Occurrence of non‐gastric cancer in the digestive tract after remote partial gastrectomy: Analysis of an Amsterdam cohort

Abstract

If peptic ulcer surgery favors the formation of carcinogenic N-nitroso compounds in the gastric remnant, an increased risk of cancer at sites in the gastrointestinal tract distant from the stomach might be predicted. To estimate the risk of carcinomas in the digestive tract, other than the stomach, occurring after partial gastrectomy, we analyzed an Amsterdam cohort of 2,633 post-gastrectomy patients operated on for benign disease between 1931 and 1960. Mortality in the study population was compared with the general Dutch population through person-year analysis. An excess mortality of biliary tract cancer (O/E:2.64; CL:1.32-4.72; p less than 0.01) and pancreatic cancer (O/E:1.65; CL:1.06-2.44; p less than 0.05) was found in males more than 5 years after surgery; females showed only an increased risk of pancreatic cancer in the first 5 years postoperatively (O/E:15.33; CL:1.85-55.43; p less than 0.01), probably due to misdiagnosis. All other non-gastric sites of the digestive tract carried no increased risk for cancer. In males, mortality due to colorectal cancer more than 5 years post-operatively was significantly decreased (O/E:0.58; CL 0.34-0.92; p less than 0.01). The excess mortality of biliary-tract and pancreatic cancer in males, which increases with the duration of post-operative interval, is consistent with a dose-response phenomenon. This study therefore supports the hypothesis that carcinogens are not only locally activated in the gastric remnant, but are hepatically excreted and initiate cancer in the biliary tree and pancreatic duct. Further exploration of this mechanism of carcinogenesis is warranted, since it may also explain the pathogenesis of pancreatic and biliary cancers in patients without gastrectomy.

Pancreatic cancer after remote peptic ulcer surgery

“…8 Furthermore, our present analysis provides insight into the pancreatic cancer risk after a long postoperative intervalmore than 25 years after the initial surgery. The additional eight pancreatic cancer deaths seen since our previous analysis all occurred 30 years or more after peptic ulcer surgery.…”

“…8 Briefly, the study population consisted of 2633 patients who underwent gastrectomy for benign conditions in the academic medical center of the University of Amsterdam between 1931 and 1960. There were 2300 men and 333 women; 207 patients had a Billroth I, and 2343 a Billroth II, and in 83 patients the type of gastrectomy was not specified.…”

“…8 Follow up of this cohort is still complete and 82% of the cohort has now died. Therefore, the present analysis was performed to investigate whether the previously suggested increasing trend for pancreatic cancer risk after peptic ulcer surgery could be further evaluated and definitively established.…”

“…Patients with a remote partial gastrectomy for benign ulcer disease may constitute a high risk group for pancreatic cancer, [3][4][5][6][7][8][9] although reports are conflicting. [10][11][12][13][14] The mechanism by which partial gastrectomy may contribute to the development of pancreatic cancer is unclear, but an increased production of N-nitroso compounds and nitrosamines in the operated stomach is thought to play a role.…”

Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer

“…Of 16 previous studies that have examined gastrectomy as a risk factor for pancreatic cancer, ten reported a positive association (McLeanRoss et al, 1982;Mack et al, 1986;Caygill et al, 1987;Offerhaus et al, 1987;Mills et al, 1988;Farrow and Davis, 1990;Tersmette et al, 1990;Eide et al, 1991;Mooller and Toftgaard, 1991;Bueno de Mesquita et al, 1992), while six studies in addition to ours found no association (Wynder et al, 1973;Maringhini et al, 1987;La Vecchia et al, 1990;Jain et al, 1991;Kalapothaki et al, 1993;Gullo et al, 1996). Of only four studies that examined history of ulcer in relation to pancreatic cancer risk, none found an association in accord with our findings (Mack et al, 1986;La Vecchia et al, 1990;Jain et al, 1991;Bueno de Mesquita et al, 1992).…”