sulindac and Abdominal-Neoplasms

Aim of this study is to evaluate the outcome of long-term conservative treatment with sulindac and high-dose selective estrogen receptor modulators (SERMs) for sporadic and FAP-associated desmoid tumors. Desmoids are very rare tumors in the general population but occur frequently in FAP patients, being encountered in 23-38 %. Treatment of desmoids is still most controversial since response cannot be predicted and they are prone to develop recurrence. This study included all desmoid patients that were treated and followed at our institution and had completed at least 1 year of treatment. Response was defined as stable size or regression of desmoid size between two CT or MRI scans. A total of 134 patients were included. 64 (47.8 %) patients had a confirmed diagnosis of FAP, 69 (51.5 %) patients were sporadic. Overall 114 (85.1 %) patients showed regressive or stable desmoid size. Patients with previous history of multiple desmoid-related surgeries showed less-favorable response. The mean time to reach at least stable size was 14.9 (±9.1) months. After regression or stabilization, medication was tapered in 69 (60.5 %) of the treated patients with only one long-term recurrence after >10 years. The results of this study fortify the role of sulindac and high-dose SERMs as an effective and safe treatment for both, sporadic and FAP-associated desmoid tumors. While invasive treatment frequently results in high recurrence rates, high morbidity and high mortality, this conservative treatment is successful in most patients. The recurrence rate is negligible with no desmoid-related mortality in this large series. Therefore surgical resection, especially for mesenteric desmoids, should be deferred favoring this convincingly effective, well tolerated regimen.

Topics: Abdominal Neoplasms; Adenomatous Polyposis Coli; Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Fibromatosis, Aggressive; Humans; Male; Middle Aged; Selective Estrogen Receptor Modulators; Sulindac; Treatment Outcome

Intra-abdominal desmoid disease is one of the most common extra-intestinal manifestations of familial adenomatous polyposis. Small bowel obstruction occurs frequently in affected patients and is notoriously difficult to treat. The aim of this study was to review the management and outcome of desmoid-related small bowel obstruction.. This was a retrospective, descriptive study of patients with familial adenomatous polyposis and intra-abdominal desmoid disease who developed small bowel obstruction. Demographic data and data concerning the presentation, diagnosis and treatment of the bowel obstructions were abstracted from the polyposis database or patients' records. Patients with obstruction unrelated to desmoid disease were excluded.. There were 47 patients (30 women and 17 men). Median age at first bowel obstruction was 24.2 (interquartile range 19.2-34.2) years. The median time from index surgery to first bowel obstruction was 4.1 (interquartile range 1.5-9.0) years. Twenty-two patients had a colectomy and ileorectal anastomosis and 21 a proctocolectomy and ileoanal pouch. Obstruction was treated medically in 29% of cases and surgically in 69%. Thirteen patients had total parental nutrition. Thirty (63.8%) had a second episode of small bowel obstruction at a mean of 5.3 years after the first, 50% of which were treated medically. Eighteen (37.5%) patients had more than two episodes of bowel obstruction. There were 118 operations, including lysis of adhesions (29), small bowel resection (14), bypass (12), ileostomy (12), desmoid excision (9) and stricturoplasty (2).. Desmoid-related small bowel obstruction in familial adenomatous polyposis patients requires multiple surgical strategies to restore a patent gastrointestinal tract. WHAT DOES THIS PAPER ADD TO THE LITERATURE?: This is the only series in the literature specifically addressing small bowel obstruction in patients with familial adenomatous polyposis and intra-abdominal desmoid disease. The data show that small bowel obstruction is common, tends to recur, but can be successfully managed by a combination of medical and well selected surgical treatment.

Topics: Abdominal Neoplasms; Adenomatous Polyposis Coli; Adolescent; Adult; Antineoplastic Agents; Cohort Studies; Colectomy; Duodenal Obstruction; Female; Fibromatosis, Aggressive; Humans; Ileal Diseases; Ileostomy; Intestinal Obstruction; Jejunal Diseases; Male; Middle Aged; Parenteral Nutrition, Total; Proctocolectomy, Restorative; Recurrence; Retrospective Studies; Sulindac; Time Factors; Young Adult

Topics: Abdominal Neoplasms; Adenomatous Polyposis Coli; Antineoplastic Agents; Fibromatosis, Aggressive; Humans; Sulindac; Tamoxifen; Treatment Outcome

Desmoid tumors are mesenchymal nonmetastasizing neoplasms. Although rare in the general population, they are a common extracolonic manifestation of familial adenomatous polyposis (FAP). Because of high tumor recurrence rates, surgery has been less than satisfactory in the treatment of desmoid tumors. In the current study, high doses of tamoxifen in combination with sulindac were used to treat severe desmoid tumors to avoid surgery.. Since 1992, 25 patients at Heinrich Heine University (Dusseldorf, Germany) were treated with a combination of tamoxifen and sulindac. In the current study, 17 patients with FAP-associated and 8 patients with sporadic desmoid tumors received 120 mg of tamoxifen and 300 mg of sulindac daily. Every 6 months, the protracted course of desmoid growth was measured by computed tomography and/or magnetic resonance imaging scans. Tumor responses were characterized as progressive disease, stable disease (SD), partial regression (PR), and complete regression (CR).. Of the group of patients who received tamoxifen and sulindac as a primary treatment, all three patients with sporadic desmoid tumors demonstrated cessation of growth, and 10 of the 13 patients with FAP-associated tumors achieved either a PR or CR. In the sporadic desmoid tumor group, eight of nine patients developed tumor recurrences after undergoing surgery at other institutions. Of these, two patients had SD and two patients had a PR to CR.. The patients with desmoid tumors who were managed conservatively with high-dose tamoxifen and sulindac had the best outcome. Desmoid tumor recurrence after surgery was high and in the FAP-associated tumor group, therapy with tamoxifen and sulindac was found to be less successful. Based on this experience, the authors recommended high-dose tamoxifen and sulindac as the primary treatment for patients with FAP-associated desmoid tumors. However, to our knowledge, the best approach after surgical intervention for patients with sporadic desmoid tumors remains to be determined.

Topics: Abdominal Neoplasms; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fibromatosis, Abdominal; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Retrospective Studies; Risk Assessment; Sulindac; Survival Analysis; Tamoxifen; Treatment Outcome

Topics: Abdominal Neoplasms; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Female; Fibromatosis, Aggressive; Humans; Male; Maximum Tolerated Dose; Prognosis; Risk Assessment; Sulindac; Survival Analysis; Tamoxifen; Treatment Outcome

We investigated whether the therapeutic action of sulindac, used for the treatment of familial adenomatous polyposis, desmoid tumors, and against colon cancer, could be mediated by its active metabolite, sulindac sulfide, in cell growth and apoptosis on cell lines derived from abdominal neoplasms. Sulindac sulfide actions on cell growth and apoptosis were evaluated in epithelial human colon tumor 8 (HCT8) cell line and mesenchymal cell lines (bovine bone endothelial (BBE) cell line, desmoid tumor-derived cells, human colorectal cancer-derived fibroblasts). Sulindac sulfide (0.1-60 microg/ml) induced a dose-dependent inhibition of cell proliferation of all cell lines tested. Apoptosis was induced at doses of 20 and 40 microg/ml, respectively, in BBE and HCT8 cells with no effect on desmoid tumor cells and colorectal cancer-derived fibroblasts. Since mesenchymal cells respond to clinically effective concentrations of the compound, its preferential action on the stromal compartment of intestinal polyps, desmoid tumors and colon cancer can be proposed, with consequent regression of the tumor.

Topics: Abdominal Neoplasms; Animals; Antineoplastic Agents; Apoptosis; Cell Division; Cell Line; DNA Fragmentation; Dose-Response Relationship, Drug; Epithelial Cells; Humans; Mesoderm; Sulindac; Tumor Cells, Cultured

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