Faculty Bibliography

PURPOSE/OBJECTIVE:In 2010 the AJCC (American Joint Committee on Cancer) excluded urothelial carcinoma with subepithelial prostatic stromal invasion from the pT4a bladder cancer staging class, which is otherwise defined by direct prostatic invasion transmurally from the bladder. We determined if the new guidelines were reflective of differences in survival between subepithelial prostatic stromal invasion and transmural pT4a disease. MATERIALS AND METHODS/METHODS:A retrospective, multi-institutional cohort of cystectomy cases with subepithelial prostatic stromal invasion from the University of Chicago and Cleveland Clinic were compared to a cohort with transmural pT4a disease. All pathological specimens were rereviewed at the respective institutions. Patients were excluded from the final cohort if variant bladder cancer histology, pT3 bladder disease or extraprostatic extension of urothelial carcinoma were identified. The primary end points were cancer specific and overall survival. RESULTS:Our study sample consisted of 48 patients with subepithelial prostatic stromal invasion and 49 patients with transmural pT4a disease. Median followup was 12.8 months (IQR 4.9 to 31.4). Patients with subepithelial prostatic stromal invasion had lower rates of lymph node involvement than those with transmural pT4a disease (14.6% vs 61.2%, p <0.001) and lower rates of positive surgical margins (18.7% vs 61.2%, p <0.001). Rates of perioperative chemotherapy were similar in both groups. When comparing subepithelial prostatic stromal invasion and transmural pT4a groups, overall survival was 64.0 vs 9.8 months and median cancer specific survival was not achieved vs 16.5 months, respectively (p <0.001). CONCLUSIONS:Subepithelial prostatic stromal invasion from urothelial carcinoma has more favorable outcomes compared to transmural pT4a disease. Our results support the exclusion of subepithelial prostatic stromal invasion from the pT4a bladder urothelial carcinoma staging class.

PURPOSE/OBJECTIVE:Benign ureterointestinal anastomotic stricture is not uncommon after radical cystectomy and urinary diversion. We studied the impact of the running vs the interrupted technique on the ureterointestinal anastomotic stricture rate. MATERIALS AND METHODS/METHODS:From July 2007 to December 2008 interrupted end-to-side anastomoses were created and from January 2009 to July 2010 running anastomoses were created. The primary study end point was time to ureterointestinal anastomotic stricture. RESULTS:Of 266 consecutive patients 258 were alive 30 days after radical cystectomy, including 149 and 109 with an interrupted and a running anastomosis, respectively. The groups did not differ in age, gender, body mass index, age adjusted Charlson comorbidity index, receipt of chemotherapy or radiation, blood loss, operative time, diversion type or postoperative pathological findings. The stricture rate per ureter was 8.5% (25 of 293) and 12.7% (27 of 213) in the interrupted and running groups, respectively (p = 0.14). Univariate analysis suggested that postoperative urinary tract infection (HR 2.1, 95% CI 1.1-4.1, p = 0.04) and Clavien grade 3 or greater complications (HR 2.6, 95% CI 1.4-4.9, p <0.01) were associated with ureterointestinal anastomotic stricture. On multivariate analysis postoperative urinary tract infection (HR 2.4, 95% CI 1.2-5.1, p = 0.02) and running technique (HR 1.9, 95% CI 1.0-3.7, p = 0.05) were associated with ureterointestinal anastomotic stricture. Median time to stricture and followup was 289 (IQR 120-352) and 351 days (IQR 132-719) in the running cohort vs 213 (IQR 123-417) and 497 days (IQR 174-1,289) in the interrupted cohort, respectively. Of the 52 strictures 33 (63%) developed within 1 year. Kaplan-Meier analysis controlling for differential followup showed a trend toward higher freedom from stricture for the interrupted ureterointestinal anastomosis (p = 0.06). CONCLUSIONS:A running anastomosis and postoperative urinary tract infection may be associated with ureterointestinal anastomotic stricture. Larger series with multiple surgeons are needed to confirm these findings.

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

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

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

Purpose. Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is indicated for high-grade nonmuscle-invasive bladder cancer (NMIBC). The efficacy of BCG in patients with a history of previous pelvic radiotherapy (RT) may be diminished. We evaluated the outcomes of radical cystectomy for BCG-treated recurrent bladder cancer in patients with a history of RT for prostate cancer (PC). Methods. A retrospective chart review was performed to identify patients with primary NMIBC. We compared the outcomes of three groups of patients who underwent radical cystectomy for BCG-refractory NMIBC: those with a history of RT for PC, those who previously underwent radical prostatectomy (RP), and a cohort without PC or RT exposure. Results. From 1996 to 2008, 53 patients underwent radical cystectomy for recurrent NMIBC despite BCG. Those with previous pelvic RT were more likely to have a higher pathologic stage and decreased recurrence-free survival compared to the groups without prior RT exposure. Conclusion. Response rates for intravesical BCG therapy may be impaired in those with prior prostate radiotherapy. Patients with a history of RT who undergo radical cystectomy after failed BCG are more likely to be pathologically upstaged and have decreased recurrence-free survival. Earlier consideration of radical cystectomy may be warranted for those with NMIBC who previously received RT for PC.

OBJECTIVE:To identify the risk factors for, and complications associated with, the development of delirium after radical cystectomy. MATERIALS AND METHODS/METHODS:From July 2008 to December 2009, 59 patients, aged ≥65 years and undergoing radical cystectomy, were prospectively enrolled. The baseline cognitive status was assessed using the Mini-Mental Status Examination. Postoperative delirium was assessed using the Confusion Assessment Method. RESULTS:A total of 49 patients completed the surgery and all assessments. The incidence of postoperative delirium was 29%, with duration of 1-5 days. On univariate analysis, older age and preoperative Mini-Mental Status Examination score were associated with postoperative delirium. On multivariate analysis, only age was associated with postoperative delirium (odds ratio 1.52, 95% confidence interval 1.04-2.22, P=.03). The 2 groups did not differ in pathologic stage, length of surgery, intraoperative and postoperative narcotic usage, body mass index, age-adjusted Charlson comorbidity index, activities of daily living scores, smoking history, preoperative hematocrit, estimated blood loss, urinary tract infection, interval to a regular diet, or length of hospital stay. The patients who developed postoperative delirium were more likely to undergo readmission (odds ratio 10.7, 95% confidence interval 2.2-51.8, P=.01) and reoperation (odds ratio 9.2, 95% confidence interval 1.5-55.3, P=.03) but did not differ in the 90-day and 1-year mortality rates or incidence of postoperative complications. CONCLUSION/CONCLUSIONS:In patients aged≥65 years, a lower preoperative Mini-Mental Status Examination score and older age were significantly associated with the development of postcystectomy delirium, as measured using the Confusion Assessment Method. The patients who developed delirium were more likely to undergo readmission and reoperation. Larger studies with multiple surgeons are needed to validate these findings.

Approximately 50% of bladder cancer incidence in the United States has been attributed to known carcinogens, mainly from cigarette smoking. Following the identification of this important causative factor, many investigators have attempted to identify other major causes of bladder cancer in the environment. Genetic and epigenetic alterations related to carcinogenesis in the bladder have been linked to environmental and occupational factors unrelated to cigarette smoking and may account for a significant portion of bladder cancer cases in non-smokers. The interaction between genetics and exposures may modulate bladder cancer risk and influence the differing incidence, progression, and mortality of this disease in different genders and races. Comparative molecular studies are underway to measure the relative effects of environment and inheritance to account for observed differences in the epidemiology of bladder cancer. The use of geospatial tools and population-based data will offer further insight into the environmentally-linked causes of bladder cancer.