M. J. Hill

Fecal steroids and colorectal cancer

The fecal steroid profiles of healthy subjects were compared with those of colorectal cancer (CRC) patients. The multicomponent profiles did not differ qualitatively in that CRC patients, like control subjects, had similar fecal steroids. The major bile acids detected in fecal extracts were lithocholic acid (LCA) and deoxycholic acid (DCA). The major sterol of animal origin was cholesterol and its bacterial metabolite coprostanol, whereas the major plant sterols were beta-sitosterol, stigmasterol, campesterol, and their corresponding bacterial metabolites. CRC patients excreted higher amounts of total major bile acids (LCA and DCA) than did the control group, but this difference was not significant. However, the LCA-to-DCA ratio was much higher in the CRC group [(1.43, p less than 0.01) compared with the control group (0.72)]. The control group excreted significantly higher amounts of total neutral sterols (p less than 0.001), sterols of animal origin (p less than 0.001), and plant sterols (p less than 0.001) compared with the CRC group; the plant sterols represented a much lower proportion of excreted total neutral sterols in the CRC group (p greater than 0.001) compared with the control group. We propose the following hypotheses. The LCA-to-DCA ratio may be an important discriminant market for CRC susceptibility. The fecal LCA-to-DCA ratio may depend on the differential hepatic synthesis of their respective precursors chenodeoxycholic acid (CDCA) and cholic acid. Hepatic synthesis of CDCA may be increased by more efficient conservation of dietary cholesterol because it has been shown that cholesterol of exogenous origin is the main precursor of this bile acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Steroids and cancer: Faecal bile acid screening for early detection of cancer risk

The analyses of faecal bile acids in colorectal cancer patients, breast cancer patients and healthy control subjects is described. Faecal excretion of total bile acids was similar in the three groups. The major bile acids detected were lithocholic acid (LCA) and deoxycholic acid (DCA) and the proportions of these (LCA:DCA ratio) were diametrically opposed in the colorectal cancer patients (1.91 +/- 0.33) and control subjects (0.90 +/- 0.09). Patients with adenocarcinoma of the breast also exhibited a higher LCA:DCA ratio (1.24 +/- 0.10) than the control group. The faecal LCA:DCA ratio is an important marker of cancer risk especially cancer of the large bowel and it is suggested that it may be a useful adjunct to future screening procedures.

Analysis of metabolic profiles of steroids in faeces of healthy subjects undergoing chenodeoxycholic acid treatment by liquid-gel chromatography and gas-liquid chromatography-mass spectrometry.

The multicomponent analysis of faecal steroids is described. Steroids were removed from faeces by solvent stripping in a Soxhlet apparatus and the resulting extracts were fractionated by diethylaminohydroxypropyl Sephadex column chromatography into neutral sterols, free bile acids, glycine conjugated bile acids, taurine conjugated bile acids and sulphated steroids. In this study the method has been applied for faecal steroid analyses of healthy subjects undergoing chenodeoxycholic acid therapy. Chenodeoxycholic acid administration causes a considerable increase in the concentration of faecal lithocholic acid which is a known comutagenic bile acid. Furthermore it has been shown that conjugated bile acids can account for between 10 and 20% of the faecal bile acid pool. The method described is convenient and may be useful for epidemiological studies which require a large number of faecal samples to be analysed.

Fecal steroids and urinary volatile phenols in four Scandinavian populations

Population samples from 4 study areas showing a 3-fold variation in large bowel cancer incidence were investigated for fecal bile acid loss and concentration, fecal neutral steroid loss and concentration, and urinary loss of volatile phenols. Each sample consisted of 30 randomly selected men, aged 50-59 years. Daily loss of bile acids was found to be identical in the 4 areas, but due to differences in fecal bulk, the fecal bile acid concentration varied, showing a positive correlation with large bowel cancer incidence. No significant difference between the 4 populations emerged with regard to fecal neutral steroids or urinary volatile phenols.

Relation between severity and extent of precancerous lesions in the postoperative stomach

The relation between the severity and extent of precancerous lesions in a precancerous condition of the stomach was assessed, to find a means of reducing the endoscopic workload required for the detection of such lesions. 87 subjects who had had gastric surgery for peptic ulcer more than 20 years ago underwent gastric endoscopy and biopsy. Severity of dysplasia correlated with its extent. Severity of intestinal metaplasia correlated with its extent and with severity of dysplasia. Type of operation, but not sex or type of ulcer, was the factor most strongly associated with dysplasia. Previous Billroth II operations were more strongly associated with occurrence of dysplasia (85%) than were other operations. In patients with previous Billroth II operations, moderate and severe dysplasia were commoner around the stoma (37%) than in the body (10%). These findings indicate that there is a relation between the severity and extent of precancerous lesions, which suggests that patients with dysplasia have widespread gastric mucosal instability. They also indicate that, if endoscopic screening is limited to Bilroth II subjects and if biopsies are limited to the stoma, endoscopic workload can be reduced by 85%, with only a small reduction (15%) in detection of moderate and severe dysplasia.

Faecal steroid loss in healthy subjects during short-term treatment with ursodeoxycholic acid

Faecal steroid loss in healthy subjects during short-term treatment with ursodeoxycholic acid has been investigated. The data shows conclusively that lithocholic acid, a known co-mutagen and co-carcinogen is the major bacterial metabolite of ursodeoxycholic acid in the human intestine. Although ursodeoxycholic acid is now the drug of choice for dissolution of cholesterol gallstones, elevation of intestinal lithocholic acid may have long-term repercussions since it has been demonstrated that a high faecal lithocholic acid: deoxycholic acid ratio shows a positive correlation with the incidence of colorectal cancer.

Development of a Reliable Measure for Determining Nitrate Exposure for Use in Epidemiological Studies

Regardless of dose or matrix, 24-h urinary nitrate reliably accounts for 50 to 60% of daily nitrate ingestion, except in those individuals who are immune stimulated and endogenously synthesize nitrate and those who are achlorhydric and lose a further 23% of dietary nitrate to bacterial metabolism in the stomach. For epidemiological studies the most reliable method of determining the nitrate exposure of a population is by the analysis of 24-h urine samples from healthy volunteers. Unhealthy volunteers should not be recruited.

Salmonella typhi/paratyphi and Gallbladder Cancer

Malignant neoplasms of the gallbladder and biliary tract are rare in most populations, and this is not a disease with which the average physician is familiar. It usually arises in the fundus (55%) or mid-section (30%), with the remainder arising in the neck of the gallbladder. Histologically, they are usually adenocarcinomas (83–95%), with squamous cell carcinomas accounting for the rest. They usually appear as infiltrative or scirrhous lesions, whereas those that are papillary often are confused with dysplastic adenomas.