Deep Phenotyping the Anterior Urethral Stricture: Characterizing the Relationship Between Inflammation, Fibrosis, Patient History, and Disease Pathophysiology.

PURPOSE: Anterior urethral stricture disease (aUSD) is a complex, heterogeneous condition that is idiopathic in origin for most men. This gap in knowledge rarely affects the current management strategy for aUSD, as urethroplasty does not generally consider etiology. However, as we transition towards personalized, minimally invasive treatments for aUSD and begin to consider aUSD prevention strategies, disease pathophysiology will become increasingly important. The purpose of this study was to perform a deep phenotype of men undergoing anterior urethroplasty for aUSD. We hypothesized that unique biologic signatures and potential targets for intervention would emerge based on stricture presence/absence, stricture etiology, and the presence/absence of stricture inflammation. MATERIALS AND METHODS: Men with aUSD undergoing urethroplasty were recruited from one of 5 participating centers. Enrollees provided urethral stricture tissue and blood/serum on the day of surgery and completed patient-reported outcome measure questionnaires both pre- and postoperatively. The initial study had 3 aims: (1) to determine pediatric and adult subacute and repeated perineal trauma (SRPT) exposures using a study-specific SRPT questionnaire, (2) to determine the degree of inflammation and fibrosis in aUSD and peri-aUSD (normal urethra) tissue, and (3) to determine levels of systemic inflammatory and fibrotic cytokines. Two controls groups provided serum (normal vasectomy patients) and urethral tissue (autopsy patients). Cohorts were based on the presence/absence of stricture, by presumed stricture etiology (idiopathic, traumatic/iatrogenic, lichen sclerosus [LS]), and by the presence/absence of stricture inflammation. RESULTS: Of 138 enrolled men (120 tissue/serum; 18 stricture tissue only), 78 had idiopathic strictures, 33 had trauma-related strictures, and 27 had LS-related strictures. BMI, stricture length, and stricture location significantly differed between cohorts (P < .001 for each). The highest BMIs and the longest strictures were observed in the LS cohort. SRPT exposures did not significantly differ between etiology cohorts, with > 60% of each reporting low/mild risk. Stricture inflammation significantly differed between cohorts, with mild to severe inflammation present in 27% of trauma-related strictures, 54% of idiopathic strictures, and 48% of LS strictures (P = .036). Stricture fibrosis did not significantly differ between cohorts (P = .7). Three serum cytokines were significantly higher in patients with strictures compared to stricture-free controls: interleukin-9 (IL-9; P = .001), platelet-derived growth factor-BB (P = .004), and CCL5 (P = .01). No differences were observed in the levels of these cytokines based on stricture etiology. However, IL-9 levels were significantly higher in patients with inflamed strictures than in patients with strictures lacking inflammation (P = .019). Degree of stricture inflammation positively correlated with serum levels of IL-9 (Spearman's rho 0.224, P = .014). CONCLUSIONS: The most common aUSD etiology is idiopathic. Though convention has implicated SRPT as causative for idiopathic strictures, here we found that patients with idiopathic strictures had low SRPT rates that were similar to rates in patients with a known stricture etiology. Stricture and stricture-adjacent inflammation in idiopathic stricture were similar to LS strictures, suggesting shared pathophysiologic mechanisms. IL-9, platelet-derived growth factor-BB, and CCL5, which were elevated in patients with strictures, have been implicated in fibrotic conditions elsewhere in the body. Further work will be required to determine if this shared biologic signature represents a potential mechanism for an aUSD predisposition.

Primary mucinous adenocarcinoma of the urethra: A clinicopathological analysis of 35 cases.

AIM: Primary mucinous adenocarcinoma of the urethra represents an extremely rare entity. We sought to characterise further these tumours' clinicopathological, immunohistochemical and molecular features. METHODS AND RESULTS: Thirty-five cases were identified, occurring in 18 males and 17 females. The mean age at diagnosis was 65 years (28-89 years). The main presentation symptoms were haematuria and urinary outlet obstruction. Microscopic analysis revealed that all 35 tumours have stromal dissection by mucin. Ten tumours showed villoglandular dysplasia, nine showed mucinous metaplasia, two showed adenocarcinoma in situ and four showed signet ring cell features. All tumours were immunopositive for CEA, while immunonegative for nuclear ß-catenin; 19 of 23 (83%) expressed high molecular weight cytokeratin; 19 of 33 (58%) CK7; 28 of 34 (82%) CK20; 32 of 35 (91%) CDX2; 22 of 27 (81%) cadherin-17 (CDH-17); 26 of 29 (90%) SATB2; and one of 31 (3%) GATA3. Mismatch repair gene products, including MLH1, PMS2, MSH2 and MSH6, were immunopositive, suggesting the MSI-low genotype of mucinous adenocarcinoma of the urethra. BRAF V600E and ALK rearrangements were not detected. During the mean follow-up of 20 months, nine patients either developed distant metastasis or succumbed to the illness. CONCLUSION: Our study, encompassing the most extensive series of 35 cases of primary mucinous adenocarcinoma of the urethra, provides crucial insights into its precise diagnosis, management and potential targeted treatments. We found a greater CDX2, SATB2 and CDH17 sensitivity in these urethral tumours for the first time, to our knowledge. We identified characteristics such as an MSI-low profile, non-V600E BRAF mutations and an absence of ALK rearrangements.

Characterization of urethra closure in female neonatal mice at histological and molecular levels.

In brief: Female hypospadias is a little-known and poorly studied birth defect. This research establishes an anatomical and molecular foundation for future research to investigate the origins of this defect. Abstract: Hypospadias is a congenital anomaly of the external genitalia where the urethra does not properly close. In humans, hypospadias is mostly reported in male newborns, whereas in females hypospadias is rare, although it is generally considered to be under-reported. Improper urethra closure in the female genitalia can cause recurrent genitourinary tract infections and infertility. In mice, female hypospadias was induced by exposure to exogenous estrogenic compounds. Aside from the link between estrogen exposure and female hypospadias, the process of female urethra closure is largely unstudied, with the precise timing of urethra closure and associated molecular mechanisms remaining poorly understood. To address this gap, we determined when urethra closure occurs and identified gene expression patterns during the process of urethra closure in female neonatal mice from postnatal day (PND) 5 to 10. Using whole mount imaging and histology, we discovered that the initiation of urethra closure begins at PND7, and urethra closure is fully completed by PND10. To identify the genes associated with urethra closure, we conducted bulk RNA sequencing on female external genitalia prior to and after urethra closure. Gene ontology analyses revealed an increase in steroidogenic gene expression (Star, Hsd3b6, and Cyp17a1) during urethra closure, suggesting that the female genitalia locally produce steroids which could facilitate steroid signaling within the genitalia. With this study, we establish an anatomical timeline of female urethra closure and hypothesize a paracrine steroid signaling mechanism of urethra closure. These observations provide entry points to aid in further understanding external genital abnormalities, like hypospadias, in females.

Distribution of prostatic markers in glands of the female urethra and anterior vaginal wall-a rapid autopsy study.

BACKGROUND: There are varying reports of immunohistochemically detected prostatic marker protein distribution in glands associated with the female urethra that may be related to tissue integrity at the time of fixation. AIM: In this study we used tissue derived from rapid autopsies of female patients to determine the distribution of glandular structures expressing prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) along the female urethra and in surrounding tissues, including the anterior vaginal wall (AVW). METHODS: Tissue blocks from 7 donors that contained the entire urethra and adjacent AVW were analyzed. These tissue samples were fixed within 4-12 hours of death and divided into 5-mm transverse slices that were paraffin embedded. Sections cut from each slice were immunolabeled for PSA or PSAP and a neighboring section was stained with hematoxylin and eosin. The sections were reviewed by light microscopy and analyzed using QuPath software. OBSERVATIONS: In tissue from all donors, glandular structures expressing PSA and/or PSAP were located within the wall of the urethra and were present along its whole length. RESULTS: In the proximal half of the urethra from all donors, small glands expressing PSAP, but not PSA, were observed adjacent to the and emptying into the lumen. In the distal half of the urethra from 5 of the 7 donors, tubuloacinar structures lined by a glandular epithelium expressed both PSA and PSAP. In addition, columnar cells at the surface of structures with a multilayered transitional epithelium in the distal half of the urethra from all donors expressed PSAP. No glands expressing PSA or PSAP were found in tissues surrounding the urethra, including the AVW. CLINICAL IMPLICATIONS: Greater understanding of the distribution of urethral glands expressing prostatic proteins in female patients is important because these glands are reported to contribute to the female sexual response and to urethral pathology, including urethral cysts, diverticula, and adenocarcinoma. STRENGTHS AND LIMITATIONS: Strengths of the present study include the use of rapid autopsy to minimize protein degradation and autolysis, and the preparation of large tissue sections to demonstrate precise anatomical relations within all the tissues surrounding the urethral lumen. Limitations include the sample size and that all donors had advanced malignancy and had undergone previous therapy which may have had unknown tissue effects. CONCLUSION: Proximal and distal glands expressing prostate-specific proteins were observed in tissue from all donors, and these glands were located only within the wall of the urethra.

High frequency of concomitant squamous metaplasia in bulbar urethral stricture and its association with reconstructive delay and urethral rest.

PURPOSE: To determine the prevalence of concomitant squamous metaplasia (SM), the initial histological change from normal urethra to urethral stricture, in bulbar urethral strictures and to investigate the associated clinical factors. METHODS: A retrospective review was conducted on 165 male patients with bulbar urethral strictures who underwent excision and primary anastomosis (EPA) between 2010 and 2020, for whom complete clinical data and excised urethral specimens were available. An experienced pathologist histologically evaluated concomitant SM in paraffin sections of the proximal end of the excised urethra blinded to the clinical data. Disease duration was calculated as the period from the initial diagnosis of urethral stricture to the date of EPA. The association between concomitant SM and clinical background was investigated. RESULTS: SM was identified in 86 (52.1%) patients. The median disease duration in patients with SM (38 months) was significantly longer than that in patients without SM (9 months, p < 0.0001). In multivariate analysis, the longer disease duration, non-traumatic stricture etiology, and failure to maintain urethral rest with urinary diversion via a suprapubic tube for more than 90 days were independent factors predicting concomitant SM. No significant difference was observed in success rates of EPA between patients with SM (93.2%) and those without SM (97.5%, p = 0.18). CONCLUSIONS: Reconstructive urologists need to be aware that concomitant SM is frequent in patients with bulbar urethral stricture, especially in those with long disease duration and those who were voiding volitionally during the period of urethral rest.

Surgical management of urethral obstruction secondary to perineal liposarcoma in a dog: a case report.

BACKGROUND: Swelling of the perineal region in male dogs is most commonly caused by a perineal hernia. Clinical signs associated with perineal hernia are constipation, tenesmus or stranguria. This case report documents a rare cause of perineal swelling created by the growth of a malignant tumour leading to urethral obstruction and subsequent stranguria. CASE PRESENTATION: An 11-year-old neutered male German Shepherd was presented for swelling in the perineal region and stranguria for three days. Complete blood count and serum biochemistry were unremarkable. Ultrasound revealed a heterogeneous mass in the perineal region. Retrograde urethrography showed a severe narrowing of the urethra caudal to the pelvis. A fine-needle aspirate of the mass was highly suspicious for liposarcoma. Staging was performed by computed tomography (CT) of the thorax and abdomen. Total penile amputation in combination with pubic-ischial pelvic osteotomy, transposition of the remaining urethra through the inguinal canal, V-Y-plasty cranial to the prepuce and preputial urethrostomy were performed to remove the tumour. Histopathology confirmed a well-differentiated liposarcoma with complete histological margins. Six months after the surgery the dog was doing well and there were no signs indicating local tumour recurrence. CONCLUSIONS: Wide surgical excision is generally recommended for soft tissue sarcomas, however this is sometimes not feasible for large tumours. In the case reported here, tumour resection was achieved by a combination of several surgical techniques with a good clinical outcome.

Time-dependent progress of lower urinary tract dysfunction in streptozotocin-induced diabetic rats with or without low-dose insulin treatment.

Objectives: To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Methods: Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra in vivo were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra in vitro were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Results: Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. In-vivo urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. Conclusions: DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.

Carcinoma in situ within the bladder trigone with an isolated metastasis to the prostate without involvement of prostatic urethra: a unique case report.

BACKGROUND: Carcinoma in situ of the bladder is a high-grade cancer that originates in the superficial layer of the bladder. It has the potential to invade nearby organs, and it can spread through blood and lymphatic circulation to distant parts of the body. CASE PRESENTATION: A 58-year-old non-smoker male presented with gross and microscopic hematuria. His family history included his father's recent bladder cancer. Initial investigations showed hematuria, inflammation, negative urine culture, digital rectal examination revealed an enlarged right lobe of the prostate, and an elevated Prostate-Specific Antigen level. Histopathological examination of samples taken from the bladder mucosa and the prostate confirmed urothelial carcinoma in situ in the bladder and prostate. Further evaluation revealed no other metastasis. The tumor was classified as T4aN0M0. The patient underwent radical cystoprostatectomy and histopathological examination showed that the tumor invading the muscularis propria of the bladder as well as the prostatic glands, but no malignancy was found in prostatic urethra and other areas. The patient was discharged three weeks post-operation and completed on adjuvant chemotherapy consisting of Gemcitabine, and Cisplatin to prevent of relapse. The patient is currently in a good healthy. CONCLUSION: The occurrence of bladder cancer metastasizing to the prostate without involving the prostatic urethra is uncommon and requires precise diagnostic techniques for accurate tumor classification. Early management is advised to enhance the prognosis for the patient.

Female Urethral Cavernous Hemangioma: Introducing Treatment and Follow-Up Course of Three Cases.

Cavernous hemangioma is a benign vascular tumor occurring in all parts of the urinary system, including the kidney, bladder, prostate, ureter, and rarely urethra. Urethral cavernous hemangiomas are mostly seen in male patients, and only a few cases of female urethral hemangiomas are reported. Herein, we present the management and follow-up course of 3 cases of female urethral cavernous hemangioma. All 3 cases were menopause women complaining of lower urinary tract symptoms. Definitive diagnosis is made by histopathologic evaluation. In case of large or pedunculated masses, initial surgical resection is highly recommended. Regular follow-up of patients in order to prevent any recurrence is suggested.

[The application of full-length urethral preservation without anastomosis in single-port laparoscopic radical prostate cancer].

Objective: To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP). Method: This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control. Result: All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 µg/L. Conclusions: The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.

Utility of Magnetic Resonance Imaging for Localizing Prostate Cancer Near the Urethra in Men Who Are Candidates for Focal Gland Ablation.

PURPOSE: Given that treatment near the urethra is often limited to reduce side effects, in this study we aim to determine whether prostate MRI can accurately identify the distance of prostate cancer to the urethra in a cohort of men who were potential candidates for focal gland ablation. MATERIALS AND METHODS: A single-institution analysis was performed of men who underwent MRI, targeted biopsy, and radical prostatectomy from July 2012 to April 2021. Men who were candidates for focal gland ablation were identified. The ability of MRI to identify prostate cancer within 5 mm of the prostatic urethra as confirmed on whole-mount pathology was assessed. Multivariate regression was utilized to determine characteristics associated with prostate cancer within 5 mm of the urethra on whole-mount pathology. RESULTS: In 48 out of 67 men (72%), the tumor was within 5 mm of the urethra on whole-mount pathology. MRI was concordant with whole-mount pathology in 49 out of 67 men (73%). The sensitivity of MRI for identifying cancer within 5 mm of the urethra was 77% (65%-89%) and the specificity was 63% (42%-89%). The positive predictive value was 84% (range 73%-95%) and negative predictive value was 52% (32%-73%). In adjusted analysis, PSA density and Prostate Imaging-Reporting and Data System were not significantly associated with having prostate cancer within close proximity of the urethra. CONCLUSIONS: A significant number of men who are potential candidates for focal gland ablation have cancer within close proximity to the urethra that could serve as a significant source of in-field recurrence. The sensitivity of MRI for identifying these lesions is 77% and can be used to further improve patient selection for focal gland ablation.

High-grade and low-grade HPV-induced urethral lesions treated by CO2 laser under colposcopy.

OBJECTIVES: This study is reporting the CO2 laser treatment efficiency on urethral lesions caused by human papillomavirus (HPV) and the correlation between the type of lesion high-grade and low-grade on the histology and the HPV genotype(s). METHODS: Sixty-nine patients (59 men and 10 women) with urethral lesions were screened for HPV genotype(s) by in situ hybridisation and PCR. HPV lesions were biopsied and p16INK4a expression was tested to confirm urethral high-grade squamous intraepithelial lesions (U HSIL) on the histology prior to CO2 laser treatment under colposcopy. The patients were followed up for 12 months. RESULTS: We observed urethral low-grade squamous intraepithelial lesions (U LSIL) in 54/69 cases (78.3%) and U HSIL in 7/69 cases (10%) confirmed by p16INK4a staining. Then we looked at the HPV genotype present in each lesion. We observed the following: 31/69 (45%) patients have a unique HPV genotype, with 12/31 (38.7%) of high risk; 21/54 (38.8%) of U LSIL and 1/7 (14%) of U HSIL have HPV low-risk and high-risk coinfections. Efficient treatment with CO2 laser under colposcopy was done using a meatal spreader to help visualisation of 20 mm in the distal urethra. We cured 64/69 (92.7%) patients at 3 months with 4/69 (5.7%) meatotomy and persistent 1/67 (1.4%) urethral stricture at 12 months. CONCLUSIONS: HSIL was present in the urethra without being able to define specific clinical criteria. Treatment with a CO2 laser under colposcopy with a meatus spreader is a simple surgical procedure with high efficiency and few complications that could prevent the risk of HPV-induced carcinoma.

Robot-assisted laparoscopic anterior urethral diverticulectomy.

INTRODUCTION AND HYPOTHESIS: A 31-year-old patient with a history of fetal sacrococcygeal teratoma requiring tumor resection and pelvic reconstruction in infancy presented with a 3-year history of recurrent vulvar abscesses and voiding dysfunction. Magnetic resonance imaging demonstrated a fluid collection posterior to the pubic bone and inferior to the bladder. The objective was to demonstrate the key steps in the resection and repair of an anterior urethral diverticulum via robot-assisted laparoscopic approach. METHODS: Cystoscopy followed by robot-assisted laparoscopic retropubic dissection was used for resection of an anterior urethral diverticulum followed by urethral reconstruction. RESULTS: Cystoscopy revealed a large anterior cavity at the midpoint of the urethra consistent with an anterior urethral diverticulum. This likely tracked inferiorly toward her vulva during repeated episodes of infection expressing through her recurrent abscesses. Retropubic space exploration revealed dense fibrotic tissue adherent to the underside of the pubic tubercule contiguous with the anterior urethral diverticulum, which was successfully resected. CONCLUSIONS: Female anterior urethral diverticulum is a rare entity. A robot-assisted laparoscopic approach can be safely utilized to identify and resect an anterior urethral diverticulum. Key points include optimization of port placement, use of a council-tip catheter to facilitate bladder drainage in the setting of distorted pelvic anatomy, and multi-layered tension-free urethral closure with flap placement.

Comparison of oral morbidity and mid-term efficacy of anterior urethroplasty using an autologous tissue-engineered graft (MukoCell®) versus native oral mucosa graft.

OBJECTIVE: Our study aimed to compare surgical success rate (SR) and oral morbidity of augmentation urethroplasty for anterior urethral strictures using autologous tissue-engineered oral mucosa graft (TEOMG) named MukoCell® versus native oral mucosa graft (NOMG). METHODS: We conducted a single-institution observational study on patients undergoing TEOMG and NOMG urethroplasty for anterior urethral strictures >2 cm in length from January 2016 to July 2020. SR, oral morbidity, and potential risk factors of recurrence were compared between groups were analyzed. A decrease of maximum uroflow rate < 15 mL/s or further instrumentation was considered a failure. RESULTS: Overall, TEOMG (n = 77) and NOMG (n = 76) groups had comparable SR (68.8% vs. 78.9%, p = 0.155) after a median follow-up of 52 (interquartile range [IQR] 45-60) months for TEOMG and 53.5 (IQR 43-58) months for NOMG. Subgroup analysis revealed comparable SR according to surgical technique, stricture localization, and length. Only following repetitive urethral dilatations, TEOMG achieved lower SR (31.3% vs. 81.3%, p = 0.003). Surgical time was significantly shorter by TEOMG use (median 104 vs. 182 min, p < 0.001). Oral morbidity and the associated "burden" in patients' quality of life were significantly less at 3 weeks following the biopsy required for TEOMG manufacture, compared to NOMG harvesting and totally absent at 6 and 12 months postoperatively. CONCLUSIONS: The SR of TEOMG urethroplasty appeared to be comparable to NOMG at a mid-term follow-up but taking into account the uneven distribution of stricture site and the surgical techniques used in both groups. Surgical time was significantly shortened, since no intraoperative mucosa harvesting was required, and oral complications were diminished through the preoperative biopsy for MukoCell® manufacture.

Brain-Derived Neurotrophic Factor Is Indispensable to Continence Recovery after a Dual Nerve and Muscle Childbirth Injury Model.

In women, stress urinary incontinence (SUI), leakage of urine from increased abdominal pressure, is correlated with pudendal nerve (PN) injury during childbirth. Expression of brain-derived neurotrophic factor (BDNF) is dysregulated in a dual nerve and muscle injury model of childbirth. We aimed to use tyrosine kinase B (TrkB), the receptor of BDNF, to bind free BDNF and inhibit spontaneous regeneration in a rat model of SUI. We hypothesized that BDNF is essential for functional recovery from the dual nerve and muscle injuries that can lead to SUI. Female Sprague-Dawley rats underwent PN crush (PNC) and vaginal distension (VD) and were implanted with osmotic pumps containing saline (Injury) or TrkB (Injury + TrkB). Sham Injury rats received sham PNC + VD. Six weeks after injury, animals underwent leak-point-pressure (LPP) testing with simultaneous external urethral sphincter (EUS) electromyography recording. The urethra was dissected for histology and immunofluorescence. LPP after injury and TrkB was significantly decreased compared to Injury rats. TrkB treatment inhibited reinnervation of neuromuscular junctions in the EUS and promoted atrophy of the EUS. These results demonstrate that BDNF is essential to neuroregeneration and reinnervation of the EUS. Treatments aimed at increasing BDNF periurethrally could promote neuroregeneration to treat SUI.

Is colorectal mucosa a reasonable graft alternative to buccal grafts for urethroplasty?: A comparison of graft histology and stretch.

OBJECTIVE: To compare the histological properties and stretch of colorectal mucosal grafts (CMG) and buccal mucosal grafts (BMG) and to evaluate the impact of age, medical comorbidity and tobacco use on these metrics. MATERIALS AND METHODS: Samples of BMGs from patients undergoing augmentation urethroplasty were sent for pathologic review. CMGs were collected from patients undergoing elective colectomy. CMGs were harvested fresh, at full thickness from normal rectum/sigmoid. Patients with inflammatory bowel disease, prior radiation, or chemotherapy were excluded. RESULTS: Seventy two BMGs and 53 CMGs were reviewed. While BMGs and CMGs were both histologically composed of mucosal (epithelium + lamina propria) and submucosal layers, the mucosal layer in CMG had crypts. The outer epithelial layers differed significantly in mean thickness (BMG 573µm vs. CMG 430µm, p=0.0001). Mean lamina propria thickness and submucosal layer thickness also differed significantly (BMG 135µm vs. CMG 400µm, p<0.0001; BMG 1090µm vs. CMG 808µm, p = 0.007, respectively). Mean delta stretch, as to length and width, was greater for CMG (118% x 72%) compared to BMGs (22% x 8%), both p<0.001. CONCLUSION: CMGs and BMGs significantly differ histologically in layer composition, width and architecture, as well as graft stretch. Given its elastic properties, CMG may be useful in covering large surface areas, but its thin epithelium, thick lamina propria and additional muscularis mucosal layer could impact graft take and contracture.

Robotic approach to vesicourethral anastomotic stenosis and resection of remaining prostate after radical prostatectomy.

OBJECTIVE: To show a total transabdominal robotic approach to an extensive recalcitrant vesicourethral anastomotic stenosis (VUAS) after open radical prostatectomy (ORP) with end-to-end anastomosis. While there is very little literature on the matter and even fewer videos showing the actual surgical view with a step-by-step explanation in complex cases, VUAS robotic transabdominal surgery provides better view and reach, with potentially better continence results, without the need for pubectomy. METHODS: A 72-year-old male was submitted to a failed ORP for Gleason 3+4 localized cancer 2 years before, where the wrong plane of dissection left behind prostate remnants and the seminal vesicles, which evolved with a complex stenosis and recurrent episodes of acute urinary retention (AUR) that started two weeks after the first catheter removal. Five endoscopic procedures in total were unsuccessful and AUR reoccurred. A vesico-urethral cystography (VUC) and multiparametric prostate and urethral MRI found the seminal vesicles with prostate remnants, two centimeters urethral stenosis from bladder neck to bulbar urethra and periurethral fibrosis with no evidence of residual tumor. PSA was 1.2 and prostate biopsy showed no tumor on prostate remnant. A transabdominal robotic approach was chosen. RESULTS: Prostate residue, bladder neck and periurethral fibrosis were excised, with healthy mucosa found on both ends. End-to-end anastomosis was successful. Drain and catheter were removed on the 1st and 14th post-operative day, respectively, with good urinary stream. A VUC at 30 days showed a patent bladder neck. Incontinence was 3 pads/day after catheter removal and decreased to 1 pad/day after 180 days. CONCLUSION: VUAS may reach 15% (1, 2) and endourologic therapies are first-line choices, however, recalcitrant cases require reconstruction (3-6). The most common approach is perineal, with high incontinence rates, reaching >90% (7, 8). The retropubic alternative has better but also discouraging numbers of up to 58% incontinence rates (9). Though with 100% social continence results, the 2021 European guidelines still could not recommend the robotic procedure as standard of care due to evidence limited to anecdotal reports (10-12).

[Primary melanoma of female urethra: A case diagnosed in Ouagadougou]. / Mélanome primitif de l'urètre féminin : à propos d'un cas diagnostiqué à Ouagadougou.

We report a case of primary melanoma of a female urethra diagnosed at a non-metastatic stage in a 48-year-old patient with a history of breast carcinoma treated with radiotherapy and hormone therapy. The patient was consulting for dysuria, hematuria, and perineal pain. The clinical examination found a prolapsed and black mass, developed at the expense of the urethra and located at the anterosuperior part of the vulva. The mass biopsy revealed a proliferation of fusiform and globular cells loaded with black pigment expressing the anti-HMB 45 and PS 100 antibodies. The extension assessment showed an absence of secondary localization. The patient underwent total cystourethrectomy without inguinal lymphadenectomy. There was no recurrence observed on day 100 following the surgery.

Urethrectomy at the time of radical cystectomy for non-metastatic urothelial carcinoma of the bladder: a collaborative multicenter study.

INTRODUCTION: The optimal management of the urethra in patients planned for radical cystectomy (RC) remains unclear. We sought to evaluate the impact of urethrectomy on perioperative and oncological outcomes in patients treated with RC for non-metastatic urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: We assessed the retrospective data from patients treated with RC for UCB of five European University Hospitals. Associations of urethrectomy with progression-free (PFS), cancer-free (CSS), and overall (OS) survivals were assessed in univariable and multivariable Cox regression models. We performed a subgroup analysis in patients at high risk for urethral recurrence (UR) (urethral invasion and/or bladder neck invasion and/or multifocality and/or prostatic urethra involvement). RESULTS: A total of 887 non-metastatic UCB patients were included. Among them, 146 patients underwent urethrectomy at the time of RC. Urethrectomy was performed more often in patients with urethral invasion, T3/4 tumor stage, CIS, positive frozen section analysis of the urethra, and those who received neoadjuvant chemotherapy, underwent robotic RC, and/or received an ileal conduit urinary diversion (all p < 0.001). Estimated blood loss and the postoperative complication rate were comparable between patients who received an urethrectomy and those who did not. Urethrectomy during RC was not associated with PFS (HR 0.83, p = 0.17), CSS (HR 0.93, p = 0.67), or OS (HR 1.08, p = 0.58). In the subgroup of 276 patients at high risk for UR, urethrectomy at the time of RC decreased the risk of progression (HR 0.58, p = 0.04). CONCLUSION: In our study, urethrectomy at the time of RC seems to benefit only patients at high risk for UR. Adequate risk assessment of UCB patients' history may allow for better clinical decision-making and patient counseling.

Intermittent urethral infusion of dimethylsulfoxide for urethral amyloidosis: a case report and literature review.

Urethral amyloidosis (UA) is a very rare condition. We here report the case of a 63-year-old male patient who was admitted to our outpatient department due to aggravating dysuria, frequent urination, pain during intercourse, and a gradually enlarging mass at the ostium of his urethra, which he first notice one year earlier. Pathological tissue biopsy of urethral ostium mass confirmed UA. Intermittent urethra infusion of dimethyl sulfoxide was performed and the treatment effect is satisfactory.