Hepatobiliary effects of obesity and weight-reducing surgery.

Obesity clearly increases the risk of gallstone formation. The role of nucleating factors may be most decisive in transforming merely saturated bile into a gallstone-forming solution. Weight loss in the short run may promote stone formation but in the long run may be beneficial if it is maintained. UDCA appears to be a promising prophylactic agent against gallstone formation during weight loss regardless of whether it is achieved by diet alone, by jejunoileal bypass, or by gastric restriction surgery.

Effect of estradiol upon serum enzymes in primary biliary cirrhosis.

The repeated observation of a fall in serum enzymes at midmenstrual cycle in an untreated patient with primary biliary cirrhosis stimulated a study of estrogen administration in five patients with primary biliary cirrhosis. One patient was premenopausal, one patient was postmenopausal and three had had oophorectomy. After 2 weeks of ethinyl estradiol, AST was under 100 IU per dl in all and had decreased by 50% or more in 4 of 5 patients. gamma-glutamyltransferase and alkaline phosphatase fell by 50 and 30% or more, respectively, in all patients. The decreases in serum enzymes were statistically significant in all patients for gamma-glutamyltransferase, in 4 of 5 for AST and in 3 of 5 for alkaline phosphatase. One patient developed increased icterus leading to withdrawal of estradiol. Withdrawal of estradiol was followed by return toward control values over variable periods, usually 1 to 4 weeks. Repeated courses of estradiol reproduced these enzyme changes. These observations indicate that estradiol in the doses used (0.05 mg per day) reversibly lowers serum enzyme values in biliary cirrhosis. The mechanism of the effect is unexplained, but an immune system alteration may be responsible.

The morphological effects of chenodeoxycholic acid on human gastric mucosa.

Morphology of human gastric mucosa was examined by light microscopy before and after exposure to suspensions of chenodeoxycholic acid tablets. During gastroscopy with a flexible instrument the gastric mucosa of eight control subjects without gastric disease was biopsied. In five other patients the chenodeoxycholic acid tablet suspension was instilled immediately after control biopsies of mucosa. Subsequent biopsies were collected after 10-15 min exposure to the suspension. Surface mucosal cells regularly showed development of clear cytoplasmic vacuoles, marked cytoplasmic condensations, and pyknosis of the nuclei. Appreciable changes in relative cytoplasmic staining density, loss of intactness of cells, and loss of surface mucous cell granules were observed less frequently. Thus, exposure of gastric mucosa to chenodeoxycholic acid tablet suspensions may be associated with histological changes in surface mucosal cells.

Encephalopathy following jejunoileostomy.

A neurological syndrome characterized by episodes of confusion, slurred speech, and unsteadiness is described in patients who have undergone jejunoileostomy for obesity. This syndrome has been noted in seven of 110 patients studied, although it may be more common. It appears to subside spontaneously or may respond to oral food restriction, with or without intravenous fluid plus vitamins and minerals. Episodes tend to recur in a given patient. Reversible changes in the EEG have been observed. Pertinent clinical and laboratory findings are described but no definite etiologic factor has been identified. The possible mechanisms involved in this syndrome of metabolic encephalopathy following jejunoileostomy are discussed.

Assessment of jejunoileostomy for obesity--some observations since 1976.

In this review, which only partially covers the data available, it is pointed out that the evaluation of the results of jejunoileostomy may depend upon the criteria used by the observers, and disclosure of the true effects of the operation may depend upon the long-term follow-up of the patients. With increasing length of observation, it has become apparent that problems such as vitamin D deficiency, renal stone formation, continued steatorrhea, gallstones, zinc and copper deficiency, and even renal failure may be seen with disturbing frequency. Some of these may be preventable, others may be correctable and, indeed, the overall incidence of genuinely severe problems may, in the long run, be sufficiently low so as to make the benefits of jejunoileostomy outweigh the hazards. The rate of patient satisfaction is high, quality of life is generally improved and psychosocial and economic benefits of jejunoileostomy are apparent. The operation may also be a better alternative than the physical hazards of continuing obesity. Whether or not gastric bypass represents a true improvement over jejunoileostomy will depend upon the conclusions reached after applying to it the same searching scrutiny that is being used to examine the long-term results of jejunoileostomy.

Effect of sphincteroplasty on gallbladder function and bile composition.

The effect of sphincteroplasty on bile concentration and composition and on gallbladder function was investigated in the dog. Gallbladder and hepatic bile samples were analyzed for cholesterol, phospholipid (lecithin), bile salt concentration and individual bile salt content. Motor function was studied by cholecystokinin-cholecystography with changes in gallbladder volume computed from the radiographs. All bile samples were cultured and at the conclusion of the experiments, the gallbladders were histologically examined. Sphincteroplasty did not alter biliary cholesterol concentration but the concentration of lecithin and bile salts decreased in gallbladder bile and increased in hepatic bile (p less than .001). These changes depict a trend toward greater lithogenicity for gallbladder bile and lesser lithogenicity for hepatic bile. Postoperative analysis of individual bile salts in gallbladder bile showed an increase in monohydroxy and dihydroxy bile salts and a decrease in trihydroxy bile salts (p less than .001). This tendency has been shown to be conducive to gallstone formation. The concentrating ability of the gallbladder was partially eliminated by sphincteroplasty but gallbladder filling and motor response to stimulation by cholecystokinin was not affected. All gallbladders demonstrated histologic changes of chronic inflammation and all developed a significant bacterial flora following sphincteroplasty. It is concluded that cholecystectomy should always be performed following transduodenal sphincteroplasty not because of any resultant abnormality of motor function, as has previously been held, but because of the resultant abnormality of gallbladder pathophysiology.

Fecal fat, bile acid, and sterol excretion abd biliary lipid changes in jejunoileostomy patients.

Fecal fat, bile acid, and neutral sterol excretion and biliary bile acid, phospholipid, and cholesterol were studied in 36 patients 6 to 12 months after jejunoileostomy for obesity. No relationship was observed between the degree of steatorrhea and weight loss, although fecal fat rose sharply in all except 2 patients. Mean neutral sterol excretion in feces was unchanged after operation except in cholecystectomized patients. No relationship could be demonstrated between serum cholesterol decrease and fecal biel acid, which rose 3-fold, or between cholesterol and the sum of fecal fat and neutral sterol. Fecal excretion of cholic and deoxycholic acid together increased more than the total excretion of cxcretion patterns were demonstrable: moderate fecal fat (24 g or less on 65-g intake) was associated with a predominance of secondary bile acids in feces and in bile; high fecal fat (above 24 g/day) was associated with predominantly primary bile acids. A high incidence of gallstones or previous cholecystectomy (36%) was found preoperatively and of 25 patients with normal cholecystograms, four developed stones and five had nonvisualization of gallbladder 6 to 12 months postoperatively. Bile saturation ratio and lithogenic index were not consistently changed postoperatively. No clear cut increase in lithogenic potential or in bile acid (lithocholic acid) hepatotoxic potential after jejunoileostomy was demonstrable.

Ileal bypass for obesity: postoperative perspective.

Initially, diarrhea is almost universal but becomes self-limited unless the patient persists in overeating. Weight loss averages 75 to 100 lb the first year, with a stable level generally achieved after 18 months. Among the serious potential complications are enteritis, kidney stones, gallstones, and hepatopathology. Some can be anticipated and kept at bay by prophylactic measures like high-protein intake.