The effect of wide resection during radical prostatectomy on surgical margins.

INTRODUCTION: The impact of nerve-sparing on positive surgical margins during radical prostatectomy (RP) remains unclear. The objective of this study was to determine the incidence of positive surgical margins with a wide resection compared to a nerve-sparing technique. METHODS: A consecutive, single-surgeon patient cohort treated between August 2010 and November 2014 was reviewed. A standardized surgical approach of lobe-specific nerve-spare or wide resection was performed. Lobe-specific margin status and tumour stage were obtained from pathology reports. Univariable and multivariable associations between nerve management technique and lobe-specific positive surgical margin were determined. RESULTS: Of 388 prostate lobes, wide resection was performed in 105 (27%) and nerve-sparing in 283 (73%). In 273 lobes without extra-prostatic extension (EPE), 0 of 52 (0%) had a positive margin when wide resection was performed compared to 20 of 221 (9%) if nerve-sparing was performed (p=0.02). In 115 lobes with EPE, 11 of 53 (21%) had a positive margin if wide resection was performed compared to 28 of 62 (45%) if nerve-sparing was performed (p=0.006). In multivariable analysis, the risk of a positive margin was decreased among patients who received wide resection as compared to nerve-spare (RR 0.43, 95% CI 0.26-0.71; p=0.001). CONCLUSIONS: Surgical techniques to reduce positive surgical margins have become increasingly important as more patients with high-risk cancer are selecting surgery. The risk of a positive margin was greatly reduced using a standardized wide resection technique compared to nerve-sparing.

Active surveillance in Canadian men with low-grade prostate cancer.

BACKGROUND: Recent guidelines recommend against routine screening for prostate cancer, partly because of the risks associated with overtreatment of clinically indolent tumours. We aimed to determine the proportion of patients whose low-grade prostate cancer was managed by active surveillance instead of immediate treatment. METHODS: We reviewed data for patients who were referred to the Ottawa regional Prostate Cancer Assessment Clinic with abnormal results for prostate-specific antigen (PSA) or prostate examination between Apr. 1, 2008, and Jan. 31, 2013. Patients with subsequent biopsy-proven low-grade (Gleason score 6) cancer were included. Active surveillance was defined a priori as monitoring by means of PSA, digital rectal examination and repeat biopsies, with the potential for curative-intent treatment in the event of disease progression. RESULTS: Of 477 patients with low-grade cancer, active surveillance was used for 210 (44.0%), and the annual proportion increased from 32% (11/34) in 2008 to 67% (20/30) in 2013. Factors associated with immediate treatment were palpable tumour, PSA density above 0.2 ng/mL(2) and more than 2 positive biopsy cores. Factors associated with surveillance were age over 70 years and higher Charlson comorbidity index. Of 173 men who received immediate surgical treatment, 103 (59.5%) had higher-grade or advanced-stage disease on final pathologic examination. Of the 210 men with active surveillance, 62 (29.5%) received treatment within a median of 1.3 years, most commonly (52 [84%]) because of upgrading of disease on the basis of surveillance biopsy. INTERPRETATION: Active surveillance has become the most common management strategy for men with low-grade prostate cancer at our regional diagnostic centre. Factors associated with immediate treatment reflected those that increase the risk of higher-grade tumours.

Supplementation with α-lipoic acid, CoQ10, and vitamin E augments running performance and mitochondrial function in female mice.

Antioxidant supplements are widely consumed by the general public; however, their effects of on exercise performance are controversial. The aim of this study was to examine the effects of an antioxidant cocktail (α-lipoic acid, vitamin E and coenzyme Q10) on exercise performance, muscle function and training adaptations in mice. C57Bl/J6 mice were placed on antioxidant supplement or placebo-control diets (n = 36/group) and divided into trained (8 wks treadmill running) (n = 12/group) and untrained groups (n = 24/group). Antioxidant supplementation had no effect on the running performance of trained mice nor did it affect training adaptations; however, untrained female mice that received antioxidants performed significantly better than placebo-control mice (p ≤ 0.05). Furthermore, antioxidant-supplemented females (untrained) showed elevated respiratory capacity in freshly excised muscle fibers (quadriceps femoris) (p ≤ 0.05), reduced oxidative damage to muscle proteins (p ≤ 0.05), and increased expression of mitochondrial proteins (p ≤ 0.05) compared to placebo-controls. These changes were attributed to increased expression of proliferator-activated receptor gamma coactivator 1α (PGC-1α) (p ≤ 0.05) via activation of AMP-activated protein kinase (AMPK) (p ≤ 0.05) by antioxidant supplementation. Overall, these results indicate that this antioxidant supplement exerts gender specific effects; augmenting performance and mitochondrial function in untrained females, but does not attenuate training adaptations.

Exercise increases mitochondrial PGC-1alpha content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis.

Endurance exercise is known to induce metabolic adaptations in skeletal muscle via activation of the transcriptional co-activator peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α). PGC-1α regulates mitochondrial biogenesis via regulating transcription of nuclear-encoded mitochondrial genes. Recently, PGC-1α has been shown to reside in mitochondria; however, the physiological consequences of mitochondrial PGC-1α remain unknown. We sought to delineate if an acute bout of endurance exercise can mediate an increase in mitochondrial PGC-1α content where it may co-activate mitochondrial transcription factor A to promote mtDNA transcription. C57Bl/6J mice (n = 12/group; ♀ = ♂) were randomly assigned to sedentary (SED), forced-endurance (END) exercise (15 m/min for 90 min), or forced endurance +3 h of recovery (END+3h) group. The END group was sacrificed immediately after exercise, whereas the SED and END+3h groups were euthanized 3 h after acute exercise. Acute exercise coordinately increased the mRNA expression of nuclear and mitochondrial DNA-encoded mitochondrial transcripts. Nuclear and mitochondrial abundance of PGC-1α in END and END+3h groups was significantly higher versus SED mice. In mitochondria, PGC-1α is in a complex with mitochondrial transcription factor A at mtDNA D-loop, and this interaction was positively modulated by exercise, similar to the increased binding of PGC-1α at the NRF-1 promoter. We conclude that in response to acute altered energy demands, PGC-1α re-localizes into nuclear and mitochondrial compartments where it functions as a transcriptional co-activator for both nuclear and mitochondrial DNA transcription factors. These results suggest that PGC-1α may dynamically facilitate nuclear-mitochondrial DNA cross-talk to promote net mitochondrial biogenesis.