Understanding the Role of Adenosine Receptors in the Myofibroblast Transformation in Peyronie's Disease.

BACKGROUND: Peyronie's disease (PD) is a chronic fibrotic disease of the penis affecting a significant number of men worldwide without effective medical treatments. Myofibroblasts are pivotal in the pathogenesis of PD. Adenosine and adenosine receptors have been suggested to be involved in the pathophysiology of fibrosis. AIM: To understand the role of adenosine receptors in myofibroblast transformation in PD. METHODS: Fibroblasts were isolated from the non-PD tunica albuginea (TA) tissue and PD plaque tissue and were transformed into myofibroblasts using transforming growth factor (TGF)-ß1. Quantification of α-smooth muscle actin and adenosine receptors (adenosine receptor A1 [ADORA1], adenosine receptor A2A, adenosine receptor A2B [ADORA2B], and adenosine receptor A3) was performed using immuno-cytochemistry, in-cell enzyme-linked immuno-sorbent assay (ICE), and real-time reverse transcription quantitative polymerase chain reaction. The effect of various adenosine receptor agonists or antagonists on TGF-ß1-induced myofibroblast transformation was measured using ICE. OUTCOMES: Expression of adenosine receptors in myofibroblasts obtained from human TA and the effect of adenosine receptor ligands on myofibroblast transformation were investigated. RESULTS: The experiments showed that the protein and messenger RNA levels of α-smooth muscle actin in non-PD TA cells and PD plaque-derived cells were significantly higher in cells exposed to TGF-ß1 than those not treated with TGF-ß1. 2 of 4 adenosine receptors (ADORA1 and ADORA2B) were found to be expressed in both cell populations. Among various adenosine receptor agonists/antagonist investigated, only ADORA2B agonist, BAY 60-6583, significantly inhibited myofibroblast transformation in a concentration-dependent manner when applied simultaneously with TGF-ß1 (IC50 = 30 µmol/L). CLINICAL TRANSLATION: ADORA2B agonists may be clinically efficacious in early-stage PD. STRENGTHS & LIMITATIONS: The strength of this study is the use of primary fibroblasts from human TA. Limitation of the study is the high concentrations of the ligands used. CONCLUSION: The effect of an ADORA2B agonist on TGF-ß1-induced myofibroblast transformation shows a novel potential therapeutic target for PD if applied during early, non-stable phase of PD. Mateus M, Ilg MM, Stebbeds WJ, et al. Understanding the Role of Adenosine Receptors in the Myofibroblast Transformation in Peyronie's Disease. J Sex Med 2018;15:947-957.

Total Phallic Reconstruction Using the Radial Artery Based Forearm Free Flap After Traumatic Penile Amputation.

INTRODUCTION: Although genital injuries in civilian centers are rare, the scenario is completely different in the battlefield. If the penile distal stump is not adequate for primary reimplantation or it cannot be found, then delayed penile reconstruction needs to be considered. AIM: To report a single-center experience with total phallic reconstruction using radial artery based forearm free flap (RAFFF) after penile traumatic loss. METHODS: We retrospectively reviewed the clinical records of 10 patients who underwent total phallic reconstruction with the use of the RAFFF from September 2001 through August 2015 after traumatic amputation of the penis. MAIN OUTCOME MEASURES: Patients' baseline features, surgical outcomes, complications, and satisfaction are reported. RESULTS: The average age at the time of penile reconstruction was 36 years (range = 27-52 years). The causes of penile loss were self-amputation owing to an acute schizophrenic episode (n = 2), road traffic accident (n = 3), blast injury (n = 3), donkey bite (n = 1), and Fournier gangrene (n = 1). The average time from the trauma to reconstruction with the RAFFF was 7 years (range = 2-15 years). The urethral stump was adequate for primary anastomosis, with phallic neourethra construction in six patients. The remaining patients had complete avulsion of the penis and were voiding though a perineal urethrostomy. In consequence, they required a two-stage urethroplasty. An acute arterial thrombosis of the microsurgical anastomosis occurred in two patients and was managed successfully with immediate exploration. A neourethra stricture and fistula occurred in one patient, which needed revision. All patients who underwent complete urethral reconstruction could void and ejaculate from the tip of the phallus. After a median follow-up of 51 months (range = 1-114 months), all patients were satisfied with the size, cosmetic appearance, and sensation of the phallus. Six patients underwent inflatable penile prosthesis implantation and could engage in penetrative sex. However, revision surgery was needed in three patients (infection, n = 2; mechanical failure, n = 1). CONCLUSION: Despite the high incidence of postoperative complications and the possible need for multiple operations, in expert hands and in large-volume centers, penile reconstruction with the RAFFF after traumatic loss of the penis yields excellent results and allows patients to regain sexual and urinary functions.

Total phallic reconstruction using radial artery based forearm free flap phalloplasty in patients with epispadias-exstrophy complex.

PURPOSE: We report our experience with total phallic construction using the radial artery forearm free flap in patients with bladder/cloacal exstrophy and micropenis-epispadias complex. MATERIALS AND METHODS: We retrospectively reviewed notes on the 16 patients with bladder/cloacal exstrophy and micropenis-epispadias complex treated with total phallic construction using the radial artery based forearm free flap between January 2003 and October 2013. Surgical outcome, phallic cosmesis, complications, eventual need for revision surgery and patient satisfaction were recorded during followup. RESULTS: This technique allowed reconstruction of a cosmetically acceptable phallus in 15 patients. In 1 patient the distal third of the phallus was lost due to acute thrombosis of the arterial anastomosis immediately postoperatively. At a median followup of 20.5 months (range 2 to 38) 15 patients (93%) were fully satisfied with phallic cosmesis and size. Urethral stricture and fistula were the most common complications, which developed only at the native neourethral anastomosis. They were successfully managed by revision surgery. After revision surgery 11 of the 12 patients who underwent penile prosthesis implantation achieved sexual intercourse. CONCLUSIONS: The radial artery based forearm free flap is a good technique for total phallic construction in patients with bladder/cloacal exstrophy and micropenis-epispadias complex, providing reliable cosmetic and functional results.

Factors influencing intracytoplasmic sperm injection (ICSI) outcome in men with azoospermia.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The management of patients with non-obstructive azoospermia (NOA) and some cases of obstructive azoospermia involves testicular sperm extraction (TESE or micro-dissection TESE) combined with intracytoplasmic sperm injection (ICSI). Several studies have investigated the effect of the male age, the cause of azoospermia, testicular histopathology, the type of sperm used, and the use of pentoxyphilline, on the ICSI cycle outcome in men with azoospermia. The present study showed that none of these factors influenced the ICSI outcome in men with azoospermia, thus once sperm is found in an azoospermic male, no other male factor seems to influence the ICSI outcome. To our knowledge this is the first study to comment on the outcome of ICSI in men with NOA based on testicular histopathology. OBJECTIVES: To access the effect of: male age, the cause of azoospermia (obstructive azoospermia vs non-obstructive azoospermia [NOA]), testicular histopathology, the type of sperm used (fresh vs frozen-thawed), and the use of pentoxyphilline on the intracytoplasmic sperm injection (ICSI) cycle outcome in men with azoospermia. To our knowledge this is the first study to comment on the outcome of ICSI in men with NOA based on testicular histopathology. PATIENTS AND METHODS: A retrospective analysis of 137 testicular sperm extraction-ICSI cycles performed between 2001-2010, involving 103 men with azoospermia, with 26 couples having repeat cycles. RESULTS: Analysis of the results did not show any statistically significant differences in the fertilization, embryo cleavage, clinical pregnancy, live birth and miscarriage rates in relation to the male age, cuase of azoospermia, testicular histopathology, type of sperm used and the use of pentoxyphilline. CONCLUSION: Once sperm is found in a man with azoospermia, no other male factor seems to influence the ICSI outcome.

Anterolateral Thigh Flap Phalloplasty for Individuals Assigned Female at Birth.

Anterolateral thigh flap phalloplasty is a suitable alternative for individuals assigned female at birth who do not want a visible donor site, but careful patient selection is essential to reduce the risk of complications.

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.

Urological and Gynaecological Considerations for the Use of Gonadotropin-releasing Hormone Analogues in Transgender and Nonbinary Adolescents: A Narrative Review.

CONTEXT: Gonadotropin-releasing hormone analogues (GnRHAs) delay the progression of puberty in transgender and nonbinary (TGNB) adolescents and reduce the impact of dysphoria due to ongoing physical development. The intervention remains contentious despite growing evidence to support this practice. OBJECTIVE: To stimulate discussion on this topical issue in the urological and gynaecological community given potential ramifications for future fertility, physical development, and options for gender affirmation surgery (GAS). EVIDENCE ACQUISITION: We conducted searches of the MEDLINE (from 1946) and Embase (from 1974) databases for the benefits and potential challenges of hormone blockade in TGNB adolescents on February 1, 2022. Evidence with a primary focus on clinical issues of interest to urologists and gynaecologists was objectively synthesised and reported. EVIDENCE SYNTHESIS: The onset of puberty represents a period of distress for TGNB adolescents as secondary sexual characteristics develop. GnRHAs are prescribed to inhibit sex hormone production, but the decision to treat should be balanced against the known (and unknown) adverse effects. Fertility preservation is more likely to be successful if GnRHA treatment is delayed for as long as possible. Some adolescents may decide to stop GnRHA use to harvest spermatozoa or oocytes before starting gender-affirming hormone treatment. Transfeminine individuals should consider that options for genital GAS may become more limited, as vaginoplasty with penile skin inversion requires an adequate stretched penile length. Transmasculine individuals may no longer require chest reconstruction for breast development. CONCLUSIONS: Offers of GnRHA treatment to TGNB adolescents should be balanced by careful preparation and counselling. Urologists and gynaecologists can complement the expertise of specialist psychosocial and adolescent endocrinology teams, and should be involved early in and throughout the treatment pathway to maximise future functional and surgical outcomes. PATIENT SUMMARY: Puberty blockers for transgender and nonbinary adolescents have benefits, but timing is important to preserve fertility and surgical options.

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.

ESSM Position Statement "Sexual Wellbeing After Gender Affirming Surgery".

INTRODUCTION: Much has been published on the surgical and functional results following Gender Affirming Surgery ('GAS') in trans individuals. Comprehensive results regarding sexual wellbeing following GAS, however, are generally lacking. AIM: To review the impact of various GAS on sexual wellbeing in treatment seeking trans individuals, and provide a comprehensive list of clinical recommendations regarding the various surgical options of GAS on behalf of the European Society for Sexual Medicine. METHODS: The Medline, Cochrane Library and Embase databases were reviewed on the results of sexual wellbeing after GAS. MAIN OUTCOMES MEASURE: The task force established consensus statements regarding the somatic and general requirements before GAS and of GAS: orchiectomy-only, vaginoplasty, breast augmentation, vocal feminization surgery, facial feminization surgery, mastectomy, removal of the female sexual organs, metaidoioplasty, and phalloplasty. Outcomes pertaining to sexual wellbeing- sexual satisfaction, sexual relationship, sexual response, sexual activity, enacted sexual script, sexuality, sexual function, genital function, quality of sex life and sexual pleasure- are provided for each statement separately. RESULTS: The present position paper provides clinicians with statements and recommendations for clinical practice, regarding GAS and their effects on sexual wellbeing in trans individuals. These data, are limited and may not be sufficient to make evidence-based recommendations for every surgical option. Findings regarding sexual wellbeing following GAS were mainly positive. There was no data on sexual wellbeing following orchiectomy-only, vocal feminization surgery, facial feminization surgery or the removal of the female sexual organs. The choice for GAS is dependent on patient preference, anatomy and health status, and the surgeon's skills. Trans individuals may benefit from studies focusing exclusively on the effects of GAS on sexual wellbeing. CONCLUSION: The available evidence suggests positive results regarding sexual wellbeing following GAS. We advise more studies that underline the evidence regarding sexual wellbeing following GAS. This position statement may aid both clinicians and patients in decision-making process regarding the choice for GAS. Özer M, Toulabi SP, Fisher AD, et al. ESSM Position Statement "Sexual Wellbeing After Gender Affirming Surgery". Sex Med 2022;10:100471.

ESSM Position Statement on Surgical Treatment of Peyronie's Disease.

INTRODUCTION: Patients with Peyronie's disease may experience significat distress. The choice of treatment depends on a variety of factors, including the stage of the disease, the presence of pain, severity and direction of the curvature, penile length and the quality of erectile function. AIM: To review the evidence associated with surgical treatment of Peyronie`s Disease and provide clinical recommendations on behalf of the European Society for Sexual Medicine. 131 peer-reviewed studies and systematic reviews, which were published from 2009 to 2019 in the English language, were included. METHODS: MEDLINE, Google Scholar and EMBASE were searched for randomized clinical trials, meta-analyses, open-label prospective and retrospective studies. MAIN OUTCOME MEASURE: The panel provided statements on clinically relevant questions including patient involvement in the decision process, indications for surgery, choice of the approach, and the management of patient expectations. A comparison of the different grafts used in patients who have undergone plaque incision/excision and grafting in order to identify an ideal graft, has been carried out. The prevalence of postoperative complications has been summarized. Levels of evidence were provided according to the Oxford 2011 criteria and Oxford Centre for Evidence-Based Medicine recommendations. RESULTS: In order to allow shared decision making, a patient preoperative counselling regarding the pros and cons of each intervention is recommended. In particular, adverse effects of surgical treatments should be discussed to set realistic understanding and expectations of surgical outcomes and ultimately improve postoperative satisfaction rates. Surgical treatment should be only offered in the chronic phase of the condition, when the deformity and/or degree of erectile dysfunction, prevent patients from engaging in satisfying sexual interaction, or if the deformity is the cause of severe bother. CONCLUSIONS: Current European Society for Sexual Medicine recommendations cover several aspects of Peyronie's disease treatment. These recommendations aim both to ensure patients and partners have accurate and realistic expectations of their treatment options, as well as to formulate algorithms to guide clinician management pathways. Osmonov D, Ragheb A, Ward S et al, ESSM Position Statement on Surgical Treatment of Peyronie's Disease. Sex Med 2022;10:100459.

The management of residual curvature after penile prosthesis implantation in men with Peyronie's disease.

OBJECTIVE: • To report our experience in the management of residual curvature after implantation of a penile prosthesis in men with Peyronie's disease (PD). PATIENTS AND METHODS: • From January 1985 to June 2009, 62 (29%) of the 209 patients with PD that have undergone the insertion of a penile prosthesis have required an additional straightening procedure to correct the residual curvature after the insertion of the cylinders of the implant. • The types of additional manoeuvres, their success in correcting the residual curvature and eventual complications have been reported. RESULTS: • Among the additional straightening procedures, modelling was more successful in achieving straightening when performed on an inflatable device (84%) than on a malleable implant (54%). • If the curvature persisted after modelling or if the curvature was ventral, straightening was achieved with tunical plications or incision with or without grafting. CONCLUSION: • Although it is common for the simple implantation of cylinders alone to straighten the penis, some patients will present a residual curvature that must be successfully corrected with additional straightening procedures.

The surgical management of lichen sclerosus of the glans penis: our experience and review of the literature.

INTRODUCTION: Lichen sclerosus (LS) of the glans penis is a chronic, progressive, scleroatrophic inflammatory process of unknown etiology affecting the glans penis, prepuce, and urethra and may lead to severe impairment of sexual and urinary function. AIMS: To report our experience of surgical management of LS of the glans penis. MAIN OUTCOME MEASURES: Complications, patients' satisfaction, cosmesis, resolution of pain and puritus, and postoperative sexual function and were recorded retrospectively. METHODS: The surgical outcome of the 31 patients who have undergone resurfacing of the glans penis with the use of skin grafting for the management of genital LS in our institute is reported. RESULTS: After a median follow-up of 12.8 months, 26 patients (84%) were fully satisfied with cosmetic and functional results, and 71% of them have resumed sexual activity. CONCLUSIONS: Resurfacing of the glans penis represents a simple and reproducible technique for the management of LS and yields excellent functional and cosmetic results.

Total urethral construction with the radial artery-based forearm free flap in the transsexual.

OBJECTIVE: to report our experience of using a radial artery-based forearm free flap urethroplasty (RAFFFU) inside a pre-fashioned pedicled pubic phalloplasty for female-to-male gender reassignment. PATIENTS AND METHODS: a neourethra based on the RAFFF was incorporated into a previously constructed phalloplasty in 27 patients. Surgical outcome, patients' satisfaction and voiding sensation of the neourethra were subjectively and prospectively assessed by direct questioning during the follow-up. RESULTS: after a median follow-up of 9.2 months, all patients who completed the two stages of the procedure were able to void from the tip of the phallus while standing. Donor-site morbidity was minimal, with all patients reporting a complete recovery of forearm sensation and mobility. The overall satisfaction rate was 92%. CONCLUSIONS: the RAFFFU is the best technique of total urethral construction in female-to-male transsexuals who opt not to undergo a RAFFF phalloplasty.

The role of vacuum pump therapy to mechanically straighten the penis in Peyronie's disease.

OBJECTIVE: to assess the efficacy of vacuum therapy in mechanically straightening the penile curvature of Peyronie's disease (PD). PATIENTS AND METHODS: Modelling of the tunica albuginea has been shown to be possible during penile implant surgery and this principle has been applied as an alternative conservative therapy. In all, 31 patients with PD (mean duration 9.9 months; mean age 51 years, range 24-71) completed the study. Over a 12-week period, the patients used a vacuum device (Osbon ErecAid, MediPlus, High Wycombe, UK) for 10 min twice daily. The assessment at study entry and at completion after 12 weeks included the International Index of Erectile Function questionnaire, a perceived pain intensity score, stretched penile length measurement and the angle of penile deformity after an intracavernous injection with prostaglandin E1. RESULTS: there was a clinically and statistically significant improvement in penile length, angle of curvature and pain after 12 weeks of using the vacuum pump. Of the 31 patients, 21 had a reduction in the angle of curvature by 5-25 degrees, three had worsening of the curvature and there was no change in the remaining seven. The curvature was corrected surgically in 15 patients while the remaining 16 (51%) were satisfied with the outcome. CONCLUSION: vacuum therapy can improve or stabilize the curvature of PD, is safe to use in all stages of the disease, and might reduce the number of patients going on to surgery.

Total phallic reconstruction after penile amputation for carcinoma.

OBJECTIVE: To report our experience of total phallic reconstruction (TPR) with the use of the radial-artery free flap (RAFF) in patients who have had a subtotal penectomy for penile or urethral cancer, as the goal of TPR is the creation of a sensate and cosmetically acceptable phallus with an incorporated neourethra that allows the patient to void while standing, and with the insertion of a penile implant to resume sexual activities, improving quality of life. PATIENTS AND METHODS: The notes of the 15 patients who had undergone RAFF TPR between January 1998 and May 2008 were reviewed retrospectively. The surgical outcome, cosmesis of the phallus, complications, eventual need for revision surgery and patient satisfaction were recorded during the follow-up. RESULTS: This technique allowed the reconstruction of a cosmetically acceptable phallus in all patients. After a median (range) follow-up of 20 (1-68) months all patients were satisfied with the cosmesis and size of the phallus, and 14 were able to void while standing. Among the seven patients who have subsequently had insertion of a penile prosthesis, five can now engage in sexual intercourse. Urethral strictures and fistulae were the commonest complications in, respectively, three and four cases, and one patient had his penile prosthesis explanted because of infection. CONCLUSIONS: RAFF phalloplasty is an excellent technique for TPR, giving excellent cosmetic and functional results.

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.

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.

Subjective and objective results in surgical correction of adult acquired buried penis: A single-centre observational study.

OBJECTIVE: The purpose of this study was to provide a detailed analysis of surgical and functional outcomes after correction of acquired buried penis in the adult. MATERIALS AND METHODS: From 2006 to 2016, we retrospectively reviewed 47 patients undergoing surgical treatment for the correction of buried penis. Functional and surgical outcomes, as well as patients' satisfaction were the main endpoints. RESULTS: The most common complains at presentation were recurrent uro-genital infections, sexual dysfunction, voiding dysfunction and Lichen Sclerosus (LS). Surgical management steps included: circumcision (27.66%), scrotoplasty (19.14%), V-Y skin plasty (4.25%), split thickness skin graft (STSG) 12.76%, full thickness skin graft (FTSG) 36.17%, suprapubic fat pad excision (57.44%), abdominoplasty (25.53%), division of the suspensory ligament (36.17%). Postoperative complications were recorded in 15% of patients. Vaginal penetration and erectile function ended up being more effective in 97.87% (46/47) and 42.55% (20/47) of patients. Improvement in penile erogenous sensation was in 6.38% (3/47). Aesthetic appearance of genitalia fully satisfied 36.17% of patients (17/47). Overall patients' satisfaction rate resulted 76.59% (36/47). CONCLUSION: Management of adult acquired buried penis still remains a challenging task to achieve, however excellent cosmetic results can be obtained by surgical reconstruction.

Antifibrotic Synergy Between Phosphodiesterase Type 5 Inhibitors and Selective Oestrogen Receptor Modulators in Peyronie's Disease Models.

BACKGROUND: Peyronie's disease (PD) is a fibrotic disorder of the penile tunica albuginea, characterised by the formation of a localised fibrous plaque that can lead to deformity and erectile dysfunction. Nonsurgical therapeutic options for PD are limited in efficacy and safety. Myofibroblasts are key cells in the pathogenesis of PD, and inhibition of myofibroblast transformation has been suggested as a therapeutic option. OBJECTIVE: To identify potential drugs using a novel phenotypic assay and then to test them using in vitro and in vivo models of PD. DESIGN, SETTING, AND PARTICIPANTS: We have developed and validated a phenotypic screening assay that measures myofibroblast transformation, by which we tested 21 compounds that were suggested to be efficacious in treating PD. The successful hits from this assay were further tested using in vitro and in vivo models of PD. RESULTS AND LIMITATIONS: The new assay was able to detect transforming growth factor-ß1-induced myofibroblast transformation. Using this assay, phosphodiesterase type 5 inhibitors (PDE5i) and selective oestrogen receptor modulators (SERMs) were identified to significantly inhibit myofibroblast transformation. A PDE5i (vardenafil) and an SERM (tamoxifen) inhibited myofibroblast transformation, collagen gel contraction, and extracellular matrix production in a synergistic fashion. In a rat model of PD, the antifibrotic effect of the combination of vardenafil and tamoxifen was greater than that of each drug alone. This study is limited by not providing a molecular mechanism for the proposed synergy. CONCLUSIONS: This is the first demonstration of a synergistic activity between a PDE5i and an SERM discovered through a phenotypic screening approach. Future clinical trials using a combination of these drugs should be considered during the active phase of PD, given the early evidence of benefit in both in vitro and in vivo models. PATIENT SUMMARY: This report suggests that the combination of a phosphodiesterase type 5 inhibitor and a selective oestrogen receptor modulator may be efficacious in treating Peyronie's disease in its active phase.

The management of genital lymphoedema.

OBJECTIVES: To report our experience and management of genital lymphoedema, as this condition can be extremely debilitating and difficult to manage. PATIENTS AND METHODS: The clinical records of 90 patients with genital lymphoedema who presented between 1998 and 2007 were retrospectively reviewed. The surgical management of 34 patients consisted of the excision of the affected skin and of the subcutaneous layers. This involved scrotal excision in 15 patients with primary closure. Skin grafts were required in seven patients for penile shaft cover. The results for cosmesis, recovery of sexual function, patient's satisfaction and complications are discussed. RESULTS: In all, 56 patients were successfully managed conservatively by treating the underlying condition, antibiotic administration, compression and elevation of the genitalia. The remaining 34 patients required surgical management with an overall excellent cosmetic result and a significant improvement in sexual function. CONCLUSIONS: When surgery is necessary for genital lymphoedema, the new techniques described provide excellent cosmetic and functional results.