Malcolm C. Bateson

Clofibrate therapy and gallstone induction.

Two hundred consecutive patients, referred to a clinic established for the management of serum lipid disorders, were studied to assess the prevalence of gallbladder disease: 163 patients agreed to cholecystography of whom 23 had gallstones; 5 other patients had had cholecystectomy. There was a strong associction between clofibrate therapy and gallstones, which were found in 9 of 18 patients. Fifty-six patients with normal gallbladders had duodenal bile analyzed for lipid composition, and results were compared with those from 15 other patients with gallstones but normal serum lipids. Bile in hyperlipidemia and normolipidemic controls contained less cholesterol (9.21±3.48 mol/100 mol) than in clofibrate-treated patients (13.33±3.48 mol/100 mol, P<0.01), and in gallstone patients with normal serum lipids (11.87±4.52 mol/100 mol). There was no relationship demonstrable between patterns of hyperlipidemia or ischemic heart disease and the presence of gallbladder disease. There was also no association between biliary lipid composition and serum lipids or low-animal-fat diet. It is concluded that clofibrate therapy markedly increases biliary cholesterol content and is a potent lithogenic agent in patients not otherwise especially prone to gallstones. Since its role in prevention of ischemic heart disease is now uncertain, its continued wide use warrants close scrutiny.

Effect of Gallstone-Dissolution Therapy on Human Liver Structure

To assess potential toxic effects liver biopsies were performed before and after 6–8 months therapy with chenodeoxycholic acid (CDCA), 750 mg daily, in 6 patients with gallbladder stones. Minor fatty change and lipofuscin were seen prior to therapy, which tended to increase afterwards. Otherwise there was no consistent change on light microscopy. Electron microscopy showed parallel changes in the hepatocytes with no marked damage. There was a patchy loss of microvilli in the biliary epithelium. However, there was a significant increase in sinusoidal lipocytes or Ito cells, which was seen in every case. These 6 patients were representative of a group of 20 patients in whom serum liver function tests have been followed monthly for at least 6 months. During this period aspartate aminotransferase levels rose slightly but significantly, the mean remaining within the normal range. There was a trend to a decline in α-glutamyl transpeptidase levels, but this was less impressive and not statistically significant.

Clinical investigations in gastroenterology

1. Helicobacter Pylori. 2. Upper Digestive Endoscopy. 3. Intubation. 4. Oesophagus. 5. Stomach. 6. Small Intestine. 7. Absorption. 8. Colon and Rectum. 9. Gastrointestinal Bleeding. 10. Stool Examination. 11. Pancreas. 12. Liver Biochemistry. 13. Liver Biopsy. 14. Liver Imaging and Manometry. 15. Gallblader and Bile Ducts. 16. Ascites and the Peritoneum. Appendix 1: Antibiotic Prophylaxis in Gastrointestinal Endoscopy (BSG Guidelines). Appendix 2: BSP Dyspepsia Management Guidelines. Appendix 3: Chronic Diarrhoea. Further Reading: Procedures. Interpretation. Reference Textbooks. Index.

Colon and rectum

The importance of the rectal examination cannot be over-stressed: it should ideally form part of every complete bowel examination. A measure of the importance of the rectal examination is gauged by the fact that about 15% of all large bowel cancers can be felt digitally. It is usually possible to reach further with a finger than can be seen with an anoscope.

Liver Imaging and Manometry

The anatomy of the liver and spleen and the physiology of the portal circulation can be investigated in numerous ways. Some of the techniques are too specialized for general use, but many have found a place in routine diagnosis.

Ascites and the peritoneum

The aetiology of ascites may be obvious from the history and physical examination. However, it is generally necessary to examine the fluid microscopically, chemically and bacteriologically. Even when the cause is clinically apparent, for example hepatic cirrhosis and portal hypertension, it may not be possible to exclude either superimposed infection or hepatocellular cancer.

Gallbladder and Bile Ducts

Gallbladder stones form the majority of biliary disease, and are conveniently detected by ultrasonography (US).

Upper digestive endoscopy

The exact diagnosis of patients with haematemesis, dyspepsia and other upper abdominal symptoms cannot be made on the history alone. Diseases may simulate each other and different disorders can affect the same patient. Fibreoptic endoscopy with photography, biopsy and cytology has played a major role in evaluation and management. The technique is safe with a few contraindications, but requires training and experience to yield good results. It is usual for operators and assistants to wear disposable waterproof gloves. Special precautions are needed for patients known to carry hepatitis B virus, and those known or suspected of carrying HIV, including gowns and masks with visors. Endoscopy staff should be immunized against hepatitis B.

Gallbladder disease and hyperlipoproteinemia

To The Editor: The observations of Ahlberg et al (1) on gallbladder disease in Sweden suggest an association with type IV endogenous hypertriglyceridemia. As the authors state, these results are quite different from those in Scotland (2). This could reflect factors other than differences between countries. Although the prevalence of gallbladder disease in Sweden (3, 4) is much higher than in other Western countries (3, 57), the cholecystectomy rate in gallbladder disease is similar (17.7-20.3%) (3, 7) to figures from Scotland (13.8%) (5) and North America (24.1%) (6). This fact is important in the analysis of the conclusions of Ahlberg et al (1), because as previously mentioned by coauthor Einarsson (8), the apparent association between type IV endogenous hypertriglyceridemia and gallbladder disease was entirely due to the large number of patients who had cholecystectomies. Thus in the second report of the Stockholm study (1) there had been no less than 45 cholecystectomies in the 210 consecutive patients admitted with hyperlipidemia. Only 30 other patients actually had gallstones at the time of admission. A cholecystectomy rate of 60% in gallbladder disease is extremely high even by Swedish criteria. The group of patients studied was therefore unrepresentative of the general population for factors other than hyperlipidemia and simple gallbladder disease. There could be various explanations for this. There is a known chance association of diseases in hospital inpatients (9). Unconscious selection could occur if, for instance, doctors included serum lipid estimation in the assessment of patients with symptoms of gallbladder disease. Only a third of the hyperlipidemia patients had symptomatic heart disease, and the indication for measurement of serum lipids in the others is not clear, but could have related to their cholecystectomy. Current results in Dundee, Scotland, confirm the reported (2) lack of association between gallbladder disease and raised serum triglycerides (Table 1). Consecutive patients attending a lipid clinic were studied, and almost all referrals were ischemic heart disease patients and their relatives. The standardized gallbladder disease prevalence rates are identical with those found in the general population, both in a concurrent necropsy series and in a cholecystography survey of patients referred to the clinic but who were found to have normal serum lipids (2, 7). The cholecystectomy rate in hyperlipidemia patients with gallbladder disease was 12.5% (3 out 24 patients), similar to that observed in the community. Gallbladder d isease is common, and many claimed associations have subsequently been found to be doubtful or spurious (10), eg, those with hy-