Prostaglandin E2-mediated secretory diarrhea in villous adenoma of rectum: effect of treatment with indomethacin.

Biochemical and clinical evidence is presented to indicate that prostaglandin (PG)E2 is the mediator of fluid and electrolyte secretion by villous adenomas of the rectum. A 64-yr-old man with a 2-mo history of mucous diarrhea had, on admission, prerenal uremia, severe hyponatremia, and hypokalemia. At sigmoidoscopy an 11 X 11-cm villous adenoma of the rectum was revealed. The rectal fluid discharge was 1800-1825 ml/day, with sodium and potassium concentrations of 150 and 12 mEq/L, respectively. Immunoreactive PGE2 levels in the rectal effluents were high (viz. 1160-1250 pg/ml vs. 200-395 pg/ml) compared with those in stool water from patients with infectious diarrhea. The concentration of vasoactive intestinal polypeptide (VIP) in the tumor was lower (viz. 10.5 pmol/g vs. 100-700 pmol/g) than in normal colonic mucosa. Indomethacin treatment (24 mg X 4 daily) reduced the rectal PGE2 excretion from 2.2 to 0.3 microgram/day and caused a decrease in the rectal fluid loss of 850 ml/day associated with a similar reduction in rectal sodium excretion. Discontinuing medication, a rise in the rectal excretions of PGE2, fluid, and sodium was observed. In conclusion, PGE2 formation in the villous adenoma appears to be the cause of fluid secretion by the abnormal tumor epithelium. The use of PG synthetase inhibitors may facilitate the preoperative correction of severe fluid-electrolyte deficits in patients with large villous adenomas of the rectum.