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Gastrointestinal Intraluminal Ph in Normal Subjects and Those with Colorectal Adenoma Or Carcinoma

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Gastrointestinal Intraluminal Ph in Normal Subjects and Those with Colorectal Adenoma Or Carcinoma Gut, 1990,31, 1355-1357 1355 Gastrointestinal intraluminal pH in normal subjects Gut: first published as 10.1136/gut.31.12.1355 on 1 December 1990. Downloaded from and those with colorectal adenoma or carcinoma G Pye, D F Evans, S Ledingham, J D Hardcastle Abstract colorectal cancer but only with total non-starch Recent evidence suggests that the production polysaccharide. 14 of colorectal carcinogens is facilitated when In a comprehensive review of recent hypo- the pH of the colonic contents is alkaline. It theses for the origin of colorectal cancer,'5 Bruce follows that the colonic intraluminal pH of was unable to support enthusiastically the patients with colorectal neoplasms should be evidence in favour ofa bacterial origin of colonic higher than in normal subjects. Gastro- carcinogens but did find evidence to support the intestinal pH has been measured in 30 patients role ofdietary fats and fibre as well as faecal pH. with colorectal cancer and 37 patients with benign colorectal adenomas (using a pH sensi- tive radiotelemetry capsule). These values SUBJECTS AND METHODS have been compared with those recorded in 66 A total of 133 pH studies were successfully normal subjects. No differences in gastro- performed. Sixty six normal volunteers com- intestinal pH were found and the results did pleted the study (47 men, median age 26 years, not support the hypothesis that colonic pH range 21-82 years). None of the volunteers had plays a role in the aetiology of colorectal any history ofcolorectal disease. neoplasia. Thirty seven patients with benign adenoma- tous polyps underwent pH studies (24 men, median age 66 years, range 49-80 years). Nine- Much evidence has accumulated to suggest that teen had adenomas > 1-5 cm in diameter and 10 intraluminal carcinogens are important in the had rectal polyps and 27 were in the colon. development of colorectal neoplasia. Hill et al' Thirty patients with adenocarcinoma of the drew together epidemiological, histopathologi- colon or rectum completed pH studies (17 men, cal, and metabolic data and concluded that the median age 62 years, range 50-76 years). Ten intraluminal degradation of cholesterol and had Dukes's stage A tumours and there were 19 http://gut.bmj.com/ primary bile acids by bacterial enzymes could rectal tumours and 11 colonic tumours. lead to the production of intraluminal Intraluminal pH may be measured by the carcinogens. ingestion of a small pH sensitive radiocapsule In 1981 Thornton2 reviewed the evidence (Remote Control Systems) which passes easily relating to the aetiology of colorectal cancer and along the gastrointestinal tract, eventually being put forward a hypothesis. He suggested that a passed in the stool. Subjects wore an aerial belt high colonic pH promoted, or at least facilitated, around the abdomen which received the emitted on September 30, 2021 by guest. Protected copyright. colonic bacterial degradation of primary bile signal from the capsule. This was connected to a acids and cholesterol to carcinogens and that portable receiver-recorder (John Caunt Scien- intraluminal pH was influenced by the acidifying tific, Oxon) to allow ambulatory recording ofpH effect of dietary fibre fermentation in the colon. data for up to 48 hours.'6 There is evidence that the bacterial enzymes Each subject swallowed the radiocapsule with responsible for bile acid degradation are in- the help of water after an overnight fast. Once hibited at a pH of less than 6 5.35 Colorectal the radiocapsule had left the stomach (associated cancer is uncommon in black Africans and they with a pH reading greater than 5 0) normal diet have lower faecal pH than white Africans,6 and was permitted. A surface location chart was kept vegetarian Seventh Day Adventists (who also to indicate the topographical position of the have a low risk of colorectal cancer) have faecal radiocapsule throughout the study. This was pH values lower than those of American patients done by the use of a small directional detector with colorectal cancer.7 which could localise the radiocapsule to within Increased dietary fibre may lead to a fall in 5 cm. faecal pH by its colonic fermentation to produce The pH data were analysed as previously short chain fatty acids.689 A reduced proportion reported'6 and mean pH values calculated for the Department of Surgery, of secondary bile acids in bile has been found proximal small bowel (the -first hour of small University Hospital, after the administration of wheat bran'" or lac- bowel recording), the distal small bowel (the Queen's Medical Centre, tulose,' and lactulose has been found to reduce final hour of small bowel recording), the inter- Nottingham G Pye colonic pH." vening mid small bowel, the proximal colon (the D F Evans This supports the idea that colonic acidifica- first four hours of the colonic part of the record- S Ledingham tion may reduce bile acid degradation in the ing), the distal colon (the last four hours of the J D Hardcastle colon. The pentose fraction of fibre is meta- colonic recording, provided the radiocapsule had Correspondence to: Mr G Pye, Department of bolised to produce short chain fatty acids'2 and travelled beyond the splenic flexure), and the Surgery, E Floor, West Block, its intake had an inverse relationship with mor- intervening 'mid colon.' Each subject completed University Hospital, Nottingham NG7 2UH. tality rates for colorectal cancer in a UK study.'3 a dietary history questionnaire to establish their Accepted for publication It has been suggested, however, that there is no normal fibre intake. 2 February 1990 connection between the pentose fraction and Comparisons were made between each of the 1356 Pye, Evans, Ledingham, Hardcastle TABLE I Mean (SD) gastrointestinal pH in patients with adenomas and carcinomas and in patients failed to show any significant differences normal subjects (n= 133) to size or site and no differences according polyp Gut: first published as 10.1136/gut.31.12.1355 on 1 December 1990. Downloaded from Normal Adenoma Carcinoma Combined neoplasia were found according to stage or site of the Site (n=66) (n=37) (n=30) (n=67) tumour in the carcinoma patients. Proximal small bowel 6-6(0 5) 6-6(0 5) 6-8 (0 5) 6-7 (0-4) Dietary fibre intakes were similar in each of Midsmallbowel 7-4(0 4) 7-2(0 6) 7-1(0 6) 7-2(0-5) the three study groups (normal subjects: median Distal small bowel 7-5 (0 5) 7-4 (0 5) 7-3 (0 5) 7-4 (0-6) Wholesmallbowel 7-3(0-3) 7-1 (0 5) 7-1(0 5) 7-1(0 5) (range) 22 (8-62) g/day; adenoma patients: Right colon 6-4 (0 6) 6-6 (0 7) 6-4 (0 7) 6-5 (0 6) median (range) 19 (8-60) g/day; carcinoma Mid colon 6-6 (0 8) 7 0 (0 7) 6-7 (0 7) 6-8 (0-6) Left colon 7 0 (0 7) 7-3 (0 8) 7-3 (0 8) 7-3 (0-8) patients: median (range) 23 (11-38) g/day) and Whole colon 6-6 (0 7) 7 0 (0 7) 6-7 (0 7) 6-8 (0-7) no correlation was found between subjects' colonic pH values and the estimation of their dietary fibre intake. study groups and the effect of site, type, and Discussion stage of tumour together with age, sex, and No differences have been shown in small bowel dietary fibre intake were examined by analysis or large bowel intraluminal pH among normal of variance. subjects and those with colorectal neoplasia. This study was fully approved by the Ethical Tumour site, size of adenoma, and stage of Committees of the University of Nottingham carcinoma did not exert any influence. and Nottingham University Hospital. All radio- The colonic pH hypothesis2 suggested that capsules were recovered at the completion of the alkaline pH in the colon could be associated with studies, none remaining lodged proximal to neoplastic change, and Hill'8 suggested that the neoplastic lesions. step at which the particular effect ofpH could act was to promote enlargement ofsmall adenoma to form larger (potentially malignant) adenomas. Results If colonic pH plays a role in the initiation or Mean pH values for each of the subject groups promotion of neoplastic changes in the mucosa, are given according to anatomical sites in then differences might have been expected Table I. The normal pH profile showed a rise in between normal subjects and subjects with pH from the proximal small bowel to the distal adenomas or carcinomas. The exact stage at small bowel followed by a noticeable drop in pH which pH exerts its influence might have deter- as the radiocapsule entered the caecum. There- mined the point of difference to be between after, the pH again increased as the radiocapsule normal mucosa and small adenoma, small and passed to the distal colon. No significant dif- large adenoma, large adenoma and early carci- ferences associated with age (Table II) or sex noma or early and advanced carcinoma. No such http://gut.bmj.com/ were found by analysis ofvariance. point was found. A similar pattern was seen in the patients with Why have these results failed to support colorectal adenomas or carcinomas. There were Thornton's hypothesis?2 The hypothesis rests no significant differences among the three heavily on the assertion that the important groups when compared at each ofthe anatomical bacterial enzymes are inhibited at low pH, and sites. Combining the adenoma and carcinoma he cites two studies to support this.34 The data in patients to give a 'neoplasia' group again failed to these studies relate only to qualitative in vitro on September 30, 2021 by guest.
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