Ketan K. Badani

Analysis of intracorporeal compared with extracorporeal urinary diversion after robot-assisted radical cystectomy: Results from the international robotic cystectomy consortium

BACKGROUND Intracorporeal urinary diversion (ICUD) has the potential benefits of a smaller incision, reduced pain, decreased bowel exposure, and reduced risk of fluid imbalance. OBJECTIVE To compare the perioperative outcomes of patients undergoing extracorporeal urinary diversion (ECUD) and ICUD following robot-assisted radical cystectomy (RARC). DESIGN, SETTING, AND PARTICIPANTS We reviewed the database of the International Robotic Cystectomy Consortium (IRCC) (18 international centers), with 935 patients who had undergone RARC and pelvic lymph node dissection (PLND) between 2003 and 2011. INTERVENTION All patients within the IRCC underwent RARC and PLND as indicated. The urinary diversion was performed either intracorporeally or extracorporeally. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Demographic data, perioperative outcomes, and complications in patients undergoing ICUD or ECUD were compared. All patients had at least a 90-d follow-up. The Fisher exact test was used to summarize categorical variables and the Wilcoxon rank sum test or Kruskal-Wallis test for continuous variables. RESULTS AND LIMITATIONS Of 935 patients who had RARC and PLND, 167 patients underwent ICUD (ileal conduit: 106; neobladder: 61), and 768 patients had an ECUD (ileal conduit: 570; neobladder: 198). Postoperative complications data were available for 817 patients, with a minimum follow-up of 90 d. There was no difference in age, gender, body mass index, American Society of Anesthesiologists grade, or rate of prior abdominal surgery between the groups. The operative time was equivalent (414 min), with the median hospital stay being marginally longer for the ICUD group (9 d vs 8 d, p=0.086). No difference in the reoperation rates at 30 d was noted between the groups. The 90-d complication rate was not significant between the two groups, but a trend favoring ICUD over ECUD was noted (41% vs 49%, p=0.05). Gastrointestinal complications were significantly lower in the ICUD group (p ≤ 0.001). Patients with ICUD were at a lower risk of experiencing a postoperative complication at 90 d (32%) (odds ratio: 0.68; 95% confidence interval, 0.50-0.94; p=0.02). Being a retrospective study was the main limitation. CONCLUSIONS Robot-assisted ICUD can be accomplished safely, with comparable outcomes to open urinary diversion. In this cohort, patients undergoing ICUD had a relatively lower risk of complications.

Single luminal epithelial progenitors can generate prostate organoids in culture

The intrinsic ability to exhibit self-organizing morphogenetic properties in ex vivo culture may represent a general property of tissue stem cells. Here we show that single luminal stem/progenitor cells can generate prostate organoids in a three-dimensional culture system in the absence of stroma. Organoids generated from CARNs (castration-resistant Nkx3.1-expressing cells) or normal prostate epithelia exhibit tissue architecture containing luminal and basal cells, undergo long-term expansion in culture and exhibit functional androgen receptor signalling. Lineage-tracing demonstrates that luminal cells are favoured for organoid formation and generate basal cells in culture. Furthermore, tumour organoids can initiate from CARNs after oncogenic transformation and from mouse models of prostate cancer, and can facilitate analyses of drug response. Finally, we provide evidence supporting the feasibility of organoid studies of human prostate tissue. Our studies underscore the progenitor properties of luminal cells, and identify in vitro approaches for studying prostate biology.

Active surveillance for renal cortical neoplasms.

PURPOSE We retrospectively evaluated our single center experience with patients with renal cortical neoplasms who elected active surveillance. MATERIALS AND METHODS We retrospectively evaluated our urological oncology database between January 1993 and January 2009, identifying a total of 223 renal cortical neoplasms in 212 patients that were initially managed by active surveillance. We described patient and tumor characteristics, and assessed the differences between patients who remained on AS and those who underwent delayed intervention or progressed with metastasis. RESULTS Median patient age was 71 years at active surveillance initiation and the median Charlson comorbidity index was 3. Median tumor size was 2.8 cm (range 0.5 to 13.7) at study enrollment and 3.7 cm (range 0.9 to 14.1) at final assessment. The median growth rate in the entire cohort was 0.34 cm per year (range 0.29 to 2.3). Median followup was 35 months (range 6 to 137). Active surveillance failed in 15 patients (7%), of whom 4 (2%) progressed to metastasis and 11 (5%) required intervention. When comparing cases of failed active surveillance with those that continued, there were statistical differences in initial tumor size (2.61 vs 3.64 cm, p = 0.019), final tumor size (3.56 vs 5.17 cm, p = 0.001) and growth rate (0.34 vs 1.75, p = 0.001). There was no correlation between initial tumor size and growth rate (Pearsons coefficient r = 0.006, p = 0.932). A total of 14 patients died of another medical condition. Only 1 cancer related death (0.5%) was reported in the entire cohort. CONCLUSIONS Active surveillance for renal cortical neoplasms in select older patients with comorbidities is a reasonable treatment option. At 3-year followup we noted a 7% failure rate.

Clinical Outcomes After Radical Prostatectomy in Diabetic Patients Treated With Metformin

OBJECTIVES To investigate the relationship between diabetes and metformin use with outcomes after radical prostatectomy (RP) for clinically localized cancer. METHODS A total of 112 diabetic metformin users and 98 diabetic non-metformin users treated with RP from 1990 to 2009 were identified. Nondiabetic controls were match using their 5-year risk of biochemical recurrence (BCR) as calculated by the preoperative Kattan nomogram. RESULTS A total of 616 patients were evaluated in this study. There was no significant difference between nondiabetic and diabetic patients, including metformin users, with respect to age, clinical stage, preoperative prostate-specific antigen (PSA) score, pathologic Gleason score, and pathologic stage. Diabetic patients, including metformin users, were more likely to be of African American or Hispanic background than were nondiabetic controls (P = .001). The estimated 5-year BCR-free survival was 75.0% for nondiabetic patients, compared with 66.1% for metformin users and 59.3% for diabetic non-metformin users (P = .004). In multivariate analysis, metformin use was not significantly associated with risk of BCR (HR = 0.94; 95% CI = 0.6-1.5, P = .817). However, being diabetic, regardless of metformin use, resulted in a 55% increase in risk of BCR (HR = 1.55; 95% CI = 1.03-2.33, P = .034). CONCLUSIONS Diabetes, regardless of metformin use, was significantly associated with an increased likelihood of BCR after RP. Metformin use did not prove to be of any benefit. These observations underscore the importance for further studies evaluating the metabolic pathways that affect prostate cancer biology.

Validating the Use of the Mimic dV-trainer for Robotic Surgery Skill Acquisition Among Urology Residents

OBJECTIVE To compare robotic surgery skill acquisition of residents trained with Mimic dVTrainer (MdVT) and da Vinci Surgical System (dVSS) console. No standardized curriculum currently exists for robotic surgical education. The MdVT is a compact hardware platform that closely reproduces the experience of the dVSS. METHODS Sixteen urology trainees were randomized into 3 groups. A baseline evaluation using dVSS was performed and consisted of 2 exercises requiring endowrist manipulation (EM), camera movement and clutching (CC), needle control (NC), and knot-tying (KT). Groups 1 and 2 completed a standardized training curriculum on MdVT and dVSS, respectively. Group 3 received no additional training. After completion of the training phase, all trainees completed a secondary evaluation on dVSS consisting of the same exercises performed during baseline evaluation. RESULTS There was no difference in baseline performance scores across the 3 groups. Although Group 3 showed no significant improvement in EM/CC domain (P = .15), Groups 1 and 2 had statistically significant improvement in EM/CC domain (P = .039 and P = .007, respectively). The difference in improvement between Groups 1 and group 2 was not statistically different (P = .21). Only Group 2 trainees showed significant improvement in the NC and KT domains during secondary evaluation (P = .02). CONCLUSION Curriculum-based training with MdVT or dVSS significantly improves robotic surgery aptitude. Similar improvements are seen for exercise domains shared between MdVT and dVSS groups. Follow-up studies are necessary to assess the efficacy of MdVT over a wider spectrum of domains.

Gleason 6 prostate cancer: Translating biology into population health

PURPOSE Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. MATERIALS AND METHODS Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. RESULTS The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. CONCLUSIONS The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

Natural History of Renal Cortical Neoplasms During Active Surveillance With Follow-up Longer Than 5 Years

OBJECTIVES To present our experience with patients who elected active surveillance for renal cortical neoplasms (RCNs) with ≥5 years of follow-up. Few data are available regarding the long-term natural history of RCNs during surveillance. METHODS We retrospectively reviewed our urologic oncology database and identified 44 patients with 51 RCNs who had received active surveillance for >5 years of follow-up. The patient and tumor characteristics and tumor growth rate and overall survival data were evaluated. RESULTS The median patient age was 71.7 years (range 55-92), with 32 patients (72.7%) having a Charlson comorbidity index of ≥2. The median tumor size was 2.67 cm (range 0.9-8.6) at diagnosis. Biopsy was performed in 17 patients (38.6%). Of these 17 patients, clear cell renal cell carcinoma was diagnosed in 15 and papillary renal cell carcinoma in 2 patients. The median follow-up was 77.1 months (range 60-137), and the median growth rate was 0.15 cm/y. Of these patients, 2 (4.5%) required delayed intervention. One underwent laparoscopic radical nephrectomy because of a high tumor growth rate, and one elected to withdraw from active surveillance because of personal anxiety, despite having a stable tumor size for 72 months. The latter patient underwent laparoscopic renal cryoablation. Histopathologic examination revealed clear cell renal cell carcinoma in both cases. No metastases or cancer-related deaths occurred in our cohort; 1 patient died of cardiovascular disease. CONCLUSIONS Most RCNs undergoing surveillance for >5 years grew slowly. The metastatic potential appeared minimal in patients who demonstrated low or absent tumor growth for a long period.

Impact of surgeon and volume on extended lymphadenectomy at the time of robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium (IRCC)

Lymph node dissection and its extend during robot‐assisted radical cystectomy varies based on surgeon related factors. This study reports outcomes of robot‐assisted extended lymphadenectomy based on surgeon experience in both academic and private practice settings.

Active surveillance for larger (cT1bN0M0 and cT2N0M0) renal cortical neoplasms.

OBJECTIVES To report our experience with patients undergoing active surveillance (AS) with Stage T1bN0M0 and T2N0M0 tumors. AS is a reasonable option for selected patients with renal cortical neoplasms (RCNs). Most patients undergoing AS are high-risk surgical candidates with Stage T1a lesions. The natural history of larger (Stage cT1bN0M0 and cT2N0M0) RCNs remains undefined. METHODS Our institutions institutional review board-approved urologic oncology database was reviewed and identified 229 patients undergoing AS for RCNs. Of this cohort, 36 patients with 42 RCNs ≥4 cm were monitored at regular intervals with imaging. Patients with metastatic disease were excluded. The patient demographics, presentation, comorbidity level (Charlson comorbidity index), tumor size, tumor growth rate, and survival data were recorded. A failure of AS was defined as a progression to metastasis or a change from AS to a delayed surgical intervention. RESULTS The mean Charlson comorbidity index was 2.83, with 52.8% of patients having an index of ≥3, indicating a high surgical risk. The mean tumor size on the initial computed tomography scan was 7.13 cm (range 4-13.7), and the mean growth rate was 0.57 cm/y (range 0-5.9). With a mean follow-up of 36 months (range 6-96), 5 patients (13.8%) had failure. Three lesions were treated with laparoscopic radical nephrectomy and found to be pT2N0M0 on final pathologic examination. Two patients (5.6%) in this cohort developed metastatic disease, and no cancer-specific deaths occurred. CONCLUSIONS Patients with Stage T1bN0M0 and T2N0M0 RCNs, monitored for a mean follow-up of 3 years, demonstrated a growth rate of 0.57 cm/y, with only 5.6% of patients progressing to metastatic disease.

Optimal strategy for penile rehabilitation after robot‐assisted radical prostatectomy based on preoperative erectile function

Removing of prostate for the treatment of localized prostate cancer is associated with a variable loss of erectile function due to injury of the nerves of erection during operation. Some researchers have reported that after nerve‐sparing radical prostatectomy (RP), the natural recovery time of erectile function is at least 2 years. Factors such as thermal damage, ischaemic injury, mechanically induced nerve stretching and the local inflammatory effects of surgical trauma may also impair the cavernous nerves during RP. The concept of penile rehabilitation was first studied by Montorsi et al. in 1997. They showed that the use of any drug or device at or after RP could maximize the recovery of erectile function. Penile rehabilitation programmes (PRPs) with vasoactive agents, such as oral phosphodiesterase‐5 inhibitors (PDE5Is), intraurethral and intracavernosal vasoactive agents, and vacuum erection devices (VEDs) can protect erectile tissue integrity and prevent corporal smooth muscle atrophy and diminish collagen formation. The present findings are consistent with previous reports that PRPs have a significant beneficial effect on early erectile function recovery and that preoperative erectile function is one of the important predictors of erectile function after RP. Patients can be referred for penile rehabilitation if they have any degree of erectile function (mild, moderate or normal) before operation. We also showed that the combination of PDE5Is and VEDs for PRPs offers the shortest erectile function recovery period.