Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

The Bilateral Pedicled Epilated Scrotal Flap: A Powerful Adjunctive for Creation of More Neovaginal Depth in Penile Inversion Vaginoplasty

Background: Penile inversion vaginoplasty is a commonly performed genital gender-affirming procedure in transgender women. The creation of an adequate functional neovaginal depth in cases of too little usable penile skin is a challenge. The bilateral pedicled epilated scrotal flap (BPES-flap) can be used as an easy adjunctive technique and may serve as a tool in the surgical armamentarium of the gender surgeon. Aim: To describe the use, dissection, design subtypes, and surgical outcomes of the BPES-flap in vaginoplasty. Methods: Perioperative considerations and different flap design subtypes were described to illustrate the possible uses of the BPES-flap in vaginoplasty. A retrospective chart study was performed on the use of this flap in 3 centers (blinded for review purposes). Outcomes: The main outcome measures are description of surgical technique, flap design possibilities, and postoperative complications. Results: A total of 42 transgender women were included (median age: 28 years (range 18–66), mean body mass index: 24.5 ± 3.5). The mean penile length and width preoperatively were 9 ± 3.1 and 2.9 ± 0.2 cm, respectively. With a mean follow up of 13 ± 10 months, total flap necrosis occurred in one case (2.4%). Partial flap necrosis occurred also in one. Neovaginal reconstruction was successful in all patients with a mean vaginal depth of 13.5 ± 1.3 cm and width of 3.3 ± 1.3 cm. Partial prolapse of the neovaginal top occurred in 3 patients (7%). Clinical Implications: The BPES-flap is a useful addition to the arsenal of surgeons performing feminizing genital reconstructive surgery. Strengths & Limitations: Strenghts comprise (1) the description of the surgical technique with clear images, (2) completeness of data, and (3) that data are from a multicenter study. A weakness is the retrospective nature with limited follow-up time. Conclusion: The BPES-flap is a vascularized scrotal flap that can be raised on the bilateral inferior superficial perineal arteries. It may be used for neovaginal depth creation during vaginoplasty and may be quicker to perform than full-thickness skin grafting. Nijhuis THJ, Özer M, van der Sluis WB, et al. The Bilateral Pedicled Epilated Scrotal Flap: A Powerful Adjunctive for Creation of More Neovaginal Depth in Penile Inversion Vaginoplasty. J Sex Med 2020;17:1033–1040

The GenderCOS project : study protocol for the development of two international Core Outcome Sets for genital gender affirming surgery

Background: Worldwide an increasing number of transgender and gender diverse individuals are requesting genital Gender Affirming Surgery (gGAS). For both masculinizing and feminizing gGAS various procedures and techniques are employed. Current literature on gGAS reports heterogeneous, non-standardized and often ill-defined outcomes. Presently, no consensus exists on what outcomes should be evaluated in order to assess the clinical results and the effectiveness of these procedures, which precludes development of evidence-based treatment guidelines.Aims: This international consensus study aims to develop Core Outcome Sets (COS) for both masculinizing and feminizing gGAS. These represent the minimum sets of outcomes recommended to be measured and reported in all clinical trials pertaining to gGAS.Methods: Two Core Outcome Sets for masculinizing and feminizing gGAS will be developed in parallel by following the Core Outcome Measures in Effectiveness Trials (COMET) guidelines. The stages of development for each set are: i) Identify outcomes measured and reported in previous research through a systematic review of the literature; ii) Identify outcomes suggested by transgender and gender diverse individuals during focus groups and interviews; iii) Combine and structure the outcomes into a preliminary outcome list; iv) Conduct e-Delphi surveys among stakeholders (i.e. professionals in transgender healthcare and transgender individuals) in which all potential outcomes will be rated on level of importance; and v) Decide on the final COS during an online consensus meeting.Discussion: This study will produce minimum, core sets of relevant outcomes for gGAS, through reaching international consensus with key stakeholders, including transgender individuals. Development of these COS will enable the measurement and reporting of relevant and standardized outcomes, facilitating continued scientific advancement of this field