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Objectives To compare data on transperineal template biopsy (TPTB) under general anesthesia (GA) compared with local anesthesia (LA) procedures using the PrecisionPoint™ Transperineal Access System (PPTAS) in relation to tolerability, cancer detection rate, complications, and cost. Methods A prospective pilot cohort study of patients undergoing transperineal biopsy was performed. Patients were excluded if they had concurrent flexible cystoscopy or language barriers. Patients had a choice of GA or LA. A prospective questionnaire on Days 0, 1, 7, and 30 was applied. The primary outcome was patient tolerability. Secondary outcomes were cancer detection rate, complication rate, and theater utilization. Results This study included 80 patients (40 GA TPTB and 40 LA PPTAS). Baseline characteristics including age, prostate‐specific antigen (PSA), digital rectal examination (DRE), findings, and prostate volume were comparable between the groups (p = 0.3790, p = 0.9832, p = 0.444, p = 0.3939, respectively). Higher median prostate imaging‐reporting and data system (PI‐RADS) score of 4 (interquartile range [IQR] 2) versus 3 (IQR 1) was noted in the LA group (p = 0.0326). Pain was higher leaving recovery in the GA group however not significantly (p = 0.0555). Median pain score at LA infiltration was 5/10 (IQR 3), with no difference in pain at Days 1, 7, or 30 (p = 0.2722, 0.6465, and 0.8184, respectively). For GA versus LA, the overall cancer detection rate was 55% versus 55% (p = 1.000) with clinically significant cancer in 22.5% versus 35% (p = 0.217). Acute urinary retention (AUR) occurred in 5% of GA and 2.5% of LA patients (p = 1.000). The GA cohort spent longer in theater and in recovery with a median of 93.5 min versus 57 min for the LA group (p =

OBJECTIVES: To assess whether metformin reduces radio-resistance and increases survival in men undergoing external beam radiation therapy (EBRT) for prostate cancer (PCa), and to determine its effect on hypoxia inducible factor 1-α (HIF1α). PATIENTS AND METHODS: All patients treated with curative intent with EBRT for PCa at a major cancer centre between 2000 and 2007 were included in this study. The outcome measures of time to biochemical failure (BF), metastasis, PCa-specific mortality and overall survival (OS) were analysed in those taking metformin vs those not, using competing risk and Cox regression models. To determine metformin's effect on HIF1α expression and survival in vitro, PC3 cells with high basal HIF1α levels were subjected to increasing doses of metformin after H2 O2 -induced oxidative stress. RESULTS: A total of 2055 eligible cases, including 113 who were on metformin, were identified, with a median follow-up of 95.7 months. There were no differences in age, initial prostate-specific antigen level, Gleason score, T-stage, D'Amico risk class or duration of androgen deprivation therapy (ADT) between patients who were or were not on metformin. Treatment with metformin did not result in any apparent improvement in time to BF, time to metastasis detection or OS, but there was a 1.5-fold increase in PCa-specific deaths (P = 0.045) in patients on metformin and ADT when adjusted for cancer risk and comorbidities. When comparing patients on high-dose metformin (>1 g/d) with those on low-dose metformin (≤1 g), there was no difference in either time to metastases or time to BF. In vitro metformin at a high concentration of 100 μM did not reduce HIF1α expression, nor did metformin affect the PC3 cell survival when exposed to oxidative stress (H2 O2 ). CONCLUSIONS: No association was found between the use of metformin and time to metastasis detection, time to BF or OS in patients undergoing radiation therapy with or without ADT for PCa. In vitro, low therapeutic concentrations of metformin had no effect on HIF1α, and this observation could explain the conflicting evidence for the effectiveness of metformin in men undergoing EBRT for PCa. Higher, more toxic doses of metformin may be required to inhibit the mammalian target of rapamycin-HIF1α pathway in this patient group.

Pacific Islands mission teachers were powerful agents of culture change in Oceania, and the Christianity they taught is part of the ideological and constitutional under-pinnings of several independent Pacific Island states. Their fullest impact was felt in the period between the 1880s and 1914, when vast distances were being crossed and diverse populations reached by evangelists from half a dozen Pacific nationalities. Below the common religious motivations professed by the Islands teachers there were sharp contrasts in expectations and behaviour. This paper compares the Samoan, Fijian, and Queensland Melanesian missionaries in Papua, a colony where Islanders were concentrated in larger numbers than elsewhere. The Samoans are given the greater balance of analysis in the paper, because the 187 male Samoans outnumbered both the Fijians (110 males) and Queensland Melanesians (46), and because the Samoans’ expectations diverged more sharply from those of their Euro-pean colleagues than was the case with their Fijian and Queensland Melanesian contemporaries.