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Xue J, Liu Y, Ye H, Feng C, Wu D. Perioperative Testosterone Supplementation Improves Short-Term Outcomes of Anterior Urethroplasty in Hypogonadal Models: Insights from a Preclinical Rabbit Study. Urology 2025:S0090-4295(25)00336-X. [PMID: 40209999 DOI: 10.1016/j.urology.2025.04.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 03/20/2025] [Accepted: 04/03/2025] [Indexed: 04/12/2025]
Abstract
OBJECTIVE To investigate whether perioperative androgen supplementation could improve surgical outcomes of anterior urethroplasty, particularly in hypogonadal patients, we evaluated the effects and mechanisms of systemic androgen supplementation at different doses in a castrated New Zealand rabbit model of bulbar urethroplasty. METHODS Fifteen castrated and five non-castrated adult male New Zealand rabbits were randomized into four groups: non-castrated control (NC), castrated control (0 mg/kg), physiological dose (2.5 mg/kg), and supraphysiological dose (5 mg/kg) of testosterone propionate. All rabbits underwent bulbar urethroplasty via end-to-end anastomosis and were sacrificed one month postoperatively. Plasma testosterone levels, urethrograms, gross specimens, histopathological data, immunofluorescence, and transcriptomic profiles were assessed and compared among the groups. RESULTS Plasma testosterone levels in the castrated control group (5.88 ± 0.19 nmol/L) were significantly lower than those in the physiological dose group (7.56±0.53 nmol/L), supraphysiological dose group (8.98±0.35 nmol/L), and NC group (7.30±0.29 nmol/L; p<0.0001). One month postoperatively, androgen supplementation significantly increased urethral lumen diameter, urethral circumference, AR, and CD31 expression compared to the castrated control group (p<0.001). Transcriptomic analysis revealed upregulation of angiogenesis-related genes and suppression of fibrosis-related genes in the androgen-supplemented groups, along with modulation of inflammatory, proliferative, and metabolic pathways. CONCLUSION Perioperative androgen supplementation increases urethral lumen diameter, enhances peri-urethral vascularization, and suppresses short-term fibrosis-related gene expression, thereby improving outcomes of bulbar urethroplasty in hypogonadal rabbits. However, the long-term effects and clinical applicability of systemic androgen supplementation warrant further investigation.
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Affiliation(s)
- Jingdong Xue
- Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
| | - Yifan Liu
- Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
| | - Hanchu Ye
- Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
| | - Chao Feng
- Division of Andrology, Department of Reproductive Medicine, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, China.
| | - Denglong Wu
- Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
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Zhang W, Zhang J, Jiao D, Tang Q, Gao X, Li Z, Yang F, Zhao Z, Yang L. Single-Cell RNA Sequencing Reveals a Unique Fibroblastic Subset and Immune Disorder in Lichen Sclerosus Urethral Stricture. J Inflamm Res 2024; 17:5327-5346. [PMID: 39157587 PMCID: PMC11330248 DOI: 10.2147/jir.s466317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 08/02/2024] [Indexed: 08/20/2024] Open
Abstract
Purpose Lichen sclerosus urethral stricture disease (LS USD) is a refractory and progressive disease primarily affecting the anterior urethra in males. Various potential etiological factors, such as genetics, autoimmunity, infection, and exposure to infectious urine, have been suggested. However, the accurate etiology of LS in the male urethra remains unclear. Patients and Methods In this study, we conducted single-cell RNA sequencing to identify the transcriptional profiles of three patients with LS USD and three patients with non-LS USD. Immunofluorescence was used to confirm the single-cell sequence results. Results Our study revealed distinct subsets of vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) with high proportions in LS USD, contributing to the tissue microenvironment primarily involved in proinflammatory and immune responses. In particular, FBs displayed a unique subset, Fib7, which is exclusively present in LS USD, and exhibited high expression levels of SAA1 and SAA2. The accumulation of macrophages, along with the dysregulated ratios of M1/M2-like phenotype macrophages, may be engaged in the pathogenesis of LS USD. Through cell-cell communication analysis, we identified significant interactions involving CXCL8/ACKR1 and CCR7/CCL19 in LS USD. Remarkably, Fib7 exhibited exclusive communication with IL-1B macrophages through the SAA1/FPR2 receptor-ligand pair. Conclusion Our study provides a profound understanding of the tissue microenvironment in LS USD, which may be valuable for understanding the pathogenesis of LS USD.
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Affiliation(s)
- Wei Zhang
- Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China
| | - Jiayu Zhang
- Department of Urology, Air Force Hospital of Southern Theater Command, Guangzhou, Guangdong, 510062, People’s Republic of China
| | - Dian Jiao
- Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China
| | - Qisheng Tang
- Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China
| | - Xiaoping Gao
- Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China
| | - Zhenyu Li
- Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China
| | - Fa Yang
- Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China
| | - Zhiguang Zhao
- Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China
| | - Longfei Yang
- Department of Transfusion Medicine, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China
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Gul A, Ekici O, Zengin S, Barali D, Keskin T. Investigation of risk factors in the development of recurrent urethral stricture after internal urethrotomy. World J Clin Cases 2024; 12:2324-2331. [PMID: 38765734 PMCID: PMC11099401 DOI: 10.12998/wjcc.v12.i14.2324] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/08/2024] [Accepted: 04/01/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Urethral stricture is a condition that often develops with trauma and results in narrowing of the urethral lumen. Although endoscopic methods are mostly used in its treatment, it has high recurrence rates. Therefore, open urethroplasty is recommended after unsuccessful endoscopic treatments. AIM To investigate the risk factors associated with urethral stricture recurrence. METHODS The data of male patients who underwent internal urethrotomy for urethral stricture between January 2017 and January 2023 were retrospectively analyzed. Demographic data, comorbidities, preoperative haemogram, and biochemical values obtained from peripheral blood and operative data were recorded. Patients were divided into two groups in terms of recurrence development; recurrence and non-recurrence. Initially recorded data were compared between the two groups. RESULTS A total of 303 patients were included in the study. The mean age of the patients was 66.6 ± 13.6 years. The mean duration of recurrence development was 9.63 ± 9.84 (min-max: 1-39) months in the recurrence group. Recurrence did not occur in non-recurrence group throughout the follow-up period with an average time of 44.15 ± 24.07 (min-max: 12-84) months. In the comparison of both groups, the presence of diabetes mellitus (DM), hypertension (HT), and multiple comorbidities were significantly higher in the recurrence (+) group (P = 0.038, P = 0.012, P = 0.013). Blood group, postoperative use of non-steroidal anti-inflammatory drugs, preoperative cystostomy, cause of stricture, iatrogenic cause of stricture, location and length of stricture, indwelling urinary cathater size and day of catheter removal did not differ between the two groups. No statistically significant difference was observed between the two groups in terms of age, uroflowmetric maximum flow rate value, hemogram parameters, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting blood sugar, creatinine, glomerular filtration rate, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, monocyte-lymphocyte ratio and AST/ALT ratios. CONCLUSION In patients with urethral stricture recurrence, only the frequency of DM and HT was high, while inflammation marker levels and stricture-related parameters were similar between the groups.
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Affiliation(s)
- Abdullah Gul
- Department of Urology, University of Health Sciences, Bursa Yüksek İhtisas Education and Research Hospital, Bursa 16100, Türkiye
| | - Ozgur Ekici
- Department of Urology, University of Health Sciences, Bursa City Hospital, Bursa 16000, Türkiye
| | - Salim Zengin
- Department of Urology, University of Health Sciences, Bursa Yüksek İhtisas Education and Research Hospital, Bursa 16100, Türkiye
| | - Deniz Barali
- Department of Urology, University of Health Sciences, Bursa Yüksek İhtisas Education and Research Hospital, Bursa 16100, Türkiye
| | - Tarik Keskin
- Department of Urology, University of Health Sciences, Bursa Yüksek İhtisas Education and Research Hospital, Bursa 16100, Türkiye
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Mondal S, Jana A, Sarkar D. Low Serum Testosterone as a Poor Prognostic Marker in Urethral Stricture: A Single-Center Prospective Longitudinal Study. Cureus 2024; 16:e58895. [PMID: 38800237 PMCID: PMC11117178 DOI: 10.7759/cureus.58895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/24/2024] [Indexed: 05/29/2024] Open
Abstract
Introduction Androgens play a key role in modulating periurethral and preputial vascularity, cavernosal smooth muscle integrity, and penile growth. As a result, low testosterone may adversely affect the severity and outcome of urethral stricture patients. So, to find out the hormonal influence on the clinical outcome of urethral stricture we conducted a prospective longitudinal study at our institute. Methods The study was conducted at the Department of Urology, Institute of Post Graduate Medical Education & Research (IPGMER), Kolkata, India, from February 2023 to September 2023. This study was approved by the Institutional Ethics Committee at IPGMER, Kolkata with the approval number IPGMER/IEC/2023/436. Hormonal levels in patients with diagnosed non-traumatic urethral stricture were compared with patients without stricture. Patients with any overt hormonal abnormality or androgen-secreting tumor were excluded. A morning 10 cc blood sample was collected for testosterone, follicle-stimulating hormone, luteinizing hormone, and thyroid-stimulating hormone. The association of hormonal levels was measured in both groups and compared statistically. Any association of hypogonadism (testosterone <300 ng/dL) with respect to length, severity, and recurrence of urethral stricture was also studied. Results Forty patients with urethral stricture and same number of patients without stricture were included in the study. The mean testosterone level was found to be significantly low in patients with stricture (386 ng/dL vs 660 ng/dL). The age-wise distribution also showed low mean testosterone compared to patients without stricture. The incidence of hypogonadism is also found to be higher in stricture patients (47.5% vs 27.5%). It was also observed low testosterone is more prevalent in pan-anterior stricture (10/40) and long-segment stricture(>2 cm). Patients with stricture were also followed up for 6 months for recurrence of symptoms. Thirteen patients had recurrence. Patients with recurrence had significantly low serum testosterone (272 ng/dL vs 440 ng/dL). Conclusion Our study documented stricture patients with low serum testosterone have poor outcomes. Low testosterone level is strongly associated with longer stricture and increased risk of stricture recurrence.
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Affiliation(s)
- Soumya Mondal
- Urology, Institute of Post Graduate Medical Education & Research, Kolkata, IND
| | - Amitayu Jana
- Urology, Institute of Post Graduate Medical Education & Research, Kolkata, IND
| | - Debansu Sarkar
- Urology, Institute of Post Graduate Medical Education & Research, Kolkata, IND
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Jamil ML, Perecman A, Sherman A, Sullivan T, Christ K, Hansma A, Burks E, Vanni AJ. Urinary microbiome differences between lichen sclerosus induced and non-lichen sclerosus induced urethral stricture disease. World J Urol 2023; 41:2495-2501. [PMID: 37421420 DOI: 10.1007/s00345-023-04490-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Accepted: 06/09/2023] [Indexed: 07/10/2023] Open
Abstract
OBJECTIVE To describe differences in the urinary microbiome of patients with pathologically confirmed lichen sclerosus (LS) urethral stricture disease (USD) vs non-lichen sclerosus (non-LS) USD pre- and post-operatively. METHODS Patients were pre-operatively identified and prospectively followed, all underwent surgical repair and had tissue samples obtained to make a pathological diagnosis of LS. Pre- and post-operative urine samples were collected. Bacterial genomic DNA was extracted. Alpha and beta diversity measurements were calculated and compared. A zero-inflated negative binomial model was utilized to compare taxa abundances between disease status and surgery status. RESULTS Urine samples were obtained from both cohorts, 69 samples in total: 36 samples were obtained pre-operatively and 33 samples were obtained post-operatively. Ten patients provided both a pre-operative and post-operative urine sample. Twenty-six patients had pathological evidence of LS and 33 patients did not. There was a statistically significant difference in alpha diversity between the pre-operative urine samples of patients with non-LS USD and LS USD, (p = 0.01). There was no significant difference in alpha diversity within post-operative urine samples between patients with non-LS USD and LS USD, (p = 0.1). A significant difference was observed in Weighed UniFrac distances with respect to disease and operative status, (p = 0.001 and 0.002). CONCLUSIONS LS USD have significant alterations in diversity and differential abundance of urine microbiota compared to non-LS USD controls. These findings could be used to guide further investigations into the role of the urinary microbiome in LS USD pathogenesis, severity of presentation, and stricture recurrence.
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Affiliation(s)
- Marcus L Jamil
- Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA, 01805, USA
| | - Aaron Perecman
- Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA, 01805, USA
| | - Amanda Sherman
- Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA, 01805, USA
| | - Travis Sullivan
- Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA, 01805, USA
| | - Kimberly Christ
- Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA, 01805, USA
| | - Alexandra Hansma
- Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA, 01805, USA
- Tufts University, Medford, MA, USA
| | - Eric Burks
- Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA, 01805, USA
- Tufts University, Medford, MA, USA
- Boston Medical Center, Boston, Massachusetts, USA
| | - Alex J Vanni
- Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA, 01805, USA.
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Mora EMM, Champer MI, Huang W, Campagnola PJ, Grimes MD. Collagen is More Abundant and Structurally Altered in Lichen Sclerosus. Urology 2023; 173:192-197. [PMID: 36509210 PMCID: PMC10038846 DOI: 10.1016/j.urology.2022.11.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/28/2022] [Accepted: 11/29/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To test the hypothesis that genital skin and male urethra affected by lichen sclerosus (LS) has increased collagen content and altered collagen structure. METHODS We used picrosirius red to stain and image collagen in human urethral, vulvar, and foreskin specimens with and without LS. Using Image J software, we quantified and compared (1) collagen content (using 2o metrics: collagen proportionate area [CPA] and collagen fiber count), (2) collagen fiber length and width, and (3) collagen structure using the texture analysis technique gray level co-localization matrix (GLCM) with respect to LS status and tissue type. RESULTS We analyzed 23 LS specimens (vulva n=9, urethra n=7, foreskin n=7) and 29 non-LS specimens (vulva n=9, urethra n=7, foreskin n=13). Fiber count and CPA were significantly higher in all LS specimens compared to non-LS specimens (CPA: mean±SD 0.971±0.03 vs 0.948±0.02, P < .007; fiber count: mean±SD = 2906±127 vs 2509±78 fibers; P = .003). Collagen fiber width and length were similar with respect to LS status. GLCM analysis showed decreased inverse difference moment and increased entropy in LS tissues indicative of less homogeneous and more disorganized tissue structure (P<.001). CONCLUSION LS tissues have greater collagen content compared to non-LS tissues. Quantitative assessment of collagen organization, using GLCM, revealed less homogeneity and more disorganization of collagen in LS compared to non-LS tissues. Taken together, our findings suggest that alterations in physical tissue properties seen in LS may be due to both increased collagen abundance and altered structure.
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Affiliation(s)
- Eduardo M Miranda Mora
- Department of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI
| | - Melissa I Champer
- Department of Biomedical Engineering, University of Wisconsin, Madison, WI
| | - Wei Huang
- Department of Pathology, School of Medicine and Public Health, University of Wisconsin, Madison, WI
| | - Paul J Campagnola
- Department of Biomedical Engineering, University of Wisconsin, Madison, WI
| | - Matthew D Grimes
- Department of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI.
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Saurabh N. Significance of inflammatory biomarkers and urethral histology in patients with urethral stricture disease in relation to treatment outcome—a single centre prospective study in the north-eastern part of India. AFRICAN JOURNAL OF UROLOGY 2022. [DOI: 10.1186/s12301-021-00252-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Abstract
Background
Inflammation plays a very important role in defining the urethral stricture. Inflammatory biomarkers may play an important role in predicting the underlying pathophysiology as well as outcome of surgery. Histology of urethral strictures along with histology of urethra proximal and distal to stricture segment may have a role in predicting the outcome of the surgery. The literature discussing this aspect is rare; thus, this novel study aimed to find out the role of inflammatory biomarkers and urethral histology in predicting the outcome of surgery in urethral stricture disease.
Methods
This prospective study had 105 patients with age more than 15 years with urethral stricture. Baseline characteristics, routine blood tests including inflammatory blood markers (CRP, ESR, HbA1C, fasting insulin, serum ferritin, etc.) were recorded. They underwent various types of surgery, and first biopsy was taken from stricture segment and second biopsy from proximal to stricture segment and third biopsy from distal to stricture segment and evaluated for the presence of features of lichen sclerosus and inflammation. Primary endpoint was to diagnose the role of inflammatory biomarkers and histology of stricture in stricture recurrence.
Results
Their mean age was 43.3 ± 13.46 years. Mean CRP of 11.54 ± 3.64 in patients with failure and 9.59 ± 2.77 in patients with successful outcome (p 0.025). Other inflammatory biomarkers like HbA1C, fasting insulin, ESR, serum ferritin, NLR had no significant correlation with the outcome. The presence of features of lichen sclerosus like hyperkeratosis and severe inflammation in stricture segment predicted higher likelihood of failure. Histology of proximal and distal segment of urethral stricture had no significant relationship in predicting outcome. Staged urethroplasty with buccal mucosal graft outperformed single-stage urethroplasty in biopsy-proven LS strictures.
Conclusions
The present study found a negative impact of increased CRP and the presence of features of lichen sclerosus in urethral histology with the outcome of urethral stricture disease. Thus, our study confirms that inflammatory biomarkers (CRP) and histology of stricture segment play a significant role predicting the outcome of surgery.
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Marantidis J, Sussman RD. Etiology and Evaluation of Female Urethral Strictures. CURRENT BLADDER DYSFUNCTION REPORTS 2022. [DOI: 10.1007/s11884-021-00637-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Kohli H, Childs B, Sullivan TB, Shevtsov A, Burks E, Kalantzakos T, Rieger-Christ K, Vanni AJ. Differential expression of miRNAs involved in biological processes responsible for inflammation and immune response in lichen sclerosus urethral stricture disease. PLoS One 2021; 16:e0261505. [PMID: 34910765 PMCID: PMC8673646 DOI: 10.1371/journal.pone.0261505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 12/05/2021] [Indexed: 11/27/2022] Open
Abstract
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.
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Affiliation(s)
- Harjivan Kohli
- Department of Urology, Lahey Hospital & Medical Center, Burlington, Massachusetts, United States of America
| | - Brandon Childs
- Department of Urology, Lahey Hospital & Medical Center, Burlington, Massachusetts, United States of America
| | - Travis B. Sullivan
- Department of Translational Research, Lahey Hospital & Medical Center, Burlington, Massachusetts, United States of America
| | - Artem Shevtsov
- Department of Pathology, Boston University School of Medicine, Boston, Massachusetts, United States of America
| | - Eric Burks
- Department of Pathology, Boston University School of Medicine, Boston, Massachusetts, United States of America
| | - Thomas Kalantzakos
- Department of Translational Research, Lahey Hospital & Medical Center, Burlington, Massachusetts, United States of America
| | - Kimberly Rieger-Christ
- Department of Urology, Lahey Hospital & Medical Center, Burlington, Massachusetts, United States of America
- Department of Translational Research, Lahey Hospital & Medical Center, Burlington, Massachusetts, United States of America
| | - Alex J. Vanni
- Department of Urology, Lahey Hospital & Medical Center, Burlington, Massachusetts, United States of America
- * E-mail:
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Pagan L, Ederveen RAM, Huisman BW, Schoones JW, Zwittink RD, Schuren FHJ, Rissmann R, Piek JMJ, van Poelgeest MIE. The Human Vulvar Microbiome: A Systematic Review. Microorganisms 2021; 9:2568. [PMID: 34946169 PMCID: PMC8705571 DOI: 10.3390/microorganisms9122568] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 11/25/2021] [Accepted: 12/03/2021] [Indexed: 02/07/2023] Open
Abstract
The link between cancer and the microbiome is a fast-moving field in research. There is little knowledge on the microbiome in ((pre)malignant) conditions of the vulvar skin. This systematic review aims to provide an overview of the literature regarding the microbiome composition of the healthy vulvar skin and in (pre)malignant vulvar disease. This study was performed according to the PRISMA guidelines. A comprehensive, electronic search strategy was used to identify original research articles (updated September 2021). The inclusion criteria were articles using culture-independent methods for microbiome profiling of the vulvar region. Ten articles were included. The bacterial composition of the vulva consists of several genera including Lactobacillus, Corynebacterium, Staphylococcus and Prevotella, suggesting that the vulvar microbiome composition shows similarities with the corresponding vaginal milieu. However, the vulvar microbiome generally displayed higher diversity with commensals of cutaneous and fecal origin. This is the first systematic review that investigates the relationship between microbiome and vulvar (pre)malignant disease. There are limited data and the level of evidence is low with limitations in study size, population diversity and methodology. Nevertheless, the vulvar microbiome represents a promising field for exploring potential links for disease etiology and targets for therapy.
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Affiliation(s)
- Lisa Pagan
- Centre for Human Drug Research, 2333 CL Leiden, The Netherlands; (L.P.); (B.W.H.); (M.I.E.v.P.)
- Department of Gynecology and Obstetrics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Roos A. M. Ederveen
- Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands;
- Department of Obstetrics and Gynaecology and Catharina Cancer Institute, Catharina Ziekenhuis, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands;
| | - Bertine W. Huisman
- Centre for Human Drug Research, 2333 CL Leiden, The Netherlands; (L.P.); (B.W.H.); (M.I.E.v.P.)
- Department of Gynecology and Obstetrics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Jan W. Schoones
- Directorate of Research Policy (Formerly: Walaeus Library), Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;
| | - Romy D. Zwittink
- Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;
| | - Frank H. J. Schuren
- Netherlands Organisation for Applied Scientific Research, TNO, 3704 HE Zeist, The Netherlands;
- Leiden Skin Institute, 2333 CL Leiden, The Netherlands
| | - Robert Rissmann
- Centre for Human Drug Research, 2333 CL Leiden, The Netherlands; (L.P.); (B.W.H.); (M.I.E.v.P.)
- Leiden Skin Institute, 2333 CL Leiden, The Netherlands
- Leiden Amsterdam Center for Drug Research, Leiden University, 2300 RA Leiden, The Netherlands
| | - Jurgen M. J. Piek
- Department of Obstetrics and Gynaecology and Catharina Cancer Institute, Catharina Ziekenhuis, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands;
| | - Mariëtte I. E. van Poelgeest
- Centre for Human Drug Research, 2333 CL Leiden, The Netherlands; (L.P.); (B.W.H.); (M.I.E.v.P.)
- Department of Gynecology and Obstetrics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
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Samarska IV, Dani H, Bivalacqua TJ, Burnett AL, Matoso A. Histopathologic and clinical comparison of recurrent and non-recurrent urethral stricture disease treated by reconstructive surgery. Transl Androl Urol 2021; 10:3714-3722. [PMID: 34804815 PMCID: PMC8575568 DOI: 10.21037/tau-21-477] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 08/26/2021] [Indexed: 11/21/2022] Open
Abstract
Background Urethral stricture is a relatively frequent problem often requiring multiple surgical interventions. The objective of this study was to compare the clinicopathologic features of urethral resections from patients who underwent open end-to-end anastomotic urethroplasty and later recurred compared to those who did not. Methods A retrospective review of the pathology files identified 36 consecutive patients who underwent urethroplasty. The histopathological analysis included evaluation of the inflammatory infiltrate based on the predominant (>50%) cell type: lymphocyte-rich, neutrophil-rich, plasma cell-rich, and mixed; length and thickness of the fibrous plaque; and the cellularity of the fibrous plaque: cellular (>40 stroma nuclei/HPF) or paucicellular (<40 stroma nuclei/high power field). Results Ten (28%) patients recurred, and 26 (72%) did not. There was no significant difference between recurrent and non-recurrent cases in age, race, comorbidities, location of the stricture, and etiology. All patients with recurrent strictures showed dense paucicellular fibrotic plaques (10/10; 100%), while this was seen in 14/26 (53.8%) non-recurrent cases (P=0.01). Only one patient with cellular fibrosis showed recurrence during follow-up. The log-rank test shows that time to recurrence is significantly shorter in patients with paucicellular fibrosis compared to those with cellular fibrosis (P=0.036). The inflammation consisted of a mixed population of CD3(+) T-lymphocytes, CD20(+) B-lymphocytes, and CD68(+) histiocytes, and there was no difference in the composition of the inflammation between groups. All cases with plasma cell-rich infiltrate showed normal IgG4:IgG. Conclusions Our study supports reporting cellularity of the fibrous plaque as a potential predictor of outcome in patients undergoing reconstructive urethroplasty. Patients with paucicellular fibrosis are at increased risk of recurrence.
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Affiliation(s)
- Iryna V Samarska
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands.,Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Hasan Dani
- Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Trinity J Bivalacqua
- Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.,Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Arthur L Burnett
- Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.,Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Andres Matoso
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.,Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.,Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
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12
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Kühnke L, Fisch M, Vetterlein MW. [Contemporary management of urethral strictures in women]. Aktuelle Urol 2021; 52:260-267. [PMID: 33860480 DOI: 10.1055/a-1367-6565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Urethral strictures in women are rare and patients may present with varying symptoms. Hence, clinical guidelines regarding diagnostic algorithms and treatment approaches are scarce. Several small case series have presented results for several operative techniques, but patient cohorts are generally heterogeneous and relatively small, which hampers reliable comparability across institutions. The present narrative review aims to provide a contemporary overview of the literature regarding the clinical and therapeutical approach in women with urethral strictures.Iatrogenic reasons such as previous catheterization or genitourinary surgical interventions are the most common cause of female urethral strictures. In daily clinical routine, physical examination is the cornerstone for differential diagnosis and may aid in the decision to expand diagnostic workup by urethrocystoscopy, urethrography, or magnetic resonance imaging in case of suspected anatomic or morphologic cause of voiding disorder. Endoscopic approaches such as dilation or urethrotomy only provide short-term symptomatic relief and open urethroplasty is more commonly associated with durable long-term success. Regarding the surgical approach, there are comparable operative techniques at hand, using vaginal or labial flaps or oral mucosal grafts. Given the relative rarity of female urethral strictures with only small case series published, a statement regarding the superiority of one approach over the other is hardly possible. As for all rare disorders, multi-institutional, large patient series are needed to generate reliable evidence and to improve standards in the perioperative care of women with urethral strictures.
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Affiliation(s)
- Lennart Kühnke
- Klinik und Poliklinik für Urologie, Universitätsklinikum Hamburg-Eppendorf
| | - Margit Fisch
- Klinik und Poliklinik für Urologie, Universitätsklinikum Hamburg-Eppendorf
| | - Malte W Vetterlein
- Klinik und Poliklinik für Urologie, Universitätsklinikum Hamburg-Eppendorf
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13
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Abstract
Lichen sclerosus (LS), or balanitis xerotica obliterans as it was previously known, is a chronic inflammatory lymphocyte-mediated scarring dermatosis that often affects the preputial skin and glans, leading to phimosis and urethral strictures if left untreated. We present a narrative review of the literature assessing its aetiology and pathogenesis and discuss its links to penile cancer and its medical and surgical management. Possible hypotheses for the development of LS include chronic exposure to trapped urine, leading to changes in the epithelial structure. This is supported by the fact that circumcision is often curative in the early stages of the disease. Although circumcision can be curative, the use of topical steroids is typically the first-line treatment and may preserve the foreskin and forgo the need for circumcision altogether. Patients should be made aware of a possible association with penile cancer. Although the majority of cases can be treated by medical therapy and circumcision, a significant number of patients may also require penile reconstructive procedures.
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Affiliation(s)
- Rachel Kwok
- Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
| | - Taimur T Shah
- Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.,Department of Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Suks Minhas
- Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.,Department of Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
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Synchronous genitourinary lichen sclerosus signals a distinct urinary microbiome profile in men with urethral stricture disease. World J Urol 2020; 39:605-611. [PMID: 32274566 DOI: 10.1007/s00345-020-03198-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 03/31/2020] [Indexed: 01/09/2023] Open
Abstract
PURPOSE Alterations in the urinary microbiome have been associated with urological diseases. The microbiome of patients with urethral stricture disease (USD) remains unknown. Our objective is to examine the microbiome of USD with a focus on inflammatory USD caused by lichen sclerosus (LS). METHODS We collected mid-stream urine samples from men with LS-USD (cases; n = 22) and non-LS USD (controls; n = 76). DNA extraction, PCR amplification of the V4 hypervariable region of the 16S rRNA gene, and sequencing was done on the samples. Operational taxonomic units (OTUs) were defined using a > 97% sequence similarity threshold. Alpha diversity measurements of diversity, including microbiome richness (number of different OTUs) and evenness (distribution of OTUs) were calculated and compared. Microbiome beta diversity (difference between microbial communities) relationships with cases and controls were also assessed. RESULTS Fifty specimens (13 cases and 37 controls) produced a 16S rRNA amplicon. Mean sample richness was 25.9 vs. 16.8 (p = 0.076) for LS-USD vs. non-LS USD, respectively. LS-USD had a unique profile of bacteria by taxonomic order including Bacillales, Bacteroidales and Pasteurellales enriched urine. The beta variation of observed bacterial communities was best explained by the richness. CONCLUSIONS Men with LS-USD may have a unique microbiologic richness, specifically inclusive of Bacillales, Bacteroidales and Pasteurellales enriched urine compared to those with non-LS USD. Further work will be required to elucidate the clinical relevance of these variations in the urinary microbiome.
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Medical and Surgical Management of Genital Lichen Sclerosus. CURRENT SEXUAL HEALTH REPORTS 2020. [DOI: 10.1007/s11930-020-00258-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Chung ASJ, Suarez OA. Current treatment of lichen sclerosus and stricture. World J Urol 2019; 38:3061-3067. [DOI: 10.1007/s00345-019-03030-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 11/18/2019] [Indexed: 10/25/2022] Open
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