associated with combination therapy for 2 categories of malignancies: NMSC alone and all other hematologic/solid tumors. The excess risk of cancer with combination therapy was 0.6 events per 100 patient-years for both categories, yielding a NNH of 167 per patient-year of treatment for each. There were only 2 lymphomas observed in our dataset, both in the combination therapy group, corresponding with an event rate of 0.14 events per 100 patient-years in the combination therapy group. This corresponds with a NNH of 714 per patient-year of treatment. The precision of this estimate is limited by the small number of events, but the point estimate is generally consistent with that previously reported by Kandiel et al1 and Khan et al.2 The lymphoma in the patient taking adalimumab and methotrexate occurred in a female with a 24-year smoking history who was 52 years old at the time of study entry. She had complained of increased abdominal pain on study day 277. Computed tomography (CT) of the abdomen revealed lymphadenopathy in the left periaortic location and along the left common external and internal iliac arteries. A CT-guided percutaneous core biopsy of the left lower quadrant mass revealed lymphoma, which was diagnosed on study day 299, 4 days after the last dose of adalimumab. The patient had a history of intolerance to azathioprine (treatment duration information for azathioprine is not available) and had been receiving methotrexate at 12.5 mg/wk for approximately 2.5 years at the time the lymphoma was diagnosed. Information about previous CT exposure is not available. The event was considered ongoing as of study day 354, and further information is not available. MARK T. OSTERMAN, on behalf of the study authors Division of Gastroenterology Penn Presbyterian Medical Center Philadelphia, Pennsylvania
References 1. 2.
Kandiel A, et al. Gut 2005;54:1121–1125. Khan N, et al. Gastroenterology 2013;145:1007–1015.
Conﬂicts of interest The author discloses the following: Mark Osterman has served as a consultant for AbbVie, Inc, Elan Pharmaceuticals, Janssen, and UCB Pharma; and has received grant support from UCB Pharma. Funding AbbVie, Inc, funded the studies and was responsible for the study design, research analysis, data collection, and review and approval of the publication.
that CP is strongly associated with pancreatic cancer and carries an high risk of death. However, concerning the strikingly high rate of pancreatic cancer after CP diagnosis, some important points that can elucidate the results of this research should be included. Diagnosing pancreatic cancer at its early stage is difﬁcult, and some early stage pancreatic cancers are often misdiagnosed as CP. In this research, pancreatic cancer occurred in 4.26% of patients (510/11,972) associated with CP and the hazard ratio was 6.9 (95% CI, 7.5–11.8). Most of the pancreatic cancers (338/510; 66.27%) were established 1 year after CP diagnosis. Bang et al1 excluded these 338 patients from the time-dependent relationship analysis between CP and pancreatic cancer. However, these 338 patients were included in the other analyses of the current research. In our opinion, patients with suspected CP should be excluded from the current study, and a period of 1 year is an insufﬁcient basis for excluding patients of pancreatic cancer misdiagnoses. In almost all CP research, particularly involving CP cancer, patients who exhibited pancreatic cancer within 2 years of follow-up were excluded to avoid discrepancies.2–6 Some studies even used another 5 years to mitigate misdiagnoses further.2,4,6 This study included some asymptomatic CP patients whose CP diagnoses were occasionally established by physical examinations or evaluations for other diseases. These patients may present a different disease course (progression of cancer) from that of symptomatic CP. Thus, a subgroup analysis should be conducted. This study showed that 66.7% of pancreatic cancer was observed during the ﬁrst year of follow-up, and that pancreatic cancer incidence over 2–4 years was signiﬁcantly higher than over 5–8 years or 9–16 years. This ﬁnding indicates that a narrow observation window exists after early CP diagnosis for detecting pancreatic cancer as either misdiagnosed CP or secondary to CP. Unfortunately, no effective strategy for monitoring pancreatic cancer has been proposed to date. We have conducted studies on the early diagnosis of pancreatic cancer with great efforts, but have achieved insigniﬁcant results. BAI-RONG LI Department of Gastroenterology LIANG-HAO HU ZHAO-SHEN LI Department of Gastroenterology and Digestive Endoscopy Center Changhai Hospital The Second Military Medical University Shanghai, China
Chronic Pancreatitis and Pancreatic Cancer Dear Editor: We read with great interest the recently published study on the mortality, cancer, and comorbidity of chronic pancreatitis (CP) patients reported by Bang et al.1 We concur
References 1. 2. 3. 4.
Bang UC, et al. Gastroenterology 2014;146:989–994. Lowenfels AB, et al. N Engl J Med 1993;328:1433–1437. Ekbom A, et al. J Natl Cancer Inst 1994;86:625–627. Talamini G, et al. Am J Gastroenterol 1999;94: 1253–1260.
542 5. 6.
Correspondence Wang W, et al. Pancreatology 2011;11:16–23. Ueda J, et al. Surgery 2013;153:357–364.
Acknowledgments H.L.H. and L.B.R. contributed equally to this work. Conﬂicts of interest The authors disclose no conﬂicts.
Reply. Thanks to Li et al for their interesting comments. The authors raise some important points regarding retrospective database studies on pancreatic cancer incidence among patients with chronic pancreatitis (CP). The key question is whether patients with pancreatic cancer in our cohort actually suffered from CP or may have been misdiagnosed with CP during examinations that ﬁnally demonstrated a pancreatic cancer. This is a general concern in retrospective studies using databases and the method to account for that uncertainty is to disregard cases of pancreatic cancer that are diagnosed within a certain period of time after the diagnose of CP. The preferable latency period has been 2 years, which to our knowledge was introduced by Lowenfels et al1 and has been used in later studies as well.2–5 The background for selection of 2 years of latency period seems not to be evidence based and more likely arbitrary. Furthermore, we do not know whether the excluded patients in these studies actually did also suffer from CP. It should also be remembered that CP patients may go undiagnosed for years, which could shorten the observed latency period between CP and pancreatic cancer diagnosis. According to Danish data, approximately 1000 persons are diagnosed with pancreatic cancer annually and the 1-year survival is 26% (www.cancer.dk). In our material the median survival time with pancreatic cancer without surgery was 86 days (Q1-Q3, 35–235). The observed survival time was independent of time since CP diagnoses: 0–1 year, 104 (39–280); 1–2 years, 67 (19–168); and >2 years, 117 (34–362) days. Hence, it is less likely that patients survive pancreatic cancer for >1 year. We think these considerations justify our approach to exclude the patients with pancreatic cancer within only 1 year of the diagnosis of CP. Furthermore, the results from retrospective studies should be interpreted with precaution; however, post hoc exclusion of patients based on assumptions could be hazardous. To address the request from Li et al, we have excluded the 338 patients with pancreatic cancer within 1 year of CP, and recalculated the hazard ratio (HR) of pancreatic cancer among patients with CP compared with our controls. We then found that 1.48% of the patients with CP and 0.21% of our controls developed pancreatic cancer yielding a HR of 4.5 (95% CI, 3.6–5.7). For other types of cancer, only small changes in the results were observed, which did not change the overall conclusion (not reported). Finally, we want to draw attention to the 388 patients in our study who were diagnosed with pancreatic cancer within 1 year of CP diagnosis. Whether CP was truly present or not should not change the conclusion that diagnostic
Gastroenterology Vol. 147, No. 2
attention should be given especially in the early phase of CP because 2.9% of patients with newly diagnosis of CP are diagnosed with a pancreatic cancer within 1 year. ULRICH CHRISTIAN BANG Department of Endocrinology Copenhagen University Hospital of Hvidovre Hvidovre, Denmark THOMAS BENFIELD Department of Infectious Diseases University Hospital of Hvidovre and Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Hvidovre, Denmark LARS HYLDSTRUP Department of Endocrinology Copenhagen University Hospital of Hvidovre and Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Hvidovre, Denmark FLEMMING BENDTSEN Department of Gastroenterology University Hospital of Hvidovre and Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Hvidovre, Denmark JENS-ERIK BECK JENSEN Department of Endocrinology Copenhagen University Hospital of Hvidovre and Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Hvidovre, Denmark
References 1. 2. 3. 4. 5.
Lowenfels AB, et al. N Engl J Med 1993;328:1433–1437. Ekbom A, et al. J Natl Cancer Inst 1994;86:625–627. Malka D, et al. Gut 2002;51:849–852. Talamini G, et al. Am J Gastroenterol 1999;94:1253–1260. Wang W, et al. Pancreatology 2011;11:16–23.
Conﬂicts of interest The authors disclose no conﬂicts.
Transient Elastography in Primary Sclerosing Cholangitis—the Value as a Prognostic Factor and Limitations Dear Editor: We read with interest the recent work by Corpechot et al1 describing the diagnostic and prognostic value of transient