Faculty Bibliography

Introduction/UNASSIGNED:To evaluate overall survival (OS) of T1a kidney cancers stratified by histologic subtype and curative treatment including partial nephrectomy (PN), percutaneous ablation (PA), and radical nephrectomy (RN). Materials and Methods/UNASSIGNED:We queried the National Cancer Data Base (2004-2015) for patients with T1a kidney cancers who were treated surgically. OS was estimated by Kaplan-Meier curves based on histologic subtype and management. Cox proportional regression models were used to determine whether histologic subtypes and management procedure predicted OS. Results/UNASSIGNED:= 0.392) were observed. Adjusted Cox regression showed worse OS for PA than PN among patients with clear cell (HR 1.58, 95%CI [1.44-1.73], papillary RCC (1.53 [1.34-1.75]), and chromophobe RCC (2.19 [1.64-2.91]). OS was worse for RN than PN for clear cell (HR 1.38 [1.28-1.50]) papillary (1.34 [1.16-1.56]) and chromophobe RCC (1.92 [1.43-2.58]). Predictive models using Cox proportional hazards incorporating histology and surgical procedure alone were limited (c-index 0.63) while adding demographics demonstrated fair predictive power for OS (c-index 0.73). Conclusions/UNASSIGNED:In patients with pathologic T1a RCC, patterns of OS differed by surgery and histologic subtype. Patients receiving PN appears to have better prognosis than both PA and RN. However, the incorporation of histologic subtype and treatment modality into a risk stratification model to predict OS had limited utility compared with variables representing competing risks.

Electronic-cigarettes (E-cigs) are marketed as a safe alternative to tobacco to deliver the stimulant nicotine, and their use is gaining in popularity, particularly among the younger population. We recently showed that mice exposed to short-term (12 wk) E-cig smoke (ECS) sustained extensive DNA damage in lungs, heart, and bladder mucosa and diminished DNA repair in lungs. Nicotine and its nitrosation product, nicotine-derived nitrosamine ketone, cause the same deleterious effects in human lung epithelial and bladder urothelial cells. These findings raise the possibility that ECS is a lung and bladder carcinogen in addition to nicotine. Given the fact that E-cig use has become popular in the past decade, epidemiological data on the relationship between ECS and human cancer may not be known for a decade to come. In this study, the carcinogenicity of ECS was tested in mice. We found that mice exposed to ECS for 54 wk developed lung adenocarcinomas (9 of 40 mice, 22.5%) and bladder urothelial hyperplasia (23 of 40 mice, 57.5%). These lesions were extremely rare in mice exposed to vehicle control or filtered air. Current observations that ECS induces lung adenocarcinomas and bladder urothelial hyperplasia, combined with our previous findings that ECS induces DNA damage in the lungs and bladder and inhibits DNA repair in lung tissues, implicate ECS as a lung and potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, whether ECS poses any threat to humans is not yet known and warrants careful investigation.

OBJECTIVES/OBJECTIVE:Our aim was to determine whether using an organ transplant-based(TB) approach reduces postoperative complications(PCs) following radical nephrectomy(RN) and tumor thrombectomy(TT) in renal cell carcinoma(RCC) patients with level II-IV thrombi. METHODS:A total of 390(292 non-TB/98 TB) IRCC-VT Consortium patients who received no preoperative embolization/IVC filter were included. Stepwise linear/logistic regression analyses were performed to determine significant multivariable predictors of intraoperative estimated blood loss(IEBL), number blood transfusions received, and overall/major PC development within 30days following surgery. Propensity to receive the TB approach was controlled. RESULTS:The TB approach was clearly superior in limiting IEBL, blood transfusions, and PC development, even after controlling for other significant prognosticators/propensity score(P < .000001 in each case). Median IEBL for non-TB/TB approaches was 1000 cc/300 cc and 1500 cc/500 cc for tumor thrombus Level II-III patients, respectively, with no notable differences for Level IV patients(2000 cc each). In comparing PC outcomes between non-TB/TB patients with a non-Right-Atrium Cranial Limit, the observed percentage developing a: i) PC was 65.8%(133/202) vs. 4.3%(3/69) for ECOG Performance Status(ECOG-PS) 0-1, and 84.8%(28/33) vs. 25.0%(4/16) for ECOG-PS 2-4, and ii) major PC was 16.8%(34/202) vs. 1.4%(1/69) for ECOG-PS 0-1, and 27.3%(9/33) vs. 12.5%(2/16) for ECOG-PS 2-4. Major study limitation was the fact that all TB patients were treated by a single, experienced, high volume surgeon from one center (non-TB patients were treated by various surgeons at 13 other centers). CONCLUSIONS:Despite this major study limitation, the observed dramatic differences in PC outcomes suggest that the TB approach offers a major breakthrough in limiting operative morbidity in RCC patients receiving RN and TT.

OBJECTIVES/OBJECTIVE:To evaluate the impact of cisplatin-based neoadjuvant chemotherapy (NAC) in patients who underwent nephroureterectomy for high grade (HG) upper tract urothelial carcinoma (UTUC). METHODS:Retrospective review was conducted of patients with HG UTUC from 2011 to 2017 who underwent nephroureterectomy at two institutions. Patients with eGFR > 50 mL/min/1.73m2 were considered eligible for NAC and were referred for evaluation of NAC prior to nephroureterectomy. Patient demographics, kidney function, clinical and pathologic response rates and outcomes were analyzed. RESULTS:Of 95 patients with HG UTUC meeting inclusion criteria (mean age 72.3 years, mean pre-op eGFR 57.0 mL/min/1.73m2), 61 patients were considered eligible for NAC with eGFR > 50 mL/min/1.73m2, of which 25 (41%) received NAC. Of the patients who received NAC, 80% (20/25) of patients had clinical response on imaging and 80% (20/25) had pathologic response (<pT2N0 disease) on nephroureterectomy. On final pathology, only 20% of the NAC group had ≥pT2 disease compared to 64% of patients who proceeded directly to surgery (p = 0.001). Patients who received NAC had significantly longer progression free survival (p=0.051) and overall survival (p=0.052) compared to patients who proceeded directly to surgery. No patients progressed or were deemed ineligible for surgery due to NAC. CONCLUSIONS:Cisplatin-based NAC demonstrated a high clinical and pathologic response rate in patients with HG UTUC without compromising definitive surgical treatment. Since nephroureterectomy significantly reduces kidney function and eligibility for cisplatin-based chemotherapy after surgery, patients with HG UTUC should be considered for NAC.

Blue light cystoscopy (BLC) with hexaminolevulinate (HAL) during transurethral resection of bladder cancer improves detection of non-muscle-invasive bladder cancer (NMIBC) and reduces recurrence rates. Flexible BLC was approved by the FDA in 2018 for use in the surveillance setting and was demonstrated to improve detection. Results of a phase III prospective multicentre study of blue light flexible cystoscopy (BLFC) in surveillance of intermediate-risk and high-risk NMIBC showed that 20.6% of malignancies were identified only by BLFC. Improved detection rates in the surveillance setting are anticipated to lead to improved clinical outcomes by reducing future recurrences and earlier identification of tumours that are unresponsive to therapy. Thus, BLFC has a role in surveillance cystoscopy, and determining which patients will benefit from BLFC and optimal and cost-effective ways of incorporating this technology into surveillance cystoscopy must be developed.

PURPOSE/OBJECTIVE:To provide a contemporary understanding of chronic kidney disease (CKD) and its relevance to kidney cancer surgery. To resolve points of discrepancy regarding the survival benefits of partial nephrectomy (PN) vs radical nephrectomy (RN) by critically evaluating the results of prospective and retrospective studies in the urologic literature. MATERIALS/METHODS/METHODS:A comprehensive literature search for relevant articles listed in MEDLINE® (2002-2018) was performed using keywords radical nephrectomy, partial nephrectomy, glomerular filtration rate (GFR), kidney function, and chronic kidney disease. Selected review articles and society guidelines about CKD pertinent to urology and nephrology were also assessed. RESULTS:represents a more discerning postoperative prognostic threshold. Reported survival benefits of PN over RN demonstrated in retrospective studies are likely influenced by selection bias. The lack of survival benefit in the PN cohort of the only randomized trial of PN versus RN is consistent with data demonstrating that patients in both arms of the study had relatively low risk of mortality from CKD, when accounting for etiology of CKD and post-operative GFR levels. CONCLUSIONS:. Additional factors including non-surgical causes of CKD and degree of albuminuria can also dramatically alter the consequences of CKD following kidney cancer surgery. Urologists must have a comprehensive knowledge of CKD in order to assess the risks/benefits of PN versus RN when managing tumors with increased complexity and/or oncologic aggressiveness.