Sandip M. Prasad

Anatomic Bladder Neck Preservation During Robotic-Assisted Laparoscopic Radical Prostatectomy: Description of Technique and Outcomes

BACKGROUND Robotic-assisted laparoscopic radical prostatectomy (RALP) has been rapidly adopted despite a daunting learning curve with bladder neck dissection as a challenging step for newcomers. OBJECTIVE To describe an anatomic, reproducible technique of bladder neck preservation (BNP) and associated perioperative and long-term outcomes. DESIGN, SETTINGS, AND PARTICIPANTS From September 2005 to May 2009, data from 619 consecutive RALP were prospectively collected and compared on the basis of bladder neck dissection technique with 348 BNP and 271 standard technique (ST). SURGICAL PROCEDURE RALP with BNP. MEASUREMENTS Tumor characteristics, perioperative complications, and post-operative urinary control were evaluated at 4, 12 and 24 months using (1) the Expanded Prostate Cancer Index (EPIC) urinary function scale scored from 0-100; and (2) continence defined as zero pads per day. RESULTS AND LIMITATIONS Mean age for BNP versus ST was 57.1±6.6 yr versus 58.9±6.7 yr (p=0.033), while complication rates did not vary significantly by technique. Estimated blood loss was 183.7±95.8 ml versus 224.6±108 ml (p=0.938) in men who underwent BNP versus ST. The overall positive margin rate was 12.8%, which did not differ at the prostate base for BNP versus ST (1.4% vs. 2.2%, p=0.547). Mean urinary function scores for BNP versus ST at 4, 12, and 24 mo were 64.6 versus 57.2 (p=0.037), 80.6 versus 79.0 (p=0.495), and 94.1 versus 86.8 (p<0.001). Similarly, BNP versus ST continence rates at 4, 12, and 24 mo were 65.6% versus 26.5% (p<0.001), 86.4% versus 81.4% (p=0.303), and 100% versus 96.1% (p=0.308). CONCLUSIONS BNP versus ST is associated with quicker recovery of urinary function and similar cancer control.

Surgical Apgar Outcome Score : Perioperative Risk Assessment for Radical Cystectomy

PURPOSE Currently objective perioperative risk assessment metrics are lacking for radical cystectomy. Using a simple 10-point scale similar to neonatal Apgar assessment we evaluated whether a surgical outcome score calculated immediately after radical cystectomy would predict major complications and mortality. MATERIALS AND METHODS We identified 155 consecutive radical cystectomies performed between 2005 and 2007 at our institution. Data were collected on 45 preoperative and intraoperative variables. We used a framework established by the National Surgical Quality Improvement Program to evaluate major complications within 30 days of surgery. We used a 10-point scoring system that had been previously validated in general and vascular surgery populations, comprising estimated blood loss, lowest heart rate and lowest mean arterial pressure. RESULTS A total of 40 (26%) patients undergoing radical cystectomy experienced a major complication within 30 days of the operation. There was a progressive decrease in complications with increasing surgical Apgar score, in that patients with a low vs a high Apgar score were more likely to experience complications (OR 6.9, 95% CI 1.9-24.2). Coronary artery disease, American Society of Anesthesiologists class, intraoperative blood transfusion, volume of intravenous fluid administered and female gender were also associated with major complications (p <0.05). CONCLUSIONS In patients undergoing radical cystectomy the surgical Apgar score predicts major postoperative complications and death. This simple and objective postoperative metric may be used to dictate the intensity of care. Prospective studies are needed to determine whether treatment decisions based on this scoring system improve radical cystectomy outcomes.

Bladder cancer risk from occupational and environmental exposures

Approximately 50% of bladder cancer incidence in the United States has been attributed to known carcinogens, mainly from cigarette smoking. Following the identification of this important causative factor, many investigators have attempted to identify other major causes of bladder cancer in the environment. Genetic and epigenetic alterations related to carcinogenesis in the bladder have been linked to environmental and occupational factors unrelated to cigarette smoking and may account for a significant portion of bladder cancer cases in non-smokers. The interaction between genetics and exposures may modulate bladder cancer risk and influence the differing incidence, progression, and mortality of this disease in different genders and races. Comparative molecular studies are underway to measure the relative effects of environment and inheritance to account for observed differences in the epidemiology of bladder cancer. The use of geospatial tools and population-based data will offer further insight into the environmentally-linked causes of bladder cancer.

SPOP Promotes Tumorigenesis by Acting as a Key Regulatory Hub in Kidney Cancer

Hypoxic stress and hypoxia-inducible factors (HIFs) play important roles in a wide range of tumors. We demonstrate that SPOP, which encodes an E3 ubiquitin ligase component, is a direct transcriptional target of HIFs in clear cell renal cell carcinoma (ccRCC). Furthermore, hypoxia results in cytoplasmic accumulation of SPOP, which is sufficient to induce tumorigenesis. This tumorigenic activity occurs through the ubiquitination and degradation of multiple regulators of cellular proliferation and apoptosis, including the tumor suppressor PTEN, ERK phosphatases, the proapoptotic molecule Daxx, and the Hedgehog pathway transcription factor Gli2. Knockdown of SPOP specifically kills ccRCC cells, indicating that it may be a promising therapeutic target. Collectively, our results indicate that SPOP serves as a regulatory hub to promote ccRCC tumorigenesis.

Urothelial carcinoma of the bladder: definition, treatment and future efforts

The identification of patients with high-risk bladder cancer is important for the timely and appropriate treatment of this lethal disease. The understanding of the natural history of bladder cancer has improved; however, the criteria used to define high-risk disease and the relevant treatment strategies have remained the same for the past several decades, despite multiple large, randomized, prospective clinical trials that have evaluated the use of intravesical, surgical and systemic therapies. The genetic signature of high-risk bladder cancer has been a focus of investigation and has led to the discovery of potential molecular targets for disease identification, risk stratification and therapy. These advances, combined with a comprehensive risk assessment profile that incorporates available pathological and clinical characteristics, might improve the diagnosis and treatment of patients with bladder cancer.

The Impact of Mechanical Bowel Preparation on Postoperative Complications for Patients Undergoing Cystectomy and Urinary Diversion

PURPOSE The benefit of routine mechanical bowel preparation for patients undergoing radical cystectomy is not well established. We compared postoperative complications in patients who did or did not undergo mechanical bowel preparation before radical cystectomy. MATERIALS AND METHODS In 2008 a single surgeon (GDS) performed open radical cystectomy with an ileal conduit or orthotopic neobladder in 105 consecutive patients with preoperative mechanical bowel preparation consisting of 4 l GoLYTELY®. In 2009 radical cystectomy with an ileal conduit or orthotopic neobladder was performed in 75 consecutive patients without mechanical bowel preparation. A comprehensive database provided clinical, pathological and outcome data. RESULTS All patients had complete perioperative data available. The 2 groups were similar in age, Charlson comorbidity score, diversion type, receipt of neoadjuvant radiation or chemotherapy, blood loss, hospital stay, time to diet and pathological stage. Postoperative urinary tract infection, wound dehiscence and perioperative death rates were similar in the 2 groups. Clostridium difficile infection developed within 30 days of surgery in 11 of 105 vs 2 of 75 patients with vs without mechanical bowel preparation (p = 0.08). When adjusted for the annual hospital-wide C. difficile rate, the difference remained insignificant (p = 0.21). Clavien grade 3 or greater abdominal and gastrointestinal complications, including fascial dehiscence, abdominal abscess, small bowel obstruction, bowel leak and entero-diversion fistula, developed in 7 of 105 patients with (6.7%) vs 11 of 75 without (14.7%) mechanical bowel preparation (p = 0.08). CONCLUSIONS The use of mechanical bowel preparation for patients undergoing radical cystectomy with an ileal conduit or orthotopic neobladder does not seem to impact the rates of perioperative infectious, wound and bowel complications. Larger series with multiple surgeons are necessary to confirm these findings.

National trends in prostate cancer screening among older American men with limited 9-year life expectancies: evidence of an increased need for shared decision making.

Prostate‐specific antigen (PSA) screening for prostate cancer remains controversial. Most groups recommend informed decision making for men with 10 years of remaining life expectancy. The primary objective of this observational cohort study was to investigate the association between predicted 9‐year mortality and prostate cancer screening among American men aged ≥65 years in 2005 and 2010. The second objective was to analyze the proportions of men who discussed screening with their physicians.

Effect of Depression on Diagnosis, Treatment, and Mortality of Men With Clinically Localized Prostate Cancer

PURPOSE Although demographic, clinicopathologic, and socioeconomic differences may affect treatment and outcomes of prostate cancer, the effect of mental health disorders remains unclear. We assessed the effect of previously diagnosed depression on outcomes of men with newly diagnosed prostate cancer. PATIENTS AND METHODS We performed a population-based observational cohort study using Surveillance, Epidemiology, and End Results-Medicare linked data of 41,275 men diagnosed with clinically localized prostate cancer from 2004 to 2007. We identified 1,894 men with a depressive disorder in the 2 years before the prostate cancer diagnosis and determined its effect on treatment and survival. RESULTS Men with depressive disorder were older, white or Hispanic, unmarried, resided in nonmetropolitan areas and areas of lower median income, and had more comorbidities (P < .05 for all), but there was no variation in clinicopathologic characteristics. In adjusted analyses, men with depressive disorder were more likely to undergo expectant management for low-, intermediate-, and high-risk disease (P ≤ .05, respectively). Conversely, depressed men were less likely to undergo definitive therapy (surgery or radiation) across all risk strata (P < .01, respectively). Depressed men experienced worse overall mortality across risk strata (low: relative risk [RR], 1.86; 95% CI, 1.48 to 2.33; P < .001; intermediate: RR, 1.25; 95% CI, 1.06 to 1.49; P = .01; high: RR, 1.16; 95% CI, 1.03 to 1.32; P = .02). CONCLUSION Men with intermediate- or high-risk prostate cancer and a recent diagnosis of depression are less likely to undergo definitive treatment and experience worse overall survival. The effect of depression disorders on prostate cancer treatment and survivorship warrants further study, because both conditions are relatively common in men in the United States.

Inappropriate utilization of radiographic imaging in men with newly diagnosed prostate cancer in the United States

The use of radiographic imaging (bone scan and computerized tomography) is only recommended for men diagnosed with high‐risk prostate cancer characteristics. The authors sought to characterize utilization patterns of imaging in men with newly diagnosed prostate cancer.

Incidence, Risk Factors, and Complications of Postoperative Delirium in Elderly Patients Undergoing Radical Cystectomy

OBJECTIVE To identify the risk factors for, and complications associated with, the development of delirium after radical cystectomy. MATERIALS AND METHODS From July 2008 to December 2009, 59 patients, aged ≥65 years and undergoing radical cystectomy, were prospectively enrolled. The baseline cognitive status was assessed using the Mini-Mental Status Examination. Postoperative delirium was assessed using the Confusion Assessment Method. RESULTS A total of 49 patients completed the surgery and all assessments. The incidence of postoperative delirium was 29%, with duration of 1-5 days. On univariate analysis, older age and preoperative Mini-Mental Status Examination score were associated with postoperative delirium. On multivariate analysis, only age was associated with postoperative delirium (odds ratio 1.52, 95% confidence interval 1.04-2.22, P=.03). The 2 groups did not differ in pathologic stage, length of surgery, intraoperative and postoperative narcotic usage, body mass index, age-adjusted Charlson comorbidity index, activities of daily living scores, smoking history, preoperative hematocrit, estimated blood loss, urinary tract infection, interval to a regular diet, or length of hospital stay. The patients who developed postoperative delirium were more likely to undergo readmission (odds ratio 10.7, 95% confidence interval 2.2-51.8, P=.01) and reoperation (odds ratio 9.2, 95% confidence interval 1.5-55.3, P=.03) but did not differ in the 90-day and 1-year mortality rates or incidence of postoperative complications. CONCLUSION In patients aged≥65 years, a lower preoperative Mini-Mental Status Examination score and older age were significantly associated with the development of postcystectomy delirium, as measured using the Confusion Assessment Method. The patients who developed delirium were more likely to undergo readmission and reoperation. Larger studies with multiple surgeons are needed to validate these findings.