TGF-ß1 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. We have used primary fibroblasts derived from the TA of PD patients to explore the role of transforming growth factor beta 1 (TGF-ß1), a key signalling factor in this process. TGF-ß1 treatment elicited a range of responses from the myofibroblasts: (i) they secreted extracellular vesicles (EVs) that were more numerous and differed in size and shape from those secreted by fibroblasts, (ii) these EVs prevented TGF-ß1-induced transformation of fibroblasts in a manner that was dependent on vesicle uptake and (iii) they prevented phosphorylation of Erk1/2, a critical component in modulating fibrogenic phenotypic responses, but did not affect TGF-ß1-induced Smad-signalling. We posit that this effect could be linked to enrichment of TSG-6 in myofibroblast-derived EVs. The ability of myofibroblast-derived vesicles to prevent further myofibroblast transformation may establish them as part of an anti-fibrotic negative feedback loop, with potential to be exploited for future therapeutic approaches.

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. AIM: Identify molecular pathways that drive the irreversibility of myofibroblast transformation by analyzing the expression of the genes involved in the process in a temporal fashion. METHODS: Human primary fibroblasts obtained from tunica albuginea of patients with Peyronie's disease were transformed to myofibroblasts using transforming growth factor beta 1 (TGF-ß1). The mRNA of the cells was collected at 0, 24, 36, 48, and 72 hours after stimulation with TGF-ß1 and then analyzed using a Nanostring nCounter Fibrosis panel. The gene expression results were analyzed using Reactome pathway analysis database and ANNi, a deep learning-based inference algorithm based on a swarm approach. OUTCOMES: The study outcome was the time course of changes in gene expression during transformation of PD-derived fibroblasts to myofibroblasts. RESULTS: The temporal analysis of the gene expression revealed that the majority of the changes at the gene expression level happened within the first 24 hours and remained so throughout the 72-hour period. At 36 hours, significant changes were observed in genes involved in MAPK-Hedgehog signaling pathways. CLINICAL TRANSLATION: This study highlights the importance of early intervention in clinical management of PD and the future potential of new drugs targeting the point of no return. STRENGTHS AND LIMITATIONS: The use of human primary cells and confirmation of results with further RNA analysis are the strengths of this study. The study was limited to 760 genes rather than the whole transcriptome. CONCLUSION: This study is to our knowledge the first analysis of temporal gene expression associated with the regulation of the transformation of resident fibroblasts to profibrotic myofibroblasts in PD. Further research is warranted to investigate the role of the MAPK-Hedgehog signaling pathways in reversibility of PD.

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. This review systematically summarises the literature on the insertion of IPP in the neophallus of individuals AFAB. In particular, the described techniques, types of devices used and peri-operative and patient-reported outcomes are emphasised. An initial search of the PubMed database was performed on 16 September 2022 and an updated search was performed on 26 May 2023. Overall, 185 articles were screened for eligibility and 15 studies fulfilled the inclusion criteria and were included in the analysis. Two studies reported outcomes on the zephyr surgical implant 475 FTM device and the others reported outcomes on the Boston Scientific AMS 600/700TM CX 3-piece inflatable, AMS AmbicorTM 2-piece inflatable, Coloplast Titan® or Dynaflex devices. Overall, 1106 IPPs were analysed. The infection rate was 4.2%-50%, with most studies reporting an infection rate of <30%. Mechanical failure or dysfunction occurred in 1.4%-36.4%, explantation was required in 3.3%-41.6%, and implant revision or replacement was performed in 6%-70%. Overall, 51.4%-90.6% of patients were satisfied and 77%-100% were engaging in sexual intercourse. An IPP in a neophallus is an acceptable option to achieve rigidity for sexual intercourse. However, this challenging procedure has good reports of patient and partner satisfaction despite significant risks of complications.

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 ß1 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. OUTCOMES: The prevention of transforming growth factor ß1-induced transformation of TA-derived fibroblasts to myofibroblasts was measured in vitro. RESULTS: Statins (simvastatin, lovastatin) inhibited myofibroblast transformation in a concentration-dependent manner with half maximal inhibitory concentration values of 0.77 ± 0.07 µM and 0.8 ± 0.13 µM, respectively. Simvastatin inhibited myofibroblast transformation in a synergistic fashion when combined with vardenafil (a PDE5 inhibitor; log alpha >0). Combination of tamoxifen (a SERM) and simvastatin did not show synergy (log alpha <0). When 3 drugs (simvastatin, vardenafil, and tamoxifen) were combined, the effect was not synergistic, but rather was additive. CLINICAL IMPLICATIONS: A combination of a statin with a PDE5 inhibitor might be useful in the clinic to slow the progression of the disease in patients with early PD; however, caution should be taken with such a combination because of the reported myopathy as a side effect. STRENGTHS AND LIMITATIONS: The use of primary human cells from patients with PD is a strength of this study. The mechanisms by which these drug classes exert synergy when used in combination was not investigated. CONCLUSION: This is the first demonstration of an antifibrotic synergy between statins and PDE5 inhibitors.

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. A retrospective review of all cases presenting with foreign substance injection into the genitalia, over a 10-year period was performed. Thirty-five patients with a mean (standard deviation (SD); range) age of 36.9 (±9.1; 22-61) years at presentation were included. The mean (SD; range) time between injection and presentation was 7.8 (±5.8; 1 day-20 years) years. The most common injected substance was silicone (n = 16, 45.7%) and liquid paraffin (n = 8, 22.9%). The penile shaft (94.3%) was the most injected site. The most common presentations were cosmetic dissatisfaction (57.1%) and pain and/or swelling (45.7%). Surgery was required in 32 (91.4%) cases. Primary procedures included local excision and primary closure (n = 19, 59.4%), circumcision (n = 5, 15.6%), excision with a split skin graft or a scrotal flap reconstruction (n = 5, 15.6%). Three (8.6%) patients presented with necrosis and required acute debridement. Overall, 18 patients had more than 1 procedure, and 8 patients required 3 or more procedures. A systematic search of the literature identified 887 articles of which 68 studies were included for analysis. The most common substance injected was paraffin (47.7%), followed by silicone (15.8%). The majority of patients (77.9%) presented with pain, swelling or penile deformity. 78.8% of the patients underwent surgical treatment, which included excision and primary closure with or without the use of skin grafts (85.1% of all procedures), the use of flaps (12.3%) and penile amputation (n = 2). Complications of foreign body injection into the male genitalia can be serious resulting in necrosis and autoamputation. Surgical intervention is often required to excise abnormal tissue to manage pain and improve cosmesis.

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. PD affects 3-9% of men with treatment options limited to surgery or injection of collagenase which can only be utilised at late stages after the plaque is formed. Currently there are no approved medications that can be offered to patients presenting with early disease before the formation of the plaque. Drug repurposing may therefore be the ideal strategy to identify medical treatments to address this unmet medical need in early PD. We used primary human fibroblasts from PD patients in a phenotypic screening assay that measures TGF-ß1-induced myofibroblast transformation which is the main cellular phenotype that drives the pathology in early PD. A library of FDA-approved 1,953 drugs was screened in duplicate wells at a single concentration (10 µM) in presence of TGF-ß1. The myofibroblast marker α-SMA was quantified after 72h incubation. A positive control of SB-505124 (TGF-ß1 receptor antagonist) was included on each plate. Hits were defined as showing >80% inhibition, whilst retaining >80% cell viability. 26 hits (1.3%) were identified which were divided into the following main groups: anti-cancer drugs, anti-inflammation, neurology, endocrinology, and imaging agents. Five of the top-ten drugs that increase myofibroblast-transformation appear to act on VEGFR. This is the first phenotypic screening of FDA-approved drugs for PD and our results suggest that it is a viable method to predict drugs with potential for repurposing to treat early PD.

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. Methods: A retrospective review of the English literature was performed between January 1946 till November 2021. The data were synthesised and complemented by the expert opinion of the authors with 20 years of experience in this field. The flaps are ideally designed with an integrated urethra or alternatively, a further free flap urethroplasty can be offered. Phalloplasty is further complicated following penectomy by scarring from the previous surgery and the potential loss of structures that would normally be present at the recipient site. Results: There are limited published data with a total of 19 men recorded in the literature. Only the radial artery forearm free flap and anterolateral thigh flap have been described in this cohort of patients. Functional outcomes including standing micturition, sensation in the neophallus, and the ability to orgasm are good. Overall quality of life and satisfaction was also good despite the high risk for long-term complications of the neophallus and donor site. Conclusion: Phalloplasty following penectomy requires microsurgical transfer of a free flap or a pedicled flap to reconstruct a neophallus. An erectile device is inserted at a later stage to facilitate sexual intercourse, if desired. Surgical scarring from penectomy and the potential loss of vasculature that would normally be present at the recipient site may further complicate reconstruction. Surgical and functional outcomes are acceptable based on the limited published experience to date.

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. This narrative review highlights contemporary techniques, controversies, and innovations while addressing gaps in the literature and future directions for research.

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. Here, advancements are reviewed with a focus upon recent developments in surgical techniques and device technology.

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. International content validation of the developed tool was then undertaken via face-to-face meetings and WebEx seminars. A total of 22 h of observation led to the construction of a detailed process map consisting of 11 stages and 49 sub-stages. HFMEA identified 50 failure modes and 45 failure mode effects, nine failure modes were excluded after analysis leaving 41 key failure modes included in the checklist. The high-risk steps identified were related to corporal dilatation, incorrect sizing of the prosthesis cylinders and incorrect localisation of the superficial inguinal ring for blind reservoir placement. The final content validated IPP assessment tool (PPAT) consisted of 13 processes and 27 sub-processes. We concluded that HFMEA methodology successfully allowed for the identification of key steps within the IPP procedure from which the PPAT was developed. Formal international content validation confirmed that all key procedural steps were included in the PPAT and that completion of all steps would indicate trainee competency in the procedure. Further validation is required before the tool can be used to assess learning curves for the IPP procedure.

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. METHODS: Retrospective cohort study of 133 men with bothersome nocturnal painful erections that attended a tertiary andrology unit between 2004 and 2018. These men were divided into 3 groups. Group 1 (n = 62) contains men with sickle cell SP; group 2 (n = 40) has men with non-sickle cell SP and group 3 (n = 31) contains men with SRPE. OUTCOME: To determine the effectiveness of medical and surgical treatments for men with SP and SRPE. RESULTS: Hydroxyurea and automated exchange transfusion were the most effective treatment options in the sickle cell SP group. Hormonal manipulation and α-agonist therapies were effective in both SP cohorts (groups 1 and 2). Baclofen was the most effective therapy in men with SRPE. For men who failed medical management, implantation of a penile prosthesis resulted in complete resolution of the symptoms in men with SP (groups 1 and 2). Surgical management (penile prosthesis implantation and embolization) did not improve the patients' symptoms in the SRPE group. CLINICAL IMPLICATIONS: This study differentiates between sickle cell SP, non-sickle cell SP, and SRPE and describes effective treatment options for each group. STRENGTHS & LIMITATIONS: This is the largest cohort study for both SP and SRPE, respectively. Limitations include its retrospective nature and single-center experience. CONCLUSION: Managing men in these 3 groups differently and in accordance with the proposed treatment pathway provides a more structured approach to the management of these rare conditions. Johnson M, McNeillis S, Chiriaco G, et al. Rare Disorders of Painful Erection: A Cohort Study of the Investigation and Management of Stuttering Priapism and Sleep-Related Painful Erection. J Sex Med 2021;18:376-384.

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. In men, the mechanism of action of CC has long been thought to be limited to inhibition of the retro-control by oestrogen on the pituitary gland. However, oestrogen receptors are also expressed in the testis. Therefore, we will explore in this review the systemic effects as well as its action on reproductive function. We will describe in particular the possible effects of CC on the secretory functions of Leydig and Sertoli cells and their implication on the testicular microenvironment. CC is a costeffective and relatively safe off-label treatment for young hypogonadal men actively trying for a child or subfertile men with low testosterone with a positive effect on sperm concentration. Nevertheless, its effects on the oestrogen receptors and other signalling pathways at the testicular level remain poorly investigated. Further research, including combined treatment, could allow improving sperm morphology and sperm motility which do not seem to be significantly enhanced by CC alone.

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. Data were validated and then analysed using a software package (Tableau). RESULTS: A total of 1071 penile prosthesis procedures were included from 22 centres. The three commonest aetiological factors for erectile dysfunction were diabetes, prostate surgery and Peyronie's disease. Of the recorded data, inflatable penile prostheses were the commonest devices implanted, with 665 devices used (62.1%), whereas malleable prostheses accounted for 14.2% of the implants. Recorded intra-operative complications included urethral injury (0.7%, n = 7), corporal perforation (1.1%, n = 12) and cross-over (0.6%, n = 6). Known postoperative complications were recorded in 9.8% of patients (74/752), with the two most frequently reported being postoperative penile pain (n = 11) and scrotal haematoma (n = 14). CONCLUSION: This baseline analysis is the largest prospective registry of penile prostheses procedures to date. The data show that, over the 3-year collection period in the UK, there are now fewer surgeons performing the procedure, together with a reduction in the number of centres. Peri-operative complications were infrequent, and the rate of implant abortion (e.g. as a result of urethral injury) was very low. Further follow-up data will be required to publish long-term outcomes and patient satisfaction.

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. In this article, we provide a review of the techniques and the outcomes, according to the published literature.

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. SURGICAL PROCEDURE: RAFFF phalloplasty was conducted as a multistaged procedure: (1) TPR, (2) glans sculpting with second-stage urethroplasty when indicated, and (3) penile prosthesis implantation. MEASUREMENTS: A descriptive analysis of the patient's baseline features, surgical outcomes, and PROs was conducted. RESULTS AND LIMITATIONS: A total of 108 patients were enrolled. The median age was 32.5 yr (interquartile range [IQR] 24-46) and median follow-up was 78.5 mo (IQR 30-129). A primary anastomotic urethroplasty was performed in 90 patients (83.4%) and a staged procedure in the remainder. Four patients experienced an acute arterial thrombosis, leading to complete loss of the phallus in two. Immediate surgical exploration saved the flap in two cases of venous thrombosis. Urethral complication occurred in 49.1% of patients. The multivariate logistic regression analysis showed an association (p=0.04) between the staged urethral reconstruction and the incidence of urethral complications. The limitations of our study are its retrospective nature and the lack of control. CONCLUSIONS: Despite the high incidence of postoperative complications and the possible need for revisions, TPR in the genetic male with PI using a RAFFF yields satisfactory aesthetic and functional results. PATIENT SUMMARY: in this report, we looked at the outcomes from TPR in a large population of male patients with penile inadequacy either due to congenital micropenis, or from traumatic or surgical amputation. Our results support the idea that penile reconstruction with a forearm free flap leads to satisfactory outcomes.

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. AIM: To investigate whether PDE5is and SERMs can reverse transforming growth factor beta 1 (TGF-ß1)-induced myofibroblast transformation and determine the point of no return. METHODS: In-Cell enzyme-linked immunosorbent assay was used to quantify TGF-ß1-induced myofibroblast transformation of human primary fibroblasts isolated from tunica albuginea (TA) of patients undergoing surgery for treatment of PD. Extracellular matrix production and collagen contraction assays were used as secondary assays. Reverse transcription-quantitative polymerase chain reaction and In-Cell enzyme-linked immunosorbent assay were used to measure drug target expression. PDE5i (vardenafil) and SERM (tamoxifen) were applied at various time points after TGF-ß1. OUTCOMES: Reversibility of myofibroblast transformation and drug target expression were investigated in a time-dependent manner in TA-derived fibroblasts. RESULTS: Vardenafil or tamoxifen could not reverse the myofibroblast traits of alpha-smooth muscle actin expression and extracellular matrix production, whereas only tamoxifen affected collagen contraction after 72 hours of TGF-ß1 treatment. Phosphodiesterase 5A and estrogen receptor (ER)-ß were downregulated after 72 hours, and estrogen receptor -α protein could not be quantified. Tamoxifen could prevent myofibroblast transformation until 36 hours after TGF-ß1 treatment, whereas vardenafil could prevent only 24 hours after TGF-ß1 treatment. This was mirrored by downregulation of drug targets on mRNA and protein level. Furthermore, antifibrotic signaling pathways, peroxisome proliferator-activated receptor gamma and betaglycan (TGFB receptor III), were significantly downregulated after 36 hours of TGF-ß1 exposure, as opposed to upregulation of profibrotic thrombospondin-1 at the same time point. CLINICAL TRANSLATION: This study suggests that using PDE5is and SERMs might only help for early-phase PD and further highlights the need to test drugs at the appropriate stage of the disease based on their mechanism of action. STRENGTHS & LIMITATIONS: The study uses primary human TA-derived fibroblasts that enhances translatability of the results. Limitations include that only 1 example of PDE5i- and SERM-type drug was tested. Time course experiments were only performed for marker expression experiments and not for functional assays. CONCLUSION: This is the first study to demonstrate that timing for administration of drugs affecting myofibroblast transformation appears to be vital in in vitro models of PD, where 36 hours of TGF-ß1 treatment can be suggested as a "point of no return" for myofibroblast transformation. Ilg MM, Stafford SJ, Mateus M, et al. Phosphodiesterase Type 5 Inhibitors and Selective Estrogen Receptor Modulators Can Prevent But Not Reverse Myofibroblast Transformation in Peyronie's Disease. J Sex Med 2020;17:1848-1864.

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. Climate data were compiled from monthly norms based on location, as well as specific data regarding temperature, dew point, and humidity from dates of surgery. Rigorous statistical analysis was performed. We found that penile prosthesis infections occurred more commonly in June (n = 24) and less frequently during the winter months (n = 39), with the lowest number occurring in March (n = 11). One-hundred thirty-nine infections occurred at average daily temperatures greater than 55 °F, compared to 72 infections at less than 55 °F. The incidence rate ratio for this trend was 1.93, with a p-value of <0.001. Humidity results were similar, and fungal infections correlate with daily humidity. Infected implants performed in the fall and summer were over 3 and 2.3 times, respectively, more likely to grow Gram-positive bacteria compared to implants performed in spring (p = 0.004; p = 0.039). This was consistent across geographic location, including in the Southern hemisphere. We found trends between climate factors and IPP infection like those seen and proven in other surgical literature. To our knowledge these data represent the first exploration of the relationship between temperature and infection in prosthetic urology.

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. Nonetheless, the placement of penile prosthesis within a phalloplasty enables trans men to achieve a once near-impossible goal of penetrative sexual intercourse without an external device.

Penile Reconstruction and the Role of Surgery in Gender Dysphoria.

Gender dysphoria is the distress that occurs when there is a mismatch between birth-assigned gender and expressed gender. Penile reconstruction may ameliorate the risk of suicide due to mental illness, social harassment, and isolation commonly experienced by these individuals. The ideal aim is to allow micturition while standing and penetrative intercourse with full sensation, but there is no universal agreement on the ideal flap design. Contemporary options for penile reconstruction include metoidioplasty and phalloplasty using either a pedicled or free flap. The most common flap currently performed is the radial artery forearm free flap. Secondary procedures following phalloplasty may include glansplasty, scrotoplasty, and insertion of penile and testicular prostheses. Patient summary: Penile reconstruction is offered to transgender men as part of their transition from female to male. Penile reconstruction may ameliorate the high risk of suicide due to mental illness, social harassment, and isolation commonly experienced by these individuals. Many techniques can be used for penile reconstruction with good outcomes, but none can fully satisfy all the needs of individuals seeking penile reconstruction.