Faculty Bibliography

INTRODUCTION/BACKGROUND:Nutritional status has been increasingly recognized as an important predictor of prognosis and surgical outcomes for cancer patients. We evaluated the effect of preoperative malnutrition on the development of surgical complications and mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS/METHODS:Using data from the American College of Surgeons National Surgical Quality Improvement Program, we evaluated the association of poor nutritional status with 30-day postoperative complications and overall mortality after RNU from 2005 to 2015. The preoperative variables suggestive of poor nutritional status included hypoalbuminemia (< 3.5 g/dL), weight loss within 6 months before surgery (> 10%), and a low body mass index. RESULTS:A total of 1200 patients were identified who had undergone RNU for UTUC. The overall complication rate was 20.5% (n = 246), and mortality rate was 1.75% (n = 21). On univariate analysis, patients who experienced a postoperative complication were more likely to have hypoalbuminemia (25.0% vs. 11.4%; P < .001) and weight loss (3.7% vs. 1.0%; P = .003). After controlling for baseline characteristics and comorbidities, hypoalbuminemia was found to be a significant independent predictor of postoperative complications (odds ratio, 2.09; 95% confidence interval, 1.29-3.38; P = .003). Hypoalbuminemia was also a significant independent predictor of mortality (odds ratio, 4.31; 95% confidence interval, 1.45-12.79; P = .008) on multivariable regression analysis. CONCLUSION/CONCLUSIONS:Our results have shown that hypoalbuminemia is a significant predictor of surgical complications and mortality after RNU for UTUC. This finding supports the importance of patients' preoperative nutritional status in this population and suggests that effective nutritional interventions in the preoperative setting could improve patient outcomes.

BACKGROUND:The American Society of Anesthesiologists physical status classification system, modified Charlson Comorbidity Index (mCCI), and modified Frailty Index have been associated with complications after urologic surgery. No study has compared the predictive performance of these indexes for postoperative complications after radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS/METHODS:Data from 1516 patients undergoing elective RC for bladder cancer were extracted from the 2005 to 2011 American College of Surgeons National Surgical Quality Improvement Program for a retrospective review. The perioperative outcome variables assessed were occurrence of minor adverse events, severe adverse events, infectious adverse events, any adverse event, extended length of hospital stay, discharge to a higher level of care, and mortality. Patient comorbidity indexes and demographic data were assessed for their discriminative ability in predicting perioperative adverse outcomes using an area under the curve (AUC) analysis from the receiver operating characteristic curves. RESULTS:The most predictive comorbidity index for any adverse event was the mCCI (AUC, 0.511). The demographic factors were the body mass index (BMI; AUC, 0.519) and sex (AUC, 0.519). However, the overall performance for all predictive indexes was poor for any adverse event (AUC < 0.52). Combining the most predictive demographic factor (BMI) and comorbidity index (mCCI) resulted in incremental improvements in discriminative ability compared with that for the individual outcome variables. CONCLUSION/CONCLUSIONS:For RC, easily obtained patient mCCI, BMI, and sex have overall similar discriminative abilities for perioperative adverse outcomes compared with the tabulated indexes, which are more difficult to implement in clinical practice. However, both the demographic factors and the comorbidity indexes had poor discriminative ability for adverse events.

Background/UNASSIGNED:Stage T1a renal cell carcinoma (RCC) (tumors <4 cm) is usually curable. Nephron-sparing partial nephrectomy (PN) has replaced radical nephrectomy (RN) as the standard of care for these tumors. Radical nephrectomy remains the first alternative treatment option, whereas percutaneous ablation (PA), a newer, nonsurgical treatment, is recommended less strongly because of the relative paucity of comparative PA data. Objective/UNASSIGNED:To compare PA, PN, and RN outcomes. Design/UNASSIGNED:Observational cohort analysis using inverse probability of treatment-weighted propensity scores. Setting/UNASSIGNED:Population-based SEER (Surveillance, Epidemiology, and End Results) cancer registry data linked to Medicare claims. Patients/UNASSIGNED:Persons aged 66 years or older who received treatment for T1a RCC between 2006 and 2011. Interventions/UNASSIGNED:PA versus PN and RN. Measurements/UNASSIGNED:RCC-specific and overall survival, 30- and 365-day postintervention complications. Results/UNASSIGNED:4310 patients were followed for a median of 52 months for overall survival and 42 months for RCC-specific survival. After PA versus PN, the 5-year RCC-specific survival rate was 95% (95% CI, 93% to 98%) versus 98% (CI, 96% to 99%); after PA versus RN, 96% (CI, 94% to 98%) versus 95% (CI, 93% to 96%). After PA versus PN, the 5-year overall survival rate was 77% (CI, 74% to 81%) versus 86% (CI, 84% to 88%); after PA versus RN, 74% (CI, 71% to 78%) versus 75% (CI, 73% to 77%). Cumulative rates of renal insufficiency 31 to 365 days after PA, PN, and RN were 11% (CI, 8% to 14%), 9% (CI, 8% to 10%), and 18% (CI, 17% to 20%), respectively. Rates of nonurologic complications within 30 days after PA, PN, and RN were 6% (CI, 4% to 9%), 29% (CI, 27% to 30%), and 30% (CI, 28% to 32%), respectively. Ten percent of patients in the PN group had intraoperative conversion to RN. Seven percent of patients in the PA group received additional PA within 1 year of treatment. Limitations/UNASSIGNED:Analysis of observational data may have been affected by residual confounding by provider or from selection bias toward younger, healthier patients in the PN group. Findings from this older study population are probably less applicable to younger patients. Use of SEER-Medicare linked files prevented analysis of patients who received treatment after 2011, possibly reducing generalizability to the newest PA, PN, and RN techniques. Conclusion/UNASSIGNED:For well-selected older adults with T1a RCC, PA may result in oncologic outcomes similar to those of RN, but with less long-term renal insufficiency and markedly fewer periprocedural complications. Compared with PN, PA may be associated with slightly shorter RCC-specific survival but fewer periprocedural complications. Primary Funding Source/UNASSIGNED:Association of University Radiologists GE Radiology Research Academic Fellowship and Society of Interventional Radiology Foundation.

Tobacco smoke (TS) contains numerous cancer-causing agents, with polycyclic aromatic hydrocarbons (PAHs) and nitrosamines being most frequently cited as the major TS human cancer agents. Many lines of evidence seriously question this conclusion. To resolve this issue, we determined DNA adducts induced by the three major TS carcinogens: benzo(a)pyrene (BP), 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanoe (NNK), and aldehydes in humans and mice. In mice, TS induces abundant aldehyde-induced γ-hydroxy-propano-deoxyguanosine (γ-OH-PdG) and α-methyl-γ-OH-PdG adducts in the lung and bladder, but not in the heart and liver. TS does not induce the BP- and NNK-DNA adducts in lung, heart, liver, and bladder. TS also reduces DNA repair activity and the abundance of repair proteins, XPC and OGG1/2, in lung tissues. These TS effects were greatly reduced by diet with polyphenols. We found that γ-OH-PdG and α-methyl-γ-OH-PdG are the major adducts formed in tobacco smokers' buccal cells as well as the normal lung tissues of tobacco-smoking lung cancer patients, but not in lung tissues of nonsmokers. However, the levels of BP- and NNK-DNA adducts are the same in lung tissues of smokers and nonsmokers. We found that while BP and NNK can induce BPDE-dG and O⁶-methyl-dG adducts in human lung and bladder epithelial cells, these inductions can be inhibited by acrolein. Acrolein also can reduce DNA repair activity and repair proteins. We propose a TS carcinogenesis paradigm. Aldehydes are major TS carcinogens exerting dominant effect: Aldehydes induce mutagenic PdG adducts, impair DNA repair functions, and inhibit many procarcinogens in TS from becoming DNA-damaging agents.

Purpose Neoadjuvant chemotherapy followed by radical cystectomy (RC) is a standard of care for the management of muscle-invasive bladder cancer (MIBC). Dose-dense cisplatin-based regimens have yielded favorable outcomes compared with standard-dose chemotherapy, yet the optimal neoadjuvant regimen remains undefined. We assessed the efficacy and tolerability of six cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) in patients with MIBC. Patients and Methods In this prospective, multicenter phase II study, patients received ddGC (gemcitabine 2,500 mg/m² on day 1 and cisplatin 35 mg/m² on days 1 and 2) every 2 weeks for 6 cycles followed by RC. The primary end point was pathologic downstaging to non-muscle-invasive disease (< pT2N0). Patients who did not undergo RC were deemed nonresponders. Pretreatment tumors underwent next-generation sequencing to identify predictors of chemosensitivity. Results Forty-nine patients were enrolled from three institutions. The primary end point was met, with 57% of 46 evaluable patients downstaged to < pT2N0. Pathologic response correlated with improved recurrence-free survival and overall survival. Nineteen patients (39%) required toxicity-related dose modifications. Sixty-seven percent of patients completed all six planned cycles. No patient failed to undergo RC as a result of chemotherapy-associated toxicities. The most frequent treatment-related toxicity was anemia (12%; grade 3). The presence of a presumed deleterious DNA damage response (DDR) gene alteration was associated with chemosensitivity (positive predictive value for < pT2N0 [89%]). No patient with a deleterious DDR gene alteration has experienced recurrence at a median follow-up of 2 years. Conclusion Six cycles of ddGC is an active, well-tolerated neoadjuvant regimen for the treatment of patients with MIBC. The presence of a putative deleterious DDR gene alteration in pretreatment tumor tissue strongly predicted for chemosensitivity, durable response, and superior long-term survival.

BACKGROUND:Diffusion-weighted imaging (DWI) provides insight into the pathophysiology underlying renal dysfunction. Variants of DWI include intravoxel incoherent motion (IVIM), which differentiates between microstructural diffusion and vascular or tubular flow, and diffusion tensor imaging (DTI), which quantifies diffusion directionality. PURPOSE/OBJECTIVE:To investigate the reproducibility of joint IVIM-DTI and compare controls to presurgical renal mass patients. STUDY TYPE/METHODS:Prospective cross-sectional. SUBJECTS/METHODS:Thirteen healthy controls and ten presurgical renal mass patients were scanned. Ten controls were scanned twice to investigate reproducibility. FIELD STRENGTH/SEQUENCE/UNASSIGNED:Subjects were scanned on a 3T system using 10 b-values and 20 diffusion directions for IVIM-DTI in a study approved by the local Institutional Review Board. ASSESSMENT/RESULTS:Retrospective coregistration and measurement of joint IVIM-DTI parameters were performed. STATISTICAL ANALYSIS/METHODS:Parameter reproducibility was defined as intraclass correlation coefficient (ICC) >0.7 and coefficient of variation (CV) <30%. Patient data were stratified by lesion side (contralateral/ipsilateral) for comparison with controls. Corticomedullary differentiation was evaluated. RESULTS:In controls, the reproducible subset of REnal Flow and Microstructure AnisotroPy (REFMAP) parameters had average ICC = 0.82 and CV = 7.5%. In renal mass patients, medullary fractional anisotropy (FA) was significantly lower than in controls (0.227 ± 0.072 vs. 0.291 ± 0.044, P = 0.016 for the kidney contralateral to the mass and 0.228 ± 0.070 vs. 0.291 ± 0.044, P = 0.018 for the kidney ipsilateral). In the kidney ipsilateral to the mass, cortical Dp,radial was significantly higher than in controls (P = 0.012). Conversely, medullary Dp,axial was significantly lower in contralateral than ipsilateral kidneys (P = 0.027) and normal controls (P = 0.044). DATA CONCLUSION/UNASSIGNED:REFMAP-MRI parameters provide unique information regarding renal dysfunction. In presurgical renal mass patients, directional flow changes were noted that were not identified with IVIM analysis alone. Both contralateral and ipsilateral kidneys in patients show reductions in structural diffusivities and anisotropy, while flow metrics showed opposing changes in contralateral vs. ipsilateral kidneys. LEVEL OF EVIDENCE/METHODS:2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Purpose: To compare the effectiveness of standard treatment using partial nephrectomy and personalized management strategies for small renal tumors using a simulation model.
Material(s) and Method(s): A decision-analytic model was constructed to compare life expectancy of management strategies for small renal tumors using: (1) uniform treatment with partial nephrectomy; or personalized options incorporating (2) percutaneous ablation; (3) biopsy, with triage of renal cell carcinoma (RCC) to nephron-sparing therapy; (4) watchful waiting for growth; and (5) MRI-based selection of papillary RCC for watchful waiting. The model included patient age, gender, chronic kidney disease (CKD) stage, renal functional decline specific to treatment type, comorbidities, benign and malignant tumors, RCC subtypes, and differential risks of cancer progression. Decisionmaking based on histologic subtype from biopsy was tested in sensitivity analysis.
Result(s): Partial nephrectomy was favored in patients of all ages with normal renal function. Otherwise, personalized strategies improved life expectancy compared with partial nephrectomy. The favorability of personalized therapy depended upon CKD stage, tumor anatomy and comorbidities. For example, patients with CKD stages 2 or 3a and moderate or high tumor anatomic complexity were most effectively treated with MRI-based management when they had no comorbidities (+ 2.57 years for MRI vs. partial nephrectomy in CKD 3a, Nephrometry Score 10), but with Charlson Comorbidity Index >=1, biopsy or watchful waiting for growth were most effective. Biopsy-based management became most effective in multiple patient subcategories when histologic subtype guided treatment selection.
Conclusion(s): Personalized treatment selection for small renal tumors likely improves life expectancy for patients with abnormal renal function

BACKGROUND:Radical nephrectomy (RN) with/without (±) thrombus excision (ThE) is the undisputed standard treatment for kidney cancer (KC) with renal or caval thrombus (Th). However, partial nephrectomy (PN) ± ThE may be considered in rare cases due to imperative (I) indications. OBJECTIVE:To evaluate the efficacy of IPN ± ThE and to compare it with RN ± ThE for KC with Th. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Records of 2,549 patients undergoing surgery for KC with Th at 24 institutions between 1971 and 2014 were retrospectively reviewed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/UNASSIGNED:Primary outcomes were overall survival (OS) and cancer specific survival (CSS), renal function variation after surgery and complications. Secondary outcomes were predictors of OS and CSS for IPN cases. To reduce bias IPN group was matched with RN using a propensity score with greedy algorithm on the basis of age, gender, tumor size, TNM, and histology. RESULTS AND LIMITATIONS/CONCLUSIONS:Forty-two patients underwent IPN ± Th. All thrombi were ≥level I; 5 patients experienced Clavien ≥ 3 complications with 2 complications-related deaths. At 27.3 (interquartile range: 7.1-47.7) months OS and CSS were 54.8% and 78.6%, respectively whereas at 9.7 (interquartile range: 1.4-43.7) months eGFR change was -17.3 ± 27.0ml/min. On univariate analysis tumour size, preoperative eGFR, transfusions, hospital stay, high serum creatinine, operating time, complications, lymphadenectomy, and metastases related to an increased risk of death. After matching (n = 38 per arm) no significant differences were present except for tumor necrosis (IPN = 39.5%; 15.8%; P = 0.01), thrombus level (P = 0.02), so as for operating time (P = 0.27), perioperative transfusions (P = 0.74) and complications (P = 0.35). A 5-year OS and CSS for IPN were 57.9% and 73.7%, respectively with no significant differences with RN (OS = 63.2, P = 0.611; CSS = 68.4, P>0.99). After 14.9 months creatinine and eGFR changes were (+0.4 ± 0.6mg/dl and -23.2 ± 37.3ml/min; P = 0.2879). CONCLUSIONS:In selected cases due to imperative indications PN ± ThE is a complex procedure and may be an alternative to RN ± ThE for KC with Th yielding noninferior oncological outcomes, functional outcomes, and complications. Further studies are needed to determine the role of PN ± ThE for KC with Th.

OBJECTIVE:To describe novel 3-dimensional (3D) printing and augmented reality (AR) methods of image data visualization to facilitate anatomic understanding and to assist with surgical planning and decision-making during robotic partial nephrectomy. MATERIALS AND METHODS/METHODS:We created a video of the workflow for creating 3D printed and AR kidney models along with their application to robotic partial nephrectomy. Key steps in their development are (1) radiology examination (magnetic resonance imaging and computed tomography), (2) image segmentation, (3) preparing for 3D printing or AR, and (4) printing the model or deploying the model to the AR device. RESULTS:We demonstrate the workflow and utility of 3D printing and AR kidney models applied to a case of a 70-year-old woman with a 3.4 cm renal mass on her left pelvic kidney. A 3D printed kidney model was created using multicolor PolyJet technology (Stratasys J750), allowing a transparent kidney with coloring of the renal tumor, artery, vein, and ureter. An AR kidney model was created using Unity 3D software and deployed to a Microsoft HoloLens. The 3D printed and AR models were used preoperatively and intraoperatively to assist in robotic partial nephrectomy. To date, we have created 15 3D printed and AR kidney models to use for robotic partial nephrectomy planning and intraoperative guidance. The application of 3D printed and AR models is safe and feasible and can influence surgical decisions. CONCLUSION/CONCLUSIONS:Our video highlights the workflow and novel application of 3D printed and AR kidney models to provide preoperative guidance for robotic partial nephrectomy. The insights gained from advanced visualization can influence surgical planning decisions.

INTRODUCTION/BACKGROUND:We sought to evaluate the discordance between ureteroscopic biopsy and surgical pathology for grading and staging of upper tract urothelial carcinoma (UTUC) and to establish preoperative predictors of aggressive tumors. METHODS:We performed a retrospective review of 314 patients who underwent ureteroscopic biopsy followed by surgical management for UTUC from 2000-2016 at three institutions. Our primary outcomes were muscle-invasive (≥pT2) disease at surgical pathology and upgrading of clinical low-grade (cLG) tumors to pathologic high-grade (pHG). RESULTS:At biopsy, 61% of patients had high-grade (cHG) tumors, and 21% had subepithelial connective tissue invasion (cT1+). On final pathology, 79% had pHG tumors, and 45% had stage ≥pT2. On multivariate analysis, advanced age, cHG, and cT1+ were independently associated with ≥pT2. The combined presence of cHG and cT1+ had a PPV of 86% for muscle invasion, and the combined absence of cHG and cT1+ had a NPV of 80%. The likelihood of missing invasion on biopsy in patients with muscle-invasive disease was increased when biopsy fragments were limited to ≤1mm. Among patients with cLG disease on biopsy, 51% were upgraded at surgery. The presence of positive urine cytology was associated with an increased risk of upgrading; however, this was not statistically significant. CONCLUSIONS:cHG, cT1+ on biopsy, and advanced patient age are independent risk factors for muscle-invasive UTUC. There is a significant risk of upgrading among patients with cLG tumors on biopsy, especially when urine cytology is positive. The predictive value of biopsy can likely be improved by more extensive ureteroscopic sampling.