The Montréal Classification of urethral lengthening for phalloplasty in transmasculine patients-surgical techniques and urethral complications.

Introduction: Phalloplasties are one of the most performed genital surgeries in the treatment of gender dysphoria for transmasculine patients. Urethral lengthening is an essential component of phalloplasties. Few techniques have been described for the creation of this pars fixa urethra. The purpose of this article is to present the Montréal Classification for pars fixa urethral lengthening, to detail the surgical techniques and to report on clinical outcomes. Materials and methods: All patients undergoing phalloplasty from November 2016 to February 2019 were included in this study. Patient demographics, type of surgery and urological complications were recorded. Statistics were performed using student's T-test, Chi-squared test, Fisher's exact test and One-way ANOVA. Patients underwent either type 1, type 2, or type 3 urethral reconstruction. Results: Of the 84 total patients, 45 underwent type 1 lengthening, 28 type 2, and 11 type 3. Eighteen and 33 patients underwent single-stage and two stage anastomosis of the pars fixa to the pars pendulans neourethra, respectively. Thirty-three patients have not had any additional surgeries to date. Post-operative urological complications for immediate anastomosis and two-stage anastomosis were reported in 77.7% and 18.2% of patients, respectively. Conclusions: We propose a classification as well as a description of three types of urethral lengthening techniques. Over the last few years, we have shifted away from single-stage anastomosis and have adopted a two-stage anastomosis technique. Our experience allows us to classify urethral lengthening and to standardize care depending on patient characteristics, leading to excellent results.

Gender-Affirming Surgery in Adolescents and Young Adults: A Review of Ethical and Surgical Considerations.

BACKGROUND: The number of transgender adolescents seeking gender-affirming surgery (GAS) in increasing. Surgical care of the adolescent transgender patient is associated with several unique technical, legal, and ethical factors. The authors present a review of the current literature on gender-affirming surgery for individuals under the age of legal majority and propose directions for future research. METHODS: A scoping review of recent literature was performed to assess evidence on gender-affirming surgery in individuals under the age of legal majority. Articles were included that examined either ethical or technical factors unique to pediatric GAS. Study characteristics and conclusions were analyzed in conjunction with expert opinion. RESULTS: Twelve articles were identified that met inclusion criteria. Ten of these articles discussed ethical challenges in adolescent GAS, seven discussed legal challenges, and five discussed technical challenges. Ethical discussions focused on the principles of beneficence, nonmaleficence, and autonomy. Legal discussions centered on informed consent and insurance coverage. Technical discussions focused on the effects of puberty blockade on natal tissue. CONCLUSIONS: Surgical care of the adolescent transgender patient involves important ethical, legal, and technical considerations that must be addressed by the clinical team. As the population of individuals seeking GAS after puberty blockade increases, future research is needed describing functional and psychosocial outcomes in these individuals.

Incidence of Testicular Cancer in Transfeminine Patients following Vaginoplasty with Orchidectomy.

Background: Little is known about the prevalence of testicular cancer in the transfeminine population. Only six cases have been reported in the literature. This case series reports six additional cases of various testicular cancers found in transfeminine patients who underwent vaginoplasty with orchidectomy in our institution. Methods: In our institution, all specimens are routinely sent to pathology following vaginoplasty with orchidectomy. This permitted the identification of all positive cases of testicular cancer. A chart review was conducted to retrieve patient demographics, duration of hormonotherapy, type of neoplasm, the context of its discovery, and cancer follow-up. Results: A total of 2555 patients underwent vaginoplasty with orchidectomy between January 2016 and January 2021. All specimens were sent to pathology for analysis. A total of six (0.23% of patients) specimens revealed malignant lesions. Conclusions: Increased societal awareness toward the transgender population encourages recourse to gender-affirming procedures. Little is known about the incidence of testicular cancer in the transfeminine population. In total, 0.23% of patients in our cohort presented with positive pathology findings indicative of testicular cancer. All cancers were found to be only locally invasive, and all patients were successfully treated. We therefore encourage routine pathology examination for all specimens following vaginoplasty with orchidectomy.

The Surgical Techniques and Outcomes of Secondary Phalloplasty After Metoidioplasty in Transgender Men: An International, Multi-Center Case Series.

INTRODUCTION: Some transgender men express the wish to undergo genital gender-affirming surgery. Metoidioplasty and phalloplasty are procedures that are performed to construct a neophallus. Genital gender-affirming surgery contributes to physical well-being, but dissatisfaction with the surgical results may occur. Disadvantages of metoidioplasty are the relatively small neophallus, the inability to have penetrative sex, and often difficulty with voiding while standing. Therefore, some transgender men opt to undergo a secondary phalloplasty after metoidioplasty. Literature on secondary phalloplasty is scarce. AIM: Explore the reasons for secondary phalloplasty, describe the surgical techniques, and report on the clinical outcomes. METHODS: Transgender men who underwent secondary phalloplasty after metoidioplasty were retrospectively identified in 8 gender surgery clinics (Amsterdam, Belgrade, Bordeaux, Austin, Ghent, Helsinki, Miami, and Montreal). Preoperative consultation, patient motivation for secondary phalloplasty, surgical technique, perioperative characteristics, complications, and clinical outcomes were recorded. MAIN OUTCOME MEASURE: The main outcome measures were surgical techniques, patient motivation, and outcomes of secondary phalloplasty after metoidioplasty in transgender men. RESULTS: Eighty-three patients were identified. The median follow-up was 7.5 years (range 0.8-39). Indicated reasons to undergo secondary phalloplasty were to have a larger phallus (n = 32; 38.6%), to be able to have penetrative sexual intercourse (n = 25; 30.1%), have had metoidioplasty performed as a first step toward phalloplasty (n = 17; 20.5%), and to void while standing (n = 15; 18.1%). Each center had preferential techniques for phalloplasty. A wide variety of surgical techniques were used to perform secondary phalloplasty. Intraoperative complications (revision of microvascular anastomosis) occurred in 3 patients (5.5%) undergoing free flap phalloplasty. Total flap failure occurred in 1 patient (1.2%). Urethral fistulas occurred in 23 patients (30.3%) and strictures in 27 patients (35.6%). CLINICAL IMPLICATIONS: A secondary phalloplasty is a suitable option for patients who previously underwent metoidioplasty. STRENGTHS & LIMITATIONS: This is the first study to report on secondary phalloplasty in collaboration with 8 specialized gender clinics. The main limitation was the retrospective design. CONCLUSION: In high-volume centers specialized in gender affirming surgery, a secondary phalloplasty in transgender men can be performed after metoidioplasty with complication rates similar to primary phalloplasty. Al-Tamimi M, Pigot GL, van der Sluis WB, et al. The Surgical Techniques and Outcomes of Secondary Phalloplasty After Metoidioplasty in Transgender Men: An International, Multi-Center Case Series. J Sex Med 2019;16:1849-1859.

Characterization of myeloid cell populations in human testes collected after sex reassignment surgery.

The testis has been described in animal models as a site of immune privilege, which protects spermatids against tissue damage during inflammation. Myeloid cells, including macrophages and dendritic cells (DC), are defined as key players in the testicular immune privilege in animal models. However, their distribution and frequency in human testis remain poorly described. To overcome the challenges related to tissue sampling, we obtained testicular tissue from men under hormonal therapy who elected to have sex reassignment surgery (SRS). We examined the distribution of myeloid cell populations in tissue sections using immunohistofluorescence and evaluated their relative frequencies in fresh testicular cell suspensions compared with matched blood using multi-parametric flow cytometry. We identified 4.9% of CD45+ leucocytes in testicular cell suspensions, of which 0.4% were B cells, demonstrating a low level of blood contamination. Myeloid cells (Lin-HLA-DR+) were located in the testicular interstitium and represented a median of 23.4% of testicular leucocytes, displaying higher HLA-DR expression compared to their counterparts in blood (p=0.001). The frequency of testicular myeloid cells was not linked with the duration of hormonal therapy. Resident macrophages (CD14+CD163+) constituted the most frequent myeloid cell subset and expressed high levels of CD163. Elevated proportion of myeloid DC (CD14-CD11c+) contrasted with the paucity of plasmacytoïd DC (CD14-CD123+) in testis. Myeloid-derived suppressor cells (Lin-HLA-DR-CD33hiCD11bhi) were not detected in the testis while constituting 0.5% of blood leucocytes. For the first time, we characterized myeloid cell subsets in human testes collected after SRS, providing a basis to assess their contribution to immune privilege.

Immune tolerance properties of the testicular tissue as a viral sanctuary site in ART-treated HIV-infected adults.

OBJECTIVE: HIV persistence in long-lived infected cells and in anatomical sanctuary sites are major hurdles to HIV eradication. Testicular tissue may represent a significant viral sanctuary site as it constitutes an immunologically privileged compartment. We assessed immunotolerance properties of the testicular tissue in individuals receiving suppressive antiretroviral therapy (ART). DESIGN AND METHODS: Testicular tissue and matched blood samples were collected from six virally suppressed adults and 10 HIV-uninfected controls prior to sex reassignment surgery. T cells were purified from freshly isolated testicular interstitial cell suspensions. T-cell subsets, expression of immune activation markers and HIV DNA were assessed in matched testicular cells and peripheral blood mononuclear cells (PBMCs). RESULTS: When compared with PBMCs, testes were characterized by a lower CD4 T-cell proportion among total T cells, a decrease in the frequency of naive cells, an increase in the frequency of effector-memory T cells and an increase in CCR5 expression in both the HIV+ and HIV- groups. In HIV-infected individuals on ART, testes displayed higher T-cell immune activation (Coexpression of CD38 and Human Leukocyte Antigen - antigen D Related) than PBMCs. In both groups, testes were characterized by higher frequencies of immunosuppressive CD39 regulatory T cells and a massive increase in CD73 expression on CD8 T cells. In addition, a remarkable increase in indoleamine-pyrrole 2,3-dioxygenase immunosuppressive enzyme involved in tryptophan/kynurenine catabolism was observed in testes versus blood. Rare cells harboring HIV DNA were detected in testes from five out six participants. CONCLUSION: These findings suggest that the adenosine and tryptophan/kynurenine immune-metabolic pathways contribute to immune tolerance in testicular tissue. Our results suggest that testes may represent a distinctive HIV sanctuary site during ART.

Antiretroviral drug transporters and metabolic enzymes in human testicular tissue: potential contribution to HIV-1 sanctuary site.

OBJECTIVES: The testes are a potential viral sanctuary site for HIV-1 infection. Our study aims to provide insight into the expression and localization of key drug transporters and metabolic enzymes relevant to ART in this tissue compartment. METHODS: We characterized gene and protein expression of 12 representative drug transporters and two metabolic enzymes in testicular tissue samples obtained from uninfected (n = 8) and virally suppressed HIV-1-infected subjects on ART (n = 5) and quantified antiretroviral drug concentrations in plasma and testicular tissues using LC/MS/MS from HIV-1-infected subjects. RESULTS: Our data demonstrate that key ABC drug transporters (permeability glycoprotein, multidrug-resistance protein 1, 2 and 4, and breast cancer resistance protein), solute carrier transporters (organic anion transporting polypeptides 1B1 and 2B1, organic anion transporter 1, concentrative nucleoside transporter 1, equilibrative nucleoside transporter 2) and cytochrome P450 metabolic enzymes (CYP3A4 and CYP2D6) previously shown to interact with many commonly used antiretroviral drugs are expressed at the mRNA and protein level in the testes of both subject groups and localize primarily at the blood-testis barrier, with no significant differences between the two groups. Furthermore, we observed that PIs known to be substrates for ATP-binding cassette membrane transporters, displayed variable testicular tissue penetration, with darunavir concentrations falling below therapeutic values. In contrast, the NRTIs emtricitabine, lamivudine and tenofovir displayed favourable tissue penetration, reaching concentrations comparable to plasma levels. We also demonstrated that nuclear receptors, peroxisome proliferator-activated receptors α and γ exhibited higher gene expression in the testicular tissue compared with pregnane X receptor and constitutive androstane receptor, suggesting a potential regulatory pathway governing drug transporter and metabolic enzyme expression in this tissue compartment. CONCLUSIONS: Our data suggest the testes are a complex pharmacological compartment that can restrict the distribution of certain antiretroviral drugs and potentially contribute to HIV-1 persistence.