Treatment Of Urethral Stricture Disease Research Articles

A drug-coated balloon treatment for urethral stricture disease: Interim results from the ROBUST I study.

We aimed to investigate the safety and preliminary efficacy of the Optilume™ paclitaxel-coated balloon for the treatment of recurrent urethral stricture. Men with bulbar urethral strictures ≤2 cm with 1-4 prior endoscopic treatments were enrolled at four study sites after ethics committee approvals. All subjects were treated with mechanical balloon dilation or direct visualization internal urethrotomy prior to drug-coated balloon treatment. Patients were evaluated at 2-5 days, 14 days, three, six, and 12-months post-treatment. The primary safety endpoint was serious complications through 90 days post-procedure. The preliminary efficacy endpoint was anatomic success, defined as urethral lumen ≥14 Fr at 12 months. A total of 53 subjects were enrolled and treated; 46 completed the 12-month followup. Forty-three percent of men had undergone >1 previous dilation; the mean for the overall study population was 1.7 prior dilations. There were no serious adverse events related to the treatment within 90 days. Anatomic success was achieved in 32/46 (70%; 95% confidence interval [CI] 54-82%) at 12 months. The 14 failures included seven cystoscopic recurrences, five retreatments, and two patients who exited the study early due to symptom recurrence. One-year data indicates the Optilume paclitaxel-coated balloon is safe for the treatment of recurrent bulbar urethral strictures. Early efficacy results are encouraging and support further followup of these men through five years, as well as further investigation with a randomized trial.

Endoluminal and Endoscopic Management of Urethral Stricture

Background and Objective Urethral stricture in the male population is one the oldest described urological condition. Significant vari-ability in clinical practice means that standardized management of urethral stricture remains controversial. Since the first description of modern-day direct visual internal urethrotomy (DVIU) by Sachse in 1974, this, alongside with various endoscopic treatment techniques, continues to be by far the most commonly performed procedures for the management of urethral strictures. This article aims to summarise and review the latest literature on endoscopic management of urethral strictures. Material and Methods We conducted a Pubmed and Medline search to identify publications related to endoscopic management of male urethral strictures between 1980 and 2019. Preference was given to recent and larger studies. Original research articles, review articles, abstracts, and opinion articles were included. Keywords used for the search were “male urethral stricture,” “urethrotomy,” “DVIU,” “urethral dilation,” “urethral stent”, “intermittent self-catheterisation”, “mitomycin C”, “steroids”, and “urethroplasty.” Recent Findings The long-term efficacy of endoscopic management of urethral stricture is poor. Recent novel advances with adjunct treatment have yet to demonstrate improvement in long-term treatment success. Repeated endoluminal or endoscopic treatments, especially for long and recurrent urethral strictures, are ineffective. They appear to delay patients from receiving definitive treatments, and potentially increase complexity and decrease the success rate of any future urethral reconstructive treatment. Summary There is overwhelming evidence to suggest limited long-term efficacy of endoluminal or endoscopic treat-ments for urethral stricture. Novel adjunctive therapies showed promising initial results, but none have yet to demonstrate durable efficacy. Endoscopic treatment of urethral stricture disease should only be reserved for patients who are not willing to undergo reconstructive surgery, or not fit for anesthetics.

The Top 100 Cited Articles in Urethral Reconstruction

OBJECTIVETo examine the most cited literature in urethral reconstruction, review types of work published, and observe research trends. METHODSThe Web of Sciences Sci-Expanded Index was used to conduct a search for urethral reconstruction. References were assessed for relevance to urethral reconstruction by 2 independent reviewers and a final list of the top 100 articles ranked by citation count was obtained. For each article, citation count, publication date, corresponding author, origin institution, origin country, topic area, study design, level of evidence, and origin journal were collected. RESULTSThe mean citation count per publication was 108 (median = 94.5; range = 69-366, SD = 43) with a total of 10,874 citations for all papers since 1970. The top 100 articles were published between 1973 and 2011, came from 19 different countries and 16 different journals. Nearly half were case series and most studies were Level III evidence or lower. The United States was the largest contributor to the top 100 with 56 publications, followed by Italy (14), England (12), and Egypt (7). “Outcomes of surgical treatment for urethral stricture disease” was the most prevalent topic area comprising 55 articles in the top 100, with most articles including descriptions or outcomes of novel surgical techniques. CONCLUSIONIn this study, we discovered that the most cited literature in the field of urethral reconstruction is singularly focused and lacking in high levels of evidence. The top 100 cited articles originate primarily from the United States, focus on short-term outcomes after surgical treatment for urethral stricture disease, and are predominantly case series.

Placental membrane grafts for urethral replacement in a rabbit model: a pilot study.

Several graft materials are available for use in the treatment of urethral stricture disease. Placental membrane is being used in a variety of settings as a graft in wound healing and tissue repair. We aim to evaluate the effect of implanting decellularized human placental membrane into rabbit urethras. Dorsal onlay graft urethroplasty using prepared human placental membrane was performed in 10 New Zealand White rabbits (Oryctolagus cuniculus). After 3 months, the rabbits underwent cystourethroscopy to evaluate urethral patency. The rabbits were then euthanized and the urethras examined for pathological findings. All urethroplasties were performed without complication. There were no observed episodes of urinary retention, infection, or renal failure. Urethral patency was achieved in all rabbits 3 months postoperatively. Urothelial replacement of the placental membrane graft was observed in all rabbits without malignant transformation. Dorsal onlay urethroplasty using decellularized human placental membrane can safely be performed in a rabbit model. This pilot study demonstrated urothelial replacement of human placental membrane in the rabbit urethra without stricture formation. Placental membrane is a promising biomaterial for urethral reconstruction.

MP55-09 ENDOSCOPIC TREATMENTS PRIOR TO URETHROPLASTY: TRENDS IN MANAGEMENT OF URETHRAL STRICTURE DISEASE SINCE THE AUA GUIDELINE

INTRODUCTION AND OBJECTIVES:Endoscopic treatment of urethral stricture disease (USD) continues to be the most common treatment of USD despite its poor success compared to urethroplasty. AUA guideli...

272 Socioeconomic Factors Influence the Utilization of Urethroplasty in the Treatment of Male Urethral Stricture Disease

Male urethral stricture disease is a commonly encountered urologic condition. Treatment options include endoscopic approaches versus urethroplasty. Previously identified provider-level barriers to urethroplasty utilization include access to a reconstructive surgeon, geographic disparities in care, and provider concerns regarding complications. We sought to determine patient related and socioeconomic factors influencing urethroplasty utilization compared to endoscopic management. A retrospective review using the Healthcare Cost and Utilization Project State Inpatient and Ambulatory Surgery and Services Databases for California and Florida was performed. Adult men with a diagnosis of urethral stricture who underwent urethroplasty or endoscopic dilation/urethrotomy between 2007-2011 for California and 2009-2014 for Florida were identified by ICD-9 or CPT codes. Patients were assessed for age, insurance provider, median household income, Charlson comorbidity index, race, and number of endoscopic procedures. A stepwise multivariate analysis model was fit to assess factors influencing treatment modality (urethroplasty vs. endoscopic management). 27,641 patients were identified who underwent treatment for urethral stricture disease. 1,692 underwent urethroplasty (6.1%). Factors favoring utilization of urethroplasty include younger age, lower Charlson comorbidity score, higher income quartile, and increased number of endoscopic treatments (Figure 1). Hispanics were more likely to undergo endoscopic management compared to Caucasians.

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

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

Re-Establishing Flow Via Drug Coated Balloon for the Treatment of Urethral Stricture Disease - Registry Study

Re-Establishing Flow Via Drug Coated Balloon for the Treatment of Urethral Stricture Disease - Registry Study

A Review of the epidemiology and management of urethral stricture disease in Sub-Saharan Africa

The prevalence of urethral stricture in Sub-Saharan Africa is unknown though a few epidemiological studies show that it constitutes a huge disease burden in the region. Over the years, there has been a global change in the epidemiology and management of urethral stricture the extent of which depends on the differences in the regional and subregional economy. The latter affects the pattern of disease distribution and the available tools and expertise for their management. Sixty-one published reports were obtained from Google for this review which critically analyzed the current epidemiology, treatment of urethral stricture disease, and the challenges associated with its treatment in Sub-Saharan Africa from 2011 to 2019. The review also assessed the subregional capacity to treat urethral stricture, taking into consideration available tools, expertise, standard treatment methods, and guidelines.

Robotic Dorsal-Onlay Urethroplasty: A Case Report

Urethroplasty is considered the gold standard treatment for urethral stricture disease with over 90% success rate. Dorsal-onlay urethroplasty using buccal or skin grafts is a crucial technique for managing long anterior strictures. We report here the feasibility of performing robotic dorsal-onlay urethroplasty utilizing preputial graft. A 63-year-old man was referred for radical prostatectomy. Initial retrograde urethrogram showed urethral stricture within the membranous portion of the urethra extending into the bulbar urethra. Plan of conservative management of the prostate cancer, in addition to robotic urethroplasty utilizing a dorsal-onlay preputial skin graft. A preputial graft was harvested and placed dorsally into the bulbomembranous urethra using the Da Vinci Si system. Operative time was 2 hours, and post-operative course was uneventful. After 7.5-year follow-up, the patient remained asymptomatic and no evidence of stricture recurrence on cystoscopy. The patient did not require any intervention for either his stricture disease or prostate cancer, which did not progress on follow-up MR-US Fusion biopsies. Robotic dorsal-onlay urethroplasty is feasible and can be performed safely and efficiently without prolonging the length of the surgery. Future directions should focus on performing this surgery using smaller incisions.

Effect of dual mTOR inhibitor on TGFβ1-induced fibrosis in primary human urethral scar fibroblasts

BackgroundTGFβ1 and mTOR are considered to play important roles in fibrotic diseases. Rapamycin has been reported to inhibit urethral stricture formation in a rabbit model of urethral fibrosis. AimTo evaluate if dual mTOR inhibitor has a superior efficacy compared with rapamycin on inhibiting cell proliferation and collagen expression in human urethral scar fibroblasts (HUSFs). MethodsWe established HUSF cultures from fresh surgical specimen. The HUSFs were identified with typical fibroblast markers using immunofluorescence. Then we examined the effect of TGFβ1 on HUSFs using Cell Counting Kit-8 and Western blot. The inhibiting effects of OSI-027 (a dual mTOR inhibitor) on cell proliferation and collagen expression in TGFβ1-induced HUSFs were compared with rapamycin using Cell Counting Kit-8, Western blot, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). ResultsHUSFs were stained positive for vimentin, collagen I, and collagen III. TGFβ1 had no effect on cell proliferation but increased collagen I and collagen III expressions in HUSFs. OSI-027 was more effective inhibiting cell proliferation and collagen expression compared with rapamycin in TGFβ1-induced HUSFs. OSI-027 played a more important role in inhibiting TGFβ1-induced mTOR pathway and phosphorylation of Smad2 compared with rapamycin in HUSFs. ConclusionOSI-027 can inhibit the pro-fibrotic effects of TGFβ1 significantly compared with rapamycin in HUSFs. These findings may provide a new therapy in the adjunctive treatment of urethral stricture disease.

Catheter dwell time and diameter affect the recurrence rates after internal urethrotomy.

Cold-knife direct vision internal urethrotomy (DVIU) is frequently used as the first-line treatment for urethral stricture disease. Although the steps of the procedure are defined in detail, the duration of catheterization and the diameter of the catheter to be used after the operation are not clearly defined. The aim of this study is to evaluate the effects of catheter dwell time and diameter on recurrence rates of urethral stricture disease after DVIU. Data of 193 consecutive treatment naïve bulbar urethral stricture patients who underwent DVIU between January 2009 and June 2013 were retrospectively analyzed. Patient demographics and stricture characteristics were noted. Catheter dwell times were grouped as <5 and ≥5 days. The diameters of catheters used were 16, 18 and 22 Fr. The association between recurrence rates, catheter dwell times, and diameter were evaluated with Tukey's test and Pearson's correlation test, respectively. Overall 193 patients with a mean age of 64.51±12.99 (range: 17 to 85) years were enrolled in the study. Urethral stricture disease recurred in 45 (23.31%) patients within the first year after DVIU. Mean duration of catheterization was 7.47±4.03 and 4.79±1.94 days in patients with and without recurrences, respectively (p=0.0001). Catheter dwell times for ≥5 days were also associated with increased recurrence (p=0.0001). Of the patients with recurrent strictures, 16, 18 and 22Fr catheters were placed in 22.22%, 20% and 57.78% of the patients, respectively. Increased catheter diameter was also associated with higher recurrence rates (p=0.004). Shortening the postoperative duration of catheterization and decreasing the catheter size may result in improved recurrence rates after DVIU. Further prospective randomized trials are necessary to confirm these findings.

Effect of adipose tissue-derived stem cell injection in a rat model of urethral fibrosis.

We sought to evaluate the therapeutic effect of adi-pose tissue-derived stem cells (ADSCs) in a rat model of urethral fibrosis. Eighteen (18) male Sprague-Dawley rats (300‒350 g) were divided into three groups: (1) sham (saline injection); (2) urethral fibrosis group (10 μg transforming growth factor beta 1 (TGF-β1) injection); and (3) ADSCs group (10 μg TGF-β1 injection plus 2 × 105 ADSCs). Rat ADSCs were harvested from rat inguinal fat pads. All study animals were euthanized at two weeks after urethral injection. Following euthanasia, rat urethral tissue was harvested for histologic evaluation. Type I and III collagen levels were quantitated by Western blot analysis. TGF-β1 injection induced significant urethral fibrosis and increased collagen type I and III expression (p<0.05). Significant decrease in submucosal fibrosis and collagen type I and III expression were noted in the ADSCs group compared with the urethral fibrosis group (p<0.05). TGF-β1 induced fibrotic changes were ameliorated by injection of ADSCs. Local injection of ADSCs in a rat model of urethral fibrosis significantly decreased collagen type I and III. These findings suggest that ADSC injection may prevent scar formation and potentially serve as an adjunct treatment to increase the success rate of primary treatment for urethral stricture disease. Further animal and clinical studies are needed to confirm these results.

Current Practice Patterns Among Members of the American Urological Association for Male Genitourinary Lichen Sclerosus

To determine the practice patterns of urologists who treat male genitourinary lichen sclerosus (MGU-LS) via a national web-based survey distributed to American Urological Association members. A 20-question survey was collected from a random sample of American Urological Association members. Respondents answered questions on their practice patterns for MGU-LS diagnosis, treatment of symptomatic urethral stricture disease, surveillance, and follow-up. In total, 309 urologists completed the survey. The majority of respondents reported practicing more than 20+ years (37.5%) within an academic (31.7%) or group practice (31.1%) setting. The majority of respondents saw 3-5 men with MGU-LS per year (32.7%). The most common locations of MGU-LS involvement included the glans penis (66.2%), foreskin (26.3%), and/or the urethra (5.8%). Respondent first-line treatment for urethral stricture disease was direct visual internal urethrotomy (26.6%) and second-line treatment was referral to subspecialist (38.4%). After controlling for the number of patients evaluated with MGU-LS per year, those with reconstructive training were more likely to perform a primary urethroplasty for men with symptomatic urethral stricture disease (adjusted odds ratio 13.1, 95% confidence interval 5.1-33.8, P < .001). They were also more likely to counsel men on the associated penile cancer risks (adjusted odds ratio 4.6, 95% confidence interval 1.7-12.5, P < .01). Reconstructive urologists evaluate the most number of patients with MGU-LS and are more likely to perform primary urethroplasty for urethral stricture disease. Men with MGU-LS should be referred to a reconstructive urologist to understand the full gamut of treatment options.

Urethral Stricture Disease: Challenges and Ongoing Controversies.

Urethral Stricture Disease: Challenges and Ongoing Controversies.

Anterior Urethral Stricture Disease Negatively Impacts the Quality of Life of Family Members.

Purpose. To quantify the quality of life (QoL) distress experienced by immediate family members of patients with urethral stricture via a questionnaire given prior to definitive urethroplasty. The emotional, social, and physical effects of urethral stricture disease on the QoL of family members have not been previously described. Materials and Methods. A questionnaire was administered prospectively to an immediate family member of 51 patients undergoing anterior urethroplasty by a single surgeon (SBB). The survey was comprised of twelve questions that addressed the emotional, social, and physical consequences experienced as a result of their loved one. Results. Of the 51 surveyed family members, most were female (92.2%), lived in the same household (86.3%), and slept in the same room as the patient (70.6%). Respondents experienced sleep disturbances (56.9%) and diminished social lives (43.1%). 82.4% felt stressed by the patient's surgical treatment, and 83.9% (26/31) felt that their intimacy was negatively impacted. Conclusions. Urethral stricture disease has a significant impact on the family members of those affected. These effects may last decades and include sleep disturbance, decreased social interactions, emotional stress, and impaired sexual intimacy. Treatment of urethral stricture disease should attempt to mitigate the impact of the disease on family members as well as the patient.

Treatment of Urethral Stricture Disease by Internal Urethrotomy, Dilation, or Stenting

Management of urethral strictures depends on the characteristics of each individual case and remains a great challenge in reconstructive urology. Treatment of anterior urethral strictures usually starts with minimally invasive procedures, such as urethral dilatation or internal urethrotomy. The popularity of these methods is based on the simple application, the low complication rate, and the fact that most general urologists do not perform open urethroplasty. These methods offer faster recovery, minimal scarring, and fewer infections, although recurrence is always possible. Success depends on adequate vascularity within the underlying spongiosal tissue, which may substantially increase the failure rate. Because the recurrence rate has remained higher than it was in past decades, various modifications of urethral stricture treatment have been suggested, including laser urethrotomy and urethral stents. Since the late 1980s, two different approaches have been studied to prevent scaring contraction: permanent stent versus temporary stents left indwelling for a limited time and then removed. Although the first reports seemed to promise excellent outcomes, longer follow-up began to cast doubt on the usefulness of urethral stenting as a primary treatment modality for urethral stricture disease. The purpose of our study was to evaluate the published literature with respect to any new information on minimally invasive procedures in the treatment of urethral strictures. Patient summaryThe optimal indications for dilatation or internal urethrotomy are simple bulbar strictures <2cm without spongiofibrosis or history of previous treatment. Recurrent urethral strictures after repeated interventions are usually more complex and can render the definite open urethral surgery more difficult.

MP15-19 COLLAGENASE CLOSTRIDIUM HISTOLYTICUM FOR TREATMENT OF URETHRAL STRICTURE DISEASE IN A RAT MODEL OF URETHRAL FIBROSIS

You have accessJournal of UrologyTrauma/Reconstruction: Urethral Reconstruction (including Stricture) I1 Apr 2015MP15-19 COLLAGENASE CLOSTRIDIUM HISTOLYTICUM FOR TREATMENT OF URETHRAL STRICTURE DISEASE IN A RAT MODEL OF URETHRAL FIBROSIS Premsant Sangkum, Hogyoung Kim, Mostafa Bouljihad, Manish Ranjan, Amrita Datta, Sree Mandava, Faysal Yafi, Suresh Sikka, Asim Abdel-Mageed, and Wayne Hellstrom Premsant SangkumPremsant Sangkum More articles by this author , Hogyoung KimHogyoung Kim More articles by this author , Mostafa BouljihadMostafa Bouljihad More articles by this author , Manish RanjanManish Ranjan More articles by this author , Amrita DattaAmrita Datta More articles by this author , Sree MandavaSree Mandava More articles by this author , Faysal YafiFaysal Yafi More articles by this author , Suresh SikkaSuresh Sikka More articles by this author , Asim Abdel-MageedAsim Abdel-Mageed More articles by this author , and Wayne HellstromWayne Hellstrom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.902AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Collagenase clostridium histolyticum (CCH) has been recently FDA-approved for minimally invasive treatment of Peyronie's disease (PD). PD is a fibrotic wound-healing disorder of the tunica albuginea of the corpus cavernosum. Urethral stricture is a scarring process involving the urethral mucosa and surrounding spongy tissue of the corpus spongiosum. Increases in collagen type I and III have been documented in both conditions. We, therefore, postulate that CCH may effectively treat urethral stricture fibrosis. This is a proof of concept study using CCH for the treatment of urethral fibrosis in a rat model. METHODS Male Sprague-Dawley rats (n=24, 300–350 g) were anesthetized with 100/10 ml/kg ketamine/xylazine intraperitoneally. Urethral fibrosis was induced by TGF-β1 injection into two places of the urethra via a small penoscrotal incision. Two weeks following TGF-β1 injection, different groups were injected with 0.05 mg CCH or calcium chloride vehicle into the same area of the urethra. The rats were sacrificed at two weeks following the CCH or vehicle injection. The urethral tissues were harvested and evaluated by Hematoxilin & Eosin (H&E) and Masson trichrome staining by a single, blinded pathologist. RESULTS Histological assessment of urethral sections (H&E and Masson's trichrome stain, x400) demonstrated a normal urethral lumen surrounded by normal distribution of collagen bundles and smooth muscle cells without fibrosis in the sham group, and moderate fibrosis with densely packed collagenous stroma involving the submucosal tissues in the stricture groups. There was minimal submucosal fibrosis with a moderate amount of smooth muscle cells in the vehicle and CCH injection groups (Fig. 1). There were no complications from the CCH injection. CONCLUSIONS CCH is contraindicated in ventral plaque PD patients due to concerns of urethral complications. Our study shows that CCH was safe for urethral injection and may have a role in the treatment of urethral stricture disease. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e166 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Premsant Sangkum More articles by this author Hogyoung Kim More articles by this author Mostafa Bouljihad More articles by this author Manish Ranjan More articles by this author Amrita Datta More articles by this author Sree Mandava More articles by this author Faysal Yafi More articles by this author Suresh Sikka More articles by this author Asim Abdel-Mageed More articles by this author Wayne Hellstrom More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

961 The revised role of urethrotomy in the treatment of urethral stricture disease: Analysis of 961 cases from a single center

961 The revised role of urethrotomy in the treatment of urethral stricture disease: Analysis of 961 cases from a single center

The Use of Flaps and Grafts in the Treatment of Urethral Stricture Disease.

The use of various grafts and flaps plays a critical role in the successful surgical management of urethral stricture disease. A thorough comprehension of relevant anatomy and principles of tissue transfer techniques are essential to understanding the appropriate use of grafts or flaps to optimize outcomes. We briefly review these principles and discuss which technique may be best suited for a given anterior urethral stricture, depending on the location and length of the stricture, the presence or absence of an intact corpus spongiosum, and the availability of adequate and healthy penile skin.