Comparison of surgical vs chemical sphincterotomy using botulinum toxin for the treatment of chronic anal fissure: a meta-analysis.

OBJECTIVE: To analyse systematically prospective randomized controlled trials dealing with the effectiveness of surgical sphincterotomy (SS) vs chemical sphincterotomy (CS) using botulinum toxin for the management of chronic anal fissure (CAF). METHOD: A systematic review of the literature was undertaken. Prospective randomized controlled trials on the effectiveness of SS vs CS using botulinum toxin were selected and analysed to generate the summative outcome. RESULTS: Four prospective randomized controlled trials dealing with SS vs CS using botulinum injection, which included 279 CAF patients, were analysed. Based on the random effects model, there was a higher complication rate [Risk ratio (RR) 14.54 (-9.84, -38.9) 95% CI, df = 2, P < 0.0163] and a higher risk of transient faecal incontinence [RR 6.39 (-2.37, -15.1) 95% CI, df = 3, P < 0.0001] in the SS group than in the CS group. However, there was significant heterogeneity among the trials (Q = 8 408 891, P < 0.0001), indicating a wide confidence interval range; thus, the inferiority of SS could not be shown. SS had a significantly higher healing rate [RR 1.63, (1.34-1.91) 95% CI, df = 3, P < 0.0110] and a significantly lower recurrence rate [RR 0.35 (0.33-0.38) 95% CI, df = 3, P < 0.0221] than CS. CONCLUSION: Both CS and SS are comparable in the management of CAF. There are no differences in the complication rates and incontinence rates between the two procedures. SS has a higher healing rate and a lower recurrence rate than CS. As long as the patient is willing to accept a negligible risk of transient faecal incontinence, SS should be the first-line treatment for CAF.

High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis.

High-dose chemoradiotherapy (HDT) with autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed aggressive non-Hodgkin lymphoma (NHL). However, its role in the treatment of patients with primary refractory disease is not well defined. The outcomes of 85 patients with primary refractory aggressive NHL who underwent second-line chemotherapy with ICE with the intent of administering HDT/ASCT to those patients with chemosensitive disease were reviewed. Patients were retrospectively classified as induction partial responders (IPR) if they attained a partial response to doxorubicin-based front-line therapy or as induction failures (IF) if they had less than partial response. Forty-three patients (50.6%) had ICE-chemosensitive disease; there was no difference in the response rate between the IPR and the IF groups. Intention-to-treat analysis revealed that 25% of the patients were alive and 21.9% were event-free at a median follow-up of 35 months. Among 42 patients who underwent transplantation, the 3-year overall and event-free survival rates were 52.5% and 44.2%, respectively, similar to the outcomes for patients with chemosensitive relapsed disease. No differences were observed between the IPR and IF groups, and there were no transplantation-related deaths. More than one extranodal site of disease and a second-line age-adjusted International Prognostic Index of 3 or 4 before ICE chemotherapy were predictive of poor survival. These results suggest that patients with primary refractory aggressive NHL should receive second-line chemotherapy, with the intent of administering HDT/ASCT to those with chemosensitive disease. Newer therapies are needed to improve the outcomes of patients with poor-risk primary refractory disease.

Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma.

PURPOSE: To evaluate a chemotherapy regimen that consisted of ifosfamide administered as an infusion with bolus carboplatin, and etoposide (ICE) supported by granulocyte colony-stimulating factor (G-CSF) for cytoreduction and stem-cell mobilization in transplant-eligible patients with primary refractory or relapsed non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: One hundred sixty-three transplant-eligible patients with relapsed or primary refractory NHL were treated from October 1993 to December 1997 with ICE chemotherapy at Memorial Sloan-Kettering Cancer Center. Administration of three cycles of ICE chemotherapy was planned at 2-week intervals. Peripheral-blood progenitor cells were collected after cycle 3, and all patients who achieved a partial response (PR) or complete response (CR) to ICE chemotherapy were eligible to proceed to transplantation. Event-free and overall survival, ICE-related toxicity, and the number of CD34(+) cells collected after treatment with ICE and G-CSF were evaluated. RESULTS: All 163 patients were assessable for response, and there was no treatment-related mortality. A major response (CR/PR) was evident in 108 patients (66.3%); 89% of the responding patients underwent successful transplantation. Patient who underwent transplantation and achieved a CR to ICE had a superior overall survival to that of patients who achieved a PR (65% v 30%; P =.003). The median number of CD34(+) cells/kg collected was 8.4 x 10(6). The dose-limiting toxicity of ICE was hematologic, with 29.4% of patients developing grade 3/4 thrombocytopenia. There were minimal nonhematologic side effects. CONCLUSION: ICE chemotherapy, with ifosfamide administered as a 24-hour infusion to decrease CNS side effects, and the substitution of carboplatin for cisplatin to minimize nephrotoxicity, is a very effective cytoreduction and mobilization regimen in patients with NHL. Furthermore, the quality of the clinical response to ICE predicts for posttransplant outcome.