sulindac and Gardner-Syndrome

A 22-year-old woman with Gardner's syndrome in whom long-term sulindac therapy, without surgical treatment, was effective in inducing complete regression of colonic adenomas is reported. One hundred milligrams of sulindac was administered twice daily after endoscopic polypectomy. Follow-up colonoscopy 6 months later revealed an encouraging regression of colonic adenomas. The tumors had disappeared after 40 months of sulindac treatment. A sustained effect was identified even after 51 months. Ten milligrams of famotidine was coadministered to prevent side effects of sulindac. Although the effect of sulindac on colorectal adenomas may be transient, this therapy may be useful for postponing prophylactic colectomy, especially for the sparse type of familial adenomatous polyposis.

Topics: Adenoma; Adult; Antineoplastic Agents; Colonic Neoplasms; Female; Follow-Up Studies; Gardner Syndrome; Humans; Radiography; Remission Induction; Skull; Sulindac; Time Factors

Duodenal polyps with a malignant potential pose a serious threat to Gardner's patients. Several reports have shown regression or disappearance of colonic polyps with sulindac therapy. We report the first case of disappearance of duodenal polyps with sulindac.

Topics: Aged; Duodenal Neoplasms; Gardner Syndrome; Humans; Intestinal Polyps; Male; Recurrence; Remission Induction; Sulindac

Topics: Adenomatous Polyposis Coli; Adult; Colonic Polyps; Female; Gardner Syndrome; Humans; Intestinal Mucosa; Male; Middle Aged; Prostaglandins; Sulindac

Ten patients with large inoperable desmoid tumors in various body locations were treated with testolactone. Four tumors (40%) responded with major regressions, i.e., more than 50% reduction in volume. Eight patients received nonsteroid anti-inflammatory drugs (indomethacin, sulindac, or sulindac with warfarin and vitamin K1 [Mephyton]) for periods of 2 to 91 months. There was one major regression, one partial regression, and three instances of tumor growth arrest over periods up to 8 years. Seven patients were treated with nonsteroid anti-inflammatory drugs concurrent with or after testolactone or tamoxifen. There were five major regressions and one partial regression with extensive central necrosis of an enormous intra-abdominal tumor. The last patient has been treated for only 12 months, with no change in tumor volume. It appears that estrogens function as growth factors for desmoid tumors, and that minimization of these effects inhibits tumor growth in some, but not all, cases. In those instances where antiestrogens were not effective as single agents, the tumors usually responded to subsequent nonsteroid anti-inflammatory drug therapy. Withdrawal of estrogen may be followed by inhibition of transcription of genes that support tumor cell proliferation, and sulindac and indomethacin may augment these effects by inhibiting prostaglandin and cyclic AMP synthesis and the activity of protein kinase C. Warfarin may function as a protonophore to acidify the cytoplasm and prevent the alkalinization that is necessary to initiate DNA synthesis and cell cycle progression, again an impairment of the transcription process.

Topics: Abdominal Neoplasms; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fibroma; Gardner Syndrome; Humans; Indomethacin; Male; Remission Induction; Sulindac; Tamoxifen; Testolactone; Time Factors; Vitamin K 1; Warfarin

Sulindac causes both regression and suppression of colorectal polyps in patients with Gardner's syndrome and familial polyposis coli. Three patients with Gardner's syndrome and multiple colonic polyps had complete regression of polyps after two to three months of sulindac therapy. The implication that sulindac may prevent colorectal cancer and prophylactic surgery in patients with hereditary polyps of the colon is intriguing but has not yet been substantiated.

Topics: Adult; Child; Female; Gardner Syndrome; Humans; Male; Middle Aged; Pedigree; Sulindac

The effect of sulindac, a nonsteroid antiinflammatory drug, on colon polyposis has been evaluated in seven patients after subtotal colectomy and ileoproctostomy and in four patients with intact colons. The patients all had Gardner's syndrome or familial polyposis coli. All polyps were eliminated, except for a few that arose in the rectal mucosa and the anal canal. No cancers developed in these patients on follow-up.

Topics: Adenomatous Polyposis Coli; Adolescent; Adult; Child; Colectomy; Colonic Polyps; Combined Modality Therapy; Drug Evaluation; Female; Gardner Syndrome; Humans; Indenes; Male; Neoplasm Recurrence, Local; Sulindac

Mesenteric desmoid tumors are a recognized sequela of colectomy for polyposis coli of Gardner's type. Relentless growth and recurrence carry a poor prognosis. Recently, nonsteroidal anti-inflammatory drugs have been used to halt the growth of these tumors, presumably by interfering with prostaglandin metabolism. A 36-year-old man presented with small-bowel obstruction secondary to a large, diffuse mesenteric desmoid six years following colectomy and ileoproctostomy. Laparotomy revealed it to be unresectable. Postoperatively, he was started on sulindac (Clinoril) 100 mg twice a day. His obstruction resolved, and he remains well at 11 months. A CT scan shows diminution in the size of the tumor. Nonsteroidal anti-inflammatory agents may be an alternative to chemotherapy and radiotherapy in treating mesenteric desmoids.

Topics: Adult; Colectomy; Fibroma; Gardner Syndrome; Humans; Indenes; Male; Mesentery; Peritoneal Neoplasms; Prostaglandin Antagonists; Sulindac

Four members of a Gardner's syndrome family had rectal and colon polyposis treated with nonsteroid anti-inflammatory drugs. Three of these patients had had subtotal colectomy and ileoproctostomy and the residual polyps arose in the rectal mucosa. The polyps almost completely disappeared when sulindac was administered. Indomethacin therapy over the course of a preceding year was ineffective in one of these patients. One patient (case 4) had diffuse polyposis in an intact colon. After sulindac therapy for a year, only three small mucosal polyps could be identified by air contrast barium enema and colonoscopic examination. These observations confirm those of Pollard and Luckert [1,2] on rats with chemically induced polyposis of the intestinal tract.

Topics: Adolescent; Adult; Colonic Neoplasms; Drug Evaluation; Female; Gardner Syndrome; Humans; Indenes; Indomethacin; Male; Sulindac