ImportanceFocal therapy involves treating only the cancerous area within the prostate rather than the whole gland. Comparative effectiveness data for oncological and functional outcomes are lacking.
ObjectiveTo evaluate oncological and functional outcomes of focal therapy in comparison to radical prostatectomy in patients with clinically significant, non-metastatic prostate cancer.
DesignA 1:1 propensity score matched study, reviewing patients undergoing focal therapy or radical prostatectomy between November 2005-September 2018.
SettingProspective multicentre databases for focal therapy (high intensity focused ultrasound and cryotherapy) and radical prostatectomy were analysed for eligibility.
ParticipantsPatients with PSA<20ng/ml, Gleason=4+3 and stage=T2c that underwent radical prostatectomy or focal therapy were matched for treatment year, age, PSA, Gleason score, T-stage, maximum cancer core length and neoadjuvant androgen deprivation therapy use.
InterventionFocal therapy compared to radical prostatectomy.
Main outcome and measuresPrimary outcome was failure-free survival (FFS) defined by need for salvage whole-gland or systemic therapy or metastases. Secondary outcomes were all-cause mortality, erectile and urinary functional outcomes.
Results335/572 patients underwent radical prostatectomy, and 501/761 patients underwent focal therapy, high intensity focused ultrasound (n=626) and cryotherapy (n=135) were eligible for matching. After propensity score matching, 246 radical prostatectomy (mean [SD] age 63.4 [5.6] years, median [IQR]
The interrelationship between brown adipose tissue (BAT) and white adipose tissue (WAT) is emerging as an important factor in obesity, but the effect of impairing non-shivering thermogenesis in BAT on lipid storage in WAT remains unclear. To address this, we have characterized the metabolic phenotype of a mouse model for Costeff syndrome, in which a point mutation in the mitochondrial membrane protein Opa3 impairs mitochondrial activity. Opa3(L122P) mice displayed an 80% reduction in insulin-like growth factor 1, postnatal growth retardation and hepatic steatosis. A 90% reduction in uncoupling protein 1 (UCP1) expression in interscapular BAT was accompanied by a marked reduction in surface body temperature, with a 2.5-fold elevation in interscapular BAT mass and lipid storage. The sequestration of circulating lipid into BAT resulted in profound reductions in epididymal and retroperitoneal WAT mass, without affecting subcutaneous WAT. The histological appearance and intense mitochondrial staining in intra-abdominal WAT suggest significant 'browning', but with UCP1 expression in WAT of Opa3(L122P) mice only 62% of that in wild-type littermates, any precursor differentiation does not appear to result in thermogenically active beige adipocytes. Thus, we have identified Opa3 as a novel regulator of lipid metabolism, coupling lipid uptake with lipid processing in liver and with thermogenesis in BAT. These findings indicate that skeletal and metabolic impairment in Costeff syndrome may be more significant than previously thought and that uncoupling lipid uptake from lipid metabolism in BAT may represent a novel approach to controlling WAT mass in obesity.
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