Focal Laser Ablation of Prostate Cancer: Results in 120 Patients with Low- to Intermediate-Risk Disease.

PURPOSE: Can focal laser ablation (FLA) of low to intermediate risk prostate cancer preserve sexual and urinary function with low morbidity while providing adequate oncologic outcomes. MATERIALS AND METHODS: Transrectal FLA was done in 120 patients with low- to intermediate-risk prostate cancer. MR imaging thermometry controlled ablation. At 6 and 12 months, patients had clinical and MR imaging follow-up with biopsy of suspicious areas. Patients submitted surveys of sexual and urinary function. Multivariate logistic regression identified determinants of positive imaging and biopsies. Two-sided Wilcoxon signed rank test evaluated scores and laboratory values. RESULTS: Median patient age was 64 years, and median prostate-specific antigen (PSA) was 6.05 ng/mL. Median follow-up period was 34 months (range, 17-55 months). Gleason score was 3+3=6 in 37 (30.8%), 3+4=7 in 56 (46.7%), and 4+3=7 in 27 (22.5%) patients. Tumor stage was T1c in 89 (74.2%), T2a in 26 (21.7%), and T2b in 5 (4.2%) patients. Twenty (17%) patients had additional oncologic therapy 1 year after FLA when biopsy confirmed cancer following abnormal MR imaging. There was no difference between functional scores before and after ablation. Median PSA decreased to 3.25 at 12 months (P < .001). Tumor diameter above the median (odds ratio = 3.36; 95% confidence interval, 1.41-7.97) was the only significant predictor for positive MR imaging after treatment. CONCLUSIONS: One year after FLA, selected patients had low morbidity, no significant changes in quality of life, and 83% freedom of retreatment rate. Sexual and urinary function did not significantly change after FLA.

Atypical small acinar proliferation at index prostate biopsy: rethinking the re-biopsy paradigm.

PURPOSE: Guidelines for atypical small acinar proliferation (ASAP) diagnosed on prostate biopsy recommend repeat biopsy within 3-6 months after diagnosis. We sought to discern the rate of detecting clinically significant prostate cancer on repeat biopsy and predictors associated with progression. MATERIALS AND METHODS: We performed a retrospective chart review of patients who underwent prostate biopsy at our institution from January 1, 2008, to December 31, 2015. Gleason grade group (GGG) system and D'Amico stratification were used to report pathology and risk stratification, respectively. Logistic and linear regression analyses were performed. RESULTS: A total of 593 patients underwent transrectal ultrasound-guided prostate biopsy, of which 27 (4.6%) had the diagnosis of ASAP. Of these, 11 (41%) had a repeat biopsy. Median time from diagnosis to repeat biopsy was 147 days (IQR 83.5-247.0). Distribution across the GGG system on repeat biopsy was as follows: 7 (63.6%) benign, 3 (27.3%) GG1, and 1 (9.1%) GG2. ASAP was not associated with subsequent diagnosis of clinically significant prostate cancer (OR 0.46, 95% CI 0.064-3.247, P = 0.432). There was no association between ASAP and high cancer risk (ASAP: ß = - 0.12; P = 0.204). CONCLUSIONS: Patients diagnosed with ASAP managed according to guideline recommendations are more likely diagnosed with benign pathology and indolent prostate cancer on repeat biopsy. These findings support prior studies suggesting refinement of guidelines in regard to the appropriateness and timeliness of repeat biopsy among patients diagnosed with ASAP.

Discerning the survival advantage among patients with prostate cancer who undergo radical prostatectomy or radiotherapy: The limitations of cancer registry data.

BACKGROUND: The objective of this study was to compare the overall survival of patients who undergo radical prostatectomy or radiotherapy versus noncancer controls to discern whether there is a survival advantage according to prostate cancer treatment and the impact of selection bias on these results. METHODS: A matched cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. In total, 34,473 patients ages 66 to 75 years were identified who were without significant comorbidity, were diagnosed with localized prostate cancer, and received treatment treated with surgery or radiotherapy between 2004 and 2011. These patients were matched to a noncancer control cohort. The rates of all-cause mortality that occurred within the study period were compared. Cox proportional hazards regression analysis was used to identify determinants associated with overall survival. RESULTS: Of 34,473 patients who were included in the analysis, 21,740 (63%) received radiation therapy, and 12,733 (37%) underwent surgery. There was improved survival in patients who underwent surgery (hazard ratio, 0.35; 95% confidence interval, 0.32-0.38) and in those who received radiotherapy (hazard ratio, 0.72; 95% confidence interval, 0.68-0.75) compared with noncancer controls. Overall survival improved significantly in both treatment groups, with the greatest benefit observed among patients who underwent surgery (log rank P < .001). CONCLUSIONS: Population-based data indicated that patients with prostate cancer who received treatment with either surgery or radiotherapy had improved overall survival compared with a cohort of matched noncancer controls. Surgery produce longer survival compared with radiation therapy. These results suggest an inherent selection-bias because of unmeasured confounding variables. Cancer 2017;123:1617-1624. © 2017 American Cancer Society.

Hepatocyte growth factor, a determinant of airspace homeostasis in the murine lung.

The alveolar compartment, the fundamental gas exchange unit in the lung, is critical for tissue oxygenation and viability. We explored hepatocyte growth factor (HGF), a pleiotrophic cytokine that promotes epithelial proliferation, morphogenesis, migration, and resistance to apoptosis, as a candidate mediator of alveolar formation and regeneration. Mice deficient in the expression of the HGF receptor Met in lung epithelial cells demonstrated impaired airspace formation marked by a reduction in alveolar epithelial cell abundance and survival, truncation of the pulmonary vascular bed, and enhanced oxidative stress. Administration of recombinant HGF to tight-skin mice, an established genetic emphysema model, attenuated airspace enlargement and reduced oxidative stress. Repair in the TSK/+ mouse was punctuated by enhanced akt and stat3 activation. HGF treatment of an alveolar epithelial cell line not only induced proliferation and scattering of the cells but also conferred protection against staurosporine-induced apoptosis, properties critical for alveolar septation. HGF promoted cell survival was attenuated by akt inhibition. Primary alveolar epithelial cells treated with HGF showed improved survival and enhanced antioxidant production. In conclusion, using both loss-of-function and gain-of-function maneuvers, we show that HGF signaling is necessary for alveolar homeostasis in the developing lung and that augmentation of HGF signaling can improve airspace morphology in murine emphysema. Our studies converge on prosurvival signaling and antioxidant protection as critical pathways in HGF-mediated airspace maintenance or repair. These findings support the exploration of HGF signaling enhancement for diseases of the airspace.