Intermediate-term oncological and functional outcomes of salvage cryotherapy for the management of prostate cancer recurrence after primary brachytherapy versus primary cryotherapy: A propensity score-matched analysis.

BACKGROUND: Salvage cryotherapy (SCT) is widely used to treat prostate cancer (PCa) recurrence after radiotherapy (RT). We studied the intermediate oncological and functional outcomes of patients who underwent SCT following cryotherapy (CRYO-SCT) recurrence and compare it to recurrence after brachytherapy (BT-SCT). METHODS: An IRB-approved retrospective cohort study utilizing patient data from the Cryo On-Line Data Registry and the Duke PCa database between 1992 and 2016. Biochemical recurrence (BCR) using Phoenix criteria was the primary endpoint assessed at 2- and 5-years post-SCT. Secondary endpoints assessed functional outcomes including urinary continence, erectile function, and recto-urethral fistula. Association between treatment and biochemical progression-free survival was assessed using inverse probability weighted (IPTW) Cox proportional hazards regression. The differences in the secondary functional outcomes were assessed by Pearson's χ2 test or Fisher's exact test, corrected for IPTW. RESULTS: A total of 194 patients met inclusion criteria. The BCR rate for BT-SCT and CRYO-SCT was 23 (20.4%) and 17 (21%) at 2 years and 30 (26.5%) and 22 (27.2%) at 5 years according to Phoenix criteria. There was no statistical difference in 2 years (hazard ratio [HR] 0.9; 95% confidence interval [CI], 0.5-1.7, p = 0.7) or 5-year BCR (HR: 0.86; 95% CI, 0.5-1.5, p = 0.6) between the groups. The functional outcomes like urinary continence (p = 0.4), erectile function (p = 0.1), and recto-urethral fistula (p = 0.3) were not statistically different. CONCLUSION: CRYO-SCT appears to be well tolerated, with comparable oncological and functional outcomes to patients failing primary BT. The findings also demonstrated that SCT can render a significant number of patients biochemically free of disease after initial CRYO with minimal morbidity. SCT is a viable treatment option to salvage local PCa recurrence following either BT or cryoablation failure.

RE Re Do urethroplasty after multiple failed surgeries of pelvic fracture urethral injury.

INTRODUCTION: We quantify surgical success rate in the management of pelvic fracture urethral injury (PFUI) with repeat urethroplasty in the setting of two or more failed prior urethroplasties. MATERIALS AND MATERIALS: A retrospective analysis was completed of a single surgeon urethroplasty database from Jan 1, 2012 to June 31, 2018. Patients with a history of PFUI recurrent urethral stricture despite two or more failed prior urethroplasty procedures were included. RESULTS: We identified 87 patients that had two more more failed prior urethroplasties. These had 2 main categories. One requiring anastomotic urethroplasty and other requiring substitution urethroplasty. Total success rate was 74.75% for anastomotic group and 84.61% for substitution group with a median follow-up of 34 months (range 6-60). Overall success rate for re redo Urethroplasty was 82.70%. Bulbar urethral ischemic necrosis was identified in 14 of 64 patients (21.9%). In these cases urethral substitution measures were performed including 12 with preputial flap and tubularization, 1 sigmoid colon substitution, medial thigh flap. No significant difference was observed between the success or failure group with respect to age, BMI, stricture length, number of prior urethroplasty procedure or endoscopic procedures or comorbidities. CONCLUSIONS: Our findings demonstrate that high success rates can be achieved for repeat urethroplasty in recurrent PFUI urethral stricture after two or more failed prior urethroplasty procedures. Bulbar urethral ischemic necrosis is a common finding in this patient population. Patients should be managed at a tertiary high volume referral center.

Cholecalciferol for the prophylaxis against recurrent urinary tract infection among patients with benign prostatic hyperplasia: a randomized, comparative study.

PURPOSE: To explore the role of cholecalciferol for the prophylaxis against recurrent urinary tract infection (UTI) in patients with benign prostatic hyperplasia (BPH). METHODS: Our randomized, uncontrolled prospective study included 389 naïve BPH patients with moderate/severe symptoms, consecutively. The patients were randomly allocated to two groups; group-A included 193 patients who received tamsulosin, while group-B included another 196 patients who received tamsulosin with cholecalciferol. The study population was followed up for 2 years after the start of the treatment. For all the patients enrolled, clinical evaluation, imaging studies (abdominal and trans-rectal ultrasonography), and laboratory investigations [including urinalysis, urine culture with antibiotic susceptibility testing for positive cultures and estimation of prostate-specific antigen (PSA) level] were provided. RESULTS: The incidence rate of recurrent UTI was 9% among the study population; it was significantly higher among group-A patients compared to those of group-B (13.5% vs. 4.6%, p 0.003, OR 2.7, 95% CI 1.5-4.3). Compared to patients of group-A, those of group-B developed a significantly lower level of PSA at the end of treatment period (0.16 ± 0.03 ng/mL vs. 0.27 ± 0.08 ng/mL, p 0.043, OR 1.9, 95% CI 1.2-6.8). CONCLUSIONS: Adjuvant cholecalciferol supplementation may be protective against recurrent UTI among patients with BPH receiving tamsulosin therapy without extra adverse effects.

Considerations of germline testing in prostate cancer screening.

Prostate cancer screening remains controversial in the medical field. While screening men above 50 years can impose overdiagnosis and overtreatment, targeted screening of males with pathologic variants of genetic mutations is evolving and viewed as sensible. Identifying such patients requires genetic testing in males having family history of prostate cancer or certain ethnicity. Such strategies will likely occur as routine practice once favorable results of ongoing studies assessing genetic predisposition are released.

Tissue engineering of urinary bladder and urethra: advances from bench to patients.

Urinary tract is subjected to many varieties of pathologies since birth including congenital anomalies, trauma, inflammatory lesions, and malignancy. These diseases necessitate the replacement of involved organs and tissues. Shortage of organ donation, problems of immunosuppression, and complications associated with the use of nonnative tissues have urged clinicians and scientists to investigate new therapies, namely, tissue engineering. Tissue engineering follows principles of cell transplantation, materials science, and engineering. Epithelial and muscle cells can be harvested and used for reconstruction of the engineered grafts. These cells must be delivered in a well-organized and differentiated condition because water-seal epithelium and well-oriented muscle layer are needed for proper function of the substitute tissues. Synthetic or natural scaffolds have been used for engineering lower urinary tract. Harnessing autologous cells to produce their own matrix and form scaffolds is a new strategy for engineering bladder and urethra. This self-assembly technique avoids the biosafety and immunological reactions related to the use of biodegradable scaffolds. Autologous equivalents have already been produced for pigs (bladder) and human (urethra and bladder). The purpose of this paper is to present a review for the existing methods of engineering bladder and urethra and to point toward perspectives for their replacement.

Salvage Cryoablation for Recurrent Prostate Cancer Following Primary External Beam Radiotherapy or Primary Cryotherapy: A Propensity Score Matched Analysis of Mid-term Oncologic and Functional Outcomes.

INTRODUCTION: Local prostate cancer recurrence following radiotherapy (XRT) or cryoablation (CRYO) may be addressed with salvage cryotherapy (SCT), although little is known about how the primary treatment modality affects SCT results. Oncologic and functional outcomes of patients who underwent SCT after primary XRT (XRT-SCT) or cryoablation (CRYO-SCT) were studied. METHODS: Data was collected using the Duke Prostate Cancer database and the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression-free survival (BPFS).  Urinary incontinence, rectourethral fistula, and erectile dysfunction were secondary outcomes. The Kaplan-Meier log-rank test and univariable/multivariable Cox proportional hazards (CPH) models were utilized to evaluate BPFS between groups. RESULTS: 419 XRT-SCT and 63 CRYO-SCT patients met inclusion criteria, that was reduced to 63 patients in each cohort after propensity matching. There was no difference in BPFS at 2 and 5 years both before (P = .5 and P = .7) and after matching (P = .6 and P = .3). On multivariable CPH, BPFS was comparable between treatment groups (CRYO-SCT, HR=1.1, [0.2-2.2]).  On the same analysis, BPFS was lower in D'Amico high-risk (HR 3.2, P < .01) and intermediate-risk (HR 1.95, P < .05) categories compared to low-risk. There was no significant difference in functional outcomes between cohorts. CONCLUSION: Following primary cryotherapy, salvage cryoablation provides comparable intermediate oncological outcomes and functional outcomes compared to primary radiotherapy.

Scaffoldless tissue engineering of stem cell derived cavernous tissue for treatment of erectile function.

INTRODUCTION: As one-third of erectile dysfunction (ED) patients do not respond to phosphodiesterase-5 inhibitors, there is great demand for new therapeutic options. Adipose tissue-derived stem cells (ADSCs) represent an ideal source for new ED treatment. AIM: To test if ADSCs can be differentiated into smooth muscle cells (SMCs) and endothelial cells (ECs), if these differentiated cells can be used to engineer cavernous tissue, and if this engineered tissue will remain for long time after implantation and integrate into corporal tissue. METHOD: Rat ADSCs were isolated and differentiated into SMC and ECs. The differentiated cells were labeled with 5-ethynyl-2-deoxyuridine (EdU) and used to construct cavernous tissue. This engineered tissue was implanted in penises of normal rats. The rats were sacrificed after 1 and 2 months; penis and bone marrow were collected to assess cell survival and inclusion in the penile tissues. MAIN OUTCOME MEASURES: The phenotype conversion was checked using morphology, immunocytochemistry (immunohistochemistry [IHC]), and Western blot for SMC and EC markers. The cavernous tissue formation was assessed using rat EC antibody (RECA), calponin, and collagen. The implanted cell survival and incorporation into penis were evaluated with hematoxylin and eosin, Masson's trichrome, and IHC (RECA, calponin, and EdU). RESULTS: The phenotype conversion was confirmed with positive staining for SMC and EC markers and Western blot. The formed tissue exhibited architecture comparable to penile cavernous tissue with SMC and ECs and extracellular matrix formation. The implanted cells survived in significant numbers in the penis after 1 and 2 months. They showed proof of SMC and EC differentiation and incorporation into penile tissue. CONCLUSIONS: The results showed the ability of ADSCs to differentiate into SMC and ECs and form cavernous tissue. The implanted tissue can survive and integrate into the penile tissues. The cavernous tissue made of ADSCs forms new technology for improvement of in vivo stem cell survival and ED treatment.

Evaluation and treatment of erectile dysfunction in the aging male: a mini-review.

Before the 20th century, individuals often did not live beyond the reproductive years, and sexuality of the elderly was not an issue. However, in the current era it is known that as life expectancy improves, both men and women are seeking to preserve their sexuality into old age. While the appreciation of sexuality persists with aging, a decline in sexual activity is typically seen with, and can be attributed to both general health problems as well as specific sexual dysfunctions. Erectile dysfunction is the most frequently diagnosed sexual dysfunction in the older male population. This mini-review provides an overview of contemporary literature concerning epidemiology, pathophysiology, assessment and treatment of erectile dysfunction in the aging male.

Red Blood Cell Distribution Width Is Associated with All-cause Mortality but Not Adverse Cancer-specific Outcomes in Men with Clinically Localized Prostate Cancer Treated with Radical Prostatectomy: Findings Based on a Multicenter Shared Equal Access Regional Cancer Hospital Registry.

BACKGROUND: Recent reports with a small number of patients showed an association of red blood cell distribution width (RDW) with prostate cancer (PCa) progression. OBJECTIVE: To investigate whether preoperative RDW can serve as a prognostic marker in patients with PCa undergoing radical prostatectomy (RP) in a large, equal access, and diverse patient cohort. DESIGN SETTING AND PARTICIPANTS: Data were retrospectively collected on 4756 men treated with RP at eight Veteran Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 1999 through 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical recurrence (BCR) was the primary outcome, while metastasis, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) were secondary outcomes. RESULTS AND LIMITATIONS: The mean (standard deviation) age was 62 yr (6.1), and 1589 (33%) men were black. The median (interquartile range) follow-up was 82 mo (46-127). Preoperative RDW either as a continuous variable or when stratified by quartiles was not associated with BCR. Likewise, preoperative RDW was not associated with metastases or PCSM. However, higher RDW was significantly associated with higher ACM, both as a continuous variable (p < 0.001) and when stratified by quartiles in univariable and multivariable models (p < 0.001). RDW was found to be correlated with D'Amico risk classification of PCa. Study limitations include its retrospective nature and lack of data regarding advanced PCa. CONCLUSIONS: Preoperative RDW was not associated with PCa outcomes in men treated with RP but was associated with ACM. While RDW may be a biomarker of overall health, it is not a biomarker for PCa outcomes. These results emphasize the importance of diverse, larger sized studies in genitourinary cancer research. PATIENT SUMMARY: Prostate cancer includes a wide spectrum of diseases with different genetic, pathological, and oncological behaviors. Red blood cell distribution width is helpful in predicting the overall survival for a localized prostate cancer patient, and hence, it can help inform personalized treatment decisions and operative care.

Molecular biomarkers in the context of focal therapy for prostate cancer: recommendations of a Delphi Consensus from the Focal Therapy Society.

BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.

Evaluation of Bi-Layer Silk Fibroin Grafts for Penile Tunica Albuginea Repair in a Rabbit Corporoplasty Model.

The use of autologous tissue grafts for tunica albuginea repair in Peyronie's disease and congenital chordee is often restricted by limited tissue availability and donor site morbidity, therefore new biomaterial options are needed. In this study, bi-layer silk fibroin (BLSF) scaffolds were investigated to support functional tissue regeneration of tunica albuginea in a rabbit corporoplasty model. Eighteen adult male, New Zealand white rabbits were randomized to nonsurgical controls (NSC, N = 3), or subjected to corporoplasty with BLSF grafts (N = 5); decellularized small intestinal submucosa (SIS) matrices (N = 5); or autologous tunica vaginalis (TV) flaps (N = 5). End-point evaluations were cavernosography, cavernosometry, histological, immunohistochemical, and histomorphometric assessments. Maximum intracorporal pressures (ICP) following papaverine-induced erection were similar between all groups. Eighty percent of rabbits repaired with BLSF scaffolds or TV flaps achieved full rigid erections, compared to 40% of SIS reconstructed animals. Five-minute peak erections were maintained in 60% of BLSF rabbits, compared to 20% of SIS and TV flap reconstructed rabbits. Graft perforation occurred in 60% of TV group at maximum ICP compared to 20% of BLSF cohort. Neotissues supported by SIS and BLSF scaffolds were composed of collagen type I and elastin fibers similar to NSC. SIS and TV flaps showed significantly elevated levels of corporal fibrosis relative to NSC with a corresponding decrease in corporal smooth muscle cells expressing contractile proteins. BLSF biomaterials represent emerging platforms for corporoplasty and produce superior functional and histological outcomes in comparison to TV flaps and SIS matrices for tunica albuginea repair.

Evaluation of Bi-Layer Silk Fibroin Grafts for Tubular Ureteroplasty in a Porcine Defect Model.

Ureteral reconstruction with autologous tissue grafts is often limited by tissue availability and donor site morbidity. This study investigates the performance of acellular, bi-layer silk fibroin (BLSF) scaffolds in a porcine model of ureteroplasty. Tubular ureteroplasty with BLSF grafts in combination with transient stenting for 8 weeks was performed in adult female, Yucatan, mini-swine (N = 5). Animals were maintained for 12 weeks post-op with imaging of neoconduits using ultrasonography and retrograde ureteropyelography carried out at 2 and 4 weeks intervals. End-point analyses of ureteral neotissues and unoperated controls included histological, immunohistochemical (IHC), histomorphometric evaluations as well as ex vivo functional assessments of contraction/relaxation. All animals survived until scheduled euthanasia and displayed mild hydronephrosis (Grades 1-2) in reconstructed collecting systems during the 8 weeks stenting period with one animal presenting with a persistent subcutaneous fistula at 2 weeks post-op. By 12 weeks of scaffold implantation, unstented neoconduits led to severe hydronephrosis (Grade 4) and stricture formation in the interior of graft sites in 80% of swine. Bulk scaffold extrusion into the distal ureter was also apparent in 60% of swine contributing to ureteral obstruction. However, histological and IHC analyses revealed the formation of innervated, vascularized neotissues with a-smooth muscle actin+ and SM22α+ smooth muscle bundles as well as uroplakin 3A+ and pan-cytokeratin + urothelium. Ex vivo contractility and relaxation responses of neotissues were similar to unoperated control segments. BLSF biomaterials represent emerging platforms for tubular ureteroplasty, however further optimization is needed to improve in vivo degradation kinetics and mitigate stricture formation.

Immunocompetent Human 3D Organ-Specific Hormone-Responding Vaginal Mucosa Model of HIV-1 Infection.

The lack of appropriate experimental models often limits our ability to investigate the establishment of infections in specific tissues. To reproduce the structural and spatial organization of vaginal mucosae to study human immunodeficiency virus type-1 (HIV-1) infection, we used the self-assembly technique to bioengineer tridimensional vaginal mucosae using human cells extracted from HIV-1-negative healthy pre- and postmenopausal donors. We produced a stroma, free of exogenous material, that can be adapted to generate near-to-native vaginal tissue with the best complexity obtained with seeded epithelial cells on the organ-specific stroma. The autologous engineered tissues had mechanical properties close to native mucosa and shared similar glycogen production, which declined in reconstructed tissues of the postmenopausal donor. The in vitro-engineered tissues were also rendered immune competent by adding human monocyte-derived macrophages (MDMs) on the epithelium or in the stroma layers. The model was infected with HIV-1, and viral replication and transcytosis were observed when immunocompetent reconstructed vaginal mucosa tissue has incorporated MDMs into the stroma and infected with free HIV-1 green fluorescent protein (GFP) viral particles. These data illustrate a natural permissiveness of immunocompetent untransformed human vaginal mucosae to HIV-1 infection. This model offers a physiological tool to explore viral load, HIV-1 transmission in an environment that may contribute to the virus propagation, and new antiviral treatments in vitro. Impact statement This study introduces an innovative immunocompetent three-dimensional human organ-specific vaginal mucosa free of exogenous material for in vitro modeling of human immunodeficiency virus type-1 (HIV-1) infection. The proposed model is histologically close to native tissue, especially by presenting glycogen accumulation in the epithelium's superficial cells, responsive to estrogen, and able to sustain a monocyte-derived macrophage population infected or not by HIV-1 during ∼2 months.

Management of complex and redo cases of pelvic fracture urethral injuries.

OBJECTIVES: Pelvic fracture urethral injuries (PFUI) result from traumatic disruption of the urethra. A significant proportion of cases are complex rendering their management challenging. We described management strategies for eight different complex PFUI scenarios. METHODS: Our centre is a tertiary referral centre for complex PFUI cases. We maintain a prospective database (1995-2016), which we retrospectively analysed. All patients with PFUI managed at our institute were included. RESULTS: Over two decades 1062 cases of PFUI were managed at our institute (521 primary and 541 redo cases). Most redo cases were referred to us from other centres. Redo cases had up to five prior attempts at urethroplasty. We managed complex cases, which included bulbar ischemia, young boys and girls with PFUI, PFUI with double block, concomitant PFUI and iatrogenic anterior urethral strictures. Bulbar ischemia merits substitution urethroplasty, most commonly, using pedicled preputial tube. PFUI in young girls is usually associated with urethrovaginal fistula. Young boys with PFUI commonly have a long gap necessitating trans-abdominal approach. Our success rate with individualised management is 85.60% in primary cases, 79.13% in redo cases and 82.40% in cases of bulbar ischemia. CONCLUSION: The definition of complex PFUI is ever expanding. The best chance of success is at the first attempt. Anastomotic urethroplasty for PFUI should be performed in experienced hands at high volume centres.

Novel three-dimensional autologous tissue-engineered vaginal tissues using the self-assembly technique.

Many diseases necessitate the substitution of vaginal tissues. Current replacement therapies are associated with many complications. In this study, we aimed to create bioengineered neovaginas with the self-assembly technique using autologous vaginal epithelial (VE) and vaginal stromal (VS) cells without the use of exogenous materials and to document the survival and incorporation of these grafts into the tissues of nude female mice. Epithelial and stromal cells were isolated from vaginal biopsies. Stromal cells were driven to form collagen sheets, 3 of which were superimposed to form vaginal stromas. VE cells were seeded on top of these stromas and allowed to mature in an air-liquid interface. The vaginal equivalents were implanted subcutaneously in female nude mice, which were sacrificed after 1 and 2 weeks after surgery. The in vitro and animal-retrieved equivalents were assessed using histologic, functional, and mechanical evaluations. Vaginal equivalents could be handled easily. VE cells formed a well-differentiated epithelial layer with a continuous basement membrane. The equivalent matrix was composed of collagen I and III and elastin. The epithelium, basement membrane, and stroma were comparable to those of native vaginal tissues. The implanted equivalents formed mature vaginal epithelium and matrix that were integrated into the mice tissues. Using the self-assembly technique, in vitro vaginal tissues were created with many functional and biological similarities to native vagina without any foreign material. They formed functional vaginal tissues after in vivo animal implantation. It is appropriate for vaginal substitution and disease modeling for infectious studies, vaginal applicants, and drug testing.

A novel method in decision making for the diagnosis of anterior urethral stricture: using methylene blue dye.

OBJECTIVE: The use of methylene blue dye (MB) to highlight anatomical structures in urology has been well-established. Urethral stricture may extend about a centimeter beyond the abnormal area seen on urethrogram. Although the current literature suggests a tension-free and end- to- end anastomosis after excision of the strictured urethral segment with spongiofibrosis and surrounding corpus spongiosum in short bulbar strictures, some centers dealing with urethroplasty prefer anastomosis for short bulbar strictures while others prefer augmentation. With this study, use of MB for delineating stricture line and assessing spongiofibrosis in the diagnosis of urethral stricture was evaluated. MATERIAL AND METHODS: Five cc MB including 10 mg/mL is diluted with 10 cc saline. In the first scenario, MB is gently injected into urethra via the meatus before the urethroplasty procedure. Meanwhile, the extent of urethral segment stained by MB is noted. In the second scenario (MB spongiosography) in short bulbar stricture, insulin needles are inserted in spongiosa of the stricture site distally and proximally. MB is gently injected with distal needle. The two remaining needles are then observed. Presence of MB efflux in proximal needle implies deficiency of significant spongiofibrosis, so buccal augmentation is performed. Absence of efflux of MB implies significant spongiofibrosis and anastomotik site excised. RESULTS: Four hundred and ninety-two consecutive cases prospectively evaluated between 2010 and 2014. Precise staining of stricture was successfully observed in 464 (94%) patients. Grossly normal appearing urothelium remained pink. Histopathology confirmed that the stained urethra had a stricture. Of the 22 short bulbar idiopathic strictures, in 18 (82%) MB was seen across the stricture and urethral transection was avoided. Anastomosis was performed in 4 (18%) cases where no MB went across the primary excision. There were no known allergic complications. CONCLUSION: MB aids in delineating the urethral lumen and exact site of stricture that needs augmentation. MB Spongiography in short bulbar strictures could be used as a beneficial guide in relation to the type of urethral repair to be performed in terms of augmentation versus excision and anastomosis.

Optimization of the current self-assembled urinary bladder model: Organ-specific stroma and smooth muscle inclusion.

INTRODUCTION: Due to the complications associated with the use of non-native biomaterials and the lack of local tissues, bioengineered tissues are required for surgical reconstruction of complex urinary tract diseases, including those of the urinary bladder. The self-assembly method of matrix formation using autologous stromal cells obviates the need for exogenous biomaterials. We aimed at creating novel ex-vivo multilayer urinary tissue from a single bladder biopsy. METHODS: After isolating urothelial, bladder stromal and smooth muscle cells from bladder biopsies, we produced 2 models of urinary equivalents: (1) the original one with dermal fibroblasts and (2) the new one with bladder stromal cells. Dermal fibroblasts and bladder stromal cells were stimulated to form an extracellular matrix, followed by sequential seeding of smooth muscle cells and urothelial cells. Stratification and cellular differentiation were assessed by histology, immunostaining and electron microscopy. Barrier function was checked with the permeability test. Biomechanical properties were assessed with uniaxinal tensile strength, elastic modulus, and failure strain. RESULTS: Both urinary equivalents could be handled easily and did not contract. Stratified epithelium, intact basement membrane, fused matrix, and prominent muscle layer were detected in both urinary equivalents. Bladder stromal cell-based constructs had terminally differentiated urothelium and more elasticity than dermal fibroblasts-based equivalents. Permeation studies showed that both equivalents were comparable to native tissues. CONCLUSIONS: Organ-specific stromal cells produced urinary tissues with more terminally differentiated urothelium and better biomechanical characteristics than non-specific stromal cells. Smooth muscle cells could be incorporated into the self-assembled tissues effectively. This multilayer tissue can be used as a urethral graft or as a bladder model for disease modelling and pharmacotherapeutic testing.

Stem cell applications for pathologies of the urinary bladder.

New stem cell based therapies are undergoing intense research and are widely investigated in clinical fields including the urinary system. The urinary bladder performs critical complex functions that rely on its highly coordinated anatomical composition and multiplex of regulatory mechanisms. Bladder pathologies resulting in severe dysfunction are common clinical encounter and often cause significant impairment of patient's quality of life. Current surgical and medical interventions to correct urinary dysfunction or to replace an absent or defective bladder are sub-optimal and are associated with notable complications. As a result, stem cell based therapies for the urinary bladder are hoped to offer new venues that could make up for limitations of existing therapies. In this article, we review research efforts that describe the use of different types of stem cells in bladder reconstruction, urinary incontinence and retention disorders. In particular, stress urinary incontinence has been a popular target for stem cell based therapies in reported clinical trials. Furthermore, we discuss the relevance of the cancer stem cell hypothesis to the development of bladder cancer. A key subject that should not be overlooked is the safety and quality of stem cell based therapies introduced to human subjects either in a research or a clinical context.

False fracture of the penis: Different pathology but similar clinical presentation and management.

INTRODUCTION: Penile fracture is the most common presentation of acute penis. Rupture of the superficial dorsal penile vein (s) may mimic penile fractures with similar clinical presentation but with intact corporeal bodies. Our aim of the study is to highlight superficial dorsal penile vein (s) injury as true emergency with better prognosis. SUBJECTS AND METHODS: Sixty-eight patients with suspected penile fractures presented to our hospital between June 2007 and January 2013. Out of these, 11 patients showed intact tunica albuginea on exploration with injured dorsal penile vein (s) identified. Records of such 11 cases were reviewed regarding age, etiology, symptoms, physical signs, findings of surgical exploration and post-operative erectile function. RESULTS: All 11 patients were injured during sexual intercourse and presented with penile swelling and ecchymosis and gradual detumescence. Mild penile pain was encountered in 5 cases and the "snap" sound was noted in 2 cases. Examination revealed no localized tenderness, or tunical defect. All the patients regained penile potency without deformity after surgical ligation of the severed vessels. One patient developed penile hypoesthesia. CONCLUSION: Although the classic "snap" sound and immediate detumescence are usually lacking in the symptomology of dorsal penile vein rupture, its clinical presentation can be indistinguishable from true penile fracture. Surgical exploration is still required to avoid missing tunical tear with possible future complications. The long-term outcome and prognosis are excellent.

Can computed tomography--assisted virtual endoscopy be an innovative tool for detecting urethral tissue pathologies?

OBJECTIVE: To test if virtual endoscopy (VE) enabled by 3-dimensional computed tomographic (CT) scanner with supporting software allows for practical clinical interrogation and evaluation of the urethral lumen and anatomy in an animal model. METHODS: Assessment of urethral anatomy and repair results was performed in 18 male beagles using conventional retrograde urethrography, CT-assisted retrograde urethography, and voiding urethrocystography. The image slices from these studies were processed using TeraRecon software to create a virtual representation of the urethra and compared with conventional urethrography and postmortem analysis of retrieved urethras for diagnostic assessment and correlation. RESULTS: CT-assisted VE showed the orientation, size, and gross morphology of urethral anatomy, including the lesions in all the 18 animals studied. The VE showed patent urethra in 12 dogs, stenosed urethra in 3 dogs, urethral diverticulum with stricture in 2 animals, and fistula in one. These findings correlated with those of conventional diagnostic methods. The findings of the voiding and retrograde virtual urethrocystoscopy studies were also comparable. CONCLUSION: These results demonstrate that CT-assisted VE is able to identify the anatomic landmarks in an animal model. This allows for detection of the site of different pathologies and their relations to important structures such as urethral sphincters and the bladder neck. Digital imaging might be used to identify urethral pathologies with greater details and characterization of the lesions when compared with the conventional urethrocystography.