Faculty Bibliography

INTRODUCTION/BACKGROUND:Penectomy for PC is useful in staging, disease prognosis, and treatment. Limited studies have evaluated its surgical complications. We sought to assess these complications and determine predictive models to create a novel risk score for penectomy complications. PATIENTS AND METHODS/METHODS:A retrospective review of patients undergoing PC surgical management from the 2005-2016 American College of Surgeons National Surgical Quality Improvement Program was performed. Data were queried for partial and total penectomy among those with PC. To develop predictive models of complications, we fit LASSO logistic, random forest, and stepwise logistic models to training data using cross-validation, demographic, comorbidity, laboratory, and wound characteristics as candidate predictors. Each model was evaluated on the test data using receiver operating characteristic curves. A novel risk score was created by rounding coefficients from the LASSO logistic model. RESULTS:A total of 304 cases met the inclusion criteria. Overall incidence of penectomy complications was 19.7%, where urinary tract infection (3.0%), superficial surgical site infection (3.0%), and bleeding requiring transfusion (3.9%) were most common. LASSO logistic, random forest, and stepwise logistic models for predicting complications had area under the curve (AUC) [95% confidence interval] values of 0.66 [0.52-0.81], 0.73 [0.63-0.83], and 0.59 [0.45-0.74], respectively. Eleven variables were included in the risk score. The LASSO model-derived risk score had moderately good performance (area under the curve [95% confidence interval] 0.74 [0.66-0.82]). Using a cutoff point of 6, the score attains sensitivity 0.58, specificity 0.74, and kappa 0.26. CONCLUSION/CONCLUSIONS:PC management through penectomy is associated with appreciable complications rates. Predictive models of penectomy complications performed moderately well. Our novel prognostic risk score may allow for improved preoperative counseling and risk stratification of men undergoing surgical management of PC.

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 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: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/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/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: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.