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Purpose: Our objective was to examine whether perioperative blood transfusion is associated with venous thromboembolism following radical cystectomy adjusting for both patient- and disease-related factors., Materials and Methods: Patients who underwent radical cystectomy for bladder cancer from 1980-2020 were identified in the Mayo Clinic cystectomy registry. Blood transfusion during the initial postoperative hospitalization was analyzed as a 3-tiered variable: no transfusion, postoperative transfusion alone, or intraoperative with or without postoperative transfusion. The primary outcome was venous thromboembolism within 90 days of radical cystectomy. Associations between clinicopathological variables and 90-day venous thromboembolism were assessed using multivariable logistic regression, with transfusion analyzed as both a categorical and a continuous variable., Results: A total of 3,755 radical cystectomy patients were identified, of whom 162 (4.3%) experienced a venous thromboembolism within 90 days of radical cystectomy. Overall, 2,112 patients (56%) received a median of 1 (IQR: 0-3) unit of blood transfusion, including 811 (38%) with intraoperative transfusion only, 572 (27%) with postoperative transfusion only, and 729 (35%) with intraoperative and postoperative transfusion. On multivariable analysis, intraoperative with or without postoperative blood transfusion was associated with a significantly increased risk of venous thromboembolism (adjusted OR 1.73, 95% CI 1.17-2.56, P = .002). Moreover, when analyzed as a continuous variable, each unit of blood transfused intraoperatively was associated with 7% higher odds of venous thromboembolism (adjusted OR 1.07, 95% CI 1.01-1.13, P = .03)., Conclusions: Intraoperative blood transfusion was significantly associated with venous thromboembolism within 90 days of radical cystectomy. To ensure optimal perioperative outcomes, continued effort to limit blood transfusion in radical cystectomy patients is warranted.

Objective: To compare the perioperative and oncologic outcomes associated with RCNU to a matched cohort undergoing RC alone. Simultaneous radical cystectomy and nephroureterectomy (RCNU) for synchronous upper tract and bladder urothelial carcinoma is an uncommon procedure. Sparse literature exists comparing outcomes in patients treated with radical cystectomy (RC) alone versus RCNU., Methods: Adults treated with RCNU for urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC) between 1980 and 2020 were identified. Patients were matched 2:1 to patients undergoing RC alone for UCB based on age (+/- 5 years), gender, BMI (+/- 5), Charlson Comorbidity Index, pathologic staging (stage ≤pT2 vs >pT2), and receipt of neoadjuvant chemotherapy. Outcomes included overall survival (OS), recurrence free survival (RFS), cancer specific survival (CSS), 30-day complications, length of stay (LOS), operative time, and estimated blood loss (EBL)., Results: A total of 39 patients undergoing RCNU were identified and matched to 74 patients undergoing RC. There were no significant differences in LOS, EBL, or 30-day complication rates. Operative time was significantly longer in the RC cohort. OS (HR 0.58, CI 0.35-0.97, P = .036) was significantly better for patients undergoing RC alone, while no significant difference was noted in RFS (HR 0.65, 0.34-1.24) and CSS (HR 0.58, CI 0.31-1.08, P = .08)., Conclusions: Patients undergoing RCNU had significantly lower OS compared to a matched group of patients undergoing RC alone. Perioperative outcomes between the groups did not differ significantly. This data can inform patient counseling for treatment of this rare disease state., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Intraoperative hypothermia (IOH) has been suggested to adversely impact outcomes following surgery. The objective of this study was to evaluate the association between IOH and survival following radical cystectomy (RC)., Methods: Patients who underwent RC for bladder cancer from 2003 to 2018 were identified in our cystectomy registry. Intraoperative temperatures were extracted from the anesthesia record. IOH was defined as a median intraoperative temperature <36°C, and severe IOH as ≤ 35°C. Time under 36°C was assessed as a continuous variable. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method. Associations between IOH and outcomes were assessed with multivariable Cox proportional hazards models., Results: A total of 852 patients were identified, among whom 274 (32%) had IOH. Median follow up among survivors was 4.9 years (IQR 2.4-8.7), during which time 483 patients died, including 343 from bladder cancer. Two-year survival was not significantly different between patients with and without IOH (CSS: 74% vs. 71%, P= 0.31; OS: 68% vs. 67%, P= 0.13). Following multivariable adjustment, neither IOH nor time under 36°C was significantly associated with survival. A total of 37 patients (4.3%) had severe IOH. These patients were observed to have significantly lower 2-year OS (56% vs. 68%, P= 0.005); however, this association did not remain statistically significant after multivariable adjustment (P= 0.92)., Conclusion: IOH was not independently associated with survival following RC. These data do not support IOH as a prognostic factor for cancer outcomes among patients undergoing RC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Up to one in ten patients undergoing cystectomy with urinary diversion develop a ureteroenteric stricture (UES). Despite unrecognized ureteral obstruction contributing to infection, nephrolithiasis, and/or progression of kidney disease, the long-term natural history and risk factors associated with UES remains understudied. Herein, we report our single institutional experience with the long-term incidence, clinical presentation, and risk factors associated with UES formation following urinary diversion., Methods: We reviewed 2,285 patients who underwent RC with urinary diversion between 1980-2008. UES was defined as radiographic evidence of ureteral obstruction at the level of the ureteroenteric anastomosis. The diagnosis of benign UES was confirmed by pathology. UES-free survival was estimated using the Kaplan-Meier method. The association between clinicopathologic features and the development of a UES were assessed using multivariable models., Results: A total of 192 (8%) patients developed a benign UES, at a median of 7 months (IQR 4-24) following RC, with 5% occurring after 10 years. Seventy seven percent of patients exhibited signs and/or symptoms of ureteral obstruction. Patients who developed a UES had a greater body mass index (BMI) (28 vs. 27), operative time (330 vs. 301 minutes) and were more likely to experience a <30-day Clavien ≥3 complication (all P<0.05). Receipt of abdominal radiation and smoking history were not significantly associated with UES stricture risk. On multivariable analysis, only greater BMI (per 1-unit increase) (OR 1.06, 95% CI: 1.02-1.09; P=0.0009) and <30-day Clavien ≥3 complication (OR 2.85, 95% CI: 1.90-4.28; P<0.0001) were associated with the development of a UES. Development of UES was associated with renal function deterioration., Conclusions: UES was identified in 8% of patients following RC with urinary diversion, with the majority presenting with symptoms. While the majority of these occur in the first 2 years after surgery, a patients' risk for the development of this complication persists beyond 10 years. Due to the adverse sequelae of UES, long-term functional and imaging surveillance following urinary diversion is warranted, and early reconstruction should be considered., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)

Introduction: The objective of the study was to determine whether sarcopenia is associated with pathologic and survival outcomes for patients with muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC)., Patients and Methods: We identified MIBC patients treated with cisplatin-based NAC in our cystectomy registry from 2000 to 2016. Pre- and post-NAC computed tomography images were analyzed with BodyCompSlicer, a validated body composition assessment tool. Sarcopenia was defined as a skeletal muscle index (SMI) below sex-specific international consensus values. Associations of clinical features with pathologic downstaging ( .05). Meanwhile, only post-NAC sarcopenia (hazard ratio, 1.90; 95% confidence interval, 1.02-3.56; P = .04) was independently associated with an increased risk of CSM., Conclusion: Sarcopenia after NAC and before RC appeared to be prognostic. Although skeletal muscle mass declined significantly during NAC, neither the degree of muscle loss nor pretreatment SMI were significantly associated with downstaging after NAC and RC. These data do not support the use of sarcopenia as a risk stratification tool for selection of patients for or monitoring response to NAC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: QT prolongation is an independent risk factor for sudden death, stroke, and all-cause mortality. However, additional studies have shown that in certain settings, QT prolongation may be transient and a result of external factors., Objective: In this study, we evaluated the clinical characteristics and outcomes of patients seen in the emergency department (ED) with QT prolongation., Methods: Between November 2010 and June 2011, 7522 patients had an electrocardiogram (ECG) obtained during their evaluation in the ED. Clinical, laboratory, and therapeutic information was collected for all patients with QT prolongation (i.e., ≥ 500 ms and QRS < 120 ms). Potential QT-inciting factors (drugs, electrolyte disturbances, and comorbidities) were synthesized into a pro-QT score., Results: Among the 7522 patients with an ECG obtained in the ED, a QT alert was activated in 93 (1.2%; mean QTc 521 ± 34 ms). The majority of ED patients (64%) had more than one underlying condition associated with QT prolongation, with electrolyte disturbances in 51%, a QT prolonging condition in 56%, and QT-prolonging drugs in 77%. Thirty-day mortality was 13% for patients with QT prolongation noted in the ED., Conclusions: One percent of patients evaluated with an ECG in the ED activated our prolonged QTc warning system, with most demonstrating > 1 QT-prolonging condition. Thirty-day mortality was significant, but it requires further investigation to determine whether the QTc simply provided a non-invasive indicator of increased risk or heralded the presence of a vulnerable host at risk of a QT-mediated sudden dysrhythmic death., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Commonly used drugs in hospital setting can cause QT prolongation and trigger life-threatening arrhythmias. We evaluate changes in prescribing behavior after the implementation of a clinical decision support system to prevent the use of QT prolonging medications in the hospital setting. We conducted a quasi-experimental study, before and after the implementation of a clinical decision support system integrated in the electronic medical record (QT-alert system). This system detects patients at risk of significant QT prolongation (QTc>500ms) and alerts providers ordering QT prolonging drugs. We reviewed the electronic health record to assess the provider's responses which were classified as "action taken" (QT drug avoided, QT drug changed, other QT drug(s) avoided, ECG monitoring, electrolytes monitoring, QT issue acknowledged, other actions) or "no action taken". Approximately, 15.5% (95/612) of the alerts were followed by a provider's action in the pre-intervention phase compared with 21% (228/1085) in the post-intervention phase (p=0.006). The most common type of actions taken during pre-intervention phase compared to post-intervention phase were ECG monitoring (8% vs. 13%, p=0.002) and QT issue acknowledgment (2.1% vs. 4.1%, p=0.03). Notably, there was no significant difference for other actions including QT drug avoided (p=0.8), QT drug changed (p=0.06) and other QT drug(s) avoided (p=0.3). Our study demonstrated that the QT alert system prompted a higher proportion of providers to take action on patients at risk of complications. However, the overall impact was modest underscoring the need for educating providers and optimizing clinical decision support to further reduce drug-induced QT prolongation.

In radical cystectomy specimens with bladder cancer, lymphatic and vascular invasion are often reported as 'angiolymphatic' or 'lymphovascular' invasion, terms that combine the findings of tumour within simple endothelial-lined lymphatic spaces and tumour within muscle-lined blood vessels. It is unclear if these patterns of invasion have different prognostic significance. In addition, there are conflicting data regarding the significance of lymphatic, vascular and perineural invasion in patients with bladder cancer. Herein, we studied 1504 patients treated by radical cystectomy for bladder cancer at our institution and followed for a mean of 10.6 years. Cases were re-reviewed by a urological pathologist for lymphatic invasion defined as tumour within a non-muscle-lined endothelial-lined lymphatic space, vascular invasion defined as tumour in a muscle-lined blood vessel, and perineural invasion defined as tumour within the perineural sheath. Associations of clinical and pathological features with bladder cancer death were evaluated using Cox proportional hazards regression models and summarised with hazard ratios and 95% confidence intervals. Survival was estimated by the Kaplan-Meier method. Multivariate analysis showed that lymphatic and vascular invasion but not perineural invasion were significantly associated with cancer specific survival (p<0.0001 and p=0.02, respectively). There was a significant association of lymphatic and vascular invasion but not perineural invasion with involved regional lymph nodes (p<0.0001 and p=0.004, respectively). In patients with metastasis to regional lymph nodes, lymphatic invasion remained significantly associated with outcome (p=0.02). The frequency of lymphatic and vascular invasion varied amongst histological subtypes of bladder cancer. Vascular and lymphatic invasion should be clearly defined and reported for radical cystectomy specimens containing bladder cancer., (Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate oncological outcomes after radical cystectomy (RC) in patients with plasmacytoid urothelial carcinoma (UC) and to compare survival to that in patients with pure UC of the bladder., Materials and Methods: We identified 46 patients with plasmacytoid UC and 972 with pure UC who were treated with RC between 1980 and 2009. All pathologic specimens were re-reviewed by a single GU pathologist. Patients were matched 1:2 by age, gender, Eastern Cooperative Oncology Group performance status, pathologic tumor stage, and nodal status to patients with pure UC. Survival was estimated using the Kaplan-Meier method and compared with the log rank test., Results: Patients with plasmacytoid UC were more likely to have extravesical disease (≥pT3) (83% vs 43%, P < .0001) and positive margins (31% vs 2.1%, P < .0001) than patients with pure UC. Plasmacytoid UC was associated with decreased overall survival (27% vs 45% at 5 years, relative risk [RR] 1.4, P = .04), cancer-specific survival (36% vs 57% at 5 years, RR 1.7, P = .01), and local recurrence-free survival (63% vs 81% at 5 years, RR 2, P = .01). When patients with plasmacytoid UC were matched to those with pure UC, there were no significant differences in 5-year overall, cancer-specific, and local or distant recurrence-free survival., Conclusion: Plasmacytoid UC is associated with a high rate of locally advanced disease and positive margins at RC, as well as increased local recurrence rates. Further research is necessary to delineate adjuvant or neoadjuvant treatment strategies to improve local cancer control of this rare subtype of UC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the association of ABO blood type with clinicopathologic outcomes and mortality among patients with urothelial carcinoma of the bladder treated with radical cystectomy (RC)., Patients and Methods: We identified 2,086 consecutive patients who underwent RC between 1980 and 2008. Postoperative recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan Meier method and compared with the log-rank test. Cox proportional hazards regression models were used to evaluate the association of ABO blood type with outcomes., Results: A total of 913 (44%), 881 (42%), 216 (10%), and 76 (4%) patients had blood type O, A, B, and AB, respectively. Median postoperative follow-up among survivors was 11.0 years (interquartile range: 7.7-15.9y). Overall, 1,561 patients died, with 770 deaths attributable to bladder cancer. Non-O blood type was associated with significantly worse 5-year RFS (65% vs. 69%; P = 0.04) and/or CSS (64% vs. 70%; P = 0.02). In particular, among patients with≤pT2N0 disease, the 5-year RFS for those with non-O vs. O blood type was 75% vs. 82%, respectively (P = 0.002), whereas the 5-year CSS was 77% vs. 85%, respectively (P = 0.001). Moreover, on multivariable analysis, blood type A remained independently associated with an increased risk of cancer-specific mortality (hazard ratio = 1.22; P = 0.01)., Conclusions: Non-O blood type, particularly blood type A, is associated with a significantly increased risk of death from bladder cancer among patients undergoing RC. If validated, the utility of a multimodal therapy approach, including perioperative chemotherapy, or more frequent postoperative surveillance in this cohort warrants further study., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Patients undergoing surgery are often exposed to QT-inciting factors that may increase the risk for complications. We evaluated the clinical characteristics and outcomes of patients with QTc ≥500 ms within the first 24 hours after surgery as identified by an institution-wide electrocardiogram alert system. From November 2010 to June 2011, 470 patients exhibited an electrocardiographically isolated QTc ≥500 ms. QT prolongation after surgery was the setting for >1 of every 10 QTc alerts (59 patients). We determined the presence of QT prolonging medical conditions, drugs, electrolyte abnormalities, and the surgical patient's clinical outcome. The average preoperative QTc of the 59 patients demonstrating perioperative QT prolongation was 463 ± 56 ms with a postoperative QTc increase of 54 ± 37 ms. Most patients (n = 48, 83%) had ≥1 known QT-inciting factor before surgery. Compared with presurgical findings, there was a significant increase in pro-QTc score after surgery (1.8 ± 1.5 vs 3.5 ± 2.0, p <0.01) indicating a greater burden of perioperative QT-inciting factors. In conclusion, nearly all cases of QT prolongation could be explained by known etiologic or iatrogenic factors suggesting that maladaptive cardiac repolarization is most likely not a transient, postoperative stress response and may be avoided by altering clinical management., (Copyright © 2015 Elsevier Inc. All rights reserved.)

QT prolongation is an independent risk factor for cardiovascular mortality in adults. However, there is little information available on pediatric patients with QT prolongation and their outcomes. Herein, we evaluated the prevalence of QT prolongation in pediatric patients identified by an institution-wide QT alert system, and the spectrum of their phenotype. Patients with documented QT prolongation on an ECG obtained between November 2010 and June 2011 were included. There were 1303 pediatric ECGs, and 68 children had electrographically isolated QT prolongation. Comprehensive review of medical records was performed with particular attention to QT-prolonging clinical, laboratory, and medication data, which were summarized into a pro-QTc score. Overall, 68 (5 %) pediatric patients had isolated QT prolongation. The mean age of this pediatric cohort was 9 ± 6 years, and the average QTc was 494 ± 42 ms. All children had 1 or more QT-prolonging risk factor(s), most commonly QT-prolonging medications. One patient was identified with congenital long QT syndrome (LQTS), which was not previously diagnosed. In one-year follow-up, only one pediatric death (non-cardiac) occurred (1.5 %). Potentially QT-offending/pro-arrhythmic medications were changed in 80 % of pediatric patients after the physician received the QT alert. Children with QT prolongation had very low mortality and minimal polypharmacy. Still, medications and other modifiable conditions were the most common causes of QT prolongation. Children with a prolonged QTc should be evaluated for modifiable QT-prolonging factors. However, if no risk factors are present or the QTc does not attenuate after risk factor modification/removal, the child should be evaluated for congenital LQTS.

Objective: To review our experience with radical cystectomy for small cell carcinoma of the bladder, to compare outcomes with a cohort of patients with urothelial carcinoma, and to determine the effect of adjuvant chemotherapy and pathology re-review in this setting., Methods: Among 2427 patients who underwent radical cystectomy, 68 patients had small cell carcinoma of the bladder. Patients with small cell carcinoma of the bladder were compared with an unmatched cohort of 1146 patients with urothelial carcinoma, and were then matched (1:2) based on TNM stage. Survival was estimated using the Kaplan-Meier method, and Cox models were used to evaluate association of clinicopathological features with outcome., Results: Among the 68 small cell carcinoma of the bladder patients, 37 (54%) were found to have small cell carcinoma of the bladder only after pathology re-review. Patients with small cell carcinoma of the bladder had a higher rate of advanced (pT3/4) tumor stage (84% vs 46%; P < 0.0001) and pN+ disease (37% vs 20%; P = 0.001) compared with patients with urothelial carcinoma. When matched for stage and lymph node status, no significant difference in 5-year cancer-specific survival was observed between the two groups (27% vs 29%; P = 0.64). Among small cell carcinoma of the bladder patients, those receiving adjuvant chemotherapy had improved 5-year overall survival compared with patients who did not receive adjuvant chemotherapy (43% vs 20%; P = 0.03), and a trend toward superior cancer-specific survival (40% vs 23%; P = 0.07)., Conclusions: Small cell carcinoma of the bladder is often an unrecognized pathological entity, which is associated with a higher rate of locally advanced and N+ disease. However, although when matched for pathological features, survival outcomes appear similar to urothelial carcinoma. Small cell carcinoma of the bladder patients receiving adjuvant chemotherapy had improved overall survival and cancer-specific survival, and these results require further investigation., (© 2015 The Japanese Urological Association.)

We developed and implemented a 'CPOE-QT Alert' system, that is, clinical decision support integrated in the computerized physician order entry system (CPOE), in 2011. The system identifies any attempts to order medications with risk of torsade de pointes (TdP) for patients with a history of significant QT prolongation (QTc ≥500 ms) and alerts the provider entering the order. We assessed its impact by comparing orders and subsequent medication administration before and after activation of the system. We found a significant decrease in the proportion of completed order per ordering attempt after system activation (94% (1293/1379) vs 77% (1888/2453), difference 16.8%; p<0.001). This resulted in a 13.9% reduction in the administration of those medications to patients. A significant decrease was observed across all provider types, educational levels, and specialties. The CPOE-QT Alert system successfully reduced exposure to QT-prolonging medications in high risk patients., (© The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: We evaluate the clinical presentation, management and outcomes of patients undergoing cystectomy for refractory hemorrhagic cystitis., Materials and Methods: We identified 21 patients with refractory hematuria treated with cystectomy at our institution between 2000 and 2012. Clot evacuation, bladder fulguration and bladder irrigation had failed in all patients before cystectomy. In addition, 45% of patients had received prior intravesical therapy (aminocaproic acid, alum or formalin), hyperbaric oxygen therapy (25%), nephrostomy tube placement for attempted urinary diversion (15%) and/or selective bladder angioembolization (5%)., Results: Median patient age at surgery was 77 years (IQR 72, 80) and 81% (17 of 21) of patients were male. The most common etiology for hemorrhagic cystitis was prior radiation therapy for prostate cancer (17, 81%). Median time from receipt of radiation to cystectomy in these patients was 91 months (IQR 73, 125). Median ASA® (American Society of Anesthesiologists) score at cystectomy was 3 and median preoperative hemoglobin was 10.2 gm/dl. Median length of stay after cystectomy was 10 days (IQR 7, 19). Severe (Clavien grade III to V) complications were noted in 42% of patients (8 of 19) and the 90-day mortality rate in this cohort was 16% (3 of 19). With a median postoperative followup of 13 months (IQR 4, 21), the 1 and 3-year overall survival was 84% and 52%, respectively., Conclusions: Cystectomy for hemorrhagic cystitis is associated with a high risk of perioperative complications and mortality, consistent with the baseline clinical status of this patient cohort and, as such, should remain a last resort to control bleeding after failure of conservative measures., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate survival among patients with urothelial carcinoma (UC) within the prostate in order to assess the impact of depth of tumour invasion as well as the importance of a concurrent bladder tumour., Patients and Methods: We identified 201 patients who underwent radical cystectomy (RC) between 1980 and 2006 and were found to have UC involving the prostate. All specimens were re-reviewed by a genitourinary pathologist. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Cox hazard regression models tested the association of clinicopathological variables with outcome., Results: In all, 93 patients had pTis disease in the prostate, 43 had pT2 tumours, and 66 patients were pT4a. The median follow-up was 10.5 years. The 5-year cancer-specific survival for patients with pTis, pT2, and pT4a prostate UC was 73%, 57%, and 21% respectively (P < 0.001). On multivariable analysis, higher prostate tumour stage (hazard ratio [HR] 2.09; P = 0.01), positive lymph node status (HR 2.09; P = 0.002), and concurrent ≥pT3 bladder cancer (HR 4.16; P < 0.001) were significantly associated with an increased risk of death from UC., Conclusions: Among patients with prostatic UC involvement, depth of tumour invasion was significantly associated with cancer-specific mortality, validating the staging reclassification. Concurrent locally advanced bladder cancer also negatively impacted survival, suggesting the potential prognostic value of reporting a secondary tumour stage in such cases., (© 2013 The Authors. BJU International © 2013 BJU International.)

Background: While perioperative blood transfusion (BT) has been associated with adverse outcomes in multiple malignancies, the importance of BT timing has not been established., Objective: The objective of this study was to evaluate whether intraoperative BT is associated with worse cancer outcomes in bladder cancer patients treated with radical cystectomy (RC)., Design, Setting, and Participants: Outcomes from two independent cohorts of consecutive patients with bladder cancer treated with RC were analyzed., Outcome Measurements and Statistical Analysis: Recurrence-free survival, cancer-specific survival (CSS), and overall survival were estimated and multivariate analyses were performed to evaluate the association of BT timing with cancer outcomes., Results and Limitations: In the primary cohort of 360 patients, 241 (67%) received perioperative BT, including 162 intraoperatively and 79 postoperatively. Five-year CSS was 44% among patients who received an intraoperative BT versus 64% for patients who received postoperative BT (p=0.0005). After multivariate analysis, intraoperative BT was associated with an increased risk of cancer mortality (hazard ratio [HR]: 1.93; p=0.02), while receipt of postoperative BT was not (p=0.60). In the validation cohort of 1770 patients, 1100 (62%) received perioperative BT with a median postoperative follow-up of 11 yr (interquartile range: 8.0-15.7). Five-year RFS (p<0.001) and CSS (p<0.001) were significantly worse among patients who received an intraoperative BT. Intraoperative BT was independently associated with recurrence (HR: 1.45; p=0.001), cancer-specific mortality (HR: 1.55; p=0.0001), and all-cause mortality (HR: 1.40; p<0.0001). Postoperative BT was not associated with risk of disease recurrence or cancer death., Conclusions: Intraoperative BT is associated with increased risk of bladder cancer recurrence and mortality., Patient Summary: In this study, the effects of blood transfusion on bladder cancer surgery outcomes were evaluated. Intraoperative blood transfusion, but not postoperative transfusion, was associated with higher rates of recurrence and cancer-specific mortality., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Pretreatment neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been associated with adverse survival in a variety of malignancies. However, the relationship between NLR and oncologic outcomes following radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) has not been well studied., Objective: To evaluate the association of preoperative NLR with clinicopathologic outcomes following RC., Design, Setting, and Participants: We identified 899 patients who underwent RC without neoadjuvant therapy at our institution between 1994 and 2005 and who had a pretreatment NLR., Outcome Measurements and Statistical Analysis: Preoperative NLR (within 90 d prior to RC) was recorded. Recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox proportional hazard and logistic regression models were used to analyze the association of NLR with clinicopathologic outcomes., Results and Limitations: Median postoperative follow-up was 10.9 yr (interquartile range: 8.3-13.9 yr). Higher preoperative NLR was associated with significantly increased risks of pathologic, extravesical tumor extension (odds ratio [OR]: 1.07; p=0.03) and lymph node involvement (OR: 1.09; p=0.02). Univariately, 10-yr cancer-specific survival was significantly worse among patients with a preoperative NLR (≥2.7 [51%] vs. <2.7 [64%]; p<0.001). Moreover, on multivariate analysis, increased preoperative NLR was independently associated with greater risks of disease recurrence (hazard ratio [HR]: 1.04; p=0.02), death from bladder cancer (HR: 1.04; p=0.01), and all-cause mortality (HR: 1.03; p=0.01)., Conclusions: Elevated preoperative NLR among patients undergoing RC is associated with significantly increased risk for locally advanced disease as well as subsequent disease recurrence, and cancer-specific and all-cause mortality. These data suggest that serum NLR may be a useful prognostic marker for preoperative patient risk stratification, including consideration for neoadjuvant therapy and clinical trial enrollment., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: QT prolongation on electrocardiogram (ECG) is a risk marker of ventricular arrhythmias and all-cause mortality. Left ventricular hypertrophy (LVH) on ECG is also associated with poor outcome. Patients satisfying ECG voltage criteria for LVH frequently show concomitant QT prolongation., Objective: This study aimed to explore the impact of marked QT prolongation on all-cause mortality in patients copresenting with LVH voltage criteria and prolonged QT on ECG., Methods: We evaluated 3364 ECGs with corrected QT (QTc) interval ≥460 ms detected by Mayo Clinic's QT alert system from November 2010 through June 2011. Every ECG with QTc interval ≥460 ms was evaluated for the presence of LVH voltage criteria by using Sokolow-Lyon voltage, Cornell voltage, and Cornell product., Results: Concomitant LVH voltage criteria were present in 181 of 3364 ECGs (5.3%) with QTc interval ≥460 ms. Mortality during a follow-up period of 217 ± 184 days was 13% (23 of 181). Independent of age and hypertension, the QTc interval predicted mortality in patients with LVH voltage criteria (hazard ratio 1.31 per 10-ms increase; 95% confidence interval 1.09-1.58; P < .01). Patients with LVH voltage criteria and QTc interval ≥500 ms had highest mortality (log rank, P < .001)., Conclusion: The QTc interval was an independent predictor of mortality in patients with concomitant LVH voltage and prolonged QTc interval on ECG. Mortality was highest in those with QTc interval ≥500 ms. QT prolongation on ECGs with concomitant LVH voltage criteria should not be regarded as a harmless byproduct of LVH, but should be used as a significant marker of increased mortality risk similar to that in patients without LVH voltage criteria., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The authors evaluated sarcopenia as a predictor of cancer-specific survival (CSS) and overall survival (OS) among patients with urothelial cancer of the bladder undergoing radical cystectomy (RC)., Methods: The lumbar skeletal muscle index (SMI) of 205 patients treated with RC for urothelial cancer between 2000 and 2007 was measured. Sarcopenia was classified according to international consensus definitions (SMI of < 55 cm(2)/m(2) for men and < 39 cm(2)/m(2) for women). The CSS and OS were estimated using the Kaplan-Meier method and compared with the log-rank test. Variables associated with CSS and all-cause mortality were summarized with hazard ratios (HRs)., Results: Of 205 patients, 141 (68.8%) were sarcopenic. Patients with sarcopenia were older, but were otherwise similar to patients without sarcopenia with respect to sex, Charlson comorbidity index, American Society of Anesthesiologists score, Eastern Cooperative Oncology Group performance status, receipt of neoadjuvant chemotherapy, TNM stage of disease, and tumor grade (P > .05 for all). The median follow-up was 6.7 years, during which time 135 patients died, including 91 who died of bladder cancer. Sarcopenic patients had significantly worse 5-year CSS (49% vs 72%; P = .003) and OS (39% vs 70%; P = .003) compared with patients without sarcopenia. Moreover, sarcopenia was found to be independently associated with both increased CSS (HR, 2.14; P = .007) and all-cause mortality (HR, 1.93; P = .004) on multivariable analysis., Conclusions: The presence of sarcopenia was found to significantly increase a patient's risk of CSS and all-cause mortality after undergoing RC for bladder cancer., (© 2014 American Cancer Society.)

Purpose: We evaluated the outcome in patients with late recurrence of urothelial carcinoma after radical cystectomy., Materials and Methods: We identified 2,091 patients who underwent radical cystectomy at our institution between 1980 and 2006. Survival was estimated using the Kaplan-Meier method and compared based on recurrence timing (less than 5 years vs 5 or greater) and location (urothelial vs nonurothelial) using the log rank test. Cox proportional hazard regression models were used to evaluate variables associated with late recurrence and death from bladder cancer., Results: Median postoperative followup was 16.6 years. Late recurrence was identified in 82 patients (3.9%). On multivariate analysis younger age (p = 0.0008), nonmuscle invasive disease (p = 0.01) and prostatic urethral involvement (p <0.0001) were significantly associated with an increased risk of late recurrence. Five-year post-recurrence cancer specific survival was significantly worse after recurrence within 5 years from radical cystectomy vs after late recurrence (17% vs 37%, p = 0.001). Patients with nonurothelial late recurrence had adverse 5-year cancer specific survival compared to those with urothelial late recurrence (19% vs 67%, p <0.0001). On multivariate analysis younger patient age (HR 1.01, p = 0.003), muscle invasive disease (HR 1.31, p <0.0001) and nonurothelial recurrence site (HR 2.76, p <0.0001) but not time to recurrence (p = 0.38) were associated with a significantly increased risk of death from bladder cancer following recurrence after radical cystectomy., Conclusions: Late recurrence is uncommon after radical cystectomy. Younger patient age, nonmuscle invasive disease and prostatic urethral involvement were associated with a significantly increased risk of late recurrence. Interestingly, time to recurrence was not associated with a subsequent risk of patient death., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Micropapillary urothelial carcinoma exhibits amplification of the human epidermal growth factor receptor, ERBB2(HER2), and overexpression of the ERBB2 protein product. The clinical significance of this has yet to be established. The objective of this study was to examine ERBB2 amplification and protein expression in micropapillary urothelial carcinoma and stage-matched typical urothelial carcinoma treated by radical cystectomy to assess the frequency of amplification and protein expression, and to determine the association with cancer-specific survival. Pathologic material and data from patients undergoing cystectomy at Mayo Clinic between 1980 and 2008 were reviewed. ERBB2 amplification by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry were assessed. Univariate and multivariate Cox proportional hazards regression models were used to evaluate for associations of ERBB2 amplification and protein expression with survival. ERBB2 amplification was identified in 9 (15%) of 61 micropapillary carcinomas compared with 9 (9%) of 100 urothelial carcinomas. In patients with micropapillary carcinoma, ERBB2 amplification was associated with a nearly threefold increased risk of cancer death. ERBB2 amplification (hazard ratio 4.3; P=0.0008) remained associated with an increased risk of death from bladder cancer among patients with micropapillary urothelial carcinoma on multivariate analysis. The association of cancer-specific survival and ERBB2 amplification was not seen in patients with urothelial carcinoma. ERBB2 immunohistochemistry correlated with ERBB2 amplification but there was no association of ERBB2 protein expression and survival. ERBB2 amplification is more frequent in micropapillary urothelial carcinoma than typical urothelial carcinoma, and patients with micropapillary carcinoma who have ERBB2 amplification have worse cancer-specific survival than those who do not. Identification of ERBB2 amplification in micropapillary carcinoma could provide important prognostic information and possibly provide a role for ERBB2 targeted therapy.

Objective: To evaluate the association of blood type (non-O vs O) with venous thromboembolism (VTE) risk after radical cystectomy (RC) for bladder cancer., Methods: From 1980 to 2005, we identified 2076 consecutive patients with RC for whom blood type was available in 2008 (96.7%). We evaluated the association of blood type with postoperative VTE using logistic regression, controlling for patient age, tumor, and nodal stage, Eastern Cooperative Oncology Group (ECOG) performance status, body-mass index (BMI), and number of lymph nodes removed at surgery., Results: A total of 865 of 2076 patients (41.7%) had O blood type, 1143 (55.0%) were non-O, and 68 (3.3%) were missing. Median follow-up was 11.1 years, during which time VTE developed in 216 patients (10.4%). No significant differences were noted between those with O vs non-O blood type regarding patient age (median 69 years vs 69, P = .87), ECOG (P = .69), BMI (median 27.5 vs 28.1, P = .12), tumor stage (P = .97), pN+ status (15.6% vs 15.2%, P = .79), or number of nodes removed (median 9 vs 8, P = .43). On multivariate analysis, non-O blood type was associated with a nearly two-fold increased risk of VTE (odds ratio [OR] = 1.85, P = .007)., Conclusion: Non-O blood type was independently associated with an increased risk of VTE after RC. These patients should be counseled accordingly, and may benefit from increased perioperative prophylaxis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: We investigated the association of histological reclassification during pathology re-review of radical cystectomy specimens with clinicopathological outcomes in patients initially classified with urothelial carcinoma., Materials and Methods: We identified 1,211 patients initially diagnosed with urothelial carcinoma at radical cystectomy between 1980 and 2005. All pathological specimens were re-reviewed by a urological pathologist. Survival was estimated using the Kaplan-Meier method and compared with the log rank test., Results: Of 1,211 cases previously recorded as pure urothelial carcinoma 406 (33%) were reclassified as variant histology. The most common variant histologies identified were squamous in 151 patients (37%) and micropapillary in 62 (15%). Variant histology on re-review was associated with a higher rate of extravesical disease (71%) than urothelial carcinoma at initial diagnosis (52%) or pure urothelial carcinoma on re-review (42%, p<0.0001). Median postoperative followup was 11.1 years, during which 976 patients died, including 564 of bladder cancer. Notably, reclassification resulted in significant stratification of 10-year cancer specific survival, which was 50% in patients with pure urothelial carcinoma after re-review, 47% in those with urothelial carcinoma on initial interpretation and 42% in those with variant histology on re-review (p=0.03). Ten-year overall survival in patients with urothelial carcinoma on re-review, urothelial carcinoma at initial interpretation and variant histology on re-review was 29%, 27% and 24%, respectively (p=0.04)., Conclusions: Pathological re-review of radical cystectomy specimens identified variant histology in a third of patients. These variants are associated with a high rate of locally advanced disease, which may impact the noted rates of cancer specific and overall survival. Thus, it is critical to be aware of re-review status when interpreting outcomes from historical data sets and stratifying risk., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated oncological outcomes after radical cystectomy in patients with the nested variant of urothelial carcinoma and compared survival to that in patients with pure urothelial carcinoma of the bladder., Materials and Methods: We identified 52 patients with the nested variant who were treated with radical cystectomy between 1980 and 2004. Pathological specimens were re-reviewed by a single genitourinary pathologist. Patients were matched 1:2 by age, gender, ECOG (Eastern Cooperative Oncology Group) performance status, pathological tumor stage and nodal status to patients with pure urothelial carcinoma. Survival was estimated using the Kaplan-Meier method and compared with the log rank test., Results: Patients with the nested variant had a median age of 69.5 years (IQR 62, 74) and a median postoperative followup of 10.8 years (IQR 9.3, 11.2). Nested variant cancer was associated with a high rate of adverse pathological features since 36 patients (69%) had pT3-T4 disease and 10 (19%) had nodal invasion. Eight patients (15%) with nested variant cancer received perioperative chemotherapy. When patients with the nested variant were matched to a cohort with pure urothelial carcinoma, no significant differences were noted in 10-year local recurrence-free survival (83% vs 80%, p = 0.46) or 10-year cancer specific survival (41% vs 46%, p = 0.75)., Conclusions: The nested variant of urothelial carcinoma is associated with a high rate of locally advanced disease at radical cystectomy. However, when stage matched to patients with pure urothelial carcinoma, patients with the nested variant did not have an increased rate of recurrence or adverse survival. Further studies are required to validate these findings and guide the optimal multimodal treatment approach to these patients., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: While the receipt of a perioperative blood transfusion (PBT) has been associated with an increased risk of mortality for a number of malignancies, the relationship between PBT and survival following radical cystectomy (RC) for bladder cancer (BCa) has not been well established., Objective: To evaluate the association of PBT with disease recurrence and mortality following RC., Design, Setting, and Participants: We identified 2060 patients who underwent RC at the Mayo Clinic between 1980 and 2005. PBT was defined as transfusion of allogenic red blood cells during RC or postoperative hospitalization., Outcome Measurements and Statistical Analysis: Survival was estimated using the Kaplan-Meier method and was compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of PBT with outcome, controlling for clinicopathologic variables., Results and Limitations: A total of 1279 patients (62%) received PBT. The median number of units transfused was 2 (interquartile range [IQR]: 2-4). Patients receiving PBT were significantly older (median: 69 yr vs 66 yr; p<0.0001), had a worse Eastern Cooperative Oncology Group performance status (p<0.0001), and were more likely to have muscle-invasive tumors (56% vs 49%; p = 0.004). Median postoperative follow-up was 10.9 yr (IQR: 7.9-15.7). Receipt of PBT was associated with significantly worse 5-yr recurrence-free survival (58% vs 64%; p = 0.01), cancer-specific survival (59% vs 72%; p<0.001), and overall survival (45% vs 63%; p<0.001). On multivariate analyses, PBT remained associated with significantly increased risks of postoperative tumor recurrence (hazard ratio [HR]: 1.20; p = 0.04), death from BCa (HR: 1.31; p = 0.003), and all-cause mortality (HR: 1.27; p = 0.0002). Among patients who received PBT, an increasing number of units transfused was independently associated with increased cancer-specific mortality (HR: 1.07; p<0.0001) and all-cause mortality (HR: 1.05; p<0.0001). Limitations include selection bias and lack of standardized transfusion criteria., Conclusions: We found that PBT is associated with significantly increased risks of cancer recurrence and mortality following RC. While external validation is required, continued efforts to reduce the use of blood products in these patients are warranted., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To determine the phenotype and outcome of patients with QTc of at least 500 ms and to create a pro-QTc risk score for mortality., Patients and Methods: An institution-wide computer-based QT alert system was developed and implemented at Mayo Clinic in Rochester, Minnesota. This system screens all electrocardiograms (ECGs) performed and alerts the physician if the QTc is 500 ms or greater. Between November 10, 2010, and June 30, 2011, 86,107 ECGs were performed in 52,579 patients. Clinical diagnoses, laboratory abnormalities, and medications known to influence the QT interval were collected from the medical records and summarized in a new pro-QTc score. Survival was compared with that of the 51,434 Mayo Clinic patients with a QTc less than 500 ms during the same period., Results: QT alerts were sent for 1145 patients (2%); of these, 470 (41%) had no other identifiable ECG reason for QT prolongation (eg, pacing). All-cause mortality during a mean ± SD of 224 ± 174 days of follow-up was 19% in those with QTc of 500 ms or greater compared with 5% in patients with QTc less than 500 ms (log-rank P<.001). The pro-QTc score was an age-independent predictor of mortality (pro-QTc score: hazard ratio, 1.18; 95% CI, 1.05-1.32; P=.006; age: hazard ratio, 1.02; 95% CI, 1.01-1.03; P=.004.). QT-prolonging medications accounted for 37% of the pro-QTc score., Conclusion: This novel institution-wide QT alert system identified patients with a high risk of mortality. The pro-QTc score, reflecting patients' multimorbidity and multipharmacy, was an independent predictor of mortality. The QT alert system may increase a physician's awareness of a high-risk patient. Potentially lifesaving interventions can be facilitated by reducing the modifiable factors of the pro-QTc score., (Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose: Micropapillary (MP) bladder cancer is a rare variant of urothelial carcinoma (UC) which has been associated with an aggressive natural history. We sought to report the outcomes of patients with MP bladder cancer treated with radical cystectomy (RC) and compare survival to patients with pure UC of the bladder., Methods: We identified 73 patients with MP bladder cancer and 748 patients with pure UC who underwent RC at our institution with median postoperative follow-up of 9.6 years. MP patients were stage-matched 1:2 to patients with pure UC. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test., Results: MP cancers were associated with a high rate of adverse pathologic features, as 48/73 patients (66 %) had pT3/4 tumors and 37 (50 %) had pN+ disease. Ten-year cancer-specific survival in MP patients was 31 %, compared with 53 % in the overall cohort with pure UC (p = 0.001). When patients with MP bladder cancer were then stage-matched to those with pure UC, no significant differences between the groups were noted with regard to 10-year local recurrence-free survival (62 vs. 69 %; p = 0.87), distant metastasis-free survival (44 vs. 56 %; p = 0.54), or cancer-specific survival (31 vs. 40 %; p = 0.41)., Conclusion: MP cancers are associated with a higher rate of locally advanced disease. However, when matched to patients with pure UC, patients with MP tumors did not have increased local/distant recurrence or adverse cancer-specific survival following RC.

Purpose: To our knowledge long-term oncologic outcomes following partial cystectomy for urothelial carcinoma remain to be defined. We evaluated patterns of recurrence and survival among matched patients treated with partial vs radical cystectomy for bladder cancer., Materials and Methods: We identified 86 patients who underwent partial cystectomy for pT1-4N0-1Mx urothelial carcinoma between 1980 and 2006 at our institution. They were matched 1:2 to patients undergoing radical cystectomy based on age, gender, pathological T stage and receipt of neoadjuvant chemotherapy. Survival was estimated using Kaplan-Meier analysis and compared with the log rank test., Results: Median postoperative followup was 6.2 years (range 0 to 27). No difference was noted for 10-year distant recurrence-free survival (61% vs 66%, p = 0.63) or cancer specific survival (58% vs 63%, p = 0.67) between patients treated with partial and radical cystectomy, respectively. Interestingly, 4 of 86 patients (5%) who underwent partial cystectomy showed extravesical pelvic tumor recurrence postoperatively vs 29 of 167 (17%) who underwent radical cystectomy (p = 0.004). In addition, 33 of 86 patients (38%) were diagnosed with intravesical recurrence of tumor after partial cystectomy and 16 of 86 (19%) initially treated with partial cystectomy ultimately underwent radical cystectomy., Conclusions: Our matched analysis demonstrated no difference in metastasis-free or cancer specific survival between select patients undergoing partial cystectomy and those undergoing radical cystectomy. Nevertheless, patients treated with partial cystectomy remain at risk for intravesical recurrence and, thus, they should be counseled and surveilled accordingly., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Ancillary cytologic tests including digital image analysis (DIA) and fluorescence in situ hybridization (FISH) have been developed to improve the sensitivity of routine cytology (RC) for the diagnosis of malignancy in pancreatobiliary strictures. The goal of this study was to retrospectively compare the performance of RC, DIA, and FISH on clinical brushing specimens., Methods: Endoscopic retrograde cholangiopancreatography brushings were obtained from 498 consecutive patients with pancreatobiliary strictures and analyzed by RC, DIA, and FISH as per standard practice. RC diagnostic categories included negative, atypical, suspicious, or positive. Aneuploid/tetraploid histograms were considered positive for DIA. FISH was performed using UroVysion (Abbott Molecular, Inc, Des Plaines, IL) and classified as negative, trisomy, tetrasomy, or polysomy., Results: The sensitivity of polysomy FISH (42.9%) was significantly higher than RC (20.1%) when equivocal RC results were considered negative (P < .001) with identical specificity (99.6%). There was a significant difference in time for diagnosis of carcinoma between FISH diagnostic categories (P < .001) and between RC diagnostic categories (P < .001). Logistic regression analysis revealed that polysomy FISH, trisomy FISH, suspicious cytology, primary sclerosing cholangitis status, and age were associated with carcinoma (P < .05)., Conclusions: Polysomy FISH had high sensitivity without compromise to specificity. DIA was not a significant independent predictor of malignancy. Multivariable modeling using RC, FISH, age, and primary sclerosing cholangitis status can be used to estimate the probability of carcinoma for an individual patient. We recommend including FISH as a routine test where available, along with RC, in the evaluation of indeterminate pancreatobiliary strictures.