Oncologic outcomes in patients with nonurothelial bladder cancer.

INTRODUCTION: We aimed to evaluate the relative prognostic impact of the most common variant histologies on disease-specific survival (DSS) in patients undergoing radical cystectomy. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Result database was used to identify patients who underwent radical cystectomy for bladder cancer from 1990 to 2007. Patients with urothelial cell carcinoma (UCC), squamous cell carcinoma (SCC), adenocarcinoma (AC), sarcoma, small cell carcinoma, signet ring carcinoma, and spindle cell carcinoma were included in the study. Multivariable analysis was performed using Cox proportional hazards model to assess independent predictors of disease-specific survival (DSS). Mortality rates were estimated using Kaplan-Meier analyses. RESULTS: A total of 14,130 patients met inclusion criteria with the following histologies: UCC (90.1%), SCC (4.6%), AC, (2.3%), sarcoma (0.8%), small cell carcinoma (0.8%), signet ring carcinoma (0.5%), and spindle cell carcinoma (0.9%). Three-year DSS was most favorable in patients with UCC (63.7%; 95% confidence interval [62.9%-64.8%]) and AC (65.3% [59.3%-70.6%]), whereas 3-year DSS was the least favorable for small cell carcinoma (41.6% [31.3%-51.6%]) and sarcoma (45.4% [35.1%-55.1%]). In the multivariable analysis, independent predictors of DSS were age, marital status, grade, T-stage, N-stage, and variant histology. With respect to UCC, there was an increased risk of disease-specific death associated with all variants except AC. Sarcoma and spindle cell carcinoma were associated with the highest risk of death. CONCLUSIONS: With the exception of AC, the most common variant bladder cancer histologies are all independently associated with worse DSS relative to UCC in patients undergoing radical cystectomy.

Effects of tumor size and location on survival in upper tract urothelial carcinoma after nephroureterectomy.

INTRODUCTION: Upper Tract Urothelial Carcinoma (UTUC) is a rare disease with few prognostic determinants. We sought to evaluate the impact of tumor size and location on patient survival following nephroureterectomy for UTUC. MATERIALS AND METHODS: Data on 8284 patients treated with radical nephroureterectomy for UTUC in the United States between 1998 and 2011 were analyzed from the National Cancer Data Base. Univariable survivorship curves were generated based on pT stage, pN stage, grade, tumor size, and tumor site (renal pelvis vs. ureter). A Cox proportional hazards model was used to evaluate the effect of age, comorbidity, T stage, lymph node involvement, tumor site, and tumor size on survival. RESULTS: The median follow-up time was 46 months. A majority of the patients were male (55.4%) with a tumor size of ≥3.5 cm (52.0%) and pT stage

Comparison of Perioperative and Early Oncologic Outcomes between Open and Robotic Assisted Laparoscopic Prostatectomy in a Contemporary Population Based Cohort.

PURPOSE: We compared rates of positive surgical margins, use of postoperative radiation therapy, and perioperative outcomes between robotic assisted laparoscopic and open radical prostatectomy in a contemporary population based cohort. MATERIALS AND METHODS: In the National Cancer Data Base from 2010 through 2011 patients who underwent robotic assisted laparoscopic prostatectomy (73,131) and open radical prostatectomy (23,804) for nonmetastatic prostate adenocarcinoma were identified. Covariates included age, race, Charlson comorbidity index, prostate specific antigen, biopsy Gleason score, clinical stage, final Gleason score, pathological T stage, lymph node dissection, nodal status, facility type, hospital volume and year of surgery. Multivariable logistic regression was used to identify factors associated with positive surgical margins, use of adjuvant/salvage radiation therapy, prolonged length of stay, readmission and 30-day mortality. Outcomes were also compared in 1:1 propensity matched cohorts. RESULTS: Analysis of propensity matched cohorts showed robotic assisted laparoscopic prostatectomy reduced the risk of positive surgical margins (OR 0.88, 95% CI 0.83-0.93, p <0.01), the use of radiation therapy (OR 0.71, 95% CI 0.63-0.80, p <0.01) and 30-day mortality (OR 0.28, 95% CI 0.13-0.60, p <0.01). The protective effect of robotic assisted laparoscopic prostatectomy for positive surgical margins was found in patients with pT2 disease only (pT2-OR 0.85, 95% CI 0.79-0.91, p <0.01; pT3-OR 0.94, 95% CI 0.86-1.04, p=0.2). Similar results were obtained using multivariable regression. CONCLUSIONS: In a contemporary large national cohort, robotic assisted laparoscopic prostatectomy was independently associated with clinically meaningful reductions in positive surgical margins, postoperative radiation therapy and 30-day mortality compared to open radical prostatectomy. The oncologic benefit was primarily in patients with organ confined disease. Limitations were those associated with any observational study, namely the potential for bias due to unmeasured confounders.

The impact of days off between cases on perioperative outcomes for robotic-assisted laparoscopic prostatectomy.

PURPOSE: To examine the effect of days off between cases on perioperative outcomes for robotic-assisted laparoscopic prostatectomy (RALP). METHODS: We analyzed a single-surgeon series of 2036 RALP cases between 2003 and 2014. Days between cases (DBC) was calculated as the number of days elapsed since the surgeon's previous RALP with the second start cases assigned 0 DBC. Surgeon experience was assessed by dividing sequential case experience into cases 0-99, cases 100-249, cases 250-999, and cases 1000+ based on previously reported learning curve data for RALP. Outcomes included estimated blood loss (EBL), operative time (OT), and positive surgical margins (PSMs). Multiple linear regression was used to assess the impact of the DBC and surgeon experience on EBL, OT, and PSM, while controlling for patient characteristics, surgical technique, and pathologic variables. RESULTS: Overall median DBC was 1 day (0-3) and declined with increasing surgeon case experience. Multiple linear regression demonstrated that each additional DBC was independently associated with increased EBL [ß = 3.7, 95% CI (1.3-6.2), p < 0.01] and OT [ß = 2.3 (1.4-3.2), p < 0.01], but was not associated with rate of PSM [ß = 0.004 (-0.003-0.010), p = 0.2]. Increased experience was also associated with reductions in EBL and OT (p < 0.01). Surgeon experience of 1000+ cases was associated with a 10% reduction in PSM rate (p = 0.03) compared to cases 0-99. CONCLUSIONS: In a large single-surgeon RALP series, DBC was associated with increased blood loss and operative time, but not associated with positive surgical margins, when controlling for surgeon experience.

National trends in the management of low and intermediate risk prostate cancer in the United States.

PURPOSE: To our knowledge factors affecting the adoption of noncurative initial management in the United States for low risk prostate cancer on a population based level are unknown. We measured temporal trends in the proportion of patients with low and intermediate risk prostate cancer who elected noncurative initial treatment in the United States and analyzed the association of factors affecting management choice. MATERIALS AND METHODS: We identified 465,591 and 237,257 men diagnosed with low or intermediate risk prostate cancer using NCDB and SEER (2004 to 2010), respectively. We measured the proportion of men who elected noncurative initial treatment and used multivariate logistic regression analysis to evaluate factors affecting the treatment choice. RESULTS: During the study period noncurative initial management increased in patients at low risk from 21% to 32% in SEER and from 13% to 20% in NCDB (each p < 0.001). This increase was not reflected in our overall study population (SEER 20% to 22% and NCDB 11% to 13%) since the proportion of patients with Gleason score 6 or less decreased with time (61% to 49% and 61% to 45%, respectively). From 2004 to 2010 older age, lower prostate specific antigen, earlier clinical stage, increased comorbidity index and not being married were associated with a higher likelihood of noncurative initial management (each p < 0.05). CONCLUSIONS: Two independently managed, population based data sets confirmed a temporal increase in noncurative initial management in patients with low risk PCa that did not translate into greater use overall in those at low and intermediate risk combined. These contrasting results are likely due to grade migration resulting in fewer men being classified as with low risk PCa based on Gleason score.

Population based analysis of incidence and predictors of open conversion during minimally invasive radical prostatectomy.

PURPOSE: We used population based data to measure the rates and risk factors of open conversion during minimally invasive radical prostatectomy in the United States. MATERIALS AND METHODS: We retrospectively analyzed the records of 87,415 patients in the NCDB who underwent minimally invasive radical prostatectomy between 2010 and 2011. We compared surgical outcomes and treatment facility characteristics between converted and nonconverted cases. Multivariable analysis was done to evaluate conversion risk factors. RESULTS: There were 82,338 robot-assisted (94%) and 5,077 laparoscopic (6%) radical prostatectomies, and 1,080 conversions (1.2%). Fewer robot-assisted cases were converted than laparoscopic cases (0.9% vs 6.5%, p <0.001). The median yearly treatment facility volume of minimally invasive radical prostatectomy was 32 (IQR 10-72). Patients who underwent conversion were more likely to be rehospitalized within 30 days (4.4% vs 2.7%, p = 0.002) and have a postoperative hospital stay of greater than 2 days (40.4% vs 15.1%, p <0.001) than those without conversion. Facilities in the lowest quartile of the yearly volume of the minimally invasive procedure represented 3.8% of minimally invasive radical prostatectomies but accounted for 22.9% of conversions. The second, third and fourth quartiles of yearly treatment facility minimally invasive volume predicted a lower likelihood of conversion compared to the first quartile (each p <0.001). Facility type (eg academic or community) did not predict conversion. Black race (vs white OR 1.52, 95% CI 1.24-1.86, p <0.001) and laparoscopic radical prostatectomy (OR 4.68, 95% CI 3.79-5.78, p <0.001) predicted higher odds of conversion. CONCLUSIONS: Open conversion during minimally invasive radical prostatectomy is a rare event. However, it is significantly more likely for pure laparoscopic surgery, in black men and at low volume facilities. Facility type did not affect conversion rates.

Locoregional small cell carcinoma of the bladder: clinical characteristics and treatment patterns.

PURPOSE: Because small cell carcinoma of the bladder is a relatively rare tumor type, literature about its treatment remains limited. We determined patterns of care and survival after treatment in what is to our knowledge the largest series to date of patients with locoregional small cell carcinoma of the bladder. MATERIALS AND METHODS: We identified patients with localized/locally advanced (cTis-cT4, cN0 or cM0) bladder small cell carcinoma diagnosed between 1998 and 2010 from the National Cancer Database (NCDB). Treatment was categorized as bladder preservation therapy, radical cystectomy alone, bladder preservation therapy with multimodal treatment or radical cystectomy plus multimodal treatment. We performed Kaplan-Meier overall survival analysis to evaluate differential survival between treatment groups. RESULTS: A total of 625 patients met study inclusion criteria. Median age at diagnosis was 73 years (range 36 to 90) and 65% of patients presented with cT2 disease. Patients were treated with bladder preservation therapy (174 or 27.8%), bladder preservation therapy plus multimodal treatment (333 or 53.3%), radical cystectomy alone (46 or 7.4%) and radical cystectomy plus multimodal treatment (72 or 11.5%) with a 3-year overall survival rate of 23% (95% CI 15-32), 35% (95% CI 30-45), 38% (95% CI 17-60) and 30.1% (95% CI 16-47), respectively. Overall survival was most favorable for radical cystectomy alone plus neoadjuvant chemotherapy with a 3-year rate of 53% (95% CI 19-79). CONCLUSIONS: In the United States locoregional small cell carcinoma of the bladder develops predominantly in white males, in whom treatment is performed at metropolitan, comprehensive community cancer centers. Most patients were treated with bladder preservation therapy and most received multimodal therapy. Patients who received neoadjuvant chemotherapy followed by radical cystectomy had the most favorable survival.

Increasing utilization of neoadjuvant chemotherapy for muscle-invasive bladder cancer in the United States.

The treatment and management of advanced urothelial carcinoma of the bladder is a considerable therapeutic challenge. Prospective, randomized clinical trial data demonstrate a survival advantage for those patients who receive chemotherapy prior to radical cystectomy. Despite the overall survival benefits, results from both institutional and administrative datasets suggest that historical use of a neoadjuvant chemotherapy paradigm is remarkably low. This review will evaluate the recent trends in pre-operative chemotherapy utilization that suggest small, but progressively increased use-currently on the order of 20 % of radical cystectomy patients. Additionally, this analysis will explore the various processes and structural barriers that preclude its receipt such as patient age and comorbidity, as well as physician preference, delay to potentially curable surgery, geographic region, distance to treatment facility, and socioeconomic status.

Evaluating the Differences of Wound Related Complications in Robotically Assisted Radical Cystectomy vs Open Radical Cystectomy.

OBJECTIVE: To determine whether robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) compared to open radical cystectomy (ORC) or RARC with extracorporeal urinary diversion (ECUD) would result in a decreased rate of surgical site complications. RARC has been shown to be non-inferior to ORC. Both RARC and ORC are complicated by a high rate of perioperative morbidity, including wound-related complications, which may be decreased by a robotic approach with intracorporeal diversion. METHODS: A retrospective review of our bladder cancer database for patients undergoing radical cystectomy from 2013-2021. Patients were stratified by surgical technique as RARC with ICUD vs ORC vs RARC with ECUD. Surgical site complications were measured at both 30- and 90-day intervals. RESULTS: Of the 269 patients, 127 (47.2%) had RARC with ICUD, 118 (43.7%) had ORC, and 24 (8.9%) had RARC with ECUD (mean ages 71.0, 69.5, and 67.5, respectively). A comparison of the 3 groups demonstrated statistical significance at both the 30-day (P <.001) and 90-day (P <.001) timeframes for total surgical site complications, with RARC with ICUD having the fewest amount of patients experiencing a surgical site complication (0.8%) followed by ORC (25.4%) and RARC with ECUD (29.2%). CONCLUSION: Overall, we observed lower surgical site complication rates among patients undergoing RARC with ICUD compared to patients who underwent ORC or RARC with ECUD. This study suggests that decreased surgical site complications may be one benefit of the minimally invasive approach, particularly in patients at high risk for surgical site complications after radical cystectomy.

National trends in the use of partial nephrectomy: a rising tide that has not lifted all boats.

PURPOSE: Treatment of organ confined renal masses with partial nephrectomy has durable oncologic outcomes comparable to radical nephrectomy. Partial nephrectomy is associated with lower risk of chronic kidney disease and in some series with better overall survival. We report a contemporary analysis on national trends of partial nephrectomy use to determine partial nephrectomy use over time, and whether nontumor related factors such as structural attributes of the treating institution or patient characteristics are associated with the underuse of partial nephrectomy. MATERIALS AND METHODS: We performed an analysis of the NIS (National Inpatient Sample), which contains 20% of all United States inpatient hospitalizations. We included patients who underwent radical or partial nephrectomy for a renal mass between 2002 and 2008. Survey weights were applied to obtain national estimates of nephrectomy use and to evaluate nonclinical predictors of partial nephrectomy. RESULTS: A total of 46,396 patients were included in the study for a weighted sample of 226,493. There was an increase in partial nephrectomy use from 15.3% in 2002 to 24.7% in 2008 (p <0.001). On multivariate analysis hospital attributes (urban teaching status, nephrectomy volume, geographic region) and patient socioeconomic status (higher income ZIP code and private/HMO payer) were independent predictors of partial nephrectomy use. CONCLUSIONS: Since 2002 the national use of partial nephrectomy for the management of renal masses has increased. However, the adoption of partial nephrectomy at smaller, rural and nonacademic hospitals lags behind that of larger hospitals, urban/teaching hospitals and higher volume centers. A lower rate of partial nephrectomy use among patients without private insurance and those living in lower income ZIP code areas highlights the underuse of partial nephrectomy as a quality of care concern.

Computer-aided Veress needle guidance using endoscopic optical coherence tomography and convolutional neural networks.

During laparoscopic surgery, the Veress needle is commonly used in pneumoperitoneum establishment. Precise placement of the Veress needle is still a challenge for the surgeon. In this study, a computer-aided endoscopic optical coherence tomography (OCT) system was developed to effectively and safely guide Veress needle insertion. This endoscopic system was tested by imaging subcutaneous fat, muscle, abdominal space, and the small intestine from swine samples to simulate the surgical process, including the situation with small intestine injury. Each tissue layer was visualized in OCT images with unique features and subsequently used to develop a system for automatic localization of the Veress needle tip by identifying tissue layers (or spaces) and estimating the needle-to-tissue distance. We used convolutional neural networks (CNNs) in automatic tissue classification and distance estimation. The average testing accuracy in tissue classification was 98.53 ± 0.39%, and the average testing relative error in distance estimation reached 4.42 ± 0.56% (36.09 ± 4.92 µm).

Survival characteristics of localized pediatric adrenocortical carcinoma managed with adenectomy: A national cancer center database analysis.

INTRODUCTION: Pediatric adrenocortical carcinoma (ACC) is a rare malignancy, encompassing less than 0.2% of all childhood malignancies. Due to the scarcity of this diagnosis, it is often managed according to guidelines established for adults, as there is a lack of reliable evidence regarding optimal adjuvant treatment options for pediatric patients. It is our aim to identify recent treatment trends as well as clinical and tumor characteristics and their impact on overall survival. METHODS: Using the National Cancer Data Base (NCDB), this study identified 49 patients under 18 years old with localized ACC (M0) undergoing adrenalectomy from 2004 to 2017. Kaplan-Meier analysis was performed to determine overall survival (OS) from patient characteristics and treatments received. Comparison of survival was performed using the log rank test. RESULTS: The median age of our cohort was 3 years old with a slight female predominance of 61%. The median tumor size was 9.4 cm, and patients older than 4 years were significantly (p = 0.03) more likely to present with larger tumors (11.33 cm vs 8.76 cm). Adjuvant treatment in the form of systemic therapy was administered in 20 of 49 (41%) patients and radiation therapy in 2 of 49 (4%) patients. Three-year OS for patients 4 years old and younger was 92.6% vs 61.8% for those older than 4 years (p = 0.002). Patients presenting with tumor size ≥9 cm had worse three-year OS compared to those with tumors <9 cm (95.24% vs 67.1% respectively, p = 0.02, Fig. 1). In patients with tumors ≥ 9 cm, younger children age 0-4 years had significantly (p = 0.04) higher OS rates than older children age 5-17 years. CONCLUSIONS: ACC is a rare pediatric malignancy with a female predominance. Those older than 4 years and those with presenting tumor size ≥9 cm have decreased overall survival rates after adrenalectomy for localized disease. Additionally, children older than 4 have poorer prognosis, even after controlling for larger tumor size. This is the largest contemporary series of localized pediatric ACC to date. However, multi-institutional prospective cohort or randomized-controlled trials are necessary to better evaluate relevant prognostic factors and the role of adjuvant therapies following adrenalectomy.

Early and late perioperative outcomes following radical cystectomy: 90-day readmissions, morbidity and mortality in a contemporary series.

PURPOSE: Radical cystectomy remains associated with significant morbidity. Most series report outcomes with relatively short-term followup that may underestimate the true magnitude of the procedure and many report length of hospital stay but ignore readmission rates. We analyzed the predictors of early (30 days or less), late (31 to 90 days) and cumulative 90-day hospital readmissions, as well as morbidity and mortality rates. MATERIALS AND METHODS: We reviewed our prospectively collected database of 753 patients who underwent radical cystectomy for urothelial cancer between January 2001 and December 2007. We examined the relationship between clinical variables and readmission rates during the early, late and 90-day postoperative period, and reviewed mortality and perioperative morbidity rates. RESULTS: There were 200 (26.6%) patients readmitted in the first 90 days following radical cystectomy. Of these patients 148 (19.7%) were readmitted early, 81 (10.8%) were readmitted late, and 29 (3.9%) had an early and late readmission. Logistical regression revealed gender (OR 1.50, 95% CI 1.00-2.27, p = 0.05), age adjusted Charlson comorbidity index (OR 1.19, 95% CI 1.06-1.34, p = 0.003) and any postoperative complications before discharge home (OR 1.84, 95% CI 1.19-2.83, p = 0.006) as independent predictors of 90-day readmission. The 30 and 90-day mortality rates were 2.1% (16) and 6.9% (52), respectively. CONCLUSIONS: Readmission rates after radical cystectomy are significant, approaching 27% within the first 90 days. Gender and age adjusted Charlson comorbidity index were independent predictors providing preoperative information identifying patients more likely to require readmission or possibly to benefit from a longer initial hospital stay.

Preoperative hydronephrosis predicts extravesical and node positive disease in patients undergoing cystectomy for bladder cancer.

PURPOSE: Preoperative hydronephrosis may be associated with a worse outcome in patients who undergo radical cystectomy for invasive bladder cancer. We characterized the prognostic significance of hydronephrosis, and its relationship to cancer stage and outcome. We also evaluated concordance between the side of identifiable hydronephrosis and concomitant pelvic lymph node metastasis. MATERIALS AND METHODS: We analyzed information from our prospectively collected database of patients who underwent radical cystectomy for bladder cancer from January 2001 to December 2007. We examined the relationship between hydronephrosis and clinical variables as well as survival outcome. Hydronephrosis was diagnosed intraoperatively or by radiographic imaging within 3 months of radical cystectomy. RESULTS: Of 753 patients 244 (32%) were diagnosed with hydronephrosis. Logistic regression modeling revealed that hydronephrosis was an independent predictor of extravesical disease (OR 2.01, 95% CI 1.37 to 2.96, p <0.001) and node positive disease (OR 1.94, 95% CI 1.29 to 2.91, p = 0.001). Of patients with hydronephrosis 88 (36.1%) had concomitant node positive disease and 74 (30.3%) had node positive disease on the same side as hydronephrosis. Thus, hydronephrosis predicted the side of nodal involvement in 74 of 88 patients (84%) with identifiable hydronephrosis and node positive disease. CONCLUSIONS: Hydronephrosis is an independent predictor of advanced bladder cancer stage, and it predicts extravesical disease and node positive disease. Thus, it could prove useful to select patients for neoadjuvant chemotherapy before surgery. The strong correlation between hydronephrosis side and nodal metastasis may have implications for surgical staging and approach.

Risk factors for urothelial carcinoma of the prostate in patients undergoing radical cystoprostatectomy for bladder cancer.

OBJECTIVE: To examine the risk factors for urothelial carcinoma (UC) involvement of the prostate in patients undergoing radical cystoprostatectomy (RCP) for bladder cancer, as such involvement has both prognostic and therapeutic implications. PATIENTS AND METHODS: We examined 308 consecutive men from 1998 to 2005 who had RCP for UC of the bladder, with whole-mount processing of their prostate. Prostatic involvement was categorized by site of origin (the bladder or the prostatic urethra) and, in the case of prostatic urethral origin, by depth of invasion, i.e. dysplasia/carcinoma in situ (CIS), involving the prostatic urethra, prostatic ductal invasion or prostatic stromal invasion. The impact of pathological characteristics was evaluated. RESULTS: In all, 121 (39.3%) patients had some form of urothelial involvement of the prostate, of whom 59 (48.8%) had dysplasia/CIS of the prostatic urethra, 20 (16.5%) had ductal involvement and 32 (26.4%) had stromal involvement. Multivariate analysis showed that bladder CIS (odds ratio 2.0, 95% confidence interval, 1.2-3.6, P = 0.012) and trigonal involvement of bladder tumours (2.0, 1.1-3.7, P = 0.028) were independent risk factors for urothelial involvement of the prostate. CONCLUSION: There was prostatic involvement with UC in nearly 40% of patients undergoing RCP. In this study CIS and trigonal involvement were independent predictors of risk, but were not adequate enough to accurately identify most patients who have UC within their prostate; further prospective studies are needed to more accurately predict risk factors and depth of invasion.

Outcomes of patients undergoing radical cystoprostatectomy for bladder cancer with prostatic involvement on final pathology.

OBJECTIVE: To evaluate the impact of prostatic urothelial carcinoma (PUC) on survival of patients with bladder cancer undergoing radical cystoprostatectomy (RCP). PATIENTS AND METHODS: From 1998 to 2005, 463 consecutive RCPs were performed for UC of the bladder. Patients with PUC at final pathology were grouped by route of prostatic invasion (bladder origin or prostatic urethral origin) and by depth of invasion (carcinoma in situ, ductal invasion, and stromal invasion). Univariate and multivariate survival analyses were performed. RESULTS: In all, 35% (162/463) of patients had PUC. The 3-year overall survival (OS) was 58.2% for patients who did not have PUC, 59.2%, 51.7%, and 16.8% in order of increasing depth of prostatic invasion for patients with PUC of urethral origin, and 6.7% for patients with bladder-origin PUC. Survival differed significantly between stromal and non-stromal PUC (P < 0.001). Patients with PUC of bladder origin had a higher rate of positive lymph nodes (LNs) than patients with stromal PUC of prostate origin (74.3% vs 27.8%, P < 0.001), but survival was similar (P = 0.619). On multivariate analysis, age (P = 0.035), increasing bladder stage (P = 0.003), stromal invasion (P = 0.002) and positive LNs (P < 0.001) were predictors of poor OS. CONCLUSION: Depth of prostatic invasion correlates with outcome. While prostatic involvement originating in the bladder is associated with higher rates of positive LNs, survival is similar to patients with stromal involvement of urethral origin. Age, bladder tumour stage, prostatic stromal involvement and positive LNs predict adverse outcome. Our data support separate staging of the prostate in RCP specimens.

Medical student involvement in website development.

BACKGROUND: The digital management of educational resources and information is becoming an important part of medical education. AIMS: At Vanderbilt University School of Medicine, two medical students sought to create a website for all medical students to act as each student's individual homepage. METHOD: Using widely available software and database technology, a highly customized Web portal, known as the VMS Portal, was created for medical students. Access to course material, evaluations, academic information, and community assets were customized for individual users. Modular features were added over the course of a year in response to student requests, monitoring of usage habits, and solicitation of direct student feedback. RESULTS: During the first 742 days of the VMS Portal's release, there were 209,460 student login sessions (282 average daily). Of 348 medical students surveyed (71% response rate), 84% agreed or strongly agreed that 'consolidated student resources made their lives easier' and 82% agreed or strongly agreed that their needs were represented by having medical students design and create the VMS Portal. CONCLUSION: In the VMS Portal project, medical students were uniquely positioned to help consolidate, integrate, and develop Web resources for peers. As other medical schools create and expand digital resources, the valuable input and perspective of medical students should be solicited.

Risk of Ovarian Malignancy in Patients Undergoing Radical Cystectomy for Bladder Cancer.

OBJECTIVE: To determine whether there is an increased risk of ovarian cancer in women undergoing radical cystectomy (RC) for bladder cancer using a large population-based data source. Current American Urologic Association guidelines suggest removal of ovaries during RC in women with bladder cancer, presumably to mitigate the risk ovarian cancer. However, recent data have demonstrated an increased risk of all-cause mortality, cardiovascular disease, osteoporosis, cognitive impairment, and diminished sexual function in some populations of women after oophorectomy. METHODS: We queried the surveillance, epidemiology and end results (SEER) database for all women with a diagnosis of primary bladder cancer who underwent RC between 1998 and 2010. Patients with concurrent or subsequent primary ovarian cancer were then identified using the SEER multiple primaries dataset. Multiple primary standardized incidence ratio was calculated as an estimate of the relative risk of a concurrent or subsequent ovarian malignancy using SEER*Stat software. RESULTS: A total of 1851 women met inclusion criteria for analysis. Of this population, 221 (11.9%) women developed a subsequent nonbladder malignancy, of which 2 (0.11%) women developed subsequent ovarian cancer during the observation period. Multiple primary standardized incidence ratio for development of an ovarian malignancy was 2/4 (0.50). CONCLUSION: The risk of concurrent or subsequent ovarian malignancy in women undergoing RC for bladder cancer is very low. Therefore, oophorectomy at the time of RC may be obviated in order to mitigate the undue risk of cardiovascular disease, osteoporosis, cognitive impairment, and diminished sexual function.

Cell-penetrating peptide sequence and modification dependent uptake and subcellular distribution of green florescent protein in different cell lines.

Protein therapy holds great promise for treating a variety of diseases. To act on intracellular targets, therapeutic proteins must cross the plasma membrane. This has previously been achieved by covalent attachment to a variety of cell-penetrating peptides (CPPs). However, there is limited information on the relative performance of CPPs in delivering proteins to cells, specifically the cytosol and other intracellular locations. Here we use green fluorescent protein (GFP) as a model cargo to compare delivery capacity of five CPP sequences (Penetratin, R8, TAT, Transportan, Xentry) and cyclic derivatives in different human cell lines (HeLa, HEK, 10T1/2, HepG2) representing different tissues. Confocal microscopy analysis indicates that most fusion proteins when incubated with cells at 10 µM localise to endosomes. Quantification of cellular uptake by flow cytometry reveals that uptake depends on both cell type (10T1/2 > HepG2 > HeLa > HEK), and CPP sequence (Transportan > R8 > Penetratin≈TAT > Xentry). CPP sequence cyclisation or addition of a HA-sequence increased cellular uptake, but fluorescence was still contained in vesicles with no evidence of endosomal escape. Our results provide a guide to select CPP for endosomal/lysosomal delivery and a basis for developing more efficient CPPs in the future.