Intraoperative Blood Transfusion Is Associated With Increased Risk of Venous Thromboembolism After Radical Cystectomy.

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.

Perioperative and Oncologic Outcomes Associated with Simultaneous Radical Cystectomy and Nephroureterectomy.

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.

Association of intraoperative hypothermia with oncologic outcomes following radical cystectomy.

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.

Persistent, long-term risk for ureteroenteric anastomotic stricture formation: the case for long term follow-up.

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.

Sarcopenia and Response to Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer.

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.

Prevalence and Outcome of High-Risk QT Prolongation Recorded in the Emergency Department from an Institution-Wide QT Alert System.

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.

Providers' Response to Clinical Decision Support for QT Prolonging Drugs.

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.

Oncologic Outcomes for Patients with Residual Cancer at Cystectomy Following Neoadjuvant Chemotherapy: A Pathologic Stage-matched Analysis.

While it has been demonstrated that receipt of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) improves survival compared to RC alone, the driving factor for this benefit may be from patients with ypT0 status at surgery. Meanwhile, the implications of having residual urothelial carcinoma of the bladder (rUCB) at RC after NAC are less clear. We therefore evaluated whether survival differed between patients with rUCB at RC after NAC and stage-matched controls who underwent RC alone. Patients who underwent NAC + RC (n = 180) were matched to controls who underwent RC alone (n=324) on the basis of pT and pN stage, margin status, and year of RC. The 5-yr recurrence-free survival (RFS; 90% vs 94%; p=1), cancer-specific survival (CSS; 82% vs 93%; p=0.4), and overall survival (OS; 82% vs 82%; p=0.5) were not significantly different between the NAC and control groups for patients with ypT0N0/pT0N0 disease (n=103). Conversely, among patients with rUCB at RC (n=401), patients who received NAC had significantly worse 5-yr RFS (50% vs 63%; p=0.01), CSS (40% vs 59%; p=0.003), and OS (33% vs 48%; p=0.02). On multivariable analysis for patients with rUCB, NAC receipt remained independently associated with worse RFS (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.28-2.66; p=0.001), CSS (HR 1.81, 95% CI 1.30-2.52; p<0.001), and OS (HR 1.57, 95% CI 1.18-2.08; p=0.002). Limitations include potential for selection bias owing to the retrospective observational design. Thus, while patients who achieve a complete response to NAC have excellent survival outcomes, those with rUCB after NAC have a worse prognosis compared to stage-matched controls undergoing RC alone. It may be worthwhile considering these patients for clinical trials evaluating the role of additional treatments after RC using newer agents while we await further research on predicting which patients achieve ypT0 status from NAC before RC. PATIENT SUMMARY: On surgical removal of the bladder, patients without residual bladder cancer after neoadjuvant chemotherapy have excellent survival outcomes. However, patients with residual cancer after neoadjuvant chemotherapy and surgery have worse outcomes compared to patients undergoing surgery alone. These patients should therefore be considered for additional treatments after surgery using newer agents while we await further research on predicting which patients will benefit from neoadjuvant chemotherapy before bladder removal for cancer.

Prognostic significance of lymphatic, vascular and perineural invasion for bladder cancer patients treated by radical cystectomy.

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.

Outcomes Following Radical Cystectomy for Plasmacytoid Urothelial Carcinoma: Defining the Need for Improved Local Cancer Control.

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.

The association of ABO blood type with disease recurrence and mortality among patients with urothelial carcinoma of the bladder undergoing radical cystectomy.

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.

Frequency and cause of transient QT prolongation after surgery.

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.

Phenotype of Children with QT Prolongation Identified Using an Institution-Wide QT Alert System.

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.

Long-term results of radical cystectomy and role of adjuvant chemotherapy for small cell carcinoma of the bladder.

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.

Impact of clinical decision support preventing the use of QT-prolonging medications for patients at risk for torsade de pointes.

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.

Perioperative blood transfusion and radical cystectomy: does timing of transfusion affect bladder cancer mortality?

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.

Cystectomy for refractory hemorrhagic cystitis: contemporary etiology, presentation and outcomes.

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.

Impact of left ventricular hypertrophy on QT prolongation and associated mortality.

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.

Sarcopenia in patients with bladder cancer undergoing radical cystectomy: impact on cancer-specific and all-cause mortality.

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.

Pretreatment neutrophil-to-lymphocyte ratio is associated with advanced pathologic tumor stage and increased cancer-specific mortality among patients with urothelial carcinoma of the bladder undergoing radical cystectomy.

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.