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There were an estimated 73,510 incident cases of bladder cancer in the United States in 2012, with 55,600 and 17,910 cases in males and females, respectively (3.1 to 1 ratio).1,2 Of the 14,880 estimated deaths from bladder cancer, 10,510 were men and 4,370 women (2.4 to 1 ratio),2 demonstrating the disproportionate mortality:incidence ratio for women that is well-documented in the literature.3–7 Specifically, a study by the EUROCARE Working Group8 demonstrated a 5% absolute decreased 5-year survival for women compared to men, controlling for age and expected mortality. This phenomenon was unique to bladder cancer, as the EUROCARE study found that women appeared to have a significant survival advantage for cancers of the head and neck, esophagus, stomach, liver, and pancreas. The mechanisms for increased mortality in women with bladder cancer are not completely understood. Although advanced stage of presentation has been hypothesized, a review of the SEER database by Mungan et al. demonstrated a 5-year overall relative survival advantage for males across all stages of disease.5 Studies evaluating disparities in aggressive treatment are mixed and do not appear to explain the disparity in prognosis,9,10 nor does in-hospital mortality following aggressive therapy.11 However, for both men and women, it has been established that delays in diagnosis and treatment (specifically, a delay >6 months for diagnosis12 and >12 weeks from diagnosis to cystectomy13–16) adversely impact survival. Furthermore, recent studies suggest that relative to men, women may be at greater risk of delays in diagnosis17 and presentation with advanced disease.18 Gross hematuria is the most prognostic clinical sign of underlying urologic malignancy, with urothelial cell carcinoma present in 13% to 34.5% of cases.19,20 Microscopic hematuria is associated with malignancy in 0.5% to 10.5% of cases.20–23 As such, even in cases of asymptomatic microscopic hematuria, the American Urological Association Guidelines recommend a thorough work-up for malignancy, consisting of upper tract imaging and cystoscopy, following rule-out of obvious benign causes.24 In patients 40–59 years of age, gross hematuria carries a positive predictive value (PPV) for urologic cancer that is actually higher for women than men (6.4% vs. 3.6%).25 Nonetheless, women presenting with hematuria are less likely to see a urologist, with one study demonstrating men to be 65% more likely to receive a urologic referral.26 This is thought to be related to the differential assumption of a benign diagnosis in women.27 A recent study of patients ultimately diagnosed with bladder cancer found women to be less likely to have undergone prompt urologic consultation for their presenting symptoms and were more likely to have received 3 or more courses of antibiotics.28 If women are more likely to die from bladder cancer than men at any stage as the literature suggests,8 and that delay in diagnosis and treatment adversely impacts survival,12,14–16 timely diagnosis of bladder cancer in women is of utmost importance. Our study aims to evaluate gender disparities in the timing from clinical presentation with hematuria to the diagnosis of bladder cancer in a large nationwide cohort.

Objectives To investigate perioperative outcomes associated with cystectomy and urinary diversion for treatment-refractory benign urological disease. Methods A cohort of patients who underwent cystectomy for infection, fistula, bleeding, incontinence, neurogenic bladder or pain between January 2004 and June 2012 was established. Data included baseline demographics, indications for cystectomy and prior treatments, and complications at 30 and 90 days. Primary outcome measures were 30-day and 30 to 90-day complications. Results The study group comprised eight males and 18 females. The mean age was 57.8 years (95% CI 50.8–64.7). A total of 19 patients (73%) had resolution of their underlying urological pathology at 90 days. A total of 19 patients (73%) experienced a complication in the first 30 days, of which nine (47%) were Clavien grade III or higher. The most common 30-day complications were urinary tract infection (n = 6, 23%) and wound infection (n = 6, 23%). A total of 44% (4/9) of patients with neurogenic bladder experienced a complication within the first 30 days of cystectomy compared with 100% (8/8) of patients with radiation-induced fistula (P = 0.03) and 78% (7/9) of non-neurogenic, non-radiation-induced fistula patients (P = 0.34). Conclusions Cystectomy with urinary diversion for benign disease might be successful, but is associated with a high rate of perioperative complications. Those with radiation-induced fistula are more likely to experience complications, whereas those with neurogenic bladder carry a lower risk. Patients should be counseled appropriately regarding expected postoperative outcomes.

Purpose of review To define the incidence of perioperative morbidity following contemporary radical cystectomy and identify preoperative, intraoperative, and postoperative strategies to reduce complications. Recent findings When complications are methodically and systematically recorded, 64% of patients will sustain a complication within 90 days of radical cystectomy. Various preoperative, postoperative, and intraoperative strategies have been identified to reduce morbidity. Prior to surgery, patients should have reversible medical conditions treated, mechanical bowel preparation can be omitted if using small bowel for reconstruction, venous thromboembolism and antimicrobial infection prophylaxis should be initiated, nutrition should be optimized, and patient education should be provided. During surgery, complications can be attenuated by utilizing meticulous surgical technique, minimizing blood loss, fluid management can be guided by transesophageal cardiovascular Doppler, and lower extremity repositioning should be performed as soon as feasible. After surgery, early mobilization, incentive spirometry, early nasogastric tube removal, alvimopan usage, and judicious jejunostomy tube feeding, or total parenteral nutrition usage may reduce morbidity. Summary Morbidity is common following radical cystectomy, but careful attention to preoperative, intraoperative, and postoperative details can help reduce this risk.

Urachal adenocarcinoma has several morphologic presentations that include mucinous, enteric, signet ring cell, and not otherwise specified. Mixtures of these morphologies can occur, and percentage cut-offs are used for classification. The clinical significance of these morphologic types is currently unknown, and genetic analysis that could elucidate possible intertumoral differences has not been performed. In this study, we analyzed the micro-RNA expression profiles of 12 urachal adenocarcinomas classified using strict morphologic criteria (3 pure enteric, 3 pure mucinous, 2 signet ring cell [both 90% signet ring cell], 2 pure not otherwise specified, and 2 mixed cell types). Of 598 unique human micro-RNAs, 333 were expressed in more than 50% of the samples. Hierarchal clustering showed no distinct patterns in the genetic profiles of the morphologic types. However, there were individual micro-RNA differences when the different types were compared individually or grouped together, either by intracellular mucin production or by grouping enteric and signet ring cell together. In the later group, 13 messenger RNA species were differentially expressed (adjusted P value of ≤.05). However, these micro-RNA differences were small, suggesting more biologic similarity than differences among these entities. Thus, this study suggests that the different morphological subtypes may represent patterns of differentiation or a continuum of a single biological tumor type rather than several distinct types that arose from the urachal remnant epithelium. This finding, if further validated in larger studies, may have implications in future clinical therapeutic trials for urachal adenocarcinoma with regard to patient grouping and choice of therapy.

Non-muscle invasive bladder cancer (NMIBC) represents approximately 70% of all incident cases of bladder cancer. The financial burden of NMIBC continues to increase, underscoring the importance of efficient, evidence-based management of this disease. Consensus guidelines differ on risk definition and in management recommendations. This article reviews the incidence and financial impact of NMIBC and details the recommendations for diagnosis, treatment, and surveillance made by the American Urological Association, International Consultation on Bladder Cancer-European Association of Urology, and National Comprehensive Cancer Network. Established and developing adjunctive laboratory and imaging tests directed at diagnosis and management of NMIBC are also discussed.

In 2010 the AJCC (American Joint Committee on Cancer) excluded urothelial carcinoma with subepithelial prostatic stromal invasion from the pT4a bladder cancer staging class, which is otherwise defined by direct prostatic invasion transmurally from the bladder. We determined if the new guidelines were reflective of differences in survival between subepithelial prostatic stromal invasion and transmural pT4a disease.A retrospective, multi-institutional cohort of cystectomy cases with subepithelial prostatic stromal invasion from the University of Chicago and Cleveland Clinic were compared to a cohort with transmural pT4a disease. All pathological specimens were rereviewed at the respective institutions. Patients were excluded from the final cohort if variant bladder cancer histology, pT3 bladder disease or extraprostatic extension of urothelial carcinoma were identified. The primary end points were cancer specific and overall survival.Our study sample consisted of 48 patients with subepithelial prostatic stromal invasion and 49 patients with transmural pT4a disease. Median followup was 12.8 months (IQR 4.9 to 31.4). Patients with subepithelial prostatic stromal invasion had lower rates of lymph node involvement than those with transmural pT4a disease (14.6% vs 61.2%, p0.001) and lower rates of positive surgical margins (18.7% vs 61.2%, p0.001). Rates of perioperative chemotherapy were similar in both groups. When comparing subepithelial prostatic stromal invasion and transmural pT4a groups, overall survival was 64.0 vs 9.8 months and median cancer specific survival was not achieved vs 16.5 months, respectively (p0.001).Subepithelial prostatic stromal invasion from urothelial carcinoma has more favorable outcomes compared to transmural pT4a disease. Our results support the exclusion of subepithelial prostatic stromal invasion from the pT4a bladder urothelial carcinoma staging class.

ATIENTS PRESENTING FOR resection of renal cell carcinoma with supradiaphragmatic vena cava or right atrial extension offer a host of challenges to both their surgeons and anesthesiologists. The need to perform a complete resection while minimizing the risk of embolization and metastases, which classically calls for median sternotomy and cardiopulmonary bypass (CPB), with or without deep hypothermic circulatory arrest (DHCA), must be balanced against the risks of coagulopathy, bleeding, and neurologic insult often encountered with this approach. Recently, some have advocated sternotomy and CPB-sparing techniques that do not compromise the goal of complete tumor resection. 1 A case of attempted resection of renal cell carcinoma with level III (suprahepatic, supradiaphragmatic, infra-atrial) extension is presented.

Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients.

Objectives Ureteroenteric anastomotic strictures are common after cystectomy with urinary diversion. Endoscopic treatments have poor long-term success, although ureteral reimplantation is associated with morbidity. Predictors of successful open repair are poorly defined. Our objective was to characterize outcomes of ureteral reimplantation after cystectomy and identify risk factors for stricture recurrence. Patients and methods We performed a retrospective review of 124 consecutive patients with a total of 151 open ureteral reimplantations for postcystectomy ureteroenteric strictures between January 2006 and December 2015. Baseline clinicopathologic characteristics and perioperative outcomes were examined. Predictors for stricture recurrence were assessed by univariable testing and univariate Cox proportional hazards regression. Results Most patients underwent preoperative drainage by percutaneous nephrostomy (PCN; 43%) or percutaneous nephroureterostomy (PCNU; 44%). Major iatrogenic injuries included enterotomies requiring bowel anastomosis (3.2%) and major vascular injuries (2.4%). Overall, 60 (48%) patients suffered 90-day complications, of which 15 (12%) patients had high-grade complications. Median length of stay was 6 days [interquartile range: 5, 8] and median follow-up was 21 months [interquartile range: 5, 43]. The overall success rate per ureter was 93.4%. On univariate analysis, the only significant predictor of stricture recurrence was preoperative PCNU placement compared with PCN placement or no drainage (success rates: 85.5% vs. 98.9%, respectively, P = 0.002). Cox proportional hazards regression demonstrated that preoperative PCNU placement yielded a hazard ratio of 10.2 (95% CI: 1.27–82.6) for stricture recurrence (P

Muscle-invasive urothelial bladder cancer is a common malignancy with poor outcomes for which immune checkpoint blockade is now showing promise. Despite clinical activity of PD-1/PD-L1–targeted therapy in this disease, most patients do not benefit and resistance mechanisms remain unknown. The non–T-cell-inflamed tumor microenvironment correlates with poor prognosis and resistance to immunotherapies. In this study, we determined tumor-oncogenic pathways correlating with T-cell exclusion. We first establish in this report that T-cell–inflamed bladder tumors can be identified by immune gene expression profiling with concordance with CD8+ T-cell infiltration. Upregulation of genes encoding immune checkpoint proteins PD-L1, IDO, FOXP3, TIM3, and LAG3 was associated with T-cell–inflamed tumors, suggesting potential for sensitivity to checkpoint blockade. β-Catenin, PPAR-γ, and FGFR3 pathways were activated in non–T-cell-inflamed tumors. No difference was seen in overall somatic mutational density between groups. The three pathways identified represent targetable potential pathways of tumor-intrinsic immunotherapy resistance. Cancer Immunol Res; 4(7); 563–8. ©2016 AACR.

PURPOSE: To review the management of metastatic upper tract urothelial carcinoma (UTUC) including recent advances in targeted and immune therapies as an update to the 2014 joint international consultation on UTUC, cosponsored by the Société Internationale d’Urologie and International Consultation on Urological Diseases. METHODS: A PubMed database search was performed between January 2013 and May 2016 related to the treatment of metastatic UTUC, and 54 studies were selected for inclusion. RESULTS: The management of patients with metastatic UTUC is primarily an extrapolation from evidence guiding the management of metastatic urothelial carcinoma of the bladder. The first-line therapy for metastatic UTUC is platinum-based combination chemotherapy. Standard second-line therapies are limited and ineffective. Patients with UTUC who progress following platinum-based chemotherapy are encouraged to participate in clinical trials. Recent advances in genomic profiling present exciting opportunities to guide the use of targeted therapy. Immunotherapy with checkpoint inhibitors has demonstrated extremely promising results. Retrospective studies provide support for post-chemotherapy surgery in appropriately selected patients. CONCLUSIONS: The management of metastatic UTUC requires a multi-disciplinary approach. New insights from genomic profiling using targeted therapies, novel immunotherapies, and surgery represent promising avenues for further therapeutic exploration.

An unmet need exists for patients with high-risk non-muscle-invasive bladder cancer for whom bacille Calmette-Guérin (BCG) has failed and who seek further bladder-sparing approaches. This shortcoming poses difficult management dilemmas. This review explores previously investigated first-line intravesical therapies and discusses emerging second-line treatments for the heterogeneous group of patients for whom BCG has failed. The myriad of recently published and ongoing trials assessing novel salvage intravesical treatments offer promise to patients who both seek an effective cure and want to avoid radical surgery. However, these trials must carefully be contextualized by specific patient, tumor, and recurrence characteristics. As data continue to accumulate, there will potentially be a role for these agents as second-line or even first-line intravesical therapies. Cancer 2017;123:390-400. © 2016 American Cancer Society.

INTRODUCTION AND OBJECTIVES: Stricture of the ureteroenteric anastomosis is a complication after cystectomy with urinary diversion. Relatively little has been reported on the perioperative course during surgical repair of a ureteroenteric anastomosis. Adhesions can increase the risk of bowel injury and necessitate concomitant bowel repair. We hypothesized that the need for concomitant bowel surgery during revision of a ureteroenteric anastomosis is associated with adverse perioperative outcomes. METHODS: The National Inpatient Sample (2002-2012) was used to identify patients requiring revision of ureteroenteric anastomosis, excluding patients 0.2). Overall complication rate was 50%, with 19% UTI, 17% bleeding and 3% venous thromboembolism. Of these, only overall complications (65% vs 41%, p 0.1). Undergoing concomitant bowel surgery (OR 2.8 [1.2-6.2], p1⁄40.02) was the only independent risk factor for complications during ureteral reimplantation after controlling for demographics, clinical and hospital characteristics. CONCLUSIONS: Reimplantation of a ureteroenteric anastomosis was associated with a 50% complication rate. There were no demographic or clinical factors associated with need for concomitant bowel surgery, which was necessary in 35% of patients. Undergoing a concomitant bowel procedure was an independent predictor for perioperative complications.

To the Editor:We appreciate the interest taken in our analysis of pelvic failures after radical cystectomy (1, 2). We agree with the comments made that our study supports several notions that have more recently come to light: (1) after radical cystectomy, pelvic recurrences occur at a rate that is higher than historically reported, in up to 30% to 50% of selected patients; (2) adjuvant chemotherapy does not appear to substantially reduce the risk of pelvic failure; and (3) histology does not appear to influence the pattern of pelvic failure. Additionally, our analysis presents a few new considerations for this clinical situation: (1) margin-positive resections do not necessarily increase the risk of failure at the cystectomy bed alone; (2) a reasonable proportion of local and regional failures may occur without concurrent distant disease, suggesting a chance to influence survival with improved local and regional control; and (3) a low proportion of patients demonstrates evidence of recurrence in the cystectomy bed, suggesting a relatively higher value in covering nodal regions at risk and a possible means to reduce the risks of adjuvant local therapy. Our conclusions must be considered in the context of the retrospective, single-institution nature of the study, so we await prospective trials to help substantiate our findings. The recent presentation by Zaghloul et al (3) from the Egyptian NCI indicates that pelvic control can be reduced by adjuvant radiation therapy (3-year local-regional relapsefree survival 87%vs 69%,P

At the most recent Genitourinary Cancers Symposium in Orlando February 2015, a task force was organized to discuss issues in trial design in non-muscle invasive bladder cancer. Our aim was to provide further clarification regarding disease states following treatment of patients with intravesical BCG and to determine what events constitute progression following any treatment for non-muscle invasive bladder cancer (NMIBC). The panelists were asked to address a number of specific Tasks, enumerated below.

Level 1 evidence has demonstrated increased overall survival with cisplatin-based neoadjuvant chemotherapy for patients with muscle-invasive urothelial cancer. Usage remains low, however, in part because neoadjuvant chemotherapy will not be effective for every patient. To identify the patients most likely to benefit, we evaluated germline pharmacogenomic markers for association with neoadjuvant chemotherapy sensitivity in 2 large cohorts of patients with urothelial cancer.Patients receiving neoadjuvant cisplatin-based chemotherapy for muscle-invasive urothelial cancer were eligible. Nine germline single nucleotide polymorphisms (SNPs) potentially conferring platinum sensitivity were tested for an association with a complete pathologic response to neoadjuvant chemotherapy (pT0) or elimination of muscle-invasive cancer (pT2).The data from 205 patients were analyzed-59 patients were included in the discovery set and 146 in an independent replication cohort-from 3 institutions. The stage pT0 (26%) and pT2 (50%) rates were consistent across the discovery and replication populations. Using a multivariate recessive genetic model, rs244898 in RARS (odds ratio, 6.8; 95% confidence interval, 1.8-28.9; P = .006) and rs7937567 in GALNTL4 (odds ratio, 4.8; 95% confidence interval, 1.1-22.6; P = .04) were associated with pT0 in the discovery set. Despite these large effects, neither were associated with achievement of pT0 in the replication set. A third SNP, rs10964552, was associated with stage pT2 in the discovery set but also failed to replicate.Germline SNPs previously associated with platinum sensitivity were not associated with the neoadjuvant chemotherapy response in a large replication cohort of patients with urothelial cancer. These results emphasize the need for replication when evaluating pharmacogenomic markers and demonstrate that multi-institutional efforts are feasible and will be necessary to achieve advances in urothelial cancer pharmacogenomics.

The compliance of physicians to current guidelines for asymptomatic microhaematuria is limited and the evidence supporting asymptomatic microhaematuria as an effective screening tool for the early detection of bladder cancer is weak. Medical or surgical treatment is indicated in 13–35% of patients with asymptomatic microhaematuria, albeit mostly for benign conditions, which are more commonly the cause. The high prevalence of asymptomatic microhaematuria in the general population means that this condition poses a considerable challenge to the health-care system.

Objectives To present outcomes of a contemporary series of patients undergoing radical cystectomy (RC) for bladder cancer after previous treatment for localized cancer of the prostate (CaP). Methods A retrospective review of more than 1000 RCs performed for bladder cancer between 1995 and 2008 identified 49 patients previously treated for localized CaP. Patients were stratified according to the type of primary therapy received for CaP: any form of primary or adjuvant radiotherapy (brachytherapy or external beam radiotherapy) versus radical prostatectomy (RP) monotherapy. Perioperative data were analyzed and compared between the 2 groups. Results Of 49 patients, 40 (82%) underwent primary or adjuvant radiotherapy and 9 (18%) RP alone. Eleven (22%) patients received a continent diversion. Mean estimated blood loss (EBL) and hospital stay were 979 mL and 12 days, respectively. Extravesical disease (≥pT3a) was present in 23 patients (57.5%) in the radiotherapy group and in 2 patients (22%) in the RP group. Ten patients (all in the radiotherapy group) had a positive margin, 9 (90%) of whom had pathologic T4 disease. The overall major perioperative complication rate was 41%. Of the 6 patients with an ONB (all after RP), 4 had severe incontinence. Conclusions Patients undergoing RC after previous treatment for localized CaP are at increased risk for perioperative morbidity. Patients should be counseled that orthotopic diversion after RP may be associated with significant incontinence. Extravesical disease is more prevalent in patients treated with previous radiation. We observed a high rate of positive margins associated with pathologic T4 disease in this cohort.

Background Perioperative hypothermia has been reported to increase the occurrence of cardiovascular complications. By increasing the activity of sympathetic nervous system, perioperative hypothermia also has the potential to increase cardiac injury and dysfunction associated with subarachnoid hemorrhage. Methods The Intraoperative Hypothermia for Aneurysm Surgery Trial randomized patients undergoing cerebral aneurysm surgery to intraoperative hypothermia (n = 499, 33.3 degrees +/- 0.8 degrees C) or normothermia (n = 501, 36.7 degrees +/- 0.5 degrees C). Cardiovascular events (hypotension, arrhythmias, vasopressor use, myocardial infarction, and others) were prospectively followed until 3-month follow-up and were compared in hypothermic and normothermic patients. A subset of 62 patients (hypothermia, n = 33; normothermia, n = 29) also had preoperative and postoperative (within 24 h) measurement of cardiac troponin-I and echocardiography to explore the association between perioperative hypothermia and subarachnoid hemorrhage-associated myocardial injury and left ventricular function. Results There was no difference between hypothermic and normothermic patients in the occurrence of any single cardiovascular event or in composite cardiovascular events. There was no difference in mortality (6%) between groups, and there was only a single primary cardiovascular death (normothermia). There was no difference between hypothermic and normothermic patients in postoperative versus preoperative left ventricular regional wall motion or ejection fraction. Compared with preoperative values, hypothermic patients had no postoperative increase in cardiac troponin-I (median change 0.00 microg/l), whereas normothermic patients had a small postoperative increase (median change + 0.01 microg/l, P = 0.038). Conclusion In patients undergoing cerebral aneurysm surgery, perioperative hypothermia was not associated with an increased occurrence of cardiovascular events.

In marker lesion experiments a single bladder tumor is deliberately left unresected for later ablation by intravesical instillation of a novel agent. While the benefits are clear, eg the opportunity to examine the effect of therapy on measurable disease, the safety and medical ethics of these experiments are less obvious. We review the goals, inclusion criteria, definition of success, agents used, effectiveness, safety and ethics of marker lesion studies, and suggest a framework for future experiments.Published bladder cancer studies using the marker lesion concept were identified with a MEDLINE search through March 2009.A total of 23 well documented marker lesion studies were identified involving more than 1,200 patients. Most agents studied were cytotoxins (mitomycin-C, epirubicin, gemcitabine, valrubicin, apaziquone) or immune response modifiers (bacillus Calmette-Guerin, tumor necrosis factor-alpha, interferon-alpha, granulocyte-macrophage colony-stimulating factor). The highest complete response rate in intermediate risk patients (67%) was attained with apaziquone. Patients who achieved a complete response with this agent also had a prophylactic benefit with a 2-year recurrence-free rate of 45.2% compared to 26.7% in those who did not achieve a complete response. The complete response rate in bacillus Calmette-Guerin trials ranged from 32% to 61%. Marker lesion experiments were deemed safe with progression to T2 disease in only 7 patients (0.6%) and only when high risk patients were selected.Marker lesion studies are most appropriate for the evaluation of novel anticancer therapeutics. Only patients with multiple recurrent, noninvasive, low grade tumors (intermediate risk) should be recruited. Primary end points should be complete response and recurrence rates after 2 to 3 years.

Background Although hypothermia and barbiturates improve neurologic outcomes in animal temporary focal ischemia models, the clinical efficacy of these interventions during temporary occlusion of the cerebral vasculature during intracranial aneurysm surgery (temporary clipping) is not established. Methods A post hoc analysis of patients from the Intraoperative Hypothermia for Aneurysm Surgery Trial who underwent temporary clipping was performed. Univariate and multivariate logistic regression methods were used to test for associations between hypothermia, supplemental protective drug, and short- (24-h) and long-term (3-month) neurologic outcomes. An odds ratio more than 1 denotes better outcome. Results Patients undergoing temporary clipping (n = 441) were assigned to intraoperative hypothermia (33.3 degrees +/- 0.8 degrees C, n = 208) or normothermia (36.7 degrees +/- 0.5 degrees C, n = 233), with 178 patients also receiving supplemental protective drug (thiopental or etomidate) during temporary clipping. Three months after surgery, 278 patients (63%) had good outcome (Glasgow Outcome Score = 1). Neither hypothermia (P = 0.847; odds ratio = 1.043, 95% CI = 0.678-1.606) nor supplemental protective drug (P = 0.835; odds ratio = 1.048, 95% CI = 0.674-1.631) were associated with 3-month Glasgow Outcome Score. The effect of supplemental protective drug did not significantly vary with temperature. The effects of hypothermia and protective drug did not significantly vary with temporary clip duration. Similar findings were made for 24-h neurologic status and 3-month Neuropsychological Composite Score. Conclusion In the Intraoperative Hypothermia for Aneurysm Surgery Trial, neither systemic hypothermia nor supplemental protective drug affected short- or long-term neurologic outcomes of patients undergoing temporary clipping.

Little is known about the health related quality of life of women who have undergone continent urinary diversion. We compared health related quality of life outcomes for women who underwent radical cystectomy with an orthotopic neobladder or Indiana pouch.From 1995 to June 2008 a single surgeon (GDS) performed radical cystectomy with an orthotopic neobladder in 47 women and radical cystectomy with an Indiana pouch in 45. A comprehensive database provided clinical, pathological and outcomes data. The validated Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index was mailed to 92 patients.Complete data were available for 87% of patients treated with radical cystectomy with an orthotopic neobladder and 93% of those treated with radical cystectomy with an Indiana pouch, with a median followup of 34 and 24 months, respectively (p = 0.8). Median (IQR) age was 65 (58, 71) and 61.5 (51, 67) years for patients with an orthotopic neobladder and Indiana pouch, respectively (p = 0.03). No significant differences were found for pathological stage, nodal status, blood loss, Clavien grade III or greater complications, adjuvant therapy or hospital stay between the 2 treatment groups, or between respondents and nonrespondents. Five-year survival rates for patients with an orthotopic neobladder and Indiana pouch were 65% and 58%, respectively (p = 0.9). There were 21 (75%) living patients with an orthotopic neobladder and 19 (61%) with an Indiana pouch who completed the Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index, and physical (p = 0.53), social (p = 0.97), emotional (p = 0.61), functional (p = 0.55) and radical cystectomy specific (p = 0.54) health related quality of life domains were not significantly different between the groups.Women undergoing radical cystectomy with an orthotopic neobladder vs an Indiana pouch have similar health related quality of life outcomes. Larger series with longer followup and multiple surgeons are necessary to confirm these findings.

With the advent of minimally invasive surgery (MIS) for treating urologic malignancies, emphasis has been placed on reducing patient morbidity and resuming normal activity. We sought to clarify whether open surgeons (OS) have modified their techniques, surgical equipment, and perioperative management in response to this trend.A survey sent to all members of the Society of Urologic Oncology assessed changes that OS performing radical retropubic prostatectomy have made in analgesia, operative technique, perioperative management, and follow-up patterns. We also assessed OS sense of competition from MIS. Surgeon perception of the influence MIS had on these changes was scored from 0 to 4 (0 = not at all, 1 = slightly, 2 = moderately, 3 = greatly, 4 =completely). Overall and major influence by MIS included scores 1-4 and 3-4, respectively.Reduced radical retropubic prostatectomy (RRP) case volume because of MIS competition was reported by 20 OS (24%), with 27 OS (32%) starting to perform MIS, and 20 (24%) doing mostly/exclusively MIS. MIS has influenced OS to reduce incision length (overall influence 56%/major influence 33%), operative time (40%/12%), blood loss (31%/17%), and transfusion rate (33%/14%). MIS has influenced OS to use new instruments (48%/44%) or loupes (20%/9%), modify dissection (45%/31%) or anastomotic technique (14%/12%), and increase the use of hemostatic agents (48%/19%). MIS has reduced convalescence in OS patients by reducing length of stay (52%/28%), time to a regular diet (40%/18%), duration of drain (21%/16%) and Foley (32%/15%), time to return to work (49%/25%), and exercise (44%/21%). MIS has changed follow-up of OS patients by increasing the use of clinical pathways (14%/9%) and validated questionnaires (22%/13%).To date, the influence of MIS on the OS has not been comprehensively assessed. This survey finds that OS report that MIS serves as major competition to the open technique and that it has influenced them to modify their surgical technique, reduce convalescence, and alter follow-up recommendations.

Lymph node-positive bladder cancer is a systemic disease in the majority of patients. Adjuvant chemotherapy given shortly after surgery, when tumor burden is low, seems reasonable, yet there is no proof that it improves survival. In this retrospective study, we compare the outcomes of patients with microscopic lymph node positive bladder cancer (pN1 or pN2) treated with radical cystectomy followed by adjuvant chemotherapy and those who declined chemotherapy.Sixty-seven patients with lymph node positive bladder cancer (26 pN1 and 41 pN2) who underwent radical cystectomy between April 1995 and April 2005 were reviewed. Combined adjuvant chemotherapy (gemcitabine and cisplatin in most patients) was given to 35 patients (52%), but declined by 32 (48%). The two groups were similar in performance status, postoperative complication rate, and N stage but deferring patients were on average 5 years older and had a more advanced T stage. Study primary endpoint was overall survival (OS).Adjuvant chemotherapy was well tolerated and 28/35 patients (80%) completed all 4 cycles. Median OS of patients given adjuvant chemotherapy was 48 months compared with 8 months for declining patients (hazard ratio 0.13, 95% CI 0.04-0.4, P0.0001). Multivariate age adjusted analysis showed that adjuvant chemotherapy was an independent factor affecting OS (hazard ratio 0.2, P0.0001).This study supports the use of adjuvant chemotherapy after radical cystectomy in patients with node positive bladder cancer. Study design and patient imbalances make it impossible to draw definitive conclusions.

The traditional anatomical description of the seminal vesicles is based on autopsy and imaging studies. Trans-peritoneal robotic-assisted laproscopic surgery, with its three-dimensional magnified view and miniature articulated working instruments, provides an opportunity to perform accurate dissections of the seminal vesicles even when extremely long and tortuous. We used specimens obtained by robotic-assisted laparoscopic radical prostatectomy (RLRP) for accurate anatomic assessment of the dimensions of the seminal vesicles. Digital photos of 78 specimens from men (mean age 59 ± 6.1 years) who underwent RLRP were analyzed using the Image Pro Plus software. Seminal vesicle dimensions were correlated with patients’ age, weight, height, prostate weight, sexual function profile (SHIM) and symptom severity score of the lower urinary tract symptoms (IPSS). We found that the length of the seminal vesicles is highly variable (range of 8.5–94.6 mm). The average seminal vesicle length was 31 ± 10.3 mm and its average volume 7.1 ± 5.2 ml. The right seminal vesicle was significantly larger than the left in length, width and volume (P

Partial nephrectomy has been established as a standard of care for T(1a) renal tumors. Laparoscopic partial nephrectomy (LPN) has been described as more difficult to perform than open partial nephrectomy (OPN). We compare our series of LPN and OPN.From October 2002 to January 2006, 76 LPNs were performed for patients with clinical T(1a) tumors. These patients were matched with a cohort of patients who underwent OPN for solitary tumors of 4 cm or smaller in diameter. The cohorts were compared with regard to demographics, perioperative data, and outcomes.The patient populations were demographically similar. Although mean tumor size was smaller in the laparoscopic cohort (2.5 v 2.9 cm, P=0.002), the OPN cohort demonstrated shorter operative (193 v 225 min, P=0.004) and ischemia times (20.5 v 32.8 min). LPN was associated with less blood loss (212 v 385 mL, P0.001) and shorter hospital stay (2.5 v 5.6 days, P0.001), however. One positive margin occurred in each of the LPN and OPN cohorts. Intraoperative complications were similar, although LPN was associated with fewer postoperative complications. Of note, two LPN (2.6%) patients had emergent reoperation and complete nephrectomy because of postoperative hemorrhage.Despite increased operative and ischemia times, LPN patients demonstrated quicker recovery and fewer postoperative complications. Two patients in the LPN group, however, had emergent complete nephrectomy because of hemorrhage. We conclude that LPN is still an evolving alternative to OPN in patients with small renal tumors.

Prostate cancer Gleason score 3 + 3 = 6 is currently the most common score assigned on prostatic biopsies. We analyzed the clinical variables that predict the likelihood of a patient with biopsy Gleason score 6 to harbor a higher grade tumor.The study population consisted of 448 patients with a mean age of 59.1 years who underwent radical prostatectomy between February 2003 to October 2006 for Gleason score 6 adenocarcinoma. The effect of preoperative variables on the probability of a Gleason score upgrade on final pathological evaluation was evaluated using logistic regression, and classification and regression tree analysis.Gleason score upgrade was found in 91 of 448 patients (20.3%). Logistic regression showed that only serum prostate specific antigen and the greatest percent of cancer in a core were significantly associated with a score upgrade (p = 0.0014 and 0.023, respectively). Classification and regression tree analysis showed that the risk of a Gleason score upgrade was 62% when serum prostate specific antigen was higher than 12 ng/ml and 18% when serum prostate specific antigen was 12 ng/ml or less. In patients with serum prostate specific antigen lower than 12 ng/ml the risk of a score upgrade could be dichotomized at a greatest percent of cancer in a core of 5%. The risk was 22.6% and 10.5% when the greatest percent of cancer in a core was higher than 5% and 5% or lower, respectively.The probability of patients with a prostate biopsy Gleason score of 6 to conceal a Gleason score of 7 or higher can be predicted using serum prostate specific antigen and the greatest percent of cancer in a core. With these parameters it is possible to predict upgrade rates as high as 62% and as low as 10.5%.

Radiofrequency ablation (RFA) has emerged as a minimally invasive nephron-sparing treatment for small (

OBJECTIVES The intraoperative complexity of laparoscopic partial nephrectomy (LPN) for upper pole renal tumors is recognized. We report on the technical feasibility and operative outcomes of LPN for upper pole tumors (UPLPN) and lower pole tumors (LPLPN), and open partial nephrectomy (UPOPN) for upper pole tumors. METHODS We retrospectively reviewed our database of LPNs performed by a single surgeon from October 2002 to February 2006. All solitary, upper and lower pole tumors in patients with a normal contralateral kidney were included. The perioperative outcomes were assessed. UPOPNs performed in the same institution by a separate surgeon were analyzed and compared separately with the UPLPN group. RESULTS Three groups, UPLPN (20 patients), LPLPN (33 patients), and UPOPN (24 patients), were analyzed. The UPLPN and LPLPN groups had similar perioperative outcomes. The intraoperative and postoperative major complications were also comparable between the UPLPN and LPLPN groups (17% versus 12%, P = 0.68 and 22% versus 6%, P = 0.07, respectively). The mean pathologic tumor size was larger (3.2 versus 2.3 cm, P = 0.05) and the mean operative time significantly shorter (187 versus 244 minutes, P = 0.02) in the UPOPN group than in the UPLPN group. The UPOPN group had a trend toward fewer intraoperative complications compared with the UPLPN group (4% versus 17%, P = 0.17). The final pathologic surgical margins were negative in all three groups. CONCLUSIONS LPN for upper pole renal tumors is technically feasible and may have comparable outcomes to LPN for lower pole tumors. However, performing open nephron-sparing surgery is still the standard of care because it may offer fewer complications and reduce the risk of ischemic damage to the kidney.

Background The success of cancer immunotherapies has highlighted the potent ability of local adaptive immune responses to eradicate cancer cells by targeting neoantigens generated by somatic alterations. However, how these factors interact to drive the natural history of muscle-invasive bladder cancer (MIBC) is not well understood. Objective To investigate the role of immune regulation in MIBC disease progression, we performed massively parallel T-cell receptor (TCR) sequencing of tumor-infiltrating T cells (TILs), in silico neoantigen prediction from exome sequences, and expression analysis of immune-related genes. Design, setting, and participants We analyzed 38 MIBC tissues from patients who underwent definitive surgery with a minimum clinical follow-up of 2 yr. Outcome measurements and statistical analysis Recurrence-free survival (RFS) was determined. TCR diversity was quantified using Simpson's diversity index. The main analyses involved the Mann-Whitney U test, Kaplan-Meier survival analysis, and Cox proportional hazards models. Results and limitations Low TCRβ chain diversity, correlating with oligoclonal TIL expansion, was significantly correlated with longer RFS, even after adjustment for pathologic tumor stage, node status, and receipt of adjuvant chemotherapy (hazard ratio 2.67, 95% confidence interval 1.08–6.60; p =0.03). Patients with both a high number of neoantigens and low TCRβ diversity had longer RFS compared to those with fewer neoantigens and high TCR diversity (median RFS 275 vs 30 wk; p =0.03). Higher expression of immune cytolytic genes was associated with nonrecurrence among patients with low TCR diversity or fewer neoantigens. Limitations include the sample size and the inability to distinguish CD8 + and CD4 + T cells using TCR sequencing. Conclusions These findings are the first to show that detailed tumor immune-genome analysis at definitive surgery can identify molecular patterns of antitumor immune response contributing to better clinical outcomes in MIBC. Patient summary We discovered that clonal expansion of certain T cells in tumor tissue, possibly targeting cancer-specific antigens, contributes to prevention of bladder cancer recurrence.

We assessed the association of temporal, socioeconomic and environmental factors with bladder cancer mortality in the United States. Our hypothesis was that bladder cancer mortality is associated with distinct environmental and socioeconomic factors with effects varying by region, race and gender.NCI (National Cancer Institute) age adjusted, county level bladder cancer mortality data from 1950 to 2007 were analyzed to identify clusters of increased bladder cancer death using the Getis-Ord Gi* statistic. Socioeconomic, clinical and environmental data were assessed using geographically weighted spatial regression analysis adjusting for spatial autocorrelation. County level socioeconomic, clinical and environmental data were obtained from national databases, including the United States Census, CDC (Centers for Disease Control and Prevention), NCHS (National Center for Health Statistics) and County Health Rankings.Bladder cancer mortality hot spots and risk factors for bladder cancer death differed significantly by gender, race and geographic region. From 1996 to 2007 smoking, unemployment, physically unhealthy days, air pollution ozone days, percent of houses with well water, employment in the mining industry and urban residences were associated with increased rates of bladder cancer mortality (p0.05). Model fit was significantly improved in hot spots compared to all American counties (R(2) = 0.20 vs 0.05).Environmental and socioeconomic factors affect bladder cancer mortality and effects appear to vary by gender and race. Additionally there were temporal trends of bladder cancer hot spots which, when persistent, should be the focus of individual level studies of occupational and environmental factors.

Objectives To determine the time to bladder cancer diagnosis from initial infection-like symptoms and its impact on cancer outcomes. Methods Using Surveillance, Epidemiology and End Results-Medicare, we designed a retrospective cohort study identifying beneficiaries aged ≥66 years diagnosed with bladder cancer from 2007 to 2009. Patients were required to have a hematuria or urinary tract infection claim within 1 year of bladder cancer diagnosis (n = 21 216), and have 2 years of prior Medicare data (n = 18 956) without any precedent hematuria, bladder cancer or urinary tract infection claims (n = 12 195). The number of days to bladder cancer diagnosis was measured, as well as the impact of sex and presenting symptom on time to diagnosis, pathology, and oncological outcomes. Results The mean time to bladder cancer diagnosis was 72.2 days in women versus 58.9 days in men (P < 0.001). A logistic regression model identified the greatest predictors of ≥pT2 pathology were both women (odds ratio 2.08, 95% confidence interval 1.70–2.55) and men (odds ratio 1.71, 95% confidence interval 1.49–1.97) presenting with urinary tract infection. Cox proportional hazards analysis identified an increased risk of mortality from bladder cancer and all causes in women presenting with urinary tract infection (hazard ratio 1.37, 95% confidence interval 1.10–1.71, and hazard ratio 1.47, 95% confidence interval 1.28–1.69) compared with women with hematuria. Conclusions Women have a longer interval from urinary tract infection to diagnosis of bladder cancer. Urinary tract infection presentation can adversely affect time to diagnosis, pathology and survival. Time to diagnosis seems not to be an independent predictor of bladder cancer outcomes.

To examine the effect of surgical approach on regional lymphadenectomy (LND) performance and inpatient complications for radical nephroureterectomy (NU) using a national administrative database.The National Inpatient Sample (2009-2012) was used to identify patients who underwent NU for urothelial carcinoma. Cohorts were stratified by performance of LND. Covariates included patient demographics, comorbidity, hospital characteristics, hospital volume, performance of LND, surgical approach (open [ONU], laparoscopic [LNU], or robotic [RNU]), and complications. Multivariable logistic regression was used to identify factors associated with LND performance and complications.A weighted population of 14,059 (85%) without LND and 2,560 (15%) with LND was identified. LND was more common in RNU (27%) compared with ONU (15%) and LNU (10%) (P0.01). On multivariable analysis, when compared with ONU, RNU was associated with increased odds of LND performance (odds ratio [OR] = 1.9, 95% CI: [1.3-2.8]; P = 0.001), whereas LNU was associated with decreased odds of LND performance (OR = 0.6, 95% CI: [0.4-0.8]; P = 0.004). Multivariable analysis of risk factors for complications demonstrated lower odds of complications with RNU (OR = 0.6, 95% CI: [0.4-0.8]; P = 0.001), whereas performance of LND increased the risk of complications (OR = 1.3, 95% CI: [1.001-1.7]; P = 0.049).When compared with ONU, RNU increased the odds of LND performance and had a lower inpatient complication rate, whereas LNU reduced the odds of LND performance and had no significant effect on inpatient complication rates. Performance of LND was independently associated with higher inpatient complication rates.

Urologic tumors invading the inferior vena cava can be a difficult management problem. They are traditionally dealt with utilizing hypothermic circulatory arrest through central cannulation for cardiopulmonary bypass performed through a median sternotomy in addition to the large abdominal incision for the kidney tumor. We describe a single incision approach utilizing normothermic cardiopulmonary bypass to address this technical challenge.

INTRODUCTION AND OBJECTIVES: Practices including reresection of the tumor site, induction course of Bacille CalmetteGuerin (BCG), and use of early cystectomy, have been recommended for patients with Stage T1 urothelial cancer of the bladder. We examined a population-based database to investigate current patterns of care among Stage T1 bladder cancer patients and factors that influence decisions and survival. METHODS: We interrogated the SEER-Medicare database to identify all patients with an initial diagnosis of stage T1 bladder cancer; those with mixed T1 and CIS were excluded. The number of patients undergoing reresection within 3 months of the initial resection were identified. Subsequent treatment after initial biopsy was identified (intravesical BCG or chemotherapy, cystectomy, or none). Patients were characterized for age, race, gender, education, and income. Time to cystectomy, cancer-specific survival and overall survival were determined. RESULTS: Among the 14,302 patients with stage T1 tumors, only 15% overall underwent reresection increasing from 8% in the first 5 years to 18% in the last 5 years. A minority of patients (13.5%) received adjuvant therapy after initial diagnosis including intravesical BCG in 6% (though this has increased to 9.5% in the last five years) and intravesical mitomycin in 7.5%. Patients receiving BCG were more likely to live in the West or Midwest. Among patients undergoing cystectomy, 2.0% occurred early (within 6 months) after initial resection and 4.3% after 6 months (mean time 21 months) though these rates have increased to 6% and 7.5%, respectively, in the past 5 years. Patients undergoing cystectomy were younger, more likely to be white and a lower comorbidity rate though wealth and education had no impact on these rates. Patients receiving BCG had a better cancer-specific and overall survival compared to mose who received mitomycin and no adjuvant therapy. Patients who underwent an early cystectomy had a modestly improved survival over those who underwent a late cystectomy. CONCLUSIONS: While reresecting tumor sites is now recommended in patients with T1 bladder tumors, this approach is still under utilized. BCG Intravesical therapy, especially after reresection, is minimally used though it appears to be associated with improved survival. Early cystectomy may need to be strongly considered for T1 bladder cancer especially in light of the ongoing shortage of BCG.

of preoperative antibiotics within 30 days of surgery was not associated with development of CDI (p1⁄40.46). While the incidence of CDI was higher among patients with Indiana pouch compared to ileal conduit and orthotopic neobladder (11.2% vs. 10% and 3.3%, respectively), the type of urinary diversion did not seem to influence rates of CDI in multivariate analysis (p1⁄40.061). CONCLUSIONS: The development of CDI occurs in up to 10% of patients undergoing radical cystectomy for bladder cancer. Our study demonstrates that preoperative use of antacid therapy, postoperative acute renal failure, and large cumulative intravenous antibiotic dosages are associated with the development of CDI.

Marking the optimal location for a stoma preoperatively enhances the likelihood of a patient's independence in stoma care, predictable pouching system wear times, and resumption of normal activities. Urologists and certified ostomy nurses are the optimal clinicians to select and mark stoma sites, as this skill is a part of their education, practice, and training. However, these providers are not always available, particularly in emergency situations. The purpose of this position statement, developed by the Wound, Ostomy and Continence Nurses Society in collaboration with the American Urological Association and the American Society of Colon and Rectal Surgeons, is to provide a guideline to assist clinicians (especially those who are not surgeons or WOC nurses) in selecting an effective stoma site.

The role of tissue engineering in the cystectomy population rests on the principle of sparing healthy intestinal tissue while replacing diseased bladder. Over the last 25 years advances in cell biology and material science have improved the quality and durability of bladder replacement in animals. The neo-urinary conduit ([NUC]-Tengion) employs autologous fat smooth muscle cells which are seeded onto synthetic, biodegradable scaffolds. This seeded construct is then implanted in the patient and purportedly regenerates native urinary tissue to serve as a passive channel connecting the ureters to the skin surface. Preclinical animal studies as well as the first phase I human trial implanting the NUC are reviewed. While the ultimate goal of creating a durable, effective, tissue-engineered conduit is still in its infancy, important technical and experimental strides have been made.