Urological Society of Australia and New Zealand (USANZ) and Australasian Chapter of Sexual Health Medicine (AChSHM) for the Royal Australasian College of Physicians (RACP) clinical guidelines on the management of erectile dysfunction.

INTRODUCTION: These clinical practice recommendations by the Urological Society of Australia and New Zealand (USANZ) and the Australasian Chapter of Sexual Health Medicine (AChSHM) for the Royal Australasian College of Physicians (RACP) provide evidence-based clinical guidelines on the management of erectile dysfunction (ED) in Australia. MAIN RECOMMENDATIONS: A comprehensive clinical history and a tailored physical examination are essential (Level of evidence [LoE] 3; GRADE B). Laboratory testing should include fasting glucose, lipid profile and total testosterone level (LoE 3; GRADE A). Specialised diagnostic tests are recommended in selected cases and the patient should be counselled accordingly (LoE 4; GRADE B). Lifestyle changes and optimisation of existing medical conditions should accompany all ED treatment regimens (LoE 1; GRADE A). Oral phosphodiesterase type 5 inhibitor (PDE5i) is an effective first line medical therapy (LoE 1; GRADE A). Intracavernosal injections and vacuum erection devices are recommended as second line therapy (LoE 1; GRADE B). A penile prosthesis implant can be considered in men who are medically refractory or unable to tolerate the side effects of medical therapy (LoE 4; GRADE B). Pro-erectile regenerative therapy remains largely experimental (LoE 3; GRADE B). CHANGES IN MANAGEMENT AS A RESULT OF THESE GUIDELINES: Modification of lifestyle behaviour, management of reversible risk factors and optimisation of existing medical conditions remain pivotal, and existing standard ED therapies are often effective and safe following cardiovascular risk stratification. Caution should be exercised on the use of regenerative technology in ED due to unknown long term outcomes.

A clinical pathway for the management of Peyronie's disease: integrating clinical guidelines from the International Society of Sexual Medicine, American Urological Association and European Urological Association.

OBJECTIVE: To provide a clinical framework and key guideline statements to assist clinicians in the evidence-based management of Peyronie's disease (PD). METHODS: We conducted a review of the published literature relevant to PD management, with an emphasis on published clinical guidelines. References used in the text have been assessed according to their level of evidence, and guideline recommendations have been graded based on the Oxford Centre for Evidence-based Medicine Levels of Evidence. RESULTS: The management of PD involves taking a detailed penile and sexual history, with a focused penile examination to identify plaque and hourglass deformity, and digital photographs of the erect curved (deformed) penis. Penile colour Duplex ultrasonography evaluates tunical plaque and underlying cavernosal smooth muscle and blood flow variables. The current therapy for PD can be divided into two main groups, namely, medical therapy and penile reconstructive surgery, and the patient should be counselled on the benefits and risks of each treatment option. CONCLUSIONS: Peyronie's disease remains a clinical challenge and presents a considerable therapeutic dilemma as the current therapy addresses existing penile curvature only and is not very effective in preventing future penile fibrosis and/or reversing underlying erectile dysfunction.

Prevalence of penile curvature: a population-based cross-sectional study in metropolitan and rural cities in Australia.

OBJECTIVE: To evaluate the prevalence of penile curvature and health-seeking behaviour in Australian men. PATIENTS AND METHODS: A population-based, cross-sectional anonymous web-based survey was designed, and men aged between 35 and 75 years in major and rural metropolitan cities across Australia were invited to participate. Respondents were screened for self-reported symptoms of penile curvature and their impact on various psychosexual domains. RESULTS: Of a total of 1782 men who responded, 333 men (19%) reported a bend or curve in their penis and completed the main section of the questionnaire to address the impact of penile curvature on various psychosexual domains. A third of men with penile curvature (32%) reported penile curvature of ≥ 30°, with approximately equal proportions among the three age groups (33% in those aged 35-49 years, 37% in those aged 50-64 years, and 30% in those aged 65-75 years) and with no significant difference detected in the penile curvature characteristics between men in major metropolitan and those in rural cities across Australia. One in six men reported an adverse impact of penile curvature in their lives, complaining of penile pain or discomfort when they had an erection, while 26% of men were bothered by the appearance of their penis and 20% were bothered when they tried to have sexual intercourse. Men aged 35-49 years were more likely than those aged 65-75 years to be bothered by the penile curvature (31% vs 18%; P < 0.05) and men in the age group 65-75 years were twice as likely to have trouble with sexual intercourse compared with other age groups (39% vs 18%; P < 0.05). CONCLUSIONS: This first population-based study to estimate the prevalence of penile curvature in Australia highlighted that penile curvature is common and has a significant adverse impact on psychosexual functions.

Acute management of priapism in men.

UNLABELLED: What's known on the subject? and What does the study add? Priapism is a rare event. However, various medications and medical conditions may increase the risk. Priapism can be ischaemic, non-ischaemic or stuttering. It is paramount to distinguish the type of priapism, as misdiagnosis may lead to significant morbidity. Ischaemic priapism represents a compartment syndrome of the penis and is therefore a medical emergency. A delay in management may significantly affect future erectile function. Stuttering priapism represents recurrent subacute episodes of ischaemic priapism, which may lead to erectile dysfunction. Thus episodes must be minimised. Non-ischaemic priapism is not a medical emergency. However, misdiagnosis and injection with sympathomimetic agents can result in system absorption and toxicity. This review article provides a summary of the evaluation and management of priapism. Furthermore, a step by step flow chart is provided to guide the clinician through the assessment and management of this complex issue. OBJECTIVES: To review the literature regarding ischaemic, non-ischaemic and stuttering priapism. To provide management recommendations. PATIENTS AND METHODS: A Medline search was carried out to identify all relevant papers with management guidelines for priapism. RESULTS: Ischaemic priapism represents a compartment syndrome of the penis and urgent intervention is required to decrease the risk of erectile dysfunction. Non-ischaemic priapism is not a medical emergency; however, it can result in erectile dysfunction. The treatment objective for stuttering priapism is to reduce future episodes with systemic treatments, whilst treating each ischaemic episode as an emergency. CONCLUSIONS: Priapism is a complex condition that requires expert care to prevent complications and irreversible erectile dysfunction.

The International Penile Prosthesis Implant Consensus Forum: clinical recommendations and surgical principles on the inflatable 3-piece penile prosthesis implant.

Despite significant scientific advances in the modern three-piece inflatable penile prosthesis implant surgery, it is not without surgical risks and can carry additional cosmetic and psychosocial consequences in poorly selected and consented individuals. To address this problem, an international group of key opinion leaders and high-volume prosthetic surgeons reviewed the current guidelines and clinical evidence, discussed their experiences, and formed a consensus regarding inflatable penile prosthesis surgery. The findings of this consensus panel were presented at the 17th biennial Asia Pacific Society of Sexual Medicine scientific meeting. The experts concluded that proper patient selection, informed consent and strict adherence to safe surgical principles are important to optimize clinical outcomes. Furthermore, most intraoperative complications, if recognized, can be addressed intraoperatively to enable placement of the device at the time of initial surgery. Men with significant corporal fibrosis due to Peyronie's disease, prior prosthesis explantation and priapism, and men who have undergone construction of a neophallus, as well as men who receive concurrent continence surgery, are complex cases requiring additional care and advanced techniques to obtain optimal surgical outcomes. Variability in patient care - in terms of postoperative antibiotic use, pain management, scrotal care, and cycling of the penile prosthesis implant - must be reduced to enable optimization and assessment of outcomes across patient groups.

Seq-Well: A Sample-Efficient, Portable Picowell Platform for Massively Parallel Single-Cell RNA Sequencing.

Seq-Well is a low-cost picowell platform that can be used to simultaneously profile the transcriptomes of thousands of cells from diverse, low input clinical samples. In Seq-Well, uniquely barcoded mRNA capture beads and cells are co-confined in picowells that are sealed using a semipermeable membrane, enabling efficient cell lysis and mRNA capture. The beads are subsequently removed and processed in parallel for sequencing, with each transcript's cell of origin determined via the unique barcodes. Due to its simplicity and portability, Seq-Well can be performed almost anywhere.

BRAF V600E Mutant Colorectal Cancer Subtypes Based on Gene Expression.

PURPOSE: Mutation of BRAF at the valine 600 residue occurs in approximately 10% of colorectal cancers, a group with particularly poor prognosis. The response of BRAF mutant colorectal cancer to recent targeted strategies such as anti-BRAF or combinations with MEK and EGFR inhibitors remains limited and highly heterogeneous within BRAF V600E cohorts. There is clearly an unmet need in understanding the biology of BRAF V600E colorectal cancers and potential subgroups within this population. EXPERIMENTAL DESIGN: In the biggest yet reported cohort of 218 BRAF V600E with gene expression data, we performed unsupervised clustering using non-negative matrix factorization to identify gene expression-based subgroups and characterized pathway activation. RESULTS: We found strong support for a split into two distinct groups, called BM1 and BM2. These subtypes are independent of MSI status, PI3K mutation, gender, and sidedness. Pathway analyses revealed that BM1 is characterized by KRAS/AKT pathway activation, mTOR/4EBP deregulation, and EMT whereas BM2 displays important deregulation of the cell cycle. Proteomics data validated these observations as BM1 is characterized by high phosphorylation levels of AKT and 4EBP1, and BM2 patients display high CDK1 and low cyclin D1 levels. We provide a global assessment of gene expression motifs that differentiate BRAF V600E subtypes from other colorectal cancers. CONCLUSIONS: We suggest that BRAF mutant patients should not be considered as having a unique biology and provide an in depth characterization of heterogeneous motifs that may be exploited for drug targeting. Clin Cancer Res; 23(1); 104-15. ©2016 AACR.

mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice.

Gastrointestinal cancers are frequently associated with chronic inflammation and excessive secretion of IL-6 family cytokines, which promote tumorigenesis through persistent activation of the GP130/JAK/STAT3 pathway. Although tumor progression can be prevented by genetic ablation of Stat3 in mice, this transcription factor remains a challenging therapeutic target with a paucity of clinically approved inhibitors. Here, we uncovered parallel and excessive activation of mTOR complex 1 (mTORC1) alongside STAT3 in human intestinal-type gastric cancers (IGCs). Furthermore, in a preclinical mouse model of IGC, GP130 ligand administration simultaneously activated mTORC1/S6 kinase and STAT3 signaling. We therefore investigated whether mTORC1 activation was required for inflammation-associated gastrointestinal tumorigenesis. Strikingly, the mTORC1-specific inhibitor RAD001 potently suppressed initiation and progression of both murine IGC and colitis-associated colon cancer. The therapeutic effect of RAD001 was associated with reduced tumor vascularization and cell proliferation but occurred independently of STAT3 activity. We analyzed the mechanism of GP130-mediated mTORC1 activation in cells and mice and revealed a requirement for JAK and PI3K activity but not for GP130 tyrosine phosphorylation or STAT3. Our results suggest that GP130-dependent activation of the druggable PI3K/mTORC1 pathway is required for inflammation-associated gastrointestinal tumorigenesis. These findings advocate clinical application of PI3K/mTORC1 inhibitors for the treatment of corresponding human malignancies.