Health Related Quality of Life of Patients with Bladder Cancer in the RAZOR Trial: A Multi-Institutional Randomized Trial Comparing Robot versus Open Radical Cystectomy.

PURPOSE: We evaluated health related quality of life following robotic and open radical cystectomy as a treatment for bladder cancer. MATERIALS AND METHODS: Using the Randomized Open versus Robotic Cystectomy (RAZOR) trial population we assessed health related quality of life by using the Functional Assessment of Cancer Therapy (FACT)-Vanderbilt Cystectomy Index and the Short Form 8 Health Survey (SF-8) at baseline, 3 and 6 months postoperatively. The primary objective was to assess the impact of surgical approach on health related quality of life. As an exploratory analysis we assessed the impact of urinary diversion type on health related quality of life. RESULTS: Analyses were performed in subsets of the per-protocol population of 302 patients. There was no statistically significant difference between the mean scores by surgical approach at any time point for any FACT-Vanderbilt Cystectomy Index subscale or composite score (p >0.05). The emotional well-being score increased over time in both surgical arms. Patients in the open arm showed significantly better SF-8 sores in the physical and mental summary scores at 6 months compared to baseline (p <0.05). Continent diversion (versus noncontinent) was associated with worse FACT-bladder-cystectomy score at 3 (p <0.01) but not at 6 months, and the SF-8 physical component was better in continent-diversion patients at 6 months (p=0.019). CONCLUSIONS: Our data suggests lack of significant differences in the health related quality of life in robotic and open cystectomies. As robotic procedures become more widespread it is important to discuss this finding during counseling.

Predictors of Recurrence, and Progression-Free and Overall Survival following Open versus Robotic Radical Cystectomy: Analysis from the RAZOR Trial with a 3-Year Followup.

PURPOSE: The RAZOR (Randomized Open versus Robotic Cystectomy) trial revealed noninferior 2-year progression-free survival for robotic radical cystectomy. This update was performed with extended followup for 3 years to determine potential differences between the approaches. We also report 3-year overall survival and sought to identify factors predicting recurrence, and progression-free and overall survival. MATERIALS AND METHODS: We analyzed the per protocol population of 302 patients from the RAZOR study. Cumulative recurrence was estimated using nonbladder cancer death as the competing risk event and the Gray test was applied to assess significance in differences. Progression-free survival and overall survival were estimated by the Kaplan-Meier method and compared with the log rank test. Predictors of outcomes were determined by Cox proportional hazard analysis. RESULTS: Estimated progression-free survival at 36 months was 68.4% (95% CI 60.1-75.3) and 65.4% (95% CI 56.8-72.7) in the robotic and open groups, respectively (p=0.600). At 36 months overall survival was 73.9% (95% CI 65.5-80.5) and 68.5% (95% CI 59.8-75.7) in the robotic and open groups, respectively (p=0.334). There was no significant difference in the cumulative incidence rates of recurrence (p=0.802). Patient age greater than 70 years, poor performance status and major complications were significant predictors of 36-month progression-free survival. Stage and positive margins were significant predictors of recurrence, and progression-free and overall survival. Surgical approach was not a significant predictor of any outcome. CONCLUSIONS: This analysis showed no difference in recurrence, 3-year progression-free survival or 3-year overall survival for robotic vs open radical cystectomy. It provides important prospective data on the oncologic efficacy of robotic radical cystectomy and high level data for patient counseling.

Primary robotic RLPND for nonseminomatous germ cell testicular cancer: a two-center analysis of intermediate oncologic and safety outcomes.

OBJECTIVE: To evaluate the intermediate-term oncologic outcomes and safety profile of the largest case series of primary robotic retroperitoneal lymphadenectomy for low-clinical-stage non-seminomatous germ cell testicular cancer. METHODS: This was a two-center retrospective analysis of robotic RPLND cases for low-clinical-stage (stage I-IIB) non-seminomatous germ cell testicular cancer in the primary setting. Demographic, perioperative, operative and oncologic variables were collected between March 2008 and May 2019. Descriptive analyses were performed and presented as medians with interquartile ranges for continuous variables and frequency and proportions for categorical variables. A survival analysis of time to recurrence was performed using Cox proportional hazards model. Using logistic regression, risk factors for complications were analyzed. Both univariate and multivariate analyses were performed. RESULTS: A total of 58 patients (CS 1 = 56, CS IIA = 2, CS IIB = 0) were identified. The median follow-up was 47 months and the 2-year recurrence-free survival rate was 91%. The five recurrences were all out of the performed dissection template (pelvis = 1 and lung = 4). Only five patients (29%) with occult metastasis underwent adjuvant chemotherapy. The median operative time was 319 min [interquartile range (IQR) 276-355 min], estimated blood loss was 100 ml (IQR 75-200 ml), node count was 26 (IQR 20-31), and length of stay 2 d (IQR 1-3 days). There were 2 (3.3%) intraoperative complications, 19 (32.7%) 30-day postoperative complications to include 14 (24.1%) Clavien grade I, 4 (6.9%) Clavien grade II, 1 (1.7%) Clavien grade III and 0 Clavien grade IV complications. No statistical significance was found on multivariate or univariate analysis for survival analysis of time to recurrence and risk factors for complications. CONCLUSIONS: This study represents the largest case series of primary R-RPLND for the treatment of low-stage non-seminomatous germ cell tumors (NSGCT). With 47 months of follow-up and a low rate of adjuvant chemotherapy, intermediate oncologic efficacy appears to be comparable to the gold standard open approach.

Loss of SETD2 Induces a Metabolic Switch in Renal Cell Carcinoma Cell Lines toward Enhanced Oxidative Phosphorylation.

SETD2, a histone H3 lysine trimethyltransferase, is frequently inactivated and associated with recurrence of clear cell renal cell carcinoma (ccRCC). However, the impact of SETD2 loss on metabolic alterations in ccRCC is still unclear. In this study, SETD2 null isogenic 38E/38F clones derived from 786-O cells were generated by zinc finger nucleases, and subsequent metabolic, genomic, and cellular phenotypic changes were analyzed by targeted metabolomics, RNA sequencing, and biological methods, respectively. Our results showed that compared with parental 786-O cells, 38E/38F cells had elevated levels of MTT/Alamar blue levels, ATP, glycolytic/mitochondrial respiratory capacity, citrate synthase (CS) activity, and TCA metabolites such as aspartate, malate, succinate, fumarate, and α-ketoglutarate. The 38E/38F cells also utilized alternative sources beyond pyruvate to generate acetyl-CoA for the TCA cycle. Moreover, 38E/38F cells showed disturbed gene networks mainly related to mitochondrial metabolism and the oxidation of fatty acids and glucose, which was associated with increased PGC1α, mitochondrial mass, and cellular size/complexity. Our results indicate that SETD2 deficiency induces a metabolic switch toward enhanced oxidative phosphorylation in ccRCC, which can be related to PGC1α-mediated metabolic networks. Therefore, this current study lays the foundation for the further development of a global metabolic analysis of cancer cells in individual patients, which ultimately will have significant potential for the discovery of novel therapeutics and precision medicine in SETD2-inactivated ccRCC.

Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial.

BACKGROUND: Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy. METHODS: The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676. FINDINGS: Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI -9·6% to 10·9%; pnon-inferiority=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group). INTERPRETATION: In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types. FUNDING: National Institutes of Health National Cancer Institute.

Single-dose perioperative mitomycin-C versus thiotepa for low-grade noninvasive bladder cancer.

INTRODUCTION: Mitomycin-C (MMC) and thiotepa are intravesical agents effective in reducing the recurrence of low-grade noninvasive bladder cancer when instilled perioperatively. No studies have compared these agents as a single-dose perioperative instillation. This study tests whether there is a difference in recurrence-free survival in patients with low-grade noninvasive bladder cancer who received intravesical MMC versus thiotepa. MATERIALS AND METHODS: A retrospective review was performed of patients who underwent cystoscopic excision of a bladder mass identified as a small, low-grade, treatment-naïve, noninvasive, wild-type urothelial carcinoma of the bladder and who received either intravesical thiotepa (30 mg/15 cc) or MMC (40 mg/20 cc) between January 1, 2002, and January 1, 2016. Data were collected for demographic characteristics, comorbid conditions, operative information, surveillance, and recurrence. The primary outcome was disease-free survival. Cohorts were compared via the doubly robust estimation approach, which used logistic regression to model the probability of recurrence. RESULTS: Of 154 total patients, 84 received intravesical MMC; 70, thiotepa. No statistical differences were shown between groups for age, sex, race, body mass index, smoking status, or baseline comorbid conditions; mass size, tumor multifocality, or tumor grade; and unadjusted recurrence rates (MMC, 36.0%; thiotepa, 46.0%; p = .33) at similar median follow up (MMC, 20.4; thiotepa, 22.8 months; p = .46). The robust logistic regression analysis yielded no differences in recurrence rates between MMC and thiotepa (OR, 0.65 [95% CI, 0.33-1.31]; p = .23). No episodes of myelosuppression or frozen pelvis were identified. CONCLUSIONS: As single-dose perioperative agents, both thiotepa and MMC were associated with similar recurrence-free survival rates.

Role of robot-assisted retroperitoneal lymph node dissection in malignant mesothelioma of the tunica vaginalis: case series and review of the literature.

INTRODUCTION: The management of malignant mesothelioma of the tunica vaginalis (MMTVT) is not clearly defined. Retroperitoneal lymph node dissection has been reported as a potential management option. Herein we present our experience with robot-assisted retroperitoneal lymph node dissection (RARPLND) in our series of patients with MMTVT. MATERIALS AND METHODS: The Mayo Clinic cancer registry was queried from 1972-present for all patients who had a diagnosis of MMTVT. Six patients were identified, five of whom were treated with RPLND, where four underwent RARPLND. RESULTS: In five patients who underwent RPLND, the median age was 50 years (IQR 34-51). Four patients originally presented with right sided symptomatic hydroceles, while one presented with right sided chronic epididymitis. Orchiectomy (one simple, two inguinal radical) was performed in three patients prior to presentation. Preoperative cross-sectional imaging, including PET-CT scan in three patients, was negative for lymphadenopathy or metastasis. RARPLND was performed in 4/5 (80%) cases and concomitant hemiscrotectomy in 4/5 (80%) cases. Full bilateral template was performed in three patients and right modified template was performed in the remaining two. Median lymph node yield was 29 (IQR 22-32) and median blood loss was 275 cc (IQR 200-300). Positive retroperitoneal lymph nodes were found in 3/5 (60%) cases. All patients who underwent RARPLND were discharged home on postoperative day one. Mean follow up was 27 months (range 3-47). No patients recurred. CONCLUSIONS: Regardless of the approach, RPLND may provide a diagnostic benefit in patients who present with MMTVT, with the robotic approach affording a potentially expedited recovery.

Stage Dependence, Cell-Origin Independence, and Prognostic Capacity of Serum Glycan Fucosylation, ß1-4 Branching, ß1-6 Branching, and α2-6 Sialylation in Cancer.

Glycans represent a promising but only marginally accessed source of cancer markers. We previously reported the development of a molecularly bottom-up approach to plasma and serum (P/S) glycomics based on glycan linkage analysis that captures features such as α2-6 sialylation, ß1-6 branching, and core fucosylation as single analytical signals. Based on the behavior of P/S glycans established to date, we hypothesized that the alteration of P/S glycans observed in cancer would be independent of the tissue in which the tumor originated yet exhibit stage dependence that varied little between cancers classified on the basis of tumor origin. Herein, the diagnostic utility of this bottom-up approach as applied to lung cancer patients (n = 127 stage I; n = 20 stage II; n = 81 stage III; and n = 90 stage IV) as well as prostate (n = 40 stage II), serous ovarian (n = 59 stage III), and pancreatic cancer patients (n = 15 rapid autopsy) compared to certifiably healthy individuals (n = 30), nominally healthy individuals (n = 166), and risk-matched controls (n = 300) is reported. Diagnostic performance in lung cancer was stage-dependent, with markers for terminal (total) fucosylation, α2-6 sialylation, ß1-4 branching, ß1-6 branching, and outer-arm fucosylation most able to differentiate cases from controls. These markers behaved in a similar stage-dependent manner in other types of cancer as well. Notable differences between certifiably healthy individuals and case-matched controls were observed. These markers were not significantly elevated in liver fibrosis. Using a Cox proportional hazards regression model, the marker for α2-6 sialylation was found to predict both progression and survival in lung cancer patients after adjusting for age, gender, smoking status, and stage. The potential mechanistic role of aberrant P/S glycans in cancer progression is discussed.

Loss of histone H3 lysine 36 trimethylation is associated with an increased risk of renal cell carcinoma-specific death.

Sequencing of clear cell renal cell carcinomas identified loss-of-function mutations of SETD2, a gene that encodes a nonredundant methytransferase responsible for histone H3 lysine 36 trimethylation (H3K36me3), and H3K36me3 is progressively deregulated in metastases. However, few data exist regarding the impact of loss of H3K36me3 on outcomes. We assessed the association of SETD2 DNA alterations and mRNA expression with overall survival using The Cancer Genome Atlas clear cell renal carcinoma data (N=411). Additionally, we assessed the association of H3K36 loss of methylation with renal cell carcinoma-specific survival and progression-free survival using an independent cohort at Mayo Clinic (N=1454). Overall survival, renal cell carcinoma-specific survival and progression-free survival were estimated using Kaplan-Meier method, and differences in survival across groups was compared using Cox regression models, adjusted for age and the Mayo SSIGN (stage, size, grade, and necrosis) score. In The Cancer Genome Atlas cohort, SETD2 DNA alterations or mRNA expression was not associated with overall survival (P>0.05). In the Mayo cohort, patients with H3K36me3-negative tumors were two times more likely to experience renal cell carcinoma-specific death than patients with H3K36me3-positive tumors (hazard ratio, 2.23; 95% confidence interval, 1.77-2.81); P<0.0001. After stratifying for the SSIGN score, H3K36me3-negative tumors in the low-risk SSIGN group had a worse renal cell carcinoma-specific survival (hazard ratio, 2.18; 95% confidence interval, 1.09-4.36); P=0.03. Although SETD2 DNA and mRNA alterations are not associated with overall survival, we provide evidence that deregulation of the H3K36me3 axis is associated with a higher risk of renal cell carcinoma-specific death. This association remains significant after stratifying for the SSIGN score, particularly among those patients with low-risk tumors.

Detection of tumor-associated cells in cryopreserved peripheral blood mononuclear cell samples for retrospective analysis.

BACKGROUND: Cryopreserved peripheral blood mononuclear cells (PBMCs) are commonly collected in biobanks. However, little data exist regarding the preservation of tumor-associated cells in cryopreserved collections. The objective of this study was to determine the feasibility of using the CellSieve™ microfiltration assay for the isolation of circulating tumor cells (CTCs) and circulating cancer-associated macrophage-like cells (CAMLs) from cryopreserved PBMC samples. METHODS: Blood samples spiked with breast (MCF-7), prostate (PC-3), and renal (786-O) cancer cell lines were used to establish analytical accuracy, efficiency, and reproducibility after cryopreservation. The spiked samples were processed through Ficoll separation, and cryopreservation was followed by thawing and microfiltration. RESULTS: MCF-7 cells were successfully retrieved with recovery efficiencies of 90.5 % without cryopreservation and 87.8 and 89.0 %, respectively, on day 7 and day 66 following cryopreservation. The corresponding recovery efficiencies of PC-3 cells were 83.3 % without cryopreservation and 85.3 and 84.7 %, respectively, after cryopreservation. Recovery efficiencies of 786-O cells were 92.7 % without cryopreservation, and 82.7 and 81.3 %, respectively, after cryopreservation. The recovered cells retained the morphologic characteristics and immunohistochemical markers that had been observed before freezing. The protocols were further validated by quantitation of CAMLs in blood samples from two patients with renal cell carcinoma (RCC). The recovery rates of CTCs and CAMLs from cryopreserved samples were not statistically significant different (P > 0.05) from matched fresh samples. CONCLUSIONS: To our knowledge, this is the first report that CAMLs could be cryopreserved and analyzed after thawing with microfiltration technology. The application of microfiltration technology to cryopreserved samples will enable much greater retrospective study of cancer patients in relation to long-term outcomes.

NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

Robot-assisted retroperitoneal lymph node dissection: technique and initial case series of 18 patients.

OBJECTIVE: To evaluate outcomes of the first 18 patients treated with robot-assisted retroperitoneal lymph node dissection (RA-RPLND) for non-seminomatous germ cell tumours (NSGCT) and paratesticular rhabdomyosarcoma (RMS) at our institution. PATIENTS AND METHODS: Between March 2008 and May 2013, 17 patients underwent RA-RPLND for NSGCT and one for paratesticular RMS. Data were collected retrospectively on patient demographics, preoperative tumour characteristics, and perioperative outcomes including open conversion rate, lymph node (LN) yield, rate of positive LNs, operative time, estimated blood loss (EBL), and length of stay (LOS). Perioperative outcomes were compared between patients receiving primary RA-RPLND vs post-chemotherapy RA-RPLND. Medium-term outcomes of tumour recurrence rate and maintenance of antegrade ejaculation were recorded. RESULTS: RA-RPLND was completed robotically in 15 of 18 (83%) patients. LNs were positive in eight of 18 patients (44%). The mean LN yield was 22 LNs. For cases completed robotically, the mean operative time was 329 min, EBL was 103 mL, and LOS was 2.4 days. At a mean (range) follow-up of 22 (1-58) months, there were no retroperitoneal recurrences and two of 17 (12%) patients with NSGCT had pulmonary recurrences. Antegrade ejaculation was maintained in 91% of patients with a nerve-sparing approach. Patients receiving primary RA-RPLND had shorter operative times compared with those post-chemotherapy (311 vs 369 min, P = 0.03). There was no significant difference in LN yield (22 vs 18 LNs, P = 0.34), EBL (100 vs 313 mL, P = 0.13), or LOS (2.75 vs 2.2 days, P = 0.36). CONCLUSION: This initial selected case series of RA-RPLND shows that the procedure is safe, reproducible, and feasible for stage I-IIB NSGCT and RMS in the hands of experienced robotic surgeons. Larger studies are needed to confirm the diagnostic and therapeutic utility of this technique.

Massive renal size is not a contraindication to a laparoscopic approach for bilateral native nephrectomies in autosomal dominant polycystic kidney disease (ADPKD).

OBJECTIVE: To determine if massive renal size should be a contraindication for attempting a laparoscopic approach to bilateral native nephrectomies in patients with autosomal dominant polycystic kidney disease (ADPKD). PATIENTS AND METHODS: We retrospectively reviewed all laparoscopic bilateral nephrectomies performed for ADPKD at our institution from 1 January 2000 to 31 December 2012. We stratified patients by kidney weight (with or without at least one kidney weighing >2500 g) and compared perioperative data, complications, and status of kidney allografts. Additionally, the subset of patients with at least one kidney weighing >3500 g was compared with the rest of the cohort. RESULTS: We identified 68 patients; mean (range) individual kidney weight was 1984 (197-5042) g. In all, 24 patients had at least one kidney weighing >2500 g, yet patients in this group were not significantly different from the rest of the cohort for complications, estimated blood loss, transfusion rate, or duration of hospitalisation. For those who underwent simultaneous renal allotransplantation, native kidney size was not associated with graft outcomes. Additionally, of the six patients with at least one kidney weighing >3500 g, only one required a blood transfusion, and the group had no intraoperative or postoperative Clavien grade ≥3 complications. None of the cohort required conversion to open surgery. CONCLUSION: Massive size of polycystic kidneys is not a contraindication to attempting a laparoscopic approach to bilateral nephrectomies in an experienced, high-volume centre.

The RAZOR (randomized open vs robotic cystectomy) trial: study design and trial update.

The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot-assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health-related quality of life (HRQL) measures with a primary endpoint of 2-year progression-free survival (PFS). RAZOR is a multi-institutional, randomized, non-inferior, phase III trial that will enrol at least 320 patients with T1-T4, N0-N1, M0 bladder cancer with ≈160 patients in both the RARC and ORC arms at 15 participating institutions. Data will be collected prospectively at each institution for cancer outcomes, complications of surgery and HRQL measures, and then submitted to trial data management services Cancer Research and Biostatistics (CRAB) for final analyses. To date, 306 patients have been randomized and accrual to the RAZOR trial is expected to conclude in 2014. In this study, we report the RAZOR trial experimental design, objectives, data safety, and monitoring, and accrual update. The RAZOR trial is a landmark study in urological oncology, randomizing T1-T4, N0-N1, M0 patients with bladder cancer to ORC vs RARC, PLND and urinary diversion. RAZOR is a multi-institutional, non-inferiority trial evaluating cancer outcomes, surgical complications and HRQL measures of ORC vs RARC with a primary endpoint of 2-year PFS. Full data from the RAZOR trial are not expected until 2016-2017.

NCCN Clinical Practice Guidelines Prostate Cancer Early Detection, Version 2.2015.

Prostate cancer represents a spectrum of disease that ranges from nonaggressive, slow-growing disease that may not require treatment to aggressive, fast-growing disease that does. The NCCN Guidelines for Prostate Cancer Early Detection provide a set of sequential recommendations detailing a screening and evaluation strategy for maximizing the detection of prostate cancer that is potentially curable and that, if left undetected, represents a risk to the patient. The guidelines were developed for healthy men who have elected to participate in the early detection of prostate cancer, and they focus on minimizing unnecessary procedures and limiting the detection of indolent disease.

Robot-assisted retroperitoneal lymph node dissection in testicular cancer.

Robotic surgical techniques are now being applied in the setting of retroperitoneal lymphadenectomy (RPLND) for testicular cancer. While laparoscopic RPLND has not been widely accepted, reports of robot assisted RPLND (RARPLND) are emerging. This manuscript will review the application of RPLND for testicular cancer, evolution of minimally invasive techniques, the controversies, and current status of RARPLND.

Postoperative changes in serum CO2 as an indicator of postoperative complications after radical cystectomy.

The purpose of this article was to review the relationship of postoperative CO2 levels to the risk of complications after radical cystectomy. In this review, we summarize the existing body of literature on the topic as well as metabolic complications after urinary diversion. Currently, there are no studies that specifically examine CO2 levels in the context of complications after radical cystectomy; therefore, we also present our own institutional data which demonstrate that a drop in postoperative CO2 levels is highly predictive of complications, the most common of which is failure to thrive. These data indicate that significant changes in CO2 levels prior to discharge after a radical cystectomy may be a harbinger of forthcoming complications.

Venous thromboembolism after urological surgery.

PURPOSE: We determined the rates of deep venous thromboembolism and pulmonary embolism after common urological procedures in the United States. MATERIALS AND METHODS: The NSQIP database was used to identify common urological procedures performed between January 1, 2005 and December 31, 2011. A total of 82,808 patients were included in the study. RESULTS: Overall 633 (0.76% of 82,808 subjects) deep venous thromboses occurred within 30 days of surgery in this cohort of patients treated with common urological procedures. Among procedures performed at least 500 times the rates of deep venous thrombosis were highest for cystectomy/urinary diversion (3.96% [71/1,792]), partial cystectomy (2.35% [17/722]) and open radical nephrectomy (1.67% [45/2,702]). The rates of deep venous thrombosis were lowest in patients undergoing laparoscopic colpopexy (0.00% [0/707]), placement of a female sling (0.08% [9/10,648]) and hydrocelectomy/spermatocelectomy/varicocelectomy (0.13% [3/2,333]). A total of 349 (0.42%) pulmonary embolisms occurred in this cohort, with cystectomy/urinary diversion having the highest rate overall (2.85% [51/1,792]). Multivariate logistic regression revealed that age greater than 60 years, functional status, history of disseminated cancer, congestive heart failure, anesthesia time greater than 120 minutes and chronic steroid use were independently associated with the formation of deep venous thrombosis/pulmonary embolism. A limitation of the study is that no data were available on thromboembolic prophylaxis. CONCLUSIONS: While deep venous thrombosis and pulmonary embolism are uncommon after urological surgery, this study is the first to our knowledge to provide a comprehensive comparison of deep venous thrombosis/pulmonary embolism rates across a full spectrum of various urological procedures in American patients. This study should give the reader a better understanding of the exact risk faced by the patient when undergoing common urological procedures.

Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype.

BACKGROUND: The significance of androgen receptor (AR) expression in triple-negative breast cancer (TNBC) is unclear, and published studies so far have been inconclusive. METHODS: A tissue microarray was constructed using tissue obtained from 119 patients with primary TNBC and stained for AR expression. Other tissue types obtained included recurrent TNBC, normal breast tissue, adjacent ductal carcinoma-in situ (DCIS), lymph node (LN) and distant metastases. Positive AR expression was defined as ≥10% nuclear staining. RESULTS: Epithelial tissue was present and evaluable in 94 TNBC patients with a total of 177 tissue cores. AR expression in TNBC was 22 of 94 (23%). AR expression was higher in normal breast tissue (88%) and adjacent DCIS (73% overall). All LN metastases from AR-positive TNBC patients were also AR positive; in addition, no AR-negative TNBC patient had AR-positive LNs. AR expression was associated with older patient age (63 vs. 57 years, respectively, p = 0.051) and LN metastases (p = 0.033). Locoregional recurrence and overall/disease-specific survival were similar between AR-positive and AR-negative patients, although AR-positive patients had more advanced disease. On multivariate analysis, the presence of LN metastases was associated with poorer recurrence-free survival in AR-positive patients (hazard ratio, 4.34) (p = 0.031). CONCLUSIONS: The AR is expressed in normal breast tissue, and expression decreases with advancement to DCIS and invasive cancer. AR-positive TNBC was more common in older patients and had a higher propensity for LN metastases. AR-positive TNBC may represent a breast cancer subtype with unique features that may be amenable to treatment with alternative targeted therapies.

Perioperative complications after neoadjuvant chemotherapy and radical cystectomy for bladder cancer.

INTRODUCTION: Few data on the perioperative outcomes of cystectomy after neoadjuvant chemotherapy (NAC) exist. In this study, we evaluated whether patients who had previously received NAC were at higher risk of developing perioperative complications. MATERIALS AND METHODS: The National Surgical Quality Improvement Program (NSQIP) database was searched to identify cystectomies performed between January 1, 2005 and December 31, 2011. Of 1394 patients identified, about one-tenth (n = 122 [8.8%]) received NAC. A propensity-weighted comparative analysis of perioperative morbidity was conducted. RESULTS: In unadjusted comparisons, patients undergoing cystectomy after NAC were more likely to have peripheral nerve deficits (1.6% [2/122] versus 0.2% [3/1272]; p = .01), blood transfusions (37.7% [46/122] versus 27.5% [350/1272]; p = .02), and unplanned readmissions (11.5% [14/122] versus 6.6% [84/1272]; p = .04), but were less likely to require hospitalization longer than 8 days (45.1% [55/122] versus 58.8% [748/1272]; p = .01). Propensity-weighted adjustments showed that cystectomy after NAC produced little increased risk of perioperative surgical complications except for peripheral nerve deficits (3.2% [4/122] versus 0.3% [3/1166]; propensity score-adjusted odds ratio [PS-OR], 13.1; 95% CI, 1.90-90.8; p = .01) and resulted in better rates of wound dehiscence (0.8% [1/122] versus 3.3% [38/1166]; PS-OR, 0.20; 95% CI, 0.04-0.89; p = .04) and sepsis (4.9% [6/122] versus 11.4% [134/1166]; PS-OR, 0.36; 95% CI, 0.17-0.76; p = .01). No differences in 30 day mortality were noted. CONCLUSIONS: NAC is not associated with perioperative complications after cystectomy. As expected, there was an increase in peripheral nerve deficits in the neoadjuvant chemotherapy group, but this was likely due to the known neurotoxicity of the cisplatin agents.