Yair Lotan

Epidemiology and Risk Factors of Urothelial Bladder Cancer

CONTEXT Urothelial bladder cancer (UBC) is a disease of significant morbidity and mortality. It is important to understand the risk factors of this disease. OBJECTIVE To describe the incidence, prevalence, and mortality of UBC and to review and interpret the current evidence on and impact of the related risk factors. EVIDENCE ACQUISITION A literature search in English was performed using PubMed. Relevant papers on the epidemiology of UBC were selected. EVIDENCE SYNTHESIS UBC is the 7th most common cancer worldwide in men and the 17th most common cancer worldwide in women. Approximately 75% of newly diagnosed UBCs are noninvasive. Each year, approximately 110 500 men and 70 000 women are diagnosed with new cases and 38 200 patients in the European Union and 17 000 US patients die from UBC. Smoking is the most common risk factor and accounts for approximately half of all UBCs. Occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons are other important risk factors. The impact of diet and environmental pollution is less evident. Increasing evidence suggests a significant influence of genetic predisposition on incidence. CONCLUSIONS UBC is a frequently occurring malignancy with a significant impact on public health and will remain so because of the high prevalence of smoking. The importance of primary prevention must be stressed, and smoking cessation programs need to be encouraged and supported.

BAP1 loss defines a new class of renal cell carcinoma

The molecular pathogenesis of renal cell carcinoma (RCC) is poorly understood. Whole-genome and exome sequencing followed by innovative tumorgraft analyses (to accurately determine mutant allele ratios) identified several putative two-hit tumor suppressor genes, including BAP1. The BAP1 protein, a nuclear deubiquitinase, is inactivated in 15% of clear cell RCCs. BAP1 cofractionates with and binds to HCF-1 in tumorgrafts. Mutations disrupting the HCF-1 binding motif impair BAP1-mediated suppression of cell proliferation but not deubiquitination of monoubiquitinated histone 2A lysine 119 (H2AK119ub1). BAP1 loss sensitizes RCC cells in vitro to genotoxic stress. Notably, mutations in BAP1 and PBRM1 anticorrelate in tumors (P = 3 × 10−5), and combined loss of BAP1 and PBRM1 in a few RCCs was associated with rhabdoid features (q = 0.0007). BAP1 and PBRM1 regulate seemingly different gene expression programs, and BAP1 loss was associated with high tumor grade (q = 0.0005). Our results establish the foundation for an integrated pathological and molecular genetic classification of RCC, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.

Sensitivity and specificity of commonly available bladder tumor markers versus cytology: results of a comprehensive literature review and meta-analyses

OBJECTIVES To determine the clinical utility of urine-based bladder tumor markers (UBBTMs) and cytology in the treatment of patients with transitional cell carcinoma on the basis of their statistical performance. METHODS A comprehensive literature review was performed using Medline (1966 to current) and other search engines. Data regarding the statistical performance of UBBTMs were double extracted and rectified. Studies addressing comparable patient populations were combined and hierarchical Bayesian meta-analyses performed to calculate the sensitivity and specificity of commonly used UBBTMs, as well as urinary cytology. Patient populations were stratified by tumor stage and grade when data were presented in an extractable fashion. RESULTS The literature review yielded 54 publications, 338 distinct patient groups (controls, screening population, patients with cancer, strata based on grade and stage) and more than 10,000 patients. The number of groups varied from 1 to 18, and the number of patients ranged from less than 100 to more than 1500 for the various markers. All UBBTMs have better sensitivity compared with cytology, especially for low-grade/stage disease, but do not match cytology regarding specificity. In patients with grade 1 and 2 tumors, several UBBTMs are significantly superior statistically in terms of sensitivity compared with cytology. The sensitivity for transitional cell carcinoma in situ (Tis) is surprisingly poor for all UBBTMs. CONCLUSIONS UBBTMs can be used for follow-up of low-grade/stage tumors but should not replace cystoscopy. All UBBTMs have better sensitivity than cytology and could potentially replace routine cytology during patient follow-up.

Systematic Review of Complications of Prostate Biopsy

CONTEXT Prostate biopsy is commonly performed for cancer detection and management. The benefits and risks of prostate biopsy are germane to ongoing debates about prostate cancer screening and treatment. OBJECTIVE To perform a systematic review of complications from prostate biopsy. EVIDENCE ACQUISITION A literature search was performed using PubMed and Embase, supplemented with additional references. Articles were reviewed for data on the following complications: hematuria, rectal bleeding, hematospermia, infection, pain, lower urinary tract symptoms (LUTS), urinary retention, erectile dysfunction, and mortality. EVIDENCE SYNTHESIS After biopsy, hematuria and hematospermia are common but typically mild and self-limiting. Severe rectal bleeding is uncommon. Despite antimicrobial prophylaxis, infectious complications are increasing over time and are the most common reason for hospitalization after biopsy. Pain may occur at several stages of prostate biopsy and can be mitigated by anesthetic agents and anxiety-reduction techniques. Up to 25% of men have transient LUTS after biopsy, and <2% have frank urinary retention, with slightly higher rates reported after transperineal template biopsy. Biopsy-related mortality is rare. CONCLUSIONS Preparation for biopsy should include antimicrobial prophylaxis and pain management. Prostate biopsy is frequently associated with minor bleeding and urinary symptoms that usually do not require intervention. Infectious complications can be serious, requiring prompt management and continued work into preventative strategies.

Transvaginal laparoscopic nephrectomy: Development and feasibility in the porcine model

OBJECTIVES To assess feasibility of laparoscopic nephrectomy completed entirely by way of the vagina in the porcine model. METHODS Six transvaginal laparoscopic nephrectomies were performed in female farm pigs. Two acute and two 1-week survival animals were used for the study. Before killing the survival animals, a second transvaginal laparoscopic nephrectomy was performed on the remaining renal unit. For one renal unit, the laparoscopic nephrectomy was completed entirely by way of the vagina. In five renal units, a single, 5-mm transabdominal trocar for the laparoscope was required to facilitate visualization. RESULTS The operative time for the procedure completed entirely by way of the vagina was 360 minutes, and the mean operative time for the procedures requiring placement of a single 5-mm transabdominal trocar was 210 minutes. In 5 cases, dissection, control of the renal pedicle, and extraction of the kidney were successfully completed using a transvaginal approach. In 1 acute case, an uncontrollable vascular injury occurred during placement of the Endo-GIA stapler, resulting in exsanguination. In all other cases, the mean blood loss was less than 30 mL, and no significant perioperative complications were noted. Both survival pigs had normal bowel and bladder function before being killed. CONCLUSIONS Complete transvaginal laparoscopic dissection and nephrectomy is feasible in the porcine model using a single, 5-mm abdominal trocar for visualization. A completely transvaginal laparoscopic nephrectomy was performed once, but limitations imposed by the porcine anatomy and by the currently available instrumentation made the procedure very cumbersome. Additional development of this technique in animal models and improved instrumentation is needed before clinical assessment is warranted.

Cost Comparison of Robotic, Laparoscopic, and Open Radical Prostatectomy for Prostate Cancer

BACKGROUND Demand and utilization of minimally invasive approaches to radical prostatectomy have increased in recent years, but comparative studies on cost are lacking. OBJECTIVE To compare costs associated with robotic-assisted laparoscopic radical prostatectomy (RALP), laparoscopic radical prostatectomy (LRP), and open retropubic radical prostatectomy (RRP). DESIGN, SETTING, AND PARTICIPANTS The study included 643 consecutive patients who underwent radical prostatectomy (262 RALP, 220 LRP, and 161 RRP) between September 2003 and April 2008. MEASUREMENTS Direct and component costs were compared. Costs were adjusted for changes over the time of the study. RESULTS AND LIMITATIONS Disease characteristics (body mass index, preoperative prostate-specific antigen, prostate size, and Gleason sum score 8-10) were similar in the three groups. Nerve sparing was performed in 85% of RALP procedures, 96% of LRP procedures, and 90% of RRP procedures (p<0.001). Lymphadenectomy was more commonly performed in RRP (100%) compared to LRP (22%) and RALP (11%) (p<0.001). Mean length of hospital stay was higher for RRP than for LRP and RALP. The median direct cost was higher for RALP compared to LRP or RRP (RALP:

Nomograms provide improved accuracy for predicting survival after radical cystectomy

6752 [interquartile range (IQR):

Management Of Ureteral Calculi: A Cost Comparison And Decision Making Analysis

6283-7369]; LRP:

Preoperative Hydronephrosis, Ureteroscopic Biopsy Grade and Urinary Cytology Can Improve Prediction of Advanced Upper Tract Urothelial Carcinoma

5687 [IQR:

A Gain-of-Function Mutation in DHT Synthesis in Castration-Resistant Prostate Cancer

4941-5905]; RRP: