Improved quality of life by combined transplantation in Hirschsprung's disease with a very long aganglionic segment

Improved quality of life by combined transplantation in Hirschsprung's disease with a very long aganglionic segment

Improved Quality of Life by Combined Transplantation in Hirschsprung’s Disease With a Very Long Aganglionic Segment By Revillon Yann, Aigrain Yves, Ja...

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Improved Quality of Life by Combined Transplantation in Hirschsprung’s Disease With a Very Long Aganglionic Segment By Revillon Yann, Aigrain Yves, Jan Dominique, Yandza Thierry, Goulet Olivier, and Lacaille Florence Paris, France

Background/Purpose: The treatment of children with Hirschsprung’s disease beginning in the proximal jejunum remains a challenge for the pediatric surgeon. These patients need a definitive parenteral nutrition, which could lead to a liver impairment. The goal of this work is to assess the quality of life after combined liver, intestine, and right colon transplantation.

pull-trough (Duhamel procedure 2, Swenson procedure 1) was performed from 6 to 24 months after the transplantation. The follow-up after the transplantation ranges from 2 to 6 years. These 3 patients are completely off total parenteral nutrition with bowel movements 2 to 3 times a day. Two patients are continent day and night, and one is continent during the day only.

Methods: This is a retrospective study of 3 patients. Data regarding symptomatology, radiographic and operating findings, postoperating recovery, and quality of life were analyzed and compared with the quality of life before the transplantation.

Conclusions: Intestinal transplantation is feasible with good results even when a liver impairment needs a combined intestine and liver transplantation. The right colon transplantation, in our experience, does not impair the results. The quality of life after the transplantation is better than before. J Pediatr Surg 38:422-424. Copyright 2003, Elsevier Science (USA). All rights reserved.

Results: The suspicion of a very long intestinal aganglionosis should be derived from the intestinal biopsies. Three combined liver, intestine, and right colon transplantation operations have been performed. The immunosuppression included steroids, tacrolimus, and azathioprine. An abdominal


HE TREATMENT of children with Hirschsprung’s disease beginning in proximal jejunum is always a challenge for the pediatric surgeon. The length of the normal ganglionic segment is so short that these patients need jejunostomy and definitive total parenteral nutrition (TPN). Sepsis and onset of TPN very early in life may lead to liver impairment. Among the 26 patients receiving combined liver and small bowel transplant in our unit, 5 had Hirschsprung’s disease as indicated. We reported on the results in the 3 patients in whom the surgical treatment after transplantation was considered as total, that is, after the pull-through and the closure of the ileostomy. Two patients were not included in this study because the pull-through after the combined transplantation was not yet performed. The goal of this work is to compare the quality of life before and after definitive treatment.

INDEX WORDS: Total parenteral nutrition, Hirschsprung’s disease, liver failure, liver transplantation, intestinal transplantation.

MATERIALS AND METHODS This is a retrospective study of 3 patients. These patients were treated at the Hoˆpital des Enfants Malades and at the Hoˆpital Robert Debre´ in Paris.

Case 1 A female infant was born on June 2, 1992. She presented with intestinal atresia with microcolon, and an ileostomy was performed. The histologic study confirmed Hirschsprung’s disease. Three other procedures were necessary to relieve obstruction and the ileostomy was finally located 50 cm from the ligament of Treitz. TPN was necessary starting in the neonatal period. Abnormalities in liver function tests were observed as soon as July 1993 (one year of age). A combined liver, intestine, and right colon transplant was performed on September 14, 1997 (5 years of age). The postoperative immunosuppression included tacrolimus, azathioprime, and steroids. The patient was discharged home one month and a half after transplantation. A Swenson procedure was performed on February 5, 1998. The ileostomy was closed 6 months later. The postoperative course was uneventful.

Case 2

From Hoˆpital des enfants Malades, Paris, France. Presented at the 33rd Annual Meeting of the American Pediatric Surgical Association, Phoenix, Arizona, May 19-23, 2002. Address reprint requests to Revillon Yann, Hoˆpital des Enfants Malades, 149 rue de Se`vres, 75743 Paris, Cedex 15, France. Copyright 2003, Elsevier Science (USA). All rights reserved. 0022-3468/03/3803-0027$35.00/0 doi:10.1053/jpsu.2003.50072

A male infant was born on September 19, 1997. He presented with a neonatal intestinal obstruction with dilatation of the proximal intestine. Six surgical procedures were necessary before obtaining a wellfunctioning ostomy located 15 cm from the ligament of Treitz. TPN support was initiated in the neonatal period. A Kimura procedure was performed without improvement of intestinal function. Liver impairment was evidenced early on liver biopsy that showed periportal fibrosis. A combined liver intestine and right colon transplantation was performed on July 11, 2000 (3 years of age). The immunosuppression included tacrolimus and steroids. A fistula


Journal of Pediatric Surgery, Vol 38, No 3 (March), 2003: pp 422-424



between a gastrostomy and colostomy was observed and healed spontaneously. A Duhamel pull-through procedure was performed on June 1, 2001 (4 years of age). The postoperative course was uneventful. Chylothorax was observed after removal of central catheter 5 months posttransplantation.

Case 3 This neonate was born on December 2, 1992. Neonatal intestinal obstruction was observed, and an ileostomy was performed 6 days after birth. Finally, a jejunostomy was performed 25 cm from the ligament of Treitz 9 months later. In January 1994 (at 2 years of age), a Kimura procedure was performed but was unsuccessful. The child remained dependent on TPN support. Liver impairment was evidenced on liver biopsy that showed liver cirrhosis. A combined liver intestine and right colon transplantation was performed on May 25, 1997 (at 41⁄2 years of age). The immunosuppression incruded tacrolimus, steroids, and azathioprine. The postoperative course was complicated by a duodenal and ileal fistula. Two additional surgical procedures were necessary to heal the fistulas. A Duhamel pull-through procedure with a ileostomy was performed on February 3, 1998 (at 5 years of age). The ileostomy was closed on June 26, 1998.


These 3 patients are alive with a posttransplantation follow-up of 2, 41⁄2, and 6 years. All patients are weaned from the nutritional assistance, and they receive normal oral feedings. One patient received complementary caloric intake using enteral nutrition (600 mL nutrition 4 times a week). These patients have one to 4 bowel movements a day. All patients are continent. One patient uses diapers during the night. The growth and height curves are normal. The immunosuppression therapy is mainly tacrolimus and steroids. Steroids are given on alternate days. Two patients have mild hypertension that is well controlled with adalate. The renal function is normal in all 3 patients. One patient presented with a transient increase in serum creatinine during an episode of dehydration caused by viral diarrhea. Neither severe rejection episodes nor severe sepsis were observed. DISCUSSION

We want to discuss the results of the definitive treatment (combined liver, intestine, and colon transplantation and pull-through) of these 3 patients with a very long aganglionic segment. The incidence of total colonic aganglionosis with ileal involvement is estimated at 1 case in 50,000 live births. In the medical literature, the mortality rate ranges from 8% to 30%.1-2 When the normally innervated small bowel is shorter than 60 cm, the probability for definitive TPN dependency is high. In our patients, the length of the normal bowel segment ranged from 15 to 50 cm. Before the Definitive Treatment The normal small bowel plexus is always difficult to identify, and many procedures often are necessary to

select the ideal level for the stoma. In 2 patients, intestinal absorption was not improved by a Kimura procedure. There is no surgical procedure (reverse loop, Kimura procedure) able to improve the intestinal absorption. Intraluminal bacterial overgrowth is common with repeated episodes of sepsis. Septicemia is common (on average 7 episodes per child). Ileal dysmotility is found in all cases and is more likely to be congenital rather than a consequence of bowel distension. TPN support is mandatory but carries a risk of associated intrahepatic cholestasis. Infection and intestinal stasis contribute to the occurrence of intrahepatic cholestasis in neonates after abdominal surgery.3 The lack of venous access is a permanent threat. Finally, before transplantation, these 3 patients are exemplary of the difficulties encountered in the surgical treatment of Hirschsprung’s disease with a very long aganglionic segment. Many surgical procedures were performed without improving the TPN dependency. After the Definitive Treatment Liver, intestine, and right colon are transplanted en bloc. The liver is harvested with the bile duct and the duodenum, so that there is no biliary reconstruction. An ileostomy always is performed.4 The choice of the pull-through technique depends on the surgeon’s choice (Hoˆ pital des Enfants Malades/ Swenson procedure; Hoˆ pital Robert Debre´ /Duhamel procedure). Recently, another patient was treated successfully by transplantation, and a Duhamel pull-through procedure. The length of follow-up is too short to assess the results. The combined colon transplantation in our experience has not impaired the results. On the contrary, the colon transplantation has permitted fecal continence. The current immunosuppression is based on tacrolimus given orally as soon as possible along with steroid therapy. However, intestinal allograft rejection remains a major complication making it necessary to maintain a high level of immunosuppression. Even a long time after transplantation, the risk of rejection remains quite high. In addition, the differential diagnosis between rejection and PTLD, Epstein Barr virus, cytomegalovirus, and other viral enteritis may be difficult. Antibodies against the IL2 receptor and Sirolimus are some new and useful tools that may improve the results. Weaning the patient from TPN support and maintaining a normal oral diet currently is observed. The stomies are closed, and the children are continent. The liver function tests are normal, and weight and height are normal. The quality of life is improved significantly, and school performance is normal. The risk of the immunosuppression, sepsis and PTLD is well controlled by reducing the level of immunosuppression. The main problem probably is the risk of death at the time of the surgical procedure. In our



experience, one patient died 3 weeks after the combined transplantation. The death was related to fungal sepsis. There is no precise score to assess quality of life after transplantation. We found that these patients after transition from TPN dependence to posttransplant TPN independence describe significant improvement in most areas of quality of life. In May 2000, Saxton et al.,5 concluded in their report “Near total intestinal aganglionosis”: “If, in the future, surgery is to be the ultimate cure, that cure may reside within the realm of small bowel transplantation.” Today, combined liver, intestine and right colon transplantation is a new tool but it remains a poten-

tially life-threatening procedure. The isolated intestine and right colon transplantation is less dangerous to perform. Because of improvements in TPN management, we have not, in the recent years, observed the development of severe liver impairment in our patients. In the near future, it would probably be possible to plan the transplantation before the onset of the liver impairment. When the length of the normal intestine is less than 60 cm, this procedure has to be discussed very early. Size matching has limited the pool of organ donors. The development of new techniques such as reduced-size combined liver intestine graft may increase the donor pool.

REFERENCES 1. Nihoul Fekete C, Ricour C, Martelli H, et al: Total colonic aganglionosis with or without ileal involvement: A review of 27 cases. J Pediatr Surg 21:251-254, 1986 2. Fouquet V, De Lagausie P, Faure C, et al: Do pronostic factors exist for total colonic aganglionosis with ileal involvement? J Pediatr Surg 37:71-75, 2002 3. Kubota A, Yonekura T, Hoki M, et al: Total parenteral nutri-

tion—Associated intrahepatic cholestasis in infants: 25 year’ experience. J Pediatr Surg 35:1049-1051, 2000 4. Jan D, Michel JL, Goulet O, et al: Up-to-date evolution of surall bowel transplantation in children with intestinal failure. J Pediatr Surg 34:841-843, 1999 5. Saxton ML, Ein SH, Hophner J, et al: Near total intestinal agangionosis: Long term follow-up of a morbid condition. J Pediatr Surg 35:669-672, 2000

Discussion M. Ziegler (Boston, MA): I just wanted to congratulate you, Dr Revillon. That is a spectacular outcome to have 3 survivors of this disease. The American experience is not nearly as favorable. As you know, we propose that there is an alternate way of managing these patients, that is, extended myectomy, a so-called bridge to transplantation. There are a number of children here in the United States as well as other parts of the world who have had extended myectomy and myotomy. I think the downside of applying that treatment or “bridge” is that a number of patients have been subjected to multiple procedures, and when they have been referred for transplantation, they have had end-stage liver disease. In fact, to my knowledge, there is only a singular survivor of bowel and liver-bowel transplant in the Unitd States whose primary diagnosis was extended Hirschsprung’s disease. My question to you is, what is your practice? When would you refer for transplantation in this population? Would you refer for transplantation simply based on the diagnosis of 60 cm or less of jejunum? Or would you, in fact, give such patients a trial to see what their ability would be to support themselves with enteral nutrition for a period of time? Y. Revillon (response): We begin by a period of enteral nutrition, and we propose this transplantation

after 2 years of age. I think that the main problem is that many patients who are coming to our department come too late with too many surgical procedures, and the transplantation is very difficult to perform. M. Schwartz (Wilmington, DE): I think this is an excellent presentation. For those in the audience who may not be as familiar with this field, Dr Revillon and his group in Paris have been major contributors to bowel transplantation in the pediatric age group for quite a long time. This is another excellent contribution from this group. The question that I would direct to you is why do you think this group of patients did better than the overall results? One other comment that I would like to make is that the excellent results in this patient series point out the advantage of a pediatric surgeon being involved in transplantation and also having a greater understanding of the primary disease. Y. Revillon (response): Thank you, Dr. Schwartz, for your very kind remarks. I think that it is better for the child to undergo transplant by a pediatric surgeon, and I think that this is one reason for our success. Also, I think that probably we are very lucky with our job and I think that a good surgeon has to be lucky.