Search

Purpose: To better understand the pathophysiology of lichen sclerosus (LS) urethral stricture disease (USD), we aimed to investigate expression profiles of microRNAs (miRNAs) in tissue samples from men undergoing urethroplasty., Methods: Urethral stricture tissue was collected from 2005-2020. Histologic features diagnostic of LS were the basis of pathologic evaluation. Foci of areas diagnostic for LS or non-LS strictures were chosen for RNA evaluation. In an initial screening analysis, 13 LS urethral strictures and 13 non-LS strictures were profiled via miRNA RT-qPCR arrays for 752 unique miRNA. A validation analysis of 23 additional samples (9 LS and 14 non-LS) was performed for 15 miRNAs. Statistical analyses were performed using SPSS v25. Gene Ontology (GO) analysis was performed using DIANA-mirPath v. 3.0., Results: In the screening analysis 143 miRNAs were detected for all samples. 27 were differentially expressed between the groups (false discovery p-value <0.01). 15 of these miRNAs individually demonstrated an area under the curve (AUC)>0.90 for distinguishing between between LS and non-LS strictures. 11-fold upregulation of MiR-155-5p specifically was found in LS vs. non-LS strictures (p<0.001, AUC = 1.0). In the validation analysis, 13 of the 15 miRNAs tested were confirmed to have differential expression (false discovery p-value <0.10)., Conclusions: To our knowledge this is the first study evaluating miRNA expression profiles in LS and non-LS USD. We identified several miRNAs that are differentially expressed in USD caused by LS vs other etiologies, which could potentially serve as biomarkers of LS USD. The top eight differentially expressed miRNAs have been linked to immune response processes as well as involvement in wound healing, primarily angiogenesis and fibrosis., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Performing 1-stage urethroplasty in patients with urethral strictures caused by lichen sclerosus (LS) is hotly debated among reconstructive urologists due to conflicting reports of success. Therefore, the objective of this study was to determine the pooled incidence of stricture recurrence following 1-stage buccal mucosal graft (BMG) urethroplasty in patients with LS, to determine the impact of surgical technique on recurrence and to compare recurrence risk between patients with and without LS after 1-stage repairs., Materials and Methods: A systematic review was conducted in accordance with PRISMA criteria. The primary outcome was pooled incidence of recurrence, which was calculated using a Der-Simonian-Laird binary random effects model with a Freeman-Tukey arcsine transformation. A total of 21 studies were included, of which 15 provided data for comparative analyses., Results: Pooled data from 625 LS patients revealed a stricture recurrence rate of 10% (95% CI 6-14). Among studies with longer followup (≥24 months), this increased to 18%. Among patients with penile urethral involvement, studies utilizing a penile skin incision had significantly higher pooled recurrence rates than those utilizing penile invagination (p=0.004). Across all studies, there was no evidence to suggest a difference in pooled recurrence rate between patients with and without LS (p=0.36). However, across only long-term studies, recurrence risk was significantly higher for patients with LS (OR 1.83, p=0.05)., Conclusions: One-stage BMG urethroplasty is likely a viable surgical option for patients with LS-related strictures; however, high-quality data are limited. Future multi-institutional, long-term prospective studies are needed to assess durability of 1-stage repair.

Purpose: We evaluated the success of minimally invasive management of lichen sclerosus with topical and intraurethral clobetasol, as defined by improvement in patient reported outcome measures and nonprogression to surgery., Materials and Methods: We conducted a review of our prospective ongoing quality improvement study to determine outcomes of our current standard practice for males with penile and urethral biopsy proven lichen sclerosus. Data were collected between 2011 and 2019, and included patient demographic information, medical and surgical histories, and location and extent of lichen sclerosus related pathology. The primary outcomes for this study were voiding function and voiding related quality of life, and were assessed using the AUASS (American Urological Association Symptom Score) and quality of life bother index, respectively., Results: We identified 42 patients with biopsy proven lichen sclerosus related urethral stricture disease. Of these patients 85.7% were treated with intraurethral steroids alone and did not require surgical intervention. Median AUASS significantly improved from 12 to 8, and median quality of life bother index improved from 4 ("mostly dissatisfied") to 2 ("mostly satisfied"). Average stricture length of those with penile urethral disease and bulbar urethral disease was 4.8 cm (SD 3.0) and 16.2 cm (SD 6.5), respectively. Median followup was 8.4 months (IQR 2.6-26.4)., Conclusions: Lichen sclerosus related urethral stricture disease can be effectively managed with intraurethral steroids. This minimally invasive management strategy improves patient reported voiding symptoms and voiding quality of life.

Purpose: Urethroplasty of lichen sclerosus strictures has a significantly higher failure rate than strictures due to other causes. We sought to determine predictors of urethroplasty failure in men with lichen sclerosus urethral stricture disease by evaluating protein expression profiles., Materials and Methods: Urethral tissue was excised from patients with lichen sclerosus who were undergoing urethroplasty of urethral stricture disease at a single institution. A tissue microarray was created with cores from each sample. Immunohistochemistry was performed to compare protein expression related to inflammation, cell cycle disruption, oxidative stress, hormone receptor status and infection. Stricture recurrence was defined by the need for a subsequent unanticipated procedure for urethral stricture disease., Results: We evaluated 50 men with lichen sclerosus urethral stricture disease, including 31 with successful reconstruction and 19 with recurrent stricture. Recurrent strictures expressed lower levels of several inflammatory markers and had a lower Ki-67 mitotic index and significantly higher vascular endothelial growth factor levels than nonrecurrent strictures., Conclusions: To our knowledge this is the first study to use tissue protein expression to identify risk factors for urethroplasty failure among men with lichen sclerosus urethral stricture disease. Our findings suggest that recurrent lichen sclerosus strictures demonstrate a suppressed inflammatory response, a decreased cell turnover rate, and poor oxygenation and nutrient delivery. Prospective studies are needed to clarify the role of these pathways in the pathophysiology of lichen sclerosus urethral stricture disease, determine whether preoperative biopsy can predict urethroplasty success, help counsel patients and develop future treatments.

Purpose: Histopathology can provide insights into disease mechanisms but to date it has been poorly described for urethral stricture. The purpose of this study was to comprehensively describe histopathological findings of stricture specimens obtained at the time of anterior urethroplasty., Materials and Methods: All pathological specimens of men who underwent anterior urethroplasty of urethral stricture disease from 2010 to 2017 at a single institution were rereviewed by a single blinded pathologist directed to rule out lichen sclerosus and then describe inflammatory cell type and severity when present. Cohorts comprising strictures with no inflammation, minimal to mild inflammation or moderate to severe inflammation were developed and stricture, patient and surgical outcome characteristics were compared., Results: Histopathology slides from 100 anterior urethroplasty cases were reviewed. Two or more lichen sclerosus characteristics were present in 21% of specimens and 44% of specimens showed chronic inflammation, which was minimal in 20%, mild in 39%, moderate in 39% and severe in 2%. Lymphocytes in 86% of specimens and plasma cells in 12% were the predominant cell types. Patients with inflammatory stricture reported worse overall health. Inflammation was largely absent from isolated bulbomembranous strictures (9%) and more common in lichen sclerosus strictures (100%). The 11% overall failure rate was not affected by the presence (7%) or absence (14%) of inflammation., Conclusions: Chronic inflammation is prevalent in a significant percent of urethral stricture disease specimens. Associations with worse overall health suggest systemic mediators. Absent inflammation in bulbomembranous strictures suggests a unique pathophysiology in this region. The presence of inflammation did not affect surgical outcomes at mid-term followup.

Introduction: Given the poor understanding of the pathophysiology of genital lichen sclerosus (GLS) and a lack of accepted definitive diagnostic criteria, we proposed to survey pathologists regarding their understanding of GLS. We hypothesized that significant disagreement about GLS will exist., Materials and Methods: All urologists participating in the Trauma and Urologic Reconstruction Network of Surgeons identified genitourinary (GUP) and dermatopathologists (DP) at their respective institutions who were then invited to participate in an online survey regarding their experience with diagnosing GLS, GLS pathophysiology and its relationship to urethral stricture disease., Results: There were 23 (12 DP, 11 GUP) pathologists that completed the survey. The most agreed upon criteria for diagnosis were dermal collagen homogenization (85.7%), loss of the normal rete pattern (33.3%) and atrophic epidermis (28.5%). No pathologists believed GLS had an infectious etiology (19% maybe, 42% unknown) and 19% believed GLS to be an autoimmune disorder (42% maybe, 38% unknown); 19% believed LS to be premalignant, but 52% believed it was associated with cancer; 80% believed that LS could involve the urethra (DP (92%) versus GUP (67%); p = 0.272). Of those diagnosing urethral GLS, 80% of DUP believed that GLS must first involve the glans/prepuce before involving the urethra, while all GUP believed that urethral disease could exist in isolation (p = 0.007)., Conclusions: There was significant disagreement in this specialized cohort of pathologists when diagnosing GLS. A logical first step appears to be improving agreement on how to best describe and classify the disease. This may lead to improve treatments.

Several factors such as genetic susceptibility, autoimmunity, hormones, infections, local trauma, urine, and occlusion have been speculated to play a role in the pathogenesis of lichen sclerosus. We report two male patients with lichen sclerosus around 'ectopic' urethral openings and the opposing surfaces of the penile shaft and scrotum, providing further evidence in support of urine and occlusion as contributing factors in the development of lichen sclerosus.

Introduction: Panurethral stricture associated with lichen sclerosus is a therapeutic challenge. We present the analysis of our results using two urethroplasty techniques based on oral mucosa graft., Material and Method: Retrospective study in patients with long anterior urethral stricture (>8cm) associated with lichen sclerosus. Patients received urethroplasty with oral mucosa graft technique according Kulkarni (n=25) or two-step Johanson-Bracka urethroplasty (n=15). Demographics, operative time, complications (Clavien-Dindo), hospital stay, days with catheter, EAV postoperative pain, failure rate, need for retreatment and functional data including IPSS, QoL, Qmax, post void residual (PVR) are evaluated., Results: In all cases there was involvement of glandular and penile urethra, and in 75% of bulbar urethra. A single graft was used in 22.5%, two in 72.5% and three in 5%. Patients treated at a single step were younger (P=.007). Although the length of the stenosis was equivalent in both techniques (P=.96), relapse and complication rates were higher in two-step surgery (P=.05 and P=.03; respectively) and so was operative time (P<.0001) and overall stay (P=.0002). There were no differences in preoperative IPSS, QoL, Qmax or PVR, neither in postoperative values of IPSS or Qmax; but there was a difference in QoL (P=.006) and PVR (P=.03) favouring single-step urethroplasty. VAS pain on postoperative day 1 was also lower in Kulkarni urethroplasty than in the first step of Johanson-Bracka technique (P<.0001)., Conclusions: In patients with lichen sclerosus and long anterior urethral stricture Kulkarni urethroplasty provides more efficient and better patient reported outcomes than Johanson-Bracka urethroplasty. It also prevents cosmetic, sexual and voiding temporary deterioration inherent to 2-step surgery., (Copyright © 2016. Publicado por Elsevier España, S.L.U.)

Purpose: Lichen sclerosus (LS) in men is poorly understood. Though uncommon, it is often severe and leads to repeated surgical interventions and deterioration in quality of life. We highlight variability in disease presentation, diagnosis, and patient factors in male LS patients evaluated at a tertiary care center., Materials and Methods: We retrospectively reviewed charts of male patients presenting to our reconstructive urology clinic with clinical or pathologic diagnosis of LS between 2004 and 2014. Relevant clinical and demographic information was abstracted and descriptive statistics calculated. Subgroup comparisons were made based on body mass index (BMI), urethral stricture, and pathologic confirmation of disease., Results: We identified 94 patients with clinical diagnosis of LS. Seventy percent (70%) of patients in this cohort had BMI >30 kg/m(2), and average age was 51.5 years. Lower BMI patients were more likely to suffer from urethral stricture disease compared to overweight counterparts (p=0.037). Patients presenting with stricture disease were more likely to be younger (p=0.003). Thirty percent (30%) of this cohort had a pathologic diagnosis of LS., Conclusions: Urethral stricture is the most common presentation for men with LS. Many patients endure skin scarring and have numerous comorbidities. Patient profile is diverse, raising the concern that not all patients with clinical diagnosis of LS are suffering from identical disease processes. The rate of pathologic confirmation at a tertiary care institution is alarmingly low. Our findings support a role for increased focus on pathologic confirmation and further delineation of the subtype of disease based on location and clinical manifestations.

Purpose: Using pathological examination we evaluated the involvement of lichen sclerosus in urethral strictures in men., Materials and Methods: We performed an observational, descriptive, retrospective study of patients treated for genital lichen sclerosus who had at least 1 biopsy positive for lichen sclerosus. Study exclusion criteria were malignant penile lesions, incomplete data on personal charts and biopsies negative for lichen sclerosus. Preoperative evaluation included clinical history, physical examination, urine culture, post-void residual urine measurement, uroflowmetry and urethrography. Biopsies were taken from the foreskin, penile skin, glans, urethral meatus, mucosa of the navicularis, and penile and bulbar urethra to confirm the lichen sclerosus diagnosis and spread of the disease through the urethra. Patients were classified into 5 groups by surgical procedure., Results: Included in the study were 99 patients with a median age of 46 years who were diagnosed with genital lichen sclerosus. Of 274 biopsies 234 (85.4%) were positive for lichen sclerosus. Group 1 included 39 patients who underwent circumcision, group 2 included 15 who underwent meatotomy, group 3 included 15 who underwent navicularis urethroplasty, group 4 included 17 who underwent penile urethroplasty and group 5 included 13 who underwent perineal urethrostomy. Lichen sclerosus was documented by histology in the meatus in 91.5% of cases, in the navicularis in 84.4% and in the penile urethra in 70.6%. All biopsies from the bulbar urethra were negative., Conclusions: Involvement of lichen sclerosus through the navicularis and penile urethra was documented. No sign of lichen sclerosus was found in the bulbar urethra., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We reviewed the literature regarding the clinical presentation, etiology, natural history, and medical and surgical management of lichen sclerosus in men., Materials and Methods: We performed a comprehensive search of the literature in PubMed, MEDLINE and other electronic databases between 1950 and 2006 using the key words lichen sclerosis, balanitis xerotica obliterans and urethral stricture. Our search resulted in 1,268 sources containing the words lichen sclerosus or balanitis xerotica obliterans. We reviewed 68 articles in the peer reviewed journals and 2 chapters on this subject., Results: Lichen sclerosus is a chronic, lymphocyte mediated skin disease that was first described in 1887. It shows a predilection for the anogenital area in men and women. Much has been discovered regarding the epidemiology, natural history and histological features of this disease process during the last century, including the discovery of a strong association between lichen sclerosus and squamous cell carcinoma. The techniques of medical and surgical management of this disorder are still being elucidated. Biopsy of the initial lesion for definitive diagnosis and long-term followup of affected patients are well established, critical elements in the management of lichen sclerosus., Conclusions: Lichen sclerosus is a chronic, debilitating condition that may progress to cause significant voiding complications. Biopsy is recommended in all patients suspected of having lichen sclerosus to rule out squamous cell carcinoma. Further research is needed to improve the prevention, understanding and treatment of this challenging condition.

Purpose: We report our experience with buccal mucosa grafts for anterior urethral strictures. We compared outcomes in the pendulous and bulbar urethra as well as the impact of lichen sclerosus on success., Materials and Methods: A total of 53 men underwent buccal mucosa graft urethroplasty from 1997 to 2004 for strictures of all etiologies, including lichen sclerosis in 13. Of the patients 46 underwent 1-stage repair and 7 with full-thickness circumferential disease underwent multistage repair. For 1-stage repair strictures were limited to the bulb in 33 cases and they involved the pendulous urethra in 13. A dorsal onlay was used in 24 cases and a ventral onlay was used in 22. For multistage urethroplasty 2 strictures were in the bulbar urethra and 5 were in the pendulous urethra. Success was defined as no postoperative procedures or complications., Results: The success rate of all urethroplasties was 81% (43 of 53 cases) at a mean followup of 52 months. For bulbar vs pendulous urethroplasty the success rate was 86% (30 of 35 cases) vs 72% (13 of 18, p = 0.23). For 1-stage urethroplasty by graft location success was achieved in 20 of 24 cases (83%) for dorsal onlay vs 17 of 22 (77%) for ventral onlay (p = 0.61), in 18 of 21 (86%) for bulbar-dorsal onlay, in 10 of 12 (83%) for bulbar-ventral onlay, in 2 of 3 (66%) for pendulous-dorsal onlay and in 7 of 10 (70%) for pendulous-ventral onlay. For multistage urethroplasty success was achieved in 2 of 2 cases (100%) for bulbar repair vs 4 of 5 (80%) for pendulous repair. In the 13 patients with lichen sclerosus success was achieved in 4 of 8 (50%) with 1-stage repair vs 4 of 5 (80%) with multistage repair (p = 0.28). Complications developed in 10 of 53 cases (19%), including fistula in 1, urinary tract infection in 1 and stricture in 8 that required treatment, including dilation in 3, internal urethrotomy in 4 and perineal urethrostomy in 1. Five of these 8 recurrent strictures (63%) developed in patients with lichen sclerosus, including 4 in urethras in which 1-stage repair was done for lichen sclerosus. There were no donor site complications, postoperative erectile dysfunction or chordee., Conclusions: A buccal mucosa graft placed dorsally or ventrally remains an excellent graft material in the bulbar and pendulous urethra. When lichen sclerosus is present, careful consideration should be given to complete excision of the diseased urethra with multistage repair vs accepting a higher rate of stricture recurrence with 1-stage repair.