sulindac and Fibroma

We report the case of a 22-year-old-man having a familial adenomatous polyposis coli treated by total colectomy with ileo-rectal anastomosis. Two years after the operation, an asymptomatic mesenteric fibromatosis appeared which was nonresectable due to mesenteric vessels infiltration. Nine years later, sulindac therapy was started for residual polyps in the rectal stump. This treatment was taken intermittently, during periods of 1 to 8 months, for 6 years. After 4 years of treatment, the tumor was no longer palpable. Four years after sulindac discontinuation, the patient was operated on for suspicion of intestinal adhesion. The mesenteric fibromatosis had completely disappeared and mesenteric vessels were free. This complete macroscopic regression of a desmoid tumor after sulindac therapy emphasizes again the interest of this treatment for mesenteric fibromatosis.

Topics: Adenomatous Polyposis Coli; Adult; Anti-Inflammatory Agents, Non-Steroidal; Biopsy; Fibroma; Humans; Male; Mesentery; Peritoneal Neoplasms; Remission Induction; Sulindac; Tomography, X-Ray Computed; Treatment Outcome

Intraabdominal desmoid tumour or fibromatosis, recurrent but non-metastatic, invasive, fibroblastic proliferations, are rare tumours. From 1968 to 1989, 16 patients were treated at Gustave Roussy Institute. They were associated with familial adenomatous polyposis in 10% of cases. These tumours, observed mainly in young women (70 to 85% of cases), are aggravated by pregnancy, and spontaneous regression can occur at menopause, proving their hormonal dependence. Although histologically benign, they are serious lesions due to their invasive character; their excision is complete in only 50% of cases. They recur in 30% to 75% of cases and cause death of the patient in 30% of cases. Treatment is surgical but due to their often very slow course, and their spontaneous stabilisation in some cases, a mutilating surgical treatment (extensive small intestine resection) does not seem to be justified. Radiotherapy is effective only at doses incompatible with the site of these tumours (35 to 60 Gy). Chemotherapy has never been shown to be effective.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Fibroma; Humans; Incidence; Male; Mesentery; Middle Aged; Pelvic Neoplasms; Peritoneal Neoplasms; Pregnancy; Radiation Dosage; Retroperitoneal Neoplasms; Sulindac; Tamoxifen; Time Factors

Forty of 416 patients with familial adenomatous polyposis were noted to have intra-abdominal desmoid tumors, and a subgroup of 16 were treated with noncytotoxic drug therapy. Drugs used were sulindac (14 patients), sulindac plus tamoxifen (3 patients), indomethacin (4 patients), tamoxifen (4 patients), progesterone (DEPO-PROVERA; Upjohn Co., Kalamazoo, MI) (2 patients), and testolactone (1 patient). Therapy with these drugs for continuous periods of six months or more resulted in three complete and seven partial remissions. When treated patients were compared with untreated patients (n = 12), there were significant benefits for the treated group, both in reduction of desmoid size and in improvement of symptoms, despite the inherent selection bias against this. Sulindac was the only drug used in enough patients to permit independent evaluation of its effect, with one complete and seven partial reductions of tumor size. Some patients had a delayed response to sulindac, with tumor shrinkage occurring after an initial period of tumor enlargement. When using sulindac for the treatment of desmoid tumors, this phenomenon should be considered.

Topics: Abdominal Neoplasms; Adenomatous Polyposis Coli; Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Fibroma; Humans; Male; Neoplasms, Multiple Primary; Pain; Remission Induction; Retrospective Studies; 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

Between January 1975 and December 1983, 24 of 183 patients (13%) with familial adenomatous polyposis (FAP) seen at the Mayo Clinic had mesenteric fibromatosis (MF). MF was found most often in FAP patients with associated extra-colonic "Gardner" signs (19 patients) and those who had had previous abdominal surgery (20 patients). In 4 patients, MF appeared spontaneously. The male-to-female ratio was 0.4, with a median age of 31 years in women and 37 years in men. Ten of 24 patients (42%) had been asymptomatic prior to diagnosis at time of surgery for FAP. Complications of the disease included intestinal or urinary tract obstruction. Minimal surgical manipulation seemed to be associated with fewer postoperative complications and a lesser risk of regrowth of the tumor. Nonsurgical treatment, including tamoxifen and sulindac in combination, may be beneficial. Surgery should be reserved for relief of obstruction, and bypass is preferred to resection.

Topics: Adenomatous Polyposis Coli; Adult; Female; Fibroma; Humans; Male; Mesentery; Middle Aged; Peritoneal Neoplasms; Risk Factors; Sulindac; Tamoxifen

Seven familial polyposis patients with desmoid tumors were treated with indomethacin, sulindac, or tamoxifen either as single agents or in combination. Serial computed tomographic (CT) scan examination was employed for objective measurement of tumor size since physical examination alone was an inaccurate means to evaluate intraabdominal and retroperitoneal desmoids. Only one patient with minimal tumor burden demonstrated a favorable response with complete resolution of an abdominal wall desmoid.

Topics: Adenomatous Polyposis Coli; Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Fibroma; Humans; Indenes; Indomethacin; Male; Sulindac; Tamoxifen

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