Prevalence and predictors of female sexual dysfunction among sexually active women in the diabetes prevention program outcomes study.

OBJECTIVE: To determine the burden and identify correlates of female sexual dysfunction (FSD) among women with prediabetes (PreD) and type 2 diabetes (T2D) enrolled in the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS). METHODS: The DPPOS visit included the Female Sexual Function Index (FSFI) to determine sexual function. Of 1464 participants, 1320 (90%) completed the (FSFI) and 426 were sexually active. A backward selection multivariable logistic regression model estimated the odds of FSD for sociodemographic, clinical, and diabetes-related covariates. RESULTS: One hundred and eighty-five (43%) had a score of ≤26.55 and met the criteria for FSD. After adjustment for DPP treatment and age, urinary incontinence (UI) (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.15-3.17) and hysterectomy (OR = 1.89, 95% CI = 1.01-3.53) were associated with increased odds of FSD. Increased body mass index was protective for FSD (OR = 0.93 per kg/m2, 95% CI = 0.89-0.96). Michigan Neuropathy Screening Instrument-based peripheral neuropathy (mean±SD scores 1.1±1.3 vs. 0.9±1.1, p < 0.0001) and Electrocardiogram (ECG)-based autonomic dysfunction measures (mean ± SD heart rate levels 64.3 ± 6.8 vs. 65.6 ± 10.2, p = 0.008) were associated with FSD. There were no differences in diabetes rates between women who did (66.5%) and did not (66%) have (p = 0.7). CONCLUSIONS: FSD is prevalent in women with PreD and T2D. Our findings suggest that FSD is associated with neuropathic complications commonly observed in PreD and T2D.

Prevalence and predictors of erectile dysfunction among men in the diabetes prevention program outcomes study.

OBJECTIVE: To determine burden and identify correlates of erectile dysfunction (ED) among men with prediabetes (PreD) and type 2 diabetes (T2D) enrolled in the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS). RESEARCH DESIGN AND METHODS: The 2017 DPPOS visit included administration of the International Index of Erectile Function. Of 648 male participants, 88 % (n = 568) completed the survey. Associations between sociodemographic, behavioral, clinical, and glycemic measures at time of ED assessment, and ED were examined using multivariable logistic regression models in men with PreD and T2D separately. RESULTS: Overall, 218 (38 %) men met ED criteria. Prevalence was similar in men with PreD (41 %) and T2D (37 %) (p = 0.4). In all men, age (p < 0.001) increased odds of ED. Among men with PreD, those assigned to intensive lifestyle intervention (ILS), but not metformin, had decreased odds of ED compared with the placebo group (OR = 0.35, 95 % CI = 0.13, 0.94). Non-Hispanic White race was associated with increased odds of ED compared with other races (OR = 4.3; 95 % CI = 1.92, 9.65). Among men with T2D, ED risk did not differ by DPP treatment assignment; however, individuals with metabolic syndrome defined by National Cholesterol Education Program criteria, had increased odds of ED (OR = 1.85, 95 % CI = 1.14, 3.01), as did individuals with depression (OR = 2.05; 95 % CI = 1.10, 3.79). CONCLUSIONS: ED is prevalent in men with PreD and T2D. Our finding of reduced odds of ED in men randomized to ILS and with PreD suggests a potential opportunity for risk mitigation in the prediabetes interval. In men who have progressed to T2D, metabolic factors appear to be associated with ED.

Urinary symptoms and female sexual dysfunction in women with type 1 diabetes: the role of depression.

BACKGROUND: Some reports suggest that women with type 1 diabetes (T1D) have a greater burden of female sexual dysfunction (FSD) than women without T1D, but the etiology of this elevated risk is poorly understood. AIM: To examine the associations between FSD and urinary incontinence/lower urinary tract symptoms (UI/LUTS) in women with T1D and to evaluate how depression may mediate these relationships. METHODS: LUTS and UI symptoms were assessed in women with T1D who participated in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Multivariable logistic regression models estimated associations between FSD and UI/LUTS (overall and specific domains) and the impact of depression on these associations. OUTCOMES: FSD was measured with the Female Sexual Function Index-Reduced. RESULTS: In total, 499 self-reported sexually active women completed validated assessments of sexual and urinary function (mean ± SD age, 47.7 ± 7.6 years; T1D duration, 23.4 ± 5.15 years). FSD was reported in 232 (46%) responders. The frequency of UI and LUTS was 125 (25.1%) and 96 (19.2%), respectively. Neither UI nor its subcategories (urge, stress) were associated with FSD. Although LUTS (odds ratio [OR], 1.75; 95% CI, 1.09-2.77) and its symptoms of urgency (OR, 1.99; 95% CI, 1.09-3.61) and incomplete emptying (OR, 2.44; 95% CI, 1.23-4.85) were associated with FSD, these associations were attenuated following adjustment for depression and antidepressant medication use. Depression indicators were independently associated with FSD overall and across domains. CLINICAL IMPLICATIONS: The complex interplay of voiding dysfunction, mental health, and sexual function warrants further investigation to understand the potential implications for patient assessment, goal setting, treatment, and care planning. STRENGTHS AND LIMITATIONS: Data are from a prospective study of individuals with T1D. These results are unable to explore cause-and-effect relationships among LUTS, UI, depression, and FSD. The sample may not be representative of the general population of women with T1D. Because participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study are mostly White, generalizing the findings to other races and to type 2 diabetes may not be appropriate. While exclusion of sexually inactive women likely biases our findings toward the null, this design element permitted study of LUTS and UI in relation to aspects of FSD, the primary objective of this study. CONCLUSIONS: The significant associations between LUTS/UI and FSD among middle-aged women with T1D were greatly attenuated when depression was considered a mediating factor.

Management of male stress urinary incontinence in high-risk patients: a narrative review.

Background and Objective: The artificial urinary sphincter (AUS) remains the gold standard for treatment of stress urinary incontinence (SUI). However, highly complex patients such as those with bulbar urethral compromise, bladder pathology, and lower urinary complications pose a particular challenge for the surgeon. In this article, we will address critical risk factors and synthesize existent data across relevant disease states to support surgeons in successful management of SUI in high-risk patients. Methods: A comprehensive review of current literature was performed utilizing the search term "artificial urinary sphincter" in conjunction with any of the following additional terms: "radiation", "urethral stricture", "posterior urethral stenosis", "vesicourethral anastomotic stenosis", "bladder neck contracture", "pelvic fracture urethral injury", "penile revascularization", "inflatable penile prosthesis", and "erosion". Guidance is provided based upon expert opinion where existing literature was sparse or nonexistent. Key Content and Findings: Several known patient risk factors are associated with AUS failure and can ultimately lead to device explantation. Each risk factor requires careful consideration and investigation, or intervention as appropriate, prior to device placement. Optimization of urethral health, confirmation of anatomic and functional stability of the lower urinary tract, and thorough patient counseling are a necessity for these high-risk patients. Several surgical strategies to decrease device complications can be considered: optimization of testosterone, avoidance of 3.5 cm AUS cuff, transcorporal AUS cuff placement, relocation of AUS cuff site, use of lower pressure-regulating balloon, penile revascularization, and intermittent nocturnal deactivation. Conclusions: A number of patient risk factors are associated with AUS failure and can ultimately lead to device explantation. We present an algorithm for management of high-risk patients. Optimization of urethral health, confirmation of anatomic and functional stability of the lower urinary tract, and thorough patient counseling are a necessity for these high-risk patients.

Patients' Experiences With the Removal of a Ureteral Stent: Insights From In-depth Interviews With Participants in the USDRN STENTS Qualitative Cohort Study.

OBJECTIVE: To describe the experiences of patients undergoing stent removal in the USDRN Study to Enhance Understanding of Stent-Associated Symptoms (STENTS), a prospective, observational cohort study of patients with short-term ureteral stent placement post-ureteroscopy. METHODS: We conducted a qualitative descriptive study using in-depth interviews. Participants reflected on (1) painful or bothersome aspects of stent removal, (2) symptoms immediately after removal, and (3) symptoms in the days following removal. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. RESULTS: The 38 participants interviewed were aged 13-77 years, 55% female, and 95% White. Interviews were conducted 7-30 days after stent removal. Almost all participants (n = 31) described that they experienced either pain or discomfort during stent removal, but for most (n = 25) pain was of short duration. Many participants (n = 21) described anticipatory anxiety related to the procedure, and several (n = 11) discussed discomfort arising from lack of privacy or feeling exposed. Interactions with medical providers often helped put participants at ease, but also increased discomfort for some. Following stent removal, several participants described lingering pain and/or urinary symptoms, but these largely resolved within 24 hours. A few participants described symptoms persisting for more than a day post stent removal. CONCLUSION: These findings on patients' experiences during and shortly after ureteral stent removal, particularly the psychological distress they experienced, identify opportunities for improvement in patient care. Clear communication from providers about what to expect with the removal procedure, and the possibility of delayed pain, may help patients adapt to discomfort.

The Patient Voice: Stent Experiences After Ureteroscopy-Insights from In-Depth Interviews with Participants in the USDRN STENTS Nested Qualitative Cohort Study.

Purpose: Ureteral stents are commonly used after ureteroscopy and cause significant discomfort, yet qualitative perspectives on patients' stent experiences remain unknown. We describe psychological, functional, and interpersonal effects of post-ureteroscopy stents and whether additional patient-reported assessments may be needed. Materials and Methods: Using a qualitative descriptive study design, we conducted in-depth interviews with a nested cohort of participants in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS). Participants shared their symptoms with a post-ureteroscopy stent and described symptom bother and impact on daily activities. All interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. During analysis, participants' experiences with interference in daily activities were categorized into three groups based on their impact: minimal, moderate, and substantial. Results: All 39 participants experienced pain, although descriptions varied and differentiated between feelings of pain vs discomfort. Almost all experienced urinary symptoms. Only a few reported other physical symptoms, although several psychological aspects were identified. In the areas of sleep, mood, life enjoyment, work, exercise, activities of daily living, driving, childcare, and leisure/social activities, the stent had little impact on daily living among participants placed in the minimal group (n = 12) and far greater impact for participants in the substantial group (n = 8). For patients in the moderate group (n = 19), some daily activities were moderately or substantially affected, whereas other activities were minimally affected. Conclusions: Counseling to better prepare patients for the impact of stent-associated symptoms may help mitigate symptom burden. While existing instruments adequately cover most symptoms, additional assessments for other domains, particularly psychological factors, may be needed.

Urethral Stricture Disease Guideline Amendment (2023).

PURPOSE: The symptoms of urethral stricture are non-specific and may overlap with other common conditions that can confound diagnosis. Urologists play a key role in the initial evaluation of urethral stricture, currently provide all accepted treatments, and must be familiar with the evaluation, diagnostic tests, and surgical treatments for urethral stricture. MATERIALS AND METHODS: A systematic review of the literature using the Pubmed, Embase, and Cochrane databases (search dates January 1, 1990 to January 12, 2015) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of urethral stricture in men. The review yielded an evidence base of 250 articles after application of inclusion/exclusion criteria. The search for the 2023 Amendment was modified to included females and males (search dates December 2015-October 2022 for males; January 1990-October 2022 for females) and a new Key Question on sexual dysfunction was added (search dates: January 1990-10/2022). After inclusion and exclusion criteria were applied, 81 studies were added to the existing evidence base. RESULTS: Once a urethral stricture is diagnosed, clinicians should determine the length and location of the stricture in order to inform treatment. After a period of urethral rest, patients with short (<2cm) bulbar urethral stricture may be treated endoscopically. Urethroplasty may be performed by an experienced surgeon in patients with first time or recurrent anterior and posterior urethral strictures. The best treatment option for urethral stricture in female patients is urethroplasty using oral mucosa grafts or vaginal flaps rather than endoscopic treatment. CONCLUSION: This guideline provides evidence-based guidance to clinicians and patients regarding how to recognize symptoms and signs of a urethral stricture/stenosis, carry out appropriate testing to determine the location and severity of the stricture, and recommend the best options for treatment. The most effective approach for a particular patient is best determined by the individual clinician and patient in the context of that patient's history, values, and goals for treatment.

Risk Factors for Increased Stent-associated Symptoms Following Ureteroscopy for Urinary Stones: Results From STENTS.

PURPOSE: The STudy to Enhance uNderstanding of sTent-associated Symptoms sought to identify risk factors for pain and urinary symptoms, as well as how these symptoms interfere with daily activities after ureteroscopy for stone treatment. MATERIALS AND METHODS: This prospective observational cohort study enrolled patients aged ≥12 years undergoing ureteroscopy with ureteral stent for stone treatment at 4 clinical centers. Participants reported symptoms at baseline; on postoperative days 1, 3, 5; at stent removal; and day 30 post-stent removal. Outcomes of pain intensity, pain interference, urinary symptoms, and bother were captured with multiple instruments. Multivariable analyses using mixed-effects linear regression models were identified characteristics associated with increased stent-associated symptoms. RESULTS: A total of 424 participants were enrolled. Mean age was 49 years (SD 17); 47% were female. Participants experienced a marked increase in stent-associated symptoms on postoperative day 1. While pain intensity decreased ∼50% from postoperative day 1 to postoperative day 5, interference due to pain remained persistently elevated. In multivariable analysis, older age was associated with lower pain intensity (P = .004). Having chronic pain conditions (P < .001), prior severe stent pain (P = .021), and depressive symptoms at baseline (P < .001) were each associated with higher pain intensity. Neither sex, stone location, ureteral access sheath use, nor stent characteristics were drivers of stent-associated symptoms. CONCLUSIONS: In this multicenter cohort, interference persisted even as pain intensity decreased. Patient factors (eg, age, depression) rather than surgical factors were associated with symptom intensity. These findings provide a foundation for patient-centered care and highlight potential targets for efforts to mitigate the burden of stent-associated symptoms.

First Series Using Ultrasonic Propulsion and Burst Wave Lithotripsy to Treat Ureteral Stones.

PURPOSE: Our goal was to test transcutaneous focused ultrasound in the form of ultrasonic propulsion and burst wave lithotripsy to reposition ureteral stones and facilitate passage in awake subjects. MATERIALS AND METHODS: Adult subjects with a diagnosed proximal or distal ureteral stone were prospectively recruited. Ultrasonic propulsion alone or with burst wave lithotripsy was administered by a handheld transducer to awake, unanesthetized subjects. Efficacy outcomes included stone motion, stone passage, and pain relief. Safety outcome was the reporting of associated anticipated or adverse events. RESULTS: Twenty-nine subjects received either ultrasonic propulsion alone (n = 16) or with burst wave lithotripsy bursts (n = 13), and stone motion was observed in 19 (66%). The stone passed in 18 (86%) of the 21 distal ureteral stone cases with at least 2 weeks follow-up in an average of 3.9±4.9 days post-procedure. Fragmentation was observed in 7 of the burst wave lithotripsy cases. All subjects tolerated the procedure with average pain scores (0-10) dropping from 2.1±2.3 to 1.6±2.0 (P = .03). Anticipated events were limited to hematuria on initial urination post-procedure and mild pain. In total, 7 subjects had associated discomfort with only 2.2% (18 of 820) propulsion bursts. CONCLUSIONS: This study supports the efficacy and safety of using ultrasonic propulsion and burst wave lithotripsy in awake subjects to reposition and break ureteral stones to relieve pain and facilitate passage.

Ablating Lgr5-expressing prostatic stromal cells activates the ERK-mediated mechanosensory signaling and disrupts prostate tissue homeostasis.

Functional implication of stromal heterogeneity in the prostate remains incompletely understood. Using lineage tracing and light-sheet imaging, we show that some fibroblast cells at the mouse proximal prostatic ducts and prostatic urethra highly express Lgr5. Genetic ablation of these anatomically restricted stromal cells, but not nonselective ablation of prostatic stromal cells, rapidly induces prostate epithelial turnover and dedifferentiation that are reversed following spontaneous restoration of the Lgr5+ stromal cells. RNA sequencing (RNA-seq) analysis indicates that ablating the Lgr5+ stromal cells activates a mechanosensory response. Ablating the Lgr5+ stromal cells impairs the control of prostatic ductal outlet, increases prostate tissue stiffness, and activates the mitogen-activated protein kinase (MAPK). Suppressing MAPK overrides the elevated epithelial proliferation. In summary, the Lgr5+ stromal cells regulate prostate tissue homeostasis and maintain its functional integrity in a long-distance manner. Our study implies that the cells at organ junctions most likely control organ homeostasis by sustaining a balanced mechanoforce.

Urologic complications in diabetes.

Urologic complications such as bladder and sexual dysfunction among men and women with diabetes have received relatively little attention. This is despite emerging evidence that demonstrates that urologic complications increase with age in the general population and are more common in individuals with diabetes compared to those without diabetes. Here we summarize the latest information about the epidemiology of urologic complications in the setting of diabetes and the most recent findings regarding pathophysiology. In addition, we identify knowledge gaps and need for future funding to address these gaps that will reduce the burden of urologic complications in diabetes and optimize quality of life for all individuals affected by it.

Complex Penile Surgery: Plication, Grafting, and Implants.

Surgical treatments for Peyronie's disease and erectile dysfunction are generally straightforward and associated with excellent outcomes. However, severe (>60°) and multidirectional curvature, hourglass deformity, severe penile shortening, and ossified plaque may complicate surgery in patients with Peyronie's disease. Similarly, a history of priapism, prior implant infection, and penile injury can pose challenges to successful implant surgery secondary to severe corporal fibrosis. Thus, when these pathophysiological processes cause severe fibrosis and loss of function of the tunica albuginea and deep cavernosal spaces, adjunctive reconstructive techniques are necessary. Herein, we integrate the literature regarding surgical management of complex Peyronie's disease and erectile dysfunction with emphasis on plication, grafting, and implants to achieve satisfactory outcomes across the full range of etiology and degree of surgical complexity.

Quality of life impact and recovery after ureteroscopy and stent insertion: insights from daily surveys in STENTS.

BACKGROUND: Our objective was to describe day-to-day evolution and variations in patient-reported stent-associated symptoms (SAS) in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS), a prospective multicenter observational cohort study, using multiple instruments with conceptual overlap in various domains. METHODS: In a nested cohort of the STENTS study, the initial 40 participants having unilateral ureteroscopy (URS) and stent placement underwent daily assessment of self-reported measures using the Brief Pain Inventory short form, Patient-Reported Outcome Measurement Information System measures for pain severity and pain interference, the Urinary Score of the Ureteral Stent Symptom Questionnaire, and Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index. Pain intensity, pain interference, urinary symptoms, and bother were obtained preoperatively, daily until stent removal, and at postoperative day (POD) 30. RESULTS: The median age was 44 years (IQR 29,58), and 53% were female. The size of the dominant stone was 7.5 mm (IQR 5,11), and 50% were located in the kidney. There was consistency among instruments assessing similar concepts. Pain intensity and urinary symptoms increased from baseline to POD 1 with apparent peaks in the first 2 days, remained elevated with stent in situ, and varied widely among individuals. Interference due to pain, and bother due to urinary symptoms, likewise demonstrated high individual variability. CONCLUSIONS: This first study investigating daily SAS allows for a more in-depth look at the lived experience after URS and the impact on quality of life. Different instruments measuring pain intensity, pain interference, and urinary symptoms produced consistent assessments of patients' experiences. The overall daily stability of pain and urinary symptoms after URS was also marked by high patient-level variation, suggesting an opportunity to identify characteristics associated with severe SAS after URS.

Diabetic Peripheral Neuropathy and Urological Complications in Type 1 Diabetes: Findings From the Epidemiology of Diabetes Interventions and Complications Study.

OBJECTIVE: To evaluate associations between diabetic peripheral neuropathy (DPN) and urological complications in men and women with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Measurements of DPN at Epidemiology of Diabetes Intervention and Complications (EDIC) years 1, 14, and 17 and urological complications at EDIC year 17 were examined in 635 men (mean age 51.6 years, diabetes duration 29.5 years) and 371 women (mean age 50.6 years, diabetes duration 29.8 years) enrolled in the Diabetes Control and Complications Trial (DCCT)/EDIC study. DPN was defined by symptoms, signs, and abnormal electrophysiology or by abnormal Michigan Neuropathy Screening Instrument (MNSI) examination or questionnaire scores. RESULTS: Erectile dysfunction (ED) in combination with lower urinary tract symptoms (LUTS) was reported in 15% of men and female sexual dysfunction (FSD), LUTS, and urinary incontinence (UI) in 16% of women. Adjusted for age, drinking status, BMI, depression, DCCT/EDIC time-weighted mean HbA1c, microalbuminuria, hypertension, triglycerides, and statin medication use, the odds of reporting ED and LUTS versus no ED or LUTS at EDIC year 17 were 3.52 (95% CI 1.69, 7.31) times greater in men with confirmed DPN at EDIC year 13/14 compared to men without confirmed DPN. Compared to men without DPN, men with DPN based on abnormal MNSI examination or questionnaire scores had significantly higher odds of reporting ED and LUTS versus no ED or LUTS at EDIC year 17. There were no significant differences in DPN between women reporting both FSD and LUTS/UI compared with those without FSD or LUTS/UI at EDIC year 17. CONCLUSIONS: In long-standing T1D, DPN is associated with the later development of urological complications in men.

Longitudinal patterns of urinary incontinence and associated predictors in women with type 1 diabetes.

AIMS: Urinary incontinence (UI) in women is a dynamic condition with numerous risk factors yet most studies have focused on examining its prevalence at a single time. The objective of this study was to describe the long-term time course of UI in women with type 1 diabetes (T1D). METHODS: Longitudinal data in women with T1D were collected from 568 women in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. Over a 12-year period, participants annually responded to whether they had experienced UI in the past year. RESULTS: We identified four categories of UI in this population over time: 205 (36.1%) women never reported UI (no UI), 70 (12.3%) reported it one or two consecutive years only (isolated UI), 247 (43.5%) periodically changed status between UI and no UI (intermittent UI), and 46 (8.1%) reported UI continuously after the first report (persistent UI). Compared to women reporting no/isolated UI, women displaying the intermittent phenotype were significantly more likely to be obese (OR: 1.86, 95% CI 1.15, 3.00) and report prior hysterectomy (OR: 2.57, 95% CI: 1.39, 4.77); whereas women with persistent UI were significantly more likely to have abnormal autonomic function (OR: 2.36, 95% CI: 1.16-4.80). CONCLUSIONS: UI is a dynamic condition in women with T1D. Varying risk factors observed for the different phenotypes of UI suggest distinctive pathophysiological mechanisms. These findings have the potential to be used to guide individualized interventions for UI in women with diabetes.

Mechanical characterization of fibrotic and mineralized tissue in Peyronie's disease.

Peyronie's disease affects penile mechanics, but published research lacks biomechanical characterization of affected tunica albuginea. This work aims to establish mechanical testing methodology and characterize pathological tissue mechanics of Peyronie's disease. Tunica albuginea was obtained from patients (n = 5) undergoing reconstructive surgery for Peyronie's disease, sectioned into test specimens (n = 12), stored frozen at -20 °C, and imaged with micro-computed tomography (µCT). A tensile testing protocol was developed based on similar soft tissues. Correlation of mechanical summary variables (force, displacement, stiffness, work, Young's modulus, ultimate tensile stress, strain at ultimate tensile stress, and toughness) and µCT features were assessed with linear regression. Specimens empirically grouped into hard or soft stress-strain behavior were compared using a Student's t-test. Surface strain and failure patterns were described qualitatively. Specimens displayed high inter- and intra-subject variability. Mineralization volume was not correlated with mechanical parameters. Empirically hard tissue had higher ultimate tensile stress. Failure mechanisms and strain patterns differed between mineralized and non-mineralized specimens. Size, shape, and quantity of mineralization may be more important in determining Peyronie's disease plaque behavior than presence of mineralization alone, and single summary variables like modulus may not fully describe mechanical behavior.

Geometrical Model of Free Skin Graft for the Optimization of Glans Reconstruction after Partial Penectomy / Modelo geométrico de injerto de piel libre para la optimización de reconstrucción de glande tras penectomía parcial

Introduction and Objective The management of penile carcinoma is very disabling and mutilating, bur early treatment can be curative. Our group systematically performs oncological management with immediate penile reconstruction and preservation of the organ (partial penectomy, resurfacing, or glansectomy) when feasible. Due to the low incidence of penile carcinoma, it is difficult to achieve experience in penile reconstruction using free grafts in a standardized and reproducible way. Therefore, we herein present the results of the use of an inanimate model to identify the most efficient geometric way to procure and apply a free skin graft to reconstruct the penis. Methods A preclinical inanimate model of the penis was developed to simulate the surgical reconstruction using a free skin graft. Six different geometric skin-graft models were created and tested. For each of them, we measured graft's surface area as well as the discarded surface after placing the graft on the penis for reconstruction. We also measured the amount of suture lines required for reconstruction. All of these measurements in the six different models were compared. Results Based on the six models, we identified that the longitude of the graft must measure the same as the maximum perimeter of the glans in order to have a square that enables the complete coverage of the penile defect. The total graft area for the first 4 models was of 40 cm2; for models 5 and 6, it was of 60 cm2. The average discarded area of the graft was of 18.135 cm2 (range: 12 cm2 to 30 cm2). Models 4 years 6 were the ones with the least discarded tissue: 12 cm2. The average amount of suture lines to secure the different model grafts was 7.3 (range: 5 to 12). The models that required the least amount of suture lines were number 1 and 4, with a total of 5 suture lines. Conclusions The double trapezoid is the most efficient model to reconstruct the glans after organ-sparing oncological management. Our results contribute to establish a more standardized and predictable technique to reconstruct the penis.

Introducción y Objetivo El manejo del cáncer de pene es muy mutilante y discapacitante. Pero el manejo quirúrgico oportuno puede ser curativo. Nuestro grupo realiza de manera sistemática el manejo oncológico con reconstrucción inmediata del pene y preservación del órgano (penectomía parcial, desepitelización, o gladectomía) cuando sea viable. Como la incidencia de cancer de pene es baja, lograr obtener la experiencia en reconstrucción de pene con el uso de injertos libres de manera estandarizada y reproducible resulta difícil. Por lo tanto, presentamos en este artículo los resultados de un modelo inanimado para identificar la forma geométrica mas eficiente de obtener y aplicar un injerto de piel libre para reconstruir el pene. Materiales y Métodos Se desarrolló un modelo preclínico y inanimado del pene para que se simulara su reconstrucción quirúrgica con el uso de un ijerto de piel libre. Desarrollamos y evaluamos seis modelos geométricos de injerto de piel distintos. Para cada uno, medimos el area total del injerto y la del tejido desechado tras ponerlo en el pene para la recosntrucción. También medimos la cantidad de líneas de sutura necesarias para la recosntrucción. Comparamos todas las medidas entre los seis modelos distintos. Resultados De los 6 modelos diferentes, encontramos que la longitud del injerto debe tener la misma medida que el perímetro máximo del glande para que se tenga un cuadrado que nos permita cubrir todo el defecto del pene. El area total de los 4 modelos iniciales fue de 40 cm2, y el area de los modelos 5 y 6 fue de 60 cm2. El area promedio del tejido desechado en los injertos fue de 18,135 cm2 (rango: 12 cm2 a 30 cm2). Los modelos 4 y 6 fueron los que tuvieron la menor cantidad de tejido desechado: 12 cm2. El promedio de la cantidad de líneas de sutura para atar los distintos modelos de injerto fue de 7,3 (rango: 5 a 12). Los modelos con la menor cantidad de líneas de sutura fueron el 1 y el 4, con un total de 5 líneas. Conclusiones El modelo de doble trapezoide es el más eficiente para reconstruir el glande tras el majejo oncológico en que se preserva el órgano. Nuestros resultados contribuyen para establecer una técnica de reconstrucción del pene más estandarizada y previsible.

Genome-Wide Association Study Identifies Two Novel Loci Associated with Female Stress and Urgency Urinary Incontinence.

PURPOSE: Genome-wide association studies have not identified replicable genetic risk loci for stress or urgency urinary incontinence. MATERIALS AND METHODS: We carried out a discovery stage, case control, genome-wide association study in 3 independent discovery cohorts of European women (8,979) for stress incontinence, urgency incontinence, and any incontinence phenotypes. We conducted replication in 6 additional studies of European ancestry (4,069). We collected bladder biopsies from women with incontinence (50) to further investigate bladder expression of implicated genes and pathways and used symptom questionnaires for phenotyping. We conducted meta-analyses using inverse variance fixed effects models and whole transcriptome analyses using Affymetrix® arrays with replication with TaqMan® polymerase chain reaction. RESULTS: In the discovery stage, we identified 16 single nucleotide polymorphisms genotyped or imputed at 5 loci that reached genome-wide significance (p <5×10-8). In replication, rs138724718 on chromosome 2 near the macrophage receptor with collagenous structure (MARCO) gene (replication p=0.003) was associated with stress incontinence. In addition, rs34998271 on chromosome 6 near the endothelin 1 (EDN1) gene (replication p=0.0008) was associated with urgency incontinence. In combined meta-analyses of discovery and replication cohorts, associations with genome-wide significance for these 2 single nucleotide polymorphisms were confirmed. Transcriptomics analyses showed differential expression of 7 of 19 genes in the endothelin pathway between stress and urgency incontinence (p <0.0001). CONCLUSIONS: We uncovered 2 new risk loci near the genes endothelin 1 (EDN1), associated with urgency incontinence, and macrophage receptor with collagenous structure (MARCO), associated with stress incontinence. These loci are biologically plausible given their roles in smooth muscle contraction and innate host defense, respectively.