The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease

Abstract

Although Helicobacter pylori (H. pylori) seropositivity is linked to an excess risk of pancreatic cancer, the biologic mechanism is unknown. Gastric ulcer is primarily associated with corpus colonization of H. pylori, atrophic gastritis and formation of N-nitrosamines. Duodenal ulcer is a marker of antral colonization, hyperacidity and uninhibited secretin release. We estimated relative risks for pancreatic cancer among patients with gastric or duodenal ulcer, based on a register-based retrospective cohort study with 88,338 patients hospitalized for gastric ulcer and 70,516 patients for duodenal ulcer recorded in the Swedish Inpatient Register between 1965 and 2003. Following operation, the 14,887 patients who underwent gastric resection and 8,205 with vagotomy were analyzed separately. Multiple record-linkages allowed complete follow-up and identification of all incident cases of pancreatic cancer until December 31, 2003. Standardized incidence ratios (SIRs) estimated relative risks. During years 3-38 of follow-up, we observed a 20% excess risk (95% confidence interval [CI] 10-40%) for pancreatic cancer among unoperated gastric ulcer patients. The excess increased to 50% (95% CI 10-110%) 15 years after first hospitalization (p for trend 5 0.03). SIR was 2.1 (95% CI 1.4-3.1) 20 years after gastric resection. Unoperated duodenal ulcer was not associated with pancreatic cancer risk, nor was vagotomy. Our results lend indirect support to the nitrosamine hypothesis, but not to the hyperacidity hypothesis in the etiology of pancreatic cancer. ' 2006 Wiley-Liss, Inc.Key words: pancreatic cancer; gastric ulcer; duodenal ulcer; gastrectomy; vagotomy; risk; cohort Pancreatic cancer is the most deadly neoplasm in humans.1 Little is known about its etiology apart from known relationships with smoking, a family history, and some rare genetic susceptibility syndromes. Alleged causal links with diabetes and nonhereditary chronic pancreatitis remain under debate.2 Possible association between a history of gastroduodenal diseases and pancreatic cancer was first suggested by an early case-control study, 3 in which a strong association between subtotal gastrectomy and pancreatic cancer was reported. The authors postulated that one of the possible mechanisms is via increased Nnitroso compounds in gastric juice after the operation. Recently, a moderately strong association with Helicobacter pylori (H. pylori) infection was reported. 4,5 Although confounding from unknown causal factors cannot be ruled out as an explanation, there are at least three hypothetical models for the influence of H. pylori on pancreatic carcinogenesis. Firstly, bacterial invasion of the organ and local chronic inflammation, is conceivable but there are no reports in the literature of H. pylori growth in pancreatic tissue or ducts. The second, more plausible, hypothesis involves predominantly gastric antral colonization, hyperchlorhydria, uninhibited secretin release, attendant elevations in basal pancreatic bicarbonate output and pancreatic ductular hyperp...

Epidemiology, Risk Factors and Clinical Presentation

“…The putative mechanism is also still unknown and speculative, as diseases associated either with acid hypersecretion (peptic ulcer) and hyposecretion (pernicious anaemia) have also been associated with PDAC. Interestingly, the risk after peptic ulcer is only elevated many years after surgery and not increased in unoperated (Luo et al 2007) subjects, suggesting that an unbalance in the oxidative stress due to achlorhydria, may be the factor associated with an increased risk (Capurso et al 2004). …”

Gastrectomy and risk of pancreatic cancer: systematic review and meta-analysis of observational studies

“…Of the 19 full-text articles, 4 studies [18,19,28,29] were excluded because effect estimates could not be calculated from available raw data, even if we tried to contact authors of the original studies. Thus, 11 case-control studies [20,[25][26][27][34][35][36][37][38][39][40] and 4 cohort [41][42][43][44]studies were identified and included in the meta-analysis. Although a language restriction was not placed on the search, all included studies were reported in English.…”

“…We took a systematic review of these studies. Two studies [42,43] provided raw data for subgroup analysis of postoperative interval. Study conducted by Lou reported that patients who underwent gastrectomy had a 20 % excess risk of PaC compared to the general population.…”

“…Two studies [25,43] provided available data for subgroup analysis of the underlying peptic ulcer. Luo found that relative risk of gastrectomy performed in duodenal ulcer patients (RR = 1.6; 95 % CI = 1.1-2.1) may be stronger than that in gastric ulcer patients (RR = 1.5; 95 % CI = 1.1-2.0).…”

“…Only one study [43] provided RR with corresponding CI for subgroup analysis about type of gastrectomy. Luo found that patients receiving Billroth II resection (RR = 1.7; 95 % CI = 1.2-2.3) might have a stronger relative risk of PaC than those receiving Billroth I resection (RR = 1.4; 95 % CI = 1.0-1.9).…”