romoved CBD stones by use of endoscopic sphincterotomy technique and placed ENBD tube. We performed preoperative cholangiography, which revealed filling defect in the left main intrahepatic duct with proximal intrahepatic ductal dilatation. The filling defect was regarded as previously undetected intrahepatic stone. We decided to perform laparoscopic cholecystectomy and laparoscopic exploration of the left main intrahepatic duct. After laparoscopic exposure of the left main intrahepatic duct with merticulous dissection of the soft tissue around the hepatic hilum, ductotomy was applied on it. Followed by the extraction of the intrahepatic stone, which revealed benign mass in the frozen
section biopsy. After open exploration of the left intrahepatic duct, primary closure of the ductotomy site was performed. In conclusion, laparoscopic exploration of the left main intrahepatic duct can be one of the therapeutic option for the removal of the stones around the left main intrahepatic duct. And this technique seems to promote the ability of laparoscopic exploration of the left intrahepatic duct.
FP-90 Bax Gene Therapy for Xenotransplanted Human MKN-45 Gastric Cancer Cells Shunsuke Kagawa 1, Yousuke Tsunemitsu 2, Naoyuki Tokunaga 2, Masahiko Nishizaki2, Shoichiro Ohtani2, Bingliang Fang3, Noriaki Tanaka2, Toshiyoshi Fujiwara1 1 Center for Gene and Cell Therapy, Okayama University Hospital, Japan, 2Dept of Gastroenterological Surgery, Okayama Univercity Graduate School of Medicine and Dentistry, Japan 3The University of Texas, M. D. Anderson Cancer Center, USA Background and purpose: An adenoviral vector expressing the tumour suppressor p53 gene (Ad/p53) is currently under clinical evaluation for various cancers. We recently developed a binary adenoviral vector system that can express the strong proapoptotic gene Bax (Ad/PGK-GV16+Ad/GT-Bax: Ad/Bax). To evaluate the potential of Bax gene therapy for gastric cancer, we assessed its antitumour effect in comparison with that of p53. Methods: The human gastric cancer cell lines were treated with Ad/Bax or Ad/p53, and cell viability, transgene expression, and caspase activation were assessed in vitro. To compare the antitumour effects of Ad/Bax and Ad/p53 treatment in vivo, subcutaneous tumours and peritoneal dissemination of MKN-45 cells were generated in nude mice. Each mouse underwent intratumoral or intraperitoneal administration of viruses and the growth of implanted tumours was observed after treatment. Results: Treatment with Ad/Bax and Ad/p53 resulted in marked Bax and p53 protein expression and effective apoptosis induction in MKN-1, MKN-7, and MKN-28 cells in vitro. In contrast, MKN-45 cells showed resistance to Ad/p53 and only treatment with Ad/Bax resulted in activation of caspase 3 expression and massive apoptosis. Ad/Bax treatment was more effective in suppressing both subcutaneous and peritoneally disseminated MKN-45 tumours compared with Ad/p53 treatment. Conclusion: Ad/Bax treatment significantly inhibited the growth of even p53 resistant gastric cancer in vitro and in vivo. Therefore, adenovirus mediated Bax gene transfer may be useful in gene therapy for gastric cancers.
FP-91 Efficacy of Preoperative Radiation to Portal Vein Tumor Thrombus in Main Trunk or First Branch for Patients with Hepatocellular Carcinoma Toshiya Kamiyama, Takahito Nakagawa, Kazuaki Nakanishi, Hirofumi Kamachi, Kazuhito Uemura, Michiaki Matsushita, Satoru Todo General Surgery, Hokkaido University Graduate School, Japan Background: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in main trunk or first branch is very poor, even if hepatic resection could be performed. Aim: Efficacy of preoperative radiation (RT) to PVTT in main trunk or first branch for the tumor in the hepatic parenchyma was
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evaluated.Patients and method: The objects were 45 cases of the hepatectomized patients with HCC which involved tumor thrombus in main portal trunk or first branch from 1978 to 2003. Radiation to PVTT was performed preoperatively. A total dose was 3050Gy in 10 fractions. Group-R was the patients who underwent hepatectomy with preoperative RT. Group-N were the patients with no preoperative treatments. Survival was calculated using the Kaplan-Meire method. The prognostic factors were analyzed with univariate and multivariate analysis. Results: Numbers of Group-R and Group-N were 11 and 34. Survival rates of Group-R and Group-N at 1 year were 80.8% and 25.6%. Group-R showed better prognosis than Group-N significantly (p=0.0231). Sex, tumor differentiation, serum albumin and preoperative RT were ranked as significant prognostic factors with univariate analysis. Multivariate analysis revealed these factors as significant prognostic factors. In the patients treated with preoperative RT, the patients with the complete necrotic tip of PVTT were longer survived than those with the incomplete necrotic tip. Conclusion: Preoperative RT for patients with HCC which involved PVTT in main trunk or first branch is effective. This method would be a new promising modality in HCC with PVTT in main trunk or first branch.
FP-92 Poorly Differentiated Adenocarcinoma and Mucinous Carcinoma of the Colon and Rectum Show Higher Rates of Loss of Heterozygosity and Loss of E-cadherin Expression due to Methylation of Promoter Region Takamitsu Kanazawa, Toshiaki Watanabe, Hirokazu Nagawa Surgical Oncology, Tokyo University, Japan Purpose Previous studies have reported that poorly differentiated adenocarcinoma and mucinous carcinoma of the colon and rectum (Por & Muc) show a low incidence and poor prognosis. However, genetic alterations and tumorigenesis of Por & Muc remain unclear. We analyzed the genetic and epigenetic alterations of Por & Muc to clarify the difference from those of well-differentiated adenocarcinoma (WD). Methods First, we evaluated the loss of heterozygosity (LOH) on 4 chromosomes (2p, 5q, 17p, 18q) frequently observed in colorectal cancer. Second, to determine largescale allelic losses, we performed wide-ranging allelotyping study. Using 27 microsatellite markers spanning every 10cM on chromosome 17 and 18, we defined the LOH-ratio as the proportion of markers which show LOH out of 27 markers. Third, we evaluate the methylation of E-cadherin. Results With respect to LOH of 4 loci, higher rates of LOH were observed in Por & Muc and a statistical significance was found on the markers adjacent to MSH2, and SMAD4/DCC. Moreover, as the evidence of large-scale allelic imbalance, the average LOH-ratio was higher in Por & Muc (0.70), than in WD (0.24). (p=0.01) Methylation analysis showed that 54.5% of Por & Muc demonstrated hypermathylation of the E-cadherin. In immunohistochemistry, 77.8% of Por & Muc showed abnormal expression of E-cadherin. Hypermethylation of E-cadherin correlated significantly with abnormal expression. (p=0.047) Conclusions These results suggest that the higher rates of LOH contribute to Por & Muc tumorigenesis and most of Por & Muc lose normal E-cadherin expression, partly because of the methylation of promoter region.
FP-93 Correlation between Drainage Area Volume of Middle Hepatic Vein and Early Liver Function after Left Liver Harvesting Junichi Kaneko, Sugawara Yasuhiko, Matsui Yuuichi, Akamatsu Nobuhisa, Kishi Yoji, Satou Shouichi, Sano Keiji, Imamura Hiroshi, Kokudo Norihiro, Makuuchi Masatoshi Transplantation Surgery, Graduate School of Medicine, University of Tokyo, Japan Background: Complete outflow is impossible to maintain on both sides in donors undergoing hemi-liver graft harvesting, because the middle hepatic vein (MHV) can be preserved on only one side. The area in which outflow veins are disrupted becomes congested, and does not sufficiently regenerate. Methods: The subjects of the study were 60 living donors who provided the left liver with caudate lobe, including the MHV. The midpoint between the tributaries of the MHV and the right hepatic vein was determined preoperatively with computed tomography. The midpoint between the tributaries of the MHV and right hepatic vein and the borderline between the right and left liver were used to predict the MHV drainage area volume. Total bilirubin levels, the prothrombin time international normalization ratio, and alanine aminotransferase were measured in donors on postoperative days 1, 3, 5 and 7. Results: The parameters that correlated with the MHV drainage area volume included total bilirubin on days 5 and 7, prothrombin time international normalization ratio on day 3, and alanine aminotransferase on day 7. Conclusions: Middle hepatic vein drainage area volume, calculated using the present method, correlated with early liver function after left liver harvesting with the MHV.
FP-94 Clinical Impact of Pattern of Infiltration in Superficial Squamous Cancer of the Esophagus Masahiro Kaneko, Harushi Osugi, Nobuyasu Takada, Masashi Takemura, Shigeru Lee, Yushi Fujiwara, Satoshi Nishizawa, Hiroshi Iwasaki Department of Gastroenterological Surgery, Osaka City University, Graduate School of Medicine, Japan Aim: Correlation of pattern of infiltration with lymphatic spread in superficial cancer was studied. Patients and method: 73 superficial squamous cancers, from 73 patients were subjected. The pattern of infiltration was classified into 4 groups (A: without dropped cancer nest (DCN), B: with DCN but without destruction of basal layer, C: with destruction of basal layer of DCN, D: with invasive growth). The depth of invasion was classified into 6 groups (m1: remained within the epithelium, m2: with partial invasion into the lumina propria musosae, m3: with invasion nearly to the muscularis mucosae, sm1: with invasion to shallow submusosal layer, sm2: middle submusosal layer, sm3: deep submusosal layer). Results: The pattern of infiltration were as follows; A: 10, B: 28, C: 14, D: 21. The groups C and D invaded deeper than groups A and B (P 0.01). Lymphatic invasion was significantly more frequent in groups C and D (P 0.01). In 65 patients who had esophagectomy, lymph node metastasis were found in 13, and all patients were in groups C and D. Recurrences were found in 8 patients and all patients were in groups C and D. Survival was more closely relat-
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ed with the infiltrative pattern than the depth of invasion. Discussion: EMR can be curative for the m3 and sm1 lesions without DCM or without destruction of basal layer of DCN. But, for the patient with lesions associated with destruction of basal layer of DCN or invasive growth, esophagectomy with lymph node dissection should be indicated.
FP-95 Surgical Outcome of Six Cases of Hepato-Ligamento-Pancreatoduodenectomy (HLPD) for Biliary Malignancies Yuji Kaneoka, Akihiro Yamaguchi, Masatoshi Isogai, Tohru Harada, Junji Washizu, Kiyoshi Aikawa Surgery, Ogaki Municipal Hospital, Japan [Purpose] To demonstrate the surgical outcome of HLPD. [Patients and Results] Between 1996 and 2003, we experienced six cases of HLPD for four gallbladder carcinomas and two cholangiocarcinomas. Age of the subjects was 56 to 79 years, mean age was 67.2 years. In the cases of gallbladder carcinoma, two received the right trisectionectomy and the other two received the extended right hepatectomy. Portal vein reconstruction was performed by end-to-end fashion in three and by graft-interposition in one. Arterial reconstruction was required in only one case using the jejunal artery. Two cases of trisectionectomies were dead of liver abscess and septemia in two months after surgery, and the other cases could tolerate the surgery but dead of hepatic and peritoneal recurrence in 10 and 13 months after surgery, respectively. In the cases of cholangiocarcinoma, both received the extended left hepatectomy, portal reconstruction using the external iliac vein graft, and arterial reconstruction using the middle colic artery. Prior case presented the vascular involvement and peripancreatic lymphnodes metastases histologically, the patient is healthy and still alive 5 years and 8 months after surgery without recurrence. Recent case with the paraaortic lymph node metastases has been alive with the local recurrence 9 months after surgery. In our HLPD cases, histological curative resection without paraaortic lymphnode metastasis was achieved only in 2. [Conclusion] We consider that HLPD is still a challenging operation, however, some patients could survive under the strict indication, absence of paraaortic lymphnode metastases and the limited biliary invasion to the remnant liver.
FP-96 Insulinoma - Is Diagnostic Delay Inevitable? Rajendra Kumar Karwasra, Sanjeev Parshad Surgery & Surgical Oncology, Postgraduate Institute of Medical Sciences, Rohtak, India Insulinoma is the most common endocrinal tumor of the pancreas, but it is difficult to diagnose because of its subtle clinical presentation. The symptoms closely mimic psychiatric disorders and, such patients are often treated by psychiatrists for long periods. We present a patient who had multiple episodes of fainting for variable duration while working in fields but he become normal on arrival in the hospital. Every time his investigations were also normal and therefore ultimately treated in psychiatry department till he landed in emergency with coma, which was found to be hypoglycemic in nature. Ultrasonography revealed a small lesion in pancreas and Insulinoma was suspected, but this could not be picked up on CT and MRI. However patient was explored and 2 x 1.5 cm. size
tumor was enucleated from the head of pancreas. We conclude that though diagnostic delay in these patients seems inevitable however diagnosis of insulinoma should be made on a high index of clinical suspicion and biochemical confirmation before labeling the patient psychiatric. Imaging modalities usually fail to localize the tumor because of its small size. Literature also supports this and interestingly Ultrasonography is the most sensitive (60%) as compared to CT scan (24%) and gadolinium based MRI (40%) for this pathology of pancrease.
FP-97 Primary Hepatic Carcinoid - A Rarity Rajendra Kumar Karwasra, Sanjeev Parshad Surgery & Surgical Oncology, Postgraduate Institute of Medical Sciences, Rohtak, India Primary hepatic carcinoid tumors (PHCTs) are extremely rare, and fewer than 50 cases have been reported in the English-language literature. We present a case of primary hepatic carcinoid in a forty year old female, who presented with right hypochondriac mass of few months duration. Ultrasonograpy revealed a huge space occupying lesion of liver which was reported as Haemangioma of right lobe on CT scan and therefore needle biopsy / cytology was deferred. However, on exploration it was found to be a big solid tumor involving almost whole of the right lobe of liver. Left lobe was normal and there was no mass lesion in the rest of the viscera and no lymphnodes were enlarged. Trisegmentectomy was performed and patient stood the procedure well. Final histopathological examination and immunohistochemistry revealed it to be a Carcinoid. Thorough search for any primary lesion was made but none was found. Six cycles of adjuvant Cisplatin with 5 FU were given and patient is well after one year of follow-up. We conclude that since carcinoids are relatively slow growing tumors, even if the lesion is big, major resection should be performed because resection is the treatment of choice for PHCT and offers long-term survival. Clinical details of patient, operative procedure, histo-pathological details along with review of literature will be presented.
FP-98 Functional Evaluation of Laparoscopic Fundoplication for GERD Natsuya Katada, Shinichi Sakuramoto, Nobuyuki Kobayashi, Nobue Futawatari, Shinichi Kuroyama, Shiro Kikuchi, Masahiko Watanabe Surgery, Kitasato University, Japan Laparoscopic fundoplication as minimally invasive surgery for GERD was functionally evaluated . Methods: Eighteen patients (7 males, 11 females, mean age: 63yr.) with GERD were reviewed. Hiatus hernia was noted in all cases. LA classifications of reflux esophagitis (grade A:B:C:D) were 4:1:11:2. Of those, laparoscopic Nissen fundoplication (LN) was performed for 6 patients with normal esophageal body motility, laparoscopic Toupet fundoplication (LT) was performed for 11 patients with poor esophageal body motility, laparoscopic Collis-Nissen (LCN) procedure was applied for a patient with short esophagus. The LES pressures on esophageal manometry were compared before and 3 month after surgery. Twenty-four hour esophageal pH monitoring was performed before and 3 month after surgery. Results: The persistent dysphagia was noted in a patient who had LT, the recurrence of
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acid reflux was noted in a patient who had LT. The preoperative dysphagia was improved in a patient who had LCN. Both subjective and objective data were improved in the remaining 15 patients. The LES pressure increased from 10.0±4.3 to 23.0±6.1 (mmHg, mean±SD, p<0.05) in LN, increased from 11.2 ±4.5 to 14.9±4.3 (mmHg, NS) in LT. The %time pH<4 on esophageal pH monitoring decreased from 15.9±7.6% to 0.2±0.3% (p<0.01) in LN, and decreased from 23.4±23.9% to 7.1±15.7% (NS) in LT. Conclusion: Laparoscopic fundoplication was effective for patients with GERD, resulting in controlling symptoms. Careful preoperative evaluation of patients is critical in order to avoid postoperative complications or failure.
FP-99 Helicobacter Pylori (H.pylori) Infection-Negative Gastric Cancer in a Japanese Population Shunji Kato1, Norio Matsukura1, Tomohiro Kanda1, Noriko Matsuda1, Itsurou Fujita1, Takeshi Okuda1, Takashi Mizutani1, Teruo Kiyama1, Katsuya Tsukada2, Zenya Naito3, Takashi Tajiri1 1 Surgery for Organ Function and Biological Regulation, 2Division of Pathology, 3Integrative Pathology, Nippon Medical School, Japan H.pylori infection rates are closely associated with the development of gastric cancer, although the prevalence of H.pylori infection varies by the ethnicity, location and race. Even though detection systems for H.pylori infection-negative status in patients have not been completely established yet, only 2% of the gastric cancer patients in Japanese were reported to be H.pylori negative as detected by multiple detection systems including pathological and serological diagnosis. In our experience, only 4% of almost 800 primary gastric cancer patients were H.pylori negative displaying neither the anti- H.pylori antibodies nor atrophy in the gastric mucosa detected by biomarkers for pepsinogen I and pepsinogen I/II ratio. And only 10 cases out of 768 cases have no traces for H. pylori infections by both serological and pathological detection methods, and no gastric mucosal atrophy in the stomach. On the other hand, Epstein-Barr (EB) virus is related to cases of gastric carcinogenesis, in affected populations reported, and is approximately 2 to 16% of these cases worldwide. In our study for cardiac gastric cancers or secondary cancers in the remnant stomach, EB virus tested positive in 34% of the 54 gastric cancer cases in which, one forth were H. pylori negative patients. Both EB virus and H.pylori negative cases were 11% of the total. Even though a small fraction of the gastric cancer patients displayed multi-factorial carcinogenesis without infection, but a risk for gastric cancer still exists in a Japanese population. Pathological characteristic for gastric cancer cases will be represented.
FP-100 ABO-Incompatible Living Donor Liver Transplantation with a New Strategy in a Single Center Trial Naoki Kawagishi, Kazushige Satoh, Yoshitaka Enomoto, Yorihiro Akamatsu, Satoshi Sekiguchi, Tatsuya Fukumori, Keisei Fujimori, Susumu Satomi Division of Advanced Surgical Science and Technology, Tohoku University, Japan PURPOSE The donor shortage problem encouraged us to perform living donor liver transplantation (LDLT) across the ABO
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blood barrier. The survival rate in ABO-incompatible transplantations was much poorer than in ABO-compatible recipients for the early experiences, but the introduction of novel immunosuppressive regimens and apheresis has yielded excellent results in ABOincompatible transplantations. METHODS In our institution we experienced 10 ABO-incompatible patients out of 79 LDLT. Those were 5 infants, 3 children and 2 adults. The titer of IgM or IgG more than 16 was the indication for preoperative apheresis. PE or DFPP was performed consecutive 3 days before transplantation and the patients were also administered azathiopurine or MMF 3 days before the transplantation followed by tacrolimus or cyclosporine, as well as methylpredonisolone. Three patients had anti-CD20Ab (rituximab) after operation and 2 patients also had intrahepatic artery or intraportal infusion of prostaglandin E1 and methylpredonisolone. RESULTSNine out of the ten patients were survived. Six patients had preoperative apheresis. Seven patients had acute rejection and five patients were steroid resistant rejections followed by DSG and apheresis. One patient who had accelerated rejection was dead due to liver failure. Three patients who were administered rituximab did not have severe rejections and adverse effects. In the peripheral blood of a patient who had rituximab, CD19 positive lymphocytes were less than 1% until 13 month after LDLT. CONCLUSION Rituximab and vessel infusion therapy have the possibility to become the new strategy for the ABO-incompatible liver transplantation.
FP-101 Primigravida Have Little Knowledge of the Risks of Faecal Incontinence after Childbirth Michael Keighley1, Jasminder Matharu2, Peter Thompson3 1 University of Birmingham, Queen Elizabeth Hospital, 2University of Birmingham, 3Birmingham Women’s Hospital, UK INTRODUCTION To investigate whether pregnant mothers are aware about the risks and treatment of faecal incontinence (FI) after childbirth compared with haemorrhoids and constipation. METHODS A questionnaire delivered to 236 patients attending antenatal clinic. RESULTS There are 6 non valid replies and 20 declined. Of the remaining 210; 91 were primigravidas and 119 were mulltiparous. 89 (42%) did not know about the risk of faecal incontinence compared with only 59 (28%) for haemorrhoids and 52 (25%) for constipation (p<0.01). 61 (29%) thought FI was common and 60 (29%) considered FI to be rare. Lack of knowledge of FI was less than common in multips (35%) compared with primips (53%). 54 (26%) thought that FI was difficult to treat; primips 19 (21%) versus multips 35 (30%). Only 3 (3%) primips had received information about bowel problems after childbirth compared with 33 (27%) amongst multips. Although 34% expressed embarrassment about discussing FI symptoms, 89% would seek help and 77% agreed that treatment would be worth while. CONCLUSIONS Awareness of the risks of FI and the difficulties of successful treatment is more common amongst multips than primips because of lack of information on bowel problems in antenatal clinics.
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FP-102 Sentinel Lymph Node Mapping (SLNM) in Colon Cancer using Patent Blue Wendy Kelder, Jelle Wesseling, Dries Braat, John Plukker 1 Surgery, University Medical Center Groningen, The Netherlands The purpose of our study is to test the sentinel node concept with patent blue in colon carcinoma with focused examination of the sentinel node. In addition, we look for aberrant lymphatic drainage patterns. Our study population consisted of patients with histologically proven colon carcinoma without distant metastasis. SLNM was carried out by injection of 1-3 ml of Patent blue subserosally around the tumor. The first 4 blue nodes were marked with a suture. After marking, routine resection was performed. The tumor and non-sentinel nodes were examined according to standard guidelines. The sentinel node were serially sectioned at intervals of 100 microns. Each section was analyzed with hematoxylin and eosin staining as well as immunohistochemical staining with CAM 5.2. A total of 23 patients were included in the study. The procedure was performed successfully in 22 patients. The sentinel node was negative in 14 patients. In 12 of these 14 patients, the non-sentinel node was also negative, which leads to a negative predictive value of 86%. 8 patients showed metastasis in the sentinel node of which 5 only showed metastasis after immunohistochemistry. This leads to an upstaging of 23%. The accuracy in this study was 20/22 (91%). Aberrant lymphatic drainage leading to extended resection was seen in 3 patients (14%). SLNM with Patent blue in colon carcinoma is feasible and accurate. It leads to an upstaging of nodal status in 23 % of patients and can detect aberrant lymphatic drainage which might lead to therapeutic consequences in the future.
FP-103 Advance in Laparoscopic Approach to Crohn’s Disease Hermann Kessler, W. Hohenberger Department of Surgery, University of Erlangen, Germany INTRODUCTION: Beyond elective ileocecal resection, laparoscopic surgery in Crohn’s disease may be difficult by adverse factors like friable tissue, inflammatory tumor formation and frequent preoperative complications as fistulas, abscesses and bowel obstruction. METHODS: Forty patients(21 female) with Crohn’s disease were operated on laparoscopically-assisted during a period of 4 years. The median age was 34 years(19-75). In 7 cases, ileostomy or bowel exploration was performed, mostly for perianal disease. In 13 uncomplicated cases, ileocecal resection, hemicolectomy or ileal resection was carried out, eventually combined with strictureplasties or appendectomy. In 20 patients, there was recurrent disease (8) and/or complications had occurred as ileus, sealed perforations, abscess formations (4) and fistulas (10) to other organs. RESULTS: In the 13 uncomplicated cases, median operative time was 195 min (120-250). The median length of hospital stay was 8 days (6-27). There was one postoperative anastomotic leak demanding reoperation in a patient who had been treated by highdosage immunosuppressives. In the 20 complicated cases, the small bowel was explored completely after adhesiolysis. In 13 cases, small and large bowel was resected, in 4 of these with extended seg-
ments of ileum or colon. In 5 cases, two separate segments of ileum and colon were resected. In 2 cases of recurrent Crohn’s disease, only small bowel was resected, in one of them with 6 additional strictureplasties. There were no intraoperative complications and no reoperations. The median length of hospital stay was 9 days (6-18). CONCLUSIONS: Even complicated cases of Crohn’s disease with previous surgery, fistulas, abscesses and sealed perforations may be treated safely by laparoscopic technique.
FP-104 c-Met Protein Expression in Colorectal Cancer, Adenoma and its Relationship with Established Clinicopathologic Parameters Jin Kim, Gyeong Chul Lee, Hong Young Moon, Byong Wook Min, Jun Won Um, Seong Ock Suh Surgery, Korea University Hospital, Korea PURPOSE: Hepatocyte growth factor (HGF) stimulates proliferation, migration and morphogenesis of epithelial cells by specific binding to its receptor c-met. Abnomalities of the c-met oncogene have been studied in cancers of many organs including thyroid, lung, pancreas, and stomach. However, little is known about the clinical significance of c-met oncogene abnormalities in colorectal carcinoma. In our study, we investigated amplication and overexpression of the c-met gene in colorectal adenoma and adenocarcinoma then analyzed the clinicopathologic significance between them. METHODS: Expression of c-met was analyzed by PCRSSCP (Polymerase chain reaction-single strand conformational polymorphism) and localized in the tissues using immunohistochemistry. RESULTS: c-met protein was detected in 42.5% (17/40) of colorectal cancer and 10.0% (4/40) of colorectal adenoma (p=0.001). In colorectal cancer, the proportion of expression of c-met protein was 0% (0/40) in stage I, 47.6% (10/40) in stage II, 53.8% (7/40) in stage III, 0% (0/40) in stage IV. c-met protein expression was 18.8% (3/40) in tumors invade into muscularis propria(MP), 58.3% (14/40) in beyond MP tumor. Tumor invasion depth was stastically significant factor (p=0.022) for c-met expression. CONCLUSIONS : The c-met protein expression was related to the depth of invasion of colorectal cancer, and the c-met protein expression was siginficantly different. between adenoma and adenocarcinoma.
FP-105 Clinicopathological Study on Intraductal Papillary Mucinous Tumor of the Pancreas Toshihisa Kimura, Makoto Murakami, Yasuo Hirono, Hiroyuki Maeda, Takanori Goi, Makoto Ishida, Atsushi Iida, Kanji Katayama, Akio Yamaguchi First Department of Surgery, Faculty of Medicine, University of Fukui, Japan PURPOSE AND METHODS: There are still some unanswered questions regarding intraductal papillary mucinous tumors (IPMT) such as how the differential diagnosis of benign or malignant can be made clinically. We studied 14 patients IPMT(adenoma in 8 patients, invasive carcinoma in 6 patients) clinicopathologically. RESULTS: The prevalence of symptoms was higher in IPMT carcinoma than IPMT adenoma. In cystic size, IPMT carcinoma lager than 3cm in diameter was 5/6 while IPMT adenoma lager
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than 3cm in diameter was 2/8. IPMT has overt communication between the cystic tumor and the pancreatic duct system, and dilatation of main pancreatic duct was often observed with IPMT carcinoma. And the visual identification of papilla of vater dilation or mucin secretion were distinguishing feature, that was detected in 5/6 of IPMT carcinoma, but in 1/8 of IPMT adenoma. By angiography, vascular encasement was detected in 3/6 of IPMT carcinoma, on the contrary, it was not detected in IPMT adenoma. The following surgical procedures were performed: pancreaticoduodenectomy (n=8), distal pancreatectomy (n=3), partial pancretectomy (n=2), probe lapalatomy (1). 11patients are presently well without any recurrence. CONCLUSIONS: The incidence of carcinoma in IPMT was higher in the main duct type than in the branch type. Our observations suggested IPMT carcinoma seemed to be lower grade malignant rather than invasive ductal carcinoma of the pancreas because of its low incidence of lymphnode metastasis and low potential of invasive growth.
FP-106 Is Surgical Resection of Carcinoma of the Pancreas a Battle against Nerve Invasion? - Retropancreatic Invasion and Extrapancreatic Nerve Plexus Invasion Wataru Kimura The First Department of Surgery, Yamagata University School of Medicine, Japan There are many ambiguous aspects of retropancreatic invasion of carcinoma of the head of the pancreas, especially with regard to its definition and general recognition and to how it differs from invasion of the extrapancreatic nerve plexus. Histologically, retropancreatic invasion means that carcinoma invades over the pancreatic parenchyma and reaches the arteries, veins and nerves of various sizes that exist between the parenchyma and a loose connective tissue membrane, i.e., the fusion fascia. Extrapancreatic nerve plexuses are divided into seven parts. Three parts, the first and second parts of the plexus of the pancreatic head and the plexus of the superior mesenteric artery, are very important in surgical pathology. The extrapancreatic plexus seems to start from the left end of the uncus to join the plexus of the mesenteric artery and celiac ganglion. In the pancreatic head, the parenchyma arteries and veins of the pancreaticoduodenal arcades, as well as nerve tissue and the first and second nerve plexuses and the superior mesenteric nerve plexus exist on the abdominal side of the fusion fascia. Carcinoma of the head of the pancreas invades through the pancreatic parenchyma, following the arteries, veins and nerves between the parenchyma and fusion fascia, and then spreads horizontally toward the superior mesenteric artery or celiac axis. We should recognize these different patterns of spreading of carcinoma of the head of the pancreas.
FP-107 Possibility of Extended Lymph Node Dissection for Advanced Gastric Cancer Taira Kinoshita, Masaru Konishi, Toshio Nakagohri, Shinichirou Takahashi, Naoto Gotohda, Norio Saito, Masanori Sugitou, Masaaki Itou, Akihiro Kobayashi Surgical Oncology, National Cancer Center Hospital East, Japan According to the Japanese Guide Lines, standard width of lymph
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node dissection for advanced gastric cancer is D2 (level 2). Prophylactic extended lymph node dissection is only permitted in clinical trial. JCOG (Japan Clinical Oncology Group) conducted a trial to clarify significance of para-aortic lymph node dissection which finished accrual of more than 500 patients and is waiting for the final analyses. (Purpose) to clarify significance of para-aortic lymph node dissection for advanced gastric cancer. (Patients and Methods) Between 1992 and 2002, 374 patients received para-aortic lymph node dissection with curative intent in our institution. Rate of histologically proven metastasis and their 5-year survival with other background data were analyzed. (Results) Among these 374 cases, 57 (15.2%) had histologically proven metastasis. Their 5-year survival rate is 22%. Six patients have survived more than 5 years. When compared with cases without para-aortic lymph node dissection (29.0%), morbidity rate of the dissected patients was high (49.5%). However, mortality rate was nearly the same in two groups (dissected:0.6%, not dissected:1.0%). (Conclusions) Considering the incidence of histologically proven metastasis, a high 5-year survival rate and a low mortality rate, para-aortic lymph node dissection for advanced gastric cancer seems feasible and significant. After the appearance of the effective anti-cancer drug, S-1, significance of paraaortic lymph node dissection for advanced gastric cancer should be reevaluated in a different setting trial including neoadjuvant chemotherapy.
FP-108 Sharing the Middle Hepatic Vein between Donor and Recipient: Left Liver Graft Harvesting by Preserving a Thick V8 in Donor Yoji Kishi, Yasuhiko Sugawara, Hiroshi Imamura, Keiji Sano, Junichi Kaneko, Yuichi Matsui, Nobuhisa Akamatsu, Norihiro Kokudo, Masatoshi Makuuchi Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan Purpose: There are many reports of surgical procedures to minimize the hepatic congestion in partial liver transplantation, but most refer only to the congestion of right liver. Here we report a technique to minimize the congestion in the donor after left liver graft harvesting. Methods: If a thick tributary of the MHV draining the segment VIII (V8) converged into the root of the MHV in a donor of left liver, this branch was considered to be preserved in donor side. The volume of congested area when V8 was ligated was predicted preoperatively by computed tomography and examined intraoperatively by the clamp test. Postoperative regeneration of donor liver was evaluated by the computed tomography volumetry. Results: This technique was used in three cases. The regeneration rate of the right paramedian sector was 27, 38, and 8%, and that of right lateral sector was 31, 63, and 39% in each donor respectively after 3 months. No severe complications occurred in the donors. Conclusions: V8 preservation in donor who underwent left liver resection led to satisfactory regeneration both of the right paramedian and lateral sectors and can minimize congestion in remnant liver.
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FP-109 Chemotherapy using Gemcitabine for Unresectable and Recurrent Biliary Tract Cancer Chie Kitami1, Isao Kurosaki2, Naoyuki Yokoyama2, Daisuke Sato2, Katsuyoshi Hatakeyama2 1 Niigata University Graduate School of Medical and Dental Sciences, Niigata, 2Digestive and General Surgery, Niigata University Graduate School of Medical and Dnetal Sciences, Niigata, Japan Purpose: There have not been established the standard chemotherapy for advanced biliary tract cancer. Gemcitabine has recently been introduced into clinical practice and displays a broad range of activity in a variety of tumors. We used gemcitabine for the patients with unresectable and recurrent biliary cancer to evaluate the clinical potential in the treatment of biliary cancer. Patients and Methods: Six patients received gemcitabine therapy (2 with unresectable bile duct cancer, 2 with unresectable gall bladder cancer, 2 with recurrent bile duct cancer) and were evaluated the response and toxicity. In four patients with unresectanle cancer, 3 patients had tumors invading hepatic artery, portal vein, and hepatoduodenal ligament, and one patient had peritoneal dissemination. One of the recurrent patients was performed hepatectomy for recurrent hepatic tumor from the bile duct cancer. Patients were given gemcitabine 1000mg/ m2 for 30 minutes on a weekly schedule for 3 weeks followed by a week rest and UFT 300mg /day or TS-1 100mg /day were administered on days 1-5, 8-12, 15-19. Result: The median survival times in these patients were 16.5 months (range 8-29 months). Toxicity consisted of grade 2/3 leukopenia in 3 patients with no episode of febrile nertoropenia, oral mucositis in one patient, tremor in one paient. A total administration of gemcitabin was average of 3.3 cycles per patient. Conclusion: Although further investigation is needed, gemcitabine is a promising agent for the treatment of advanced and recurrent biliary tract cancer.
FP-110 Anatomical Analysis of a Posterior Segment in Liver with Tree Dimensional Image of Computed Tomography Susumu Kobayashi, Ryu Munemasa, Wataru Takayama, Akihiro Cho, Makoto Sugaya, Naoyuki Hanari, Noriyuki Hattori, Tadashi Okada Department of Surgery, Chiba Prefecture Hospital of Sawara, Japan Background. We proposed that right lobe should be divided into three segments of anterior ventral, anterior dorsal and posterior portions. Couinaud separated a posterior segment into S6 and S7. However a interpositonal plate between S6 and S7 is not clear, and the distribution of the branches has many variations. We investigated the distribution of P6 and P7 branches and discussed the appropriate segmentation. Methods. We reconstructed three-dimensional portography from CTAP image in 100 cases. Among these cases, we clarified the portal vein distribution into Ppa, Ppb, Ppc, and P7, and investigated the positional relationship between the portal vein and right hepatic vein. Results and Conclusions. 1: The frequencies of the portal vein distribution were as follows; Ppa+P7, 39%; Ppa+ Ppb+P7,33%; Ppa+ Ppb+Ppc+P7,28%. 2: 56% of Ppa (the first branch of P6) located in the ventral side of right hepatic vein. These results indicated that it is difficult to clarify the posterior segment into P6 and P7,
and that the posterior segment involve the ventral portion of right hepatic vein in over 50 % of cases.
FP-111 Risk Factors for Surgical Complications in Gastric Cancer: Analysis of Data Obtained from JCOG9501, a Trial Comparing Extended and Super-Extended Lymphadenectomies Yasuhiro Kodera1, Mitsuru Sasako2, Seiichiro Yamamoto2, Takeshi Sano 2, Atsushi Nashimoto3, Akira Kurita4, Hiroshi Furukawa5, Satoshi Kobayashi6, Taira Kinoshita7, Kunikazu Arai8, Hiroshi Isozaki9 1 Department of Surgery II, Nagoya University Graduate School of Medicine, 2National Cancer Center, 3Niigata Cancer Center, 4 National Shikoku Cancer Center, 5Sakai City Hospital, 6Kanagawa Cancer Center, 7National Cancer Center East, 8Tokyo Metropolitan Komagome Hospital, 9Ohmoto Hospital, Japan Background: Extended lymphadenectomy for gastric carcinoma was associated with high mortality and morbidity in several multicenter randomized trials in the West. Although mortalities reported from the Japanese institutions were much lower, most of data analyzed were of retrospective nature. Method: Using data from 523 patients registered for a prospective randomized trial comparing extended (D2) and super-extended (D2 plus paraaortic lymph node dissection) lymphadenectomies (JCOG9501), risk factors for overall complications and major surgical complications (anastomotic leakage, intraabdominal abscess, and pancreatic fistula) were identified by multivariate logistic regression analysis. Results: Mortality and morbidity were 0.8% (4 of 523) and 24.5% (128 of 523), respectively. Pancreatectomy (relative risk 5.61, 95% confidence interval 1.95~16.16) and prolonged operating time (relative risk 1.61, 95% confidence interval 1.16~2.25) were the most important risk factors for overall complications. Body mass index of 25 kg/m2 or above, pancreatectomy, and age greater than 65 years were factors significantly influencing the occurrence of major surgical complications. Conclusion: Mortality for radical gastrectomy is remarkably low among specialized institutions in Japan. Distal pancreatectomy is a major risk factor for postoperative complications and should be reserved for T4 stage patients. Older age and obesity should be considered when planning surgery.
FP-112 Prognostic Significance of Intraperitoneal Cancer Cells in Gastric Carcinoma: Detection of CK20 mRNA in the Peritoneal Washes in Addition to CEA Yasuhiro Kodera1, Hayao Nakanishi2, Michitaka Fujiwara1, Seiji Ito3, Yoshitaka Yamamura3, Hiroyuki Yokoyama1, Norifumi Ohashi1, Kenji Ysuboi1, Masahiko Koike1, Kenji Hibi1, Akimasa Nakao1 1 Department fo Surgery II, Nagoya University Graduate School of Medicine, 2Aichi Cancer Center Research Institute, 3Aichi Cancer Center Hospital, Japan Background: Presence of free cancer cells in the peritoneal cavity is a significant prognostic factor for gastric carcinoma. Application of real-time reverse transcriptase-polymerase chain reaction (RTPCR) technique with carcinoembryonic antigen (CEA) mRNA as a target enhanced sensitivity. An additive role of evaluating cytokeratin 20 (CK20) mRNA was explored.
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Methods: Peritoneal washes were obtained from 195 gastric carcinoma patients during surgery. CEA, CK20, and glyceraldehyde-3phosphate dehydrogenase (GAPDH) mRNA levels were quantified using LightCycler with fluorescent hybridization probes. Results: The CK20/GAPDH ratio (CK20 mRNA normalized by the expression of GAPDH) was reasonably specific (specificity of 92%) but was limited in terms of sensitivity (64% at the optimal cutoff value) for detecting disseminated cancer cells. CEA had a potential as more sensitive target for RT-PCR. A multi-marker analysis by which samples positive for either CK20 or CEA are considered positive for cancer cells (sensitivity 74%) was identified as a significant independent prognostic determinant along with invasion of the serosa and node metastasis by a multivariate analysis using Cox regression hazards model. Conclusions: A multi-marker analysis with the combination of CEA and CK20 RT-PCR is adequate for detection of free cancer cells and could be useful for identifying candidates for postoperative adjuvant chemotherapy.
FP-113 Transcriptional Induction of Colonic Cancer Cell Adhesion to Endothelial Cells by Hypoxia Tetsufumi Koike1, Naoko Kimura1, Guo-Yun Chen1, Keiko Miyazaki1, Mineko Izawa1, Tomonori Yabuta2, Kensuke Kumamoto2, Seiichi Takenoshita2, Reiji Kannagi1 1 Division of Molecular Pathology, Aichi Cancer Center Reserch Institute, Japan, 2Department of Surgery 2, Fukushima Medical Univ., Japan Cancer cells acquire an ability to cope with their hypoxic conditions through several metabolic changes, which are mainly mediated by the transcriptional factors called hypoxia-inducible factors (HIFs). We investigated gene expression in cultured human colon cancer cells induced by hypoxic conditions using DNA microarray and RT-PCR techniques, with special reference to carbohydrate determinants having cell adhesive activity and related cell adhesion molecules. Hypoxic culture of colon cancer cells induced a marked increase in expression of selectin ligands, the sialyl Lewis x and sialyl Lewis a determinants at the cell surface, and this led to a definite increase in the cancer cell adhesion to endothelial E-selectin (PNAS, 101: 8132, 2004). The transcription of genes for fucosyltransferase VII, sialyltransferase ST3Gal-I and UDP-galactose transporter-1, which have been known to be involved in the synthesis of the carbohydrate ligands for E-selectin, was significantly induced in cancer cells by hypoxic culture. In addition, a remarkable induction was detected in expression of the genes for syndecan-4 and a5-integrin, the cell adhesion molecules, which enhanced adhesion of the cancer cells to fibronectin. The transcriptional induction of these genes by hypoxia was reproduced in the luciferase reporter assays for these genes, which were significantly suppressed by the co-transfection of a dominant-negative form of HIF. These results indicate that the metabolic shifts of cancer cells partly mediated by HIFs significantly enhance their adhesion to vascular endothelial cells, through both selectin- and integrin-mediated pathways, and suggest that this enhancement further facilitates hematogenous metastasis of cancers and tumor angiogenesis.
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FP-114 Preoperative Diagnosis of Obturator Hernia, 5 Cases Experience Masaki Koizumi1, Masao Ogata1, Yasuaki Mori2, Joji Matori2, Kiichiro Uchiyama2, Akira Tokunaga1 1 Institute of Gastroenterogy, Nippon Medical School 2nd Hospital, Japan, 2Ebina General Hospital, Japan Obturator hernia has been thought to be difficult to diagnose and easy to repair. Most patients are elderly, weak, and emaciated. Before CT scan developed, delayed diagnosis of strangurated obturator hernia lead to high mortality (10-50%). In these days, the hernia can be easily diagnosed by CT scan. The correct diagnosis rate before operation (82.9%) improved the mortality of this disease (3.9%). However the incidence of bowel resection (49.8%) is still high.In order to avoid bowel resection as possible as we can, early diagnosis and early operation are very important. Non-strangrated obturator hernia could be determined by CT scan when the interval of external obturator muscle and pectineal muscle is larger than 10 mm. If connective tissue shadow is appeared in that space, more certainly.This abstract describes 5 cases of obturator hernia diagnosed by CT scan preoperatively, during 3 years period. All patients were emaciated women, over 80’s. One case repeated reduction and re-strangulation, and another case occurred the contralateral hernia after the initial hernia repaired. Preoperative pelvic CT films in 2 cases showed nonstrangulated obturator hernia. We would like to stress the usefulness of active CT screening for high risk case or suspected case. It could reveal non-strangurated obturator hernia and allow us select more minimally invasive surgery. Near future obturator hernia will be easy to diagnose and easy to repair.
FP-115 Cytomegalovirus Infection in Severe Ulcerative Colitis Tetsu Kojima, Toshiaki Watanabe, Keisuke Hata, Masaru Shinozaki, Hirokazu Nagawa Surgical Oncology, The University of Tokyo, Japan PURPOSE: Cytomegalovirus infection has been reported as an exacerbating factor of inflammatory bowel disease recently but it is not clear how Cytomegalovirus infection affects ulcerative colitis. The aim of this study is to investigate clinicopathological features of Cytomegalovirus infection in ulcerative colitis. METHODS: Surgical specimens were examined for Cytomegalovirus infection by hematoxylin and eosin staining and/or immunohistochemical staining in 120 patients with ulcerative colitis underwent total colectomy in our hospital. Also risk factors of Cytomegalovirus infection in severe ulcerative colitis were investigated by multivariate analysis. RESULTS: Cytomegalovirus infection was detected in 6 cases (5 %). In the point of view of operative indication, Cytomegalovirus infection was detected in 5 of 23 cases (22%) with severe ulcerative colitis, 1 of 74 cases (1.3%) with refractory ulcerative colitis and none of 23 cases (0%) with ulcerative colitis-associated colorectal cancer or dysplasia. The ratio of Cytomegalovirus infection in patients with severe ulcerative colitis was significantly higher than that in patients with refractory ulcerative colitis and ulcerative colitis-associated colorectal cancer or dysplasia (p=0.0001). Age at the time of operation was significantly higher in the group of
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Cytomegalovirus infected severe ulcerative colitis than that of the non-Cytomegalovirus infected severe ulcerative colitis (p=0.02). Gender, total steroid dose of life, total steroid dose of one month before operation and immunosuppressive agents (azathioprine, 6mercaptopurine and methotrexate) were not the risk factors of Cytomegalovirus infection. CONCLUSIONS: Cytomegalovirus infection was significantly frequent in severe ulcerative colitis and risk factor of Cytomegalovirus infection was an advanced age in severe ulcerative colitis.
FP-116 Radical Bile Duct Resection for Extrahepatic Bile Duct Cancer Masaru Konishi, Taira Kinoshita, Toshio Nakagohri, Shinichiro Takahashi, Naoto Gotohda Surgery, National Cancer Center Hospital East, Japan Purpose: Although pancreatoduodenectomy or hepatectomy is commonly used for extrahepatic bile duct cancer, bile duct resection represents an attractive operation for isolated bile duct cancer. Methods: Between 1992 and 2004, 28 patients with bile duct cancer (hilar 9, middle 18, distal 1) underwent bile duct resection. Eight patients underwent palliative resection and 5 patients with high risk condition underwent bile duct resection without lymphadenectomy. The other 15 patients (hilar 2, middle 13) underwent bile duct resection with radical lymphadenectomy (BD-R). Indications for BD-R comprised bile duct cancer which did not invade to adjacent organ and localized in the bile duct between the liver and pancreas. In this study, we analyzed BD-R. Results: The morbidity rate was 20%, and there were no operative deaths. These rates were better than those in the patients undergoing pancreatoduodenectomy or hepatectomy. There were one patient with stage I, eight patients with stage II, nine patients with stage III. The 5-year survival rates were 40%, as compared with 24% in the patients undergoing pancreatoduodenectomy or hepatectomy with stage I-III. Moreover, in the patients with curative resection, the 5-year survival rate was 49%. Five patients died as a result of distant metastasis. The recurrence sites were the liver only in 3 patients, liver and distant lymphnodes in 1 patient, and dissemination in 1 patient, which likely could not be avoided by the extensive operations. Conclusion: Bile duct resection with radical lympnadenectomy represented a safe and attractive option for bile duct cancer without adjacent organ invasion.
FP-117 Selection of the Treatment of Common Bile Duct Stone Hiroyuki Konomi1, Kiichirou Kobayashi1, Eiji Miyatake2, Koji Hokazono1, Shuji Shimizu2, Masao Tanaka1 1 Department of Surgery and Oncology, Graduate School of Medical Science, 2Department of Endoscopic Diagnostics and Therapeutics, Kyushu University Hospital, Japan Strategy for the treatment of common bile duct (CBD) stones has become complicated with the advent of laparoscopic cholecystectomy as a standard treatment for cholecystolithiasis. Laparoscopic cholecystectomy combined with endoscopic sphincterotomy (LC+ES) and laparoscopic CBD exploration (LCBDE) are two major treatments for CBD stones in the era of laparoscopic surgery. Aim: To investigate surgical outcome after LC+ES and
LCBDE retrospectively and determine the standard strategy for CBD stones. Methods: Fifty-two patients of either LC+ES (n=23) or LCBDE (n=29) were enrolled in the study. The number of treatment session(s), operation time, blood loss, complication(s) and stone recurrence were reviewed. Background differences between the two groups regarding the sex, age, CBD diameter, number and size of CBD stones were not significant. Results: The number of treatment sessions was significantly greater in LC+ES group. Operation time was longer in LCBDE group; however, there was no significant difference in blood loss. Retained stones (13.8 %), bile leak (2.4%) occurring only after LCBDE could be managed conservatively. There was no mortality in either group. Stones recurred in 6.9% of LCBDE and 4.4% of LC+ES. There was no statistically significant difference between the two groups regarding these complications. Conclusions: LCBDE is a favorable selection because it is the one-stage procedure and obviates the need for ES. However, retained stones and bile leaks occurred exclusively after LCBCE and operation time was significantly longer. Further technical and instrumental improvements are essential for safer and more efficient LCBDE. LC+ES may still be a satisfactory selection at the moment.
FP-118 Mediastinal Pancreatic Pseudocysts, Case Reports and Review of Literature Istvan Kovacs, Lukaes Veres, Peter Sapy 2nd Department of Surgery, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Hungary Pancreatic mediastinal pseudocyst is a rare condition and remain a challenging problem. Sixty-five cases have been reported in the English Language literature over the past 25 years. Currently, there is some debate concerning the appropriate management of large pancreatic pseudocysts. The last five years 103 patients were treated with pancreatic pseudocysts. Tvelwe patients underwent CT gaided percutaneous drainage. 89 patients were enteric drainage. Cystectomy were performed in two cases. Cystogastrostomy 33, Juras intervention 12, Cystoduodenostomy 20, Wirsungocystojejunostomy 7, wirsungocystogastrostomy 13, splenectomy with pancreatic tail resection in one case was performed. Fourteen patients had grater than 10 cm the pseudocyst size. Three cases had mediastinal pseudocyst. The most common primary cause were chronic alcoholism, and gallstones indicated secondary pancreatitis and trauma. The indications of interventions were sepsis, pain, biliary and gastric outlet obstruction. In cases with mediastinal pseudocyst were chest or back pain, dysphagia, dyspnoe, nausea and vomiting and weight loss. The mediastinal pseudocysts entered the mediastinum through the oesophageal or aortic hiatus in two, through the foramen Morgagni in one case. Several reports described direct penetration through the diaphragm. After adequate internal drainage the mediastinal mass and components are rapidly disappear, included clinical manifestations and compliences. There was no perioperative death. The aims of operative management of pancreatic pseudocysts to evacuate the cyst contents and prevent the serious complications of cyst rupture, haemorrhage, infections, intestinal obstruction, external compression of heart and lung. The basis of our experience the most expedient method is an internal drainage procedure, preferably cystogastrostomy.
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FP-119 Results of Different Kind Surgery of Pancreatic Head and Periampullary Tumours Istvan Kovacs, P Arkossy, J Hallay, P. Sapy 2nd Department of Surgery, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Hungary The aim was the comparison of operative outcome, nutritional recovery and survival of patients who underwent Whipple pancreaticoduodenectomy (WP), pylorus preserving pancreaticoduodenectomy (PPPD) and palliative therapy of periampullary tumours. From 1999 to 2004 we observed 126 patients due to pancreas and periampullary tumours. The tumour located in the head of pancreas in 76 patients and 27 patients in the ampullary region. 16 tumours originated from the ampulla of Vater and 7 from common bile duct. The operability rate was in patients with pancreatic head tumours 27% (21pst) and 59% (19pst) with periampullary tumours. Considering 40 resections: 3 WP, 31 PPPD, and six local excisions. The mortality rate was 2 (5%). The elevated serum level of CA 199 is a sensitive marker in the case of pancreatic cancer. The postoperative complications were in 8 (20%) patients. Delayed gastric emptying was more common in the PPPD group resulting longer hospitalisation. In PPPD group there was a better nutritional recovery, increased body weight and serum albumin level. There was no significant difference between the survival of WP and PPPD group. We found better survival in patients with periampullary tumour. Our data provided many evidences about the advantage of PPPD in the patients with periampullary tumours. There is no difference between the survival rates of WP and PPPD. The long term results and quality of life is better after PPPD.
FP-120 Role of Chemosensitivity Test in Advanced Gastric Cancer Tetsuro Kubota1, Yoshiro Saikawa1, Yoshihide Otani1, Masashi Yoshida1, Koichiro Kumai2, Masaki Kitajima1 1 Department of Surgery, 2Division of Diagnostic and Therapeutic Endoscopy, Keio University, Japan [Purpose] To clarify the usefulness of chemosensitivity test in evaluating the post-operative cancer chemotherapy for advanced gastric cancer, 7 trials were investigated. [Clinical Chemosensitivity Test Result] Between 1994 and 2003, 7 studies were conducted using MTT assay (MTTA) or histoculture drug response assay (HDRA), comparing the survival outcome in sensitivity and resistant group. Patients were split into groups according to stage III or IV gastric cancer, and then categorized into sensitive and resistant cases as determined by the assay. When the background factors were adjusted, 186 sensitive patients showed favorable survival outcome than 199 cases whose specimens were detected to be resistant. [Molecular Biological Chemosensitivity Test] Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme of (fluorinated) pyrimidine degradation that plays a significant role in the pharmacokinetics of 5-fluorouracil (5-FU). To clarify the resistant mechanism of 5-FU, DPD mRNA and enzymatic activity were compared with 5-FU sensitivity, using 7 human tumor xenografts in nude mouse, and 138 gastric cancer specimens in 5 trials, in which high DPD-expression resulted in 5-FU low sensi-
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tivity with reproducibility. [Conclusion] Chemosensitivity testing, based on the MTT assay and HDRA, was useful in evaluating the appropriate cancer chemotherapy for patients with stage III/IV gastric cancer without peritoneal dissemination. The reproducibility was confirmed in this usefulness of chemosensitivity test for 10 years, and the important role of DPD in 5-FU-resistance for 5 years. The further prospective trial is under planning to clarify the usefulness of chemosensitivity test in evaluating the postoperative cancer chemotherapy for advanced gastric cancer.
FP-121 Extended D2 (D2+) Lymphadenectomy for Gastric Cancer does not Increase the Perioperative Complication Rate Jan Kulig, Tadeusz Popiela, Piotr Kolodziejczyk, Marek Sierzega, Polish Gastric Cancer Study Group 1st Department of Surgery, Jagiellonian University, Poland Background: A multicentre, randomised, clinical trial involving 8 academic centres to evaluate the potential benefits of extended lymphadenectomy in patients with curatively resected GC. Methods: Between January 1998 and December 2003, 781 patients qualified for gastric resection due to GC were screened for eligibility to participate in the study. Standard D2 lymphadenectomy was defined according to the Japanese Classification of Gastric Carcinoma. Extended D2 lymph node dissection (D2+) consisted of D2 lymphadenectomy and additional removal of para-aortic nodes. Results: Of 781 patients who underwent laparotomy, 379 were found not to satisfy eligibility criteria. The remaining 402 were randomly allocated to group A (standard D2) or group B (extended D2 lymphadenectomy). After the final evaluation of surgical specimens a total of 291 patients were included to the final analysis; Group A - N=151, group B - N=140. Perioperative mortality rates for group A and B were 4.4% and 0.7%, respectively (p=0.08). Although the overall perioperative morbidity rates were slightly higher in group A (31.2%) than in group B (22.0%), the observed difference was not statistically significant (0.06). Thirty-four (16.8%) patients in group A developed surgical complications , compared to 18 (12.8%) in group B (p=0.30). The incidence of individual complications was comparable in both groups. Non-surgical complications were observed in 49 (24.3%) group-A-patients and 20 (14.2%) patients in group B (p=0.02). Pulmonary complications were more frequent in group A. Conclusions: Our findings suggest that D2+ lymph node dissection does not increase the rate of perioperative complications.
FP-122 3 Cases of Aberrantly Protruded Lipomas of the Cord, Resembl the Interstitial Hernia, Treated with Prolene Hernia System Kaori Kumakura, Gen Shimada, Shintaro Sakurai Surgery, St. Luke’s International Hospital, Japan [Back ground] According to Gilbert, the lateral triangle of the groin sometimes lacks the coverage of the transversalis muscle and it may become site of the interstitial hernia. Cord lipoma is protrusion of the preperitoneal fat through the internal ring, mostly associated with an indirect inguinal hernia. We experienced three cases of aberrantly located cord lipoma, which penetrated the transversus abdominis and internal oblique muscles within the lateral trian-
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gle. [Case outline] In all three cases, preoperative diagnosis were indirect inguinal hernias. After opening the inguinal canal, we found 1x2cm sized fatty tissue, located between the external oblique aponeurosis and the internal oblique muscle, 1cm cephalic to the internal ring. As the dissection progressed, it was found out to be the aberrantly protruded cord lipoma, resemble the interstitial hernia within the lateral triangle. The lipoma was pulled down to the the internal ring and resected. High dissection of indirect hernia sac was completed and it was reduced into the preperitoneal space. The medial and lateral triangle, including the internal ring and the defect, which the aberrantly protruded cord lipoma penetrated, were doubly covered with the underlay and onlay patch of the Prolene Hernia System. No recurrence developed. [Conclusion] If this type of aberrantly located cord lipoma is misdiagnosed as solely indirect hernia and repaired with a plug into the intrnal inguinal ring alone, recurrence is predictable. It’s important not to miss a defect in the lateral triangle, independent to the internal ring and PHS is useful to repair it.
FP-123 Active Bleeding from the Ascending Colon Diverticulum Localized and Evaluated the Severalty by the Serial Enhanced CT Scan Preoperatively ; A Case Report Kaori Kumakura, Gen Shimada, Shintaro Sakurai Surgery, St. Luke’s International Hospital, Japan [Back ground] Patients with the active bleeding from the colonic diverticula require surgical interventions in some situations. Making an accurate localization of the bleeding point is desirable to carry out operations safely. Colonoscopy, angiography, and scintigraphy have been standard modalities for the localization. But they are time consuming and sometimes impossible to use for unstable patients. Hereby, a case of the active bleeding from the ascending colon diverticulum successfully diagnosed by the serial enhanced CT scan is presented. [Case outline] A 50 years old generally healthy lady had hematochezia and came to our outpatient clinic. Colonoscopy showed multiple diverticulum without active bleeding. She had been followed up by the outpatient clinic. 4 months later that episode, she was brought to the emergency room with brisk hematochezia. The enhanced CT scan revealed extravasations of the contrast medium to the hepatic flexure of the ascending colon lumen. Although vital signs were stable, CT was repeated to evaluate whether active bleeding is continuing. It showed increasing the volume of contrast medium which suggested persisting bleeding and an emergency operation was indicated. Right hemicolectomy was performed. The ascending colon with multiple diverticulum was filled with clot. Patient was good condition after the operation. [Conclusion] Enhanced CT scan can be a feasible diagnostic modality to evaluate hematochezia patients.
FP-124 Kinase Mutations and Imatinib Response in Taiwanese Patients with Metastatic Gastrointestinal Stromal Tumor: Experience at Chang Gung Memorial Hospital Wen-Ling Kuo, Chun-Nan Yeh, Yi-Yin Jan, Miin-Fu Chen General Surgery Department, Chang Gung Memorial Hospital, Taiwan Purpose Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoform of kit or kinase plateletderived growth factor receptor alpha (PDGFR) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of Taiwanese patients with advanced GIST. Method and materials Between 2001 and 2004, 26 metastatic or advanced GIST patients who treated with imatinib mesylate were reviewed. The tumor was examined for mutations of KIT or PDGFRA and the mutation types were correlated with clinical outcomes. We also assessed anitumor response and the safety and tolerability of the drug. Results There were 15 men and 11 women with the mean age 55.5 years (range 28-81). Therapy was well tolerated, although mild edema was common. Overall, 17 patients (65.4%) had a partial response, 5 stationary disease (19.2 %), 4 progressive disease (15.4%). Activating mutations of KIT were found in all the 17 tested patients and no PDGFRA mutant isoforms was found. In patients with GISTs haboring exon 11 kit mutations, the partial response rate (PR) was 84.6%, whereas patients with tumors containing an exon 9 KIT mutation had PR rates of 66.7% (not significant). Conclusions Imatinib induced a sustained objective response in more than half of patients with advanced unresectable or metastatic GISTs. Activating mutations of KIT are found in the vast majority of GISTs.
FP-125 Results of Surgical Resection for 445 Cases of Hepatocellular Carcinoma with Assesment of Makuuchi Criterion and Clip Score Shigehiro Kure, Tetsuya Kaneko, Shin Takeda, Soichiro Inoue, Akimasa Nakao Digestive Surgery II, Graduate School and Faculty of Medicine, Nagoya University, Japan Objective To evaluate the efficacy of the Makuuchi criterion in determining an appropriate hepatectomy, and the efficacy of the CLIP score in predicting the prognosis for patients with hepatocellular carcinoma undergoing a hepatectomy. Summary Background Data The Makuuchi criterion was proposed to decide an appropriate hepatectomy for a hepatic tumor in an impaired liver, but there is no report on the re-evaluation of the criterion’s validity in other institutions. Also, there are few reports evaluating the CLIP score that is limited to a hepatectomy. Methods We conducted our study on 445 patients with hepatocellular carcinoma, resected from January 1986 to March 2003. We evaluated several factors, including mortality, survival, surgical procedure, bleeding, the postoperative max level of serum total bilirubin, the CLIP score, the ICG K value, and the Makuuchi criterion.
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Results Our study showed that the Makuuchi criterion was not concerned with long term prognosis, but intraoperative bleeding, the mortality rate, and the postoperative max serum bilirubin level were significantly less in the conformity group. We also found that the CLIP score predicted the prognosis significantly. Massive bleeding was significantly associated with mortality (p < 0.0001). Conclusions The Makuuchi criterion was confirmed to be helpful in performing a safe and appropriate hepatectomy for patients with hepatocellular carcinoma and a liver dysfunction. However, it could not predict the prognosis after the hepatectomy. The CLIP score is effective in predicting the prognosis for hepatocellular carcinoma, even for patients undergoing a hepatectomy.
FP-126 Five-year Results and Perioperative Morbidity of Laparoscopic-assisted Colectomy vs. Open Colectomy for Colorectal Cancer Takeshi Kurihara, Masazumi Okajima, Satoshi Ikeda, Katsufumi Kawabori, Hiroyuki Egi, Yasuyo Ishizaki, Masanori Yoshimitsu, Noriaki Tokumoto, Jiro Okiyama, Naoyuki Ogawa, Manabu Kurayoshi, Michinori Arita, Yasutomo Ojima, Toshimasa Asahara Department of Surgery, Division of Frontier Medical Science, Hiroshima University, Japan Purpose: Laparoscopic-assisted colectomy (LAC) was introduced as the operation method for not only early colorectal cancer (CRC) but also advanced colorectal cancer since 1998 in our department. Our contraindication of LAC is T4 in all regions and T2-T4 in rectal Rb region. The aim of study is to compare safety and efficacy of LAC and open colectomy (OC) for CRC. Materials and Methods: We assessed 171patients who were received LAC, and 189 patients who were received OC during the period from 1998 to 2003. Five-year overall and disease free survival rates and perioperative morbidity were analyzed. Results: Five-year overall and disease free survival rates of patients who had LAC vs. OC were Stage I (93 cases 100%, 98.3% vs. 27 cases 100%, 92.3%, p=0.2534), Stage II (32 cases 94.7%, 94.7% vs. 27 cases 83.3%, 81.7%, p=0.7037, 0.2310) and Stage III (33 cases 84.1%, 67.3% vs. 82 cases 69.6%, 58.7%, p=0.5418, p=0.187). There were no intraoperative complications. The incidence rate of postoperative complications in the patients who had LAC vs. OC were anastomotic leak (0.6% vs. 3.2%), adhesive ileus (2.3% vs. 6.3%), wound infection (10.5% vs. 10.5%), pneumonia (0% vs. 1.1%), intraabdominal abscess (0.6% vs. 2.6%) and pneumothrombosis (0% vs. 0.5%). Conclusions: In our series of patients, there was no statistically significant difference in the complication and survival rates between LAC group and OC group. We believe the results show that LAC for CRC is likely to be a safe and an acceptable procedure in the range of our operative indications.
FP-127 Prognostic Value of MIB-1 and PCNA Expression in Periampullary Carcinoma of Vater Toshiaki Kurokawa, Tsutomu Sato, Makoto Kume, Satoshi Shibata, Tomoyuki Kusano, Masato Yoshioka, Go Watanabe, Yuzo Yamamoto Department of Gastroenterological Surgery, Akita University, Japan BACKGROUND: Postoperative recurrence of the periampullary
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carcinoma of Vater is one of the great concerns for surgeons. To determine the relation among the proliferative factors, clinicopathological variables and prognosis, immunohistochemical scoring (labeling index; LI) of MIB-1 and PCNA were analyzed quantitatively in cases of periampullary adenocarcinoma of Vater. METHODS: Nineteen patients with periampullary carcinoma of Vater who underwent pancreatoduodenectomy were included in this retrospective study. The relationship between MIB-1 LI and PCNA LI, and the clinicopathological variables according to the TNM classification were studied. RESULTS: Thirteen out of 19 cases showed recurrence or regrowth of the tumor. In nine cases, recurrence occurred within 15 months after operation. Univariate analysis revealed that MIB-1 LI and microscopic lymphnode involvement were significantly correlated to the prognosis. Three-year survival rate in cases of MIB-1 LI>20 was significantly lower than that in cases of MIB-1 LI<20 (8% and 82%, respectively, p<0.01). In comparison with microscopic LN involvement, 3-year survival rate was 0% in cases of positive LN involvement and 55% in negative cases (p<0.01). No significant correlation was found between the size of tumor, microscopic lymphatic or vascular invasion, perineural invasion or PCNA LI. There was no statistical correlation between the indices of MIB-1 and PCNA. According to the multivariate analysis, only MIB-1 LI showed significant correlation with prognosis. CONCLUSION: These results indicate that MIB-1 LI provides significant prognostic value predicting recurrence of the periampullary carcinoma of Vater independent of PCNA LI and other clinicopathological variables.
FP-128 Significance of 3-Dimensional CT for Preoperative Biliary Evaluation in Hilar Cholangiocellular Carcinoma Fumiki Kushihata, Taro Nakamura, Taiji Toyama, Hiromi Otani, Kazuo Honda, Nobuaki Kobayashi Department of Surgery, Ehime University School of Medicine, Japan Background: A precise preoperative evaluation is crucial in radical resection of hilar cholangiocarcinoma. Method: We describe the efficacy of 3-dimensional CT in preoperative intrahepatic biliary evaluation by presenting four recently resected cases. Results: All the patients complained of abdominal pain or jaundice, but the ICG15’ was within the normal limits. Dynamic-CT showed dilation of the peripheral biliary tree, but no enhanced mass in the hilus. In all cases, MRCP and ERCP showed stenosis of the hilar biliary tract and the variation of the intrahepatic biliary tree, but were unable to localize the tumor precisely. For precise evaluation, one patient underwent PTC tubography, which clearly localized the tumor. Three-dimensional cholangiography, based on multislice DIC or ERBD CT using a volume-rendering method, showed clear variation in the intrahepatic biliary tree in two cases, and a precise view of the tumor in the look-down view from above or the look-up view from below, in all cases. The 2- and 3-dimensional biliary findings allowed precise localization of the tumors. We successfully performed two extended right hepatectomies, one extended right hepatic trisegmentectomy, and a left hepatectomy combined with a caudate lobectomy and biliary reconstruction. Conclusion: The greatest advantage of a 3-dimensional cholangiogram, derived using multi-detector CT, is that it provides precise, easy-to-understand 3-dimensional intrahepatic surgical anatomy of the biliary tract.
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FP-129 Prediction of Outcome in Severe Acute Pancreatitis by Computed Tomography Severity Index M. W. Kwan1, Y. C. Wong2, C. C. Cheung1, K.W. Lau1 1 Department of Surgery, 2Department of Radiology,Tuen Mun Hospital, Hong Kong, China Purpose: Balthazar and Ranson demonstrated the applicability of computed tomography (CT) criteria in predicting mortality. We retrospectively reviewed the prognostic value of CT severity index in terms of death, length of hospital stay and need for necrosectomy. Methods: We reviewed all patients admitted to our hospital from 2001 to 2003 with a primary diagnosis of acute pancreatitis. The inclusion criteria is that a CT scan had been performed during the hospitalization. The CT films were reviewed by a single radiologist. Severity index was determined by the CTSI of Balthazar and Ranson. Outcomes measured were death, length of hospital stay and the need for necrosectomy. Statistical analysis was performed using Chi-square test. Results: There were 335 cases of acute pancreatitis during that 3-years period. 67 cases had a CT scan performed and were included into our study. The mean age was 58 years old. The mean hospital stay was 21days ( 2-142), and the mean CTSI was 3.18 ( 0-10). The overall mortality was 14% ( n=10). CTSI > 4 was correlated with prolonged hospital stay ( P< 0.01). However, the prediction of mortality and hospital stay were not significant. ( P>0.05). With a CTSI>4, patients were 7.5 times more likely to have prolonged hospital stay (> 20days) compared with their counterpart CTSI<4. Conclusion: Computed tomography (CTSI) is applicable in predicting hospital stay. However additional factors are needed to predict mortality and need for necrosectomy in severe pancreatitis.
FP-130 The Protective Role of Heme Oxgenase-1 on Liver after Hypoxic Preconditioning in Rats I-Rue Lai1, Ming-Chieh Ma2, Chau-Fong Chen2, King-Jen Chang1 1 Surgery, National Taiwan University Hospital, 2Department of Physiology, National Taiwan University College of Medicine, Taiwan Background: Hypoxic preconditioning (HP) confers cytoprotection against ischemia/reperfusion (I/R) injury, this effect is in part due to the induction of heme oxygenase-1. This experiment evaluates liver cell damage after I/R injury in HP rats. Methods: HP rats were prepared by exposure (15hours day-1) to an altitude chamber (5500m) for 2 weeks. Partial hepatic ischemia was produced in the left lobes for 45 minutes followed by 180 minutes of reperfusion. Zinc-protoporphyrin IX (ZnPP), a specific inhibitor of HO enzymatic activity, was subcutaneously injected 1 hour before the I/R injury in separate groups of sea-level (SL)control and HP rat. Serum alanine transaminase (ALT) levels, liver HO-1 mRNA and protein, and HO enzymatic activity were measured. Results: Heme oxygenase-1 (HO-1) was induced in the livers of rats exposed to HP. The levels of HO-1 mRNA and protein were obviously overexpressed after two weeks of hypoxic preconditioning. HP diminished the elevation of serum ALT levels after I/R injury (83.7±4.9 U L-1)when compared with SL controls (280.8±19.4 U L-1) and HP+ ZnPP pre-treated groups (151.3±4.4 U L-1). The heme oxygenase activity in treated rats also correlated
these results (237.9±19.8 pmol mg-1 protein hr-1 for the HP group, 164.3±12.7 pmol mg-1 protein hr-1 for the HP+ ZnPP, and 182.6±8.9 pmol mg-1 protein hr-1 for the SL controls. Conclusions: Our results indicated that the induction of HO-1 in hypoxic preconditioning played a protective role against hepatic I/R injury.
FP-131 Total Hepatic Vascular Block with Caval Flow Preservation using Endo Tracheal Tube on Tumor Resection Toar Jean Maurice Lalisang, Benny Philippi, Agi Satria Putranto, Arnold Binsar Simanjuntak, Nasrul Liza Surgery, Digestive Division, University of Indonesia /Cipto Mangunkusumo Hospital, Indonesia Total hepatic vascular exclusion was accepted as a save technique on liver resection to decrease blood lost. The caval flow preservation in the total vascular block was chosen as a technique due to the minor side effect to haemodynamic, cardiovascular and respiration system. We report a modification of Total vascular hepatic block with caval flow preservation using endo tracheal tube (ETT), which inserted in the caval vein. The cuff of the ETT was inflated at the point of 3 hepatic vein confluences with the caval vein to occlude the vein back flow. The caval flow from inferior goes through to the ETT canal to the right atrium. For the hepatic inflow “Pringle maneuver” was performed using vascular clamp. Patient male, 80 years old with HCC at segment 5&6 was resected with this procedure. Two segmentectomy were performed, blood lost 600 cc, operative time 200 minutes.Acites present through drainage tube, due to low albumins and heal 14 days p.o. The patient was hospitalized 16 days. First and third month review he was in a good clinical and laboratory condition. Conclusion the total hepatic vascular block using ETT for caval preservation were simple, no effect on homodynamic and visible to be performed.
FP-132 Application of Right Hemihepatic Vascular Exclusion in Liver Resection Dong-Shik Lee, Hong-Jin Kim, Dong-Shik Lee, In-Hoo Kim, SungSu Yun, Young-Suk Jo, Se-Won Kim Surgery, Yeungnam University Hospital, Korea Purpose: Control of bleeding and preservation of liver function are still major keys for successful liver resection. We applied right hemihepatic vascular exclusion (RHVE) in patient with right lobe liver tumor to verify the usefulness and safety of RHVE. Methods: Between March 1998 and August 2002, 12 patients (Control group) underwent right liver surgeries without inflow occlusion, 22 patients (RHVE group) underwent right liver surgeries under RHVE. Hemodynamic changes during operation, amount of transfusion and liver function after operation were compared between two groups. Results: The mean duration of RHVE was 32.3±13.9 (15-60) minutes. The mean arterial pressure of control and RHVE group after liver resection were reduced, but these changes were not statistically significant. The amount of transfusion in RHVE group (2.66±1.4 unit) was significantly lower (p<0.05) than that of control group (4.56±3.3 unit). AST/ALT level of the RHVE were significantly higher on the POD#1 but there were no statistically significant differences on the POD#3, 5 and 7. Also, the differences in changes of total bilirubin and IL-6 after liver resection were not significant. Cirrhotic patients in
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both groups were compared with the same analysis. Only the amount of transfusion in RHVE group were significantly lower (p<0.05) than that of control group. Conclusion: RHVE is safe and useful procedure for right liver surgery with minimal blood loss, but without significant hemodynamic alteration and functional deterioration. These characteristics are shown especially in cirrhotic liver and non-anatomical resection of metastatic cancer.
FP-133 Application and Outcomes of Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma Dong-Shik Lee, Hong-Jin Kim, Dong-Shik Lee, In-Hoo Kim, SungSu Yun, Young-Suk Jo Surgery, Yeungnam University Hospital, Korea Background/Aims; Curative surgical resection is the most effective treatment for hepatocellular carcinoma (HCC). However, the long term prognosis after curative resection remains unsatisfactory because of a high rate of intrahepatic recurrence. Therefore, effective treatment of intrahepatic recurrent HCC is very important in prolonging prognosis after resection of HCC. The purposes of this study were to evaluate the clinicopathologic characteristics and to clarify the outcome of the patients after repeat hepatectomy for recurrent HCC. Materials; From March 1991 to February 2004, 16 patients underwent repeat hepatectomy for recurrent HCC. The clinicopathologic and follow-up data were evaluated retrospectively. Results; There was no significant difference in the average of ICG R15 between primary (11.2±1.8%) and repeat hepatectomy (18.2±2.8%). A significant difference was seen in the average of tumor size between primary (3.6±0.5 cm) and repeat hepatectomy (2.9±1.9 cm). The average of tumor number for both primary and repeat hepatectomy was equal (1.3±0.6). The number of cases of multicentric occurrence of HCC (12 cases) was more than intrahepatic metastasis HCC (4 cases). The mean interval between the primary and repeat hepatectomy was 48.0±33.0 months (13-136 months). The average of survival time after primary hepatectomy was 83.6±36.3 months. The cumulative 1, 3, 5, and 7 year diseasefree survival rates after primary hepatectomy were 100%, 62.5%, 25%, and 12.5%. The cumulative 1, 3, 5, and 7 year survival rates after primary hepatectomy were 100%, 100%, 85.9%, and 75.3%, respectively. Conclusion; The repeat heptectomy leads to satisfactory outcomes for selected patients with intrahepatic recurrent HCC.
FP-134 Survival and Pattern of Recurrence after Curative Resection of Colorectal Cancer: Review of 1064 Patients in a Single Institution Yee Man Lee1, Wai Lun Law2 1 Surgery, Queen Mary Hospital, 2Queen Mary Hospital, Hong Kong, China Background: Recurrence is common in colorectal cancer after curative resection. We conducted this study to evaluate the survival and pattern of recurrences in a single institution to guide our follow up plan. Method: In a single institution, patients operated between 1996 to 2001 for curative resection of colorectal cancer and had adequate clinical data for analysis were recruited. For statistical analysis, Chi-square or Fisher exact tests were used for nominal variables and Mann-Whitney U test for continuous vari-
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ables. The cumulative survival and comparison between groups was analyzed with Kaplan-Meier method and Log-rank test respectively. The result was considered statistically significant if p<0.05. Results: The study recruited 576 patients with colonic cancers and 488 patients with rectal cancers. The median follow up periods were 28 months and 33 months respectively. The 5-year survival rate was similar between colonic and rectal cancers (stage I: 94.4 versus 94.9 months, p=0.537; stage II: 77.2 versus 78.7 months, p= 0.611; stage III: 63.7 versus 55.1 months, p=0.644). The overall recurrence rate was 21%. Patients with rectal cancers had significantly more local recurrence (8.7% vs 3.7%, p=0.035). The incidence of systemic recurrence was similar in colonic and rectal cancers (22.6% vs 26.1%, p=0.169). The resection rate for recurrent disease was 8%. Conclusion: About one fifth of patients developed recurrence after curative resection for colorectal cancers, the resection rate for recurrent disease was unacceptably low. Strategy is needed to detect recurrence at an earlier stage in order to improve the survival after recurrence.
FP-135 A New Compression Anastomosis Device for Colonic Surgery Shlomo Lelcuk1, Israel Nudelman1, Vladimir Ze’ev Fuko1, Nir Waserberg1, Yaron Niv1, Moshe Rubin1, Amir Szold2, Alex Geller1, Doron Kopelman3 1 Surgery B, Rabin Medical Center, Beilinson Campus, Tel Aviv University, 2Tel Aviv Sourasky Medical Center, 3Haemek Medical Center Afula, Israel GI anastomosis is a crucial step in almost all GI procedures. In the search for a better surgical device to perform these anastomoses, a new instrument, the Compression Anastomosis Clip (CAC), was investigated. The CAC (NiTi Medical Technologies Ltd., Netanya, Israel) is a double ring device made of nickel titanium that when cooled loses its rigidity and can be opened to an angle of about 30 deg. In that condition, it can be spread apart to enable easy introduction through a 5mm incision made in the two edges of the colon wall at the stumps left after resection.At body temperature (37 deg C in the intestine), the rings close tightly, creating the compression anastomosis. The two incisions are closed together by suturing and, within about 5-7 days, the clip is excreted with the stool, creating a perfect natural anastomosis. In our present study, 60 patients with colonic tumors were assigned to be anastomised with a stapler or with the CAC. In all the post-op parameters, such as hospital stay, bowel movements resumption, start of intake, complications, etc. the study group demonstrated results that were equal or better than the control group. A six-month follow-up by colonoscopy showed a perfect anastomosis. Our study showed that the use of the CAC is safe, clean, quicker and user friendly.
FP-136 Technique Innovation of Hepatic Artery Reconstruction in Living Donor Liver Transplantation Xiangcheng Li, Xuehao Wang, Feng Zhang The Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, China Objective: Hepatic arterial reconstruction is one of the most difficult procedures in living-donor liver transplantation. If hepatic artery thrombosis occurs after liver transplantation, the recipient
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clinical prognosis will be uneventful. The aim of this study was to summarize the experience of the microsurgical technique in the reconstruction of hepatic artery in living donor liver transplantation. Methods: thirty cases of LDLT have been performed in our Center from Jan 2001 to Dec, 2003. In 30 cases, left lobe with middle hepatic veins was harvested in 20 cases, left lateral lobe in 3 cases and right lobe in 7 cases. Depend on intra-operative ultrasound and pre-operation evaluation, donor operation was determined on the anatomic analysis of hepatic veins, portal veins and hepatic artery. The branch of the recipient’s hepatic artery needs to be dissected as peripherally as possible. Hepatic arterial reconstruction was performed using microsurgical technique with direct end-to-end anastomosis (recipient hepatic artery to graft hepatic artery) as long as possible with interrupted 8-0 Prolene sutures and double clip. Result: 5 grafts have two hepatic arterial branches. The hepatic arteries in 16 cases were less than 2mm in diameter. The range time required for an arterial reconstruction was 2440min. Hepatic artery thrombosis was occurred in 2 cases (6%), both of which needed retransplantation. Conclusions: The microsurgical technique in reconstruction of hepatic artery has significantly decreased the incidence of hepatic artery thrombosis and has significantly improved the surgical outcome in living donor liver transplantation.
FP-137 Biliary Reconstruction with Microsurgical Technique in Living Donor Liver Transplantation Xiangcheng Li, Xuehao Wang, Feng Zhang The Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, China Objective: Biliary tract complications remain one of the most serious problems after living donor liver transplantation. Duct-to-duct biliary anastomosis is the manner of choice for biliary reconstruction. The authors performed LDLT with microsurgical technique, and this study assessed retrospectively the relation between the manner of reconstruction and complications. Methods: Between Jan 2001 and Dec 2003, 30 patients (7-40 years of age) underwent LDLT using right lobe in 7 cases , left lobe in 20, left lateral lobe in 3. Biliary reconstruction was duct-to-duct biliary anas tomosis with microsurgical technique. Results: All patients underwent duct-to-duct biliary reconstruction using the donor right or left hepatic duct with the recipient’s bile duct. biliary leakage was encountered in three patients. One case developed biliary stricture. One case developed bile peritonitis after take out T tube. The overall Biliary complication rate was 25%. Conclusion: We conclude duct-to-duct biliary reconstruction with microsurgical technique is feasible and effective in LDLT.
FP-138 Serum Cytokeratin 19 Fragment CYFRA 21-1 Level Reflects Hepatocellular Carcinoma Metastasis: Study in Nude Mice Model and Clinical Patients Yan Li1, Zhao-You Tang2, Bo Tian2, Hong-Yin Yuan1, Guo-Liang Yang1, Yun-Feng Zhou1 1 Department of Oncology, Zhongnan Hospital of Wuhan University, 2Liver Cancer Institute of Fudan University, China Objective Our previous comparative proteomics study on high and low metastatic human hepatocellular carcinoma (HCC) cell
strains revealed that cytokeratin 19 (CK19) was expressed in cells with higher metastasis potential, we further studied serum CK19 fragment CYFRA21-1 level in HCC patients and nude mice model of HCC metastasis to explore its significance in HCC progression. Methods HCC cell line HCCLM3 was injected subcutaneously into 30 BALB/C-nu/nu nude mice, which were were sacrificed 2, 3, 4, 5, 6, and 7 weeks after injection, respectively, and the serum CYFRA21-1 and pulmonary metastases were determined. Serum CYFRA21-1 levels of 101 normal controls and 108 pathologyproven HCC patients were also determined, and their correlation with clinico-pathologic parameters was studied. Results In nude mice model, CYFRA21-1 level increased significantly when pulmonary metastases occurred. Among 108 HCC patients, 24 (22.2%) had increased serum CYFRA21-1 level. The percentage of poor differentiated tumor was higher in CYFRA21-1 increased cases (37.5%, 9/24) than in CYFRA21-1 normal cases (20.2%, 17/84) ( 2=7.362,P<0.05). Moreover, the presence of portal vein tumor emboli was significantly higher in CYFRA21-1 increased cases (33.3%, 6/24) than in CYFRA21-1 normal cases (6.0%, 5/84) ( 2=7.403,P<0.01). Conclusions CYFRA21-1 level in this nude mice model of HCC metastasis increased rapidly when lung metastasis occurred. Increased CYFRA21-1 level in some HCC patients was related to portal vein tumor emboli, poor tumor differentiation and advanced tumor stages. [Key words] Hepatocellular carcinoma; Metastasis; Animal model; CYFRA21-1
FP-139 Systemic Approach toward Preventing Common Bile Duct Injury in the Era of Laparoscopic Cholecystectomy Heng-Hui Lien, Chiu-Chuan Huang, Ching-Shui Huang, Min-Yin Shi, Der-Fang Chan, Nai-Yuan Wang, Feng-Chuan Tai General Surgery, Cathay General Hospital, Taiwan Purpose: For preventing common bile duct injury during laparoscopic cholecystectomy (LC), we wish to construct a safe system for performing LC base on our experience and the idea of medical error, accident analysis, and quality control of medical practice. Methods: Over five thousands cases of LC had been performed in our hospital and there were no major CBD injury happened after first two thousands of LCs. The formulate check list for performing LC and the training program for junior surgeons were presented. 27 CBD injuried cases include six our own and nineteen referred cases were also collected for analysis. The original operative video tapes of CBD injured cases could be collected in eight cases for detail check. Results: inexperienced technique, inadequate equipments, Acute inflammation, routine procedures were not fully obeyed, uncertain strategy of conversion, unsecured warming feedback system, and unfamiliar surgical team all can result in CBD injury. Beside these finding we also present our suggest which was not mentioned elsewhere include: stepwise teaching program, Critical check point during LC, and error-proving procedure of LC. Conclusion: CBD injury could be reduced effectively through safe operating system, standard training protocoland, standard procedure.
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FP-140 Analysis Long-term Disease Free Survival after Curative Resection of Primary Small Bowel Gastrointestinal Stromal Tumors Keng-Hao Liu, Chun-Nan Yen, Yi-Yin Jan, Miin-Fu Chen General Surgery, Chang-Gung Memorial Hospital, Taiwan Background And Aims: Informaiton regarding the clinocopathological factors, immunophenotype, and mitotic count in the disease free survival with primary small bowel gastrointestinal stromal tumors (GISTs) after curative surgical resection are limited. The report aims to determine factors to predict long-term disease free survival after curative resection. Method: One hundred patients with C-KIT positive small bowel GISTs undergoing surgical resction at Department of Surgery, Chang-Gung Memorial Hospital. Taipei, Taiwan between 1983 to 2002 were retrospectively reviewed. Result: There are 52 men and 48 women with a median age 56.5 year-old. The curative resection wsa obtained in 85 patients. The follow-up time ranged from 5 to 202 months. The 1-,3, and -5 year survival rate were 91.6%, 75.1%, and 67.3% respectively. THe 1-,3-,and 5- year disease-free survival rate were 85.2%, 53.8%,and 43.7% respectively. 44 of 85 patients develop tumor recurrence during follow-up period. Survival analysis according to clinicopathological factors, immunophenotype and mitotic counts by univariate log-rank test and multicariate Cox proportional hazzard model. Tumor size< 5cm, mitotic count< 5/50, and Ki-67 index< 10% were three independent factors predicting long-term survival for patients woth small bowel GISTs after curative resection. Conclusion: Curative resection is aim of surgical treatment of small bowle GISTs. High recurrence rate was noted after curative resection. Tumor size and mitotic counts can predict long term disease free survival for patients with small bowel GISTs after curative resction.
FP-141 Prospective Evaluation of Multi-Detector CT for Treatment Decision Making of Extrahepatic Bile Duct Carcinoma Atsuyuki Maeda, Katsuhiko Uesaka, Tomoki Ebata, Kazuya Matsunaga, Hideyuki Kanemoto Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Centre, Japan AIMS: The aim of this study was to prospectively evaluate the usefulness of multi-detector computed tomography (MDCT) in treatment decision making of extrahepatic bile duct carcinoma. METHODS: When a new patient suspicious of extrahepatic bile duct carcinoma was referred to our hospital, MDCT was performed at first. Hepato-biliary disease conference members evaluated MDCT images to determine the stage of the disease. Tumors of stage IV on UICC-TNM classification were categorized as certainly unresectable. Encasement of the portal vein was not considered a deterrent to resection. When stage III or less, the tumors were classified as probably resectable. We verified whether the intended treatment, especially surgical procedure planned according to the MDCT images, was completed or not. RESULTS: Between September 2002 and April 2004, 46 patients with extrahepatic bile duct carcinoma were enrolled in this prospective study. Of all 46 tumors, 28 were classified as probably resectable, 18 as certainly unresectable, and none as probably unresectable, respectively. Of 28 tumors classified as probably respectable, 27
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were in fact resectable at surgery. One tumor, which was unresectable, was a gallbladder cancer with prominent lymphnode metastases. Nonsurgical treatment was performed for all tumours defined as certainly unresectable. Cholangiography was obtained in 22 patients. Cholangioscope was performed in 4 patients with suspicious superficial spread. Microscopically, positive surgical margin was identified in 4 (14%, three carcinoma in situ and one invasive). CONCLUSIONS: MDCT provides reliable information for the staging of extrahepatic bile duct carcinoma. This noninvasive technique will replace other invasive staging methods.
FP-142 Short Term Functional Results after Partial Intersphincteric Resection for Low Rectal Cancer Koutarou Maeda, Masahisa Matsumoto, Tunekazu Hanai, Harunobu Sato, Masahisa Matumoto, Yoshikazu Koide, Hiroyuki Aoyama, Hiroshi Matuoka, Hidenori Katuno, Taro Ishikawa, Masuo Funahashi Department of Surgery, Fujita Health University, Japan Object: To evaluate short term anorectal function following partial intersphincteric resection (ISR) for very low rectal cancer by comparing those of conventional per anal anastomosis (conventional method) and IO- double stapling technique (IO-DST). Patients and methods: Fifty-seven patients (conventional method11, ISR 15, IO-DST 31, mean age 58 years, male 38) were enrolled in the study. All patients underwent TME with coverning colostomy. Anoretal manometry was performed before operation and stoma closure. Bowel frequency and presence or absence of soiling were interviewed before initial operation and one month after stoma closure. Length form anal verge to the tumor and length from anal verge to anastomotic site were significantly shorter in ISR than in conventional method and IO-DST. Length of distal margin in the specimen was shorter in ISR than in IO-DST. Maximum resting pressure and length of high pressure zone decreased significantly after initial operation in ISR, however no significant changes were observed in every method after operation. Bowel frequency increased significantly after initial surgery in ISR and conventional method, however frequency of soiling did not show any significant change after surgery in all methods. Conclusions: Partial ISR is a feasible procedure for very low rectal cancer from the point of short term function results when compared with conventional method and IO-DST.
FP-143 Surgical Anatomy of Hepatic Hilum with Special Reference of the Plate System and Extrahepatic Bile Ducts Hideki Masunari, Hiroshi Shimada, Itaru Endo, Yoshiro Fujii, Kuniya Tanaka, Hitoshi Sekido, Shinji Togo Dept. of Gastroenterological Surgery, Yokohama City Univ., Japan Background. When resecting hilar cholangiocarcinoma,the surgeon cannot visualize the hilar vessels through thick connective tissue known as the plate system. Little has been reported regarding the anatomical relationship between the plate system and the extrahepatic bile ducts. Methods. Twenty-five formalin-fixed cadaveric livers were dissected carefully and 7 were sectioned sagittally.The extent,composition and distribution of the extrahepatic bile ducts within the system were investigated.The length between the confluence of the hepatic ducts and the branch point of the
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segmental ducts (level-I) and the length between the branch point of the segmental duct and the root of the segmental Glisson’s pedicle (level-II) were measured. Results. The hilar plate was a fan-shaped structure. The hilar and the umbilical plate meaured 30.8±9.7mm (Mean ± SD on the right side and 41.8±10.0 mm on the left side from the confluence of the hepatic duct. Histologically, dense connective tissue with abundant capillaries, lymphatic vessels, and neural fibers were observed. Length of each segmental bile ducts (Level-I+II) were 22.4±6.9, 59.0±2.1, 64.5±3.5, 56.3±6.4, 51.9±6.4, 50.8±4.2, 41.6±0.7 mm in B1pcp, B2, B3, B4, B5, B8, B6+7, respectively. When the hilar plate was cut at 2cm and 3cm from the confluence of the hepatic ducts, mean number of bile duct orifices were 6.3 and 9.3, respectively. In the former case, continuity of the plate was maintained, however the latter cases the plate was divided into left and right part. Conclusions. The bile ducts in the plate system correspond to the extrahepatic bile ducts and their lengths are variable for every segment.Knowing the lengths of the resectable extrahepatic bile ducts is useful for deciding which segment should be resected according to the cancerous invasion.
FP-144 Antineoplaston AS2-1 Induces G1 Cell Cycle Arrest and Apoptosis against Colon Cancer Cells Keiko Matono, Yutaka Ogata, Yasumi Araki, Nobuya Ishibashi, Seiichirou Shida, Takamasa Fukumitu, Tomoaki Mizobe, Kazuo Shirouzu Surgery, Kurume University, Japan Introduction: Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine, were first described by Burzynski in 1976. The small peptides reportedly control neoplastic growth and have minimum adverse effects. However, the molecular mechanisms of the antitumor effects are not well known. In the present study, we have investigated antitumor mechanisms of Antineoplaston AS2-1 against colon cancer cells. Methods: We tested Antineoplaston AS2-1 on in vitro and in vivo cell growth activity in human colon cancer cells. The cell cycle by FACS, the expression of cell cycle regulators by western blot, and the apoptosis induction by anexin V stain were evaluated. Results: Antineoplaston AS2-1 inhibited proliferation of both human colon cancer cells and implanted tumor growth in nude mice in a dose and a time dependent manner. FACS demonstrated G1 cell arrest by treatment with 2 mg/ml of AS2-1 in the KM12SM cells and HCT116 cells. However, by treatment with high dosage (5mg/ml) of AS2-1 the cell cycle analysis showed increase of the G2 phase cells in HCT116 cells. The protein levels of cyclin-dependent kinase (cdk)-2, cyclin E, cdk-4, cyclin D in the colon cancer cells significantly decreased and the level of p16 and p21 increased time and dose dependently with antineoplaston AS2-1 treatment. And antineoplaston AS2-1 decreased the level of phosphorylated retinoblastoma protein. In both cells, treatment with 5 mg/ml of AS2-1 significantly induced apoptosis. Conclusion: Antineoplaston AS2-1 showed antitumor effects against colon cancer through the G1 arrest and consequential induction of apoptosis.
FP-145 Prospective Study of Neoadjuvant Chemoradiation and Surgery Alone on the Basis of Preoperative Staging for a Treatment of Esophageal Cancer Hisahiro Matsubara, Tetsuro Urashima, Shin-Ichi Okazumi, Hideaki Shimada, Tohru Shiratori, Kiyohiko Shuto, Yoshihiro Nabeya, Taito Aoki, Yasushi Okazaki, Yasunori Akutsu, Takanori Nishimori, Isamu Hoshino, Takenori Ochiai Department of Academic Surgery, Graduate School of Medicine, Chiba University, Japan We have started three fields lymph nodes dissection from 1983. These experiences have clarified that this operative procedure was not sufficient for a far advanced esophageal carcinoma. The far advanced esophageal cancer contained three groups - metastatic lymph nodes spreaded in three fields, the number of lymph nodes were over 5 nodes, or locally far advanced T stage (T4) -. 5-yaer survivals of these cases are less than 15%. On the other hand, the combination of chemotherapy and radiotherapy is an accepted treatment. On the basis of these data, we have started preoperative chemoradiation for these three groups from 1998. Surgery alone was chosen for the patients who don’t belong to these three group. The preoperative therapy consists of concurrent chemoradiation as follows. CDDP is administrated at a dose of 15mg/m2 (day1 to 5), and 5-fluorouracil is also given at a dose of 500mg/m2 (day 0 through 4). A total dose of 40Gy was delivered in 20 fractions of 2Gy each. And then 3weeks later, esophagectomy with three fields lymph nodes dissection was undergone. No operative death was seen. Perioperative morbidity has not increased. It can be carried out safely. Overall 5-year survivals improved to 44.8%, respectively. On the other hand, overall 5-year survivals surgery alone group are 68.1%, respectively. These grouping are very useful for avoiding unnecessary preoperative treatment. Pretreatment staging, especially lymph node status, is the important factor for preoperative chemoradiation. This strategy is effective and safe for esophageal cancer patients.
FP-146 Novel Cytokine Gene Therapy Using in Vivo Electroporation Hisahiro Matsubara, Naoyuki Hanari, Isamu Hoshino, Tetsuro Urashima, Yasunori Akutsu, Takanori Nishimori, Taichi Kawashima, Yasuo Yoneyama, Kazuyuki Matsushita, Yukimasa Miyazawa, Takenori Ochiai Department of Academic Surgery, Graduate School of Medicine, Chiba University, Japan Our previous reports showed that retroviral transduction of human esophageal cancer cells with IL-2 or GM-CSF gene abolished their tumorigenicity. Inoculation of these cytokine producer cells into the vicinity of parental tumors which had developed in nude mice suppressed subsequent tumor growth. In order to transfect efficiently cytokine cDNA into tumor cells, we tested the usefulness of an in vivo electroporation method. Furthermore, we examined efficacy of Interleukin-21 (IL-21) gene. IL-21 is a recently identified novel cytokine that play an important role in the regulation of B, T and NK cell functions. Human esophageal cancer cells (T.Tn,TE2) were subcutaneously injected into BALB/c nu/nu mice. After tumors developed, the plasmid DNA which harbored IL-2, GM-CSF or IL-21 gene were injected intratumorally. Tumors that were transfected with the IL-2, the GM-CSF or the
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IL-21 gene using the electroporation showed growth retardation compared with tumors that received only electroporation. Furthermore, mice that harbored the tumors which were transfected with the IL-2, the GM-CSF or the IL-21 survived significantly longer that those that had the tumors which were transfected with control cDNA. These data collectively suggest that the usage of IL-21 for novel immuno-gene therapy. Cytokine gene transfer using in vivo electroporation could be an extreme useful and convenient therapeutic strategy for esophageal cancer.
FP-147 Diagnostic Significance in Promoter Methylation of hMLH1 and BRAF Pathogenic Mutations between HNPCC and Sporadic MSI-H Colorectal Cancers Nagahide Matsubara1, Takeshi Nagasaka1, Kenji Notohara2, Henry T. Lynch3, Jeremy R Jass4, Noriaki Tanaka1 1 Dept. of Gastroenterological Surg. and Surgical Oncology, Okayama Univ. Grad. School of Med. and Dentistry, 2Dep. of Pathology, Kurashiki Central Hosp., Japan, 3Dept. of Int. Med., Crighton University, USA, 4Dept. of Pathology., MacGill University, Canada Although colorectal cancers (CRCs) with MSI-H are thought to share diagnostically common features regardless of whether the cancers occur in the context of HNPCC or sporadically, discrimination between HNPCC and sporadic MSI-H is not easy. Loss of function of hMLH1 due to either germline mutation or promoter hypermethylation is considered to cause a critical distinction between HNPCC and sporadic MSI-H. In this study, we studied entire methylation status of hMLH1 promoter of HNPCC and sporadic MSI-H CRC by our newly developed methylation allele specific direct sequencing. Upstream promoter showed frequent methylation in almost all samples examined including normal mucosa, sporadic MSI-H, and HNPCC. On the other hand, a key CpG islands in downstream promoter close to CCAAT box (CBF recognition site) were positively related to the hMLH1 expression. Most of sporadic MSI-H samples showed methylation in this region and promoter hypermethylation in other genes. Almost all sporadic MSI-H showed BRAF pathogenic mutation but non of the HNPCC had BRAF mutation. Recruiting HNPCC by family history (AS II) sometimes too strict and underdiagnose because of a small family size. In combination of MSI test and promoter hypermethylation of hMLH1 could offer a prominent method to recruit HNPCC in a cost effective manner by excluding sporadic MSI-H CRC from all MSI-H CRC.
FP-148 Management of Bile Duct Injury during Laparoscopic Cholecystectomy Masamichi Matsuda, Goro Watanabe, Masaji Hashimoto Surgery, Toranomon Hospital, Japan Laparoscopic cholecystectomy (lap-chol) may result in serious biliary complications. Our experience with biliary injuries were reviewed and techniques of management as well as outcomes were discussed. Among our 2555 lap-chol patients, bile duct injuries occurred in 17 patients (0.7 %). The most common cause of bile duct injury during lap-chol was difficulties of dissection due to severe adhesions and inflammations around the cystic duct (10 patients). While in 7 patients, less inflammations existed
Journal of Gastrointestinal Surgery
(“easy” gallbladder), and the injury occurred due to misidentification of the common bile duct as the cystic duct. All these injuries were recognized during surgery and were managed via laparotomy. Fourteen minor injuries were repaired primarily with t-tube placement. Three were complete transaction and biliary-duodenal anastomoses were performed with transhepatic biliary drainage (ERBD) or nasobiliary drainage (ENBD). Both t-tube and RTBD/ENBD-tube were kept placing in the bile duct more than three weeks. One patient developed repeated cholangitis, which were treated conservatively. Another patient developed bile duct strictures that was treated with biliary stenting. The rest of the patients are well and alive with normal liver enzyme levels after one to 13 years of follow-up evaluation. We conclude that when we repair the injured bile duct, enough drainage and stenting of anastomosis at least three weeks is necessary to prevent bile duct strictures or repeated cholangitis.
FP-149 Clinicopathologic and Biological Prediction of Lymph Node Metastasis in Superficial Esophageal Squamous Cell Carcinoma Masataka Matsumoto, Shoji Natsugoe, Hiroshi Okumura, Tetsuro Setoyama, Yasuto Uchikado, Naoya Yokomakura, Hideo Arima, Sumiya Ishigami, Shizuo Nakano, Takashi Aikou Department of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Japan Purpose: Prediction of lymph node metastasis (LNM) is one of the most important problems to select the appropriate treatment for patients with superficial esophageal squamous cell carcinoma (ESCC). The purpose of the present study is to clarify the risk factors of lymph node metastasis clinicopathologically and biologically. Methods: We examined the relationship between clinicopathologic factors and LNM in 109 patients with ESCC invading into lamina muscularis mucosae or submucosal layer. Furthermore, we investigated the expression of cyclin D1 (CD1), E-cadherin (Ecad) and VEGF-C for primary tumor immunohistochemically, and evaluated the correlation with LNM. Results: Tumor macroscopic appearance, tumor size, depth of tumor invasion and existence of LNM by preoperative endoscopic ultrasound were useful predictive factors of LNM. With regard to biological markers, overexpression of CD1 and VEGF-C significantly correlated with LNM (p<0.0001 and p<0.05, respectively). Moreover patients with reduced or negative expression of E-cad had high positive rate of LNM (p<0.005). Combined expression of CD1, E-cad and VEGFC enabled us to predict LNM more accurately. Twenty patients with CD1(+) /E-cad(-)/VEGF-C (+) expression pattern had LNM (Positive predictive value: 87% (20/23)). On the other hand, no patients with CD (-)/E-cad (+)/VEGF-C (-) expression pattern had LNM (Negative predictive value: 100% (36/36)). We could not predict 11 patients with LNM by endoscopic ultrasound, but in which 9 patients could be predicted by considering for expression of three biological markers. Conclusions: We can predict LNM of ESCC more accurately by using molecular technique as well as conventional endoscopic ultrasound and computed tomography.
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FP-150 Pharmacological Preconditioning Effects: Prostaglandin E1 Induces Heat-Shock Proteins Immediately after Ischemia/Reperfusion of the Mouse Liver Ken-Ichi Matsuo1, Shinji Togo1, Hitoshi Sekido1, Tomoyuki Morita2, Masako Kamiyama1, Daisuke Morioka1, Toru Kubota 1, Yasuhiko Miura1, Kuniya Tanaka1, Takashi Ishikawa 1, Yasushi Ichikawa 1, Itaru Endo1, Hitoshi Goto3, Hiroyuki Nitanda3, Yasushi Okazaki4, Yoshihide Hayashizaki4, Hiroshi Shimada1 1 Gastroenterological Center, Yokohama City University Medical Center, 2Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine/Laboratory for Genome Exploration Research Group, RIKEN Genomic Science Center (GSC), 3Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University/Laboratory for Genome Exploration Research Group, RIKEN Genomic Science Center (GSC), 4Laboratory for Genome Exploration Research Group, RIKEN Genomic Science Center (GSC), Japan Background/Aims: Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilatation and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion (I/R) injury in vivo using a complementary DNA (cDNA) microarray. Methods: PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 min and then reperfused. Livers were harvested 0, 10 and 30 min post-reperfusion. Messenger RNA was extracted, and the samples were labelled with two different fluorescent dyes and hybridised to the RIKEN set of 18,816 full-length enriched mouse cDNA microarrays. Results: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels 180 min post-reperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86 and glutathione Stransferase were up-regulated 0 min post-reperfusion in the PGE1 group. Conclusions: Our results suggested that PGE1 induces HSPs immediately after I/R. HSPs might therefore play an important role in the protective effects of PGE1 against I/R injury of the liver.
FP-151 Prospective Neurophysiologic Investigation Following Sphincter-Preserving Operation for Rectal Carcinoma Impact on Pudendal Nerve Function Hiroyoshi Matsuoka1, Tadahiko Masaki1, Masanori Sugiyama2, Yutaka Atomi2 1 Department of Surgery, Kyorin University, 2Kyorin University, Japan Objective: To clarify the impact of sphincter-preserving surgery on the pudendal nerve. Summary Background Data: Pudendal neuropathy is one of the causative factors for soiling after the procedure of restorative proctocolectomy for ulcerative colitis and adenomatosis coli. However, there has been no report clarifying the impact of sphincter-preserving operation for colorectal carcinoma on pudendal nerve function and its relation to postoperative evacuatory disorder. Methods: Twenty-three consecutive patients
undergoing resection for rectal or sigmoid colon carcinoma were assessed with a patient’s questionnaire, anorectal manometry, and pudendal nerve terminal motor latency study (PNTML) before and 6 months after surgery. Results: Eleven patients (48%) had postoperative evacuatory disorder. The prevalence of lower anastomosis was significantly higher in the group with evacuatory disorder. In manometry, maximum tolerable volume and neorectal capacity were significantly smaller in the evacuatory disorder group than in the non-evacuatory disorder group. In PNTML, 5 patients showed no pudendal reflex on both sides and 2 patients on one side in the evacuatory disorder group postoperatively. The 5 patients with negative reflex on both sides all had a low level anastomosis (3-5 cm from the anal verge). Multivariate analysis revealed that low anastomosis (p<0.001) and absence of bilateral or unilateral pudendal nerve reflex (p=0.06) were independent risk factors for evacuatory disorder. Conclusion: Loss of the pudendal nerve reflex may contribute to evacuatory disorder after sphincterpreserving operation in patients with rectal carcinoma.
FP-152 A Case Report of Hepatocellular Carcinoma Associated with Cystic Formation Kazuo Matsuyama, Yorihiko Ogata, Toshiyuki Hirose, Masashi Kanoh, Fumio Chikugo, Toshinobu Matsumura, Masayuki Sumitomo, Hitoshi Miki, Shigeharu Takai, Ryozo Fujino, Kazuyoshi Kurogami, Toshifumi Mukaijo, Masamichi Takahashi Surgery, Tokushima Prefectural Central Hospital, Japan We reported a case of hepatocellular carcinoma associated with marked cystic formation. The patient was a female aged 70 years. Because general fatigue and anorexia occurred, Abdominal CT test was conducted and hepatic mass was pointed out. Contrast-CT test showed a tumor of 6 cm in diameter in the medial segment of the left lobe of the liver. As the border was stained with arterial phase, the center was not imaged and the tumor was diagnosed as vascular proliferating type hepatic tumor associated with marked cystic change. MRI test showed that the border of the tumor was lobular and part thereof was of septal structure. The tumor was diagnosed as hepatocellular carcinoma associated with bleeding in tumor, hepatic cystadenocarcinoma or hepatic sarcoma. Abdominal angiography showed not only marked vascular proliferation and tumor stain in the area of the middle hepatic artery but also early venous return. The tumor size was 5×5×4 cm in size and was in contact with the middle hepatic vein but it did not invade the vein. Left hepatic lobectomy was performed. Histopathologically the center of the tumor was cystic with colliquative necrosis. The tumor cell was consisted of well or poorly differentiated trabecular structure and sarcomatous section. The tumor was thus diagnosed as poorly differentiated hepatocellular carcinoma. The patient was discharged from our hospital on the 19th day after operation. At the moment when 20 months have passed since the operation, the patient is alive without any recurrence of carcinoma.
FP-153 Surgery for IBD in Children and Adolescents Wiktor Roman Meissner, Piotre Krokowicz, Michal Drews Chair and Department of Surgery, Karol Marcinkowski University of Medical Sciences, Poland Recent decades have brought a constant rise of the incidence of
Abstract of 19th WC-ISDS
IBD both in adults and children. Despite a considerable progress in pharmacology, in the presence of massive haemorrhage, free perforation, fulminant colitis or acute obstruction only surgical intervention offers a chance for saving patient’s life. Aim of this study was to present the results of surgical treatment of IBD in children and adolescents. In the years 1996-2003 we operated for IBD on 176 patients. There were 18 children in this group (10,23%), 10 were operated for elective reasons and 8 interventions were emergencies. In all cases of ulcerative colitis two-step restorative proctocolectomy with J pouch anal anastomosis was performed. Patients with Crohn’s disease were treated by limited resections and/or strictureplasties.There were no postoperative deaths in the studied group. Postoperative complications were observed in 6 (33,3%) patients. In one patient treated preoperatively with large doses of Imuran postoperative histology revealed malignant lymphoma. Hospital stay ranged from 8 to 19 days ( mean 12 days). Surgery for IBD in children and adolescents becomes widely accepted method, being not seldom the only treatment modality that offers a chance for cure. Restorative proctocolectomy should be considered in many cases of younger patients with ulcerative colitis earlier, before conservative treatment, especially imunosupression and steroid therapy produce their undesired side effects. Consulting surgeon should be involved in the treatment of younger patients with IBD at much earlier stage of therapy than it is practised nowadays.
FP-154 Should we Operate Earlier on Patients with Diverticular Disease? Wiktor Roman Meissner, Piotr Krokowicz, Michal Drews Chair and Department of Surgery, Karol Marcinkowski University of Medical Sciences, Poland In Western countries diverticular disease (DD) is diagnosed in about 30% of population under 50 years of age. Regardless conservative therapy, inflammation with general symptoms recurrs in up to 35% of patients, calling for hospitalization. In patients with numerous episodes of diverticulitis the risk of complications exceeds 60%. Surgery for complicated DD is associated with marked mortality and morbidity usually implying temporary stoma. In elective operations for DD one-stage resections are feasible and the risk for complications is lower. The aim of this study was to compare the outcome of elective and urgent/emergent operations performed for DD at our Department. In the years 1980-2004 we operated on 99 patients with DD. 60 patients with the history of one or more acute attacks of pain in left iliac fossa, accompanied by fever, leucocytosis and with radiologically confirmed colonic diverticuli were operated electively. 39 patients had urgent/emergent oparations. There were no postoperative deaths in the elective surgery group and 2 deaths (5,1%) in the urgent/emergent group. Complications occured in 16 (16,2%) patients. In the group operated electively 4 patients (6,7%) had complications vs. 12 patients (30,8%) in the urgent/emergent surgery group Mean hospital stay for the elective patients was 8,2 days v.s. 13,7 days for theother gropup. We conclude that surgical intervention for diverticular disease should be considered earlier in the course of the disease. This would allow for one-stage resections and lower the risk of postoperative complications.
Journal of Gastrointestinal Surgery
FP-155 Partial or Total Fundoplication and Influence of Wrap Length on GERD Surgery Results: Prospective Randomized Study Antanas Mickevicius, Zilvinas Endzinas, Mindaugas Kiudelis, Almantas Maleckas, Juozas Pundzius Surgical, Kaunas Medical University, Lithuania Purpose of this randomized controlled study was to compare of Toupet and Nissen fundoplications and evaluate the influence of wrap length on results of treatment. Methods: 153 patients were included in the study. Preoperative severity of heartburn and dysphagia were evaluated, quality of life questionnaire SF-36 filled in. Esophagitis was assessed according to Los Angeles classification and preoperative pH-metry together with esophageal manometry were performed. One, 6 and 12 month after operation esophagitis, heartburn, dysphagia and quality of life were re-evaluated. Results: Seventy-six patients were randomized to Nissen (subgroups: 1,5cm wrap - 38; 3cm wrap- 38) and 77 to Toupet (subgroups: 1,5cm wrap- 40; 3cm wrap- 37) operations. No statistically significant differences have been found between the groups according to persistent esophagitis, heartburn, quality of life changes and treatment failures. Early postoperative dysphagia in Nissen and Toupet groups were 11,8 % and 2,6%, respectively (p<0,05). After one year dysphagia was still more common in Nissen group (p<0,05). Better control of esophagitis and less treatment failures have been found in 3 cm Toupet subgroup compared to 1,5 cm subgroup (p<0,05). Wrap length had no influence on the treatment results in Nissen group. Conclusions: Nissen and Toupet procedures produce comparable long-term results. More dysphagia cases have been observed in Nissen group. However, occurence of dysphagia was not influenced by wrap length in this group. If method of choice is Toupet procedure then 3 cm wrap is mandatory to achieve better healing of esophagitis and less GERD recurrencies.
FP-156 Combined Measurement of Hepatocyte Growth Factor and Carcinoembryonic Antigen as a Prognostic Marker for Dukes’ A or B Colorectal Cancer Patients: Results of a 5Year Study Chikao Miki1, Yasuhiro Inoue2, Jun-Ichiro Hiro2, Toshimitsu Araki2, Tsuyoshi Hatada2, Masato Kusunoki2 1 Surgery, Mie University School of Medicine, 2Second Department of Surgery, Mie University School of Medicine, Japan Purpose: There is no marker capable of differentiating Dukes’ A or B colorectal cancer patients with aggressive diseases from those with indolent diseases. We evaluated the results of 5 years worth of actual survival data to determine whether serial monitoring of serum hepatocyte growth factor (HGF) could give prognostic information on these patients. Experimental Design: Blood samples of 147 colorectal cancer patients were obtained and the serum concentration of HGF was measured. DNA was extracted from surgical specimens to investigate the loss of heterozygosity (LOH) on chromosomes 17p and 18q. Results: Elevated serum HGF levels were associated with stage progression. Although the overall positive rate of HGF in the
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patients was the same as that of the carcinoembryonic antigen (CEA), the positive rate of HGF in the Dukes’ A patients was two times higher than that of the CEA, and nearly 40% of the CEA negative patients had a positive serum HGF in the Dukes’ A or B classification. In this subgroup, patients with positive serum HGF or CEA levels had a poorer prognosis while a positive serum HGF level after surgery could predict disease recurrence. LOH at 18q was associated with lymph node and liver metastasis, whereas Dukes’ A or B patients also tended to show a higher rate of 18q LOH when they expressed positive serum CEA or HGF levels. Conclusions: A combination of serum HGF and CEA tests might be useful for selecting patients with aggressive diseases in Dukes’ A and B classification.
FP-157 Anorectal Physiology and Anal Ultrasonography are Useful for the Diagnosis and Treatment of Fecal Incontinence Toshiki Mimura, Takuma Oomi, Takekazu Arai, Kyokun Haku, Keijiro Nozawa, Keiji Matsuda, Miki Adachi, Susumu Kodaira, Kota Okinaga Department of Surgery, Teikyo University, School of Medicine, Japan Purpose: To evaluate the role of anorectal physiology and anal ultrasonography for the diagnosis and treatment of fecal incontinence. Methods: Subjects were 24 patients with fecal incontinence, who underwent anorectal physiological examinations at our institute between January 2001 and December 2003. The diagnosis and treatment, based on their symptoms, disease history and results of anorectal physiology and anal ultrasonography, were analyzed. Results: Mean age was 56 years old (range 10-75),and 12 were male. Five patients had passive fecal incontinence, 9 had urge incontinence and 9 had both. Mean St Mark’s incontinence score (perfect continence - complete incontinence=0-24) was 9.7±4.5. The causes of fecal incontinence were diagnosed in 21 patients (88%), which included sphincter injury due to previous anal surgery in 6, obstetric injury in 3, low rectal capacity after low anterior resection in 2, internal anal sphincter degeneration in 2, rectal irritability in 2, spinal cord injury in 2 and others in 4. The treatments based on these diagnosis included biofeedback in 7, medical therapy in 5, bowel habit counseling in 3, surgery in 2 (anterior sphincter repair and colostomy each) and psychotherapy in one. Six patients were followed-up without particular therapies. Conclusions: Although causes of fecal incontinence vary, diagnosis was made in 88% of patients on the basis of their symptoms, disease history and the results of anorectal physiology and anal ultrasonography. These diagnoses enabled us to choose an appropriate therapy for individual patients.
FP-158 Influence of Reconstruction of the Middle Hepatic Vein on Liver Regeneration Following Living Donor Liver Transplantation of Right Liver Grafts Shugo Mizuno, Masanobu Usui, Hiroyuki Sakurai, Akiyoshi Nemoto, Masami Tabata, Hajime Yokoi, Shuji Isaji, Shinji Uemoto First Department of Surgery, Mie University, Japan Purpose: It has been reported that right liver grafts without middle hepatic vein (MHV) drainage reconstruction resulted in conges-
tion of the anterior segment (AS) in living donor liver transplantation (LDLT). We studied the effect on graft regeneration of the AS of the liver graft with or without MHV. Methods: 31 recipients having undergone right lobe LDLT were divided into the three groups; group I (n=18) with reconstruction of MHV tributaries, group II (n=7) without reconstruction MHV tributaries, and group III (n=6) using right lobe with reconstruction of MHV. We studied laboratory liver functions for 6 months, portal venous pressure for a week, and liver regeneration assessed by CT volumetry at one week, two weeks, three weeks, one month, three months, and 6 months after LDLT. Results: Postoperative laboratory liver functions and portal vein pressure were not different significantly among the three groups. Graft weight of group II was significantly larger than that of group I. There were no significant differences in whole graft liver volume after LDLT among the three groups. However, the ratio of the AS volume to whole liver volume (AS ratio) in groups I and III were significantly higher than that in group II from 1 week to 3 months after LDLT. The AS ratio in group III was significantly higher than that in group I from 1 week to 3 weeks after LDLT. Conclusions: The AS ratio is increased in right lobe LDLT patients with MHV or MHV tributaries drainage reconstruction within 3 months after operation.
FP-159 Expression of COX1, 2 & PPAR-γ in Human Colorectal Carcinoma Tomoyuki Monma, Yuji Takebayashi, Masashi Higashimoto, Atsuko Kanzaki, Seiichi Takenoshita Department of Surgery 2, Fukushima Medical University, School of Medicine, Japan The cyclooxygenase (COX) catalyze the formation of prostaglandins, affecting cell proliferation and altering the response of the immune system in malignant cells. The inducible forms of COX and COX-2, have been shown to be important in carcinogenesis. Peroxisome-proliferator activated receptor-gamma (PPAR-γ) belongs to a family of nuclear receptors and acts as receptor for peroxisome-proliferators, steroids, retinoic acids, and polyunsaturated fatty acids. The aim of this study is to investigate he clinicopathological significance of the expressions of COX-1, COX-2 and PPAR-γ genes in 90 colorectal carcinomas. Surgical specimens of colorectal carcinoma and adjacent non-neoplastic tissues from 90 patiants with colorectal carcinomas were provided from the patients underwent surgery between 2000 though 2004. All the samples stored at -80°C and embedded in O.C.T. compound immediately before use. After examining histopathological features of the sections stained with H&E, the sections including more than 80% carcinoma cells were used for total RNA preparation. cDNA was synthesized with total RNA. We performed quantitative PCR using cDNA. The expression level of COX-1, -2 and the PPAR-γ genes expression varied from sample to sample, respectively. The expression level of COX-2 gene was significantly increased in patients with lymph nodes metastasis. The survival analysis is being performed and will be discussed in the meeting.
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FP-160 Portal Venous Gas Detected on CT in Emergency Situation: Is Surgery Necessary? Olivier Jean-Yves Monneuse1, Frank Pilleul2, Xavier Barth1, Laurent Gruner1, Bernard Allaouchiche3, Etienne Tissot1 1 Surgery, 2Radio logy, 3Intensive Care, Hospices civils de Lyon, France Background: Presence of portal venous gas has been previously reported as an indicator of poor clinical outcome, and nowadays, series described treatment without surgery. The aim of this study was to evaluate the different underlying pathologies of portal venous gas in emergency situation. Material and method: We performed a retrospective review of 11 patients consulting in emergency and presenting portal venous gas detected by computed tomography (CT) scan between July 1999 and March 2004. Assessment of patient characteristics included age, sex, CT diagnosis, ASA score, surgical findings, duration of hospital stay and mortality. All patients were followed up at 2 months after the hospitalisation. Results: All patients (4 women-7 men ranged in age from 38 to 90 years old (mean age: 64.8 years)) underwent surgical treatment in emergency. Mean pre-operative ASA score was 4.27. CT scan demonstrated surgical lesions in all cases. The patients had surgical pathologies as follows: bowel obstructions (n=4) with necrosis (n=2), arterial mesenteric ischemia (n=5), and diffuse peritonitis (n=2) due to sigmoid perforation (n=1) and diffuse colitis with septic shock (n=1). Mean of hospital duration was 14.3 days [0-48 days]. Mortality rate was 36.4% (n=4) and these patients were died in the first week after the surgery. Conclusion: In our series, detection of portal venous gas in acute abdominal pain was correlated with high pre-operative ASA score. This condition requires emergency surgical treatment to minimize the mortality rate.
FP-161 Establishment of a Highly Sensitive and Specific Detection System of Gastric Cancer Cells in the Peritoneal Washings Kazuhiko Mori1, Hayao Nakanishi2, Mitsuru Sasako3, Yoshihiro Matsuno4, Mafune Ken-Ichi1, Sasaki Hiroki1, Michio Kaminishi1 1 Gastrointestinal Surgery, Graduate School of Medicine, the University of Tokyo, 2Aichi Cancer Center Research Institute Laboratory of Pathology, 3National Cancer Center Hospital Surgical Oncology Department, 4National Cancer Center Hospital Clinical Laboratory, Japan, Purpose ; To improve the reliability of the peritoneal cytology of gastric cancer, a highly sensitive and specific detection system of malignant cells by use of multiple markers should be established. Methods ; A multiplex RT-PCR and subsequent hybridization of the labeled PCR products, which evaluate the expression of 10 marker genes, was used for the detection of malignant cells in the peritoneal washings of 180 gastric cancer patients. Results of this assay were either evaluated as a recurrence predictor or were confirmed by immunocytostaining in the corresponding cytology slides. Results ; The assay had a better sensitivity than conventional cytology with the specificity of 96% for disease recurrence. Clinical outcome of cytology negative cases with positive results of the assay were nearly identical to that of cytology positive cases. Immunostaining of the corresponding slides confirmed the minimal amount of malignant cells in the cytology negative but assay-
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positive cases. Conclusions ; RT-PCR analysis was safely applicable in peritoneal cytology of gastric cancer and may improve the sensitivity of conventional cytology. Usage of anti-MASPIN and anti-CK20 antibodies may aid pathologists in the peritoneal cytology of gastric cancer.
FP-162 Factors Affecting the Outcome of Living Donor Liver Transplantation for Primary Biliary Cirrhosis Daisuke Morioka, Kaoru Taira, Yoshihiro Hirata, Mureo Kasahara, Kenji Uryuhara, Kohei Ogawa, Yasuhiro Ogura, Mikiko Ueda, Yasutsugu Takada, Hiroto Egawa, Koichi Tanaka Organ Transplant Unit, Kyoto University Hospital, Japan Introduction. Factors affecting the outcome of liver transplantation for primary biliary cirrhosis (PBC) have not been clarified in Japan. Furthermore, although recurrent PBC after liver transplantation has been well known, the significance of that has not been defined. Aim. To clarify the factors affecting the outcome of living donor liver transplantation (LDLT) for PBC and to define the significance of recurrent PBC. Patients and methods. From November 1994 to December 2003, 338 adult (age>20) recipients underwent LDLT. Of these 338, 48 patients underwent LDLT for PBC. Outcome of LDLT for PBC was compared to that for other indications. Clinical records of these 48 PBC-patients were reviewed in order to clarify the most significant factors affecting the survival outcome of LDLT for PBC. Results. There was no statistically significant difference between survival rate after LDLT for PBC patients (1-year, 70.7%; 5-year, 64.9%) and that for non-PBC patients (1-year, 71.6%; 5-year, 64.9%). Both on univariate- and multivariate-analyses, low MELD score (<25), and employing blood relative donor have a positive impact on the survival outcome of LDLT for PBC. Recurrent PBC after LDLT was histologically proven in 7 of 48 patients but did not affect the survival outcome both on univariate- and multivariate- analysis. Conclusion. Careful observation for PBC patients before transplantation and employing blood relative donor will further improve the outcome of LDLT for PBC. Recurrent PBC after LDLT has no negative impact on the survival outcome of LDLT for PBC.
FP-163 Proliferating Factors of the Hepatocytes and Hialuronic Acid after Hepatectomy in Bile Duct Ligation-Release Rat Model Hitonobu Moriya, Atuko Ishiuchi Surgery, St. Marianna University, Japan [Introduction] Many patients who are suffering from bile duct carcinoma show hyperbilirubinemia and surgeons used to have performed reduction of obstructive jaundice such as PTBD before surgery. However, preoperative reduction of obstructive jaundice is controversial still now. We are studying the liver regeneration after hepatectomy using obstructive jaundiced and then reduced jaundiced rat model. [Materials and Methods] Thirty-six Wistar rats were divided into three groups: 1) control group, 2) sham operation group, 3) bile duct ligation (BDL) group. Obstructive jaundiced model was obtained 3 days after bile duct ligation Group
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1: 70% hepatectomy just after release the bile duct obstruction. Group 2: 70% hepatectomy 7days after the release. Group 3: 70% hepatectomy 14days after the release. PCNA was measured with Western blotting and hialuronic acid was also measured. Ki67 positive cells were counted using immunohistochemical staining at 6hours, 24hours and 48hours after hepatectomy using bile duct ligation and then released model. And also Cyclin D, CDC-2 and CDK-2 were measured to assess hepatic cell cycle. [Results] PCNA decreased gradually after hepatectomy in group1, in group2 and group3 PCNA increased after hepatectomy however. On the other hand, Ki67 increased in all groups. We measured regeneration factors like PCNA, hialuronic acide and Ki67 using Western blotting and immunohistochemical staining, and this study suggests that the speed of liver regeneration becomes slow in group 1 compared with group 2 and 3.
FP-164 Biological Differences and Similarities between Intraductal Mucinous-Papillary Neoplasms and Pancreatic Intraepithelial Neoplasms Toshiyuki Moriya, Wataru Kimura, Ichiro Hirai, Fumiaki Sakurai, Masaomi Mizutani, Jinfeng Ma, Koichi Suto, Masahiro Kamiga, Akira Fuse First Department of Surgery, Yamagata University, Japan Introduction: Intraductal mucinous-papillary neoplasms (IPMN) are defined clinical entity. Recently much researches were done to elucidate the characteristics of IPMN. However, there are a few researches to compare the biological differences and similarities between IPMN and PanIN. Aims: We examined the various oncogenes, tumor suppressors, mucin immunophenotype in a spectrum of PanINs and IPMNs to investigate the correlation with PanIN and IPMN. Methodology: Fourty tissue samples were obtained from 37 patients who underwent surgical resection for IPMN or invasive ductal carcinoma at the first department of surgery, Yamagata University Hospital (Yamagata, Japan) between 1989 and 2001. Immunohistochemistry was performed with followed antibodies in these tissue samples (HER2, DPC4, p53, MUC1, MUC2, Ki-67, CyclinA and Akt). Results: No significant differences were found between IPMN and PanIN in HER2, DPC4, Akt, Ki-67, CyclinA except p53 expression (between CIS and PanIN3: p=0.013). However MUC protein immunophenotypes were significantly different between IPMA and PanIN-2 (MUC1: p=0.011, MUC2: p=0.0004) and between CIS and PanIN-3 (MUC1: p=0.0028, MUC2: p<0.0001). Conclusions: Our results demonstrated that PanINs and IPMT reveal similar molecular characterization in the expression of each cell proliferation marker, however, MUC immunophenotypes significantly differed in early phase such as PanIN-2. The differentiation to IPMT or IDAC was recognized in early phase. Somewhat factors may play a roll in definition to IDAC or IPMT in early phase.
FP-165 The Results of Surgical Therapy in Hepatic Hydatid Cysts: Treatment with Drainage versus Treatment with Omentoplasty a 10 -Year Experience Seyed Reza Mousavi Vascular and General Surgery, Shohada Medical Center, Iran Sixty-five consecutive patients, who underwent surgery for hepatic
hydatid cysts between 10 May 1993 and 1 July 2002, were included in this study. The aim was to compare the results of surgical techniques with respect to post-operative complications, morbidity and recurrence of the disease. Patients were divided into two groups. The first group (1) of patients (n =35) were treated with omentoplasty and the second group (2) of patients (n = 30) were treated surgically with tube drainage of the cystic cavity. In the study, there were 16 (24.6%) male and 49 (75.4%) female patients, with an age range of between 14 and 81 years. In five of the patients a communication between the cyst and the biliary system was documented. Post-operative morbidity was 8% in group 1 and 42.5% in group 2 (P < 0.05). Average post-operative hospital stay was 6.5 days in group 1 and 15.6 days in group 2 (P < 0.05). During the follow-up period, which lasted from 1 to 2 years, recurrence rates were not sine in the two groups.Keywords: drainage, hydatid cysts, omentoplasty.
FP-166 Extension of Right Portal Vein Embolization to Segment IV Portal Branches: Is it Usefull? Andrea Muratore, Hedayat Bouzari, Daniele Regge, Giovanni Anselmetti, Lorenzo Capussotti Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Italy Objective: To compare segment 2-3 hypertrophy obtained by portal vein embolization (PVE) with and without extension to segment 4 in patients undergoing major hepatectomy. Summary background data: Routine embolization of segment 4 combined with right PVE has been suggested in patients candidates to right trisegmentectomy, in order to induce higher and faster hypertrophy of segments 2-3. Methods: Twenty-six consecutive patients were prospectively evaluated; the future remnant liver (FRL) volume was calculated using the portal phase of spiral CT scans before and 3-4 weeks after right PVE (Group R, N=13), which was extended to segment 4 branches in 13 patients (group L). Results: Twenty patients (76.9%) underwent the scheduled hepatic resection. Of the 6 cases who did not undergo the planned operation, five showed disease progression; in one patient (group L) there was an insufficient increase of the FRL volume due to the presence of embolizing material in the left lobe. The mean time between PVE and volume measurements was 31.8±9.3 days. The overall FRL volume increase was 53.1±24.8%; the increase for segment 4 was significantly higher in the group R than in the group L. The post-PVE volumes of segments 2-3 and the rate of volume increase were similar in the two groups: 348.4±83.1 and 67.8±30.8% respectively in group R, versus 391.2±78.05 and 56.1±35.1% respectively in group L (p=n.s.). Conclusions: Extension of embolization to segment 4 portal branches should not be routinely used since a similar volume increase of segments II-III can be simply achieved by right portal vein embolization.
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FP-167 Clinicopathological Analysis of mRNA Expression of MMPs and TIMPs in Gastric Cancer Yutaka Nagahori, Kaoru Nagahori, Masashi Momiyama, Yuta Minami, Shiho Natori, Shigeharu Komatsu, Haruki Kurosawa, Yohei Hamaguchi, Hidenobu Masui, Tadao Fukushima, Masatoshi Mogaki, Shingo Fukasawa, Hideo Hosoi Surgical Department, Yokosuka Kyousai Hospital, Japan [BACKGROUND] Matrix metalloproteinases (MMPs) are zincdependent enzymes involved in the degradation of extracellular matrix components. MMPs and Tissue Inhibitors of Metalloproteinases (TIMPs) have been suggested to play an important role in cancer development. [PURPOSE] To evaluate whether mRNA levels of MMPs and TIMPs associate with tumor progression and metastasis in human gastric cancer. [METHODS] A total of 19 patients with gastric cancer who underwent gastrectomy were enrolled in this study. Informed consents were obtained from all patients prior to the operations. Just after the gastrectomy, specimens from gastric cancer tissues and normal mucosa were excised, frozen in liqN2 and kept at -80°C. mRNA levels of MMP-2, -7, -9 and TIMP-1, -2 were assayed by real time RT-PCR using LightCycler system and analyzed from the clinicopathological view point. [RESULTS] (1) Comparison of mRNA levels between Normal Gastric Mucosae (N, n=19) and Gastric Carcinomas (C, n=19) : MMP2:N 0.152*-C 0.228*, MMP7: N 0.045-C 0.117, MMP9: N 0.168*-C 0.226*, TIMP1: N 0.387*-C 0.892*, TIMP2: N 0.052-C 0.065 (2) Comparison of mRNA levels between Differentiated Adenocarcinomas (D, n=8) and Undifferentiated Adenocarcinomas (U, n=11): MMP2: D 0.176*-U 0.264*, MMP7: D 0.066-U 0.153, MMP9: D 0.184-U 0.254, TIMP1: D 0.679*-U 1.042*, TIMP2: D 0.054-U 0.073 (3) Comparison of mRNA levels between Stage1+2 (n=5) and Stage3+4 (n=14): MMP2: 0.152*-0.246*, MMP7: 0.038*-0.141*, MMP9: 0.207-0.223, TIMP1: 0.683-0.963, TIMP2: 0.046-0.072 (*: p<0.05 ) [CONCLUSION] Increased mRNA levels of MMP-2 appear to be associated with progression and development of gastric cancer. The mRNA levels of TIMP-2 correlated to that of MMP-2.
FP-168 Sentinel Lymph Node Mapping using Infrared Ray Laparoscopy for Colorectal Cancer Koichi Nagata, Shungo Endo, Eiji Hidaka, Kishiko Tatsukawa, Yoshio Deguchi, Jun-Ichi Tanaka, Shin-Ei Kudo Digestive Disease Center, Showa University Northern Yokohama Hospital, Japan INTRODUCTION: Sentinel node (SN) mapping with dye injection is technically difficult during laparoscopy-assisted colectomy (LAC), because dye injection into the colon wall during LAC is cumbersome. Also observation of dye stain of the SN with conventional laparoscopy is difficult due to mesenteric adipose tissue. We have conducted a research on the method of SN mapping using infrared ray laparoscopy (IRL) (OLYMPUS CORP. Tokyo, Japan) during LAC for colorectal cancer and the technique of saline injection prior to dye injection. METHODS: The tumor was located by marking clips using intraoperative fluoroscopy. First, saline was injected into the colon wall
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from the serosal side using percutaneously inserted needle to assure correct injection into the colorectal wall confirmed by mild resistance and bulging on serosa. Then indocyanine green dye (ICG) (absorption spectrum: 805nm) solution was injected proximal and distal side of the tumor. SN was observed using conventional laparoscopy and IRL (infrared light: 780nm-830nm). A total of 38 patients with LAC for colorectal cancer were enrolled. RESULTS: In cases of early colorectal cancer, the sensitivity of lymph node metastasis by SN was 100%. The detectability of SN using IRL is approximately five times better than that of using conventional laparoscopy. IRL detected SN that has not been detected with conventional laparoscopy in 91.9% cases. CONCLUSION; Observation of ICG dye stain in the SN using infrared IRL was much superior to that of conventional laparoscopy. The technique of saline injection prior to dye injection facilitated SN mapping for colorectal cancer during LAC.
FP-169 Trial to Control of Pancreas Cancer Metastasis by Gene Therapy with Interferon-Beta Expression Vector Containing Liposome Takuya Nagata, Fuminori Yamagishi, Yasuharu Ohnishi, Satoshi Nozawa, Kohtaro Sasahara, Tadashi Bando, Hideki Abe, Kazuhiro Tsukada 2nd Department of Surgery, Toyama Medical and Pharmaceutical University, Japan (Purpose) Pancreas cancer has one of the worst prognoses among all the malignancies, and more effective adjuvant therapies are required. This time, we investigated the efficacy of Interferon-beta expression vector containing liposome (IAB-1) against human pancreatic cancer cells in vivo and in vitro. (Method) Human pancreatic cancer cell lines (AsPc-1) were seeded in the presence of various concentrations of IAB-1. The anti-proliferative effects of IAB-1 were evaluated by counting of viable cells or monitoring of fluorescence at 590 nm emission wavelength after Alamar-blue assay. Apoptosis inducing activity of IAB-1 was shown by annexinV and PI staining of AsPc-1 after incubation with IAB1. Metastasis inhibition assay was performed that small block of AsPc-1 cells were transplanted into the liver of nude-mouse, and 1 week later, IAB-1 was injected to the liver tumor directly. After 2 weeks, tumor sizes were compared with tumors that control vector containing liposomes were injected. (Result) IAB-1 treated human pancreas cancer cell-line AsPc-1 was shown anti-proliferative effect in dose-dependently. And it was also shown that these anti-proliferative effects were because of apoptosis that were induced by IAB-1. Interferon-beta which was secreted into supernatant from IAB-1 induced AsPc-1 cells, also had the tumor growth inhibition activity. IAB-1 injected liver tumors of nude-mice were inhibited the tumor-growth activity, compared to control vector injected liver tumor. (Conclusion) IAB-1 has a possibility of anti-proliferative effect to the metastasis of pancreas cancer.
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FP-170 Comparison of Multivisceral Resection and Standard Operation for Locally Advanced Colorectal Cancer: Analysis of Prognostic Factors for Short-term and Long-term Outcome Yuji Nakafusa, Toshiya Tanaka, Masayuki Tanaka, Yoshihiko Kitajima, Seiji Sato, Kohji Miyazaki Department of Surgery, Saga University Faculty of Medicine, Japan Purpose: The aim of the present study is to clarify the characteristics of multivisceral resection and to discuss strategies for improving the overall outcome of multivisceral resection for locally advanced colorectal cancer. Methods: The study included 323 patients who electively underwent curative surgery for colorectal carcinoma of pT3-pT4 without distant metastasis. We evaluated the short- and long-term outcome of multivisceral resection relative to that of the standard operation with multivariate analysis of the prognostic factors. Results: Of 323 patients, 53 (16.4%) received multivisceral resection due to adhesion to other organs. Multivisceral resection was significantly associated with tumor size, depth of invasion, operative blood loss, operation time, and blood transfusion (all: p<0.0001). Overall morbidity rates were 49.1% after multivisceral resection versus 17.8% after the standard operation (p<0.0001), and postoperative mortality rate was 0% in both groups (NS). Only multivisceral resection (OR; 2.725, 95%CI; 1.125~6.623, p=0.0264) was an independent factor for overall postoperative complications. The survival rate of patients after multivisceral resection was similar to that after the standard operation (5-years; 76.6% vs. 79.5%, p=0.9347). Lymph node metastasis (HR; 2.510, 95%CI; 1.460~4.315, p=0.0009) and blood transfusion (HR; 2.353, 95%CI; 1.185~4.651, p=0.0145) were independently associated with patient survival. Conclusions: For locally advanced colorectal cancer, the long-term outcome after multivisceral resection is comparable to that after the standard operation. However, it should be recognized that multivisceral resection is associated with higher postoperative morbidity. In addition, making an effort to reduce the incidence of blood transfusion may contribute to improving patient survival.
FP-171 Phase I Study of Gemcitabine and Accelerated Hyperfractionaed Radiation for Potentially Resectable Pancreatic Cancer Shoji Nakamori, Shin Nakahira, Atsushi Miyamoto, Shigeru Marubashi, Hiroaki Nagano, Keizo Dono, Koji Umeshita, Masato Sakon, Morito Monden Surgery and Clinical Oncology, Osaka University, Japan Purpose: Although neoadjuvant chemoradiation therapy with GEM is one of the promissing treatment modalities for potentially curative advanced pancreatic cancer, the tolerability and safety have been not well examined. METHODS: Sequential dose-escalation of GEM (400 mg/m2 to 800 mg/m2: 0.5 hours i.v. on day 1 and 7) and concomitant accelerated hyperfractionaed irradiation (1.5 Gy x2/day, 5 days/weeks, total dose 30Gy or 36 Gy) was performed for patients with potentially resectable pancretic cancer as follows; Level 1: GEM 400 mg/m2, 30Gy, Level 2: GEM 400 mg/m2, 36Gy, Level 3: 600 mg/m2, 36 Gy, Level 4: 800 mg/m2, 36 Gy. Minimum 3 patients were included per dosage level and recommend dose (RD) was determined. RESULTS: A total 15 patients were enrolled. Nine patients of the first 3 dose leves did
not demostrated severe toxity. Leukopenia and neutropenia of grade 4 occurred in 1 of 6 patient at level 4. Clinical effects determined by CT scan included one PR, 13 SD and one PD. Reduced CA19-9 level less than a half of that at starting time was observed 12 of 15 patients. Of 13 patients who have undergone laparotomy, 11 patients (85%) underwent R0 resection without any complications. 2 patients underwent paliative surgery due to M1 disease revealed at lapalotomy. CONCLUSION: The preoperative combination of GEM and accelerated hyperfractionaed irradiation for potentially resectable pancreativ cancer is feasible and tolerated at therapeutic doses. The RD of GEM is 800 mg/m2 combined with total dose 36 Gy accelerated hyperfractionaed irradiation in this study.
FP-172 Long-term Outcome after Curative Resection of Pancreatic Head Cancer by Post-operative Intra-arterial Infusion Chemotherapy Shoji Nakamori, Shin Nakahira, Atsushi Miyamoto, Shigeru Marubashi, Hiroaki Nagano, Keizo Dono, Koji Umeshita, Masato Sakon, Morito Monden Surgery and Clinical Oncology, Osaka University, Japan Purpose: Effective adjuvant therapy after the curative resection for pancreatic cancer should be established. Effects of intra-arterial infusion chemotharapy on the hepatic recurrence and on the survival rate still remaine unclear. Methods: A prospective randomized clinical trial of postoperative intra-arterial infusion therapy via hepatic artery was performed. Twenty seven patients were allocated randomly at operation after curative resection to an intra-arterial infusion group (13 patients) who underwent catheterization in the hepatic artery at surgery or a control(surgery alone) group (14 patients). Patients in the intra-arterial infusion group received continuous intra-arterial 5FU (125mg/day) infusion from postoperative day 2 for 4weeks and, then eight times bi-weekly intraarterial 5FU (1250mg/day) infusion at outpatient clinic. Disease free survial rate for hepatic recurrence and cumulative survival rates were compared between the both group by intention to teat method. Results: Twelve patients were completed with intra-arterial infusion without any intensive adverse effects, while one patients was not completed due to gastrointestinal toxity. One and three-years disease free survival rate for hepatic recurrence were 91% and 91% in the intra-arterial infusion group, while these were 52% and 33% in the control group (P<0.01). One and threeyears cumulative survival rates were 92% and 63% in the intraarterial infusion group, while were 69% and 23% in the control group (P<0.05). Conclusion: Post-operative intra-arterial infusion chmotherapy seems to improve the outocome of patients who underwent the curative pancreatoduodenectomy for adenocarcinoma of the pancreas due to prevention of hepatic recurrence.
FP-173 Chemoradiotherapy with and without Esophagectomy for Advanced Esophageal Squamous Cancer Tsutomu Nakamura, Kazuhiko Hayashi, Kazumi Uchida, Satoshi Takeichi, Kosuke Narumiya, Ken Takasaki Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Japan Chemoradiotherapy (CRT) has been established as a first-line
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treatment for locally advanced esophageal squamous cancer. To evaluate the role of esophagectomy after chemoradiotherapy, we reviewed the data of the patients who received CRT with and without esophagectomy. [Patients] Between 1992 and 2002, 124 patients with advanced esophageal squamous cancer who received CRT. Thirty-two patients received CRT as a neo-adjuvant therapy (<50 Gy) (Neoadjuvant group) and 92 patients received definitive CRT (>= 50 Gy). Thirty patients underwent salvage esophagectomy (Salvage group) and 62 patients did not undergo surgery (Non-surgery group). The response to CRT was pathologically evaluated in the resected specimens for the neo-adjuvant group. [Methods] Various regimen of CRT were adopted, but Cisplatin/Nedaplatin + 5-FU were administrated sequentially or concurrently in addition to radiotherapy. [Results] Response to CRT was CR in 23 (18%) patients, PR in 72 (58%), SD in 27 (22%), and PD in 2 (2%) (Response rate: 76%). Survival of the patients was significantly different according to the response to CRT (p<0.0001). Survival of responders was not different among neo-adjuvant, salvage, and non-surgery groups. Although the neo-adjuvant group patients did not have recurrence diseases three years after CRT, the other groups patients had longterm recurrence. Furthermore, the patients who received definitive CRT had long-term toxicities after treatment. [Conclusion] Although survival was not different between the patients with and without esophagectomy after CRT, strict followup might be necessary for long-term recurrence and toxicities in the patients treated with definitive CRT.
FP-174 Frequent Loss of Runx3 Gene Expression in Remnant Stomach Cancer and Adjacent Mucosa Yuen Nakase1, Chohei Sakakura2, Kouji Miyagawa2, Syuichi Kin2, Ken-Ichirou Fukuda2, Noriaki Morofuji3, Kazuma Koide3, Katsumi Shimomura4, Eigo Otsuji2, Akeo Hagiwara2, Yamagishi Hisakazu2 1 Department of Digestive Surgery, 2Digestive Surgery, Kyoto Prefectural University of Medicine, 3Department of Surgery, Kyoto First Red Cross Hospital, 4Department of Surgery, Kyoto Second Red Cross Hospital, Kyoto, Japan Purpose: RUNX3 is a novel tumor suppresser gene in gastric cancer. We examined tumorigenesis in the remnant stomach after distal gastrectomy for peptic ulcer (RB group) or gastric cancer (RM group), by analyzing RUNX3 expression. Experimental Design: Eighty-nine patients underwent distal gastrectomy for gastric cancer from the intact stomach (GCI group) and 58 patients underwent resection of the remnant stomach for gastric cancer (RB group: 34 cases, RM group: 24 cases). We detected RUNX3 and gene promoter methylation by in situ hybridization, quantitative RT-PCR and methylation-specific PCR. Results: The interval between the initial surgery and surgery for remnant gastric cancer (interval time) was 10.4 years in the RM group, and 27.5 years in the RB group. Cancers in the RB group were significantly more predominant in the anastomosis area. Within the tumor, downregulation of RUNX3 expression rate ranged from 74.7 to 85.7% in the three groups. In adjacent mucosa, downregulation of RUNX3 expression rate was 19.5% in the GCI group, 39.2% in the RB group and 47.6% in the RM group. In noncancerous mucosa of the remnant stomach in the RB group, RUNX3 expression decreased more near the anastomosis area. In the RM group, however, there were no significant differences in RUNX3 expression
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by sampling location. Conclusions: Gastric cancer pathogenesis of the RM group based on RUNX3 expression differs from the RB group. The measurement of RUNX3 expression and detection of RUNX3 methylation in remnant gastric mucosa may estimate the forward risk of carcinogenesis in the remnant stomach.
FP-175 Randomozed Controlled Study of Preoperative Chemoradiation versus Surgery Alone in Esophageal Squamous Cell Carcinoma Shoji Natsugoe, Hiroshi Okumura, Masataka Matsumoto, Testuhiro Owaki, Sumiya Ishigami, Yoshikazu Uenosono, Shizuo Nakano, Takashi Aikou Surgical Oncology and Digestive Suregry, Kagoshima University, Japan Purpose: There is an increasing interest in the role of combined therapy to achieve long-term survival for patients with resectable esophageal squamous cell carcinoma (ESCC). We evaluated the clinical results in prospective randomized controlled trial between preoperative chemoradiation therapy (CRT group) and surgery alone (surgery group). Materials and method: From 1997 through 2001, 46 patients with resectable ESCC who were 70 years or less, had no serious complications and had no multiple primary cancer in other organs, were enrolled in this study. CRT consisted of 5fluorouracil plus cisplatin and 40 Gy of radiation. Results: Although 23 patients received CRT, 3 patients were not eligible because of hematogeneous metastasis during CRT. Significant difference was not found in preoperative clinical factors between two groups. The effect of CRT was found in 12 of 20 patients. In the pathological diagnosis, the incidence of lymphatic and veneous invasion was higher in surgery group than in CRT group. Recurrent disease in surgery and CRT group was found in 9 and 14 patients, respectively. Five year survival rate was not significant different between surgery group (41.3%) and CRT group (56.6%). However, the prognosis was better in responder (85.7%) than in non-responder (30.0%) for CRT. Conclusion: This randomized trial of CRT versus surgery alone for patients with potentially resectable ESCC did not demonstrate a statistically significant survival difference. However, since this study consisted of small number of patients, the effect of CRT was evaluated in a large number of patients.
FP-176 Maximal Host Tolerance to Large-volume Hepatic Radiofrequency Ablation in a Rat Model Kelvin Kwok-Chai Ng1, Chi-Ming Lam1, Ronnie Tung-Ping Poon1, Tony Shek2, David Ho1, Sheung-Tat Fan1 1 Department of Surgery, 2Department of Pathology Centre for the Study of Liver Disease, Hong Kong, China Background: Large-volume hepatic radiofrequency ablation (RFA) has been used widely to treat large liver tumours but its maximal host tolerance is unknown. This study aimed to estimate the maximal tolerance to large-volume RFA in normal and cirrhotic rats. Materials and Methods: RFA using internally cooled electrode was performed in normal and cirrhotic Sprague-Dawlay rats. Different percentages of the liver volume by weight were ablated. Changes in serum inflammatory markers (tumour necrosis factor-
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α and interleukin-6), various end-organs function and survival rate were assessed. Results: In the normal liver groups, the concentrations of TNF-α and IL-6 were significantly elevated in the early postoperative period when 50% (TNF-α: 130.3 ± 15.6 pg/ml; IL-6: 163.2 ± 12.2 pg/ml) and 60% (TNF-α: 145.7 ± 13 pg/ml; IL-6: 180.8 ± 11 pg/ml) of the liver volume were ablated, compared with the control group (TNF-α: 30.4 ± 9.9 pg/ml, P < 0.001; IL-6: 28.4 ± 6.7 pg/ml, P < 0.001). The concentrations of TNF-α and IL-6 in other groups remained similar to those of the control group. Thrombocytopenia, prolonged clotting time, and interstitial pneumonitis occurred when 50% and 60% of the liver volume were ablated. The survival rate was 100%, 60% and 0% when 40%, 50% and 60% of the liver volume were ablated, respectively. Similar systemic inflammatory responses and poor survival rate were observed among the cirrhotic liver groups when 30% and 40% of the liver volume were ablated. Conclusion: The normal rats can tolerate RFA of 40% of liver volume with minimal morbidity and no mortality, whereas the cirrhotic rats can only tolerate 20% of the ablated liver volume. Beyond that limit, RFA was associated with significant systemic inflammatory responses and poor survival.
FP-177 Safety and Efficacy of Radiofrequency Ablation for Perivascular Hepatocellular Carcinoma without Hepatic Inflow Occlusion Kelvin Kwok-Chai Ng1, Ronnie Tung-Ping Poon1, Chi-Ming Lam1, Jimmy Yuen2, Wai-Kuen Tso2, Sheung-Tat Fan1 1 Department of Surgery, 2Department of Radiology, Centre for the Study of Liver Disease, Hong Kong, China Background: The role of radiofrequency ablation (RFA) for perivascular (< 5mm from major intrahepatic portal vein or hepatic vein branches) hepatocellular carcinoma (HCC) remains unclear due to the possible incomplete tumor ablation and the potential vascular damage. Aim of Study: This study was to evaluate the safety and efficacy of RFA for perivascular HCC without hepatic inflow occlusion. Patients and Methods: Between May 2001 and November 2003, RFA using internally cooled electrode was performed on 58 patients with perivascular HCC (median size = 3.1 cm) (group 1). No hepatic inflow occlusion was used during the ablation. The perioperative and short-term outcomes were compared with those of 104 patients with non-perivascular HCC (group 2) treated by RFA during the same time interval. Results: The morbidity rate was similar between groups 1 and 2 (19% vs. 27.6%; P = 0.251). The intrahepatic blood vessels close to the ablated tumor remained patent after RFA in all patients of group 1. There were no significant differences between groups in mortality rate (3.4% vs. 0%; P = 0.125), complete ablation rate after single session ablation (86.2% vs. 95.1%; P = 0.067), local recurrence rate (10% vs. 7%; P = 0.538) and overall survival (1year: 83.6% vs. 84.2%; 2-year: 60.9% vs. 56.9%; P = 0.627). By univariate analysis, chronic hepatitis C infection is the only factor affecting the local tumor recurrence at treatment site. Conclusions: RFA without hepatic inflow occlusion is a safe and effective treatment modality for perivascular hepatocellular carcinoma.
FP-178 Initial Experience of Radiofrequency Ablation for Ruptured Hepatocellular Carcinoma Kelvin Kwok-Chai Ng, Ronnie Tung-Ping Poon, Chi-Ming Lam, Sheung-Tat Fan Department of Surgery, Centre for the Study of Liver Disease, Hong Kong, China Background: Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening surgical emergency. The role of radiofrequency ablation (RFA) in achieving hemostasis for ruptured HCC remains to be investigated. Aim of Study: This study was to evaluate the efficacy of RFA for ruptured HCC. Patients and Methods: Between November 2001 and April 2004, RFA using internally cooled electrode was performed on 8 patients with ruptured HCC through open approach (group 1). The perioperative and short-term outcomes were compared with those of 29 patients with ruptured HCC treated by other surgical methods, including packing, suturing, argon beam coagulation, ligation of hepatic artery and hepatic resection (group 2). Results: There was no significant different between groups 1 and 2 in intraoperative blood loss (3600 ml vs. 3000 ml, P = 0.640), requirement of blood product transfusion (1.28 units vs. 1.22 units, P = 0.794), postoperative complication rate (25% vs. 31%, P = 0.741) and hospital mortality (25% vs. 48%, P = 0.423). The duration of operation was longer in group 1 (median = 190 min) than group 2 (median = 147.5 min) (P = 0.003). Apart from hemostasis, complete ablation of tumor by RFA was achieved in one patient of group 1. Conclusions: RFA is feasible for ruptured HCC in achieving hemostasis as well as tumor ablation.
FP-179 When should we Preform Laparoscopic Cholecystectomy after an Attack of Acute Cholangitis? Nancy Ching Ng, Frances Ky Cheung, Canice Tl Leung, Philip Wy Chiu, Paul Bs Lai, Enders Kw Ng Surgery, Prince of Wales Hospital, Hong Kong, China Background: ERCP is the first line treatment of acute cholangitis. However, when to perform cholecystectomy after endoscopic clearance of the common bile duct (CBD) stones is unclear. This study aims to determine whether early laparoscopic cholecystectomy is safe after resolution of acute cholangitis. Methods: We reviewed a cohort of 58 patients who had laparoscopic cholecystectomy attempted after an attack of cholangitis. There were two surgical teams operating: one team operated on their patients within 2 weeks after clearance of CBD stones, while the second team would offer interval cholecystectomy at least 8 weeks after the index admission. The outcomes of the two groups were compared. Results: Interval cholecystectomy (IC) was attempted on 40 patients while 18 patients had early cholecystectomy(EC). The two groups were comparable regarding their age, gender ratio and ASA risk. 7 patients in the delay group had premature readmission. Otherwise, the two groups were similar in median total operation time (100 mins (EC) vs 97 mins (IC); p=0.6) and median total hospital stay (12.8 days (EC) vs 12.5 days (IC); p=0.78). Postoperative complications were seen in 4 patients among the IC patients but none in the EC group; however, the
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difference was not statistically significant (p=0.29). Conclusions: Early laparoscopic cholecystectomy is feasible and safe after acute cholangitis. It has similar operation time and total hosptial stay when compared to the conventional delay approach. It prevents unexpected readmission during the waiting period.
FP-180 Optimal Indications for Sentinel Node Navigation Surgery (SNNS) using Infrared Ray (IR) and Ideal Technique for Detection of Lymph Node Metastasis in Gastric Cancer Hiroshi Nimura, Norio Mitsumori, Tomoki Koyama, Katsuhiko Yanaga Surgery, The Jikei University School of Medicine, Japan Objective: To clarify both the optimum indications for the IR method for SNNS and the ideal technique for the detection of lymph node metastasis (LNM) in gastric cancer. Methods: SNNS was performed with IR in 100 gastric cancer patients who were divided according to time of identification as follows: Biopsy Group (BG: n=29), biopsied after indocyanine green (ICG) injection, Postoperative Group (PG: n=64), examined after surgery; and Preoperative Injection Group (PIG: n=7). BG was further divided by methods of lymph node sampling into picked up subgroup (PU: n=13) and lymphatic basin dissection subgroup (LBD: n=16). Diagnostic accuracy in the 15 patients with LNM was examined, and intraoperative detection rates of LNM in PU and LBD of the 13 patients were compared. The numbers of lymphatic basins in BG and PG+PIG were also compared. Results: The diagnostic accuracy of LNM was 100%. The accuracy of intraoperative detection of LNM was 50% for PU and 100% for LBD. For tumors smaller than 40 mm with one lymphatic basin, the detection rate of BG and PG+PIG was 65% and 38%, respectively. The number of lymphatic basins in any group after ICG injection increased with time. Discussion: For IR-guided SNNS in gastric cancer, the optimal timing for ICG injection is intraoperative, and LBD is essential for accurate diagnosis.
FP-181 Results of Japanese Clinical Trial of STI571 against Advanced GIST Toshirou Nishida, Akiko Nishitani, Kiyokazu Nakajima, Shunji Endo, Hikaru Matsuda Department of Surgery, Osaka University Graduate School of Medicine, Japan [PURPOSE] STI571 is active against malignant GIST in the USA and EU. This open-labeled study examined efficacy, tolerability and evaluation methods in Japanese patients with malignant GISTs. [METHODS] The inclusion criteria were GISTs with measurable lesions and patients were randomized to either 400 or 600 mg/day of STI571. Efficacy was evaluated by CT and/or FDG-PET. [RESULTS] 82 patients (400/600 mg/day = 36/46, M/F = 53/28) were evaluated after 1-year treatment of STI571. Best response was no CR, 58 PR (400/600=22/36), 21 SD (13/8) and 2 PD (1/1). KIT and PDGFR mutations were examined in 61 and activating mutations in the genes were found 56 (55 and 1, respectively). STI571 is most active against GISTs with KIT exon 11 mutations, followed by exon 9 mutation, and the drug were not effective for GISTs with kinase domain mutations or without mutation in the genes. FDG-PET was performed 23 pts and 22
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showed baseline uptake of FDG. 19 patients with CR in PET after one month became PR (16) or long SD (3) by conventional SWOG criteria, two PET-SD patients SD or PD, PET-PD patients PD after several months. In FDG-PET, responses were seen 3 days after STI571 initiation. Adverse effects were seen all patients and most of them were Grade 1 or 2. Serious and frequent adverse effects in Japanese were blood toxicity. [CONCLUSION] STI571 was active against Japanese patients with advanced GIST with considerable safety and tolerability. FDG-PET was useful for early detection of effectiveness.
FP-182 Surgical Outcome of the Neural Tissues Preserving Para-aortic Lymph Node Dissection based on Anatomical Evaluation Masato Nomura, Chikara Kunisaki, Hiroshi Shimada, Hidetaka Ono, Yuichi Otsuka, Goro Matsuda, Hirotoshi Akiyama, Masazumi Takahashi Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan Aim: We studied anatomical distribution of para-aortic lymph nodes for effective lymph node dissection preserving neural tissues and surgical results were evaluated. Materials and Methods: Paraaortic lesions were anatomically examined in 31 cadavers. Histology was evaluated, focusing on the relationship between the paraaortic lymph nodes and the neural tissue or microvessels using transverse sections of 14 cadavers. Surgical results were also analyzed in patients with D3 gastrectomy based on anatomical findings (n= 33). Results: Anatomically, the greater and lesser splanchnic nerves merged into the celiac ganglion, which consisted of only one ganglion (type I) or several ganglia (type II). We meticulously dissected para-aortic lymph nodes by traction of neural bands according to the each type of ganglion distribution. The average number of lymph nodes was 17.4 in the area superior to superior mesenteric artery (superior site), 13.3 in the area inferior to superior mesenteric artery (inferior site). According to the number of metastatic lymph nodes (<3, >4), mean survival time was 14.7 and 9.7 months, respectively (p<0.02). With or without metastatic lymph nodes behind the neural tissue, mean survival time was 14.7 and 9.7 months, respectively (p<0.02). Conclusion: Para-aortic lymph node dissection preserving neural tissue would be useful in patients with 3 or less para-aortic metastatic lymph nodes or without metastatic lymph nodes behind the neural tissues.
FP-183 Effect of Helicobacter Pylori Infection in Experimental Gastric Carcinogenesis Koji Nozaki1, Yuzuru Ikehara2, Nobuyuki Shimizu1, Xueyuan Cao1, Harunari Tanaka2, Tsukamoto Tetsuya2, Ken-Ichi Inada2, Hayao Nakanishi2, Ken-Ichi Mafune1, Michio Kaminishi1, Masae Tatematsu2 1 Department of Gastrointestinal Surgery, Postgraduate School of Medicine, The University of Tokyo, 2Division of Oncological Pathology, Aichi Cancer Center Research Institute, Japan Purpose To explore the causal link between Helicobacter pylori infection and stomach carcinogenesis using an in vivo experimental model, we have established an experimental gastric carcinogenesis model using Mongolian gerbils. Methods Mongolian gerbils were divided into groups in the following experiments: [Experiment I] Eradicaton after long-term
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H.pylori infection model; [Experiment II] H.pylori Infection and 10% w/w high-salt diet administration model; and [Experiment III] eradication model at early, middle, or late period after H.pylori infection. In each experiment, H.pylori (ATCC43504) was used, while lansoprazole, amoxicillin and clarithromycin were used in experiment I and III for eradication of H.pylori. Results [I] H.pylori infection develops proliferative glands with a phenotypic shift of intestinalization in glandular stomach of gerbils. After eradication, these proliferative lesions improved with few remnants of the former injury. [II] H.pylori infection enhances gastric carcinogenesis not only of well-differentiated type but also poorly-differentiated and signet ring cell type. A high-salt diet and H.pylori infection acted synergistically to promote the development of stomach cancers. [III] The tumor incidence was significantly higher in animals treated with H.pylori than in the controls, and was related to the period of inflammatory status induced by H.pylori infection. Conclusions H.pylori infection strongly enhanced gastric carcinogenesis, and a high-salt diet synergistically enhanced the effect of H.pylori. Eradication at an early stage of inflammation resulted in lower incidence of gastric carcinogenesis, implying that eradication of H.pylori may be useful as a measure for prevention of gastric cancer.
FP-184 Evaluation of Surgical Treatment for Common Bile Duct Stones with Preoperative Endoscopic Papillary Stone Removal Satoshi Nozawa, Takuya Nagata, Hideki Abe, Tadashi Bando, Fuminori Yamagishi, Kohtaro Sasahara, Yoshinobu Yokoyama, Yasuharu Ohnishi, Kenichi Tazawa, Shinichiro Hirokawa, Kazuhiro Tsukada The Second Department of Surgery, Toyama Medical and Pharmaceutical University, Japan Purpose: To identify better strategy for common bile duct stones. Methods: Medical records of 30 patients, treated surgically for common bile duct stones in our institution from 1997 to 2003, were examined retrospectively. Results: Endoscopic papillary stone removal was performed if possible. All the surgeries were carried out after relief of biliary infection or obstructive jaundice if they existed. Choledocholithotomy was performed in 14 patients (Group A). In 12 patients, laparoscopic cholecystectomy, which had to be opened in two patients, was performed after endoscopic papillary stone removal (Group B). Bile duct reconstruction was performed for three patients after total gastrectomy and a patient with periampullary diverticulum (Group C). Hospital stay after surgery was significantly shorter in Group B; Group A 17.4 ± 8.7, Group B 8.5 ± 7.4, Group C 32.5 ± 15.9 days. However, total hospital stay was not significantly different among three groups. Systemic inflammatory response syndrome (SIRS) in surgical stress was observed in 13 patients. Postoperative complications were observed in nine patients. The most common was wound infection that occurred in six patients who had biliary infections prior to surgery. In the patients with postoperative SIRS or complications, the postoperative and the total hospital stay were significantly longer than in the others. Conclusions: Endoscopic papillary stone removal with subsequent cholecystectomy is beneficial for shorter postoperative hospital stay. As it cannot be selected for all patients, it would be important to prevent postoperative SIRS and complications that could be related to biliary infections before surgery.
FP-185 Anus-preserving Operation with Sphincteric Resection for Low Rectal and Anal Canal Cancer Yutaka Ogata, Shujiro Ogo, Teruo Sasatomi, Nobuya Ishibashi, Keiko Matono, Takamasa Fukumitsu, Seiichiro Shida, Kazuo Shirouzu Department of Surgery, Kurume University School of Medicine, Japan Introduction: Recently, partial resection of the deep-superficial external sphincter muscle (ESR) in addition to total resection of internal sphincter muscle (ISR) has been introduced for low rectal and anal canal cancer in our hospital. We have evaluated the postoperative results of these anus-preserving operations, and discussed the indication. Patients and Methods: Histological study on tumor spreading into the anal canal and the ishiorectal tissue was performed using whole specimen of 211 patients who underwent APR between 1982 and 2000. Post-operative anal functions and recurrence in 9 ISR and 12 ESR cases were evaluated. Results: Among 176 cases whose distal tumor margin located above the dentate line, invasion into the subcutaneal external sphincter muscle (B) in 2 cases (1%), invasion into the sphincter muscle groove (C) in 4 cases (2%), and no invasion into the ishiorectal tissue (D) were found. On the other hand, among 35 cases whose distal tumor margin located below the dentate line, A in 13 cases (37%), B in 3 cases (9%), C in 10 cases (29%), and D in 4 cases (11%) were noted. Anastomotic leakage occurred in 2 cases. All patients who received ISR retained excellent anal function without soiling. Some patients receiving ESR complained occasional night soiling but anus-preservation was satisfactory. There was no recurrence due to the anus-preservation. Conclusion: In most patients whose distal tumor margin located above the dentate line, anus-preserving operation with sphinter resection can be indicated. The ISR and ESR are excellent procedure for anus-preservation.
FP-186 Intersphincteric Resection of Distal Anal Rectal Cancer using Illuminating Perirectal Indicator Nahm-Gun Oh Surgery, Pusan National University School of Medicine, Korea Purpose: To introduce a transanal intersphincteric resection with quadrant resection of deep external sphincter for low rectal cancer for safe inferior-lateral surgical margin. Methods: Inclusion criteria were low rectal cancer within 4cm from anal verge and T-3 downstaging after radiation therapy. After transabdominal dissection in low rectal cancer was completed, a transanal intersphincteric dissection was made under guidance of transabdominal illuminating perirectal indicator, and quadrant resection of anal external sphincter and immediate levatosphincteroplasty was performed in all 18 cases. Colonic J-pouch, colo-perineal anastomosis and preventive ileostomy were performed in all 18 cases. Median follow up period was 12.4 months and patient were evaluated about postoperative complication, functional results and fecal incontinence by Kirwan classification. Results: Postoperative complications were urinary retention in 7 cases, incisional wound abscess in 3 cases, anastomotic leakage in 2 cases, anal stenosis in 2 cases, and anal wound dehiscence of levato-sphincteroplasty in 1 case due to
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radiation side effect, partial intestinal obstruction in 1 cases. There was defecational frequency in 2.7 times a day, fragmentation in 7 cases, and urgency in 6 cases. Postoperative fecal incontinence was Grade I in 7 cases, Grade II in 6 cases, Grade III in 4 cases, Grade IV in 1 cases, Grade V in 1 cases. Conclusions: This transanal intersphincteric approach with additional quadrant resection of anal external sphincter using perirectal illuminator is considered to be an effective optional procedure with acceptable functional results in very low rectal cancer T-3.
FP-187 The 9-Pouch: A New Ileal Reservoir Used in Restorative Proctocolectomy Nahm-Gun Oh Surgery, Pusan National University School of Medicine, Korea Aim: To evaluate the effectiveness of a 9-pouch configuration with a reservoir and recycled segment in restorative proctocolectomy. Methods: There were 11 patients who underwent the 9-pouch procedure. They were compared with healthy eight-control subjects. The 9-pouch configuration was constructed using one firing of a 10 cm GIA stapler to form a 12-cm reservoir. Following that, the distal ileum (15±0.5 cm) was anastomosed to the proximal portion of the pouch. Pouch function was studied 23.3±4.4 months after ileostomy closure. We measured the frequency and amount of stool. The postprandial plasma peptide YY (PYY) response and the scintigraphic studies using 99m-Tc sulfur colloid were used to study transit. Results: In the patient group, daily stool frequency and volume were 5.2±0.3 and 423.5±23.7 g, respectively. Stool seepage and pouchitis occurred in 45.5 % and 27.3%. In contrast to other pouch procedures, the postprandial increment of plasma PYY was similar the 9-pouch patients and healthy controls (P > 0.05). The integrated increment of plasma PYY for 180 minutes following meals was also not decreased in 9-pouch patient group compared with the healthy controls (1050.0±127.8 pmol/L vs. 1146.0±150.0 pmol/L, P > 0.05). Small intestinal transit time for healthy controls and the patient group averaged 89±21 and 117±12 minutes (P > 0.05). The capacity of the ileal pouch was 372±22 ml, and the efficiency of ileal reservoir evacuation was 76 %. Conclusions: The 9-pouch is a new and improved simple modification of the well-established J-pouch procedure, constructed using a single firing of a GIA stapler.
FP-188 Minimally Invasive Resection for Gastic Submucosal Tumors Shuichi Ohta, Tomika Harada, Kiyoshi Hirai, Miho Ohnishi, Morito Sakikubo, Izumi Komoto, Yukito Adachi, Masayuki Imamura Surgery, Saiseikai, Noe Hospital, Osaka, Japan Purpose: Gastric submucosal tumors represent a various spectrum of histopathologic and prognostic characteristics. It is difficult to estimate these malignant potentials before operation. So minimally invasive resection become the treatment of choice for gastric submucosal tumors. We will report the technique and result of laparoscopic intragastric surgery combined with the video endoscope and laparoscopic resection for gastric submucosal tumors in four patients. Patients and Methods: Between 2002 October to September 2003, we have performed minimally invasive resection for gastic submu-
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cosal tumors in 4 patients. There were one male and three females ranging 54 to 62 years old with a mean age of 59 years. Location of these tumors were in the lesser curvature of the body, the anterior wall of the body, greater curvature of the body and adjacent to esophagogastric junction. The laparoscopic intragastric resection combined with the video endoscope on one patient and three laparoscopic wedge resections were performed. Results: Mean operative time was 144 min (83 to 210 min). Mean intraoperative blood loss was 37.5ml (10 to 120 ml). The patients tolerated liquid diets in 1 to 3 days after operation. The length of postoperative hospital stay was 8.5days. All tumors had Immunohistologically examinations, and two gastrointestinal stromal tumors and two leiomyoma were diagnosed. Conclusions: The laparoscopic procedure is applicable for the removal of submucosal gastric tumors. The combination of the video endoscope and Laparoscopic intragastric surgery can eliminate the difficulty caused by the problematic location of the tumor.
FP-189 AKT Phosphorylation Associates with LOH of PTEN and Leads to Chemoresistance for Gastric Cancer Eiji Oki1, Eriko Tokunaga1, Manabu Yamamoto1, Masayuki Watanabe1, Masahiko Ikebe1, Yoshihiro Kakeji2, Hideo Baba1, Yoshihiko Maehara1 1 Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 2Center for the Integration of Advanced Medicine and Innovative Technology, Kyushu University Hospital, Japan Purpose. Growth factor receptor-mediated signal transduction has been implicated in conferring resistance to conventional chemotherapy on cancer cells. In this study, we describe a pathway that involves AKT/PI3K to mediate chemoresistance in gastric cancer patients. Experimental Design. Primary gastric carcinoma tissues and corresponding normal mucosa were obtained from 76 gastric cancer patients who underwent surgery in the Department of Surgery II in Kyushu University Hospital from the years 1996 to 2000. AKT activation was investigated by immunostaining with a phosphorylation-specific antibody, and LOH (loss of heterozygosity) of PTEN was studied in the same samples. Results. We found that the gastric cancer patients who had a higher AKT phosphorylation (activated AKT) appeared to have LOH of PTEN (p < 0.0008). When the chemotherapeutic sensibilities of these patients were studied in an MTT assay, it was found that the activated AKT was associated with increased resistance to multiple chemotherapeutic agents (5-fluorouracil, adriamycin, mitomycin C, and cis-platinum). When the 5-fluorouracil was used as the key drug for gastric cancer, the patients having activated AKT showed significant hyposensitivity in comparison with those who did not have activated AKT (p < 0.003). Conclusions. The results of this study indicate that AKT activation and LOH of PTEN plays an important role in conferring a broad-spectrum chemoresistance in gastric cancer patients. It also indicates that AKT may therefore be a novel molecular target for therapies or chemosensitivity tests that improve the outcomes of gastric cancer patients.
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FP-190 The Results of Pancreas Neuroendocrine Tumor Topical Diagnosis M. Okoemov1, A. Egorov2, N. Kuzin2, A. Lotov2, S. Kondrashin2 1 Moscow Medical Sechenov Academy, 2Presidental Medical Center, Outpatient Clinic No.1, Russia Aims. To estimate the topical diagnostics results of pancreas neuroendocrine tumor. Methods and patients. 220 patients with pancreas neuroendocrine tumor underwent surgery in the period of 1982-2004. Males-80, females-140, age range - 17-72 years, the average age 47.1 ± 4.9 years. Insulinoma - 188 cases, gastrinoma - 23, non-functional - 5, vipoma - 3, glucagonoma - 1. 21 (9.5%) patients had multiple tumors. 34 (15.5%) - malignant tumors. The neoplasms locations: head- 38.2%, body 32.4%, caudal -29.4% - totally 242 tumors. Results. For topical diagnostics 200 patients underwent US, 59CT, 41- MRT, 213 - selective endoscopical angiography, 14 - US. In 93 cases we did calcium stimulated right vein blood sampling measuring hormone level. Intraoperational US was done in 137 cases. The sensitivity of research methods: US - 50.3%, CT59.4%, MRT-51.2%, angiography-75.2, blood sampling - 85.9%, angiography combination (selective celiacography + upper mesentericography) with blood sampling - 94.5%, endoscopicaly US 87.5%. The intraoperational palpation located tumor in 87.6% cases. Intraoperational US was effective in 97.5%.All the patients were surgically treated. We used: anucleation of tumor - 102, distal resection of pancreas -97, pancreatoduodenal resection - 11, gastroectomy - 5, diagnostic laparotomy - 5. Conclusion. We believe that the diagnostics should be started with US and endoscopic US: when the hormonal activity is observed angiography combination with blood sampling after calcium stimulation should be used. In case of non-functional - CT with intravenous stimulation. Intraoperational US is indispensilble condition during the operation.
FP-191 MRI in the Diagnosis of Tumor and Inflammatory Diseases of Pancreas M. Okoemov, N. Gurova, A. Arutyunov Presidental Medical Center, Outpatient Clinic No.1, Russia The aim: To estimate the MRT results in detection and dissemination of pathological processes in pancreas diseases. Patients and Methods: Complex examination of 149 patients - 77 males and 72 females, the age range - 21-78 with the local alternation of pancreas structure, 124 (84%) underwent US, 13 (9%) angiography of abdominal cavity and 21 (14%) - retrograde pancreatocholangiography. Results: The first group consisted of 59 (39.6%) patients with tumors of pancreas, including: 38 (64.4%) - adenocarcinoma, 7 (11.9%)- cystadeno-carcinoma, 1 (1.6%) - leuomioma, 3 (5.2%) cystic adenoma, 4 (6.8%) - APUD - oma, 4 (6.8%) - metastatic affection of pancreas, 2 (3.3%) -mixed tumor. The second group 90 (60.4%) patients, 31 (34.4%)- pseudo - tumorlike pancreatitis, 18 (20%) -postnecrotic cysts, 4 (4.4%) -vascular affections coupled with inflammatory affection of pancreas, 37 (41.2%) -different types of chronic pancreatitis. Typical MR symptoms of volumetric and inflammatory affections of pancreatitis were recognized in all the cases, as well as the peculiarities of contrasting different tumor
types in arterial phase, which is important in executing differential diagnosis of inflammatory affections. At MRT 18 patients were recognized of having a symptom of tumor dissemination to abdominal cavity, proved during the operation (sensivity - 72.2%, specificity-97.4%). Conclusions: The specificity and adequacy of MRI in diagnosis of benign and malignant neoplasm’s of pancreatitis, preference that US and CT. Our results seem to show that capability of MRI with Gd enhancement more important in characterization of pancreatic tumor.
FP-192 The Clinicopathological Evaluation of Neoadjuvant Chemoradiation Therapy in Esophageal Squamous Cell Cancer Hiroshi Okumura, Shoji Natsugoe, Masataka Matsumoto, Takashi Aikou Surgical Oncology, Digestive Surgery, Kagoshima University School of Medicine, Japan Purpose: We have performed surgery in combination with preoperative chemoradiation therapy (CRT) for esophageal squamous cell cancer (ESCC). In this report, we evaluated the results of CRT, especially in clinicopathological response. Furthermore, we immunohistochemically investigated existence of micro-residual lesions such as single cancer cell or clustered cancer cells in resected specimens using an anti-cytokeratin antibody. Methods: The clinical and histological responses to neoadjuvant CRT were evaluated in 36 patients with ESCC. CRT consisted of low dose 5-fluorouracil plus cisplatin and 40 Gy of radiation. The evaluation of clinical and histological response was divided into three, respectively; complete response (CR and grade 3), partial response (PR and grade 2) and no change (NC and grade 1). Results: CR and PR to CRT were found in 26 of 36 (78.0%) patients. By histological grade, 17 (42.7%) patients had grade 1 tumors, 11 (30.6%) had grade 2 and 8 (22.2%) had grade 3. The number of patients with recurrent disease in grade 1, 2 and 3 was 13, 5 and 2, respectively. Hematogeneous relapse was frequently observed in grade 2or 3 cases. Although 20 patients with relapse had more than two nodal metastases, 12 patients without relapse had less than one nodal metastasis. Cytokeratin staining revealed three cases with single or clustered cancer cells in grade 3 tumors. Conclusions: We should establish the methods to evaluate not only clinicopathological effect for CRT but also existence of residual cancer cells. The strategy to prevent hematogeneous relapses in the responders should be required.
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FP-193 Promoter-Controlled Infectivity Enhanced Conditionally Replicative Adenoviral Vectors for the Treatment of Gastric Cancer Hidetaka Andrew Ono1, Julia G. Davydova1, Yasuo Adachi1, Koichi Takayama1, Victor N. Krasnykh2, Chikara Kunisaki3, Hiroshi Shimada3, David T. Curiel1, Masato Yamamoto1 1 Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, The Gene Therapy Center, University of Alabama at Birmingham, USA, 2Department of Experimental Diagnostic Imaging, MD Anderson Cancer Center, University of Texas, USA, 3Second Department of Surgery, Yokohama City University School of Medicine, Japan Purpose: Gastric cancer is the fourth most common malignancy worldwide. Adenoviral vectors (Ads) have been applied for gene therapy of various cancers because of their high transduction efficiency. However, the infectivity of gastrointestinal cancer cells is poor due to the limited expression of the Coxsackie-adenovirus receptor (CAR). In addition, few tumor specific promoters (TSPs) have been characterized for this type of cancer. To overcome these problems, we proposed TSP-driven conditionally replicating adenoviruses (CRAds) with fiber modification for virotherapy of gastric cancer. Methods: We assessed the expression profile of eight TSPs in gastric cancer cell lines and evaluated promising candidates in the context of CRAd cytocidal effect. Next, infectivity enhancement by fiber modifications was analyzed in the gastric cancer cell lines. Finally, we combined the TSP-driven CRAds of choice with the fiber modifications to augment the killing effect. Results: Out of the eight TSPs, the Midkine (MK) and cyclooxygenase-2 (Cox-2M and Cox-2L) promoters showed high transcriptional activity in gastric cancer cells. When these promoters were used in a CRAd context, Cox-2 CRAds elicited the strongest cytocidal effect. The greatest infectivity enhancement was observed with adenoviral vectors displaying 5/3 chimeric fibers. Likewise, Cox-2 CRAds with 5/3 chimeric fibers showed the strongest cytocidal effect in gastric cancer cell lines. Therefore, Cox-2 CRAds with 5/3 chimeric fiber modification showed good selectivity and infectivity in gastric cancer cells to yield enhanced oncolysis. Conclusion: Cox-2 CRAds with 5/3 chimeric fiber modification are promising for virotherapy of gastric cancer.
FP-194 Does Obese Patient Affect Laparoscopic Colorectal Surgery? Shunichi Osada, Shigeki Yamaguchi, Hirohumi Morita, Masayuki Ishii, Mitsuyoshi Ohta Colon and Rectal Surgery, Shizuoka Cancer Center Hospital, Japan (Aim) It was believed that operation for obese patient was more difficult than that of normal. To clarify the impact of obese in colorectal surgery, we investigated retrospectively. (Patients and method) Patients were studied regarding operation time (OT), blood loss (BL), and post operative hospital stay (POHS) in colorectal laparoscopic surgery (Group-L, n=94), and open surgery (Group-O, n=112). Each group was stratified by Body Mass Index (BMI), into 2 subgroups Normal (<25) and Obese (>25). (Results) Each result was as follows. Group-L-Normal (n=66): OT=212±45, BL=39±51, POHS=9.2±4.7. Group-L- obese (n=28): OT=255±67, BL=101±123, POHS=11.4±9.9. Group-O-Normal (n=90):
Journal of Gastrointestinal Surgery
OT=162±49, BL=230±246, POHS=14.4±8.9. Group-O-obese (n=22): OT=174±43, BL=293±245, POHS=13.7±6.9. OT, BL and POHS of obese patients was significantly higher than those of normal patients in laparoscopic surgey (p<0.01). It was not significant between normal and obese patients in open surgery. BL and POHS in laparoscopic surgery was significantly better than those in open surgey in each subgroup (p<0.01). (Conclusion) Obese patient affect laparoscopic colorectal surgery, but no influence on open surgery. BL and POHS of both normal and obese group in laparoscopic was less than those in open surgery, respectively.
FP-195 Clinical Significance of Ambulatory Intraesophageal Bilirubin Monitoring in Japanese Patients with Gastroesophageal Reflux Harushi Osugi, Masayuki Higashino, Masashi Takemura, Shigeru Lee, Kenichiro Fukuhara, Yushi Fujiwara, Satoshi Nishizawa, Hiroshi Iwasaki Department of Gastroenterological Surgery, Osaka City University, Postgraduate School of Medicine, Japan Purpose. Role of reflux of the duodenal contents in gastroesophageal reflux in the Japanese patients, who may have different background from the Western patients, was studied. Methods. Intraesophageal pH and bilirubin concentration was monitored using Bilitec 2000, in 43 patients with reflux symptoms and 10 normal volunteers. The ratio (%) of the duration of absorbency being 0.15 or more and pH less than 4.0 to the observation period were obtained as holding time (HT) of bilirubin and acid, respectively. Severity of esophagitis was classified following SavaryMiller classification (S-M). Results. Esophagitis was found in 37 patients, consisting of 5 patients, 10, 13, and 9 of S-M grade 1, 2, 3, and 4, respectively. Both HT of volunteers were less than 5%. Bilirubin HT was more than 5% in 3 patients among 6 without esophagitis, but none for acid. Acid HT was less than 5% in 4 patients, 2, 2, and 2 of S-M grade 1, 2, 3, and 4, respectively. Bilirubin HT was less than 5% in 1 patient of S-M grade 2. Bilirubin HT of the patients of S-M grade 3 and 4 (50.9 ± 5.8%) was significantly higher than that of grade 1 and 2 (14.9 ± 2.9%) (p < 0.0001), but not for acid. In 32 patients bilirubin HT exceeded acid HT. Bilirubin HT did not correlate to acid HT in the patients. Conclusion. Reflux of the duodenal contents was found independently and exceeded acid reflux. We found a graded increase in reflux of the duodenal contents across the spectrum of severity of esophagitis.
FP-196 Bronchoscopic Ultrasonography for Staging Supracarinal Esophageal Squamous Cell Carcinoma: Impact on Outcome Harushi Osugi, Masayuki Higashino, Masashi Takemura, Shigeru Lee, Kenichiro Fukuhara, Yushi Fujiwara, Satoshi Nishizawa, Hiroshi Iwasaki Department of Gastroenterological Surgery, Osaka City University, Postgraduate School of Medicine, Japan Purpose. The precise, accurate diagnosis of malignant airway invasion is essential to determine the likelihood of complete resection and survival of patients with invasive carcinoma of the upper esophagus. Usefulness of ultrasonic scanning of the tracheobronchial wall by bronchoscopic ultrasonography (BUS) was studied,
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and results were compared with computed tomography (CT). Patients and Methods. Sixty-six consecutive patients with advanced squamous cell carcinoma of the upper esophagus, treated from 1997 to 2000, were studied. The presence of tracheobronchial invasion was diagnosed by BUS based on an interruption in the most external hyperechoic layer of the tracheobronchus (corresponding to its adventitia). Results. BUS was completed without any complication in all patients. The accuracy of diagnosis was validated intraoperatively and was better for BUS (90%) than CT (52%) (p = 0.0005). Of the 26 patients diagnosed as invasion-free by BUS, only two patients had invasion, in comparison to seven of 22 patients who had invasion after CT suggested they did not. Survival was worse for patients diagnosed as having invasion than not having it based on CT (p = 0.0071), but the difference was more significant with BUS (p < 0.0001). Conclusion. BUS is a safe and reliable staging modality for cancer in the upper esophagus. When surgery is considered, BUS is essential to determine whether a curative resection is possible.
FP-197 Outcome of Surgical Management after Hepatic Arterial Infusion Chemotherapy for Multiple Colorectal Liver Metastases Shigeyasu Ota, Shohachi Suzuki, Takanori Sakaguchi, Masaki Azuma, Osamu Jindo, Keisuke Inaba, Toshio Nakamura, Hiroyuki Konno, Satoshi Nakamura Second Department of Surgery, Hamamatsu University School of Medicine, Japan Background: A high incidence of recurrence in remnant liver and/or extrahepatic sites has become an issue after hepatectomy for patients with multiple colorectal liver metastases. This study was conducted to clarify the significance of hepatic arterial infusion chemotherapy (HAIC) prior to surgery from the viewpoint of appropriate indication for hepatectomy in patients with 4 or more colorectal liver metastases.Methods: Twenty-seven patients with 4 or more colorectal liver metastases underwent HAIC with 5-fluorouracil (FU). After 3-11 months of HAIC, 14 patients were treated with hepatectomy. Surgical outcome in these patients was compared with that in 20 patients subjected to hepatectomy without HAIC. Results: Partial response (PR) was observed in 3 patients, stable disease (SD) in 11, and progressive disease (PD) in 13. Extrahepatic disease occurred in 11 patients with PD. Of 14 patients (3 with PR, 10 with SD, and 1 with PD) undergoing hepatectomy, recurrence was seen in 11 patients. Five of the 8 patients with hepatic recurrence underwent repeat hepatectomy. In contrast, 19 of the 20 patients without HAIC had recurrent disease after hepatectomy. Eight of the 14 patients with hepatic recurrence underwent repeat hepatectomy. The 5-year survival rate after induction of HAIC was 30% in the 27 patients receiving HAIC. The 5-year survival rate after hepatectomy was 64% in the 14 patients with HAIC and 25% in the 20 patients without HAIC (P=0.0408). Conclusions: HAIC is a useful strategy for making better patient selection for hepatectomy in treatment for 4 or more colorectal liver metastases.
FP-198 GIST of the Stomach - Surgical Indication and Procedure Yoshihide Otani1, Toshiharu Furukawa1, Yoshiro Saikawa1, Masashi Yoshida1, Tetsuro Kubota1, Koichiro Kumai2, Yoshinori Sugino3, Makio Mukai4, Masaki Kitajima1 1 Department of Surgery, 2Center for Diagnostic and Therapeutic Endoscopy, 3Department of Diagnostic Radiology, 4Department of Pathology, Keio University School of Medicine, Japan, BACKGROUND: Since 1993, we have treated 122 patients with gastric submucosal tumors in Keio University Hospital. Among them 90 lesions were diagnosed as stromal tumors. Clinicopathological findings of these cases are reviewed. INDICATION AND PROCEDURE: Our indication of laparoscopic wedge resection (LW) for submucosal tumor is; 1) 20 mm < T < 50 mm, 2) rapid increase in size indicating malignant potential, 3) location of the tumor is not on the cardia or pylorus. The cases out of these indications were treated with laparoscopy-assisted surgery (LAS) or open procedure (OP). For the strict preoperative evaluation, not only endoscopy and barium meal but also endoscopic ultrasonography were performed. In LW, entire surgical procedure was performed laparoscopically. When the tumor was located on the lesser or greater curvature, the gastric wall was devascularized and exposed using laparoscopic coagulating shears. Pulling and exposing the tumor toward the abdominal wall, wedge resection of the gastric wall was performed using multifire endoscopic staplers, maintaining a safe margin from the tumor. To avoid the tumor cell dissemination, no-touch technique keeping the capsule of the tumor intact was carefully performed. RESULTS AND DISCUSSION: Ninety stromal tumors were immunohistochemically sub-classified into GIST (60), myogenic tumor (19), neurogenic tumor (11). In these 60 patients with GIST, LW was performed in 35 patients and they started liquid meal on 1 POD and were discharged in 5 to 7 days uneventfully. The mean tumor size was 43 mm. LAS or OP were applied in 25 patients (Proximal gastrectomy 9, Wedge resection 12, distal gastrectomy 2, segmental gastrectomy 1). Fifty-six out of 60 patients (93.3%) survived without recurrence for up to 11 years’ follow-up. No recurrence including port-site recurrence was observed in the 38 patients undergoing laparoscopic surgery or laparoscopy-assisted surgery. CONCLUSION: Laparoscopic surgery for small-size stromal tumors can be regarded as a safe, curative and minimally invasive procedure.
FP-199 Combination Gene Therapy of HGF and Truncated TypeII TGF-β Receptor for Rat Liver Cirrhosis after Partial Hepatectomy Satoru Ozawa, Kazuhisa Uchiyama, Makoto Iwahashi, Mikihito Nakamori, Kentaro Ueda, Hiroki Yamaue Second Department of Surgery, Wakayama Medical University, School of Medicine, Japan Purpose: In a chirrhotic liver, the regenerative ability and specific functions are impaired, with a hepatic resection increasing the possibility of postoperative liver failure. Hepatocyte growth factor (HGF) stimulates liver regeneration, accelerates hepatic function and improves fibrosis. A truncated typeII transforming growth factor-βreceptor (TβTR), which specifically inhibits TGF-βsignaling as a dominant-negative receptor, appears to prevent the progression of liver fibrosis. We demonstrated the therapeutic efficacy of
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adenovirus-mediated HGF and TβTR gene transduction in a partial hepatectomy for liver cirrhosis. Methods: Rats were treated with dimethylnitrosamine (DMN) for 3 weeks. After a partial hepatectomy (10%), we injected AdLacZ (5×108pfu), AdTβTR, AdHGF or AdTβTR+AdHGF (1:1 total 1×109pfu) into the portal vein, followed by an additional 2-week DMN treatment. Results: In a histological examination by Azan-Mallory staining, fibrotic tissue had remarkably decreased in the livers of AdTβ− TR+AdHGF-treated rats, compared to rats treated by AdHGF alone. The liver function, including serum levels of ALT, had significantly improved in AdTβTR+AdHGF-treated rats. The number of PCNA-positive hepatocytes was significantly higher in AdTβTR+AdHGF-treated rats’ livers than in AdLacZ-treated rats. AdTβTR+AdHGF treatment markedly improved the survival rate after a partial hepatectomy. Conclusions: Our results suggest that combining HGF and TβTR gene therapy may widen the practicability of a hepatectomy in a cirrhotic liver, due to improving fibrosis, hepatic function and facilitating hepatocyte regeneration.
FP-200 Intraoperative Gastroscopy for Gastric Surgery Do Joong Park1, Hyuk-Joon Lee1, Hyung Ho Kim2, Hyun Chae Jung3, Kuhn Uk Lee2, Kuk Jin Choe2, Han-Kwang Yang1 1 Department of Surgery and Cancer Research Institute, 2Department of Surgery, 3Department of Internal Medicine, Seoul National University College of Medicine, Korea Purpose: The authors aimed to evaluate the usefulness of intraoperative gastroscopy for gastric surgery. Methods: A total of 38 patients who underwent intraoperative gastroscopy from June 2003 to June 2004 were analyzed. Surgeon decided type of operation and resection margin by combining endoscopic and operative view when gastroscopic view was offered through monitor to endoscopist and surgeon simultaneously. Results: In early gastric cancer, intraoperative gastroscopy was performed in 24 patients (8.3%) out of 288 patients who underwent open surgery during the same period. Preoperative endoscopic clipping is preferentially done. But, when clipping is not done preoperatively or the lesion is ambiguous in spite of clipping, intraoperative gastroscopy was used. Curative partial gastrectomies were possible in 22 patients. In gastric submucosal tumor, intraoperative gastroscopy was used for 7 patients who underwent laparoscopic wedge resection. It was performed to guarantee proper resection margin and to prevent stenosis before resection and to check bleeding, perforation, or stenosis after resection. There was no patient with stenosis after resection. In other disease, intraoperative gastroscopy was used in 2 emergency operations for panperitonitis in which there was no definite perforation site to rule out perforation from peptic ulcer, in 2 duodenal obstructions by a band or a bezoar to confirm the patency of duodenum after operation, and in 1 incidental gastric wall thickness during operation of other organ to identify if there was any lesion in stomach. Conclusions: Intraoperative gastroscopy was useful for operation of early gastric cancer or laparoscopic resection of submucosal tumor.
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FP-201 Evaluation of Primary Duct Closure v/s T-tube Drainage Following Choledochotomy Sanjeev Parshad, Rajendra Kumar Karwasra, Sanjay Marwah, Ishwar Singh Dept of Surgery and Surgical Oncology, PGIMS, Rohtak. Haryana, India Common bile duct (CBD) stone is the commonest cause of obstructive jaundice and cholangitis. T tube drainage of CBD following choledochotomy has been the standard practice. Halstead advocated primary closure of CBD as a safe procedure in 1897 but it is not routinely performed till today. Biliary surgery has evolved in the last decade and today laparoscopic cholecystectomy or minilap cholecystectomy are the standard procedures. Choledhochodotmy is frequently required with these procedures and T-tube drainage is routine practice. A prospective randomized trial was conducted in 40 cases of choledhocholithiasis, comparing the Primary duct closure v/s T- tube drainage following minilap- cholecystectomy. In group A of 20 patients CBD was closed with 4-0 vicryl using continuous interlocking suture where as closure over a T- tube was done in 20 patients of Group B. Patients were assessed for post operative pain, infection, sub-hepatic collection, duration of admission and followed up for one year to see for development of stricture .The results showed that the cases undergoing primary duct closure had significantly less morbidity and short hospital stay. There was no significant sub-hepatic collection and none developed stricture. We conclude that primary closure of CBD is safe, physiological and procedure of choice following routine choledochotomy. Since endoscopic procedures for CBD clearence are now widely available, retained calculi can also be managed easily. Primary duct closure can also be practiced during laparoscopic surgery and cumbersome procedure of introduction of T-tube through laparoscope can be avoided.
FP-202 Combination of Gemcitabine and Cisplatin (GC) is Superior to Gemcitabine, Leucovorin and Fluorouracil (GLF) in Chemotherapy of Unresectable Pancreatic Cancer Tadeusz Popiela, Jan Kulig, Marek Sierzega, Janusz Legutko, Anna Gurda 1st Department of Surgery, Jagiellonian University, Poland Introduction: The study evaluates effectiveness of two gemcitabine-based chemotherapy regimens for unresectable pancreatic cancer. Methods: Between Jan 2001 and Dec 2002, 64 patients with intraoperatively verified unresectable pancreatic ductal carcinoma were randomly allocated in two groups receiving gemcitabine (1000 mg/m2)and cisplatin (25 mg/m2) (GC Group) or gemcitabine (1000 mg/m2) leucovorin (200 mg/m2) and fluorouracil (1000 mg/m2) (GLF Group), once a week for 12 weeks. Chemotherapy started on the postoperative day 10-14. Effectiveness of chemotherapy was evaluated after 12-week treatment. Results: Study group consisted of 64 patients (35 males and 29 females, median age 59 years) allocated into GC (30 patients) and GLF groups (34 patients). The groups were comparable regarding gender, age, tumor advancement and type of surgery. No complete tumor response was observed. No differences were found between study groups regarding the percentage of partial tumor regression,
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stable and progressing disease. After 12-week treatment, proportion of patients with Karnofsky performance status of 80 points or higher was comparable in both groups. Similarly, no differences were observed for weight loss and consumption of analgesics. The median survival in the GC group of 222 days was significantly longer compared to GLF group of 125 days, p<0.05. There were more adverse effects in GC groupthan in GLF group (45% vs. 39%) but difference was statistically insignificant. Conclusion: GC regimen is recommended as therapy of choice in the treatmentof unresectable exocrine pancreatic cancer.
FP-203 The Role of Postoperative Adjuvant Chemotherapy in Colorectal Cancer Tadeusz Popiela, Jan Kulig, Piotr Richter, Janusz Legutko 1st Department of Surgery, Jagiellonian University, Poland The aim of this study was to assess the results of combined surgical treatment of colon cancer adjuvant chemotherapy. During 19 years prospective clinical trials were conducted and different chemotherapy schemes were analyzed - including 5-fluorouracil with immunomodulation (BCG, leucovorin or levamisole) and irinotecan (CPT11). Chemotherapy results were compared with treatment results in patients who underwent only surgical procedures. Between 1984 and 2002 surgical operations were performed in 1671 patients with colon or rectal cancer. Adjuvant chemotherapy was introduced in patients with stage II, III and IV (according to UICC/AJCC classification) who were postoperatively randomized to one of the assessed treatment schemes. The improvement of treatment results after systemic chemotherapy was obtained in stage II and III of colon cancer (p<0,04) and in stage III (p<0,05) in rectal cancer. In other stages improvement of long-term results was not statistically significant. Satisfactory results were achieved in the following treatment schemes: 5-fluorouracil/Leucovorine, 5-fluorouracil/ Levamisole and 5- fluorouracil/ irinotecan /Leucovorine. Conclusions Systemic chemotherapy improved the long-term results of surgical treatment in patients with colon and rectal cancer.
FP-204 Results of Thermoresection, the New Hepatic Resection Technique Przemyslaw Pyda, Michal Drews, Tomasz Banasiewicz, Honorata Stadnik General and Gastroenterological Surgery Department, Poznan, University of Medical Sciences, Poland The conception of this procedure is based on a short exposure of the planned incision site of liver parenchyma to a cooled-tip needle electrode, the same as the one used in thermoablations. By analogy, we suggest to name this method - thermoresection. Using this method, between August 2003 and May 2004 we resected hepatic lesions in 48 patients. In 37 cases the lesions were hepatic metastases, including 25 multiple metastases. On an average one patient had 5 metastases (of diameters ranging between 0.5 cm to 13 cm) restected. Up to 10 lesions per patient were resected during one procedure. The resection types performed included 29 local nonanatomical excisions, 11 segmentectomies and bisegmentectomies
and 8 right and left hepatectomies. No intraoperative complications followed. The average blood loss was below 170 ml and 90% of the patients did not require any transfusion. Operations usually lasted 2.5 hours (including single and multi-site resections) and hospitalization about 7 days. During the postoperative period two serious complications occurred. The first one was a hepatic abscess in a site of a resected metastasis treated with percutaneous drainage. The other was a fatal hepatic insufficiency four weeks after surgery. Provided that the results are confirmed on larger groups of patients, this new method will change our views on the treatment of hepatic lesions. Thermoresection enables simultaneous, non-anatomical resections of numerous lesions without a significant increase of the risk. Thermoresection procedures proved to be simpler and safe for patients compared to traditional methods of hepatic resection.
FP-205 The Prognostic Significance of Preoperative Plasma Level of Osteopontin for Patients with Hepatocellular Carcinoma Lun-Xiu Qin, Hui Zhang, Qing-Hai Ye, Lei Zhao, Ning Ren, HuiChuan Sun, Lu Wang, Yin-Kun Liu, Zhao-You Tang Liver Surgery, Liver Cancer Institute, China Purpose: In our previous cDNA array study, osteopontin (OPN) was found to be one of the leading differently expressed genes between hepatocellular carcinoma (HCC) with and without intrahepatic metastasis, and was confirmed to be associated with HCC metastasis with both in vitro and in vivo studies. The aim of this study was to evaluate the prognostic value of plasma OPN level for HCC patients. Experimental Design: A total of 101 patients received liver resection for HCC were enrolled. The preoperative plasma OPN levels were detected by ELISA, and their association with the clinicopathological characteristics, tumor recurrence, and patients’ survival was analyzed. Results: The median plasma OPN levels were significant different between the patients with different numbers of tumors (168.18, and 217.11 ng/ml for single and multiple, respectively, P=0.002), different Edmondson’s grades (201.24, 168.36 and 503.58 ng/ml for grade I, II, and III/IV, respectively, P=0.015), and different TNM stages (168.16, 167.54, and 216.18 ng/ml for stage I, II, and III/IV, respectively, P=0.016). A significantly higher plasma OPN level was found in patients with HCC recurrence during the follow-up time compared with those without recurrence (213.55 vs. 153.70 ng/ml; P=0.0013). A higher plasma OPN level was one leading independent prognostic factor for both OS and DFS of HCC patients. Conclusions: The plasma OPN level could be one predictive marker for the HCC recurrence after operation, and may be helpful to assess the prognosis of HCC patients before operation.
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FP-206 Gastrointestinal Stromal Tumors: Presentation, Behavior and Treatment Approaches Igor Rabin 1 , Judith Sandbank 2 , Bar Chikman 3 , Marina Maklakovsky2, Ron Lavy3, Ruth Gold-Deutch3, Zvi Halpern3, Ilan Wassermann3, Ariel Halevy3 1 Division of Surgery, Assaf Harofeh Medical Center, 2Assaf Harofeh Medical Center Institute of Pathology, 3Assaf Harofeh Medical Center Division of Surgery, Israel Purpose: To review our accumulated 15-years experience in the treatment of patients with Gastrointestinal Stromal Tumors (GISTs). Methods: Combined retrospective (1988-2000) and prospective (since 2001) study. Tumors were defined as GISTs only when displaying c-kit (CD-117) immunopositivity. Results: 73 patients entered the study, 39 males and 34 females. Age range 27 - 88 years, mean - 62.7 years. 63% of GISTs were located in the stomach, 31.5% - in the small bowel, 4.1% - in the duodenum and in one patient in the colon. 46.6% of GISTs were classified as malignant, 23.3% - as of uncertain malignancy and 30.1% - as benign tumors. 45.2% of the patients presented with a history of GI bleeding, 30.1% - with abdominal pain and 24.7% were diagnosed incidentally. 71.4% of patients under age 50 years had malignant GISTs as compared to 40.7% in patients 50 years of age and over (p = .038). 72 / 73 patients underwent variety surgical procedures. The follow up period ranged between 2 -123 months. Mean overall survival time for malignant gastric and small bowel GISTs was 111 and 51.5 months respectively (p = .0159). The mean disease-free survival period for malignant gastric and small bowel GISTs was 98.4 and 47.4 months respectively (p = .1087). Conclusions: 1. High incidence of incidental GISTs. 2. Strong correlation between age and malignancy of GISTs. 3. Small bowel GISTs have a more aggressive behavior and worse prognosis. 4. Radical surgery offers the best results.
FP-207 Surgical Treatment of Excesive Duodeno-Gastro-Esophageal Reflux (DGER) Tomislav Dusko Randjelovic, Srdjan Dikic, Nikola Milinic, Dragoljub Bilanovic, Zarko Tomislav Vuckovic, Bogdan Crnokrak Surgery, Bezanijska kosa Medical Center, Serbia and Montenegro Introduction: Latest investigations (esophageal electric impedance tests) are showing that duodenal content has the crucial role in genesis of atypical GERD manifestations and morphological changes on Barret’s epithelium (BE). Goal: Evaluation of surgical procedures in controling excesive biliary reflux. Methods: From 06/99 to 05/04, 18 female and 11 male patients, average age of 47.2 years (19-58), with atypical DGER manifestations and BE, have been surgicaly treated: group I - isoperistaltic jejunal interposition (IJI, n = 12), group II -suprapapillary duodenal switch (SDS + Toupet, n=4), and group III - ARP-Nissen (n=13). Results: Immediate 2 year follow-up: group I prompt symptom reduction and regresion in changes on esophageal mucosa; group II slower discharge, fullnes after meals and early sitaety, which in 2 patients (50%) caused surgical conversion to IJI with segment lenght of 8 cm, without mortality and with excellent results; group III residual symptoms, and in 25% there are no regresion in
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changes on esophageal mucosa, morbidity 2.8%, no mortality. Discussion: ARS is highly efficient in acid reflux control. In approximately 40% the refluxat is duodenal content, which causes severe atypical manifestations. Modern PPI therapy in this group has minor efficiency. The best results have been acheived with proximal IJI, or distal combined with ARP. SDS alone is not efficient. Conclusion: For the chosen group of patients IJI provides best long-term functional results.
FP-208 Laparoscopic Repair of Paraesophageal Hernia without Fundoplication Munir Rathore1, Arthur Mc Murray2 1 Department of Surgery, Altnagelvin Area Hospital, Londonderry, 2 Antrim Area Hospital, Antrim, NI, UK Introduction: Very few reports are available for laparoscopic paraesophageal hernia repair without fundoplication. This study was performed to compare the results of the operation with the literature. Patients & Methods: This retrospective five-year case series involved 24 patients. M:F ratio was 1:2.4 and mean age 66.4y. Mean symptom-operation interval was 62 months. 96% had comorbid factors. Mean ASA was II. Symptoms included chest pain (58%), epigastric pain (46%), heartburn (46%), dysphagia (46%), dyspnoea (46%), early satiety (42%), gastric volvulus (42%) and upper GI bleed (37%). The repair included reduction, sac excision, esophageal mobilization and cruroplasty. Of the 20 (83%) patients followed up (mean 22 months), 12 (60%) patients had follow-up Ba esophagograms. Results: Complications included esophageal perforation in one (4%), gas-forming mediastinal abscess (4%), small bowel obstruction (4%) and bilateral basal atelactasis (4%). One patient (4%) died due to duodenal perforation and myocardial infarction. The mean follow-up, for 20 patients (83%), was 22 months. Two patients (10%) had persistent post-operative dysphagia. Two (10%) had persistent postoperative reflux requiring medication. Four (16%) had recurrence, all within the first year. Mean hospital stay was 5.8 days. Symptom outcome was Visick I/II (60%), III (25%) and IV (15%). Diagnostic endoscopy (performed in 58%) had sensitivity of 14%. Conclusion: Results were consistent with laparoscopic with-fundoplication literature. Recurrence tends to take place in the first year. The literature recommends adjunct fundoplication. Mandatory follow-up esophagograms should be performed on all patients. Key steps of the operation are complete sac excision, esophageal mobilization and tension-free cruroplasty.
FP-209 The Rationale for Surgery for Morbid Obesity Munir Rathore Surgery, Altnagelvin Area Hospital, Londonderry, NI, UK Morbid obesity is a disease rather than just a clinical state and whose importance is recognised in the USA more than anywhere else. Obesity (including morbid obesity) is on the increase in wellfed nations and this trend shall continue in the next generation. The reliance on conventional weight reducing measures has shown limited success with low compliance and high rates of weight
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regain. Bariatric surgery is on record in sporadic form since 1954. The operations have evolved through jejuno-colonic bypass, jejuno-ileal bypass, bilio-pancreatic diversion, bilio-pancreatic diversion with duodenal switch, gastric restrictive procedures and resection-bypass procedures. The open surgery has now been complimented by laparoscopic surgery. Different types of operations have major and minor complications secondary to the magnitude, intestinal short-circuit, de-functioned loop, diarrhoea, dumping, electrolyte abnormalities, demineralising bone disease, hepatic cirrhosis, delayed weight regain and protein energy malnutrition, to mention a few!However level II evidence has emerged from the USA regarding the benefits of surgery for morbid obesity (bariatric surgery). These include 50-70% persistent loss of excess body weight over 7-8y, reduction of morbid obesity-related CVS, respiratory & metabolic complications, reported cure of a number of cases with NIDDM, improvement in self-esteem, psychiatric illness, work place cohesion and improvement of marital & sexual relationship as well as improvement in fertility.In this review article the role of surgery for morbid obesity has been assessed, as the well-fed world is likely to encounter the same extent of obesityrelated morbidity & mortality were the issue left to its own fate.
FP-210 Early Organ Failure and Extent of Necrosis are Determinants of Secondary Pancreatic Infections after Surgical Treatment of Sterile Necrosis B. Rau1, Hans G. Beger2 1 Department of General, Visceral, and Vascular Surgery, University of the Saarland, Germany, 2Department of General Surgery, University of Ulm, Germany The appropriate treatment of sterile necrosis (SN) in acute pancreatitis is still a matter of controversies. In this respect surgical treatment has been claimed to carry the risk of secondary pancreatic infections. However, no study has ever addressed this issue in a larger series of patients subjected to surgery for SN. Materials and Methods: Between 05/82 and 05/01 285 patients with necrotizing pancreatitis underwent surgical treatment at the Department of General Surgery, University of Ulm. Primary infected necrosis developed in 140 (49%) patients, in 145 (51%) patients necrosis was sterile. In the latter group 135 patients were further stratified into: I. Secondary pancreatic infections (sPIN) with sepsis, II. Pancreatic contaminations (CON) without sepsis, and III. Sterile courses (STER). Results: In 135 patients with sterile necrosis sPIN developed in 63 (47%) and CON in 42 (31%) patients, whereas 30 patients (22%) remained STER. The disease severity in terms of Ranson- and Apache II-scores at admission (p<0.002), the preoperative incidence of remote organ failure (p<0.008), and the extent of necrosis (p<0.009) was higher in patients with sPIN compared to the CON and STER groups. Comparing patients with sPIN and CON no difference was found with respect to time interval between onset of symptoms and the diagnosis of infection/contamination and the bacteriological spectrum isolated. Mortality rates were 38% in the sPIN, 2% in the CON, and 23% in the STER group. Conclusion: The early presence of high clinical and morphological severity is closely associated with the development of sPIN after surgery for SN. Our results strongly suggest that initial pathophysiologic events and not the surgical procedure itself is the major determinant of sPIN.
FP-211 Quantification and Allelic Imbalance Analysis of Circulating DNA in Plasma of Patients with Hepatocellular Carcinoma Ning Ren1, Lunxiu Qin1, Hong Tu2, Boheng Zhang3, Yingkun Liu3, Zhaoyou Tang3 1 Liver Cancer Institute, Zhong Shan Hospital, Fudan University, 2 Shanghai Cancer Institute, 3Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, China Purpose: To study the values of circulating plasma DNA concentration and its allelic imbalance (AI) in the diagnosis and prognostic prediction of hepatocellular carcinoma (HCC). Materials and Methods: The peripheral blood samples were collected from 79 HCC patients, 20 patients with compensated liver cirrhosis and 20 healthy volunteers. Plasma DNA was extracted and two polymorphic microsatellite markers, D8S258 and D8S264, were selected to analyze the AI of circulating DNA. Results: Compared with the healthy volunteers (mean 17.6±9.5 ng/ml), the patients with HCC and liver cirrhosis have significant higher of mean circulating plasma DNA levels (mean 47.1±43.7 ng/ml, p=0.000; 30.0±13.3 ng/ml, p=0.002, respectively). However, no significant difference was found between patients with HCC and liver cirrhosis (p=0.191). The circulating plasma DNA level was significantly higher in patients with intrahepatic spreading or vascular invasion (mean 54.3±41.6 ng/ml vs. 39.3±45.0 ng/ml, p=0.002, respectively). AI at D8S258 in plasma DNA was significantly correlated with Edmondson grade (p=0.050), TNM stage (p=0.010), 2-year DFS (p=0.044) and 2-year OS (p=0.016). However, AI at D8S264 was only associated with 1-year and 2-year DFS (p=0.027; p=0.042). Combine detecting AI at D8S258 with circulating plasma DNA concentration was independently associated with decreased DFS and OS of patients with HCC (p=0.023, p=0.001). Conclusion: Circulating plasma DNA level is not a good diagnostic marker for HCC. Combine detection of AI at D8S258 in circulating DNA with plasma DNA quantification was independently predicting marker for poor prognosis of HCC patients.
FP-212 Preliminary Report of the Effect of Neoadjuvant Radiotherapy (5 X 5 Gy) Randomized to 1 vs. 4-5 Weeks Interval on Rectal Cancer Surgery Piotr Richter1, Tadeusz Popiela1, Teresa Kowalska2, Jan Kulig1, Radoslaw Pach1 1 I Department of Surgery, Jagiellonian University, Poland, 2Institut of Oncology, Cracow, Poland Contemporary approach to treatment of locally advanced rectal cancer consists of neoadiuvant radiotherapy and radical tumor resection. Between 1999 and 2003 year 368 patients with rectal cancer underwent surgical treatment including group of 147 neoadjuvant radiotherapy. Since 2000 a model of radiotherapy dose 25 Gy applied during 5 days and time interval to operation 57 days vs. 4 to 5 weeks was randomized. From 2000 to 2003 a group (A) of 71 patients was treated according to the new radiotherapy scheme. In the group A (interval to surgery 4 to 5 weeks) downstaging was observed in 33 (46.5 %) and downsizing in 16 (22.5%) patients. In this group sphincter preserving operations were performed in 48 (67.7%) patients (anterior resection in 26 pts, anterior inferior resection in 11 pts and local resection in 2 pts). In Group B (inter-
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val to surgery 5 to 7 days ) the results were 9 (18.7%) and 4 (8.3%) respectively. In patients who underwent neoadjuvant radiotherapy (any type) lower recurrence rate was observed as in comparison with patients treated only with surgery (6.7% distant metastasis, 1.7% local relaps, 0.8% systemic and local recurrence). The long term results will be assessed after finishing the study. Conclusions Neoadjuvant radiotherapy dose 5 x 5 (25 Gy) and interval 4 to 5 weeks improves the treatment results in patients with locally advanced rectal cancer.
FP-213 Laser Lithotripsy for Residual Calculi of the Hepato-Biliary Tree Maita Teresa Pascua Rigor1, Vitus S. Hobayan2, Alex A. Erasmo3 1 Section of HBP & Upper GI Surgery, Department of Surgery, Jose R. Reyes Memorial Medical Center-Department of Health, 2 Department of Surgery, Cardinal Santos Medical Center, 3 Department of Surgery, University of Santo Tomas & Jose R. Reyes Memorial Medical Center, Philippines Objective: The study intended to evaluate the indications and procedure-associated outcome of laser lithotripsy performed among post-operative patients with residual duct calculi. Method: Design: prospective, analytic cohort study within a 9month period. Thirty consecutive patients with prior biliary exploration availed of initial T-tube tract cholangioscopy; 25 (83%) received Holmium laser. Early Outcomes: stone fragmentation, duct clearance, and procedure-related complication rates. Results: The M:F ratio was 1:2 with a mean age of 41 years. Intrahepatic calculi comprised 20 out of 30 whereas impacted stones accounted for 13 out of 30. Strictures were seen in 7 out of 30. Laser Group. The indications for lithotripsy were >/= 1.5 cm stone, impacted stone, and presence of multiple stones in: (a) a single strictured sectoral duct, (b) in both the common hepatic (mild stricture) and right main ducts, (c) in both the right sectoral ducts with main duct stricture, and (d) > 1 stricture site (posterior duct, left main duct). For difficult extractions, the averages of sessions follow: abnormal ducts- 4.5, acute-angled ducts- 3.5, impaction2.0, and >/= 1.5 cm stone- 1.5. The 6 complex features were: Stone- impaction, >/= 1.5 cm, multiple, and intrahepatic, and Duct- angulation and deformity. Laser enabled 100% success rate in fragmentation and facilitated complete clearance. Transient low-grade fever in 7 patients (28%) was the only complication noted. Conclusion: Projected in this interim study as a low-morbidity and a high-clearance therapeutic option, laser is indicated in postoperative patients with retained calculi identified to have complex features on cholangioscopy.
FP-214 Detection of CEA mRNA Expressing Cells in Peripheral Blood 7 Days after Surgery does not Influence Relapse in Colorectal Cancer(CRC) Sotaro Sadahiro, Toshiyuki Suzuki, Kenji Ishikawa, Hiroyasu Makuuchi Gastrointestinal Surgery, Tokai University, Japan Background No consensus has been reached on whether cancer
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cells detected in blood during surgery in patients (pts) with CRC may correlate with prognosis. Cancer cells could not be detected when blood was taken 7days after intravenous injection in experiment (Fidler). The aim of this study was to examine the detection of cancer cells in blood more than 7 days after curative resection may serve as a prognostic indicator. Methods Two hundred and one pts with CRC who underwent curative surgery were the subjects. Peripheral blood was collected between 7 and 10 days after resection. Cancer cells were detected using RT-PCT targeting CEAmRNA. The median follow-up period was 31 months (range 12-47 months). Results Recurrence has been confirmed in 44 pts (22%). Recurrence was noted in liver in 14 pts, locoregional in 11 pts, lung in 7 pts, peritoneum in 6 pts, lymph node in 3 pts. Cancer cells were detected in blood in 45 pts (22%). Recurrence was noted in 15 out of 45 pts positive for CEAmRNA (33%), and in 29 out of 156 pts negative for CEAmRNA (19%) (p = 0.06). There was neither statistical difference in overall survival nor disease-free survival between pts with positive CEAmRNA and pts with negative CEAmRNA, respectively (p=0.14, P=0.18). There was no correlation between recurrence site and positivity of CEAmRNA. There was significant correlation between pathological stage and overall survival or disease-free survival. Conclusion Detection of cancer cells in blood taken 7days after curative resection in patients with CRC was not associated with prognosis.
FP-215 Preoperative Chemoradiotherapy for Adenocarcinoma in the Lower Third of the Rectum—Comparison of Three Treatment Regimens Sotaro Sadahiro 1, Toshiyuki Suzuki 1, Kenji Ishikawa 1, Hiroyasu Makuuchi1, Chieko Murayama2 1 Gastrointestinal Surgery, 2Radiology, Tokai University, Japan, Preoperative radiotherapy (RT) and chemoradiotherapy (CRT) against rectal cancer decrease local recurrence and increase sphincter preserving surgery (SPS). We have performed combined preoperative RT (20Gy) and intraoperative RT (15Gy) for locally advanced rectal cancer and reported the combined therapy significantly reduced the local recurrence into 2% and improved survival. In the present study, we compared the treatment effects achieved by three kinds of preoperative treatment regimens. Methods The subjects were patients (pts) with cT3/T4 adenocarcinoma in the lower rectum. Between 1991 and 1998, 43 pts were treated with RT only (RT group). Between 1999 and 2001, 18 pts were treated with RT+oral UFT at 400 mg/m2/d (CRT-1 group). Since 2002, 18 pts were treated with RT+oral UFT+CPT-11 civ at 40 mg/m2/wk (CRT-2 group). Surgery was performed 2 weeks after completion of irradiation. Results There were no significant differences in pts’ characteristics among the groups. Percent of tumor shrinkage was 23±12 in the RT, 34±12 in the CRT-1 and 39±11 in the CRT-2, with significant difference. SPS was possible in 16% in the RT, 50% in the CRT-1 and 89% in the CRT-2, and the difference was significant. Histologic effect was positive in 5% in the RT, 22% in the CRT-1 and 28% in the CRT-2, with no significant difference. Grade 3/4 toxicity was observed only in the CRT-2. Three cases experienced hemotoxicity (17%), one diarrhea (6%). Conclusion Preoperative CRT reduces the tumor size by 30% or more, and increases SPS markedly. However, the optimal
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chemotherapy regimen employed in combination with RT requires further investigation.
FP-216 Treatment of Liver Metastasis (LM) of Colorectal Cancer (CRC). A Comparision between Natural History; Regional Chemotherapy and Surgery of the LM Farouk Safi1, Hans Guenther Beger2, Frank Branicki1, Fawaz Torab1 1 Surgery, United Arab Emirates University; Faculty of Medicine & Health Sciences, UAE, 2Uni. Clinic Ulm, Germany 294 Patients (Pts) with isolated LM of CRC were evaluated retrospectively. Pts have been treated in one institution; University clinic of Ulm; Germany. The primary CRC has been resected curatively in all pts (R0 Resections). Pts were divided in three groups. Group I included 104 pts in whom the LM were note treated either with systemic nor regional nor surgical therapy. Group II included 114 pts in whom Infusaid pumps were implanted. Regional chemotherapy of the LM has been done via FUDR in a dosage of 0.2 mg/kg/day for 14 days alternatively with saline and heparin. In group III there were 76 pts in whom the LM was resected curatively. The postoperative 30 days mortality rate were in group II 0% and III 2/76 (2.6%). Results: The three groups were compared regarding the survival rates after the diagnosis of the LM. ————————————Survival ———————————— Group n Median 1 year 2 year 3year I 104 11.7 months 49% 17% 5% II 114 21 months 82% 36% 13% III 76 38 months 93% 75% 53% Conclusion: In pts with isolated LM of CRC carcinoma the regional chemotherapy may increase the survival rate of those pts with non resectable LM within the first three years. 28% of group III pts survive 5 and 10 Years after surgery. Surgery in resectable LM is of course superior to chemotherapy and is now the only way to cure pts with LM of CRC.
FP-217 The Clinical Efficacy and Toxicity of Chemoradiation with S1/CDDP Pre-Operatively Performed against Highly Advanced Gastric Cancer Yoshiro Saikawa, Tetsuro Kubota, Tsuyoshi Kiyota, Rieko Nakamura, Tetsuya Nakamura, Yukako Akatsu, Tsunehiro Takahashi, Masashi Yoshida, Yoshihide Otani, Koichiro Kumai, Masaki Kitajima Department of Surgery, Keio University, Japan We are to clarify beneficial effect of pre-operative radiation with S-1/cisplatin (CDDP) in highly advanced gastric cancer, evaluating histological response, toxicity and patients’ quality of life (QOL). We demonstrate 8 patients with highly advanced gastric cancer (clinical Stage IV), treated with preoperative radiation (40Gy) with S-1/low-dose CDDP in a pilot study. And we report the result of clinical phase I study to determine recommended dose of CDDP in the chemoradiation. The pilot study showed high response rate of 62.5% (5/8 cases) including 5 PRs, 2 NCs, and 1 PD, and 6 out of 8 patients underwent surgery, without any surgical complication. Two patients had a histologically complete response (Grade 3 effect) and 3 patients had a partial response (Grade 2 effect), suggesting that a high histological response (5/6 cases; 83.3%) is
expected by the chemoradiation. All cases showed grade 2-4 bone marrow suppression toxicity and/or grade 0-2 gastrointestinal toxicity, while 5 out of 8 patients (62.5%) showed improvement in appetite loss at the end of the therapy, indicating that the patients’ quality of life (QOL) was improved. On the other hand, recommended dose of CDDP was determined as 6mg/m2/day in the intermittent administration (5 days for CDDP with 2 days interval, for 3weeks) through the phase I. Simultaneously, we will refer to the efficacy and toxicity in the phase I. The chemoradiation may be a powerful regimen for obtaining histological response with tolerable toxicity and improved QOL in highly advanced gastric cancer patients.
FP-218 Peritoneo-venous Shunting for the Treatment of Refractory Ascites Yumiko Sakamoto, Kazunori Furuta, Hiroki Hoshino, Masamichi Katori, Ken Simada, Tsuyoshi Takahashi, Koshi Sato, Muneki Yoshida, Masahiko Watanabe Surgery, Kitasato Umiversity,School of Medicine, Japan Peritoneovenous (PV) shunting has been known as a treatment of choice for refractory ascites. However, it is, at times, difficult to decide the timing for instituting PV shunt. We herein present our experience in P-V shunting applied to a series of patients with intractable ascites. Seven patients with refractory ascites were instituted with a PV shunt system (Denver or Le Veen) during the past 10 years. Underlying diseases of these patients included; 4 liver cirrhosis with hepatocellular carcinoma, 1 pancreatic cancer with peritoneal dissemination, 1 primary biliary cirrhosis, and 1 non-chylous ascites following pancreaticoduodenectomy (chronic pancreatitis and inanition). Some patient had been suffering a respiratory distress and/or systemic hemodynamic instability. The effectiveness of PV shunting was evaluated on the shunt patency, the patients and outcome, and so on. Following the institution of PV shunt, the body weight and abdominal girth were decreased significantly, and the shunt tube remained patent during hospitalization in all patients. Four of 7 patients were discharged from the hospital, whereas the remaining 3 patients died in 7 days after shunt operation. Among the 4 surviving patients, 1 patient experienced an episode of DIC. The shunt tube installed in these 4 patients remained patent for 2, 2, 8, and 41 months, respectively. PV shunting can be an excellent therapeutic modality for some selected patients with intractable ascites.
FP-219 Pulmonary Thromboembolism in Japanese Surgical Patients Masato Sakon1, Masataka Ikeda2, Morito Monden2 1 Surgery, Nishinomiya Munincipal Central Hospital, 2Dept of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Japan The true incidence of pulmonary thromboembolism (PE) after general surgery in Japan is unknown. The reported incidence of symptomatic (clinical) PE after general surgery in the recent Japanese literature (1985-2004.4) was reviewed, using search terms “surgery” and “pulmonary embolism” or “thromboembolism” as key words. The overall incidence of symptomatic (clinical) PE in general
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surgery was 0.29% (139/47,601). Fatal PE was reported in 0.08% (33/41,228) of all collected cases, and occurred overall in 31% (33/105) of patients with PE. In cancer surgery, the incidence of clinical PE (1.53%, 57/3,724) was considerably high, about 6 times higher than that (0.20%, 4/2,014) in non-cancer surgery. It ranged from 0.48% for colon cancer to 3.85% in operations for pancreatic neoplasm, corresponding to either a moderate or high level of risk as defined by 6th ACCP consensus recommendations. Since the incidence of PE in cancer surgery is defined as the highest level of risk in 6th ACCP consensus recommendations, the risk of Japanese surgical population may be one or two levels lower than that of western surgical population. Based on these findings, Japanese prophylaxis guidelines were adjusted one rank lower than the 6th ACCP guideline. In conclusion, the incidence of PE in Japanese surgical patients is not low as previously thought. Perioperative prophylaxis against venous thromboembolism appears essential particularly in cancer surgery, although their benefits should be further confirmed by prospective clinical investigation.
FP-220 Hepatic Resection Based on Hemodynamics of Hepatocellular Carcinoma Masato Sakon1, Hiroaki Nagano2, Syoji Nakamori2, Keizo Dono2, Shigeru Maruhashi2, Atsushi Miyamoto2, Koji Umeshita2, Morito Monden2 1 Surgery, Nishinomiya Munincipal Central Hospital, 2Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Japan The extent of hepatectomy for hepatocellular carcinoma (HCC) is still controversial. Some groups recommend extended hepatectomy while others advocate limited resection based on survival rate or disease free survival rate. Since these outcomes are markedly affected by multiple factors including muticentric carcinogenesis (MC) or underlying chronic liver disease, the scientific identification of surgical margin in HCC has not been established. We identified the tumor blood drainage area, the high-risk area of intrahepatic micrometastases (IM) by abdominal helical computed tomographic scan under hepatic arteriography and excised as surgical margin. Blood drainage area of tumor differed individually, but could be classified into marginal type (drainage into the peritumorous area), portal vein type (drainage into the portal branches) and hypovascular type. HCCs of marginal type or hypovascular type were excised mostly by nonanatomic, limited resection while those of portal vein type were excised by anatomically systematic hepatectomy. Multiple recurrent nodules were frequently found inside the drainage area and main tumors were moderate or poorly differentiated HCC, consistent with IM. Solitary recurrent nodules were mostly outside the drainage area and contained well-differentiated HCC, suggesting MC. In spite of these hepatic resections, intrahepatic recurrences were commonly found in bilateral or contralateral lobes and divided into 2 groups with a few and multiple (8 or more) recurrent nodules. CONCLUSIONS: Surgical margin varied individually according to tumor hemodynamics. Since the regional spread of IM is controlled by this procedure, tumor recurrences may result not only from MC but also from IM via systemic circulation.
Journal of Gastrointestinal Surgery
FP-221 Estimation of the Portal and Sinusoidal Pressure Changes Induced by Hepatectomy - Numerical Simulation of the Hepatic Circulation Kenji Sakurai, Seiji Ohigashi, Gen Shimada, Shintarou Sakurai, Takeki Nishio Surgery, St. Luke’s International Hospital, Japan Purpose: Assessment of the hemodynamic alternation induced by hepatectomy is mandatory during and postoperative period. The remnant hepatic function of patients or donors should be well maintained regardless of the resection purpose. The aim of this study is to estimate the pressure changes in the hepatic arterial, portal venous and hepatic venous compartments, which are considered to effect ultimately on the sinusoidal pressure and hepatic function. Methods: The hepatic circulation was modeled using an electrical analogue and the blood flows and pressures of the portal vein, hepatic artery, sinusoid and the hepatic vein were simulated at the various extensiveness of hepatic resection. Results: Both portal and sinusoidal pressures rose together as the resection rate increased and showed marked increase over 80 percent hepatic tissue mass reduction. The total hepatic blood flow also decreased drastically beyond 75% resection. Conclusions: In any type of hepatectomy, all of the hepatic vascular beds definitely decrease in size depending on the hepatic tissue masses resected. With assumption that adequate hepatic function is not expected when the sinusoidal pressure stays over 35mmHg, such a resection is unfeasible. Excessive rise of the sinusoidal pressure over this critical point should be avoided with congestion of the splanchnic area. This simulation model also helps assess the hepatic hemodynamics in specific conditions, such as the arterialization of the portal vein.
FP-222 Significance of Resecting the Head of the Pancreas for the Treatment of Gallbladder Cancer from the Perspective of Surgical Results and Mode of Lymph Node Metastasis Ryoko Sasaki 1, Hidenori Itabashi 1, Tomohiro Fujita 1, Yuichiro Takeda1, Koichi Hoshikawa1, Masahiro Takahashi1, Osamu Funato1, Hiroyuki Nitta1, Yasunori Yaegashi1, Senji Kanno2, Kazuyoshi Saito1 1 First Department of Surgery, Iwate Medical University, 2Iwate Prefectural Ofunato Hospital, Japan The significance of resecting the head of the pancreas was clinicopathologically investigated predominantly by examining the mode of lymph node metastasis in patients with gallbladder cancer. Of 65 patients who underwent resection of gallbladder cancer, 27 patients (41.5%) displayed lymph node metastasis. The breakdown of lymph node metastases was as follows: 12b (pericholedochal lymph node; 23.6%), 16 (paraaortic lymph node; 23.1%), 13 (posterior pancreatoduodenal lymph node; 18.2%), 8 (lymph node around the common hepatic artery; 13.3%), 12c (cystic lymph node; 12.7%), 12p (periportal lymph node; 7.3%) and 6 (inflapyloric lymph node; 6.3%). The 5-year survival rates according to the nodal stages were 76.2% in pN0, 30.0% in pN2, and 0% in pM1 (lymph), respectively. There was a significant difference among them (p< 0.0001). Of 49 patients with advanced gallbladder cancer, 14 patients survived more than five years after surgery. Five of six long term survivors with lymph node metastasis underwent S4aS5 resection combined with PPPD (PD). Of the 54 patients who underwent curative resection, 13 patients experienced
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recurrence: in the liver in six patients, peritoneum in four patients, lymph nodes in four patients, bone in two patients, lung in one patient and local in one patient (including duplicate cases). Extensive resection including resection of the head of the pancreas was effective in patients with up to pN2 lymph node metastasis as long as cancer could be completely removed.
FP-223 Regulatory CD4+CD25+ T Cells in Peripheral Blood and Tumors from Patients with Gastric Carcinoma, a Preliminary Study Yan-Shen Shan, Chia-Jui Yen, Chao-Jung Tsao, Pin-Wen Lin Department of Surgery, National Cheng Kung University Hospital, Taiwan Purpose: To compare lymphocyte subsets present in tumors and peripheral mononuclear cells (PBMCs) from gastric carcinoma and normal health donor. Materials and Methods: Peripheral blood, tumor and normal tissue were collected from patients with respectable advanced gastric adenocarcinoma and peripheral blood from health donor after obtaining appropriate informed consent under institutional review board approved. Tumor and normal specimens were processed by sterile mechanical dissection and digested with collagenase and hyaluronidase. Cells were separated on a Percoll density to get lymphocyte enriched suspension. Three color flow cytometry were performed to determine cell type, activation expression. The ELISA test of IL-10 was evaluated from patient’s serum. Results: Four patients with advanced gastric adenocarcioma and ten health donor were analyzed. The percentage of CD4+CD25+ T lymphocytes in patient’s peripheral blood and tumor specimens was 27.98% and 66.35%. The percentage of CD4+CD25+ T lymphocytes in health donor’s peripheral blood was 11.14%. There were increase proportions of regulatory T lymphocyte in cancer patient’s peripheral blood and especially in tumor infiltrating lymphocyte (P<0.001). The serum IL-10 level in gastric carcinoma patients and non-cancer donor was 0.236 pg/dl and 20.88 pg/dl (P=0.0175). Conclusion: Our preliminary results indicate that CD4+CD25+ regulatory T cells increase proportions in the peripheral mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TIL) of patients with gastric carcinoma. High expression of IL-10 in gastric carcinoma patients may relate to the function of regulatory T cells. As these regulatory T cells may present a barrier to tumor immunity, further strategies should be directed toward controlling their function.
FP-224 Regional Portal Hypertension Diagnosed by Ultrasonography: Imaging Findings and Diagnostic Values Baomin Shi, Wang Xy, Mu Ql, Wu Th, Xu J Dept. of General Surgery, Shandong Provincial Hospital, China PURPOSE: To investigate the diagnostic accuracy of ultrasonography for regional portal hypertension(RPH) and ascertain the best diagnosis method for RPH. METHODS Eleven cases of regional portal hypertension diagnosed by ultrasonography were retrospectively studied. Their etiological features, clinical findings, and ultrasonographic diagnosis criteria were analyzed. Other diagnosis approaches were also compared and related literature were reviewed. RESULTS Eleven patients were all verified by operation. The
diagnostic accuracy of color Doppler ultrasonography was 100%. The etiological diagnostic accuracy was 91% (10/11). CONCLUSIONS Color Doppler ultrasonography should be considered as the first choice to diagnose RPH due to its safty, accuracy, simplicity. RPH can be classified etiologically into 3 types: pancreatic RPH, splenic RPH, retroperitoneal RPH. Key words portal vein, hypertension diagnosis classification ultrasonography.
FP-225 Aberrant Expression of Lysophosphatidic Acid (LPA) Receptors in Human Colorectal Cancer Dai Shida1, Toshiaki Watanabe1, Junken Aoki2, Kotaro Hama2, Joji Kitayama1, Hironori Yamaguchi 1, Shin Sasaki 1, Hiroyuki Arai 2, Hirokazu Nagawa1 1 Department of Surgical Oncology, University of Tokyo Graduate School of Medicine, 2Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan Purpose: Lysophosphatidic acid (LPA) is a simple bioactive phospholipid with diverse effects on various cells, that interacts with three G protein-coupled transmembrane receptors, LPA1, LPA2, and LPA3. Using various colon cancer cells, we have previously reported that LPA acts as a potent stimulator of colon cancer progression, although the binding to LPA1 and LPA2 induces slightly different responses (Cancer Res 2003;63:1706-11). Thus, in this study, we investigated the LPA receptor expression profile in human colorectal cancer and in normal mucosa. Methods: Using real-time reverse-transcription polymerase chain reaction (RTPCR), we measured the expression levels of LPA1, LPA2, and LPA3 mRNA in 26 colorectal cancers and 16 corresponding normal tissue samples. We also assessed LPA2 expression immunohistochemically using a rat anti-LPA2 monoclonal antibody. Results: Normal epithelium expressed both LPA1 and LPA2 mRNA at similar levels. In comparison, colorectal cancers expressed LPA1 mRNA at a significantly lower level (0.3-fold; p<0.05), and LPA2 mRNA at a significantly higher level (3-fold; p<0.05), as compared with normal tissues. Thus, the ratio of LPA2 / LPA1 increased markedly during malignant transformation (18-fold increase). LPA3 mRNA was expressed at only a low level in both normal and cancer tissues. Immunohistochemistry also revealed high expression of LPA2 in colorectal cancer at the protein level. Conclusions: These results suggested that alteration of LPA receptor expression might be an important event in the development of colorectal cancer, and therefore, LPA and its receptors could be a chemopreventive target against colorectal cancer.
FP-226 The Risks and Extent of Lymph Node Metastasis in Superficial Esophageal Carcinoma Hideaki Shimada, Hisahiro Matsubara, Shin-Ichi Okazumi, Yoshihiro Nabeya, Tetsuro Urashima, Tooru Shiratori, Kiyohiko Shuto, Taknori Shimizu, Taito Aoki, Takenori Ochiai Academic Surgery, Chiba University Graduate School of Medicine, Japan BACKGROUND: Although the number of superficial esophageal carcinoma have been increased, the appropriate approach treatment modality has not been well defined. If it were possible to pre-
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dict lymph node metastasis and prognosis in superficial esophageal carcinoma before surgery, the appropriate patients, who do not require additional surgical resection after endoscopic resection, could be identified. STUDY DESIGN: A total of 160 patients with superficial esophageal carcinoma (SEC) underwent radical subtotal esophagectomy with lymph node dissection from 1980 to 2002. They consisted of 40 mucosal carcinoma and 120 submucosal carcinoma. On the basis of pathological data and results of surgery, the risk factors for lymph node metastases were discussed. RESULTS: The patients with small tumors (<20mm), mucosal tumor, without lymph node metastases showed significantly better survival than the other patients. The tumors with submucosal invasion, non-flat shape, lymphatic invasion and intramural metastasis induced higher risk for lymph node metastasis than the other tumors. Multivariate analysis showed that tumor depth and macroscopic shape of the tumor were independent risk factors for lymph node metastases. CONCLUSIONS: Esophagectomy with extended lymph node dissection is recommended for the patients with submucosal cancer. Cervical lymph node dissection is vital for the tumors located in upper third. Local tumor resection could be recommended for the patients with mucosal cancer without lymphatic invasion.
FP-227 P53, as a Molecular Target for Diagnosis and Treatment in Patients with GI Cancers Hideaki Shimada, Hisahiro Matsubara, Shinichi Oakzumi, Yoshihiro Nabeya, Tooru Shiratori, Akihiko Takeda, Hideki Hayashi, Yoshio Gunji, Kazuaki Nakajima, Shimizu Takanori, Takenori Ochiai Academic Surgery, Chiba University Graduate School of Medicine, Japan [PURPOSE] GI cancers are often characterized by a p53 mutation and protein accumulation. Over-expression of mutant p53 protein has been found to induce serum p53 antibodies (Abs). The possible ability of serum p53 antibodies analysis to detect tumors and treatment ability of p53 gene therapy were studied in GI cancers. [METHODS] Serum analysis of p53 antibodies was performed by enzyme-linked immunosorbent assay in 655 patients with GI cancers and 205 healthy controls. A total of 340 esophageal cancer, 123 gastric cancer and 192 colon cancer patients were analyzed for the presence of serum p53-Abs. The cut-off level of 1.3 U/ml was used to indicate sero-positive patients. Adenoviral p53 gene therapy was performed in 9 patients with non-resectable advanced esophageal squamous cell carcinoma as a phase I/II study. [RESULTS] Overall positive rates of serum p53-Abs were 32% in esophageal cancer patients, 11% in gastric cancer patients and 24% in colon cancer patients. Only 4.9% of healthy controls showed sero-positive. In the 9 patients, who was treated with p53 gene therapy, clinical minor response was observed in one patient and six patients revealed stable disease. The other tow patients revealed progressive disease. Typical adverse effects were local pain and fever for 6 to 12 hours. No serious adverse events have occurred so far in these patients. P53 gene therapy by intra-tumor injection is safe and biologically effective. [COCLUSION] p53 was a useful molecular target for diagnosis and treatment in GI cancers.
Journal of Gastrointestinal Surgery
FP-228 Diagnosis and Treatment Strategy of Local Recurrence after EMR for Superficial Esophageal Cancer Hideo Shimada, Hiroyasu Makuuchi, Yoshiyumi Kise, Osamu Chino, Takayuki Nishi Department of Surgery, Tokai University School of Medicine, Japan Aims: Endoscopic mucosal resection for early stage of esophageal cancer made rapid progress and is spread as a minimally invasive procedure. In this study we report problems of diagnosis and treatment of local recurrence after EMR. Methods: In our institution from 1989 till 2001, EMR was performed on 417cases (562 lesions) of superficial esophageal cancer. The transparent EEMR-tube was used for EMR. These patients underwent endoscopic examination with iodine staining every 6 months for detection of local recurrence and second primary lesions. Results: Local recurrence was detected at the site of EMR in 15cases(3.7%). The interval between initial treatment and detection of recurrence was 5 to 44 months (average: 14.7 months). In 11 cases, local recurrence was detected as iodine unstained area neighboring the scar. In 4 cases local recurrence was detected as submucosal protruding lesion at the anal site of the scar. The treatments for local recurrent cases were as follows. 1) Re-EMR was performed in 11 cases. 2) Surgical operation was performed in 2 cases. 3) In 2 patients, chemoradiotherapy or ethanol injection was performed. Conclusions: As for relationship between local recurrence and prognosis, we experienced only one death of detecting submucosal protruding lesion. To detect local recurrence after EMR, we should be careful of unstained area near the scar on endscopic examination and EUS or CT should be indicated for protruding lesions.
FP-229 Hepatic Arterial Infusional Chemotherapy in the Surgical Management of Bilobar Colorectal Liver Metastases Atsushi Shimizu, Yoshikazu Yasuda, Nobuyuki Houjou, Hideo Chiba, Yoshito Nihei, Hideki Sasanuma, Keisuke Yamashita, Maki Okada, Hideo Nagai Department of Surgery, Jichi Medical School, Japan PURPOSE: Hepatic resection remains the main stay of the treatment for colorectal liver metastases (CRLM). Still they are often unresectable at initial presentation because of small remnant liver volume or their ill-location and are associated with dismal prognosis. Therefore, we have used hepatic arterial infusion chemotherapy (HAI) for patients with nonresectable CRLM. Furthermore, after down-staging chemotherapy, rescue liver surgery for initially unresectable metastases has been performed in selected HAI responders. The purpose of this study was to assess the benefit of HAI and hepatic resection after preoperative chemotherapy. METHODS: From September 1992 to September 2003, 41 initially nonresectable CRLM patients received HAI after resection of primary colorectal cancer. Of these, 20 patients completed a full course of HAI, taking 10 g of 5-FU or more and were designated as a HAI group. Surgery was reconsidered in case of documented response to HAI and performed in selected cases when all tumor could be removed. Eligible candidates for the port placement but
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did not receive any HAI were analyzed as a control group. The primary endpoint was survival rate. RESULTS: The median survival time was 21 months in HAI group and 7 months in control group (p<0.05). Five patients underwent hepatectomy after neoadjuvant chemotherapy. There were three actual 3-year survivors. CONCLUSIONS: HAI for nonresectable CRLM is an effective regional therapy making rescue hepatic resection a possible treatment option and may contribute to the survival benefit of a small subset of the patients.
FP-230 Spleen-Preserving Laparoscopic Distal Pancreatectomy after Division of the Splenic Vessels Shuji Shimizu1, Masao Tanaka2, Hiroyuki Konomi2, Kazuhiro Mizumoto2, Koji Yamaguchi2 1 Endoscopic Diagnostics and Therapeutics, 2Surgery and Oncology, Kyushu University, Japan Minimally invasive surgery has achieved worldwide acceptance in various fields, but laparoscopic surgery for pancreatic diseases has been still reported only rarely. Although a spleen-preserving distal pancreatectomy has recently been introduced in open surgery because of increasing awareness of the importance of the immunological function of the spleen, use of this new procedure in laparoscopic surgery remains extremely rare. Among 23 patients undergoing laparoscopic pancreatic surgery between 1998 and 2003, we report our first case treated by laparoscopic distal pancreatectomy with splenic preservation by division of the splenic vessels. A 37year-old woman with a history of syncope was hospitalized with a diagnosis of hypoglycemia due to insulinoma. Computed tomography and magnetic resonance imaging revealed an enhanced solid mass, 1.5 cm in diameter, at the tail of the pancreas. Because the tumor was located deep in the parenchyma, laparoscopic distal pancreatectomy was performed. After localization of the tumor by intraoperative ultrasonography, the pancreas was transected with an endoscopic linear stapler. The operation time was 4 hours 52 min, and blood loss was 50g. The postoperative course was uneventful except for the appearance of focal splenic infarction 2 weeks after surgery but without any overt symptoms. Our initial experience suggests that spleen-preserving laparoscopic distal pancreatectomy with division of splenic vessels is a feasible and beneficial treatment option for benign pancreatic lesions. Although this method seemed to be technically easier than preserving the splenic vessels, more experience is necessary to fully evaluate this procedure and to overcome the risk of complications.
FP-232 Pylorus Preserving Pancreatoduodenectomy (PPPD) and Modified PPPD (Bulbus Preserving Pancreatoduodenectomy; BPPD) Takeaki Shimizu, Keiya Nikkuni, Yasuyuki Kawachi, Atsushi Nishimura Department of Surgery, Nagaoka Chuo General Hospital, Japan In the patients with the PPPD, there are many advantages at the point of weight gain, low frequency of fatty liver change and so on as compared with the patients with the pancreatoduodenectomy (PD). However, in the patients with PPPD, there were some problems such as the many gastric juice loss and long term hospital
stays. Recently, we modified the PPPD in a few points as follows: 1. keep the duodenal bulbus blood circulation, 2. preserve the duodenum about 5 cm from pylorus. In this bulbus preserving pancreatoduodenectomy (BPPD), nasogastric tube insertion period was one day and oral intake of meal was able to start at postoperative 5 days. Now, we studied the postoperative state in these two operation during this 6 years,31 cases with PPPD and 61 cases with BPPD. Results in PPPD was as follows: 1. hospital stay, 48.5 days, 2. nasogastric tube insertion period, 12.4 days, 3. oral intake of meal start, 19.8 postoperative days, 4. postoperative infection rate, 49.3%. Results in BPPD was as follows: 1. hospital stay, 23.1 days, 2. nasogastric tube insertion period, 1.1 days, 3. oral intake of meal start, 5.9 postoperative days, 4. postoperative infection rate, 11.5%. The 3 years survival rate were same in both operation. Conclusions: the postoperative performance state was significantly benefit in patients with BPPD. It was considered that the causes of this were the decrease of gastric juice loss and early intake of meal.
FP-232 Hand-assited Laparoscopic Nissen Fundoplication (HALS Nissen) Kazuyuki Shimomura1, Murata Nobuo2, Yamakawa Tatsuo2 1 Surgery, School of Modicine (Mizonokuchi Hospital), TeikyoUniversity, 2Department of Surgery, Mizonokuchi Hospital, School of Modicine, Teikyo- University, Japan Although laparoscopic surgery is being widely accepted by surgeons, some drawbacks of this procedure, mainly from that laparoscpic procedures are 2-D remote surgery without tactile sensation, are being recognised. Hand-assisted laparoscopic surgery (HALS), which started in recent years to improve these situations, provides surgeon tactile sensation and good organ handlings. Usually the indications of HALS are supposed to be associated with large resected specimen like colectomy, gasterectomy and nephrectomy. However in selected cases like in complicated or high risk patients, HALS is also useful in functional diseases like GERD (gastro esophageal reflux disease) even without surgical specimen. We would demonstrate the procedures and usefulness of Hand -assited Laparoscopic Nissen Fundoplication (HALS Nissen) for GERD. The procedures of HALS Nissen is almost similar to pure laparoscopic access, but these procedure can be performed by surgeon’s finger guide. The advanteges of HALS Nissen are mainly in the phase of blunt dissection around lower esophagus with surrounded adhesion by severe esophagitis. And it also contributes for better results in avoiding intraoperative injury in the area of esophagogastric junction. As for the procedure of sutures for fundoplication, HALS is useful to built the wrapping around fundus with appropriate pressure to fundus by finger knotting. We performed 3 HALS Nissen cases so far, And the operation time is around 1hour 30 min. All the patients discharged in 3 to 7 post operative days withoout complications. HALS Nissen procedure is considered to be a safe and useful option to GERD to promote surgical safety.
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FP-233 Comparison of Length and Quality of Survival between Gemcitabine-based Chemoradiation and 5-Fluorouracil-based Chemoradiation for Locally Unresectable Pancreatic Cancer Hiroyuki Shinchi, Sonshin Takao, Kosei Maemura, Takashi Aikou Department of Surgical Oncology, Kagoshima University School of Medicine, Japan Purpose: The purpose of this study was to compare the length and quality of survival of concurrent gemcitabine-based chemoradiation with that of concurrent 5-fluorouracil (5-FU)-based chemoradiation in patients with locally unresectable pancreatic cancer. Methods: Thirty-four patients with histologically proven locally advanced and unresectable pancreatic cancer without distant metastases were evaluated in this retrospective study. Eighteen patients received EBRT (50.4 Gy/28/fractions) with concurrent twice-weekly gemcitabine (40 mg/m 2/day) while 16 patients received EBRT with concurrent continuous infusion 5-FU (200 mg/m2/day). The length and quality of survival of the two groups were analyzed and compared. Results: The median survival and 1-year survival rate was 13.2 months and 53.3% in the 5-FU-based chemoradiation group, while the median survival has not yet been reached and 1-year survival rate was 60% in the gemcitabine-based chemoradiation group. The average monthly Karnofsky score of 78.4 in gemcitabine-based chemoradiation group was similar to that of 77.1 in the 5-FU-based chemoradiation group. No serious complications were observed in both groups. Conclusions: External-beam radiotherapy with concurrent twice-weekly gemcitabine appears to increase the length and quality of survival as compared to 5-FUbased chemoradiation and provide a first-line treatment for patients with unresectable pancreatic cancer.
FP-234 Chemosensitivity Testing Offers no Advantage for Chemotherapy of Pancreatic Cancer Marek Sierzega1, Tadeusz Popiela1, Jan Kulig1, Beata KusnierzCabala2, Janusz Legutko1, Anna Gurda1, Jerzy Naskalski2 1 1st Department of Surgery, 2Dept. of Clinical Biochemistry, Jagiellonian University, Poland The aim of this study was to evaluate if in vitro chemosensitivity testing offers any advantage for chemotherapy of pancreatic cancer. Methods: Between Jan 2001 and Dec 2002, we have collected fresh tumour samples of 103 consecutive patients who underwent laparotomy with or without pancreatic resection for pancreatic ductal carcinoma. Following enzymatic separation, cancer cells were cultured for 72 hours in 98-weel plates with standard medium supplemented with consecutive dilutions of tested chemotherapeutic drugs (gemcitabine, cisplatin, leucovorin, fluorouracil). Chemosensitivity of cells was determined with the tetrazolium colorimetric assay. Patients participating in this study were randomly allocated to two chemotherapy regimens, i.e. gemcitabine and cisplatin (GC) or gemcitabine. leucovorin, fluorouracil (GLF). Results: The study group consisted of 103 patients (55 males and 48 females, mean age 59 years) allocated into the GC group (49 patients) and the GLF group (54 patients). 47 patients underwent resective procedures and 46 laparotomy with or without bypass anastomoses. Basing on the in vitro tests, 43% patients in the GC
Journal of Gastrointestinal Surgery
group (n=21) and 37% in the GLF group (n=20) were classified as “sensitive” to the used combination of drugs while the remaining cases were regarded as “resistant” to the administered regimen of chemotherapy. No statistically significant differences were observed between “sensitive” and “resistant” cases regarding inhibition of tumour growth, clinical response (Karnofsky performance status, body weight, consumption of analgesics) and the median survival. Conclusion; Standard use of chemosensitivity testing offers no advantage for chemotherapy of unresectable pancreatic cancer.
FP-235 Dukes’ Classification as a Prognostic Indicator in Squamous Cell Carcinoma of the Thoracic Esophagus. Should the Current Staging System be Modified? Tomasz Skoczylas, Andrzej Dabrowski, Wit Juskiewicz, Krzysztof Zinkiewicz, Aleksander Ciechanski, Grzegorz Cwik, Grzegorz Wallner Second Department of General Surgery, Skubiszewski Medical University of Lublin, Poland Objective: To determine utility of Dukes’ classification as a prognostic indicator in patients with SCC of the thoracic esophagus. Methods: We analyzed 112 patients who had undergone surgical treatment (S) and 81 patients who had undergone a combinedmodality therapy (CMT) due to SCC of the thoracic esophagus. The pathological staging was determined in all the patients according to the TNM and Dukes’ classifications. The cumulative survival rates were calculated using the Kaplan-Meier method. The differences in survival between the patients in patricular stages of both classifications were estimated with the log-rank test. Results: The statistically significant difference in cumulative survival rates between the neigbouring TNM stages in S group was found only between TNM III and TNM IV (13.8 mts vs 8 mts; p=0.003). The differences in cumulative survival rates between the neigbouring stages of the TNM classification in CMT group were insignificant. The significant differences in cumulative survival between the neigbouring Dukes’ stages in S group were found between Dukes’ A and Dukes’ B (47.7 mts vs 19.4 mts; p=0.047) and between Dukes’ C and Dukes’ D (14 mts vs 8 mts; p=0.002). The significant difference in cumulative survival between the neigbouring stages in Dukes’ classification in CMT group was found between Dukes’ A and Dukes’ B (54.3 mts vs 25.8 mts; p=0.02). Conclusion: The simpler, clearer and appropriate in providing a rational prognostic significance Dukes’ classification adopted for esophageal cancer could be as good prognostic indicator as the TNM classification irrespective of the treatment applied.
FP-236 The Role of Ultrasound in the Assessment of Cervical and Abdominal Lymph Node Metastases in Patients with Squamous Cell Carcinoma of the Thoracic Esophagus Treated with Neoadjuvant Therapy Tomasz Skoczylas, Grzegorz Cwik, Andrzej Dabrowski, Grzegorz Wallner, Aleksander Ciechanski, Krzysztof Zinkiewicz Second Department of General Surgery, Skubiszewski Medical University of Lublin, Poland Objective: To establish the role of US in the assessment of cervical and abdominal lymph node metastases and its impact on making decision about surgical strategy in patients with squamous cell car-
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cinoma of the thoracic esophagus treated with neoadjuvant therapy. Methods: We analyzed a setting of 83 patients who had undergone a combined-modality treatment. The results of US lymph node assessment were compared with the results of histopathological evaluation of lymph nodes harvested during surgery (transthoracic esophagectomy and 2-field extended or 3-field lymph node dissection) and diagnostic value of cervical and abdominal US in terms of sensitivity, specificity, positive and negative predictive value were determined.Results: The sensitivity, specificity, positive and negative predictive value of the US assessment of cervical lymph node metastases were 96%, 100%, 81% and 100%, respectively. The sensitivity, specificity, positive and negative predictive value of the US assessment of abdominal lymph node metastases were 94%, 82%, 91.5% and 87%, respectively. Conclusions: The very high sensitivity and specificity of cervical US make this investigational method sufficient in the assessment of cervical nodal involvement. In esophageal cancer patients with negative cervical lymph nodes on US, three-field lymph node dissection is unnecessary. In patients in whom metastatic lymph nodes are found on cervical US one should consider to extend lymph node dissection about lymph node stations of the neck to achieve a curative resection. In patients with negative abdominal US this investigation should be supplemented by more detailed diagnostic methods.
FP-237 Intraoperative Endoscopy during Reoperation for Failed Antireflux Surgery Antonio Giovanni Spaventa1, Cesar Oscar Decanini1, Guillermo Becerril-Martinez1, Alberto Farca2, Francisco Fournier2 1 Endoscopic Surgery, 2Gastrointestinal Endoscopy, American British Cowdray Medical Center, I.A.P., Mexico Background: Reoperation after a failed laparoscopic antireflux procedure can be a difficult challenge to the laparoscopic surgeon. Most of the cases can be performed laparoscopically, taking care not to perforate the esophagus and/or stomach during the procedure. Intraoperative endoscopy can be a usefull method to minimize the risks of such perforations and of confirming adequate fundoplication to prevent further complications in such patients. Case Presentation: A 43 year old female, with a previos history of laparoscopic antireflux procedure 2 months prior to consultation, complained of food dysphagia and occasionally to fluids, soon after the procedure. She was treated with fluids only PO, prokinetics and proton pump inhibitors with no response and 8 kilograms weight loss. Esophagogram showed pseudoachalasia and passage directly to fundoplication instead of the stomach. Endoscopy confirmed stenotic cardias with an angled fundoplication. Balloon dilation was made with mild improvement. Further exacerbation of symptoms prompted surgical intervention. Laparoscopy was undertaken finding extensive adhesions and fibrosis of the esophageal hiatus, with stenosis at the diaphragmatic closure and a rotated and angled corpoplication. Dissection with harmonic scalpel was made and intraoperative endoscopy assisted to avoid esophageal and gastric perforation, the previous procedure was dissected completely and adequate Nissen fundoplication was performed. Intraoperative endoscopy confirmed the procedure. The patient had an uneventful recovery, without dysphagia and
gaining weight on follow-up examination. Conclusion: Intraoperative endoscopy during reoperations for failed antireflux procedures can minimize the risk of perforations and also confirm adequate surgical technique of the new fundoplication to prevent further complications.
FP-238 Strategy for Small-for-Size Graft in Living Donor Adult Liver Transplantation Taketoshi Suehiro, Tatsuo Shimura, Toshiyuki Okada, Kouji Okada, Shinji Hashimoto, Yasushi Mochida, Hiroyuki Kuwano Department of General Surgical Science, Gunma University, Japan (Introduction) In living donor adult liver transplantation (LDALT), small-for-size graft (SSG) has trouble to postoperative management, and has a risk of graft failure. We discuss about the strategy for SSG in LDALT. (Object) (1) Splenic artery ligation, (2) graft venoplasty (3) portal vein infusion (4) hyperbaric oxygen therapy was performed in order to prevent the SSG injury, and it evaluated about the effect. (Result) (1) Portal pressure of 11 splenic artery ligation cases fell to 21.8 to 19.8mmHg, and decreased also from the portal vein flow 1620 to 1416ml/min. Moreover, whose prognosis compared with the case, which did not litigate splenic artery, improved 2-year survival rate 100% vs.80%. (2) Graft venoplasty, decreased total bilirubin levels on 7POD 13.8 to 7.0mg/dl. It decreased also ascites on POD14 1400 to 520ml. (3) the tube was detained in portal vein and prostaglandinE1 and nafamostat mesilate was infused. In infusion group, the total bilirubin level and amount of ascites on POD14 were lower compared with non-infusion group. (4) By performing hyperbaric oxygen therapy to functional cholestasis after LDALT, the fall of bilirubin became rapid, plasma exchange and the number of times of bilirubin adsorption decreased, and hospital stay were also shortened from the 68th to 40days. (Conclusion) Examination evaluation was carried out about our strategy for SSG. By combining splenic artery ligation, graft venoplasty, portal infusion, and hyperbaric oxygen therapy to SSG, which poses a big problem in LDALT, graft injury was mitigated and it was suggested that prevention of graft failure was possible.
FP-239 Repeated Pancreatectomy for the Remnant Pancreatic Neoplasm after Pancreatoduodenectomy Maki Sugimoto, Tadahiro Takada, Hideki Yasuda, Ikuo Nagashima, Hodaka Amano, Masahiro Yoshida, Fumihiko Miura, Takahiro Isaka, Naoyuki Toyota, Kenji Takagi, Kenichiro Kato Surgery, Teikyo University School of Medicine, Japan There are very few benign or malignant diseases which arise in the remnant pancreas after pancreatectomy. A retrospective review, 355 PD performed at Teikyo university hospital during 1981-2004, 7 (19.7%) were acquired repeated pancreatectomy for the remnant pancreatic neoplasm after pancratoduodenectomy There were two cases of the recurrence of adenocarcinoma in the remnant pancreas after PD for pancreatic adenocarcinoma, a recurrence of intraductal papillary mucinous carcinoma after PD for pancreatic adenocarcinoma, an adenocarcinoma after PD for mucinous cystadenoma, an intraductal papillary mucinous adeno-
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ma after PD for pancreatic adenocarcinoma, an intraductal papillary adenocarcinoma after PD for suspicious adenocarcinoma, an adenocarcinoma among mucinous cystadenoma after PD for invasive adenocarcinoma among multiple intraductal papillary mucinous adenoma. It is difficult to assess whether the second neoplasm of the pancreatic remnant was a recurrence or a second primary neoplasm. Strict long turn observation for the development of pancreatic neoplasm should be recommend even in the remnant pancreas after pancreatectomy.
FP-240 Usefulness of 3D-CT for Preoperative Management of Hilar Cholangiocarcinoma Mitsutaka Sugita1, Itaru Endo1, Yoshiro Fujii1, Kuniya Tanaka1, Toru Kubota1, Hitoshi Sekido1, Shinji Togo1, Hiroshi Shimada1, Holger Bourquain2, Heintz Otto Peitogen2 1 Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan, 2Mevis at University of Bremen, Germany Purpose: To clarify the usefulness of combined three-dimensional computed tomography (3D-CT) of the bile duct and the portal vein for the preoperative simulation of the intraoperative bile duct transection. Subjects and Methods: Five patients with hilar cholangiocarcinoma were enrolled in this study. MDCT cholangiography and dynamic enhanced MDCT were performed in the preoperative, and a three-dimensional combined image of the bile duct and the portal vein were made from these data using the workstation (HepaVision2 and InterventionPlanner, MeVis, Bremen, Germany). After the projection of an area of cancer invasion diagnosed by cholangiography on this 3D bile duct image, an appropriate transection line of the bile duct for the curative resection was simulated. Bifurcation of the portal vein was used as a marker of the transection line of the bile ducts. And the orifice of bile ducts which were exposed to the cut surface were also identified. They were compared with the intraoperative findings. Results: In all five cases, 3D-images of bile ducts and portal veins were reproduced accurately. In one case, actual numbers of the orifice of the hilar bile ducts were less than expected number because B4 was transected at the more proximal line than the preoperative simulation. In four of five patients, curative resection was achieved. One case had extensive microscopic submucosal cancer spread, so the surgical margin of the hilar bile duct became positive for cancer. Conclusion: 3D-CT was useful for the preoperative simulation of the bile duct transection for hilar cholangiocarcinoma patients.
FP-241 Oral Insulin Improves Intestinal Recovery Following Ischemia-Reperfusion Injury in Rat Igor Sukhotnik1, Jorge Mogilner1, Naim Shehadeh2, Raanan Shamir2, Habib Hilow3, Michael Lurie1, Eitan Shiloni3 1 Rappaport Faculty of Medicine, Technion, Bnai Zion Medical Center, 2Meir Pediatric Children’s Hospital, 3Carmel Medical Center, Israel Background: Recent evidence suggests that members of the insulin- like growth factor family are involved in modulation of
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growth and differentiation of normal small bowel and of intestine following ischemia-reperfusion. Aim: To evaluate the effects of enteral insulin supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following intestinal ischemia-reperfusion (IR) in a rat. Methods: Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent laparotomy and superior mesenteric artery mobilization, IR- rats underwent superior mesenteric artery occlusion for 40 min following by one hour reperfusion, and IR-INS rats treated with oral insulin given in drinking water (1u/1ml) 48 hours before and following IR. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 24 hours following IR. A non-parametric Kruskal-Wallis ANOVA test were used for statistical analysis with P less than 0.05 considered statistically significant. Results: IR-rats demonstrated a significant decrease in bowel weight in duodenum and jejunum, mucosal weight in jejunum and ileum, villus height in jejunum and ileum compared to sham animals. IR rats also had a significantly lower cell proliferation index in jejunum and higher apoptotic index in jejunum and ileum compared to control rats. IR-INS animals demonstrated greater duodenal and jejunal bowel weight, duodenal, jejunal and ileal mucosal weight, jejunal and ileal cell proliferation index compared to IRanimals. Conclusions: Oral insulin administration decreases the mucosal injury caused by IR injury in rat.
FP-242 The Prognostic Factor for Outcome Following Second Resection for Intrahepatic Recurrence of Hepatocellular Carcinoma with Non-HCV Infection Background Hui-Chuan Sun, Hui-Chuan Sun, Zhao-You Tang, Zeng-Chen Ma, Lun-Xiu Qin, Lu Wang, Qin-Hai Ye, Jia Fan, Zhi-You Wu, XinDa Zhou Liver Cancer Institute and Zhong Shan Hospital, China Background Second resection has been proved to be a safe and effective treatment for patients with intrahepatic recurrent HCC after primary resection; however, the prognostic factors for outcome following second resection in patients with non-HCV background remained to be clarified. Methods Fifty-seven patients with intrahepatic recurrent HCC and HBV infection background received second resection from 1997 to 2003 in our institute. All of them were negative in AntiHCV and positive in HBV profile. Preoperative patient and tumor factors were analyzed. Results At time of preparing this paper, 34 had re-recurrence, 21patients died, including 1 died of liver failure without evidence of recurrence. No postoperative mortality was noted. The 1, 3, 5 year disease-free survival and overall survival after second resection were 43.2%, 31.2%, 31.2%, and 69.9%, 61.2%, 30.6%, respectively. Univariant and multivariant analysis showed that tumor size, vascular invasion and disease free interval were independent prognostic factors for disease free survival following second resection, while vascular invasion and disease free interval were independent prognostic factors for overall survival following second resection. The 3 and 4 year overall survival after second resection were 57.7% and 46.6% in patients with presence of any of two risk factors (n=46), and 100% and 100% in those with absence of both risk factors (n=11, P=0.008). Conclusions Time to recurrence and vascular invasion were the
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prognostic factors for outcome following second resection of intrahepatic recurrent HCC.
FP-243 Chemoradiation Therapy for Patients with Unresectable Mass-forming Intrahepatic Cholangiocarcinoma Koichi Suto, Wataru Kimura, Fuse Akira, Ichiro Hirai First Department of Surgery, Yamagata University School of Medicine, Japan Purpose: The purpose of the present study was to clarify the utility of chemoradiation therapy for patients with unresectable massforming intrahepatic cholangiocarcinoma (ICC). Patients and Methods: Sixteen patients with unresectable mass-forming ICC were studied. Eight patients underwent external irradiation totaling 42-60 Gy and systemic chemotherapy (7 patients underwent low dose CDDP and 5-FU, and 1 underwent EPIR and 5-FU) after 1999 (treated group), while no radiation or chemotherapy was performed for 8 patients before 1999 (untreated group). Results: No significant differences existed between treated and untreated patients on imaging, TNM factor or stage. In the treated group, minor response was achieved in 3 patients (37%). Disease was stable in three patients, and progressed in the other two. The median survival for the treated group was 17 months, while that for the untreated group was 5 months (p<0.05). Survival rates for the treated group were 62.5% at 1 year and 37.5% at 2 years. All untreated patients died within 8 months. Conclusions: Chemoradiation therapy seems to improve the prognosis of patients with unresectable mass-forming ICC.
FP-244 A Japanese Multiinstitutional Study of Intraductal Papillary Mucinous Tumor Yutaka Suzuki, Masanori Sugiyama, Nobutsugu Abe, Osamu Yanagida, Tadahiko Masaki, Toshiyuki Mori, Yutaka Atomi Department of Surgery, Kyorin University School of Medicine, Japan [Method] The Japan Pancreas Society performed a multiinstitutional, retrospective study of 1379 cases of intraductal papillary mucinous tumor (IPMT). Clinicopathologic features and postoperative long-term outcomes were investigated. [Result] IPMT were most frequently found in middle-aged to elderly (mean age 67.9 years) men and in the head of the pancreas. Communication between the cyst and pancreatic duct was observed in 61.3% of cases. Histopathologic examination of the surgical specimens revealed hyperplasia in 5.6%, adenoma in 48.0%, borderline tumors in 1.1% and adenocarcinoma in 43.6%. A total of 355 cases did not undergo surgery. The five-year survival rate of IPMT patients was 98-100% in adenoma to noninvasive carcinoma cases, 89% in minimally invasive carcinoma cases, and 57.7% in invasive carcinoma cases. In all patients with IPMT who died of tumor recurrence after surgery for IPMT, the most common recurrence was of peritoneal seeding (29.9%), followed by hepatic metastasis (25.4%). In this study, advanced age, positive symptoms, abundant mucus secretion, presence of large nodules, large cysts, remarkable dilatation of the main pancreatic duct, and/or main pancreatic duct- or combined-type IPMT were indicators of malignant IPMT. [Conclusion] The results from this study may contribute to the diagnosis and treatment of IPMT. Nevertheless, there are
issues regarding IPMT that remain to be resolved, including: (1) establishment of a reliable diagnosis system for assessing the grade of malignancy; and (2) development of a strategy for treatment of branch duct IPMT.
FP-245 Effectiveness of Flow Evaluation for CACS in Patients Treated with Pancreaticoduodenectomy Masaki Taira, Masaki Taira, Kazuyasu Nakao, Masaaki Nakahara, Masayuki Tori, Hiroki Akamatsu, Shigeyuki Ueshima Surgery, Osaka Police Hospital, Japan Purpose: Celiac axis compression syndorome (CACS) is not so rare for upper abdominal surgery, but evaluation of outcome after surgical procedure has not been established. We report usufullness of doppler ultrasonography for it. Patients and Methods: The records of three patients were reviewed. They were 77 yo female (diagnosed as bile duct carcinoma), 58 yo male (chronic pancreatitis), and 72 yo female (pancreatic head cancer). All of them experienced pancreaticoduodenectomy, and during surgery, an excision of median arcuate ligament (MAL) was performed to treat CACS. Pre- and post- operative Doppler flowmetry was performed to evaluate the treatment in each case. Intraoperative magnetic flowmetry of proper hepatic artery was performed in one case with or without clamp of gastroduodenal artery (GDA) . Results: Before excision of MAL, flow of PHA decreased (50 to 8ml/min) with clamp of GDA, although after excision of MAL, flow of PHA did not change so much (70 to 65ml/min) with clamp of GDA. In all cases, preoperative doppler ultrasonography showed hepatofugal flow of common hepatic artery, and to the contrary, postoperative flow hepatopetal. All of the patients had uneventful course after operation. Conclusion: Pancreaticoduodenectomy was successfully performed by excision of MAL. Flowmetry was useful to certify the effectiveness of treatment.
FP-246 Living Donor Liver Transplantation for Hepatocellular Carcinoma Yasutsugu Takada, Mikiko Ueda, Hiroto Egawa, Koichi Tanaka Transplantation and Immunology, Kyoto University, Japan Purpose: For patients with hepatocellular carcinoma (HCC), optimal indications of living donor liver transplantation (LDLT) have yet to be clarified. In our institute, the patient exclusion criteria include only those with extrahepatic metastasis or vascular invasion, and there is no restriction on tumor number or size. In this study, the results of our LDLT for HCC patients using such criteria were investigated. Patients and Methods: From February 1999 to March 2004, 87 patients underwent LDLT for HCC. As for underlying diseases, 49 patients had HCV-related liver cirrhosis, followed by HBV in 29 patients. The MELD score ranged from 4 to 36 (median 14). Except for 10 cases with incidental tumors, 40 patients were within Milan criteria and 37 were beyond the criteria. Sixty-five patients (75%) had previously received non-tansplant treatments for HCC, including hepatic resection in 12 patients. Median postoperative follow-up period was 31. Results: Overall patient survival rate at 3 years was 68%. Cumula-
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tive recurrence rates at 3 years were 33% and 8% in patients beyond Milan criteria and those within the criteria, respectively (p<0.05). However, there was no significant difference in 3-year recurrence-free survival rate between the two groups (58% vs. 69%). By multivariate analysis, the histological grade of malignancy and pathological tumor number were considered significant risk factors of recurrence. Conclusion: Many patients who did not meet the Milan criteria survived without tumor recurrence after LDLT. The present results suggest that favorable outcomes could be expected in patients selected by our extended criteria.
FP-247 How Long is the Optimal Anal Margin in Low Anterior Resection for Locally Advanced Low Rectal Cancer? Keiichi Takahashi, Takeo Mori, Tatsuro Yamaguchi, Hiroshi Matsumoto, Hidenori Miyamoto, Kuniyoshi Arai, Yoshiaki Iwasaki Surgery, Tokyo Metropolitan Komagome Hospital, Japan We clarified the length of the optimal anal margin in low anterior resection for advanced low rectal cancer. We carried out low anterior resection of 95 cases with locally advanced low rectal cancer curatively from 1990 to 1999 in our hospital. We carried out the modified TME that removed mesorectum below 2-3 cm from the lower margin of the tumor. We analyzed the correlation between the length of anal margin and the rate of local recurrence. We divided two groups: one was cases with local recurrence (LR (+) group) and the other was cases without local recurrence (LR (-) group). LR (+) group was 4 and LR (-) group was 91. Total local recurrent rate was 4.2%. The mean distance from the lower margin of the tumor to dentate line was 4.3±2.1cm for LR (+) group and 3.9±2.0cm for LR (-) group. There was no significant difference (t-test : p=0.7273). The mean length of anal margin was 2.3±1.2cm for LR (+) group and 1.7±0.8cm for LR (-) group. There was no significant difference (t-test: p=0.08705). The mean maximum diameter of the tumor was 7.3±3.3cm for LR (+) group and 4.4±1.8cm for LR (-) group. There was a significant difference (t-test : p=0.0042). But there was a strong correlation between the maximum diameter of the tumor and the length of anal margin (R2=0.76). There was no correlation between the length of anal margin and local recurrence. It was essential and important to keep cancer negative surgical margin of the tumor and carry out modified TME.
FP-248 cDNA Array Analysis for Prediction of Hepatic Metastasis of Colon Carcinoma Osamu Takata1, Yutaka J. Kawamura1, Junichi Sasaki1, Toshihiro Kai1, Yasuyuki Miyakura2, Hideo Nagai2, Toshihiko Tsukamoto3, Konishi Fumio1 1 Surgery, Omiya Medical Center of Jichi Medical School, 2Department of Sugery, Jichi Medical School, 3Department of Biological Chemistry of Kitasato University, Japan (Purpose) 20% of patients who underwent potentially curative colectomy would develop hepatic recurrence. Therefore we regularly treat every StageIII patient with adjuvant therapy. However, approximately 40% of StageIII patient survived without recurrence. Nobody knows whether patients will develop recurrence or won’t. cDNA array would give useful information for treatment.
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The main aim is to predict the possibility of metachronous hepatic metastasis. (Methods) Specimens were obtained from patients with colon carcinoma who underwent colectomy. The number of patients with StageIII had no recurrence over the five years was 20, the number of patients who had metachronous liver metastasis was 15, and that of patients who had synchronous liver metastasis was 20. Total RNA was isolated from whole block specimens of primary carcinoma and adjacent normal mucosa. cDNA probes which were labeled by biotin were amplified by PCR. Subsequently cDNA probes were hybridized to target cDNA which were spotted on nylon membranes. (Results) We identified 22 genes which had some relationship to hepatic recurrence. Clustering analysis could classify patients into those with and without hepatic metastasis clearly, and Principal component analysis suggested some features of each group. And we could predict the possibility of metachronous hepatic metastasis by the prediction model which was developed by supervised learning. (Conclusions) We believed that cDNA micro-array could predict high risk patients who will develop metachronous liver metastasis. This technique would become a new prognostic tool to decide the adequate indication of postoperative strategy.
FP-249 The Indications for Adjuvant Chemotherapy in Pancreatic Cancer, 5-Fluorouracil vs Gemcitabine Shin Takeda, Soichiro Inoue, Tetsuya Kaneko, Akimasa Nakao Department of Surgery II, Nagoya University School of Medicine, Japan Aim It was reported that adjuvant treatment was beneficial in pancreatic cancer. We used intravenous Gemcitabine (GEM) or 5-fluorouracil (5FU) continuously via portal vein (LPC) for only 3 weeks just after surgery. We clarify the reliable indications for adjuvant GEM or 5FU in pancreatic cancer patients, depending TS and DPD expression in resected pancreatic cancer tissues. Methods 78 (IIA 21, IIB 34, IV 23) resected specimens from patients with advanced pancreatic cancer were immunostained with anti-TS and anti-DPD antibody. The relation between intratumoral TS, DPD expression and the outcome of the pancreatic cancer patients was investigated retrospectively. Results Of the 67 tumors studied, 46 carcinomas (70%) were TS(+) and 21 (30%) were TS (-). In the TS (+) group, the LPC (+) subgroup showed a significantly higher survival rate than the no LPC subgroup (median survival, 16.4 vs 8.3 months), whereas in the TS (-) group, the median survival was 10.1 months with LPC (+). Of the 70 tumors studied, 31 carcinomas (47%) were DPD (+) and 39 (53%) were DPD (-). In the DPD (+) group, the median survival was 14.0 months with LPC, whereas in the DPD (-) group the LPC (+) subgroup showed a significantly higher survival rate than the LPC (-) subgroup (median survival, 17.8 vs 8.3 months). Moreover, overall survival in the TS (+) DPD (-) subgroup with LPC (+) was significantly better than GEM group. Conclusions In the TS (+)DPD (-) subgroup, 5FU via the portal vein is an effective adjuvant reagent for pancreatic cancer. In the TS (-)DPD (+) subgroup, GEM might be effective to prolong survival.
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FP-250 Bacterial Translocation in Patients with Colorectal Cancer Yoshio Takesue, Hiroki Ohge 1st Department of surgery, Hiroshima University, Japan PURPOSE: The aim of this study was to identify the risk factors for bacterial translocation, and its clinical significance in patients with colorectal cancer. METHODS: Mesenteric lymph node sampling was performed to identify the presence of bacterial translocation in 75 patients with colorectal cancer undergoing laparotomy. RESULTS: Bacterial translocation was identified in 29 patients (39%). The most common organism was Escherichia coli (31%). Three factors for bacterial translocation were identified, including preoperative low peripheral lymphocyte count, metastasis to the lymph nodes, and invasion depth (T3, T4). Stepwise regression analysis, however, selected only >T3 (odds ratio 4.0, 95% confidence interval 1.2-13.5). Thirty five percent of patients with bacterial translocation developed septic complications compared with 20% in patients without bacterial translocation. In multivariate analysis, bacterial translocation was not an independent risk factor for infection, with an odds ratio of 1.8 (95% confidence interval 0.56-5.96). Systemic inflammatory response syndrome developed on the first day in 62% of patients with bacterial translocation compared with 50% of patients without bacterial translocation. Adjusting for the other factors, bacterial translocation was not a significant risk factor in the occurrence of systemic inflammatory response syndrome after surgery (odds ratio 1.1, 95% confidence interval 0.37-3.29). CONCLUSION: In colorectal cancers, bacterial translocation does occur and is increased in patients with deep invasion. However this appears to be of no clinical significance.
FP-251 Advantage of Laparoscopic Surgery for Crohn’s Disease Hiroshi Tamagawa1, Riichiro Nezu2, Yoshifumi Inoue3, Fumihiro Uchikoshi4, Daisuke Kishi4, Yasuyuki Kai2, Tsunekazu Mizushima5, Chu Matsuda4, Toshinori Ito4, Hikaru Matsuda4 1 Department of Surgery, Osaka University Graduate School of Medicine, 2 Department of Surgery, Osaka Rosai Hospital, 3 Department of Surgery, Nissei Hospital, 4Surgery, Osaka University Graduate School of Medicine, 5Department of Surgery, Rinku General Medical Center, Izumisano Municipal Hospital, Japan [Purpose] Laparoscopic surgery is widely available in GI surgery, and we have tried to induce laparoscopic procedures for Crohn’s disease (CD). CD patients are often obliged to undergo reoperations and we also have engaged in the application of laparoscopic surgery for reoperative patients. [Methods] From January 1990 to May 2004, 247 operations in 177 CD patients were undertaken. These cases were studied retrospectively in terms of operative procedures correlating Vienna classification. [Results] 92 CD operations were performed under laparoscopic procedures. 83 operations were performed by laparoscopic procedures (Lap) and 9 were under hand assisted laparoscopic surgery (HALS). In terms of Vienna classification, 83 Lap operations contained that L1; 29, L2; 9, L3; 45, L4; 0 cases and B1; 3, B2; 58, B3; 22 cases individually. Moreover, 16 cases of them were tried to undergo for reoperative cases, which resulted in success. On the other hand, 155 classical laparotomy cases contained L1; 56, L2; 22, L3; 76, L4; 1 cases and B1; 22, B2; 68, B3; 65 cases individual-
ly. Thus, laparoscopic surgery, compared with laparotomy surgery, was preferentially undertaken for the stricturing lesions of CD. All of the HALS (9 cases) contained colonic lesions (L2; 2, L3; 7), and 5 of them had previous operative history. [Conclusions] Our effort to apply laparoscopic techniques including HALS in CD operation has resulted in satisfactory outcome especially for ileal or ileocolonic type. Moreover, structuring lesions seemed to be suitable for laparoscopic procedures than penetrating type.
FP-252 Adjuvant Chemoirradiation after D2 Gastrectomy for Gastric Cancer Charles Tse Kuang Tan, Jimmy Bok Yan So, Soo Chin Lee Department of General Surgery, National University of Singapore, Singapore Background Postoperative adjuvant chemoirradiation has been shown to be effective for gastric cancer in a recent multicenter trial. The role of adjuvant therapy for patients with D2 gastrectomy remains controversial. Aim To determine tolerability of adjuvant chemoirradiation after D2 gastrectomy Methods The data of patients who received chemoradiotherapy following D2 gastrectomy were prospectively collected. The adjuvant treatment comprised of 5FU + Leucovorin and radiotherapy. The side effects of the adjuvant treatment was measured using the Common Toxicity Criteria Results 37 patients who were subjected to this treatment protocol after D2 gastrectomy. 29 patients completed the chemoirradiation regime. All patients who could not complete the regime sited the reason of intolerability and half of them occurred in the 5th course. A total of ten patients were admitted to hospital during the course of chemoirradiation. Gastrointestinal disturbances of diarrhoea and vomiting were the most common side effects (78.4%). Six patients were admitted for neutropenic fever. Another was admitted after he developed a deep vein thrombosis. One patient was admitted twice, once for neutropenic fever and the second for diarrhoea. No patient developed suffered major toxic effects (grade 3 and above). Conclusion 78% of patients completed the chemoradiation regime reflecting good tolerability None of the patients suffered major toxic effects (grade 3 and above) Further studies have to be done to investigate the effect of D2 gastrectomy plus adjuvant chemoradiotherapy on the survival of these patients with resectable adenocarcinoma.
FP-253 Laparoscopy-Assisted Surgery for Colorectal Cancer Jun-Ichi Tanaka, Shungo Endo, Fumio Ishida, Eiji Hidaka, Koichi Nagata, Shin-Ei Kudo Digestive Disease Center, Showa University Northen Yokohama Hospital, Japan The aim of this study is to report the first three years experience of laparoscopy-assisted surgery for colorectal cancer (CRC) since April 2001 when our hospital was established. Three hundred and eighty patients with CRC underwent bowel resection. We applied lararoscopic bowel resection (LAC) with lymph node dissection
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(D2/D3) for advanced CRC as well as early CRC with D1 lymph node dissection where endoscopic mucosal resection was not indicated. Invasion to the adjacent organs, greater than 7 cm in size, extensive lymph node involvement, bowel obstruction, or advanced lower rectal cancer were excluded from the indication of LAC. LAC was performed in 239 (63%) patients, 151 (65%) out of 232 patients with colon cancer and 87 (59%) out of 147 patients with rectal cancer underwent LAC. Conversion to open surgery (OS) was 17 (7for T4, 2 for intestinal adhesion, 1 for bulky tumor, etc) patients. No significant difference between LAC and open surgery was found in operation time. No operative mortality, morbidity was 8.9% (anastomotic leakage7, ileus12) in LAC, 15.3% (anastomotic leakage5, ileus14) in OS. In all other cases, the immediate postoperative course was uneventful with a hospital stay of 7 to 14 days and quick resumption of physical activity. Although OS was indicated to far-advanced CRC in this study, LAC for advanced CRC was comparable to OS in terms of operation time and morbidity. LAC for advanced colorectal cancer is a feasible and safe operation with an acceptable complication rate. Recurrence rate or long-term functional outcome needs longer follow-up.
FP-254 The Indication for Splenic Vein Reconstruction after Pancreaticoduodenectomy with SMA Plexus Dissection Koichi Taniguchi, Toru Kubota, Yasuhiko Miura, Koichiro Misuta, Michio Ueda, Itaru Endo, Hitoshi Sekido, Shinji Togo, Hiroshi Shimada Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Japan (Background) We have performed the dissection around the SMA plexus after dividing the splenic vein, because it gains good visual field. (Purpose) To determine the indication for reconstruction after the division of the splenic vein. (Patients) From 1992 to 2002, 28 patients with pancreas head cancers who underwent the procedure of dividing the splenic vein were examined. The mean age was 65.0±8.8, pancreaticoduodenectomy was performed for 8 cases, pylorus-preserving pancreaticoduodenectomy was for 20 patients. (Results) The confluent pattern of the IMV was categolized into three types. Type A : the IMV flew into the splenic vein (N=18), typeB : the IMV flew into the portal vein (N=9), and typeC is others (N=1). The normograde stream in which the blood flow of the splenic vein has a direction to the portal vein were 8 cases. And the retrograde stream in which the blood flow is for the spleen were 5 cases. Postoperative complications were venous dilatation around the stomach and splenomegaly (4 cases (13.8%)). Of those cases, 3 cases had retrograde stream with no reconstruction and 1 case had isolated splenic vein. Pancytopenia was observed postoperatively in one case. (Conclusion) The division of the splenic vein can gain good visual field to dissect the neural plexus around the SMA. If the blood flow of the splenic vein is retrograde stream after the division of it, it is necessary to reconstruct the vein to change the blood flow to normograde stream.
Journal of Gastrointestinal Surgery
FP-255 Prediction of Sensitivity to 5-Fluorouracil by Quantitative Measurement of 5-Fluorouracil Metabolism-relating Gene Expression in Colorectal Cancer Masanori Terashima, Yutaka Hoshino, Miwa Katoh, Yuuko Satoh, Mika Hoshino, Yohko Odashima, Nobutoshi Soeta, Satoshi Ohtani, Seigo Kashimura, Shinichi Matsuyama, Michihiko Kogure, Mitsukazu Gotoh Departmentofsurgery1, Fukushima Medical University, Japan We had previously demonstrated that tumor sensitivity to 5-fluorouracil (5-FU) significantly correlated with the ratio of anabolic enzyme (orotate phosphoribosyl transferase; OPRT) and catabolic enzyme (dihydropyrimidine dehydrogenase; DPD) gene expression levels in gastric cancer. In the present study, we investigated the role of gene expression levels of 5-FU metabolism-relating enzymes (target enzyme; tymidylate synthase (TS), anabolic enzyme; OPRT, thymidine phosphorylase (TP), and ribonuclease reductase (RNR) and catabolic enzyme; DPD) on tumor sensitivity to 5-FU in colorectal cancer. Tumors were obtained from 25 patients with colorectal cancer. Gene expression levels were determined by quantitative real-time reverse transcription polymerase chain reaction. TS and DPD protein levels were also determined by ELISA. Tumor sensitivity to 5-FU was evaluated by in vitro ATP assay. Although DPD mRNA level did not correlate with DPD protein level, TS mRNA level significantly correlated with TS protein level. There was significant correlation between TP and DPD, OPRT and RNR gene expression levels and between OPRT and RNR gene expression levels. In concerning with the 5FU sensitivity, none of gene or protein level alone demonstrated significant correlation with 5-FU sensitivity. However, OPRT/DPD mRNA ratio significantly correlated with 5-FU sensitivity (R=0.66, p=0.0086). High OPRT/DPD ratio resulted in high sensitivity to 5-FU. From these results, it is suggested that tumors with high anabolic enzyme mRNA and low catabolic enzyme mRNA show remarkable sensitivity to 5-FU in colorectal cancer. Quantitative measurement of 5-FU metabolism-relating gene expression levels may be a good indicator for predicting sensitivity to 5-FU in patients with colorectal cancer.
FP-256 Singapore Experience of Obesity Surgery Thiow Kong Ti Ti Surgical Clinic/ Dept. of Surgery, National University Hospital/ National University of Singapore, Singapore Background The outcome of bariatric surgery has been well documented in large series in the West. In Asia, where obesity is less rampant, such surgery has been correspondingly less frequent, and there is a dearth of information on bariatric surgery on Asians. Method The outcome of a personal series of 40 patients who underwent gastric stapling and banding from 1987 to 2003 in Singapore are analysed. Results From 1987 to 1997, 26 patients underwent open gastric stapling (gastric bypass 4, vertical banded gastroplasty 22). Initial mean BMI was 43.3 kg/m 2. At 1/2, 1, 2, 4 and 8 years after surgery, mean BMI was 35.2, 31.9, 31.2, 31.1 and 34.1 kg/m2. Mean initial weight was 127.2 kg. % EWL was 42.2, 56.2, 56.9, 56.3 and 48.3%. From 1999 to 2003, 14 patients underwent lap banding, 11 by laparoscopy. Initial mean BMI was 42.9 kg/m2. At
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1/2, 1 and 2 years, mean BMI was 38.9, 36.6, and 32.6 kg/m 2. Mean initial weight was 122.6 kg. % EWL was 26.6, 38.8 and 59.2%. One patient, following perigastric insertion of lap band developed band slippage and gastric prolapse requiring removal. Since adopting the newer technique of combined pars flaccida and perigastric dissection in the last 6 patients, no band slippage has occured. Conclusion Our results of safety and low operative morbidity as well as pattern and magnitude of weight loss following gastric stapling and banding for morbidly obese patients in Singapore appears to be similar to Western experience.
FP-257 Gastro-colo-cutaneous Fistula Following PEG Procedure: A 12 Years Retrospective Review and How to Treat and, Hopefully, Prevent Them Anil Kumar Tibrewal1, John Crow2, John Brownlee1, Jeffrey Marks3 1 General Surgery, Huron Hospital, Cleveland Clinic Health System, 2Children’s Hospital and Medical Center of Akron, 3Hillcrest Hospital/Case Western Reserve University, USA Endoscopic gastrostomy has been widely used to provide access for supplemental enteral nutrition. One major complication is gastrocolo-cutaneous fistula. We reviewed the incidence of this complication at our hospital to see how this could be treated and,hopefully, prevented. Method: We searched 12 years (1989-2001) of medical records at children’s hospital and two years (2001-2003) at community General Hospital for CPT codes of PEG procedures and from these, selected those cases with complication of gastric/duodenal/colonic fistula. The charts were examined to confirm pertinence, and to abstract the necessary data. Results: Of the 334 children undergoing PEG in 12 years period, 5 cases of gastro-colo-cutaneous fistula were identified (1.5%). Treatment: All 5 cases were repaired surgically. At the community hospital the incidence rate was 1.7% (3/173 PEG). They were all treated by simple removal of the PEG tube (+/- endoscopy) without any surgical repair. Another interesting observation was made that this complication occurred in patient population where only transillumination test was used in selecting the site of PEG tube insertion (3/121). In patient population where both ‘Finger indentation method’ and ‘safetract techniques’ were used in addition to the transillumination test this complication was not observed (0/52). Conclusion: Gastro-colo-cutaneous fistula is a serious complication following PEG procedure. This complication could be treated by simple removal of the PEG tube in most cases. Further, this complication could be minimized with addition of finger indentation technique and safe tract technique in determining the site for PEG tube insertion.
FP-258 Operative Indications and Treatment of IPMN as an Entity of Pancreatic Cystic Tumors Masayuki Tori, Masaaki Nakahara, Hiroki Akamatsu, Shin Mizutani, Katsuhide Yoshitome, Tsukasa Ooyama, Shigeyuki Ueshima, Masahiko Tsujimoto, Kazuyasu Nakao Surgery, Osaka Police Hospital, Japan The purpose of this study is to clarify what’s important to decide
operative indications of IPMN. For the past five years, 7 IPMN were treated by resection (Group A) and 7 pancreatic cystic tumors were followed up, suggesting IPMN (Group B). These 14 cases were examined from histopathological and clinical viewpoints, that is, tumor markers, radiological imagings, cytology, and clinical courses. Postoperative histology of Group A revealed 3 IPMT and 4 IPMC. Maximum size of the former was all<2cm, all>2cm in the latter. CEA was elevated in 3 IPMC and 1 IPMT. Cytology of pancreatic juice was class III in 2 IPMC. Preoperative suspected diagnosis was correct in 5 cases (71.4%) in terms of malignancy. Operative procedures included 3 DP, 2 PpPD, and 2 TP. All IPMC were MPD type, while 3 IPMT consisted of 2 branch type and 1 mixed type. There were no cases of recurrence among IPMT. While, 2 IPMC were dead (3m, 10m) because of multiple liver metastasis, and 2 IPMC were alive (9m, 1y6m). The mean follow-up period of group B is 2y7m. 6 were alive and one dead, which remarkably increased and was finally diagnosed as anaplastic carcinoma by autopsy. The maximum tumor size of the other cases were all <2cm and no growth of the cystic lesion was detected during the observation. Conclusion: MPD-type IPMT should be taken into consideration as operative indication and the other cystic tumors can be followed up if maximum diameter is < 2cm and no increase of diameter is detected.
FP-259 Sentinel Node Navigation Surgery for Gastric Cancer Based on the Possibility of Lymph Node Micrometastasis Shunichi Tsujitani, Hiroaki Saito, Shigeru Tatebe, Akira Kondo Department of Surgery, Tottori University, Japan Immunostaining for cytokeratin has the advantage of simplicity, convenience and high sensitivity for detection of micrometastasis (MM) in cancers. The clinicopathological characteristics of MM in the lymph node should be clarified for the sentinel node navigation surgery for gastric cancer. In 84 cases with mucosal (M) cancer and 79 with submucosal (SM) cancer, two consecutive sections of lymph nodes were examined by hematoxylin-eosin (H&E) staining and immunostaining with CAM5.2 monoclonal antibody, respectively. The MM in the lymph nodes was found in 18% in M cancer and 25% in SM carncer with cancer-free nodes examined by H&E staining. Based on the finding of cluster formation of the MM in lymph nodes, SM cancer of more than 1.0 cm in superficial diameter may have a critical risk of recurrence in cases treated by procedures without nodal dissection. A high incidence of nodal MM was found in SM cancers of large size, a depressed type, lymphatic invasion, and deeper SM invasion. However, the spread of lymph nodes with MM could not be predicted by the characteristics of SM cancer. A lesser 5-year survival was shown in patients with nodal MM among those with SM cancer but not among those with M cancer. Procedures of limited surgery with sentinel node navigation strategy for SM gastric cancer should be established based on the intraoperative diagnosis of MM in the lymph node.
Abstract of 19th WC-ISDS
FP-260 Percutaneous Treatment of Bile Duct Injuries Tadashi Tsukamoto1, Kazuhiro Hirohashi2, Shoji Kubo2, Hiromu Tanaka2, Taichi Shuto2, Shigekazu Takemura2, Shigefumi Suehiro2 1 Surgery, Yodogawa Christian Hospital, 2Osaka City University Medical School, Japan Intraooperative bile duct injuries are relatively uncommon, but are a cause of significant morbidity and mortality. We repaired open biliary tract injuries found postoperatively in four patients without reoperation by percutaneous intervention. In three cases, biliary stents were placed percutaneously across the injured portion of the bile duct. For this procedure, special techniques were needed. The bile leaks resolved soon after insertion of the biliary stents. In the last patient, a biliary drain was inserted through the injured duct via the biliocutaneous fistula. In this case, biliary drainage alone resulted in resolution of bile leak. In this paper, we report percutaneous technique for treatment of the biliary injuries.
FP-261 Parameters for Patient Stratification in Terms of the Potential Prognostic Benefit by Lateral Nodal Dissection for Lower Rectal Cancer Hideki Ueno, Yojiro Hashiguchi, Hajime Fujimoto, Hirotoshi Kobayashi, Masayoshi Miyoshi, Hidetaka Mochizuki Department of Surgery I, National Defense Medical College, Japan Background: Accurate preoperative diagnosis of lateral nodal involvement (LNI) remains difficult and the indication of the lateral dissection has been controversy. Aim: To identify the parameter related to the effective selection of patients who could have a prognostic benefit from this procedure. Patients and Methods: 244 consecutive patients who underwent potentially curative surgery with lateral dissection (1985-2000) for advanced lower rectal cancer were reviewed. After stratifying patients into groups using parameters, the ratio of patients who had LNI and was alive at 5 years after surgery was calculated in their respective groups as the “efficiency index” of the lateral dissection. Results: LNI was observed in 41 patients (16.8%) and 87.8% of them had nodal involvement in some of the middle rectal artery / internal iliac artery / obturator regions (“vulnerable” regions). Five-year survival rate of patients having LNI was 41.6%; “efficiency index” was calculated as 7.0%. The group at high-risk of LNI could be selected by parameters such as grade III tumor differentiation in biopsy specimens or extensive mesorectal nodal involvement. However, the difference of the “efficiency index” between high- and low-risk groups did not make much difference (<3%), because survival rates of patients with LNI were significantly worse in the high-risk groups. Being dissimilar to above parameters, the largest LN’s diameter in the “vulnerable” regions measured on the slide (D) was irrelevant to the prognosis of patients with LNI, although it had positive correlation with LNI rate; and could stratify patients with different “efficiency index” (D<=5 mm, 2.0%; 5 =10mm, 12.1%). Conclusions: In terms of the potential prognostic benefit by lateral dissection, patients could be stratified most efficiently based on the nodal diameter in the “vulnerable” lateral regions, not the parameters related to the malignant potential of the primary tumors.
Journal of Gastrointestinal Surgery
FP-262 Analysis of Laparoscopic Cholecystectomy in a Single Institution: Drainage Tubes and Intra-operative Cholangiography (IOC) Meet Minimal Access Surgery (MAS)? Nozomi Ueno, Hiroshi Fukuda, Toru Ishikawa, Okazaki Taro, Makoto Shinzeki, Takeshi Nakamura Department of Surgery, Kakogawa Municipal Hospital, Japan Purpuse: To evaluate the efficacy and safety of techniques in laparoscopic cholecystectomy.Methods: Medical records of consecutive 414 patients attempted to laparoscopic cholecystectomy from December 1992 to December 2003 were reviewed retrospectively. Results: Out of 414 patients, 19 required conversion to open. 23 underwent laparoscopic cholecystectomy accompanied by different surgeries. The remaining 372 patients were completed entirely laparoscopically (Lap group).Intraoperative and postoperative complications occurred in 13 patients each. Intraoperative injuries to bile ducts occurred in 4 and postoperative bile leakage was in 2. IOC was conducted in 114. Naturally the operative time was significantly longer in IOC group (P<0.05). The frequency of use of anodynes within 3days from the operation did not differ significantly and postoperative hospital stay was significantly longer reversely in non-IOC group (P<0.05). Drains were inserted into the abdominal cavity in 343 patients. There was no statistical significance both in length of post operative hospital stay and in frequency of postoperative use of anodynes. Neither complication nor injury relevant to the two techniques was noted. Conclusion: IOC and drains did never induce laparoscopic cholecystectomy more invasive. Additionally IOC enables us to recognize stones or injuries in bile ducts in earliest stages, and drains also teach us bleedings or bile leakage. Regarding these advantages, we don’t need hesitate to conduct these techniques. A prospective randomized trial is needed to further validate techniques in laparoscopic surgery in order to improve its quality as MAS.
FP-263 Sentinel Nodes Detection, Including Micrometastasis using Radioisotope in Patients with Gastric Cancer Yoshikazu Uenosono, Shoji Natsugoe, Katsuhiko Ehi, Arigami Takaaki, Hideo Arima, Hiroshi Higashi, Sumiya Ishigami, Shuichi Hokita, Takashi Aikou Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medicine, Japan Background The presence of sentinel nodes has been documented for patients with melanoma and breast cancer. According to this concept, a sentinel node is the first lymph node receiving lymphatic flow from the primary tumor, and lymph node metastasis occurs first in the sentinel node. We investigated sentinel node identification, including micrometastasis for gastric cancer according to preoperative diagnosis. Methods One day prior to surgery, 99mTc-tin colloid was endoscopically injected into the submucosa of the stomach near the tumor. After resection of the stomach, radioisotope uptake in all dissected lymph nodes was measured during and after surgery. Lymph node metastasis and micrometastasis was examined immunohistochemically using anti-cytokeratin antibody. Results Sentinel nodes were identified in 101 of 106 patients. The
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rate of identification of sentinel nodes in patients with clinical T1 and cT2 tumors, except for 3 patients with technical failure, was 98.8% and 95.1%, respectively. Lymph node metastasis and/or micrometastasis was found in 28 patients. In all patients with cT1, at least one lymph node metastasis and/or micrometastases were included in the sentinel nodes. Sensitivity and accuracy for detection of sentinel nodes were 100%, and 100%, respectively. On the other hand, seven cT2 patients had false negative results. The sensitivity and accuracy for detection of sentinel nodes in cT2 patients was 46.2% and 69.6%, respectively. Conclusions Sentinel node navigation surgery appears to be clinically acceptable only in cT1 patients. A reduction of lymphadenectomy based on sentinel node detection is indicated for such patients.
FP-264 Gene Expression Level of Angiogenic Factors in Gastric Cancer - A Laser Capture Microdissection Plus RT-PCR Method for Formalin-fixed, Paraffin-embedded SamplesHiroyuki Uetake 1, Kenji Shitara 1, Kathleen Danenberg 2, Peter Danenberg2, Kenichi Sugihara1 1 Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Japan, 2Universty of Southern California, USA Background: It is suggested that vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and cyclooxygenase-2 (COX-2) have relevance to tumor angiogenesis. In this study, VEGF, TP and COX-2 gene expression in cancer cells (Ca) and in cancerous stroma (Str) separately studied by lasercapture microdissection (LCM) plus RT-PCR method using formalin-fixed and paraffin embedded (FFPE) specimen. Methods: Forty-seven specimens of primary gastric carcinoma were studied. LCM+RT-PCR method was performed (beta-actin as internal standard). Results: VEGF and TP gene expression levels in Ca were significantly higher than those in Str. Where as COX-2 gene expression level was higher in Str. A positive correlation between VEGF and TP gene expression level in Str rs=0.768, P<0.001, (Spearman rank correlation test:). Conclusions: LCM+RT-PCR technique may provide useful method for detection of gene expression levels of angiogenic factors ingastric cancer.
FP-265 A Phase I/II Study of Tegafur-Uracil (UFT) Plus Oral Leucovorin (LV) and Biweekly CPT-11 Therapy for Patients (PTS) with Metastatic Colorectal Cancer (CRC) Hiroyuki Uetake, Higuchi Tstsuro, Yasuno Masamichi, Enomoto Masayuki, Sugihara Kenichi Surgical Oncology, Graduate school, Tokyo Medical and Dental University, Japan Background: 5-fluorouracil plus leucovorin (5-FU/LV) and CPT11 therapy is recently widely used as a first line chemotherapy for the treatment of metastatic CRC. We performed a phase I study of UFT/LV, all oral administration regimen, plus biweekly CPT-11 therapy for metastatic CRC and reported that the maximum tolerated dose and the recommended dose (RD) of CPT-11 were 140 and 130mg/m2, respectively (ASCO 2003). Objectives of the present trial were to estimate the response rate (RR) of this regimen. Methods: Eligibility criteria were as follows; histologically proven CRC with measurable metastatic lesions, PS 0-2, age<80, adequate
organ functions, and written informed consent. No prior chemotherapy except adjuvant setting was allowed. UFT/LV was administered orally (UFT: 400 mg/m2/day, LV: 15 mg/body/day) on 5 consecutive days with 2 days’ rest for 4 weeks, and CPT-11 was infused at the RD in phase I trial (130mg/m2) on days 1 and 15. This schedule was repeated every 6 weeks. Results: Fourteen of 16 cases were treated by two or more courses of this regimen. Objective responses according to RECIST criteria were observed in 6 of the 15 pts (1 CR and 5 PRs. RR=40%). Six pts were treated without hospitalization, and for other pts 8-14 days of hospitalization in each course was necessary because of the adverse effects. Conclusions: High RR and mild toxicity profile of UFT/LV plus biweekly CPT-11 therapy may be favorable for outpatient clinic.
FP-266 A Recent Innovation in the Surgical Treatment for Hilar Cholangiocarcinoma Michiaki Unno, Michiaki Unno, Yu Katayose, Toshiki Rikiyama, Masaya Oikawa, Kuniharu Yamamoto, Tohru Onogawa, Seiki Matsuno Department of Surgery, Tohoku University, Japan Since hilar cholangiocarcinoma shows abnormalities in liver function secondary to obstructive jaundice, surgical treatment is performed in many patients. Although the gold standard of surgical treatment was hepatic lobectomy combined with resection of the caudate lobe, major resection had been restricted by the functional volume of the remnant liver. Because of the induction of preoperative percutaneous transhepatic portal embolization (PTPE), progress in diagnostic imaging represented by multi-detector row CT (MDCT), and improvements in operation techniques and postoperative management, the surgical strategy for hilar cholangiocarcinoma is becoming simplified. In this paper, we describe the results of our surgical treatment for hilar choloangiocarcinoma and discuss a recent innovation in the surgical treatment. [Patients and Methods] Seventy-seven patients with hilar cholangiocarcinoma underwent surgery at Tohoku University Hospital during the 16 years from 1989 to 2004 (55 men, 22 women). The therapeutic outcomes in the 77 patients were compared according to the period: 32 patients in the early period (1989 to 1996) and 45 patients in the late period (1997 to 2004) when PTPE and MDCT were employed. [Results] The cumulative 1, 3, and 5-year survival rates were 81%, 39% and 33%, respectively. In the late period, the rate of hepatic lobectomy increased to 84% from 66%, and the rate of curative resection increased to 64% from 56%. The 1, 3, 5-year survival rates in the late period were 90%, 56%, and 43%, respectively, and significantly improved (p<0.05) compared with the early period (72%, 24%, 16%). Especially, the 1, 3, 5-year survival rates of the patients who underwent curative resection in the late period were 100%, 85%, and 65%, respectively, and showed a greater improvement in outcome. [Conclusions] The surgical strategy for hilar cholangiocarcinoma has been simplified by progress in diagnostic imaging, such as MDCT, and improvements in surgical techniques, such as PTPE. These recent innovations brought about an improvement in the outcomes of patients with hilar cholangiocarcinoma.
Abstract of 19th WC-ISDS
FP-267 Prediction of Effects and Side Effects of Fluoropyrimidines Administered for Advanced Gastric Cancers and Criteria of Drug Selection Hisashi Usuki, Shinichi Yachida, Masanobu Hagiike, Kunihiko Izuishi, Fuminori Goda, Setsuo Okada, Hajime Maeta The First Department of Surgery, Kagawa University, Faculty of Medicine, Japan It was evaluated the relationship between the effects and side effects of some fluoropyrimidines for 161 advanced and recurrent gastric cancer cases and the contents of Thymidylate Synthesis (TS), Dihydropyrimidine Dehydrogenase (DPD) and Thymidine Phosphorylase (TP) in tumor and normal tissue. A) The cases with high DPD expression had poorer prognoses than those with low expression in the cases having fluoropyrimidines except S-1. But there was no such difference in the cases having S-1. B) DPD level in the tumor tissue of the cases without the effect of anti-cancer drug was higher than that of the cases with the effect of the drug, in the cases who having fluoropyrimidines except of S-1. C)The DPD expression of the normal gastric tissue in the cases having side effect because of S-1 was lower than that in cases without side effect. The prognoses in the cases having 5’DFUR were better than those having tegafur+uracil in the cases of higher TP expression in tumor tissue. And the criterion of the drug selection for the gastric cancer cases was tried to create.
FP-268 Characterization of the CXCR4/SDF-1 ChemokineChemokine Receptor Axis in Colorectal Neoplasia Vladimir Alexander Valera1, Beatriz Walter2, Mikako Kawahara1, Naoyuki Yokoyama1, Yu Koyama1, Haruhiko Okamoto1, Tsuneo Iiai1, Katsuyoshi Hatakeyama1 1 First Department of Surgery, 2Third Department of Anatomy, Niigata University, Japan Purpose: To elucidate the potential role of the CXCR4/SDF-1 chemokine-chemokine receptor axis in colorectal neoplasia. Methods: CXCR4 and SDF-1 mRNA levels in tumor and normal tissues from 56 patients who underwent resection for colorectal cancer (CRC) at our institution were evaluated by Real-Time PCR. Differences in gene pathways interactions and proliferative and apoptotic status of tumors was investigated by low-density microarray analysis and immunohistochemistry. Results: CXCR4 was found to be downregulated in 66% of cases (mean T/N ratio=0.54; p=0.005) whereas SDF-1 showed no significant change between tumor and normal tissues (mean T/N ratio=1.05; p=0.22). A higher level of CXCR4 downregulation for advanced T and N categories or TNM status was found. Amongst 90 genes, 20 (22%) were shown to have a statistically significant (p<0.01) differential expression between cases with CXCR4 down and up regulation. Genes involved in kinase pathways were found to be the most differentially regulated between groups, with differences ranging from 2 to 10 fold in change (p=0.01-0.03). Also, different proliferative and apoptotic characteristics for CXCR4 status were found. Conclusion: CXCR4 was found to be mostly downregulated in CRC without change in SDF-1 levels. Our results have also shown that an alteration in the protein kinase signaling pathway is the main event related to the change in CXCR4 status and that this follows proliferative and apoptotic changes. CXCR4 regulation
Journal of Gastrointestinal Surgery
can be related to early events in the malignant transformation and tumor progression of CRC.
FP-269 Clinical Relevance of the Standardized Uptake Value (SUV) in Staging Esophageal Cancer with FDG-PET Henderik Leendert Van Westreenen1, David P. Cobben1, Hendrik Van Dullemen2, Pieter Jager3, Henk Groen4, John Plukker1 1 Surgery, 2Gastroenterology, 3PET-center, 4Office for Medical Technology Assessment, Groningen University Medical Center, The Netherlands Positron emission tomography (PET) with 18-F-fluorodeoxyglucose (FDG) has been accepted in staging esophageal cancer. The increased glucose metabolism is the rationale behind FDG uptake in malignant cells. The tissue glycolysis level can be quantified by the accumulation of FDG. The most commonly used parameter to assess FDG accumulation in clinical FDG-PET imaging is the standard uptake value (SUV). The aims of this study were to investigate the relation between SUV and stage of disease and whether SUV can predict resectability and survival in patients with esophageal cancer. The studied population consisted of 40 patients with cancer of the esophagus or gastro-esophageal junction. Patients were included from January 2001 to December 2002. After measuring the SUV, patients were retrospectively divided into two groups using the median SUV as cutoff value. SUV values were evaluated according to the stage of disease, histology, age, sex, and resectability. Survival was analyzed by using the log-rank test and Cox regression analysis. The median SUVmax was 6.7(range 1.8-19.2) and median SUVmean was 5.7(range 1.4-15.7). SUVmax and SUVmean differed significantly for tumor stage and resectability. The mean survival of patients with SUVmax <6.7 and SUVmean <5.7 was 613 days compared to 262 days for patients with SUVmax >6.7 and SUVmean >5.7 (p=0.016). Cox regression analysis did not reveal a significant impact of SUV on survival independent of resectability. Conclusions: SUV can be used to predict resectability, however SUV is not an independent factor to assess the survival in patients with esophageal cancer.
FP-270 Comparison of FLT-PET and FDG-PET in the Visualization, Staging and Proliferation of Esophageal Cancer Henderik Leendert Van Westreenen1, David Cobben1, Pieter Jager2, Hendrik Van Dullemen 3, Jelle Wesseling 4, Philip Elsinga 2, John Plukker5 1 Surgery, 2PET-center, 3Gastroenterology, 4Pathology, 5Surgery, Groningen University Medical Center, The Netherlands Background: 18F-fluoro-2-deoxy-D-glucose (FDG) Positron Emission Tomography (PET) has gained acceptance for staging of esophageal cancer. However, FDG is not tumor-specific and falsepositive results may occur by accumulation of FDG in benign tissue. The new tracer 18F-fluoro-3’deoxy-3’-L-fluorothymidine (FLT) might not have these drawbacks. The aim of this study was to investigate the feasibility of FLT-PET for the detection and staging of esophageal cancer compared with FDG-PET. Furthermore, correlation between FLT uptake and proliferation of the tumor was investigated.
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Methods: 10 patients with biopsy proven cancer of the esophagus or gastroesophageal junction were conventionally staged with computed tomography, endoscopic ultrasound and ultrasound of the neck. In addition, a whole-body FLT-PET and FDG-PET were performed. Standardized uptake values were compared with proliferation expressed by Ki-67 positivity. Results: FDG PET was able to detect all esophageal cancers whereas FLT PET visualized the tumor in 8 patients. Both FDG PET and FLT PET detected lymph node metastases in only 2 out of 8 patients. FDG PET detected one cervical lymph node that was missed on FLT PET whereas FDG PET showed uptake in benign lesions in 2 patients. The uptake of FDG (median SUVmean of 6.0) was significantly higher than that of FLT (median SUVmean of 3.4). Neither FDG SUVmax nor FLT SUVmax did correlated with proliferation in the linear regression analysis. Conclusion: In this study, uptake of FDG in esophageal cancer is significantly higher compared with FLT uptake. Therefore, FLT scans will show more false-negative findings and fewer false-positive findings than do FDG scans.
FP-271 Three Stage versus Transhiatal Resection Forcarcinoma of Oesophagus Tiku Vinod, Dalteet Singh, Satish Jain Surgery and Surgical Oncology, Oswal Cancr Hospital, Ludhiana, Punjab, India Purpose: To determine the preferred procedure of resection, three stage vs. transhiatal, in carcinoma of oesophagus by observing the Peri operative mortality and morbidity and also the outcome of surgery in terms of relief of symptoms, disease free interval and survival, Retrospectively. Summary back-ground: Despite refinements of surgery, advanced anaesthesia and improved pre and post operative care little has been gained in long term survival of patients suffering from of ca oesophagus. The best surgical approach for resection of ca. oesophagus continues to be open to debate. In modern era of overall improved patient care, morbidity following extended surgery is no longer an issue. Method: Ours is a retrospective study of oesophagectomy done in three years, 2001 to 2004, Overall 42 patients have been operated. (14 three stage and 28 transhiatal). The type, extent and other characters were similar in both groups. The type of resection was determined by surgeon preference. The clinical, pathological and follow up data was compiled. Results / Conclusion: All patients had a lesion in middle or lower oesophagus .The cell type was predominantly squamous, 76%. Mortality was 7% in both groups while, interestingly, morbidity was also similar in both groups i.e. 35%. In a mean follow up of 22 months Trans hiatal group had a survival of 50% while those who underwent three stage resction had it as 56%. we believe that three stage resection has the advantages of transthoracic enbloc resection and that of neck anastomosis.
FP-272 Impact of Ductal Resection Margin Status on Long-term Survival in Patients Undergoing Resection for Extrahepatic Cholangiocarcinoma Toshifumi Wakai, Yoshio Shirai, Tetsuya Moroda, Naoyuki Yokoyama, Pauldion Venzon Cruz, Katsuyoshi Hatakeyama Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Japan PURPOSE: To clarify whether residual carcinoma in situ at ductal resection margins differs biologically from residual invasive ductal lesions in patients undergoing resection for extrahepatic cholangiocarcinoma. METHODS: A retrospective analysis was conducted of 114 patients with extrahepatic cholangiocarcinoma. In 84 patients who underwent resection the ductal resection margin status was classified into negative (n = 64), positive with carcinoma in situ (n = 11), or positive with invasive carcinoma (n = 9). The median follow-up period was 105 months. RESULTS: Ductal margin status was a strong independent prognostic factor by univariate (P = 0.0002) and multivariate (P = 0.0039) analyses. The outcome after resection was comparable between patients with negative ductal margin (median survival time, 45 months; cumulative 10-year survival rate, 40%) and those with positive ductal margin with carcinoma in situ (median survival time, 99 months; cumulative 10-year survival rate, 23%; P = 0.4742). In patients with positive ductal margins, outcome was significantly better in patients with carcinoma in situ than in those with residual invasive carcinoma (median survival time, 21 months; cumulative 5-year survival rate, 0%; P = 0.0003). Of 11 patients with residual carcinoma in situ, 4 died of local recurrence and the median disease-free survival was 89 months. CONCLUSIONS: Among patients undergoing resection for extrahepatic cholangiocarcinoma, those with residual carcinoma in situ may survive significantly longer than those with residual invasive ductal lesions. This suggests that the natural history of residual carcinoma in situ differs from that of residual invasive ductal disease in extrahepatic cholangiocarcinoma.
FP-273 Extended Hepatectomy and Hepatopancreatoduodenectomy for Advanced Gallbladder Carcinoma Junji Washizu, Yuji Kaneoka, Masatoshi Isogai, Toru Harada, Kiyoshi Aikawa, Akihiro Yamaguchi Department of Surgery, Ogaki Municipal Hospital, Japan Objective: To evaluate the surgical outcome of extended surgery for advanced gallbladder carcinoma. Patients and Methods: Sixty-eight consecutive cases were studied, 46 female and 22 male, average age of 69.6, whose gallbladder carcinoma was resected between 1994 and 2004 at Ogaki Municipal Hospital. The standard procedure for carcinoma not infiltrating the subserosal layer was cholecystectomy, whereas infiltration to or beyond the subserosal layer required segmentectomy 4a and 5 with lymph node dissection. Extended surgery was performed when invasion to the liver, hepatoduodenal ligament, and/or lymph node metastasis were present. Results and Discussion: Sixteen patients were treated with cholecystectomy, 28 with hepatectomy, and 24 with pancreatoduodenectomy. The extended surgery group included 6 extended right
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hepatectomy, 7 combined segmentectomy 4a and 5 and pancreatoduodenectomy, and 12 combined extended right hepatectomy and pancreatoduodenectomy. Hepato-ligamento-pancreatoduodenectomy was performed for 4 patients. Overall survival rate for the 68 patients was 68.2% at 1 year, 47.3% at 3 years, and 30.7% at 5 years from surgery, respectively. For the extended surgery group, the overall survival rate was 62.6% at 1 year, 37.9% at 3 years, and 11.9% at 5 years from surgery, respectively, which was significantly lower than the remaining 43 cases. When cases with residual tumor at resection were excluded, the overall survival rate was 80.4% at 1 year, 57.5 % at 3 years, and 30.7% at 5 years, which were similar to the standard surgery group. Extensive application of extended surgery may benefit selected patients who may otherwise be treated with insufficient resection.
FP-274 Expression Genomics of Rectal Cancer: Molecular Classification and Prediction of Preoperative Radiotherapy Response for Low Rectal Cancer by DNA Microarray Toshiaki Watanabe1, Yasuhiro Komuro1, Giichiro Tsurita1, Tomomichi Kiyomatsu 1, Takamitsu Kanazawa 1, Tomohiro Tada 1, Yoshihiro Kazama1, Junichiro Tanaka1, Tetsuichiro Muto2, Hirokazu Nagawa1 1 Surgical Oncology, University of Tokyo, Japan, 2Cancer Institute Hospital, Japan Purpose: In the treatment of rectal cancer, preoperative radiotherapy has been reported to be effective to reduce local recurrence rate as well as to preserve urinary and sexual function. However, the effect of radiotherapy differs between individuals. Recent advances in expression genomics have enabled the use of DNA microarray to profile gene expression of various cancers. These expression profiles may be suitable for molecular classification and prediction of treatment response. In the present study, we examined if the expression genomics could be used to tailor treatment of preoperative radiotherapy for individual patient with rectal cancer. Methods: Thirty patients with rectal cancer undergoing preoperative radiotherapy and surgery were examined. Patients were divided into three groups based on their response to preoperative radiotherapy. Response to radiotherapy was evaluated histologically in surgically resected specimens and was classified as effective (Group 1), slightly effective (Group 2) or not effective (Group 3). We examined the expression profiles in DNA microarrays that contained 12,558 features that correspond to human transcripts and compared them between three groups. Results: Among 12,558 genes, expressions of 1,467 genes were significantly different between specimens. Considering the response to preoperative radiotherapy in each specimen from three groups, we further selected 28 genes by leave-one-out method, which included PTGS2 (hCox-2), LCN2 and S100A8. By these genes, we could predict response to radiotherapy from their expression profiles. Conclusions: Gene expression profiling by DNA microarray may be used for further molecular classification to predict treatment response in rectal cancer.
Journal of Gastrointestinal Surgery
FP-275 Retrospective Analysis of the Prognosis of Patients with Gallbladder Carcinoma Following Radical Resection, and a Trial of Sentinel Lymph Node Biopsy and Systematic Partial Hepatectomy Hiroshi Yagi, Motohide Shimazu, Shigeyuki Kawachi, Minoru Tanabe, Kouichi Aiura, Go Wakabayashi, Masakazu Ueda, Masaki Kitajima Surgery, Keio University School of Medicine, Japan Purpose: The aim of this study is to evaluate factors influencing the outcome of patients with gallbladder carcinoma following radical resection, and to identify patients who may benefit from radical surgery. Methods: Sixty-one patients (12 pT1, 28 pT2, 18 pT3, 3 pT4) who underwent surgical resection for gallbladder carcinoma were retrospectively reviewed. Correlations between survival and factors such as the extent of lymph node metastasis, the status of infiltration of the hepatoduodenal ligament (Binf) and liver bed (Hinf), and other pathologic factors were analyzed. Five of the 61 patients underwent sentinel lymph node (SN) biopsy, including 4 who also underwent ICG injection into the cystic artery for systematic partial hepatectomy. Results: Univariate analysis showed that site, depth of invasion, lymph node metastasis, pathological stage, lymphatic invasion, venous invasion, perineural invasion, Binf and Hinf were significant prognostic factors. There were 18 advanced cases (15 pT2, 2 pT3, 2 pT4) who survived more than 2 years after surgery. Only one of these patients was classified as Binf(+). Eleven patients underwent extended cholecystectomy (including 3 with bile duct resection), and 4 underwent hepatectomy (including 3 with pancreatoduodenectomy). The patients who underwent SN biopsy and ICG injection prior to surgery are still alive. Conclusions: Several factors were identified that have prognostic significance for survival in patients with gall bladder carcinoma. It is suggested that radical surgery may be indicated for selected patients with advanced gallbladder carcinoma.
FP-276 Experience with Development and Clinical Use of a Small Opener for Laparoscopically Assisted Surgery Hideo Yamada1, Eiji Kanehira2, Juri Kondo1, Koichi Nakajima1, Masahiko Sato1, Takahiro Kinoshita1, Shigetaka Sazuki1, Tomorou Hishiki1 1 Endoscopic Surgery Center, Toho University Sakura Hospital, Japan, 2Endosurgery Laboratory Kanehira, Japan Objective) Organ extraction and anastomosis in the event of laparoscopic colectomy and gastrectomy is performed in direct view from a small opening; an instrument is needed to re-insufflate the peritoneal cavity and perform laparoscopy again after anastomosis is complete. Thus, the authors jointly developed a small opener for laparoscopically assisted surgery (Multi Flap Gate : afterwards, MFG) intended for protection and effective opening of the peritoneal wound and simple re-insufflation in laparoscopically assisted surgery. (Subjects and Methods) There are four aspects: a surface ring, an intraperitoneal ring, a draft protection sheet, and a tension belt; the site is opened further by pulling the latter. Reinsufflation can be performed by attachment of a converter to the ring. In addition, there is a small hole in the center and it can be
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used as a port through insertion of a cannula here. (Results) The MFG was easily attached in all cases and retraction strength was favorable. Damage to the MFG during surgical handling and trouble with regard to manipulation was not seen. The shape of the opening was almost square; extraction of organs and surgical manipulation in direct view were favorable (Conclusion) The MFG has exceptional opening strength and is an optimal instrument for laparoscopically assisted surgery that allows re-insufflation. A favorable surgical field was ensured by this instrument and laparoscopically assisted surgery can be performed; it was also useful for prevention of wound infection and cancer cell implantation.
FP-277 H.pylori Infection Related to Serum Pepsinogen and Interleukin-1 β- 511 Polymorphisms are Independent Risk Factors for Gastric Cancer in Thai Sirikan Yamada1, Takeshi Matsuhisa2, Luksana Makonkawkeyoon3, Suparp Chaidatch3, Somphon Phraephan3, Nobutaka Yamada4, Shunji Kato5, Masaru Miki5, Takashi Tajiri5, Norio Matsukura5 1 Surgery, Faculty of Medicine, Chiang Mai University, Thailand, 2 Department of Gastrointestinal Endoscopy, Tama-Nagayama Hospital of Nippon Medical School, Japan, 3Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, 4Department of Pathology, Nippon Medical School, 5First Department of Surgery, Nippon Medicl School, Japan Purpose: Recently, IL-1 β- 511 polymorphisms and Helicobacter pylori were suspected to relate to low acidity in gastric cancer. Therefore, we further study for the relation of these factors in Thai. Methods: Between 2001-2003, 56 cancer patients and 111 non cancer volunteers who underwent endoscopic examination with three point biopsy were informed consent under the ethical permission. They were collected the blood samples and biopsy tissues. We performed IL-1 β- 511 polymorphisms and tested the serum pepsinogen I and II level by radioimmunoassay technique. H. pylori antibody and tissue pathology were confirmed in both group. The p values of less than 0.05 were considered statistically significant. Results: We found significant difference of pepsinogen I/II ratio between cancer and non cancer with atrophic gastritis group, p = 0.02 , odds ratio= 2.35 (95% CI, 1.14-4.85). There was positive H. pylori antibody more frequent than negative H. pylori antibody in cancer cases, p= 0.005, odds ratio= 2.946 (95% CI, 1.4-6.39). However, only 5 cancer patients have positive H.pylori antibody with low serum pepsinogen I/II. There was no significant difference for genotype distribution, T/T, C/T,and C/C of IL-1 β polymorphisms between both groups. C/T and C/C genotype in cancer group were found more frequently than in atrophic gastritis group, but this genotype does not neither significantly relate to low serum pepsinogen I/II nor to positive H.pylori antibody. Conclusions: We suspect that Helicobacter pylori infection and low serum pepsinogenI/II ratio do not relate to Interleukin-1β- 511 polymorphisms, which is independent risk factor for gastric cancer.
FP-278 Pancreatic Juice Cytolotogy in IPMNS of the Pancreas Koji Yamaguchi, Hiroyuki Konomi, Masafumi Nakamura, Atsushi Sugitani, Kazuhiro Mizumoto, Masao Tanaka Department of Surgery and Oncology, Graduate School of Medical Scienes, Kyushu University, Japan Background: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a disease ranging from adenoma to carcinoma in situ and further to invasive carcinoma and surgical strategy is different by the grades of dysplasia. Methods: Preoperative pancreatic juice cytology in IPMNs was reviewed in 76 patients with IPMNs who underwent surgical resection. Results: The IPMN was benign in 51 patients, borderline in 13 and malignant in 12. The sensitivity of pancreatic juice cytology in malignant IPMN was 33% (4/12). In four with the 51 benign IPMNs, pancreatic juice cytology was positive for malignancy. One of the four was considered to be an overdiagnosis of cytology, but the other three were considered to be a consequence of accompanying non-invasive pancreatic carcinoma (two) or invasive ductal carcinoma (one). When IPMN was of main duct type, the sensitivity of the cytologic diagnosis in malignant IPMNs was 36%, which was significantly higher than 0% in malignant IPMNs of branch type (P=0.02). The sensitivity of the cyotologic diagnosis of malignant IPMN was 33% in the presence of the “mucinhypersecreting” condition and 0% in the absence (P=0.02). When IPMN shows mural nodules, the sensitivity of pancreatic juice cytology for malignant IPMNs was 22%, which was higher than 13% in the absence. Conclusions: These findings suggest that pancreatic juice cytology in IPMNs is useful especially in the main duct type with mucin hypersecretion and mural nodules. When the diagnosis of pancreatic juice cytology is malignant in otherwise benign-looking IPMNs, coexistence of pancreatic carcinoma should be considered.
FP-279 Expression of HER2/Neu in Gallbladder Carcinomas and its Implication for Therapy Masahiko Yamaguchi, Tetsuro Nakamura, Yoshihiro Yamamura, Shuhei Takahashi, Takashi Okuyama Surgery, Dokkyo University, School of Medicine, Koshigaya Hospital, Japan Background: It is known to be effective to treat HER2/Neu-overexpressing advanced cancer with a monoclonal antibody against HER2/Neu (trastuzumab). HER2/Neu is shown to play an essential role in carcinogenesis of gallbladder in a study using transgenic mice. Therefore, HER2/Neu expression was immunohistochemically examined in 42 cases of gallbladder carcinoma to test the availability of trastuzumab therapy. Patients and methods: Forty-two cases of gallbladder carcinoma, which were operated in our institution from 1987 to 2004, were subjected to immunohistochemical staining for HER2/Neu. Positivity of staining was compared to pathology, stage, and prognosis. Results: Twenty-seven cases (64%) were positive and 15 were negative. Pathological diagnosis revealed 19 cases of well-differentiated adenocarcinoma, 7 cases of moderately-differentiated adenocarcinoma, and 1 case of poorly-differentiated adenocarcinoma in positive cases, whereas 5 cases of well-differentiated adenocarcino-
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ma, 3 cases of moderately-differentiated adenocarcinoma, 7 cases of poorly-differentiated adenocarcinoma in negative cases. Stage III and IV positive or negative cases were all dead or recurrent. Four out of 12 (33%) stage II positive cases were dead or recurrent whereas one out of 5 (20%) stage II negative cases were dead or recurrent. Conclusion: We have shown that positive expression of HER2/Neu was recognized more than 60% of gallbladder carcinoma and mostly in highly-differentiated cancer, and appeared to indicate poor prognosis in stage II cases. It is suggested that trastuzumab may be an effective drug for advanced gallbladder carcinoma which highly expresses HER2/Neu, and immunohistochemical staining for HER2/Neu may predict prognosis of gallbladder carcinoma in stage II cases.
nonC(s), seven B&C, and 26 unknowns. Mortality rate was 7.3% (10 cases), and 2.2% (3 cases) died of postoperative liver failure. Comparison of 66 cases (32.7%) which performed hepatectomy more extended than a standard was performed to 136 cases (67.3%) to which the operation was carried out according to the Makuuchi criteria. NO significant difference was seen among both groups in the mortality, cancer-related death, hepatic insufficiency death, and also about the rate of blood transfusion. Although there was no difference in the rate of recurrence between the cases which became tw positive and the negative cases, histologically, a significant difference was accepted during the survival. [Conclusion] We concluded that residual liver capacity can be maintained as much as possible in the range even with minimum surgical margin.
Short Term Results of Laparoscopic versus Open Colorectal Cancer Surgery using Computer Chart System Shigeki Yamaguchi, Mitsuyoshi Ota, Hirofumi Morita, Masayuki Ishii Colon and Rectal Surgery, Shizuoka Cancer Center, Japan
The Role of Infliximab for Treatment of Refractory Anorectal Fistulas with Crohn’s Disease Tetsuo Yamana1, Torao Tanaka2, Masakazu Takazoe2, Rikisaburo Sahara1, Junichi Iwadare1 1 Proctology, 2Gastroenterology, Social Health Insurance Hospital, Japan
Purpose: To assess short term results of laparoscopic (lap) and open colorectal cancer surgery using computer chart system. Method: Using computer chart system, we can automatically order infusion, diet, X-ray, etc. by one click according to clinical pathway. We planned to start diet and discharge on 3rd and 8th day in lap, 4th and 10th day in open. 142 consecutive patients who underwent curative resection of colon and upper rectal cancer from Sep, 2002 to Dec, 2003 comprised this study group. Operating time, blood loss and transfusion, soft diet start, postoperative hospital stay, and complication were assessed. Results: Patients were divided in 75 lap and 67 open. Stage of each group was lap; 0: 2, I: 34, II: 22, III: 17, open; 0: 1, I: 13, II: 28, III: 25, respectively. Mean operating time was 236 min. in lap and 169 in open. Mean blood loss count was 66g in Lap and 226 in Open. Blood transfusion underwent for non in Lap and 11.9% in Open. Median days of soft diet start and hospital discharge were POD3 and 8 in lap, POD4 and 10 in open. Lap patients of 43% successfully discharged within POD8 in early phase (Sep/02 - Apr/03), and 80% in late phase (Mar/03 - Dec/03). Postoperative complications occurred in 14.7% in lap and 41.8% in open (Lap/Open: anastomotic leak:2/5, ileus:4/7, wound infection:3/8).
FP-281 Appropriate Surgical Treatment of Hepatocellular Carcinoma Naoto Yamamoto 1, Hiroshige Saito 1, Manabu Shiozawa 1, Ten’i Godai1, Yukio Sugimasa1, Toshio Imada2 1 Department of Surgery, Kanagawa Cancer Center, 2Yokohama City Center Hospital; Digestive Disease Center, Japan [Purpose] To define the appropriate range of resection of hepatocellular carcinoma (HCC). [Methods] A prospective HCC database was reviewed to identify the patients with HCC who were surgically managed. Log rank and chi-square analysis were used to identify factors predictive of morbidity, mortality, survival and recurrence. [Results] Over a 17-tear period, 194 patients were identified. The surgical resection rate was 27.2% (at the national average, it is 29.2%). HBV related was 34 persons, 103 HCV(s), 24 nonB
Purpose: The aim of this study was to clarify the efficacy of infliximab for the CD patients with refractory anorectal fistulas. Methods: CD patients with complicated anal fistulas, who had initially undergone surgical treatment, were treated with three doses (0, 2, and 6 weeks) of infliximab (5mg/kg). Patients were followed up with a mean follow-up of 9.7 months (range, 3-15) during regular office visits or by telephone interviews. Clinical responses were recorded; as remission (defined as no or minimum pain and discharge) or relapse (defined as aggravated pain and increased discharge). Patients who experienced significant adverse events during infusions were excluded. Results: Twenty patients (9 male) with a mean age of 29 (range, 16-42) were included. Initial operations were: open drainage; 2, and seton placement; 18. The types of anorectal fistulas were: trans-sphincteric; 8, suprasphincteric; 7, and rectovaginal; 5. Initial remission was achieved in all patients immediately after the infusions. Prolonged remission was observed in 9 patients (45%, transsphincteric; 3, suprasphincteric; 4, rectovaginal; 2) with a mean follow-up of 9.6 months. In the remaining 11 patients (55%), anorectal sepsis relapsed following the initial remission. The mean durations until the relapses were trans-sphincteric (5); 7.0 months; suprasphincteric (3); 2.7 months, rectovaginal (3); 6.7 months. Seven of the 11 patients needed additional surgical intervention. Conclusions: Three doses of infliximab infusions were initially effective for the CD patients with refractory anorectal fistulas. However, approximately half of the patients subsequently experienced the relapse of anorectal sepsis within a short period.
FP-283 Study of mRNA Expression of TS, DPD and OPRT in Liver Metastatic Foci Associated with Colorectal Cancer Takao Yamane, Akiyoshi Seshimo, Ryuta Fujii, Kazuki Aratake, Michio Itabashi, Noriyasu Shirotani, Shingo Kameoka Surgical Department 2, Tokyo Women’s Medical University, Japan Purpose: This study was conducted for the purpose of measuring
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mRNA levels of TS, DPD and OPRT in liver metastatic foci associated with colorectal cancer in order to retrospectively investigate and predict the correlation with prognosis. Methods: In this study, we compared mRNA expression of TS, DPD and OPRT between cancer patients who had survived for five years or more and those who had survived for less than five years using specimens embedded in paraffin by the laser capture microdissection method obtained from liver metastatic foci associated with colorectal cancer. The subjects consisted of 48 cases of surgical excision of colorectal cancer with liver metastasis who underwent surgery in this department from February 1988 to April 2003. Results: The mRNA expression levels among long-term survivors consisted of 1.18±0.71 for TS, 0.21±0.12 for DPD and 1.09±0.75 for OPRT. On the other hand, mRNA expression levels among short-term survivors (less than 5 years) consisted of 2.20±2.99 for TS, 0.33±0.28 for DPD and 1.15±0.58 for OPRT. Conclusions: The above findings indicated that lower values were demonstrated for TS and DPD among long-term survivors as compared with short-term survivors, while there were no significant differences observed between the two groups with respect to OPRT.
FP-284 Plasma Fibrinogen Level is Positively Correlated with the Lymph Node Metastasis in Advanced Gastric Cancer Hiroharu Yamashita, Joji Kitayama, Hironori Yamaguchi, Akihiro Sako, Makoto Ishikawa, Masahiro Asakage, Jun Yamada, Shoichi Kaisaki, Hirokazu Nagawa Surgical Oncology, University of Tokyo, Japan Although a positive association between malignancy and abnormal hemostatic factors is a well-know evidence for a century, clinical role of fibrinogen on cancer patients remains to be determined. We retrospectively examined the association between lymph node metastasis and preoperative plasma fibrinogen level in 884 patients with gastric cancer, who underwent gastrectomy.In patients with early gastric cancer, plasma fibrinogen level was not correlated with lymph node metastasis. However, in patients with advanced gastric cancer, the rate of lymph node metastasis was significantly higher in patients with high plasma fibrinogen level (fibrinogen>310) (p<0.0001). Multivariate analysis showed that high plasma fibrinogen level was an independent risk factor for lymph node metastasis (odds ratio 2.54, p<0.0001) as well as tumor size, serosal invasion, and lymphatic involvement. In addition, level of plasma fibrinogen was significantly correlated with the patients with pathological N stage (the average level of each groups; pN0 293, pN1 328.8, pN2 335.5, pN3 375.9, p<0.0001). High plasma fibrinogen level might be a useful predictor of lymph node metastasis and N stage in patients with advanced gastric cancer.
FP-285 Limited Hepatectomy Combined Portaazygous Devascularization and Splenectomy for Patients with Hepatic Cancer Accompanied by Portal Hypertension Ning Yang, Guangshun Yang, Junhua Lu Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China Objective To evaluate the effects, feasibility and indications of
limited hepatectomy combined portaazygous devascularization and splenectomy for patients with hepatic cancer accompanied by portal hypertension. Methods A retrospective analysis was conducted in 67 cases of patients with hepatic cancer accompanied by portal hypertension who had been undergone limited hepatectomy combined portaazygous devascularization and splenectomy. Results There were 3 cases died during 30 days after operations. The total postoperative complications developed in 26.9% (18/67). Postoperative upper digestive tract hemorrhage developed in 23.0% (14/61). The absolute survival rate in 1,3,5 years was 77.6% (45/58), 41.2% (14/34), 35.7% (5/14) respectively. By the end of April 2003, 28 patients were died during the follow-up period. Besides 3 cases died during 45 days after operations, there were 15 cases (53.6%) died of cancer recurrence or metastasis, 3 cases (10.7%) of upper digestive tract hemorrhage and 5 cases (17.9%) of liver function failure. There were 2 cases died of other causations. Conclusion In precondition of propriety indications, perfect operative procedures and proper perioperation treatments, limited hepatectomy combined portaazygous devascularization and splenectomy for patients with hepatic cancer accompanied by portal hypertension is safe and feasible. The operations could improve the total effects of hepatic cancer. (Keywords) carcinoma, hepatocellular; portal hypertesion; liver tumor/surgery; retrospective analysis.
FP-286 Clinicopathological Examination of the Pancreatic Invasive Ductal Carcinoma Developed in the Remnant 7 Years after Curative Pancreatoduodenectomy for Pancreas Cancer Chiaki Yasui1, Tsukasa Aihara1, Hidenori Yoshie1, Hiroki Matsuoka1, Masao Mitsunobu1, Ayako Sugihara2, Naoki Yamanaka1 1 Surgery, Meiwa General Hospital, Japan, 2Meiwa General Hospital, Pathology, Japan Background: Pancreatic intraepithelial neoplasia(PanIN), frequently associating with chronic pancreatitis, has been thought to be a precursor lesion of invasive ductal carcinoma (IDC). We experienced a patient in whom IDC developed in the remnant pancreas 7 years after curative pancreatoduodenectomy (PD) for IDC with PanIN. Case: The patient, 61-year-old woman, had no history of cigarette smoking, alcohol abuse or hyperglycemia. In June 1995, obstructive jaundice developed, caused by pancreatic head tumor. After biliary drainage, pylorus preserving pancreatoduodenectomy (PpPD), reconstructed by gastro-pancreatostomy, was performed. As intraopertive pathology of the pancreatic stump showed carcinoma in situ (CIS), we additionally removed the pancreatic stump, 5mm long. The main tumor was well differentiated IDC with infiltration of lymph ducts and perineural invasions. Moreover, permanent pathology of additionally resected stump showed PanIN, and one month after initial surgery, further additional resection (25mm long) was performed. This was compatible with papillary epithelial growth and goblet cell metaplasia (so call PanIN 2). Final pathologic stage was Stage 2B (pT3, pN1, pM0). In January 2003, 7 years after intial surgery, serum CA 19-9 value was elevated, and CT scan showed mass shadow in remnant pancreas. In August, we performed total remnant pancreatectomy with total gastrectomy and splenectomy. The resected specimens showed moderately diffentiated adenocarcinoma with severe fibrosis and scare islet cells. Discussion: Re-resection of the remnant pancreas comfirmed
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that PanIN is a precursor lesion of IDC with long time application. It is conceivable IDV also develops in a multicentric fashion in pancreas suffering from PanIN.
FP-287 Hepatic Resection for Hepatocellular Carcinoma in End Stage Renal Disease Patients Chun-Nan Yeh, Wei-Chen Lee, Miin-Fu Chen Surgery, Chang Gung Memorial Hospital, Taiwan Background Hepatocellular carcinoma (HCC) is a common disease in Taiwan. The prevalence of viral hepatitis infection and the subsequent development of HCC is well known to be higher in patients with end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis than among the general population. However, information on hepatic resection for ESRD-HCC patients is limited. Methods The clinical features of 26 ESRD-HCC patients who underwent hepatic resection from 1982 to 2001 were retrospectively reviewed. Meanwhile, the clinicopathological features and the outcome of 1198 HCC patients without ESRD undergoing hepatic resection were used for comparison. Results Of 1224 surgically resected HCC patients, 26 (4.2%) were ESRD-HCC. Univariate analysis revealed more associated disease, more physical signs of anemia and postoperative complications, lower hemoglobin, platelet, a- fetoprotein, elevated blood urea nitrogen (BUN) and creatinine levels, smaller tumors, lower HBs Ag positivity, higher HCV positivity, and longer hospital stays in the ESRD-HCC group compared with the HCC group. Furthermore, multivariate stepwise logistic regression analysis revealed that elevated BUN and creatinine levels were the only two independently significant factors in the patients in the ESRD-HCC group. Overall and disease-free survival rates were similar between the ESRD-HCC and HCC groups. Conclusions Elevated BUN and creatinine were the only two main independent factors differentiating ESRD-HCC from HCC patients. ESRD should not be a contraindication of hepatic resection in HCC patients. Comparable overall survival and disease-free survival can be achieved in selected ESRD-HCC patients undergoing hepatic resection when compared with conventional HCC patients.
FP-288 Thioacetamide-Induced Intestinal-type Cholangiocarcinoma in Rat Chun-Nan Yeh1, Anirban Maitra2, Kam-Fai Lee1, Yi-Yin Jan1, MiinFu Chen1 1 Surgery, Chang Gung Memorial Hospital, Taiwan, 2Johns Hopkins University, USA Background: Human cholangiocarcinoma (CCA) develops through a multistep progression model, preceded by the onset of dysplasia in the cholangiolar ductal epithelium. An animal model of multistep carcinogenesis in the biliary tree provides an avenue for chemoprevention strategies. We describe an oral thioacetamide (TAA) induced model of rat CCA that recapitulates the histologic progression of human CCA. Methods: Male Sprague-Dawley (SD) rats (n=170) were used in this study. Drinking water with TAA 300 mg / L was administered orally, and the liver was harvested and examined histologically at weekly intervals, beginning at 5
Journal of Gastrointestinal Surgery
weeks after initiation of TAA. Harvested tissues were formalinfixed and paraffin embedded for morphologic and immunohistochemical studies. Results: Multifocal bile ductular proliferation with intestinal metaplasia and increasing histologic atypia was observed by the 9th week of TAA administration. Biliary cytokeratin (CK19)-expressing invasive intestinal-type CCA with stromal desmoplasia was evident at the 16th week, and by the 22nd week, the yield rate for CCAs had increased to 100%. Invasive CCAs preceded the development of hepatic cirrhosis by at least 4 weeks; the earliest incidence of hepatic fibrosis was observed beginning at 20 weeks post-TAA administration. The progression from normal cholangioles to biliary dysplasia to invasive CCA was accompanied by upregulation of the proto-oncogenes c-met and c-erbB-2. The study was terminated at 6 months, at which time no systemic metastases or deaths were observed. Conclusions: The TAA rat model may serve as a powerful pre-clinical platform for therapeutic and chemoprevention strategies for human CCA.
FP-289 Donor Quality of Life in Living Donor Liver Transplantation Nam-Joon Yi, Jin Yong Yoo, Kyung-Suk Suh, Choon Hyuck Kwon, Jai Young Cho, Yong Beom Cho, Kuhn Uk Lee Department of Surgery, College of Medicine, Seoul National University, Korea Purpose: The safety and the impact on quality of life (QOL) of donors was the most important in living donor liver transplantation (LDLT). Patients / Methods: Questionnaires were sent to 50 donors who were followed up more than 4 months after LDLT from December 2001 to January 2003 (response rate 92.0%). The control group was selected the same number of the general public (n=42). The questionnaire consisted of donors characteristics, medical and psychosocial outcomes, and global QOL (KHP 1.0). Follow-up investigations were also performed at out patient clinic 1, 4, and 12 months after discharge. Results: The donors were more prevalent in male patient (63.0%) and most common in twenties (23.8%). The relations to the recipients were 17 offsprings (37.0%), 12 parents (26.1%), and et cetera. There was no perioperative transfusion, reoperation, and none of the donors died or has suffered life-threatening complications. Average hospital stay is 11.4 days. The mean recovery time was 1-3 months in a half of them. All donors resumed their predonation occupation or regular activity and felt no limitation. Most donors were satisfied with their donation (95.6%) and current life (87.0%) after operation. The score of QOL examined by KHP 1.0 showed that physical role of donors were more restricted but emotional health was better than that of the general public. Conclusion: Most donors in LDLT felt it to be good, but some limitation of their physical role despite of their physical recoveries. Donor follow-up needs to be emphasized and followed more systemically.
FP-290 The Role of Living Donor Liver Transplantation in Surgical Treatment for Hepatocellular Carcinoma Hajime Yokoi, Shuji Isaji, Kentaro Yamagiwa, Masami Tabata, Hiroyuki Sakurai, Masanobu Usui, Shugo Mizuno, Shinji Uemoto The First Department of Surgery, Mie university, School of Medicine, Japan OBJECTIVE. To elucidate the role of living donor liver trans-
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plantation (LDLT) in surgical treatment for patients with hepatocellular carcinoma (HCC). METHODS. The outcomes of 15 patients who underwent LDLT for HCC without distant metastasis and vascular invasion at preoperative evaluation between March 2002 and February 2004, and 131 patients who underwent curative hepatic resection (HR) for HCC in the past 14 years were investigated. RESULTS. 1) LDLT: Mean age was 56.6 years old, and most of the indications were uncontrollable tumors by conventional tretment. Child-Pugh class (A/B/C) was 3/8/4. The tumor size was 3.4±2.6cm, all of the patients had multinodular tumors, and 6 (40%) patients met the Milan criteria. One-year survival rate was 80% without significant difference according to the Milan criteria. Three patients died of non-tumor-related causes, and 1 patient is alive with lung metastasis. 2) HR: One-, 3-, and 5-year survival rates of 84 patients who met both the Milan criteria and ChildPugh class A were 94.9%, 86.3%, and 71.3%, respectively, which were significantly better than those of the other patients (P<0.01). Intrahepatic recurrence was observed in 57 patients. Child-pugh class B or C at the time of recurrence were significantly poor prognostic factors after various conventional treatments for the recurrence. When the Milan criteria was applied at the recurrence, 1-, 3-, and 5-year survival rates after the recurrence of 26 patients who exceeded the criteria (56.0%, 5.0%, and 5.0%) were significantly lower (P<0.0001) than those of 31 patients who met the criteria. (92.6%, 66.3%,and 60.8%). CONCLUSION. For resectable HCC patients with preserved liver function who met the Milan criteria, HR might be a first-line treatment with a favorable prognosis. When the recurrent tumors exceeded the Milan criteria or liver function deteriorated to ChildPugh class B or C, salvage LDLT could be employed.
FP-291 Clinicopathogical Study of Gastrointestinal Stromal Tumor of Small Intestine Miki Yokoi, Miki Yokoi, Masatoshi Kuroda, Yumiko Tanaka, Shinichiro Yoshitani, Hitoshi Saito, Takeo Kosaka, Ichiro Kita, Shigeki Takashima Department of Surgery II, Kanazawa Medical University, Japan (Objective) We reviewed clinicopathological study of 12 cases of Gastrointestinal stromal tumors (GIST) of small intestine. (Subjects) There were 29 cases of small intestinal tumors encountered from 1985 to December 2003; of these, 12 cases that were determined to be GIST served as subjects. (Results) Subjects were nine men and three women with an average age of 57.0 years of age. The site of occurrence was the jejunum in all cases, and the major axis of the tumor was an average of 5.7 cm. Immunohistologically, 12 cases were positive for ckit, 8 cases were positive for CD34, 6 cases were positive for SMA, and 2 cases were positive for S-100. The tumor was a smooth muscle type in 5 cases, a smooth muscle-neural type in 3 cases, an uncommitted type in 3 cases, and a neural type in 1 case. Malignancy was low-grade malignancy in 11 cases and high-grade malignancy in 1 case; histologically, all of the cases were determined to be malignant. Peritoneal dissemination was already seen during surgery in 1 of the 12 cases, and recurrence of liver metastasis was seen in 2 cases; the five-year survival rate was 80%. (Conclusion) Methods of diagnosing the malignancy of and treating GIST have yet to be established. There are also reports of recurrence after a long period of over 10 years post-operatively.
Accumulation of information on further cases in the future and long-term observation over time are needed.
FP-292 Gender Dimorphism in the Outcome of Preoperative Portal Embolization for Major Hepatectomy Yukihiro Yokoyama, Masato Nagino, Norihiro Yuasa, Koji Oda, Toshiyuki Arai, Tomoki Ebata, Yuji Nimura Division of Surgical Oncology, Department of Surgery, University of Nagoya Graduate School of Medici, Japan Purpose. A number of evidences indicated that gender modulate the process of hepatic regeneration. However, whether there is a gender difference in the outcome of preoperative portal vein embolization (PVE) is unknown. In this study, we analyzed the effects of gender on the outcome of PVE followed by major hepatectomy. Methods. Seventy-five patients who underwent preoperative right PVE were retrospectively analyzed. To adjust the different liver volume between male and female, the volume of the liver was divided by body surface area. Results. There was no difference between male and female in the average volume of embolized lobe and non-embolized lobe before PVE. However, non-embolized lobe in female became significantly higher than that in male after PVE. Although the percent volume of embolized lobe and that of non-embolized lobe to total liver was not significantly different before PVE, embolized lobe became significantly lower and non-embolized lobe became significantly higher in female compared to male, implying more dramatic volume change after PVE. The average plasma disappearance rate of indocyanine green for functional residual liver after PVE was 0.063±0.017 and 0.071±0.031 for male and female, respectively, and was significantly different (P=0.021). Conclusions. These results indicate that PVE induces more dramatic volume change in female liver and could renders female patient more tolerant to major hepatectomy.
FP-293 The Correlation between Quality of Life and Functional Outcome in Ulcerative Colitis and Familial Adenomatous Polyposis Patients after Total Proctocolectomy and Ileal Pouch Anal Anastomosis Eyi-Sang Yoon, Kil-Yeon Lee, Suk-Hwan Lee, Suck-Hwan Koh, SooMyung Oh, Choong Yoon Dept. of Surgery, Kyunghee University College of Medicine, Korea Purpose: The total proctocolectomy and ileal pouch anal anastomosis (IPAA) has been accepted as the operation of choice for ulcerative colitis (UC) and familial adenomatous polyposis(FAP). The aims of this study were to evaluate functional outcome and quality of life (QOL) in patients undergoing IPAA and to assess the correlation between functional outcome and QOL. Methods: The medical records of 20 patients who had undergone IPAA for UC (n=11) and FAP (n=9) from January 1993 to December 2003 were reviewed. The QOL was evaluated with the Korean version of Short Form 36 (SF-36) Questionnaire by telephone interview. Functional outcome was assessed using the Global Assessment of Function Scale (GAFS) includes functional and psychosocial variables such as bowel movements and time spent on
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toilet. The QOL of UC and FAP patients was compared with the general population matched for age and gender (n=107). Results: There were 13 women (65%) and median age was 46 years. The QOL in patients after IPAA was comparable with the healthy general population in all scales. Functional outcome and QOL scores correlated in most of dimensions. The Physical Component Score (PCS) was correlated with the daytime and nighttime incontinence (P < 0.01). The Mental Component Score (MCS) was correlated with the daytime, nighttime incontinence and daytime bowel movement (P < 0.05). Conclusions: This study demonstrates that the QOL in patients after IPAA is excellent and daytime and nighttime incontinence are significant factors influencing the QOL.
FP-294 ZD 1839 Inhibits the Growth of Gastric Cancer Cells and its Synergistic Effects by 5-FU Kazuhiro Yoshida, Kazuaki Tanabe, Yoshiyuki Wada, Kei Ukon, Jyunya Taomoto, Tetsuya Toge Hiroshima University, Research Institute for Radiation Biology and Medicine, Japan The ZD 1839 is a specific inhibitor of the tyrosine kinase of the EGFR and its inhibitory effects on several types of cancer have been reported so far. However, little is known about the effects on gastric cancer. In the present study, in order to elucidate the growth inhibitory effect, gastric carcinoma cell lines (MKN-1, 7, 28, 45, 74, KATO- III, TMK-1, HSC39) were treated by ZD 1839 and growth inhibition was examined by MTT assay. The growth of TMK-1 and MKN-28 were inhibited by ZD 1839 and the inhibition was detected as time and dose dependent manner. Moreover, the expression profiles of the cells treated with ZD1839 were examined by cDNA micro array system (Takara Cancer chip). The expression of growth factors and receptors and cell cycle regulators including cyclin D1, E, PCNA, TGF-alpha, VEGF, KGF, VEGFC and EGFR, were down regulated. On the other hand, the expression of apoptosis related genes such as cytochrome C and caspase 3, p27 were increased. Interestingly, the expression of Peroxisome proliferator activated receptor gamma (PPAR-gamma) was markedly induced in TMK-1 cells which was also confirmed by Western blot analysis. The synergistic growth inhibitory effect was observed by concomitant administration of 5-FU. These results indicate the significant role of ZD 1839 as molecular targeting therapy and opens the new therapeutic approach on gastric cancer.
FP-295 The Appearance of the Cardia, Helicobacter Pylori Infection and Histrogical Typing of the Gastric Cancer Masashi Yoshida1, Satoru Takahashi2, Koichiro Kumai3, Tetsuro Kubota1, Yoshihide Otani1, Yoshiro Saikawa1, Hideki Ishikawa4, Tetsuya Nakamura1, Naoto Kurihara5, Masaki Kitajima1 1 Department of Surgery, Keio University School of Medicine, 2 Takahashi Clinic, 3Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, 4Department of Emergency and Critical Care Medicine, Keio University School of Medicine, 5Division of Surgery, Tokyo Denryoku Hospital, Japan The purposes are to examine whether Helicobacter pylori (HP) infection is associated with the appearance of the cardia, the extent
Journal of Gastrointestinal Surgery
of atrophic mucosa, cancer of cardia or histological typing of the gastric early cancer or not. [PATIENTS AND METHODS] Two hundred fifty seven patients diagnosed as early gastric cancer in Keio university hospital and 148 patients examined in Takahashi clinic were enrolled in this study. Endoscopic findings of hiatus hernia were classified according to Keio Cancer Detection Center form (K-form: grade 0; normal, grade C; gastric mucosa was seen partially above hiatus, grade B; gastric mucosa was seen circularly less than 3cm above hiatus, grade A; gastric mucosa was seen more than 3cm above hiatus). The extent of atrophic mucosa was expressed in accordance with the Kimura-Takemoto classification. [RESULTS] Reflux esophagitis was associated with undifferentiated carcinoma, and histological typings of all patients who had esophagitis with mucosal break were undifferentiated carcinoma. HP infection was associated with the extent of atrophic mucosa, and was inversely associated with K-form and reflux esophagitis. Most of early gastric cancers were seen in open type. Most of the early cancers in closed type stomachs were undifferenciated carcinoma. All of cardia cancers were seen in open type stomach. [DISCUSSION AND CONCLUSIONS] HP infection may result in atrophy and relate to development of cancer including cancer of cardia, differentiated carcinoma and undifferentiated carcinoma. However, some of undifferentiated carcinoma develop in the closed type stomach. This may explain the reason why reflux esophagitis was associated with undifferentiated carcinoma.
FP-296 Clinical Analysis of Invasive Ductal Carcinoma of the Pancreas Naomasa Yoshida, Shigeru Kiyama, Toshiyuki Miyahara, Hiroshi Matsuo, Takafumi Sekino, Takuya Yamada, Hirofumi Takemura Advanced Surgery, Gifu University, Graduate School of Medicine, Japan (Purpose) We retrospectively analyzed the results of the patients with curative resection for invasive ductal carcinoma of the pancreas and estimated the characteristics of long survival cases. (Methods) Of a total of 42 patients operated for invasive ductal carcinoma of the pancreas at our department from 1988 to 2003, 24 patients (57.1%) with curative resection were enrolled in this study. We investigated survival rates in terms of age, stage, pathological type and combined resection of the portal vein due to invasion. (Results) The average age was 66.7±13.3 (range 30-87). Clinicopathological stage were Stage II in 3 cases, Stage III in 6 cases and Stage IV in 15 cases. Operative methods were pancreatoduodenectomy in 18 cases, distal pancreatomy in 5 cases and total pancreatomy in 1 case. We performed combined resection of the portal vein in 8 cases. The cumulative 5-year survival rate was 18.0% and median survival time was 14.0 months. 4 cases survived for more than 3 years. (2 cases more than 5 years) They were all in Stage II or III. Pathological type of them were cystic adenocarcinoma in 2 cases, papillary adenocarcinoma and well differentiated tubular adenocarcinoma in each 1 case. There were no significant differences in the survival rate in terms of age, existence of combined resection of the portal vein. (Conclusions) Prognostic factors were stage and pathological type. In curative resection the patients with combined resection of the portal vein could survive as long as the patients without invasion.
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FP-297 Probiotics Prohibit the Development of MRSA Enterocolitis in the Rat Model Yuichi Yoshida, Yoshinobu Sumiyama, Shin’ya Kusachi, Yo’ichi Arima, Jiro Nagao, Yoshihisa Saida Third Department of Surgery, Toho University, School of Medicine, Japan Background: Enterocolitis due to Methicillin-Resistant Staphylococcus aureus (MRSA) remains one of the serious postoperative complication in Japan. Due to the animal model, an MRSA colonization into lower digestive tract is turned out with a suppression of gastric acid and a great disorder of the intestinal flora, and propagation of MRSA into the lower digestive tract requires a continuity of suppression absent in the bacterial flora. Methods: Prospective randomized control study was performed using 15 male Wistar rats weighting 300g.INTERVENTIONs: Control (MRSA enteritis model): Suspension of MRSA 235 strain 109cfu/rat inoculation on 4th day pretreated oral antibiotics for 3days, and sacrificed at 8th day after 4 days of once a day intravenous administration of LMOX 80mg/kg/day, n=5). B3 (Four days of once a day oral administration of probiotics (BiothreeR(B3)) 1 g/body/rat after MRSA inoculation same as control, n=8). SHAM (Treated same as B3 which administrater substrate (lactose) 1g/body/rat)(n=5). Results: The B3 controls propagation of MRSA from 104.76 to 101.73cfu/ml in the colon due to the propagation of probiotic bacteria in the colon. Bacterial counts in the colon of the SHAM group was decreased to 102.50cfu/ml, but 60% of the SHAM rats were shown diarrhea same as control. Conclusion: Oral administration of prebiotics may be helpful to prevent the development of MRSA in the rat model.
FP-298 Efficacy of the Dissection of the Lymph Nodes along the Splenic Artery (#11) and the Splenic Hilum (#10) in Advanced Gastric Carcinoma not Invading Greater Curvature Takaki Yoshikawa, Tomohiko Osaragi, Tatsuya Yoshida, Hitoshi Murakami, Akira Tsuburaya, Osamu Kobayashi, Motonori Sairenji Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Japan Objective; Spleen or distal pancreas is often resected for the purpose of dissecting #10, however, its efficacy is controversial for treating gastric cancer. Especially in gastric tumors not invading the greater curvature (GC), most tumors do not infiltrate the spleno-gastric ligament directly and are not drained to the nodes of #10 anatomically. This study is conducted to clarify the efficacy of dissection of #10 in advanced carcinoma located in the upper third of the stomach but not invading GC. Methods; From 10/67 to 4/04, 309 patients were selected according to the following eligibility; T2-4M0P0H0, located in the upper third of stomach without invasion to GC, and after curative D2 gastrectomy with splenectomy. The efficacy of dissection of #10 was calculated by multiplying the incidence of the involvement by the respective 5-year(5y) survival rate. Results; The incidence of the metastases to #10 was 15.2%, which was different by the depth of invasion; 7.0% for MP, 10.3% for SS, 18.3% for SE, and 25.0% for SEI. In total 5y survival rate was 42.6% in patients with positive nodal status of #10, while
50.9% in negative patients(p=0.28), thus the efficacy of dissection of #10 was 6.5%. Those for T2 and T3/4 tumors were 70.0% and 63.4% (p=0.91) with efficacy of 6.4%; 34.5% and 42.2% (p=0.54) with efficacy of 6.6%, respectively. Conclusion: Splenectomy may benefit patients with T2-4 gastric cancer not adjacent to #10 or #11 lymph nodes with survival benefit around 6%.
FP-299 Up-regulation of Hypoxia-inducible Factor-1 Alpha and Vascular Endotherial Growth Factor mRNAs in Peritoneal Dissemination of Gastric Cancer Takaki Yoshikawa1, Akira Tsuburaya1, Yohei Miyagi2, Hironobu Sekiguchi2, Shunsuke Yanoma3, Tomohiko Osaragi1, Tatsuya Yoshida1, Hitoshi Murakami1, Osamu Kobayashi1, Motonori Sairenji1 1 Department of Gastrointestinal Surgery, 2Laboratory for Molecular Diagnostics/Pathology, 3Laboratory for Biochemistry, Kanagawa Cancer Center, Japan Objective; The present study was conducted to clarify a role of hypoxia-inducible factor-1 (HIF-1) in the development of peritoneal metastases of gastric cancer, by measuring mRNA levels of HIF-1 alpha and VEGF. Methods; Primary tumor, adjacent normal gastric mucosa and metastatic tissues of lymph nodes, skin, lung, and peritoneum were collected at surgery. Total RNA was extracted from each tissue and mRNA levels of HIF-1 alpha and VEGF were measured by quantitative RT-PCR. Results; Expression levels of HIF-1 alpha and VEGF were not significantly different between the primary tumors and the adjacent normal gastric mucosa in 23 paired samples. HIF-1 alpha was greatly up-regulated in the peritoneal dissemination (n=11) compared with that in the primary tumor (n=89) and the other metastases (n=5) with statistical significance (p<0.001 and p=0.006, respectively). VEGF also significantly increased in the disseminated foci than that in the primary cancer (p=0.020). Among the metastases, the peritoneal metastases expressed a trend of higher VEGF. Correlation between HIF-1 alpha and VEGF expression in the peritoneal tumors was extremely tight with a coefficient of 0.95 (p<0.001). Conclusion; There was a specific up-regulation of HIF-1 alpha and VEGF mRNAs in the disseminated foci, suggesting that HIF1 plays some role in the establishment of peritoneal metastases of gastric cancer.
FP-300 Study of Lung Metastasis Following Colorectal Cancer Yuka Yoshimura, Michio Itabashi, Tomoichirou Hiroswa, Shinpei Ogawa, Noriyasu Shirotani, Shingo Kameoka Surgical Department 2, Tokyo Women’s Medical University, Japan Purpose:This study was conducted for the purpose following up on cases of lung metastasis associated with colorectal cancer on the basis of treatment method and prognosis by identifying risk factors associated with this metastasis. Subjects: The subjects of this study consisted of 123 cases of lung metastasis (comprised of 25 cases of homochronic lung metastasis and 98 cases of heterochronic lung metastasis) among 1720 cases that underwent surgery for colorectal cancer in this department
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from 1987 to 2003. Methods: The primary focal factors and lung metastasis focal background factors of the cases of homochronic metastasis and heterochronic lung metastasis were analyzed using monovariate and multivariate analyses. In addition, the survival rate associated with each factor was calculated and a study was made of those factors that demonstrated statistical significance. Results: In the study of cases of homochronic lung metastasis, there were no significant differences observed for each factor, while significant differences were observed for liver metastasis and lymph node metastasis among cases of heterochronic lung metastasis (P<0.01). In addition, in the study of cases that underwent surgery for heterochronic lung metastasis, the survival prognosis was significantly better as compared with those cases that did not undergo surgery (P<0.01). Conclusions:Since relapse of lung metastasis occurs later as compared with liver relapse and local relapse, long-term follow-up is considered to be necessary. Cases of homochronic lung metastasis exhibited a poor survival prognosis as compared with cases of heterochronic lung metastasis. Pneumonectomy is effective for treatment of lung metastasis and long-term survival can be expected.
FP-301 GI-surgeons in Training can Accumulate High-quality Data About Surgical Techniques with the Aid of Digitalized Surgery and Spreadsheet Programs Keiichi Yoshino, Naomi Sugimoto Nursing and Medical Care, Keio University, Japan GI-surgeons in training are only allowed to observe surgery in Japan. Thus, it is usually quite difficult for them to accumulate high-quality data about GI-surgical techniques. A new program utilizing digitalization and computerization of GI-surgery was developed to help those aspiring surgeons.The trainees first measure various objects with vernier calipers in order to become accustomed to describing them by size. Immediately after the operation, a conventional appendectomy, for instance, they record the following: a) name of chief surgeon, b) name of anesthesiologist, c) patient’s ward, d) patient ID e) patient’s age and sex, f) BMI, g) thickness of subcutaneous fatty tissue, h) length of skin incision, i) volume of aspirated ascites, j) distance between ligation of appendiceal radix and stump, k) caliber of purse-string suture around appendiceal radix, l) volume of lavaged saline, and m) bite and pitch of peritoneal and skin closure. Following the patient’s discharge, additional data is recorded: a) volume of drained ascites, b) interval after surgery until flatus (in hours) and until discharge (in days), and c) medical cost. These items are then statistically processed to produce high-quality evidence, which can be used by the trainees to supplement their undergraduate training.This new program addresses short-term surgical results, which, we believe, have a close relationship with long-term results. Moreover, it can help motivate the trainees to be rigorous about gathering surgical evidence. If further developed, it could also contribute to improving the level of surgeons, anesthesiologists, staff and institution, as well as to advancing robotic.
Journal of Gastrointestinal Surgery
FP-302 A Combination Phase I Study of Weekly Paclitaxel and 5’DFUR in Patients with Unresectable or Recurrent Gastric Cancer in an Outpatient Setting Shigefumi Yoshino1, Hiroto Hayashi2, Hiroyasu Hasegawa3, Tatsuto Yamamoto4, Tomoe Katoh5, Akira Tangoku1, Kimikazu Hamano6, Masaaki Oka1 1 Surgery II, Yamaguchi University School of Medicine, 2Kanmon Medical Center, 3Tokuyama Central Hospital, 4Tsushimi Hospital, 5 Yamaguchi Rosai Hospital, 6Yamaguchi University School of Medicine, Surgery I, Japan Backgrounds: Paclitaxel (PTX) and 5’-DFUR have single-agent activity in gastric cancer. Synergistic interaction between PTX and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase. Objectives: To determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the recommended dose (RD). The DLT was set in low grade to treat the patients in the outpatient clinic. Patients and methods: PTX was administered by 1-hour intravenous infusion (level 1, 2, 3, 4: 50, 60, 70, 80 mg/m2) weekly for 3 consecutive weeks every 4 weeks. 5’-DFUR was administered orally at a fixed dose of 600mg/body everyday. Toxicity and efficacy were evaluated during the 2 cycles for 8 weeks. DLT was defined as grade 3 hematologic toxicity, grade 2 non-hematologic toxicity. The MTD was defined as the dose level at which at least two of three patients or three of six patients presented with DLT. Rsults: Twenty-one patients with a median age of 66 years were enrolled in this study. Nine patients have received prior chemotherapy. One, 2 and 3 patients developed DLT at level 2(n=6), 3(n=6) and 4(n=6), respectively. All DLT was neutropenia. Level 4 was determined as the MTD. Of 16 evaluable patients, responses included 1 CR, 7 PR, 6 SD and 2 PD for an overall response rate of 50%. Conclusion: The MTD of PTX in this combination is 80 mg/m2 and the RD is 70 mg/m2. This regimen is well-tolerated with high response rate in outpatient setting. A phase II study is conducted.
FP-303 Portal Vein Obstruction after Pediatric Living Donor Liver Transplantation Elena Yukie Yoshitoshi, Mikiko Ueda, Daisuke Morioka, Kouhei Ogawa, Mureo Kasahara, Hiroto Egawa, Koichi Tanaka Department of Transplantation and Immunology, Kyoto University Faculty of Medicine, Japan Aim: Characterize the frequency, time after operation and outcome of portal vein (PV) obstruction after pediatric LDLT. Methods: Retrospective analysis of 527 pediatric patients received primary LDLT between June 1990 and September 2003. Blood flow of the PV was checked with doppler ultrasonography every day for the first week and every other day for the first month. After that, patient’s portal blood flow was checked in the outpatient clinic. Results: 41 patients (7%) showed PV stenosis (n=29) or occlusion (n=12). Their age ranged from 4m to 17y3m (median; 1y) and weight from 3.8Kg to 44.8Kg (median; 8.5Kg). PV obstruction was detected in the first semester in 7 (17%), in the next semester in 12 (29%), in the second year in 7 (17%), between 2y and 5y in
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12 (29%) and thereafter in 2 patients (5%). Percutaneous transhepatic balloon dilatation of the PV was successful in 29 of the patients with PV stenosis. Two received PV re-anastomosis, two received re-LDLT due to graft failure. One died after re-LDLT due to infection and others are all alive. Decrease in the PV flow and decrease in the platelet count were indicative signs of PV obstruction. Conclusions: PV obstruction occurred in 7% of the pediatric patients in LDLT. Doppler ultrasonography and platelet count was an indicative marker. Early detection of PV stenosis may lead to a successful balloon dilatation avoiding graft loss.
FP-304 Is Alkaline Shift a Good Indicator for Duodenogastroesophageal Reflux? Norihiro Yuasa, Sasaki Eiji, Ikeyama Takashi, Yuji Nimura Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Japan Purpose: The intraesophageal pH>7.0 (alkaline shift) has been considered to be duodenogastroesophageal reflux (DGER), however, Bilitec 2000 that can measure bilirubin absorbance for 24 hours made direct monitoring of bile reflux possible. Patients who undergo distal gastrectomy have no sphincter to prevent duodenal juice from refluxing into the gastric remnant. The aim of this study is to evaluate usefulness of alkaline shift for DGER in patents after distal gastrectomy. Methods: Studies were performed in 32 patients who underwent distal gastrectomy followed by Billroth I (n=19), Billroth II (n=6), Roux-en-Y (n=6), and jejunal interposition (n=1) reconstruction. Simultaneous gastric pH, esophageal pH, and esophageal bilirubin monitoring was performed for 24 hr. The proximal and distal pH sensors were positioned 5 cm above and 5 cm below the esophagogastric junction, respectively. A fiberoptic sensor for bilirubin absorbance was placed 5 cm above the esophagogastric junction at the same position as the proximal pH sensor to detect DGER. Results: No correlation was evident between the percentage of time during which esophageal pH was above 7.0 and the percentage during which esophageal bilirubin absorbance was exceeding 0.14 (R=0.2, p=0.27). According to moment-to-moment comparison of pH and bilirubin absorbance, esophageal pH was above 7 in 33.9% out of total DGER time (118 hrs). Sensitivity and specificity of alkaline shift for DGER were 33.9% and 80.3%, respectively. Conclusions: Alkaline shift is not a good indicator for DGER.
FP-305 Pancreatitis-associated Protein in Pancreatitis: RNA-Inhibition Studies Michael Zenilman1, Martin Bluth2, Emad Kandil1, Yin-Yao Lin2, Dominic Viterbo2 1 SUNY Dowstate Medical Center, 2SUNY Downstate, USA Background: Pancreatitis-associated protein (PAP) is induced in acinar cells following pancreatitis, but its functional role is not clear. The presence of at least three isoforms (PAP I, II, III) has precluded gene knockout experiments. To determine PAP’s role in pancreatitis, we employed antisense oligonucleotide (ASO) and small-interference RNA technology (si-RNA). Methods: Pancreatitis was induced in rats by retrograde infusion of 4% sodium taurocholate into the pancreatic duct. Pretreatment
with ASO-PAP or saline controls were given via pancreatic subcapsular injection 24 hours prior to pancreatitis induction (n = 8 for each group). AR42J cells were treated with IL-6 and dexamethasone to induce PAP. siRNA to PAP was administered, and mRNA levels assayed by PCR. Results: After induction of pancreatitis, mRNA expression of PAP genes increased 50 fold compared to controls (P<0.05). ASO pretreatment resulted in significant inhibition of all PAPs. This inhibition resulted in increased inflammatory changes, necrosis, serum amylase levels and CRP levels (P < .05). In AR42J cells IL-6 and Dex induced all PAPs, and siRNA successfully inhibited all PAP mRNA levels. Conclusions: Inhibition of the PAP genes exacerbate pancreatitis, indicating that they are endogenous protectors of pancreas from injury. siRNA molecules can inhibit PAP genes in vitro. Antisense and siRNA technology are powerful tools to study the mechanism of the protective effect of the PAP family in pancreatitis.
FP-306 The First Successful Abdominal Cluster Transplantation for Pancreatic Carcinoma with Liver Multi-metastasis in Asia Wenhua Zhan1, Xiaoshun He2, Xiaofeng Zhu2, Jingsheng Peng2, Yi Ma2, Dongping Wang2, Weiqiang Qu2, Shiqun Qian2, Linwei Wu2, Jiefu Huang2 1 Division of Gastrointestinopancreatic Surgery, The First Hospital, Sun Yet-sen University, 2Organ Transplantation Centre and Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yatsen University, China A 28-year-old lady was admitted to the hospital with pancreatic carcinoma with multiple metastatic liver lesions. Based on the experience in surgical technique achieved in animal experiments, we performed a abdominal cluster transplantation on her on 28 May 2004. The donated grafts consisting of liver, pancreas and duodenum were harvested using the rapid multiple organ harvesting technique. After resection of total upper abdominal organs including liver, bile duct, pancreas, duodenum, stomach, spleen and a portion of jejunum, the graft was transplanted orthotopically without veno-venous bypass. The anhepatic phase was 54min and 1600ml RBC was infused. Immunosuppressive regimen utilized induction with two-dose daclizumab, mycophenolate mofetil and steroid, while holding tacrolimus for 5 days. The postoperative course has been uneventful, neither surgical complication nor rejection occurred following cluster transplantation. Both liver and pancreas function resumed to normal ! range on POD5. She is now doing well with normal diet and activities.
FP-307 Realities of Microsatellite Instability in Gastrointestinal Tract Cancers Yan Zhao1, Shinya Oda2, Eiji Oki1, Yoshihiro Kakeji1, Hideo Baba1, Yoshihiko Maehara1 1 Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, 2Institute for Clinical Research, National Kyushu Cancer Center, Japan AIM: Microsatellite instability (MSI) is regarded as a phenotypical outcome of defective DNA mismatch repair (MMR) and as characterising a unique pathway for tumourigenesis. MSI is indeed associated with various human malignancies. Despite numerous stud-
Abstract of 19th WC-ISDS
ies, reported frequencies of MSI differ widely in each malignancy. These discrepancies may derive from methodological problems left in the conventional assay techniques. We have established a new fluorescent technique where almost all of the methodological problems have been overcome. To elucidate realities of MSI in human cancer, this system has been applied to gastrointestinal cancers. METHODS: Microsatellite alterations were analysed using the High Resolution Fluorescent Microsatellite Analysis (HRFMA). RESULTS: Microsatellite changes observed in human cancer were classifiable into two subtypes, one showing relatively small changes within 6 base pairs (Type A) and the other exhibiting drastic changes over 8 base pairs (Type B). In gastric and colorectal cancers, frequencies of Type A / B MSI were 20 / 4% and 30 / 10%, respectively. In oesophageal cancer, MSI was rare. CONCLUSIONS: Use of HRFMA has elucidated realities of MSI in gastrointestinal cancers. There are two distinct subtypes with different molecular backgrounds. Thus far reported MSI, including those associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is predominantly Type B. Type A may have been missed by use of less sensitive approaches. Based upon analyses on mouse and human cells with a known MMR defect, we conclude that Type A is a direct consequence of defective MMR. Relationship between Type B and defective MMR remains unclear.
FP-308 The Effects of a Compound Chinese Herbal Medicine on Constituents of T-tube Drained Bile in Patients with Primary Choledocholithiasis Pei-Ting Zhu, Jing-Zhe Zhang, Ju Gao Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China Purpose: To study the effects of Yang-gan-li-dan (YGLD) granula, a compound Chinese herbal medicine which was considered having therapeutic effects of nourishing and modulating liver and gallbladder function according to the principle of traditional Chinese medicine, on components of postoperative T-tube drained bile in patients with primary choledocholithiasis. Methods: On 11 patients with primary bile duct pigment stones choledochostomies and T-tube bile drainage were performed. After operations the patients were treated with YGLD granula orally, and the T-tube drained bile were collected before treatment and on 1, 2, 3, 7th day after treatment to test the TBA, T-BIL, CB, UCB and MCB using HPLC technique. Results: 1. Bile TBIL and TBA gradually increased after treatment (P<0.05) . 2. Bile MCB and UCB gradually decreased after treatment (P<0.05). 3. The ratio of DCB to MCB and UCB of bile steadily increased (P<0.05). 4. The percentage of MCB and UCB in bile was decreasing while DCB was increasing during the treatment (P<0.05). Conclusions: Traditional chinese medicine YGLD granula has beneficial effects in patents with gallstone disease such as reducing bile MCB and UCB, increasing bile TBA and decreasing the lithogenesity of bile. The compound herbal medicine can be applied to the prevention of postoperative stone recurrence especially for patients with primary pigment choledocholithiasis.
Journal of Gastrointestinal Surgery