Faculty Bibliography

Radical cystectomy (RC) with urinary diversion is associated with significant morbidity, much of which arises from the interposition of bowel segments in the urinary system. A tissue-engineered alternative for urinary diversion could dramatically reduce the perioperative and long-term morbidity associated with RC. Attempts at developing a tissue-engineered incontinent urinary conduit (TEUC) have involved mechanical scaffolds and promoting tissue growth within them. Despite some preclinical success, significant obstacles remain before a TEUC is ready for clinical use. A further understanding of tissue and materials engineering may help overcome these obstacles or help to develop a new approach to tissue engineering entirely.

PURPOSE:To evaluate the accuracy of the American College of Surgeons National Surgical Quality Improvement Programs (ACS-NSQIP) surgical risk calculator in patients undergoing radical cystectomy (RC) with urinary diversion. MATERIALS AND METHODS:Preoperative characteristics of patients who underwent RC with ileal conduit or orthotropic neobladder (ONB) between 2007 and 2016 were entered into the proprietary online ACS-NSQIP calculator to generate 30-day predicted risk profiles. Predicted and observed outcomes were compared by measuring Brier score (BS) and area under the receiver operating characteristic curve (AUC). RESULTS:Of 954 patients undergoing RC, 609 (64%) received ileal conduit and 345 (36%) received ONB. The calculator underestimated most risks by 10%-81%. The BSs exceeded the acceptable threshold of 0.01 and AUC were less than 0.8 for all outcomes in the overall cohort. The mean (standard deviation) predicted vs. observed length of stay was 9 (1.5) vs. 10.6 (7.4) days (Pearson's r = 0.09). Among patients who received ONB, adequate BS (<0.01) was observed for pneumonia, cardiac complications, and death. The receiver operating characteristic curve analysis revealed moderate accuracy of calculator for cardiac complications (AUC = 0.69) and discharge to rehab center (AUC = 0.75) among patients who underwent RC with ONB. CONCLUSIONS:The universal ACS-NSQIP calculator poorly predicts most postoperative complications among patients undergoing RC with urinary diversion. A procedure-specific risk calculator is required to better counsel patients in the preoperative setting and generate realistic quality measures.

INTRODUCTION:Radical cystectomy (RC) is the standard of care for invasive nonmetastatic bladder cancer. Unfortunately, it is a complex procedure and more than half of patients experience a complication. A number of efforts to reduce perioperative morbidity have been made, including alterations in pain management, antibiotics, diet advancement, and anticoagulation. Many of these changes in management have been studied with favorable results; however, it is not clear whether complication rates following RC have improved in recent years. With this in mind we sought to evaluate current temporal trends in postoperative complication rates following RC using a large national dataset. MATERIALS AND METHODS:Using the National Surgical Quality Improvement Program participant use files from 2010 to 2015, we identified patients undergoing RC using current procedural terminology codes. Demographic information as well as 30-day complications, length of stay (LOS), readmission and death were compared according to year of operation using univariable and multivariable analysis. RESULTS:Over the 6 year period analyzed, 6,510 patients were identified for analysis. Age and comorbidity were similar across the study period. A robotic approach was used in 5.8% of the entire cohort which did not differ among years. A total of 15.9% of patients underwent a continent urinary diversion, with a trend toward decreased use in recent years, 31.5% of patients experienced a complication and this did not differ significantly among years, and 40.7% of patients required a blood transfusion overall with a trend toward decreased use. LOS decreased over time from 10.6 days in 2010 to 9.2 days in 2015 (P<0.01) whereas readmissions increased slightly over the time period to 21.4% in 2015 (P<0.01). CONCLUSIONS:RC remains a procedure associated with high morbidity. In the recent era of enhanced recovery protocols, complication rates have not changed significantly, however, there has been a consistent decline in LOS and use of blood transfusion.

OBJECTIVES:To compare outcomes and survival of open-, robotic-, and laparoscopic nephroureterectomy (ONU, RNU, LNU) using population-based data. METHODS:Using the National Cancer Database, we identified patients who underwent nephroureterectomy for localized upper tract urothelial carcinoma between 2010 and 2013. Demographic and clinicopathologic characteristics were compared among the three operative approaches. Multivariate regression analyses were used to determine the impact of approach on performance of lymphadenectomy (LND), positive surgical margins (PSM), and overall survival (OS). RESULTS:In total, there were 9401 cases identified for analysis, including 3199 ONU (34%), 2098 RNU (22%), and 4104 LNU (44%). From 2010 to 2013, utilization of RNU increased from 14% to 30%. On multivariate analysis, LND was more likely in RNU (odds ratio [OR] 1.52; p < 0.01) and less likely in LNU (OR 0.77; p < 0.01) compared with ONU. RNU was associated with decreased PSM compared with ONU (OR = 0.73; p = 0.04). After adjusting for other factors, OS was not significantly associated with surgical approach. CONCLUSIONS:RNU utilization doubled over the study period. While RNU was associated with greater likelihood of LND performance as well as lower PSM rates when compared with ONU and LNU, surgical approach did not independently affect OS.

PURPOSE/OBJECTIVE:Alvimopan has decreased ileus and need for nasogastric tube (NGT) after radical cystectomy (RC). However, the natural history of ileus versus intestinal obstruction in patients receiving alvimopan is not well defined. We sought to examine the implications of NGT placement before and after the introduction of alvimopan for RC patients. METHODS:Retrospective review identified 278 and 293 consecutive patients who underwent RC before and after instituting alvimopan between June 2009 and May 2014. Baseline characteristics and postoperative outcomes were compared by alvimopan status. Multivariate logistic regression was performed to assess the impact of alvimopan on rates of NGT placement and reoperation for bowel complications. RESULTS:The cohorts had similar age, stage, approach, and BMI. Patients receiving alvimopan had decreased ileus (16 vs 32 %, p < 0.01) but similar rates of reoperation for bowel complications (2.8 vs 2.7 %). On multivariate analysis, alvimopan was associated with lower risk of NGT placement (OR 0.30, p < 0.01). For patients requiring NGT placement, there was an increased rate of reoperation among patients receiving alvimopan compared with those who did not (28 vs 11 %, p = 0.03). Patients receiving alvimopan who needed NGT had significantly increased median length of stay (22 vs 7 days), need for TPN (66 vs 5.3 %), and readmission for ileus (10.3 vs 2.3 %) compared with those who did not require NGT. CONCLUSIONS:Alvimopan significantly reduced the incidence of ileus and NGT placement following RC. NGT placement was associated with an increased need for reoperation for bowel complications in the setting of alvimopan.

PURPOSE:International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance. METHODS AND MATERIALS:Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review. Images with LRF were exported into a treatment planning system, and IC CTVs were contoured and evaluated for adequacy of coverage of each LRF with respect to both the patient and each of 6 pelvic subsites: common iliac (CI) region, obturator region (OR), external and internal iliac region, presacral region, cystectomy bed, or other pelvic site. Revisions to the IC contours were proposed based on the findings. RESULTS:Of the 52 patients with documented LRF, 13 (25%) had LRFs that were outside of the IC CTV involving 17 pelvic subsites: 5 near the CI CTV, 5 near the OR CTV, 1 near the external and internal iliac region, and 6 near the cystectomy bed. The 5 CI failures were located superior to the CTV, and the 5 OR failures were located medial to the CTV. Increasing the superior boundary of the CI to a vessel-based definition of the aortic bifurcation, as well as increasing the medial extension of the OR by an additional 9 mm, decreased the number of patients with LRF outside of the IC CTV to 7 (13%). CONCLUSIONS:Modified IC CTVs inclusive of a slight adjustment superiorly for the CI region and medially for the OR may reduce the risk of pelvic failure in patients treated with adjuvant radiation therapy.

OBJECTIVES:Ureteroenteric anastomotic strictures are common after cystectomy with urinary diversion. Endoscopic treatments have poor long-term success, although ureteral reimplantation is associated with morbidity. Predictors of successful open repair are poorly defined. Our objective was to characterize outcomes of ureteral reimplantation after cystectomy and identify risk factors for stricture recurrence. PATIENTS AND METHODS:We performed a retrospective review of 124 consecutive patients with a total of 151 open ureteral reimplantations for postcystectomy ureteroenteric strictures between January 2006 and December 2015. Baseline clinicopathologic characteristics and perioperative outcomes were examined. Predictors for stricture recurrence were assessed by univariable testing and univariate Cox proportional hazards regression. RESULTS:Most patients underwent preoperative drainage by percutaneous nephrostomy (PCN; 43%) or percutaneous nephroureterostomy (PCNU; 44%). Major iatrogenic injuries included enterotomies requiring bowel anastomosis (3.2%) and major vascular injuries (2.4%). Overall, 60 (48%) patients suffered 90-day complications, of which 15 (12%) patients had high-grade complications. Median length of stay was 6 days [interquartile range: 5, 8] and median follow-up was 21 months [interquartile range: 5, 43]. The overall success rate per ureter was 93.4%. On univariate analysis, the only significant predictor of stricture recurrence was preoperative PCNU placement compared with PCN placement or no drainage (success rates: 85.5% vs. 98.9%, respectively, P = 0.002). Cox proportional hazards regression demonstrated that preoperative PCNU placement yielded a hazard ratio of 10.2 (95% CI: 1.27-82.6) for stricture recurrence (P<0.005). Stricture recurrence was independent of previous endoscopic interventions (P = 0.42). Stricture length was unable to be assessed. CONCLUSIONS:Postcystectomy ureteral reimplantation was associated with relatively low rates of major iatrogenic injuries and high-grade complications. Preoperative PCN placement rather than PCNU may yield better results.

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

PURPOSE:Venous thromboembolic events are a significant source of morbidity after radical cystectomy. At our institution subcutaneous heparin was historically given to patients undergoing radical cystectomy immediately before incision and throughout the inpatient stay. In an effort to decrease the overall rate of venous thromboembolism and post-discharge venous thromboembolism, a regimen including extended duration enoxaparin was initiated for patients undergoing radical cystectomy. MATERIALS AND METHODS:In January 2013 thromboprophylaxis was modified for patients undergoing radical cystectomy by replacing a regimen of subcutaneous heparin before induction and then every 8 hours until discharge home with enoxaparin daily for postoperative prophylaxis continued until 28 days after discharge. Data from our institutional radical cystectomy database for patients undergoing surgery from January 2011 to May 2014 were reviewed. The primary outcome was clinically symptomatic postoperative venous thromboembolism. Secondary outcomes included timing of venous thromboembolism and blood transfusions. Multivariate logistic regression was used to control for differences between cohorts. RESULTS:Of the 402 patients 234 underwent radical cystectomy before the change and 168 after. The enoxaparin regimen decreased the rate of venous thromboembolism (12% vs 5%, p=0.024) with the main benefit on post-discharge venous thromboembolism (6% vs 2%, p=0.039). Overall 17 of 37 (46%) venous thromboembolisms occurred after discharge home. Multivariate analysis confirmed that the enoxaparin regimen was independently associated with reduced odds of venous thromboembolism (OR 0.33, 95% CI 0.14-0.76, p=0.009). Intraoperative and postoperative transfusion rates were similar between cohorts. CONCLUSIONS:Thromboprophylaxis with extended duration enoxaparin decreased the rate of venous thromboembolism after radical cystectomy compared to inpatient only subcutaneous heparin with no increased risk of bleeding.