Risk factors for pancreatic cancer in patients with chronic pancreatitis

Abstract

The association between chronic pancreatitis (CP) and pancreatic cancer is well known. A large, multicentre, historical study, reported by Lowenfels et al, estimated the risk as 1.8% and 4% at 10 and 20 years respectively in a population where alcoholic chronic pancreatitis (ACP) was the dominant etiology. 1 Previous reports form India indicated that patients with tropical pancreatitis (TCP) appeared to have an increased risk of pancreatic cancer as compared to ACP. 2-4 In a study by Augustine P and Ramesh H (1992), it was seen that pancreatic adenocarcinoma occurred in 22 of 266 patients (8.3%) with tropical pancreatitis, suggesting that TCP was especially premalignant. 3 The more recent nationwide study from India however found only 4% incidence of pancreatic cancer in a cohort of over 1000 patients. 5 In this study, classical TCP was seen in less than 4% patients. There are multiple risk factors for development of pancreatic cancer in CP. In ACP, it is likely that in addition to alcohol consumption, smoking, and possibly some dietary and environmental factors are implicated in the pathogenesis of cancer. Pancreatic cancer has been reported to occur at a younger age in TCP. The risk factors in TCP are not clear but may relate to genetic factors in view of the high frequency of familial aggregation noted in TCP, especially in South India, in addition to the putative environmental factors. The recent literature indicates a change in profile of CP in India 6-9 with identification of novel risk factors, especially genetic factors 10 , and delayed presentation as well as delayed onset of exocrine and endocrine insufficiency. The prevalence and characteristics of pancreatic cancer in the present setting is unknown. We studied the prevalence and profile of pancreatic cancer among CP patients and associated risk factors. Materials and Methods CP patients who were enrolled and prospectively followed up in our Pancreas clinic between 2004 and 2014 were included in this study. CP was diagnosed based on the presence of typical imaging features of pancreatic calcification and/or duct dilatation with parenchymal atrophy on USG abdomen/CT scan/ERCP/MRCP/EUS studies. Patients who had consumed alcohol of at least 80g/day for 5 or more years were considered to have ACP. Patients who did not have any specific etiology for CP were considered to have idiopathic chronic pancreatitis (ICP). A multiphase MDCT scan of the abdomen using pancreas protocol was reported by a radiologist. This description was used to assign the location. Pancreatic cancer was diagnosed based on histopathological examination of resection specimens in those who underwent pancreaticoduodenectomy. Percutaneous biopsy or EUS guided FNA from the pancreatic mass was the usual method for confirmation in those who were not operable. In some cases, FNA or biopsy from liver metastases was the method of diagnosis. Histology was reported by an experienced GI pathologist who also reviewed slides reported by other pathologists. All slides were reviewed once again for the study. The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from the study subjects. Statistical analysis was done by using SPSS version 11 software (SPSS Inc, Chicago, USA). Data were reported as mean ± SD and frequencies. The nonparametric Mann-Whitney U test or Wilcoxon's test was used to compare variables without a normal distribution. All tests were two-tailed and P values less than 0.05 were considered statistically significant. Results Among 1157 patients with CP (410 ACP, 747 TCP) enrolled and followed up prospectively in our Pancreas clinic, there were 70 (42 males, 28 females) patients who developed pancreatic cancer. Sixty (85.7%) had idiopathic/tropical chronic pancreatitis (ICP/TCP) while 10(14.3%) had alcoholic chronic pancreatitis (ACP) as underlying etiology. 54 of the 70 patients had calcific pancreatitis with large dense intraductal calculi seen in all patients with TCP/ICP. The mean age of diagnosis of ACP was 55.4±8.9 years as compared to 51.4±13.1 years in TCP patients (p=0.3). The mean age of diagnosis of pancreatic cancer in ACP was 56.4±9.2 years as compared 185 Pancreatic cancer risk factors