Search

Background: Collecting, monitoring, and responding to patient-generated health data (PGHD) are associated with improved quality of life and patient satisfaction, and possibly with improved patient survival in oncology. However, the current state of adoption, types of PGHD collected, and degree of integration into electronic health records (EHRs) is unknown. Methods: The NCCN EHR Oncology Advisory Group formed a Patient-Reported Outcomes (PRO) Workgroup to perform an assessment and provide recommendations for cancer centers, researchers, and EHR vendors to advance the collection and use of PGHD in oncology. The issues were evaluated via a survey of NCCN Member Institutions. Questions were designed to assess the current state of PGHD collection, including how, what, and where PGHD are collected. Additionally, detailed questions about governance and data integration into EHRs were asked. Results: Of 28 Member Institutions surveyed, 23 responded. The collection and use of PGHD is widespread among NCCN Members Institutions (96%). Most centers (90%) embed at least some PGHD into the EHR, although challenges remain, as evidenced by 88% of respondents reporting the use of instruments not integrated. Forty-seven percent of respondents are leveraging PGHD for process automation and adherence to best evidence. Content type and integration touchpoints vary among the members, as well as governance maturity. Conclusions: The reported variability regarding PGHD suggests that it may not yet have reached its full potential for oncology care delivery. As the adoption of PGHD in oncology continues to expand, opportunities exist to enhance their utility. Among the recommendations for cancer centers is establishment of a governance process that includes patients. Researchers should consider determining which PGHD instruments confer the highest value. It is recommended that EHR vendors collaborate with cancer centers to develop solutions for the collection, interpretation, visualization, and use of PGHD.

Testicular cancer is relatively uncommon and accounts for 50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.

Objective To determine whether use of an antibiotic-irrigating wound protector (AWP) reduces infectious complications after robotic radical cystectomy with extracorporeal urinary diversion (RCUD). Methods A prospectively maintained bladder cancer database was queried for patients undergoing robotic RCUD at a tertiary referral center one year prior to implementing an AWP and one year after (2018–2020). All diversions were performed extra-corporally. 92 patients total. 46 consecutive patients using a traditional wound protector (TWP) and 46 consecutive with an AWP. Infections were classified as symptomatic urinary tract infection, blood stream infection, and surgical site infection. The incidence of infectious complications at 30- and 90-days were compared. Results Baseline patient characteristics between the 2 groups showed no statistically significant differences. The overall complication rate was 65.2% in the TWP group and 26.1% in the AWP group at 30-days, and 67.4% vs 30.4% at 90-days. Focusing on infections, the 30-day complication rate was 30.4% in the TWP group compared to 6.5% in the AWP group (P =.003). This pattern persisted at 90-days with 37.0% in the TWP group compared to 6.5% in the AWP group (P =.004). Most complications were symptomatic UTI and blood stream infections, 14/24 (58%), requiring parenteral antibiotic treatment. Conclusion We provide preliminary data showing use of an AWP can reduce infectious complications after RCUD. While larger prospective studies are warranted, our findings are a significant step towards decreasing morbidity of an already highly morbid procedure.

As the US transitions from volume- to value-based cancer care, many cancer centers and community groups have joined to share resources to deliver measurable, high-quality cancer care and clinical research with the associated high patient satisfaction, provider satisfaction, and practice health at optimal costs that are the hallmarks of value-based care. Multidisciplinary oncology care pathways are essential components of value-based care and their payment metrics. Oncology pathways are evidence-based, standardized but personalizable care plans to guide cancer care. Pathways have been developed and studied for the major medical, surgical, radiation, and supportive oncology disciplines to support decision-making, streamline care, and optimize outcomes. Implementing multidisciplinary oncology pathways can facilitate comprehensive care plans for each cancer patient throughout their cancer journey and across large multisite delivery systems. Outcomes from the delivered pathway-based care can then be evaluated against individual and population benchmarks. The complexity of adoption, implementation, and assessment of multidisciplinary oncology pathways, however, presents many challenges. We review the development and components of value-based cancer care and detail City of Hope’s (COH) academic and community-team-based approaches for implementing multidisciplinary pathways. We also describe supportive components with available results towards enterprise-wide value-based care delivery.

Heated intraperitoneal chemotherapy (HIPEC) is commonly performed at the time of tumor resection for metastatic intraabdominal tumors. Post operative complications, such as superficial wound infections or bowel leaks are common. They are largely thought to be secondary to poor wound healing due to chemotherapy-associated neutropenia. Scrotal eschars resulting in full-thickness skin necrosis have rarely been reported as a delayed complication after HIPEC. Here, we present the first case report of penile full-thickness skin necrosis after abdominal cytoreduction with HIPEC combined with ventral hernia repair and mesh placement.

INTRODUCTION AND OBJECTIVE:Extended pelvic lymph node dissection (eLND) at the time of radical prostatectomy has a staging benefit over limited pelvic lymph node dissection (LLND) but an unclear th...

Objectives To determine if eliminating the prophylactic placement of a pelvic drain (PD) after robot-assisted radical prostatectomy (RARP) affects the incidence of early (90-day) postoperative adverse events. Materials and Methods In this parallel-group, blinded, non-inferiority trial, we randomized patients planning to undergo RARP to one of two arms: no drain placement (ND) or PD placement. Patients with demonstrable intra-operative leakage upon bladder irrigation were excluded. Randomization sequence was determined a-priori using a computer algorithm, and included a stratified design with respect to low vs. intermediate/high D'Amico risk classifications. Surgeons remained blinded to the randomization arm until final eligibility was verified at the end of the RARP. The primary endpoint was overall incidence of 90-day complications which, based on our standard treatment using PD retrospectively, was estimated at 13%. The non-inferiority margin was set at 10%, and the planned sample size was 312. An interim analysis was planned and conducted when 1/3 of the planned accrual and follow-up was completed, to rule out futility if the delta margin was in excess of 0.1389. Results From 2012 to 2016, 189 patients were accrued to the study, with 92 patients allocated to the ND group and 97 patients allocated to the PD group. Due to lower than expected accrual rates, accrual to the study was halted by regulatory entities, and we did not reach the intended accrual goal. ND and PD groups were comparable in median PSA (6.3 vs 5.8 respectively, p=0.5), clinical stage (p=0.8), D'Amico risk classification (p=0.4), median lymph nodes dissected (17 vs 18, p=0.2) and proportion of patients receiving an extended pelvic lymph node dissection (70.7% vs 79.4% respectively, p=0.3). Incidence of 90-day overall and major (Clavien ≥ III) complications in the ND group (17.4% and 5.4%, respectively) was not inferior to the PD group (26.8% and 5.2%, respectively; p=0.0008 and p=0.007 for difference of proportions

Optimal management of node-positive prostate cancer patients after prostatectomy remains a challenge. We evaluated clinically localized patients who demonstrated node positivity and identified predictors for secondary treatment. From 2010 to 2015, clinically localized prostate cancer patients who underwent robot prostatectomy with extended lymphadenectomy and node-positive disease on pathologic analysis were identified. Clinical N1, M1 or salvage cases were excluded. Patients were stratified based on secondary treatments. Kaplan–Meier method was used to determine the time to biochemical and metastatic recurrence. Multivariate logistic regression was used to identify predictors for additional treatment. 145 patients (45 no additional therapy, 47 adjuvant, 53 salvage) had a median follow-up of 31.2 months. Salvage patients had higher median pre-operative prostate-specific antigen (10.8 vs. 9.7 vs. 8.2, p = 0.1), higher percentage of pathologic Gleason ≥8 (50.9 vs. 38.3% and 22.2%, p

Objective To prospectively assess the ideal dosing and the value of fluorescent sentinel lymph node (LN) detection with indocyanine green (ICG) for the detection of LN metastases in intermediate- and high-risk patients undergoing robot-assisted prostatectomy and extended pelvic LN dissection (ePLND). Patients and Methods Twenty patients received transperineal prostatic injections of ICG. Patients were cycled through 5 doses (1.25, 2.5, 3.75, 5, and 7.5 mg) so optimal ICG dosing could be discovered early. Results ICG injection was able to identify fluorescent LN (FLN) packets in all 20 patients. Compared to the higher ICG doses, the 1.25 and 2.5 mg doses had fewer FLN packets and were abandoned after 1 dose each. The median number of FLN packets was 4.0, 6.0, and 4.5 for the respective doses of 3.75, 5.0, and 7.5 mg. The external iliac group was the most common site of fluorescence in 27.2% of patients, followed by the common iliac (21.3%), obturator (20.3%), internal iliac (18.5%), and node of Cloquet (7.7%). Seven (35%) of 20 patients had node-positive disease. Of the 5 patients that had fluorescent tissue outside of our ePLND template, 1 had a positive node present in the anterior bladder neck fat. Across all patients, ICG had 62% sensitivity, 50% specificity, 8% positive predictive value, and 95% negative predictive value in detecting LN metastases. Conclusion The low sensitivity of ICG for the detection of LN metastases highlights why FLN dissection with ICG does not represent an alternative to ePLND.

Objective To report our experience with ureteroenteric anastomotic revision as initial treatment of stricture after urinary diversion. Methods An institutional review board-approved retrospective study was carried out. A total of 41 patients who underwent primary ureteroenteric anastamotic revision were identified between 2007 and 2015. Data analyzed included patient characteristics, type of diversion, estimated blood loss, operative time, change in renal function, length of stay, postoperative complications and time with nephrostomy/stent. Success of revision was defined as an improvement in hydronephrosis on radiographic imaging and/or reflux during pouchogram. Predictors of length of stay and complications were analyzed using analysis of covariance. Results A total of 50 renal units were revised with a success rate of 100%. The median length of stay was 6 days (2-16 days). There were a total of 15 complications (one major, 14 minor) in 14 patients (33% 30-day complication rate). The most common were wound infection (n = 4) and arrhythmia (n = 4). Robotic revision (n = 5) had a median length of stay of 3 days (2-4) with no complications. Conclusions Primary ureteroenteric anastomotic revisions have an excellent success rate at an experienced center and might obviate the need for multiple interventions. Open revision is associated with mostly minor complications. Robotic revision might reduce the morbidity of open revision in select cases.

INTRODUCTION AND OBJECTIVES:Benign ureteroenteric strictures (UES) may occur after radical cystectomy with urinary diversion. Timely treatment is instrumental in preventing renal insufficiency. The...

Background: Ischemia is thought to contribute to benign ureteroenteric stricture (UES) after radical cystectomy with urinary diversion (RCUD). Our institution adopted the use of ureteral perfusion assessment during all RCUDs using real-time indocyanine green angiography using the SPY fluorescence imaging platform (Stryker Corp., Kalamazoo, MI, USA). This guides the location of ureteral transection prior to ureteroenteric anastomosis. We sought to compare UES rates before and after adoption of SPY. Methods: A retrospective chart review was undertaken for the first 47 consecutive cases of RCUD using SPY as well as the previous 47 consecutive cases, which were performed without SPY. Fisher’s exact and Wilcoxon rank-sum tests were used to compare benign UES rates and the length of ureter excised during anastomosis. A p < 0.05 indicated statistical significance. Results: Median follow up was 12.0 months for SPY cases and 24.3 months for non-SPY cases. The UES rate for SPY RCUDs was 0% (0/93 ureters) compared with 7.5% (7/93 ureters) for non-SPY RCUDs ( p = 0.01). Amongst SPY RCUDs, 86 ureters had no hydronephrosis and 7 had mild hydronephrosis with reflux on loopogram. A total of 34.4% of ureters (32/93) had poor distal perfusion, requiring a more proximal anastomosis. The median length excised for ureters with poor distal perfusion was 3.8 cm, compared with 2.2 cm for ureters with good distal perfusion ( p < 0.0001). No complications attributable to the use of SPY were noted. Conclusion: Use of SPY to assess ureteral perfusion was associated with a decrease in the UES rate after RCUD. A total of 34.4% of ureters demonstrated poor distal perfusion, requiring a significantly more proximal ureteroenteric anastomosis.

INTRODUCTION AND OBJECTIVES:Radical cystectomy during multi-visceral resection for locally advanced pelvic malignancy requires urinary diversion. Outcomes with incontinent and continent urinary div...

INTRODUCTION AND OBJECTIVES:A minority of patients undergoing trimodality therapy for bladder cancer will go on to require salvage cystectomy. We report the outcomes in a small cohort of open and m...

Pelvic lymph node dissection (PLND) and retroperitoneal lymph node dissection (RPLND) remain critical components of many urologic disease processes and procedures. Dissection may provide accurate lymph node staging and confer potential therapeutic benefit. For prostate cancer management, lymph node dissection at prostatectomy provides an opportunity for staging and, when compared with other treatment options, has been shown to have a possible therapeutic benefit by lower cancer-specific death rates [1–3]. In the management of testicular cancer, RPLND is considered an established treatment option, depending on the histologic subtype and clinical stage of the disease. The robotic platform allows for a full therapeutic dissection with equivalent oncologic outcomes and shorter convalescence when compared with open RPLND [4, 5]. Finally, in the management of patients with locally advanced renal masses (T3–T4) or unfavorable clinical and/or pathologic features, a template lymph node dissection may offer improved survival [6–8].

To evaluate intermediate-term oncologic outcomes in a large series of patients who were treated with robot-assisted radical cystectomy (RARC) for urothelial carcinoma of the bladder (UCB).Between 2004 and 2010, 162 patients underwent RARC at City of Hope Cancer Center for UCB and were analyzed with respect to overall (OS), disease-specific (DSS), and disease-free survival (DFS). Descriptive statistics were used to summarize demographics and perioperative variables. The Kaplan-Meier method was used to estimate survival and recurrence. Univariable and multivariable Cox proportional hazards regression models were used to determine predictors of survival.Median follow-up was 52 months. Thirty-eight (23.4%) patients received neoadjuvant chemotherapy before RARC; 28% of patients were pT2 and 33% had final pathology status of pT3 or pT4. Median lymph node count was 28, and positive surgical margin rate was 4.3%. Local recurrence occurred in 11 (6.8%) patients. OS, DFS, and DSS at 3 years were 61%, 76%, and 83%, respectively. OS, DFS, and DSS at 5 years were 54%, 74%, and 80%, respectively. Predictors of OS and DFS on multivariable analysis were lymph node density, pathologic stage, and age-adjusted Charlson Comorbidity Index, while receipt of transfusion was also a negative predictor of OS.RARC provides an effective means of treatment of UCB in a minimally invasive fashion with comparable oncologic outcomes to that reported in the literature of open procedures.

Minimally invasive surgical treatment for bladder cancer has gained popularity but standardized data on complications are lacking. Urinary diversion type contributes to complications and to our knowledge diversion types after minimally invasive cystectomy have not yet been compared. We evaluated perioperative complications stratified by urinary diversion type in patients treated with robot-assisted radical cystectomy.We analyzed the records of 209 consecutive patients who underwent robot-assisted radical cystectomy at our institution from 2003 to 2012 with respect to perioperative complications, including severity, time period (early and late) and diversion type. All complications were reviewed by academic urologists. Urinary diversion was also done. As outcome measurements and statistical analysis, univariate and multivariate logistic regression models were used to determine predictors of various complications.The American Society of Anesthesiologists(®) (ASA) score was 3 or greater in 80% of patients and continent diversion was performed in 68%. Median followup was 35 months. Within 90 days 77.5% of patients experienced any complication and 32% experienced a major complication. The 90-day mortality rate was 5.3%. Most complications were gastrointestinal, infectious and hematological. On multivariate analysis patients with ileal conduit diversion had a decreased likelihood of complications compared to patients with Indiana pouch and orthotopic bladder substitute diversion despite the selection of a more comorbid population for conduit diversion. Continent diversion was associated with a higher likelihood of urinary tract infection. Our results are comparable to those of previously reported open and minimally invasive cystectomy series.Open or minimally invasive cystectomy is a complex, morbid procedure. Urinary diversion is a significant contributor to complications, as is patient comorbidity. Although patients with an ileal conduit had more comorbidities, they experienced fewer complications than those with an orthotopic bladder substitute or Indiana pouch diversion.

PURPOSE OF REVIEW To summarize the most current clinical applications of tissue engineering and their relevance to pediatric urology. RECENT FINDINGS Successful clinical application of engineered bladder tissue substitutes has led to an ongoing phase II clinical trial. The use of engineered tissue substitutes in hypospadias reconstruction has also been applied clinically, but has not yet gained wide acceptance. Cell injection therapy for rhabdosphincter regeneration has shown promise in adult stress urinary incontinence patients, but its applicability to the pediatric population has not been reported. To date, engineered tissue substitutes for reconstitution of the corporal bodies of the penis have been successfully applied in animal models. Renal replacement therapy has shown progress with the clinical application of human progenitor cells in hemofiltration units, and additional studies may ultimately render the engineered intracorporeal renal replacement unit a reality. SUMMARY The field of tissue engineering seeks to arm the clinician with therapeutic options that rehabilitate or reconstruct damaged organs. Recent clinical trials may transform reconstructive surgery as well as current surgical practice in patients with neurogenic bladders and urinary incontinence.

was followed by an inverse change of equal or greater magnitude. To determine clinically meaningful variation, we used an increase of 1ng/ mL that was followed by a decrease of equal magnitude across measurements. The association between each measure of variation and number of PSA measurements was assessed using linear regression. RESULTS: In 541 men studied, the cumulative incidence of discontinuing AS for definitive treatment within 5 years was 13%. Among 251(46%) patients who reached a PSA of 7ng/mL, 186(74%) decreased from this threshold at least once. 417 (77%) patients reached a PSA of 4ng/mL but their PSA measurements fluctuated around this threshold less often. In patients who reached a PSA of 4ng/ mL or 7ng/mL, the number of PSA measurements was significantly associated with the frequency of variation across each threshold (p

410 Background: Bladder cancer is the second most common urologic malignancy with over 73,350 new cases diagnosed annually of which the incidence is increasing in the elderly. Radical cystectomy (RC), the gold standard for muscle invasive disease, carries a particularly high risk of morbidity and mortality, as well as a protracted length of stay (LOS) and increased readmission rates when compared with other major urologic procedures. Furthermore, in 2013, the Institute of Medicine (IOM) declared cancer care in the US a national crisis with a priority to improve quality of care through care coordination (CC). Simultaneously, enhanced recovery after surgery (ERAS) protocols have surfaced as coordinated, evidence-based models designed to standardize medical care, improve outcomes, and lower healthcare costs. At City of Hope (COH), we evaluated our ERAS and CC pathway. Methods: In April of 2014, an ERAS and CC pathway for bladder cancer was launched at COH with an emphasis on the perioperative care of patients (pts) from a multi-disciplinary team perspective. Preoperatively, pts undergo orientation on stoma education, goals of care, and treatment expectations. The pathway clinically focuses on avoidance of bowel preparation, early feeding, minimizing narcotics, and u-opioid antagonists. On discharge, pts are closely monitored via scheduled phone calls as well as clinic visits. Quality metrics including LOS, complications, and readmissions are reported as median and interquartile range along with descriptive statistics including chi-square and Wilcoxon rank-sum tests. Results: Since implementation, the median LOS was statistically significant between cohorts with 6 days for pts on pathway compared to 8 days for those preceding the pathway (p = 0.0007). Furthermore, the complication and readmission rates have decreased from 67.5% to 50% and from 35% to 30%, respectively. Dehydration and urinary tract infection (UTI) accounted for 17.9% and 21.4% of readmissions for those prior to the pathway, while UTI occurred in 5% of pts readmitted after adhering to the pathway. Conclusions: Our ERAS and CC pathway has reduced LOS without an increase in complication nor readmission rates.

Background High-dose chemotherapy (HDCT) is a viable and potentially curative approach for patients with relapsed or refractory germ cell tumors (GCTs). However, no comparative data exist to define the optimal chemotherapeutic strategy, and little is known about the quality of life (QOL) of long-term survivors. Herein we attempt to characterize the QOL in long-term survivors who received high-dose paclitaxel, etoposide, carboplatin, and ifosfamide (TECTIC). Patients and Methods Details of the TECTIC regimen and clinical outcomes for the initial 33 patients have been reported. In the present study, we report the clinical data for 15 additional patients. Using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and the Functional Assessment of Cancer Therapy–Taxane (FACT-T) questionnaires, we surveyed all patients who survived at least 4 years after HDCT. Results Forty-eight patients were enrolled and 46 patients received protocol therapy. For all 48 patients, the median progression-free survival (PFS) and overall survival (OS) were 11.8 months (range, 5.8-not reached) and 21.7 months (range, 12.7-not reached), respectively. Seventeen patients were progression free at a median of 123.2 months (51.6-170.2 months), and 6 patients remain alive after progression with a median OS of 68.8 months (47.6-147.1 months). Of the 23 surviving patients, 18 were accessible and consented to telephone interviews. Compared with historical cohorts, survivors had a higher global health scale score (87.04 vs. 75.62; P = .02) but a lower physical functioning score (68.89 vs. 92.66; P = .0001) by the QLQ-C30 scale. Conclusions HDCT with the TECTIC regimen produces durable remissions in patients with relapsed or refractory GCTs with acceptable QOL in long-term survivors.

INTRODUCTION AND OBJECTIVES: The National Comprehensive Cancer Network prostate cancer guidelines of 2011 recommend active surveillance for patients with under 20 year life expectancy with very low risk prostate cancer, defined as T1c, Gleason score less than or equal to 6, PSA 10 ng/ml, fewer than 3 biopsy cores positive, less than or equal to 50% cancer in any one core, and PSA density 0.15ng/mL/g. The aim was to determine if these patients harbored higher risk prostate cancer after complete pathologic examination made possible after radical prostatectomy. METHODS: An IRB approved database, which contains over 6000 patients who underwent robotic assisted radical prostatectomy, was queried for patients meeting the NCCN clinical criteria for Very Low Risk Prostate Cancer. Pathologic data, biochemical recurrence-free survival (BCRFS), cancer-specific survival (CSS), and use of secondary therapy were evaluated. RESULTS: Of 1279 patients meeting the NCCN clinical criteria for very low-risk prostate cancer, 36.1% had a final Gleason sum 7, and 0.5% had a Gleason sum greater than or equal to 8 . Final pathologic staging revealed 21.3%, 74%, 3.8%, and 1.0% had pT2ab, pT2c, pT3a, pT3b disease respectively. Node dissection was performed in 302 (23.6%), and 3 patients were found to have positive nodes. Positive margins occurred in 15.3%. At a median follow up of 15 months, 3-and 5-year biochemical recurrence-free survival was 95.1% and 92.8% respectively. On multivariate analysis, predicting factors for pathologic upgrading included prostate size under 55 grams (p 0.0001), seminal vesicle invasion (p 0.0001), age (p 0.0001), and body mass index (p 0.0001). Cancer specific survival was 100%. Secondary therapy was used in 12 patients for biochemical recurrence, radiotherapy in 11 and androgen deprivation in 1 patient. CONCLUSIONS: A substantial amount of very low risk patients experience pathologic upgrading. Nevertheless, these patients experienced good BCRFS and CSS after surgery. It is unknown whether such outcomes would hold true in the absence of intervention in these patients, which could only be determined with a randomized trial. Despite a categorization as Very Low Risk Prostate Cancer by NCCN, 4.9% of patients did experience a biochemical recurrence within 3 years, and 7.2% within 5 years. With longer follow up, disease specific and overall survival data will be determined.

Cyclophosphamide induced cystitis is an established model for the study of bladder injury and wound healing. Glycosylation is an important modification mechanism that regulates the structure and function of secreted proteins and growth factors from inflammation sites. We determined the effect of cyclophosphamide induced cystitis on O-GlcNAc mediated glycosylation in the bladder.Cystitis in WT C57BL6 mice was induced with intraperitoneal cyclophosphamide. Retrieved bladders were analyzed using histology, immunohistochemistry, reverse transcriptase-polymerase chain reaction and Western blot for glycosylation associated factors.Acute bladder injury was seen up to 168 hours (7 days) after injection. Reverse transcriptase-polymerase chain reaction revealed down-regulation of O-GlcNAc transferase, a key enzyme in O-GlcNAc mediated glycosylation, at the 8, 48 and 168-hour time points. Also, the glycosidase menangioma expressed antigen 5 was up-regulated at similar time points. Western blot analysis revealed decreased glycosylated protein during cyclophosphamide induced inflammation.To our knowledge we report the first study of alterations in O-GlcNAc mediated glycosylation activity in bladders with cyclophosphamide induced cystitis. Glycosylation may have a significant role in the bladder wound healing process. Future studies of the glycosylation signaling pathways in the bladder would assist in future potential therapy for bladder inflammatory disease and cancer by elucidating pathways that guide bladder development and wound healing.

Regenerative medicine has made substantial progress in addressing congenital and acquired diseases that result in end organ failure by combining the principles of cell biology, materials science, engineering, and transplantation. This chapter will discuss the basic principles of tissue engineering and the contemporary use of stem cells in the field of urological research. It will also provide a review of leading stem cell procurement techniques utilized in contemporary tissue engineering labs. These include embryonic stem cell harvest, parthenogenesis, nuclear transfer, and most recently, induced pluripotent stem cells.

Urachal cysts are the most common urachal anomaly in the pediatric population. There is an increasing body of literature documenting successful management of urachal cysts using laparoscopic techniques. There may be an advantage, however, with the use of robot-assisted laparoscopy for reconstructive cases. We describe the techniques used for robot-assisted laparoscopic excision of a urachal cyst and bladder cuff with bladder repair in a female child. This approach is a safe and effective option for the minimally invasive management of pediatric urachal cysts.

The field of regenerative medicine continues to make substantial advancements in therapeutic strategies addressing urologic diseases. Tissue engineering borrows principles from the fields of cell biology, materials science, transplantation and engineering in an effort to repair or replace damaged tissues. This review is intended to provide a current overview of the use of stem cells and tissue engineering technologies specifically in the treatment of genitourinary diseases. Current themes in the field include the use of adult stem cells seeded onto biocompatible resorbable matrices for implantation as tissue substitutes, which is conducive to host tissue in-growth. Injection therapy of adult stem cells for organ rehabilitation is also making strong headway toward the restoration of organ structure and function. With new data describing the molecular mechanisms for differentiation, work has begun on targeting tissues for regeneration by genetic modification methods. Promising laboratory discoveries portend the emergence of a new class of clinical therapies for regenerative medicine applications in the genitourinary tract.

Purpose: Primary neuroendocrine tumors of the bladder are rare and they include small and large cell variants. We reviewed our experience with treating these tumors with radical cystectomy to evaluate their histopathological characteristics and clinical outcomes. Materials and Methods: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer at our institution, of whom 25 (1.2%) had neuroendocrine tumors of the bladder, including small cell carcinoma in 20 and large cell carcinoma in 5. Pure neuroendocrine-type histology was identified in 16 cases, including 1 with small and large cell features, while the remaining 9 had mixed histology, that is transitional cell carcinoma in 8 and adenocarcinoma in 1. Multi-agent chemotherapy was administered to 14 patients. Results: Median patient age was 68 years (range 40 to 82) and 19 patients were male (76%). A total of 19 patients (76%) had lymph node involvement, of whom 2 had small liver metastases found intraoperatively, while only 4 (16%) had organ confined tumors and 2 (8%) had extravesical, node negative disease. These tumors tended to have a flat, ulcerative gross appearance with lymphovascular invasion, carcinoma in situ and necrosis present microscopically. Median followup was 11.8 years (range 18 days to 15.1 years). Five-year overall and recurrence-free survival was 10% and 13%, respectively. There was no significant survival difference between small and large cell carcinoma. Mixed histologies tended to do better than pure neuroendocrine tumors, although this did not attain statistical significance (p = 0.064). Patients receiving multimodality therapy had significantly better overall (p = 0.051) and recurrence-free (p = 0.003) survival than those treated with cystectomy alone. Conclusions: Neuroendocrine tumors of the bladder usually present with advanced pathological stage and portend a poor prognosis. Adjuvant chemotherapy protocols may provide improved survival compared with cystectomy alone.

RESULTS: Based on qPCR analysis, RA treatment (10μM) elicited significant downregulation of the pluripotency factor OCT-4, but marked upregulation of UP1A, UP1B, UP2, UP3A, and UP3B mRNA levels in comparison to naive ESCs and spontaneously differentiating controls in both 2-D and 3-D systems. Immunohistochemistry revealed robust expression of UPs 1A, 1B, 2, and 3A in RA-treated cultures, with FACS analysis showing ~60% of the population expressing UP3A. Transient induction of early endoderm markers, SOX17, FOXA1 and FOXA2, was also observed in RA-treated ESCs at 3 and 6 d, respectively, while GATA6 expression was sustained from 6 to 9 d corresponding to maximal UP expression. GATA6-/ESCs failed to undergo RA-induced UP 1A, 1B, 2, and 3A expression while GATA6+/ESCs showed partial recovery of UP1B and UP3A expression compared to WT cells. CONCLUSIONS: We show for the first time that UE differentiation of ESCs is mediated by RA signaling mechanisms and demonstrate that GATA6 is essential in this process. In addition, the development of ESC-derived UE cells from both 2-D and 3-D cell culture systems offers a prospective cell source and delivery system for bladder tissue engineering applications.

and identified by N-terminal sequencing. MAL cDNAs were cloned and sequenced, antibodies to MAL were used to localize it in bladder urothelium by LM and EM techniques. Mice lacking the MAL gene, and those over-expressing the MAL gene, were generated by transgenic techniques. RESULTS: N-terminal sequencing of the bovine p18 identified it as the ‘myelin-and-lymphocyte-protein’ (MAL). This protein has four transmembrane domains interconnected by short hydrophilic domains. It is expressed in bladder urothelium in a differentiation-dependent manner. EM localization studies showed that it is associated with the uroplakin-delivering vesicles of all stages in urothelial umbrella cells, including the small discoidal vesicles, the mature fusiform vesicles, and the apical urothelial surface. In the latter two cases, the MAL is selectively associated with the ‘hinge areas’ that interconnect the urothelial plaques. Genetic ablation of the mouse MAL gene results in the accumulation of fusiform vesicles. Conversely, over-expression of MAL in transgenic mouse urothelium results in a reduction of the fusiform vesicles and, concurrently, the accumulation of multivesicular bodies that are involved in the endocytic degradation of uroplakins. CONCLUSIONS: Our results indicate that (i) MAL is highly expressed in bladder urothelium as a major urothelial differentiation marker, (ii) MAL knockout blocks the fusion of the fusiform vesicles with the urothelial apical surface, and (iii) MAL over-expression increases the delivery of uroplakins to apical surface and their endocytic degradation. Therefore, MAL is a key component in regulating the targeting and degradation of the uroplakin complexes, which serve as the receptor for the uropathogenic E. coli, and contribute to the bladder permeability barrier function.