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Malignant pleural mesothelioma (MPM) is a highly lethal pleural neoplasm that is often resistant to chemotherapeutic drugs, including cisplatin, and for which little is known regarding carcinogenic pathways. We used differential display to compare gene expression patterns in mesothelioma, normal pleura and normal lung, in order to better understand MPM pathobiology, and to search for genes that may facilitate drug resistance in this cancer. The human inhibitor of apoptosis protein-1 gene (IAP-1/MIHC/cIAP2) was discovered to be highly expressed in MPM. We confirmed overexpression of IAP-1 mRNA and protein in 39 additional human MPM tumor specimens and 3/5 (60%) MPM cell lines by multiple methods, including real time quantitative reverse transcription-PCR and western blot analysis. Using an antisense targeting approach, we found that attenuation of IAP-1 mRNA levels decreases baseline cell viability and increases the sensitivity of MPM cell lines to cisplatin by nearly 20-fold. Reduced IAP-1 gene expression also results in a concordant increase of the pro-apoptotic cleavage product of caspase 9 and a reduction in the number of viable tumor cells. Our observations strongly suggest that IAP-1 is at least partly responsible for promoting carcinogenesis and mediating resistance to cisplatin in many MPM tumors and that further study of this apoptotic pathway is warranted.

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Abdominal operations for rectal prolapse are associated with lower recurrence rates than perineal procedures but presumed higher morbidity. Therefore, perineal procedures are recommended for patients deemed unfit for abdominal repair. Consequently, bias confounds retrospective comparisons of the two approaches. To clarify the impact of operative approach on outcomes, we analyzed abdominal and perineal procedures in a propensity score-matched analysis. We selected patients undergoing surgery for rectal prolapse from the American College of Surgeons National Surgical Quality Improvement Program data set from 2005 to 2010. We grouped procedures as abdominal or perineal. We identified preoperative variables predictive of complications and regressed against operative approach. The resulting propensity score was used to select a matched cohort with similar clinical risk. We identified 2188 patients (848 abdominal [38.8%]; 1340 perineal [61.2%]). Patients undergoing the perineal approach had higher rates of most risk variables. Propensity matching resulted in 563 matched pairs (1126 patients) with similar clinical risk. In this matched cohort, no significant difference was found in the rate of any complication between the operative approaches; mortality was 0.9 per cent in each group ( P = 1.0). Relative risk for major morbidity after abdominal approach was 1.39 (95% confidence interval, 0.92 to 2.10; P = 0.15). Although many patients with rectal prolapse are high risk for abdominal surgery, our study indicates that many patients treated by perineal repair could be safely treated with a more durable operation.

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