The role of international partnerships in improving urethral reconstruction in low- and middle-income countries.

PURPOSE: To explore the impact of education and training in international surgical partnerships on outcomes of urethral stricture disease in low- and middle-income countries. To encourage data collection and outcomes assessments to promote evidence-based and safe surgical care. METHODS: Qualitative data were collected through observation of a reconstructive surgical workshop held by IVUmed at a host site in Dakar, Senegal. Quantitative data were collected through a retrospective review of 11 years of hospital data to assess surgical outcomes of urethral stricture disease before and after IVUmed started reconstructive workshops at the site. RESULTS: In the 11-year study period, 569 patients underwent 774 surgical procedures for urethral strictures. The numbers and types of urethroplasty techniques increased after IVUmed started its workshops. The average number of urethroplasties increased from 10 to 18.75/year. There was a statistically significant improvement in the mean success rate of urethroplasties from 12.7% before to 29% after the workshops. Anastomotic urethroplasty success rates doubled from 16.7 to 35.1%, but this was not statistically significant (p = 0.07). The improved success rate was sustained in cases performed without an IVUmed provider. CONCLUSIONS: Urethral stricture disease treatment in low- and middle-income countries is fraught with challenges due to complex presentations and limited subspecialty training. Improper preoperative management, lack of specialty instruments, and suboptimal wound care all contribute to poor outcomes. International surgical groups like IVUmed who employ the "teach-the-teacher" model enhance local practitioner expertise and independence leading to long-term improvements in patient outcomes. Tailoring practice guidelines to the local resource framework and encouraging data collection and outcomes assessment are vital components of providing responsible care and should be encouraged.

Urinary Catheter Management for Nonurologists: A Resident Driven Educational Initiative.

INTRODUCTION: Prevention of catheter associated urinary tract infection relies on timely catheter removal and care of indwelling catheters. Educational and quality improvement initiatives to prevent catheter associated urinary tract infection should address the basics of urinary catheter placement and management. Internal medicine residents are an appropriate target for these efforts and they may lack formal training in these issues. We developed a resident driven orientation session that covers basic Foley catheter management principles called the TIPS (Troubleshooting, Indications and Practice Sessions) program. METHODS: Urology residents at our institution were queried on common consultations for urinary catheter related issues. The incoming intern internal medicine class at our institution completed a pre-TIPS survey that evaluated their baseline urological experience and knowledge. A 1-hour didactic session led by urology residents was followed by hands-on directed practice with mannequins. The web based survey was repeated 1 month later. RESULTS: Of the total of 60 residents 54 (90%) completed the initial survey. In medical school 38 of 54 residents (70%) had never rotated in urology. Upon repeating the survey at 1 month the response rate was 34 of 60 residents (57%). The proportion of residents confident in their ability to troubleshoot catheter problems increased from 50% to 88% (p <0.05). Knowledge of indications, clot retention and proper catheter technique also improved (p <0.05). CONCLUSIONS: A focused educational session about common urological catheter management scenarios resulted in improved internal medicine resident confidence in catheter troubleshooting and knowledge of basic urinary catheter placement indications. These educational sessions may be a method to improve nonurology resident education and awareness of common urological issues.

Epithelial mesenchymal-like transition occurs in a subset of cells in castration resistant prostate cancer bone metastases.

TGFß is a known driver of epithelial-mesenchymal transition (EMT) which is associated with tumor aggressiveness and metastasis. However, EMT has not been fully explored in clinical specimens of castration-resistant prostate cancer (CRPC) metastases. To assess EMT in CRPC, gene expression analysis was performed on 149 visceral and bone metastases from 62 CRPC patients and immunohistochemical analysis was performed on 185 CRPC bone and visceral metastases from 42 CRPC patients. In addition, to assess the potential of metastases to seed further metastases the mitochondrial genome was sequenced at different metastatic sites in one patient. TGFß was increased in bone versus visceral metastases. While primarily cytoplasmic; nuclear and cytoplasmic Twist were significantly higher in bone than in visceral metastases. Slug and Zeb1 were unchanged, with the exception of nuclear Zeb1 being significantly higher in visceral metastases. Importantly, nuclear Twist, Slug, and Zeb1 were only present in a subset of epithelial cells that had an EMT-like phenotype. Underscoring the relevance of EMT-like cells, mitochondrial sequencing revealed that metastases could seed additional metastases in the same patient. In conclusion, while TGFß expression and EMT-associated protein expression is present in a considerable number of CRPC visceral and bone metastases, nuclear Twist, Slug, and Zeb1 localization and an EMT-like phenotype (elongated nuclei and cytoplasmic compartment) was only present in a small subset of CRPC bone metastases. Mitochondrial sequencing from different metastases in a CRPC patient provided evidence for the seeding of metastases from previously established metastases, highlighting the biological relevance of EMT-like behavior in CRPC metastases.

Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo.

BACKGROUND: Prostate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study. METHODS: Prostaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice. RESULTS: Prostate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3-5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5-4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8-AR-PSA-) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells. CONCLUSION: Human prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells.