Increased risk of cancer at multiple sites after gastric surgery for peptic ulcer.

Abstract

SUMMARY Of 5018 patients who had undergone gastric surgery at St James Hospital, Balham, at least 25 years ago, death certificates have been received for 2768, whilst 1746 patients are still alive and are flagged (Office of Populations, Censuses and Surveys (OPCS) will notify us of their death and its cause) and only 504 could not be traced. Mortality from cancers of various organs has been determined using a 'years at risk' calculation in five year bands. There was no increase in mortality risk from any cancers during the first 15 postoperative years, but from 20 years after operation there was a significant excess risk not only of cancer of the stomach (4.5-fold), but also of the large bowel (1-6-fold), bronchus (3.9-fold), pancreas (4-0-fold), biliary tract (9-1-fold), oesophagus (2.3-fold), bladder (2-4-fold), breast (4-0-fold), and cancer of all sites (3-3-fold). These findings are consistent with the production in the operated-upon stomach of circulating carcinogens with a 20 year latency period.There have been a number of studies relating surgery for peptic ulcer to the subsequent risk of gastric cancer, some showing an association'-4 and some not."7 Many possible explanations for this have been suggested, but our large study' of 2577 duodenal ulcer patients and 1385 gastric ulcer patients showed that whereas more than 20 years postsurgery both groups of patients had an excess risk of gastric cancer, during the first 20 postoperative years there was an excess risk in the gastric ulcer patients but a decreased risk in duodenal ulcer patients. Thus, an association between gastric surgery and gastric cancer in either direction or no association at all could be expected depending solely on the relative proportion of duodenal ulcer and gastric ulcer patients, and on the length of follow up.A possible mechanism for this increased carcinogenesis is that surgery results in gastric hypoacidity leading to bacterial overgrowth with consequent production of carcinogens. A hypothesis involving nitrite and N-nitroso compounds has been sug-

Increased risk of biliary tract cancer following gastric surgery

“…The literature review by Fletcher & Clarke (1968) throws doubt on such an association in these patients; however a recent study by Mazzanti et al (1986) observed a prevalence of gallstones of 36% in gastric surgery patients. Alternatively, in a previous publication (Caygill et al, 1987) we have noted that the increased risk in gastric surgery patients of cancer at sites additional to the stomach was consistent with a causal role for circulating organotropic carcinogens.…”

“…The study population was 4,466 patients treated surgically for peptic ulcer at St James Hospital, Balham between 1940 and1960 and has been reported in detail elsewhere , Caygill et al (1986, Caygill et al ( , 1987 at risk' in 5 year bands from the age at operation. The probability levels were calculated using the Poisson approximation to the binomial distribution.…”

“…However, its association with gallstones is well established (Torvik & Hoivik, 1960;Fraumeni, 1975). An increased risk of mortality from biliary tract cancer, with a latency of 20 years, has been reported after gastric surgery by Caygill et al (1984by Caygill et al ( , 1987 although an association between gastric surgery and the prevalence of gallstones is still disputed (Fletcher & Clark, 1968;Mazzanti et al, 1986). Gastric surgery is associated with an increased risk of gastric cancer (Caygill et al, 1984(Caygill et al, , 1986 and a geographical correlation between gastric and biliary tract cancers in 63 populations has been reported (Caygill et al, 1983).…”

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).…”

Gastric and Duodenal Ulcer and Risk of Bladder Cancer

“…Previous epidemiologic investigations on the issue are limited to patients who had undergone gastric surgery (2,3).…”