ISSN:
1530-0358
Keywords:
Adenoma reversion
;
Colectomy
;
Dysplasia reversion
;
FAP
;
Familial adenomatous polyposis
;
Low-dose maintenance therapy
;
NSAID
;
Prostaglandins
;
Sulindac
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract PURPOSE: This nonrandomized, controlled Phase II pilot study aims at the lowest effective dose of rectally applied sulindac to achieve and maintain adenoma reversion in colectomized patients with familial adenomatous polyposis (FAP). METHODS: The study group (n = 15) underwent proctoscopic and laboratory follow-up for polyp reversion every 6 to 12 weeks. Polyp reversion was followed by dose reduction in predefined steps. Proliferating cell nuclear antigen/cyclin (PCNA) and KI-67 proliferation indices (PI) were performed by point counting. Prostaglandin (PG)E2 and PGF2α were quantified by time-resolved competitive fluorescence immunoassay. RESULTS: All patients responded to therapy within 6 to 24 weeks. Sixty and 87 percent of patients achieved complete adenoma reversion after 48 weeks at 53 and 67 mg of sulindac per day per patient on average, respectively. Reversion was evident compared with the control group. Dose reduction by one-sixth to one-eighth of the usual oral dose was significant (Mann's trend test,P 〈 0.05). PCNA and KI-67 Pls of adenomatous and flat mucosa were significantly reduced (Wilcoxon's test,P 〈0.05). Correlation of PCNA and KI-67 Pls indicate similar reaction of different tissue structures (Spearman's rank correlation test,P 〈0.01). Nonsteroidal anti-inflammatory drug-induced redifferentiation from high-grade to low-grade dysplasia occurred in all but two patients. Tissue-PGE2 levels were greatly reduced. Unwanted, curable side effects were rare (gastritis,n =2), and laboratory controls are within detection limits. CONCLUSIONS: Low-dose rectal sulindac maintenance therapy is highly effective in achieving complete adenoma reversion without relapse in 87 percent of patients after 33 months. Rectal FAP phenotype should be crucial for the surgical decision. Colectomy with ileorectal anastomosis and regular chemoprevention might proceed to be a promising alternative to pouch procedures. Chemoprevention with lower incidence of FAP-related tumors via dysplasia reversion may be possible in the future.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02049838
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