Faculty Bibliography

PURPOSE/OBJECTIVE:While MRI-Ultrasound Fusion-targeted biopsy (MRF-TB) allows for improved detection of clinically significant prostate cancer (csPCa), concerning numbers of clinically significant disease are still missed. We hypothesize that a number of these are due to the learning curve associated with MRF-TB. We report results of repeat MRF-TB in men with continued suspicion for cancer and the institutional learning curve in detection of csPCa over time. MATERIALS AND METHODS/METHODS:Analysis of 1813 prostate biopsies in a prospectively acquired cohort of men presenting for prostate biopsy over a 4-year period. All men were offered pre-biopsy MRI and assigned a maximum Prostate Imaging - Reporting and Data System version 2 (PI-RADS) score. Biopsy outcomes of men with suspicious region of interest (ROI) were compared. The relationship between time and csPCa detection was analyzed. RESULTS:csPCa detection rate increased 26% over time in men with PI-RADS 4 and 5 (4/5) ROI. On repeat MRF-TB in men with continued suspicion for cancer, 53% of men with PI-RADS 4/5 ROI demonstrated clinically significant discordance from initial MRF-TB, compared to only 23% of men with PI-RADS 1/2 ROI. Significantly less csPCa were missed or under-graded in the most recent biopsies as compared to the earliest biopsies. CONCLUSION/CONCLUSIONS:High upgrade rates on repeat MRF-TB and increasing cancer detection rate over time demonstrate the significant learning curve associated with MRF-TB. Men with low risk or negative biopsies with persistent concerning ROI should be promptly re-biopsied. Improved targeting accuracy with operator experience can help decrease the number of missed csPCa.

BACKGROUND:Malignant angiomyolipoma is an uncommon tumor of the class of perivasciular epithelioid cell neoplasms (PEComas). These tumors are characteristically driven by deleterious mutations in the tumor suppressors TSC1 and TSC2, whose gene products typically act to inhibit mTOR. There are several cases of malignant angiomyolipoma which exhibit transient responses to mTOR inhibitors, forming the basis of current practice guidelines in malignant PEComa. However the tumors ultimately acquire resistance, and there is no well-established second-line option. Despite the increasing prevalence of immunotherapy across a wide range of solid tumors, little is known about the immune infiltrate and PD-L1 expression of angiomyolipoma. Furthermore, there is no reported case on the treatment of malignant angiomyolipoma with an immune checkpoint inhibitor. CASE PRESENTATION/METHODS:A 38 year-old man presented with gross hematuria and was diagnosed with renal epithelioid angiomyolipoma. Despite surgical resection, the tumor recurred and metastasized. Targeted genomic sequencing revealed a deleterious mutation in TSC2, and the patient was treated with the mTOR inihbitor everolimus. The patient went on to have a partial response but ultimately progressed. He was then treated with the anti-PD-1 immune checkpoint inhibitor nivolumab, and achieved a durable near-complete response which is ongoing after two years of treatment. Immunohistochemical staining of tumor tissue revealed strong PD-L1 expression and a brisk T-cell infiltrate. CONCLUSIONS:We report on the first durable systemic treatment of malignant epithelioid angiomyolipoima with the use of PD-1 antibody nivolumab. Given the absence of prospective clinical trials in this exceedingly rare disease, particularly in the second-line setting, immune checkpoint inhibitors like nivolumab should be considered.

Background and Aims: To investigate the incidence, clinicopathological factors and treatment impacting prognosis in high-grade neuroendocrine cervical carcinoma (HGNCC). Methods: The incidence of cervical cancer in 2004-2014 was obtained from the USCS. Joinpoint regression was used to analyze trends and estimate annual percentage change (APC). Clinicopathological features and survival of cervical cancer was obtained from the NC

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.

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/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.

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: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.