Non-Metastatic Clear Cell Renal Cell Carcinoma Immune Cell Infiltration Heterogeneity and Prognostic Ability in Patients Following Surgery.

Predicting which patients will progress to metastatic disease after surgery for non-metastatic clear cell renal cell carcinoma (ccRCC) is difficult; however, recent data suggest that tumor immune cell infiltration could be used as a biomarker. We evaluated the quantity and type of immune cells infiltrating ccRCC tumors for associations with metastatic progression following attempted curative surgery. We quantified immune cell densities in the tumor microenvironment and validated our findings in two independent patient cohorts with multi-region sampling to investigate the impact of heterogeneity on prognostic accuracy. For non-metastatic ccRCC, increased CD8+ T cell infiltration was associated with a reduced likelihood of progression to metastatic disease. Interestingly, patients who progressed to metastatic disease also had increased percentages of exhausted CD8+ T cells. Finally, we evaluated the spatial heterogeneity of the immune infiltration and demonstrated that patients without metastatic progression had CD8+ T cells in closer proximity to ccRCC cells. These data strengthen the evidence for CD8+ T cell infiltration as a prognostic biomarker in non-metastatic ccRCC and demonstrate that multi-region sampling may be necessary to fully characterize immune infiltration within heterogeneous tumors. Tumor CD8+ T cell infiltration should be investigated as a biomarker in adjuvant systemic therapy clinical trials for high-risk non-metastatic RCC.

The Selection for Cytoreductive Nephrectomy (SCREEN) Score: Improving Surgical Risk Stratification by Integrating Common Radiographic Features.

BACKGROUND: Careful patient selection is critical when considering cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) but few studies have investigated the prognostic value of radiologic features that measure tumor burden. OBJECTIVE: To develop a prognostic model to improve CN selection with integration of common radiologic features with known prognostic factors associated with mortality in the first year following surgery. DESIGN, SETTINGS, AND PARTICIPANTS: Data were analyzed for consecutive patients with mRCC treated with upfront CN at five institutions from 2006 to 2017. Univariable and multivariable models were used to evaluate radiographic features and known risk factors for associations with overall survival. Relevant factors were used to create the SCREEN model and compared to the International mRCC Database Consortium (IMDC) model for predictive accuracy and clinical usefulness. RESULTS AND LIMITATIONS: A total of 914 patients with mRCC were treated with upfront CN during the study period. Seven independently predictive variables were used in the SCREEN score: three or more metastatic sites, total metastatic tumor burden ≥5 cm, bone metastasis, systemic symptoms, low serum hemoglobin, low serum albumin, and neutrophil/lymphocyte ratio ≥4. Predictive accuracy measured as the area under the receiver operating characteristic curves was 0.76 for the SCREEN score and 0.55 for the IMDC model. Decision curve analysis showed that the SCREEN model was useful beyond the IMDC classifier for threshold first-year mortality probabilities between 15% and 70%. CONCLUSIONS: The SCREEN score had higher predictive accuracy for first-year mortality compared to the IMDC scheme in a multi-institutional cohort and may be used to improve CN selection. PATIENT SUMMARY: This study provides a model to improve selection of patients with metastatic kidney cancer who may benefit from surgical removal of the primary kidney tumor. We found that radiographic measurements of the tumor burden predicted the risk of death in the first year after surgery. The model can be used to improve decision-making by these patients and their physicians.

Incidental Prostate Cancer Diagnosis Is Common After Holmium Laser Enucleation of the Prostate.

OBJECTIVE: To determine the incidence of incidental prostate cancer detection (iPCa) after holmium laser enucleation of the prostate (HoLEP). The published rate of iPCa after HoLEP is widely variable from 7% to 23% and we aim to define preoperative risk factors for iPCa to inform risk-adjusted preoperative evaluation for PCa. METHODS: Consecutive patients undergoing HoLEP from 2018 to 2022 were included and comprehensive clinical data abstracted from a prospectively maintained database. iPCa was defined as a diagnosis of PCa on pathologic examination of the HoLEP specimen. Patients with and without iPCa were compared with respect to preoperative clinical variables. RESULTS: Of 913 HoLEP patients, 183 (20%) were diagnosed with iPCa. Most patients (95%) had a preoperative prostate-specific antigen (PSA), 9% had negative MRI, and 30% had negative prostate biopsy. On multivariable analysis, PSA density (OR 1.06; 95% CI 1.03, 1.10; P < .001), preoperative biopsy status (OR 0.47, CI 0.30, 0.75; P = .002), and current 5-alpha reductase inhibitor use (OR 0.64, CI 0.43, 0.97; P = .034), were associated with iPCa diagnosis. CONCLUSION: In a significantly prescreened population, we identified a 20% rate of iPCa after HoLEP. Preoperative characteristics associated with iPCa diagnosis included increasing age, increasing PSA density, and current 5-alpha reductase inhibitor use. However, these factors alone may be of limited clinical utility to prospectively identify patients at high risk of iPCa diagnosis. We suggest and advocate for development of a standardized, risk-adapted evaluation focused on expanded use of imaging and selective biopsy to prioritize identification of clinically significant PCa prior to nononcologic surgery.

Contemporary Patients Have Better Perioperative Outcomes Following Cytoreductive Nephrectomy: A Multi-institutional Analysis of 1272 Consecutive Patients.

OBJECTIVE: To evaluate factors associated with perioperative outcomes in a multi-institutional cohort of patients treated with cytoreductive nephrectomy (CN). METHODS: Data were analyzed for metastatic renal cell carcinoma patients treated with CN at 6 tertiary academic centers from 2005 to 2019. Outcomes included: Clavien-Dindo complications, mortality, length of hospitalization, 30-day readmission rate, and time to systemic therapy. Univariate and multivariable models evaluated associations between outcomes and prognostic variables including the year of surgery. RESULTS: A total of 1272 consecutive patients were treated with CN. Patients treated in 2015-2019 vs 2005-2009 had better performance status (P<.001), higher pathologic N stage (P = .04), more frequent lymph node dissections (P<.001), and less frequent presurgical therapy (P = .02). Patients treated in 2015-2019 vs 2005-2009 had lower overall and major complications from surgery, 22% vs 39%, P<.001% and 10% vs 16%, P = .03. Mortality at 90days was higher for patients treated 2005-2009 vs 2015-2019; 10% vs 5%, P = .02. After multivariable analysis, surgical time period was an independent predictor of major complications and 90-day mortality following cytoreductive surgery. CONCLUSION: Postoperative major complications and mortality rates following CN are significantly lower in patients treated within the most recent time period.

Long-Term Imaging Follow-up from the Management of Myelomeningocele Study.

BACKGROUND AND PURPOSE: Short-term results demonstrate that prenatal repair of a myelomeningocele is associated with a reduction in hydrocephalus and an increased likelihood of the reversal of Chiari II malformations compared with postnatal repair. The purpose of this study was to identify the long-term imaging findings at school age among subjects who underwent pre- versus postnatal repair of a myelomeningocele. MATERIALS AND METHODS: A subset of subjects enrolled in the Management of Myelomeningocele Study who underwent either prenatal (n = 66) or postnatal (n = 63) repair of a lumbosacral myelomeningocele and had follow-up brain MR imaging at school age were included. The prevalence of posterior fossa features of Chiari II malformation and supratentorial abnormalities and the change in these findings from fetal to school-age MR imaging were compared between the 2 groups. RESULTS: Prenatal repair of a myelomeningocele was associated with higher rates of normal location of fourth ventricle and lower rates of hindbrain herniation, cerebellar herniation, tectal beaking, brainstem distortion, and kinking at school age compared with postnatal repair (all P < .01). Supratentorial abnormalities, including corpus callosal abnormalities, gyral abnormalities, heterotopia, and hemorrhage, were not significantly different between the 2 groups (all P > .05). The rates of resolution of brainstem kinking, tectal beaking, cerebellar and hindbrain herniation, and normalization of fourth ventricle size from fetal to school age MR imaging were higher among the prenatal compared with postnatal surgery group (all, P < .02). CONCLUSIONS: Prenatal repair of a myelomeningocele is associated with persistent improvement in posterior fossa imaging findings of Chiari II malformation at school age compared with postnatal repair.

Development of Gestational Age-Based Fetal Brain and Intracranial Volume Reference Norms Using Deep Learning.

BACKGROUND AND PURPOSE: Fetal brain MR imaging interpretations are subjective and require subspecialty expertise. We aimed to develop a deep learning algorithm for automatically measuring intracranial and brain volumes of fetal brain MRIs across gestational ages. MATERIALS AND METHODS: This retrospective study included 246 patients with singleton pregnancies at 19-38 weeks gestation. A 3D U-Net was trained to segment the intracranial contents of 2D fetal brain MRIs in the axial, coronal, and sagittal planes. An additional 3D U-Net was trained to segment the brain from the output of the first model. Models were tested on MRIs of 10 patients (28 planes) via Dice coefficients and volume comparison with manual reference segmentations. Trained U-Nets were applied to 200 additional MRIs to develop normative reference intracranial and brain volumes across gestational ages and then to 9 pathologic fetal brains. RESULTS: Fetal intracranial and brain compartments were automatically segmented in a mean of 6.8 (SD, 1.2) seconds with median Dices score of 0.95 and 0.90, respectively (interquartile ranges, 0.91-0.96/0.89-0.91) on the test set. Correlation with manual volume measurements was high (Pearson r = 0.996, P < .001). Normative samples of intracranial and brain volumes across gestational ages were developed. Eight of 9 pathologic fetal intracranial volumes were automatically predicted to be >2 SDs from this age-specific reference mean. There were no effects of fetal sex, maternal diabetes, or maternal age on intracranial or brain volumes across gestational ages. CONCLUSIONS: Deep learning techniques can quickly and accurately quantify intracranial and brain volumes on clinical fetal brain MRIs and identify abnormal volumes on the basis of a normative reference standard.

Short- and long-term outcomes of polyethylene band attenuation of congenital extrahepatic portosystemic shunts in dogs: 60 cases (2010-2020).

OBJECTIVES: To report the short- and long-term outcomes following attenuation of congenital extrahepatic portosystemic shunts in dogs using a novel polyethylene band. MATERIALS AND METHODS: Records were retrospectively reviewed for dogs that underwent congenital extrahepatic portosystemic shunt attenuation by a polyethylene banding technique, at a single institution between 2010 and 2020. Short-term outcome data were collected from peri-operative clinical records with follow-up examinations, scheduled at 6 and 18 weeks post-operatively, and post-operative imaging when performed. Long-term follow-up was collected by validated owner questionnaire, telephone interview or medical records. Long-term outcomes were categorised by "excellent", "good" or "poor". RESULTS: Sixty dogs were included. Post-operative complications occurred in 10 of 60 dogs (16.7%), four major and six minor, with a peri-operative mortality of 6.7%. Persistent shunting was identified in nine of 53 dogs (17%) available for follow-up examination and four dogs underwent a revision surgery. Long-term follow-up was available for 44 dogs at a median of 75 months post-operatively (range 7 to 128). Long-term outcomes were "excellent" (26) or "good" (8) in 81.8% of dogs and "poor" (8) in 18.2%. At the time of follow-up, 30 of 44 (68.2%) dogs were not receiving any medical treatment and 27 of 28 (96.4%) questionnaire respondents were satisfied with the response to surgery. CLINICAL SIGNIFICANCE: Polyethylene band attenuation of congenital extrahepatic portosystemic shunts provides comparable outcomes to cellophane. The material used in this study is widely available and consistent while being pre-sterilised and pre-folded makes it easy to use.

Contrast-enhanced CT immediately following percutaneous microwave ablation of cT1a renal cell carcinoma: Optimizing cancer outcomes.

OBJECTIVE: To evaluate the effect of intra-procedural contrast-enhanced CT (CECT) and same-session repeat ablation (SSRA) on primary efficacy, the complete eradication of tumor after the first ablation session as confirmed on first imaging follow-up, of clinically localized T1a (cT1a) renal cell carcinoma (RCC). METHODS: 398 consecutive patients with cT1a RCC were treated with cryoablation between 10/2003 and 12/2017, radiofrequency (RFA) or microwave ablation (MWA) between 1/2010 and 12/2017. SSRA was performed for residual tumor identified on intra-procedural CECT. Kruskal-Wallis and Pearson's chi-squared tests were performed to assess differences in continuous and categorical variables, respectively. Multivariate linear regression was used to determine predictors for primary efficacy and decline in estimated glomerular filtration rate. RESULTS: 347 consecutive patients (231 M, mean age 67.5 ± 9.1 years) were included. Median tumor diameter was smaller [2.5 vs 2.7 vs 2.6 (p = 0.03)] and RENAL Nephrometry Score (NS) was lower [6 vs 7 vs 7 (p = 0.009] for MWA compared to the RFA and cryoablation cohorts, respectively. Primary efficacy was higher in the MWA cohort [99.4% (170/171)] compared to the RFA [91.4% (85/93)] and cryoablation [92.8% (77/83)] cohorts (p = 0.001). Microwave ablation and SSRA was associated with higher primary efficacy on multivariate linear regression (p = 0.01-0.03). CONCLUSION: MWA augmented by SSRA, when residual tumor is identified on intra-procedural CECT, may improve primary efficacy for cT1a RCC.

Split-bolus CT urography after microwave ablation of renal cell carcinoma improves image quality and reduces radiation exposure.

OBJECTIVE: To compare image quality and radiation dose between single-bolus 2-phase and split-bolus 1-phase CT Urography (CTU) performed immediately after microwave ablation (MWA) of clinically localized T1 (cT1) RCC. METHODS: Forty-two consecutive patients (30 M, mean age 67.5 ± 9.0) with cT1 RCC were treated with MWA from 7/2013 to 12/2013 at two academic quaternary-care institutions. Renal parenchymal enhancement, collecting system opacification and distention and size-specific dose estimate (SSDE) were quantified and image quality subjectively assessed on single-bolus 2-phase versus split-bolus 1-phase CTU. Kruskal-Wallis and Pearson's Chi-squared tests were performed to assess differences in continuous and categorical variables, respectively. Two-sample T test with equal variances was used to determine differences in quantitative and qualitative image data. RESULTS: Median tumor diameter was larger [2.9 cm (IQR 1.7-5.3) vs 3.6 cm (IQR 1.7-5.7), p = 0.01] in the split-bolus cohort. Mean abdominal girth (p = 0.20) was similar. Number of antennas used and unenhanced CTs obtained before and during MWA were similar (p = 0.11-0.32). Renal pelvis opacification (2.5 vs 3.5, p < 0.001) and distention (4 mm vs 8 mm, p < 0.001) were improved and renal enhancement (Right: 127 HU vs 177 HU, p = 0.001; Left: 124 HU vs 185 HU, p < 0.001) was higher for the split-bolus CTU. Image quality was superior for split-bolus CTU (3.2 vs 4.0, p = 0.004). Mean SSDE for the split-bolus CTU was significantly lower [163.9 mGy (SD ± 73.9) vs 36.3 mGy (SD ± 7.7), p < 0.001]. CONCLUSION: Split-bolus CTU immediately after MWA of cT1 RCC offers higher image quality, improved opacification/distention of the collecting system and renal parenchymal enhancement at a lower radiation dose.

Prenatal Diagnosis of Third and Fourth Branchial Apparatus Anomalies: Case Series and Comparison with Lymphatic Malformation.

BACKGROUND AND PURPOSE: Third and fourth branchial apparatus anomalies are rare congenital anomalies. The purpose of this study was to investigate imaging features of these lesions on fetal MR imaging in comparison with lymphatic malformations, the major competing differential diagnosis in these cases. MATERIALS AND METHODS: A retrospective review of our institutional fetal MR imaging database between 1997 and 2019 resulted in 4 patients with confirmed third and fourth branchial apparatus anomalies and 14 patients with confirmed lymphatic malformations. The imaging features were reviewed by consensus, and the Fisher exact test was used to evaluate statistically significant differences between these 2 populations. RESULTS: Four cases of third and fourth branchial apparatus anomalies were imaged at 29 weeks 1 day (range, 23 weeks 1 day to 33 weeks 4 days). All 4 cases demonstrated unilateral, unilocular cysts without reduced diffusion or hemorrhage and a medially directed beaked contour that tapered between the spine and airway at the level of the piriform sinus. Compared with 14 cases of fetal lymphatic malformations imaged at 27 weeks 6 days (range, 21 weeks 3 days to 34 weeks 6 days), third and fourth branchial apparatus cysts were significantly more likely to be unilocular (P < .005) and to have a medially beaked contour (P < .005). The combination of features of unilateral, unilocular, and medially beaked contour was observed only in the fetuses with third and fourth branchial apparatus cysts (P < .001). CONCLUSIONS: The presence of a left-sided unilocular cyst with a medially beaked contour tapering at the level of the piriform sinus suggests the diagnosis of third and fourth branchial apparatus anomaly. Accurate diagnosis in the prenatal period allows proper counseling, genetic work-up, and treatment, potentially sparing patients from recurrent infections and associated morbidity.

Effect of iodinated contrast material on post-operative eGFR when administered during renal mass ablation.

OBJECTIVE: To evaluate the effect of intravenous iodinated contrast on estimated glomerular filtration rate (eGFR) when administered immediately after thermal ablation of clinically localized T1a (cT1a) renal cell carcinoma (RCC). METHODS: This HIPAA-compliant, dual-center retrospective study was performed under a waiver of informed consent. Three hundred forty-two consecutive patients with cT1a biopsy-proven RCC were treated with percutaneous ablation between January 2010 and December 2017. Immediate post-ablation contrast-enhanced CT was the routine standard of care at one institution (contrast group), but not the other (control group). One-month pre- and 6-month post-ablation eGFR were compared using the Wilcoxon signed-rank test or the Kruskal-Wallis test. Multivariate linear regression was used to determine the effect of contrast on eGFR. A 1:1 propensity score matching was performed for all patients with a logistic model using patient, tumor, and procedural covariates. RESULTS: In total, 246 patients (158 M; median age 69 years, IQR 62-74) were included. Median tumor diameter (2.4 vs 2.5, p = 0.23) and RENAL nephrometry scores (6 vs 6, p = 0.92), surrogates for ablation zone size, were similar. Baseline kidney function was similar for the control and contrast groups, respectively (median eGFR: 70 vs 74 mL/min/1.73 m2, p = 0.29). There was an expected mild decline in eGFR after ablation (control: 70 vs 60 mL/min/1.73 m2, p < 0.001; contrast: 75 vs 71 mL/min/1.73 m2, p = 0.001). Intravenous iodinated contrast was not associated with a decline in eGFR on multivariate linear regression (1.91, 95% CI - 3.43-7.24, p = 0.46) or 1:1 propensity score-matched model (- 0.33, 95% CI - 6.81-6.15, p = 0.92). CONCLUSION: Intravenous iodinated contrast administered during ablation of cT1a RCC has no effect on eGFR. KEY POINTS: • Intravenous iodinated contrast administered during thermal ablation of clinically localized T1a renal cell carcinoma has no effect on kidney function. • Thermal ablation of clinically localized T1a renal cell carcinoma results in a mild decline in kidney function. • A decline in kidney function is similar for radiofrequency and microwave ablation of clinically localized T1a renal cell carcinoma.

Epigenetic field alterations in non-tumor prostate tissues detect prostate cancer in urine.

Prostate cancer (PC) development involves epigenetic DNA methylation changes that occur in the tumor. However, distinct DNA methylation changes have been previously found to encompass a widespread cancer field defect involving normal prostate tissue. In the current study, we analyzed a series of DNA methylation field markers to determine if they predict the presence of PC in urine. Urine samples were collected from patients undergoing prostate biopsy with biopsy-proven PC (90), and without PC (77). From the urine pellet, methylated DNA was quantified across several previously identified CpG island regions near the caveolin 1 (CAV1), even-skipped homeobox 1 (EVX1), fibroblast growth factor 1 (FGF1), natural cytotoxicity triggering receptor 2 (NCR2) and phospholipase A and acyltransferase 3 (PLA2G16) genes using bisulfite pyrosequencing. Univariate and multivariate analyses were performed. Urine cell pellets show significant increases in methylation in four of the markers from patients with PC compared to those without PC including EVX1 12.2 vs. 7.7%, CAV1 15.7 vs. 10.36%, FGF1 12.0 vs. 7.1%, and PLA2G16 12.2 vs. 8.3% [all P<0.01]. Area under the ROC Curve (AUCs) were generated for EXV1 (0.74, Odds ratios (OR) 1.09; 95% confidence intervals (CI) 0.94-1.25, CAV1 (0.72, OR 1.18; 95% CI 1.09-1.28) and PLA2G16 (0.76, OR 1.35; 95% CI 1.199-1.51). In combination, a two-marker assay performs better than prostate specific antigen (PSA), AUC 0.77 vs. PSA AUC of 0.6 (P = 0.01) with the lowest error. In addition, FGF1 distinguished between grade group 1 (GG1) and higher grade cancers (P<0.03). In conclusion, applying methylation of field defect loci to urine samples provides a novel approach to distinguish patients with and without cancer.

Field studies of pollutant removal from nursery and greenhouse runoff by constructed wetlands.

Plant nursery runoff commonly contains pesticides and nutrients that often threaten aquatic ecosystems. Constructed wetlands could be a tool to remove pesticides and nutrients from nursery runoff but have not been extensively studied in this setting. Two field-scale constructed wetlands (one subsurface-flow constructed wetland [SFCW] and one free-surface constructed wetland [FSCW]) were implemented and monitored for water quality improvement. The SFCW demonstrated significant mass reduction of 78% or greater for nitrate, orthophosphate, total nitrogen, total phosphorus, and total suspended solids. The SFCW also demonstrated significant mass reduction of 79% or greater for 10 of the 12 pesticide compounds detected in over half of the collected samples. The FSCW demonstrated significant mass reduction of 46% or greater for all nonpesticide analytes except total nitrogen. Loading rate and actual storage volume compared with inflow volume likely affected performance. Reduced size and increased loading rate of the FSCW likely reduced its ability to effectively reduce pesticides. Results from this study indicate that constructed wetlands are likely an effective tool for nursery runoff management. When designing and implementing constructed wetlands, it is important for practitioners to consider the tradeoff between system size (additional cost and land otherwise dedicated to production) and performance.

Patterns of Initial Metastatic Recurrence After Surgery for High-Risk Nonmetastatic Renal Cell Carcinoma.

OBJECTIVE: To evaluate postoperative recurrence patterns for high-risk nonmetastatic renal cell carcinoma (RCC) and to identify prognostic factors associated with site-specific metastatic recurrence using a multi-institutional contemporary cohort. METHODS: Data for nonmetastatic ≥pT3a RCC patients treated with surgery at 4 independent centers was analyzed. Initial recurrence locations were identified, and imaging templates were defined by anatomic landmarks using radiologic definitions. Prognostic factors for site specific recurrence were evaluated with univariate and multivariable analyses. RESULTS: A total of 1057 patients were treated surgically for ≥pT3a RCC. Initial recurrence location was in a single site for 160 (59.3%) patients and at multiple locations in 110 (41.7%) patients. The most common sites of metastatic recurrence were lung (144/270, 53.3%), liver (54/270, 20.0%), and bone (48/270, 17.8%). Recurrence was identified in 52 of 270 (19.3%) patients outside the chest/abdomen template, most commonly in the pelvis (25/270, 9.3%). Bone and brain metastases were the most common organs for metastases outside chest/abdomen. Patients with tumor diameter >10 cm and grade 4 were more likely to recur in the bone (HR 3.61, P <.001) and brain (HR 16.5, P <.001). CONCLUSION: Metastatic progression outside chest/abdomen imaging templates was present in 1 of 5 high risk patients at initial metastatic RCC diagnosis, most commonly in the pelvis. Patients with large (>10 cm) tumors and grade 4 histology are at highest risk for bone and brain metastases.

Comparing Outcomes for Patients with Clinical T1b Renal Cell Carcinoma Treated With Either Percutaneous Microwave Ablation or Surgery.

OBJECTIVE: To compare perioperative and oncologic outcomes for patients with clinical T1b renal cell carcinoma following treatment with microwave ablation (MW), partial nephrectomy (PN), or radical nephrectomy (RN). METHODS: Comprehensive clinical and pathologic data were collected for nonmetastatic renal cell carcinoma patients with cT1b tumors following MW, PN, or RN from 2000 to 2018. Local recurrence-free, metastasis-free, cancer-specific and overall survival were estimated using Kaplan-Meier method. Prognostic factors for complications and survival were determined using logistic regression and Cox hazard models, respectively. RESULTS: A total of 325 patients (40 MW, 74 PN, and 211 RN) were identified. Patients treated with MW were older with higher Charlson comorbidity indices compared to surgical patients. Median length of hospitalization was shorter for MW compared to surgical patients (1 day vs 4 days, P <.0001). Post-treatment estimated glomerular filtration rate decreased by median 4.5% for MW compared to 3.2% for PN (P = .58) and 29% for RN (P <.001). Median follow-up was 34, 35, and 49 months following MW, PN, and RN, respectively. Estimated 5-year local recurrence-free survival was 94.5% for MW vs 97.9% for PN (P = .34) and 99.2% for RN (P = .02). Two patients recurred after MW and underwent repeat ablation without subsequent recurrence. No difference in 5-year metastasis-free survival or cancer-specific survival was found among MW, PN, or RN. Four (10%) MW patients had high-grade complication. Only prior abdominal surgery predicted high-grade complication (OR 6.29, P = .017). CONCLUSION: Microwave ablation is a feasible alternative to surgery in select comorbid patients with clinical T1b renal cell carcinoma.

Screening of urine identifies PLA2G16 as a field defect methylation biomarker for prostate cancer detection.

BACKGROUND: Prostate cancer (PC) is a multifocal disease. DNA methylation alterations are not restricted to the immediate peritumor environment, but spatially widespread in the adjacent and distant histologically normal prostate tissues. In the current study, we utilized high-throughput methylation arrays to identify epigenetic changes in the urine from men with and without cancer. DESIGN, SETTING, AND PARTICIPANTS: DNA urine samples were enriched for methylated fragments using MBD methyl-binding antibodies and applied to high density CytoScanHD arrays. Significant loci were validated using quantitative pyrosequencing and binary logistic regression modeling applied to urine sample analyses in a training (n = 83) and validation approach (n = 84). Methylation alterations in prostate tissues using pyrosequencing at the PLA2G16 locus were examined in 38 histologically normal specimens from men with (TA, n = 26) and without (NTA, n = 12) cancer and correlated to gene expression. RESULTS: Methylation microarrays identified 3,986 loci showing significantly altered methylation in the urine samples from patients with PC compared to those without (TA vs NTA; p<0.01). These loci were then compared against subjects with their prostates removed to exclude non-prostate cell markers yielding 196 significant regions. Multiple CpGs adjacent to PLA2G16 CpG island showed increased methylation in TA compared to NTA (p<0.01) in a large validation study of urine samples. The predictive accuracy of PLA2G16 methylation at CG2 showed the highest predictive value at 0.8 (odds ratio, 1.37; 95% confidence interval, 1.16-1.62; p<0.001). Using a probability cutoff of 0.065, the sensitivity and specificity of the multivariate model was 92% and 35%. When histologically normal prostate tissues/biopsies from patients with PC (TA) were compared to subjects without cancer, significant hypermethylation of PLA2G16 was noted (odds ratio, 1.35; 95% confidence interval, 1.07-1.71; p = 0.01). CONCLUSION: PLA2G16 methylation defines an extensive field defect in histologically normal prostate tissue associated with PC. PLA2G16 methylation in urine and prostate tissues can detect the presence of PC.

Risk Factors for Complications and Nondiagnostic Results following 1,155 Consecutive Percutaneous Core Renal Mass Biopsies.

PURPOSE: The purpose of this study was to evaluate patient, tumor and technical factors associated with procedural complications and nondiagnostic findings following percutaneous core renal mass biopsy. MATERIALS AND METHODS: We reviewed core renal mass biopsies from 2000 to 2017. Complications at 30 days or less were graded using the Clavien-Dindo system. Univariate and multivariable analyses were done to evaluate associations between clinical characteristics and the risk of complications or nondiagnostic findings. RESULTS: Of the 1,155 biopsies performed in a total of 965 patients procedural complications were identified in 24 patients (2.2%), including 5 (0.4%) with major complications (Clavien 3a or greater). No patients were identified with tumor seeding of the biopsy tract. Patient age, body mass index, gender, Charlson comorbidity index, smoking, mass diameter, nephrometry score, number of cores and prior biopsy were not associated with complication risk (p = 0.06 to 0.53). Complications were not increased for patients on aspirin or those with low platelets (25,000 to 160,000/µl blood) or a mildly elevated INR (international normalized ratio) (1.2 to 2.0, p = 0.16, 0.07 and 0.50, respectively). The complication risk was not increased during the initial 50 cases of a radiologist or when a trainee was present (p = 0.35 and 0.12, respectively). Nondiagnostic findings were present in 14.6% of biopsies. Independent predictors included cystic features, contrast enhancement, mass diameter and skin-to-mass distance (p <0.001, 0.002, 0.02 and 0.049, respectively). Radiologist experience was not associated with the nondiagnostic rate (p = 0.23). Prior nondiagnostic biopsy was not associated with an increased nondiagnostic rate on subsequent attempts (19.2% vs 14.2%, p = 0.23). CONCLUSIONS: Procedural complications following biopsy are rare even with low serum platelets, a mildly elevated INR or when the patient remains on aspirin. Cystic features, hypo-enhancement on imaging, a smaller mass diameter and a longer skin-to-tumor distance increase the risk of nondiagnostic findings.

Blood Pressure Control and Other Quality of Care Metrics for Patients with Obesity and Diabetes: A Population-Based Cohort Study.

INTRODUCTION: There are no population-level estimates in the United States for achievement of blood pressure goals in patients with diabetes and hypertension by obesity weight class. AIM: We sought to examine the relationship between the extent of obesity and the achievement of guideline-recommended blood pressure goals and other quality of care metrics among patients with diabetes. METHODS: We conducted an observational population-based cohort study of electronic health data of three large health systems from 2010-2012 in rural, urban and suburban settings of 51,229 adults with diabetes. Outcomes were achievement of diabetes quality of care metrics: blood pressure, A1c, and LDL control, and A1c and LDL testing. Two blood pressure goals were examined given the recommendation for adults with diabetes of 130/80 mmHg from JNC7 and the recommendation of 140/90 mmHg from JNC8 in 2014. RESULTS: Patients in obesity classes I, II, and III with diagnosed hypertension were less likely to achieve blood pressure control at both the 140/90 mmHg and 130/80 mmHg control levels. The patients from obesity class III had the lowest likelihood of achieving control at the 130/80 mmHg goal, and control was markedly worse for the 130/80 mmHg threshold in all weight classes. There were minimal to no differences by weight class in LDL and A1c control and LDL and A1c testing. CONCLUSIONS: Although the cardiovascular risk for patients with obesity and diabetes is greater than for non-obese patients with diabetes, we found that patients with obesity are even further behind in achieving blood pressure control.

Toward deciphering the mechanistic role of variations in the Rep1 repeat site in the transcription regulation of SNCA gene.

Short structural variants-variants other than single nucleotide polymorphisms-are hypothesized to contribute to many complex diseases, possibly by modulating gene expression. However, the molecular mechanisms by which noncoding short structural variants exert their effects on gene regulation have not been discovered. Here, we study simple sequence repeats (SSRs), a common class of short structural variants. Previously, we showed that repetitive sequences can directly influence the binding of transcription factors to their proximate recognition sites, a mechanism we termed non-consensus binding. In this study, we focus on the SSR termed Rep1, which was associated with Parkinson's disease (PD) and has been implicated in the cis-regulation of the PD-risk SNCA gene. We show that Rep1 acts via the non-consensus binding mechanism to affect the binding of transcription factors from the GATA and ELK families to their specific sites located right next to the Rep1 repeat. Next, we performed an expression analysis to further our understanding regarding the GATA and ELK family members that are potentially relevant for SNCA transcriptional regulation in health and disease. Our analysis indicates a potential role for GATA2, consistent with previous reports. Our study proposes non-consensus transcription factor binding as a potential mechanism through which noncoding repeat variants could exert their pathogenic effects by regulating gene expression.