TGF-β1 induces formation of TSG-6-enriched extracellular vesicles in fibroblasts which can prevent myofibroblast transformation by modulating Erk1/2 phosphorylation.

Extracellular vesicles have emerged as important mediators of cell-to-cell communication in the pathophysiology of fibrotic diseases. One such disease is Peyronie's disease (PD), a fibrotic disorder of the penis caused by uncontrolled transformation of resident fibroblasts to alpha-smooth muscle actin positive myofibroblasts. These cells produce large amounts of extracellular matrix, leading to formation of a plaque in the penile tunica albuginea (TA), causing pain, penile curvature, and erectile dysfunction.

Temporal gene signature of myofibroblast transformation in Peyronie's disease: first insights into the molecular mechanisms of irreversibility.

Background: Transformation of resident fibroblasts to profibrotic myofibroblasts in the tunica albuginea is a critical step in the pathophysiology of Peyronie's disease (PD). We have previously shown that myofibroblasts do not revert to the fibroblast phenotype and we suggested that there is a point of no return at 36 hours after induction of the transformation. However, the molecular mechanisms that drive this proposed irreversibility are not known.

Insertion of inflatable penile prosthesis in the neophallus of assigned female at birth individuals: a systematic review of surgical techniques, complications and outcomes.

Devices such as inflatable penile prostheses (IPP) can be used to achieve erectile rigidity after phalloplasty in assigned female at birth (AFAB) individuals. The approach to inserting an IPP in a neophallus is different and more challenging compared to that of an anatomical penis due to the absence of anatomical structures such as the corpora cavernosa, and the more tenuous blood supply of the neophallus and reconstructed urethra. In addition, the ideal surgical techniques and devices for use in the neophallus have not been defined.

Statins synergize with phosphodiesterase type 5 inhibitors but not with selective estrogen receptor modulators to prevent myofibroblast transformation in an in vitro model of Peyronie's disease.

Background: Peyronie's disease (PD) is a fibrotic disorder characterized by plaque formation in the tunica albuginea (TA) of the penis, and we have previously shown that inhibition of transformation of TA-derived fibroblasts to myofibroblasts using a combination phosphodiesterase type 5 (PDE5) inhibitors and selective estrogen receptor modulators (SERMs) is effective in slowing the progression of early PD.

Aim: The study sought to investigate whether combinations of statins with PDE5 inhibitors or SERMs would affect myofibroblast transformation in vitro.

Methods: Primary fibroblasts were isolated from TA of patients with PD and stimulated with transforming growth factor β1 in the absence and presence of a range of concentrations of statins, PDE5 inhibitors, SERMs, and their combinations for 72 hours before quantifying α-smooth muscle actin using in-cell enzyme-linked immunosorbent assay.

Complications and outcomes following injection of foreign material into the male external genitalia for augmentation: a single-centre experience and systematic review.

Injection of exogenous material into the penis and scrotum has been performed for augmentation purposes. Complications include cosmetic dissatisfaction, penile necrosis and lymphoedema. We report the complications and outcomes from a single centre with an updated systematic review of the literature.

Phenotypic screening of 1,953 FDA-approved drugs reveals 26 hits with potential for repurposing for Peyronie's disease.

Drug repurposing has been shown to bring safe medications to new patient populations, as recently evidenced by the COVID-19 pandemic. We investigated whether we could use phenotypic screening to repurpose drugs for the treatment of Peyronie's disease (PD). PD is a fibrotic disease characterised by continued myofibroblast presence and activity leading to formation of a plaque in the penile tunica albuginea (TA) that can cause pain during erection, erectile dysfunction, and penile deformity.

Phalloplasty following penectomy for penile cancer.

Objective: Penile reconstruction or phalloplasty following penectomy can be offered where the functional penile length is inadequate for a man to void while standing or to have sexual intercourse. Phalloplasty is usually staged due to the complex surgical techniques required. This narrative review describes the technical concepts and summarises the contemporary outcomes following phalloplasty in this challenging cohort.

Gender Affirmation Surgery, Transmasculine.

Transmasculine genital gender affirmation surgery (GAS) is evolving rapidly due to social and surgical advances over recent decades. Important innovations include the use of free or pedicled sensate tissue flaps with integrated urethra coupled with an improved understanding of how best to offer inclusive care. Disappointingly, most publications have thus far failed to address standardization, classification systems, and prospective trials to help guide shared decision making.

Development and content validation of a competency-based assessment tool for penile prosthesis surgery.

The aim of this study was to identify potential hazards for the inflatable penile prosthesis (IPP) surgical procedure and from this develop and content validate an IPP intraoperative competency-based assessment tool. A multi-institutional longitudinal prospective observational study was conducted over a 6-month period. Healthcare Failure Mode and Effects Analysis (HFMEA) methodology was used to prospectively risk assess the IPP procedure using a collaborative multidisciplinary team (MDT) approach.

Rare Disorders of Painful Erection: A Cohort Study of the Investigation and Management of Stuttering Priapism and Sleep-Related Painful Erection.

Background: A chief complaint of men with stuttering priapism (SP) and sleep-related painful erections (SRPE) is bothersome nocturnal erections that wake them up and result in poor sleep and daytime tiredness. SP and SRPE are rare entities that have similarities in their clinical features, but that require different treatment approaches.

Aim: The aim of this study was to describe the clinical features, investigations, and effective management options for men with SP and SRPE.

Advances in Penile Prosthesis Surgery: A Clinical Update.

Despite the introduction of effective oral pharmacotherapy for the treatment of erectile dysfunction (ED), penile implants are still the standard care for patients who do not respond well to medical therapy. Since the first inflatable penile implant surgery was performed almost 40 years ago, a variety of improvements in the penile prosthesis design, and advancements in material science, surgical technique, and post-operative care have been developed to increase patients' satisfaction, as well as that of their partners. Penile implants have evolved vastly during that same time frame and now represent the cutting-edge technology, durability, and function.

Management of residual penile curvature after penile prosthesis placement.

Residual penile curvature is a common situation following the implantation of a penile prosthesis in patients with Peyronie's disease. Currently, there is a variety of options for the correction of residual curvature, including penile modeling, plication techniques, as well as tunical incision/excision with or without grafting. A literature search of PubMed and Medline databases was conducted from 1964 until 2020, using search terms for all articles in the English language.

UK practice for penile prosthesis surgery: baseline analysis of the British Association of Urological Surgeons (BAUS) Penile Prosthesis Audit.

Objectives: To undertake a prospective multicentre national audit of penile prosthesis practice in the UK over a 3-year period.

Patients And Methods: Data were submitted by urological surgeons as part of the British Association of Urological Surgeons Penile Prosthesis National Audit. Patients receiving a penile prosthesis (inflatable or malleable) were included as part of a prospective registry over a 3-year period.

Total Phallic Reconstruction in the Genetic Male.

Background: Total phallic reconstruction (TPR) is a reconstructive challenge.

Objective: To report both surgical outcomes and patient-reported outcomes (PROs) of genetic male patients undergoing TPR utilising a radial artery forearm free flap (RAFFF).

Design, Setting, And Participants: A retrospective tertiary referral centre analysis of a series of genetic male patients with penile insufficiency (PI) either due to congenital micropenis, or from traumatic or surgical amputation was conducted.

Phosphodiesterase Type 5 Inhibitors and Selective Estrogen Receptor Modulators Can Prevent But Not Reverse Myofibroblast Transformation in Peyronie's Disease.

Background: Myofibroblast transformation is a key step in the pathogenesis of Peyronie's disease (PD). Phosphodiesterase type 5 inhibitors (PDE5is) and selective estrogen receptor modulators (SERMs) can prevent the formation of fibrosis in in vitro and in vivo models of PD. However, it is unknown whether these drugs can also reverse established fibrosis.

Stimulation of Leydig and Sertoli Cellular Secretory Function by Anti-Oestrogens: Clomiphene.

Leydig and Sertoli cells are essential for the testicular homeostasis. Clinically, the testicular homeostasis is impaired in hypogonadal and subfertile men. Therapeutically, the selective oestrogen receptor modulator clomiphene citrate (CC) is frequently used to treat these patients.

Management of severe complications following penile surgery for erectile dysfunction and Peyronie disease: Three case reports.

Rationale: Erectile dysfunction (ED) and Peyronie's disease (PD) are conditions commonly observed in andrology. Despite the surgical refinement and the technical improvement in this field, even in expert hands, detrimental consequences have been reported and it can be related to patient's comorbidities or misconduct in the postoperative period. In this article we report anecdotal cases of severe complications following penile surgery for ED and PD in high volume centers, describe the strategies adopted to treat it and discuss the options that would have helped preventing these events.

Prosthetic Placement After Phalloplasty.

Significant developments have enabled the transformation of phalloplasty to a functional organ. Differences exist in the surgical placement of a prosthesis when within a phallus, such as the lack of corpora, pubic fixation requirement, distal sock placement, and the consideration of a vascular pedicle. Increased complications compared with nonphalloplasty cohorts remain one of the biggest challenges, including rates of infection, erosion, mechanical malfunction, and malposition.

Multicenter investigation on the influence of climate in penile prosthesis infection.

The purpose of this study is to investigate the relationship between inflatable penile prosthesis (IPP) infection, time of year, climate, temperature and humidity. This is a retrospective IRB-approved analysis of 211 patients at 25 institutions who underwent salvage procedure or device explant between 2001 and 2016. Patient data were compiled after an extensive review of all aspects of their electronic medical records.

Stem-cell regenerative medicine as applied to the penis.

Purpose Of Review: Tissue engineering and regenerative medicine has emerged as a new scientific interdisciplinary field focusing on developing new strategies to repair or recreate tissues and organs. This review gathers findings on erectile dysfunction and, Peyronie's disease from recent preclinical and clinical studies under heading of stem-cell regenerative medicine.

Recent Findings: Over the last 2 years, preclinical studies on rat models demonstrated the tangible beneficial role of stem cells and stromal vascular fraction in the context of preventing fibrosis and restoring erectile function in different animal models of Erectile dysfunction and Peyronie's disease.

Which patients with ischaemic priapism require further investigation for malignancy?

Ischaemic priapism (IP) is characterised by a persistent, painful penile erection lasting for >4 h. Many causes of IP have been identified including haematological dyscrasias (particularly, sickle cell disease), drugs and rarely malignancy. There are also a large proportion of men, in which no aetiology is identified.

Penile dimensions: What are surgeons measuring?

Penile dimensions and related dissatisfaction, may have significant impact upon patients whom undergo andrological surgeries. Whilst penile dimension assessment is performed as part of the andrological evaluation, little is known regarding the surgeons' opinions nor contemporary practices. This study was designed to gain further insights into the opinions and practices of clinicians regarding penile measurement and is the first paper in the literature of its kind.