Matthew H. Hayn

The Learning Curve of Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

BACKGROUND Robot-assisted radical cystectomy (RARC) has evolved as a minimally invasive alternative to open radical cystectomy for patients with invasive bladder cancer. OBJECTIVE We sought to define the learning curve for RARC by evaluating results from a multicenter, contemporary, consecutive series of patients who underwent this procedure. DESIGN, SETTING, AND PARTICIPANTS Utilizing the International Robotic Cystectomy Consortium database, a prospectively maintained and institutional review board-approved database, we identified 496 patients who underwent RARC by 21 surgeons at 14 institutions from 2003 to 2009. MEASUREMENTS Cut-off points for operative time, lymph node yield (LNY), estimated blood loss (EBL), and margin positivity were identified. Using specifically designed statistical mixed models, we were able to inversely predict the number of patients required for an institution to reach the predetermined cut-off points. RESULTS AND LIMITATIONS Mean operative time was 386 min, mean EBL was 408 ml, and mean LNY was 18. Overall, 34 of 482 patients (7%) had a positive surgical margin (PSM). Using statistical models, it was estimated that 21 patients were required for operative time to reach 6.5h and 8, 20, and 30 patients were required to reach an LNY of 12, 16, and 20, respectively. For all patients, PSM rates of <5% were achieved after 30 patients. For patients with pathologic stage higher than T2, PSM rates of <15% were achieved after 24 patients. CONCLUSIONS RARC is a challenging procedure but is a technique that is reproducible throughout multiple centers. This report helps to define the learning curve for RARC and demonstrates an acceptable level of proficiency by the 30th case for proxy measures of RARC quality.

Complications After Robot-assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

BACKGROUND Complication reporting is highly variable and nonstandardized. Therefore, it is imperative to determine the surgical outcomes of major oncologic procedures. OBJECTIVE To describe the complications after robot-assisted radical cystectomy (RARC) using a standardized and validated reporting methodology. DESIGN, SETTING, AND PARTICIPANTS Using the International Robotic Cystectomy Consortium (IRCC) database, we identified 939 patients who underwent RARC, had available complication data, and had at least 90 d of follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Complications were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center (MSKCC) system and were defined and stratified by organ system. Secondary outcomes included identification of preoperative and intraoperative variables predicting complications. Logistic regression models were used to define predictors of complications and readmission. RESULTS AND LIMITATIONS Forty-one percent (n=387) and 48% (n=448) of patients experienced a complication within 30 and 90 d of surgery, respectively. The highest grade of complication was grade 0 in 52%, grade 1-2 in 29%, and grade 3-5 in 19% patients. Gastrointestinal, infectious, and genitourinary complications were most common (27%, 23%, and 17%, respectively). On multivariable analysis, increasing age group, neoadjuvant chemotherapy, and receipt of blood transfusion were independent predictors of any and high-grade complications, respectively. Thirty and 90-d mortality was 1.3% and 4.2%, respectively. As a multi-institutional database, a disparity in patient selection, operating standards, postoperative management, and reporting of complications can be considered a major limitation of the study. CONCLUSIONS Surgical morbidity after RARC is significant when reported using a standardized reporting methodology. The majority of complications are low grade. Strict reporting of complications is necessary to advocate for radical cystectomy (RC) and helps in patient counseling.

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.

RENAL nephrometry score predicts surgical outcomes of laparoscopic partial nephrectomy

Study Type – Therapy (case series)

Plasma Antioxidants and Cognitive Performance in Middle‐Aged and Older Adults: Results of the Austrian Stroke Prevention Study

OBJECTIVES: To study the association between cognitive status and plasma concentrations of various antioxidants in middle‐aged and older individuals without neuropsychiatric disease.

Magnetic Resonance Imaging White Matter Hyperintensities in Clinically Normal Elderly Individuals Correlations With Plasma Concentrations of Naturally Occurring Antioxidants

BACKGROUND AND PURPOSE White matter hyperintensities are a common magnetic resonance imaging (MRI) observation in the elderly. They are believed to represent a subclinical form of ischemic brain damage, but the underlying pathophysiological mechanisms are still incompletely understood. We postulated that oxidative mechanisms may favor the development of these changes and therefore correlated their presence and extent with the plasma concentrations of 10 naturally occurring antioxidants. METHODS We studied 355 clinically normal volunteers 45 to 75 years of age who were randomly selected from the official community register. A 1.5-T MRI of the brain and measurements of the plasma concentrations of antioxidants including zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, alpha- and beta-carotene, retinol, gamma- and alpha-tocopherol, as well as ascorbate were performed in all study participants. White matter hyperintensities were graded as punctate, beginning confluent, and confluent abnormalities. RESULTS Punctate, beginning confluent, and confluent white matter abnormalities occurred in 101 (28.5%), 44 (12.4%), and 14 (3.9%) individuals, respectively. Study participants with white matter damage were significantly older and had a higher frequency of arterial hypertension and cardiac disease but lower serum concentrations of total cholesterol. The plasma levels of lycopene and alpha-tocopherol were significantly lower in subjects with early confluent and confluent white matter hyperintensities, while individuals with punctate foci had an antioxidant status similar to those with normal MRI scans. Alpha-tocopherol was the only antioxidant that remained significantly and inversely related to the presence of beginning confluent and confluent white matter changes after adjustment for the between-group differences in age, arterial hypertension, cardiac disease, and cholesterol. The adjusted odds ratio for early confluent and confluent white matter abnormalities was 3.70 (95% CI, 1.69 to 8.10) in the lowest compared with the highest quartile of the alpha-tocopherol concentration. The odds ratio increased to 7.11 (95% CI, 1.63 to 22.84) when quintiles of the alpha-tocopherol level were compared. CONCLUSIONS These data do not prove a causal relation, but they provide evidence of an association between low plasma concentrations of vitamin E and a higher risk of cerebral white matter disease in elderly normal subjects.

Defining Morbidity of Robot-Assisted Radical Cystectomy Using a Standardized Reporting Methodology

BACKGROUND Adverse event reporting is highly variable and nonstandardized in urologic literature, especially for robot-assisted radical cystectomy (RARC). OBJECTIVE We sought to better characterize complications in patients after RARC using a standardized reporting methodology. DESIGN, SETTING, AND PARTICIPANTS Using a prospectively maintained, single-institution database, we identified 156 consecutive patients who underwent RARC with at least 90 d of follow-up. Complications were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center (MSKCC) system and were defined and stratified by organ system. MEASUREMENTS Logistic regression models were used to define predictors of complications. Cox proportional hazard modeling and Kaplan-Meier survival analyses were used to correlate complications and 90-d mortality. RESULTS AND LIMITATIONS Fifty-two percent (81 of 156) of patients experienced a complication within 90 d of surgery. Sixty-five percent (102 of 156) of patients experienced a postoperative complication at a median follow-up of 9 mo. The highest grade of complication was grade 1 in 30 patients (19%), grade 2 in 34 patients (22%), and grade 3-5 in 38 patients (24%). Twenty-one percent (33 of 156) of patients required hospital readmission. Gastrointestinal, infectious, and genitourinary complications were most common (31%, 25%, and 13%, respectively). The 90-d mortality rate was 5.8%. CONCLUSIONS When reported using strict guidelines, surgical morbidity after RARC is significant, but the majority of complications are low grade. Despite the high prevalence of low-grade complications, the mortality rate was acceptably low. Stringent reporting of complications after RARC is essential for counseling patients, assessing surgical quality, and allowing comparisons with open radical cystectomy and among institutions.

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.

Is patient outcome compromised during the initial experience with robot-assisted radical cystectomy? Results of 164 consecutive cases.

Study Type – Therapy (case series)

Functional and immunohistochemical characterization of CB1 and CB2 receptors in rat bladder.

OBJECTIVES To determined the localization of CB(1) and CB(2) receptors in rat bladder and investigate the effect of a mixed CB(1)/CB(2) receptor agonist, ajulemic acid (AJA), on chemically evoked release of the sensory neuropeptide calcitonin gene-related peptide (CGRP). METHODS Whole rat bladders were incubated in a series of tissue baths containing physiologic salt solution to measure baseline CGRP release by enzyme immunoassay. Capsaicin (30 nM) and adenosine triphosphate (10 muM) were used to provoke CGRP release in the presence or absence of AJA. Specificity of AJA for CB(1) and CB(2) receptors was determined using antagonists. Localization was determined by immunofluorescence for CB(1) and CB(2) receptors in fixed bladders. RESULTS Immunofluorescence showed the localization of CB(1) and CB(2) receptors in the bladder. Mean baseline CGRP release was 605 +/- 62 pg/g of bladder weight, and AJA had no effect on CGRP release. The addition of adenosine triphosphate/capsaicin significantly increased the CGRP release over baseline, by 44% (P < .05), and AJA application significantly decreased CGRP release, by 29% compared with controls (P < .05). The CB(1) and CB(2) antagonists AM 251 and AM 630, respectively, reversed the blunting effect of AJA on evoked CGRP release, resulting in an increase of 40% and 38% over baseline, respectively. CONCLUSIONS CB(1) and CB(2) receptors are localized in the urothelium of rat bladder, and application of AJA inhibits the evoked release of CGRP by acting on CB(1) and CB(2) receptors. These findings identify a potential new pathway for study in the evaluation and treatment of painful bladder syndrome/interstitial cystitis.