John T. Garbutt

Malignant melanoma is the most common malignancy to metastasize to the gastrointestinal tract. In a retrospective computer-assisted data search of over 2500 patients with melanoma registered over the past 10 years, 110 patients have been identified to have premortem gastrointestinal metastatic disease (metastatic disease identified at least 6 months before death). The small intestine (35%), colon (14.5%), and stomach (7%) are the most common sites for metastases. Polypoid or ulcerating masses and intramucosal nodules are typical radiologic presentations for gastric and colonic lesions, while over 50% of the small bowel metastases are polypoid masses that many times act as leading points for intussusception. Endoscopic studies are helpful in the preoperative diagnosis of these lesions. In a subset of 38 patients with symptomatic small bowel metastatic disease, complete resections were performed in 26% of patients, with palliative bypasses being performed in 40%, despite the fact that over 50% of the patients had documented visceral metastasis in other body sites. The operative morbidity rate was 15% with no operative deaths. Ninety percent of patients gained relief of symptoms, and overall survival from the time of confirmed small bowel disease averaged 17.3 months, with a range of 6 months to 9 years. It would seem that patients with melanoma with gastrointestinal metastatic disease can benefit from aggressive radiologic and endoscopic procedures for diagnosis and staging. Only through surgical interventions for symptomatic gastrointestinal disease can the quality of life be improved and life expectancy be extended.

The effect of cholestyramine administration on the enterohepatic circulation of bile acids was studied in eight normal volunteers. In six subjects the metabolism of sodium taurocholate-(14)C was determined after its intravenous injection before and during the 6th wk of cholestyramine administration, 16 g/day. In two subjects, the metabolism of cholic acid-(14)C was observed before and during the 2nd wk of cholestyramine, 16 g/day. Bile acid sequestration resulted in a more rapid disappearance of the injected primary bile acid and its metabolic products. The composition of fasting bile acids was promptly altered by cholestyramine to predominantly glycine-conjugated trihydroxy bile acid. In four subjects, unconjugated bile acid-(14)C was administered during cholestyramine administration; the relative proportion of glycine-conjugated bile acid-(14)C before enterohepatic circulation was similar to the relative proportion of unlabeled glycine-conjugated bile acid present in duodenal contents after an overnight fast, indicating that a hepatic mechanism was responsible for the elevated ratios of glycine- to taurine-conjugated bile acid (G: T ratios) observed. The relative proportions of both dihydroxy bile acids, chenodeoxycholic and deoxycholic, were significantly reduced. Steatorrhea did not occur, and the total bile acid pool size determined after an overnight fast was unaltered by cholestyramine. These findings suggest that in normal man bile acid sequestered from the enterohepatic circulation by cholestyramine is replaced by an increase in hepatic synthesis primarily via the pathway leading to production of glycocholic acid.