Combined approach with infliximab, surgery, and methotrexate in severe fistulizing anoperineal Crohn's disease: results from a prospective study.

BACKGROUND: Infliximab is the only medical therapy that has been proven to be effective in fistulizing Crohn's disease (CD), but the recurrence rate of fistulas is high despite maintenance therapy. The aim of this prospective study was to evaluate the short- and long-term efficacy of a combined schedule with infliximab, methotrexate, and sphincter-sparing surgery in patients with severe fistulizing anoperineal CD. METHODS: From January 2006 to November 2007, all consecutive patients in three referral centers with severe fistulizing anoperineal CD were prospectively included after primary drainage. At inclusion, patients received three infliximab infusions at weeks 0, 2, and 6, and maintenance therapy with methotrexate. A second optimized surgical step consisting of at least removal of setons was performed between the second and the third infliximab infusions. RESULTS: Thirty-four CD patients (26 women; median age 38.5 years) with complex anoperineal fistula were enrolled (including 9 with recto-vaginal fistulas, and 10 with anorectal stenosis). At week 14 the response rate was 85% with 74% complete responders. At 1 year, 50% were still responders; luminal CD worsening was the major cause of relapse. Median Perineal Disease Activity Index (PDAI) and magnetic resonance imaging (MRI) scores significantly decreased from baseline to week 50. CONCLUSIONS: A combined approach with infliximab induction, two surgical sphincter-sparing steps and methotrexate is effective in achieving short-term response in severe fistulizing anoperineal CD. The best maintenance regimen remains to be determined.

Local excision of large rectal villous adenomas: long-term results.

PURPOSE: Transanal excision of rectal villous adenomas is a widely used surgical technique, because it is a one-step procedure, requiring no sophisticated instrumentation, and allowing complete histologic analysis of the excised tumor. Therefore, it ranks alongside radical surgery and palliative destructive procedures, but its results are highly variable in the published series. This discrepancy may be explained by the variable completeness of tumor excision because of potential dissection difficulties. Because intraoperative exposure may be a major limiting factor, one of us (JF) has developed a tractable cutaneomucous flap procedure to lower the rectal tumor to the anal verge, where control of the dissection line is easier. This retrospective review of consecutive patients operated on during ten-year period reports long-term results after transanal excision for large rectal villous adenomas with the tractable flap technique. PATIENTS: From 1978 to 1988, 207 consecutive patients (100 males), mean age 68 (range, 24-90) years, were operated on for an apparently benign villous rectal adenoma. Twenty-one patients (10 percent) were referred after failure of previous treatments: 11 endoscopic, 8 surgical, 1 laser, 1 radiotherapy. Mean distance of lower tumor edge from anal margin was 5.6 (range, 0-13) cm and was <10 cm in 82 percent. RESULTS: Three patients (1.5 percent), including one with a Tis carcinoma, underwent a secondary treatment for immediate gross failure of resection: one further local excision and two palliative laser destructions. Immediate postoperative course was uneventful for 96 percent; there was one death from perineal gangrenous infection, four cases of hemorrhage, and three urinary retentions. Subsequently one case of transient fecal incontinence and 11 medically managed stenoses were noted. Mean size of resected tumor was 5.4 (range, 1-17) cm. Deep excision margins concerned the rectal muscular layers in 199 patients (96 percent) and perirectal fat in 8 (4 percent). Specimen margins were negative for cancer in 175 (85 percent) and positive or unknown in 32 cases. Histologic evaluation demonstrated in situ cancer in 28 (14 percent) and invasive carcinoma in 9 (4 percent). In three patients (1 percent), two abdominoperineal resections were immediately performed (one T2 with a mucinous contingent, one T3) and one adjuvant radiotherapy (one undifferentiated T2). Four patients (2 percent) did not return for postoperative evaluation. For the remaining 198 patients, mean follow-up was 74 +/- 34 (median, 75; range, 1-168) months. Forty-four died from unrelated causes. Recurrence occurred in seven (3.6 percent) and was malignant in two, who subsequently died. Specific recurrence-free probability was 99.5 percent at one year, 96 percent at five years, and 95 percent at ten years. A lesion size >6 cm (10 vs. 1 percent for smaller tumors) and the presence of an invasive carcinoma (20 vs. 3 percent without invasive carcinoma) were significantly associated with an increased probability of recurrence at five years. CONCLUSION: Providing that adequate intraoperative exposure is obtained and advanced malignant tumors receive immediate secondary treatment, transanal resection of clinically benign, large rectal villous adenomas is safe and effective. It is an alternative to rectal resection, which exposes the patient to potentially adverse effects, and also to destructive procedures, which preclude any histologic evaluation of the tumor.