BACKGROUND Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease in women; it is associated with inappropriate activation of mammalian target of rapamycin (mTOR) signaling, which regulates cellular growth and lymphangiogenesis. Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1–2 trials involving patients with LAM. METHODS We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment — a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period. The primary end point was the difference between the groups in the rate of change (slope) in forced expiratory volume in 1 second (FEV1). RESULTS During the treatment period, the FEV1 slope was −12±2 ml per month in the placebo group (43 patients) and 1±2 ml per month in the sirolimus group (46 patients) (P<0.001). The absolute between-group difference in the mean change in FEV1 during the treatment period was 153 ml, or approximately 11% of the mean FEV1 at enrollment. As compared with the placebo group, the sirolimus group had improvement from baseline to 12 months in measures of forced vital capacity, functional residual capacity, serum vascular endothelial growth factor D (VEGF-D), and quality of life and functional performance. There was no significant between-group difference in this interval in the change in 6-minute walk distance or diffusing capacity of the lung for carbon monoxide. After discontinuation of sirolimus, the decline in lung function resumed in the sirolimus group and paralleled that in the placebo group. Adverse events were more common with sirolimus, but the frequency of serious adverse events did not differ significantly between the groups. CONCLUSIONS In patients with LAM, sirolimus stabilized lung function, reduced serum VEGF-D levels, and was associated with a reduction in symptoms and improvement in quality of life. Therapy with sirolimus may be useful in selected patients with LAM. (Funded by the National Institutes of Health and others; MILES ClinicalTrials.gov number, NCT00414648.)

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As part of an ongoing effort to evaluate alternative treatments for benign prostatic hyperplasia, we compared the outcomes of transurethral resection of the prostate with those of open prostatectomy. Men undergoing prostatectomy in Denmark (n = 36,703), Oxfordshire, England (n = 5284), and Manitoba, Canada (n = 12,090), were identified retrospectively through administrative data and followed for up to eight years. The cumulative percentage of patients undergoing a second prostatectomy was substantially higher after transurethral than after open prostatectomy (12.0 vs. 4.5 percent in Denmark, 12.0 vs. 1.8 percent in Oxfordshire, and 15.5 vs. 4.2 percent in Manitoba). The long-term age-specific mortality rates associated with transurethral prostatectomy as compared with open prostatectomy were also elevated in each country. The data on 1650 Canadian patients were used to investigate the contribution of coexisting morbid conditions to the elevated risk of death. The relative risk was 1.45 (95 percent confidence interval, 1.15 to 1.83) before risk adjustment and 1.45 (95 percent confidence interval, 1.15 to 1.84) after adjustment; the higher mortality was seen among low-risk as well as high-risk patients. These findings suggest that transurethral prostatectomy is less effective in overcoming urinary obstruction than the open operation. Our data also raise the possibility that transurethral prostatectomy may result in higher long-term mortality, although we cannot rule out potential confounding effects of unmeasured characteristics of patients.