Advancing Intraoperative Assessment of Urethral Stricture Anatomic Variation: a Prospective Proof-of-concept Study

INTRODUCTION Urethral strictures, particularly those refractory to endoscopic interventions, are commonly treated through open urethroplasty. However, predicting recurrence in homogeneous patient populations remains challenging. METHODS To address this, we developed an intraoperative urethral stricture assessment tool aiming to identify comprehensive risk predictors. The assessment includes detailed parameters on stricture location, length, urethral bed width, spongiosum thickness, obliteration grade, and spongiofibrosis extension. The tool was prospectively implemented in 106 men with anterior one-stage augmentation urethroplasty 04/2020 to 10/2021. RESULTS An intraoperative granular assessment of intricate stricture characteristics is feasible. Comparative analyses revealed significant differences between bulbar and penile strictures. Bulbar strictures exhibited wider urethral beds and thicker spongiosum compared to penile strictures (all P<0.001). The assessment showed marked variations in the degree of obliteration and spongiofibrosis extension. CONCLUSION Our tool aligns with efforts to standardize urethral surgery, providing insights into subtle disease intricacies and enabling comparisons between institutions. Notably, intraoperative assessment may surpass the limitations of preoperative imaging, emphasizing the necessity of intraoperative evaluation. While limitations include a single-institution study and limited sample size, future research aims to refine this tool and determine its impact on treatment strategies, potentially improving long-term outcomes for urethral strictures

Antigen-Specific IgG Subclasses in Primary and Malignancy-Associated Membranous Nephropathy

Membranous nephropathy (MN) is an autoimmune disease caused by binding of circulating antibodies to podocyte antigens in the kidney. For decades and still today primary MN has been considered to have an unspecified IgG4-driven autoimmune genesis, while secondary MN has been associated with other diseases, most notably cancer, and not linked to IgG4. Immunologic mechanisms of primary and malignancy-associated MN are assumed to be different, however, this has never been systematically evaluated. The identification of Phospholipase A2 Receptor 1 (PLA2R1) and Thrombospondin Type-1 Domain-Containing 7A (THSD7A) as target antigens in MN allows a pathogenesis-driven differential diagnosis. Recent data showing a molecular link between increased THSD7A-expression in tumors and THSD7A-antibody positive MN suggest a similar pathogenesis of malignancy-associated and primary MN. In order to better define the underlying immunologic processes, we systematically analyzed circulating antigen-specific IgG subclasses in the serum of 76 patients with PLA2R1-associated MN and 41 patients with THSD7A-associated MN in relationship to concurrent malignancy and disease outcome. Twenty-three patients in the study had malignancy-associated MN. We analyzed antigen-specific IgG subclasses in the serum of all patients at baseline and in 55 patients during follow-up by Western blot applying antigens derived from human kidney and lung. At baseline all 117 patients were positive for IgG4-antibodies against either PLA2R1 or THSD7A, while IgG3, IgG1, and IgG2-antibodies were found in 87, 72, and 26% of patients, respectively. There were no differences in the IgG subclass distribution between patients with primary vs. cancer-associated MN and no association with disease outcome. Moreover, levels of antigen-specific IgG4-antibodies were not different between primary and malignancy-associated MN and levels of all IgG subclasses did not differ between these groups. Both podocytes and lung bronchioles showed expression of both PLA2R1 and THSD7A when analyzed by immunofluorescence and Western blot. Every antigen-specific IgG subclass showed identical binding in both organs and autoantibodies bound the respective antigen only under non-reducing conditions. We conclude that antigen-specific IgG subclasses do not differentiate primary from malignancy-associated MN or predict disease prognosis. These data support the view that one common pathway may lead to primary and cancer-associated MN induced by PLA2R1- or THSD7A-antibodies

clinical recommendations from the european society for sexual medicine exploring partner expectations satisfaction in male and phalloplasty cohorts the impact of penile length girth and implant type reservoir placement and the influence of comorbidities and social circumstances

Abstract Introduction To date, several aspects of inflatable penile prosthesis (IPP) surgical procedure have been poorly studied. Aim The aim of this study was to review the evidence associated with IPP implantation and provide clinical recommendations on behalf of the European Society for Sexual Medicine (ESSM). Overall, 130 peer-reviewed studies and systematic reviews, which were published from 2007−2018 in the English language, were included. Methods MEDLINE and EMBASE were searched for randomized clinical trials, meta-analyses, and open-label prospective and retrospective studies. Main Outcome Measure The panel provided statements exploring patients and partner expectations, satisfaction in male and phalloplasty cohorts, the impact of penile length, girth and implant type, reservoir placement, the influence of comorbidities, and social circumstances. Levels of evidence were provided according to the Oxford 2011 criteria and graded as for the Oxford Centre for Evidence-Based Medicine recommendations. Results In the preoperative setting, it is fundamental to identify and interact with difficult patients with the intention of enhancing the surgeon's ability to establish the surgeon-patient relationship, reduce physical and legal risk, as well as enhancing patient satisfaction. To address this need, the mnemonic Compulsive, Unrealistic, Revision, Surgeon Shopping, Entitled, Denial, and Psychiatric ("CURSED") has been suggested to identify patients who are at high risk of dissatisfaction. The current recommendations suggest improving glycemic control in patients with diabetes. Available evidence suggests evaluating transplant recipients with the criteria of Barry, consisting of stable graft function for >6 months, avoidance of intra-abdominal reservoir placement, and low-dose immunosuppression. HIV status does not represent a contraindication for surgery. Smoking, peripheral vascular disease, and hypertension may be associated with an increased risk of revision surgery. Patients with spinal cord injury may receive IPP. Patients aged ≥70 years, as well as obese patients, can be offered IPP. The IPP implantation can be performed in patients with stable Peyronie's disease. Ectopic high submuscular reservoir placement can be considered as an alternative method. Clinical Implications There is a relevant lack of high-level data and definite conclusions in certain areas remain difficult to draw. Strength & Limitations All studies have been evaluated by a panel of experts providing recommendations for clinical practice. Because of lack of sufficient prospective data, some of the included studies are retrospective and this could be stated as a limitation. Conclusion This ESSM position statement provides recommendations on optimization of patient outcome by patient selection, and individualized peri- and intra-operative management. ESSM encourages centers to collaborate and to create prospective, multicenter registries in order to address this topic of increasing importance. Osmonov D, Christopher AN, Blecher GA, et al. Clinical Recommendations from the European Society for Sexual Medicine Exploring Partner Expectations, Satisfaction in Male and Phalloplasty Cohorts, the Impact of Penile Length, Girth and Implant Type, Reservoir Placement, and the Influence of Comorbidities and Social Circumstances. J Sex Med 2019;XX:XXX–XXX

Negative Self-Perception and Self-Attitude of Sexuality Is a Risk Factor for Patient Dissatisfaction Following Penile Surgery with Small Intestinal Submucosa Grafting for the Treatment of Severe Peyronie’s Disease

Objective: To assess patient satisfaction with surgical outcome, body related self-perceptions, self-attitudes of sexuality, and health related quality of life after penile surgery with small intestinal submucosa (SIS) grafting for the treatment of severe Peyronie&rsquo;s disease (PD). Material and methods: This retrospective study included 82 patients, who were treated with SIS grafting for severe PD between 2009 and 2013 at the University Medical Center Hamburg-Eppendorf. Patients were asked to complete standardized questionnaires including the International Index of Erectile Function Erectile Function domain (IIEF-EF), Short-Form (SF)-8 Health Survey, and Frankfurt Body Concept Scale-Sexuality (FKKS-SEX). Results: Follow-up was available in 58 (69.9%) patients. SIS grafting resulted in subjective straightening of the penis in 53 (91.3%) patients. After a mean follow-up of 28.9 &plusmn; 16.5 months, 24 (41.4%) patients were satisfied or very satisfied with surgical outcome. Postoperatively, the mean FKKS-SEX was 23.5 &plusmn; 5.9. In total, 36 (62.1%), 18 (31%), and four (6.9%) patients had FKKS-SEX scores corresponding to positive, neutral, and negative self-perception and self-attitude of sexuality, respectively. The mean postoperative SF-8 was 15.2 &plusmn; 6.4. Compared to the mean for German controls, patients achieved lower mean scores in the domains social functioning (50.4 &plusmn; 7.1), mental health (49.5 &plusmn; 9.2), and emotional roles (48.5 &plusmn; 6.8). Subjective shortening of the penis (Odds ratio (OR): 2.0), negative body related self-perceptions, and self-attitudes of sexuality (OR: 3.6) as well as IIEF-EF score (OR: 0.9) were risk factors for patient dissatisfaction (p-values &le; 0.02). Conclusion: A relevant number of patients is not satisfied with surgical outcome after SIS grafting for the treatment of severe PD. Subjective shortening of the penis, negative body related self-perceptions, and self-attitudes of sexuality as well as IIEF-EF score were risk factors for patient dissatisfaction

Exploring the Relationship between (De-)Centralized Health Care Delivery, Client-Centeredness, and Health Outcomes—Results of a Retrospective, Single-Center Study of Transgender People Undergoing Vaginoplasty

Introduction: Transgender health care interventions (e.g., gender-affirming surgery) support transgender and gender-diverse people to transition to their gender and are delivered in both centralized (by one interdisciplinary institution) and decentralized settings (by different institutions spread over several locations). In this exploratory study, we investigated the relationship between centralized and decentralized delivery of transgender health care, client-centeredness, and psychosocial outcomes. Methods: A retrospective analysis of 45 clients undergoing vaginoplasty at one medical center was conducted. Mann–Whitney U tests assessed differences regarding five dimensions of client-centeredness and psychosocial outcomes between the health care delivery groups. To address shortcomings regarding the small sample size, we applied a rigorous statistical approach (e.g., Bonferroni correction) to ensure that we only identified predictors that were actually related to the outcomes. Results: All aspects of client-centered care were scored average or high. Decentralized delivery of care was more client-centered in terms of involvement in care/shared decision-making and empowerment. However, participants from decentralized health care delivery settings scored lower on psychosocial health (p = 0.038–0.005). Conclusions: The factor of (de-)centralized health care delivery appears to have a significant impact on the provision of transgender health care and should be investigated by future research

Outcome of buccal mucosa graft urethroplasty: a detailed analysis of success, morbidity and quality of life in a contemporary patient cohort at a referral center

Abstract Background To evaluate outcome of buccal mucosa graft urethroplasty (BMGU) for the treatment of urethral stricture disease, including a detailed analysis of success, morbidity and quality of life (QoL). Methods Between 12/05/2008 and 07/21/2010, 187 patients with urethral stricture disease, who were treated with BMGU at our University Medical Center, received a standardized questionnaire, evaluating postoperative success, morbidity and QoL. The primary endpoint was the success, i.e., stricture recurrence-free survival plus patients’ satisfaction with surgery. Secondary endpoints included erectile function, voiding symptoms, pain and health-related QoL, which were assessed with a modified Urethral Stricture Surgery Patient Reported Outcome Measure (USS PROM), including the Erectile Function domain of the International Index of Erectile Function (IIEF-EF), Incontinence Questionnaire Male Lower Urinary Tract Symptoms Module (ICIQ-MLUTS) and EuroQol-5 dimensions (EQ-5D). Results In total, 83 patients (51.9%) completed the questionnaire. Bulbar, penile and panurethral strictures were found in 69 patients (83.1%), 13 patients (15.7%) and one patient (1.2%), respectively. The median length of the stricture was 5 cm (range: 1–16). At a median follow-up of 46 months (range: 36–54), 65 patients (78.3%) had no stricture recurrence and were satisfied with BMGU. Median scores for ICIQ-MLUTS, IIEF-EF and EQ-5D visual analogue scale were 6, 22 and 80, respectively. Based on USS PROM, postoperative improvement of QoL and satisfaction with BMGU was found in 67 patients (80.7%) and 68 patients (81.9%), respectively. Conclusions In patients with urethral stricture disease, BMGU offers excellent success, morbidity and QoL

The Impact of Circulating Tumor Cells on Venous Thromboembolism and Cardiovascular Events in Bladder Cancer Patients Treated with Radical Cystectomy

Background: Cancer is a relevant risk factor for venous thromboembolism (VTE). Circulating tumor cells (CTC) are associated with an increased risk of VTE in breast cancer. In addition, circulating cell-free nucleic acids have been associated with cardiovascular events (CVE). Objective: To investigate the association of CTC status and the risk of VTE as well as CVE in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). Methods: We collected data of 189 UCB patients treated with RC at our institution. Blood samples were acquired preoperatively and analyzed for CTC using the CellSearch&reg; system. Thirty-day postoperative complications were extracted from digital charts and graded according to the Clavien&ndash;Dindo classification (CDC). Moreover, each patient&rsquo;s individual Comprehensive Complication Index&reg; (CCI&reg;) was calculated. Results: CTC were present in 43 patients (22.8%). Overall, six patients experienced VTE (3.2%) and eight patients (4.2%) experienced CVE. There was no association of VTE or CVE according to CTC status. In total, 168 patients (89%) experienced a total of 801 complications, of which the majority was classified as &ldquo;minor&rdquo; (CDC grade &le; IIIa; 79%). There was no association between CTC status and any grade of a complication or CCI&reg;. Presence of CTC was associated with more aggressive clinicopathological UCB features. Conclusions: The overall rate of VTE and CVE was low in our study. Presence of CTC was neither associated with an increased risk of VTE nor CVE in UCB patients treated with RC. According to this study, CTC are not a qualified biomarker for individualized thromboprophylaxis management in these patients

Exploring the intersection of functional recurrence, patient-reported sexual function, and treatment satisfaction after anterior buccal mucosal graft urethroplasty

Purpose!#!To evaluate the interplay of stricture recurrence, sexual function, and treatment satisfaction after substitution urethroplasty.!##!Methods!#!Observational study of men undergoing 1-stage buccal mucosal graft urethroplasty for anterior urethral stricture between 2009 and 2016. Patients were dichotomized by self-reported treatment satisfaction. Sexual function was assessed by validated and non-validated patient-reported outcome measures. Functional recurrence was defined as symptomatic need of re-intervention. Bivariate analyses, Kaplan-Meier estimates, qualitative and quantitative analyses by uni- and multivariable regression were employed to evaluate the interplay of sexual function, functional recurrence, and treatment satisfaction.!##!Results!#!Of 534 men with bulbar (82%), penobulbar (11%), and penile strictures (7.3%), 451 (84%) were satisfied with the surgery. There were no differences in stricture location, previous treatment, graft length, or surgical technique between satisfied and unsatisfied patients (all p  ≥  0.2). Recurrence-free survival was 85% at a median follow-up of 33 mo and decreased significantly with each Likert item towards increasing dissatisfaction (p  &amp;lt;  0.001). Dissatisfied patients more often reported postoperative loss of rigidity, tumescence, reduced ejaculatory volume, ejaculatory pain, and reduced penile length (all p  ≤  0.042). In 83 dissatisfied men, functional recurrence (28%) and oral morbidity (20%) were the main drivers of dissatisfaction in qualitative analysis. Multivariable analyses revealed functional recurrence and impaired postoperative ejaculatory function as independent predictors of treatment dissatisfaction (all p  ≤  0.029) after adjusting for confounders.!##!Conclusion!#!We found an association of both functional success and sexual function with patient-reported treatment satisfaction after substitution urethroplasty. Such findings validate the clinical significance of defining the symptomatic need for re-intervention as an endpoint and underline the importance of further research evaluating sexual function before and after open urethral reconstruction

Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC)

Immune checkpoint inhibition (ICI) of the PD-1/PD-L1 axis shows durable responses in a subset of patients with metastatic urothelial carcinoma (UC). However, PD-L1 expression in tumor biopsies does not necessarily correlate with response to PD-1/PD-L1 inhibitors. Thus, a reliable predictive biomarker is urgently needed. Here, the expression of PD-L1 on circulating tumor cells (CTCs) in blood from patients with advanced UC was analyzed. For this purpose, an assay to test PD-L1 expression on CTCs using the CellSearch® system was established using cells of five UC cell lines spiked into blood samples from healthy donors and applied to a heterogeneous cohort of UC patients. Enumeration of CTCs was performed in blood samples from 49 patients with advanced UC. PD-L1 expression in ≥1 CTC was found in 10 of 16 CTC-positive samples (63%). Both intra- and inter-patient heterogeneity regarding PD-L1 expression of CTCs were observed. Furthermore, vimentin-expressing CTCs were detected in 4 of 15 CTC-positive samples (27%), independently of PD-L1 analysis. Both CTC detection and presence of CTCs with moderate or strong PD-L1 expression correlated with worse overall survival. Analyses during disease course of three individual patients receiving ICI suggest that apart from CTC numbers also PD-L1 expression on CTCs might potentially indicate disease progression. This is the first study demonstrating the feasibility to detect CTC-PD-L1 expression in patients with advanced UC using the CellSearch® system. This assay is readily available for clinical application and could be implemented in future clinical trials to evaluate its relevance for predicting and monitoring response to ICI