Browsing by Author "Boris, Ronald S."
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Item COEXISTING PROSTATE CANCER FOUND AT THE TIME OF HOLMIUM LASER ENUCLEATION OF THE PROSTATE FOR BENIGN PROSTATIC HYPERPLASIA: PREDICTING ITS PRESENCE AND GRADE IN ANALYZED TISSUE(Liebert, 2015-01) Bhojani, Naeem; Boris, Ronald S.; Monn, M. Francesca; Mandeville, Jessica A.; Lingeman, James E.; Department of Urology, IU School of MedicineObjective: To determine the incidence of prostate cancer identified on holmium laser enucleation of the prostate (HoLEP) specimens and evaluate variables associated with prostate cancer identification. Patients and Methods: All patients undergoing HoLEP between 1998 and 2013 were identified. Patients with a known history of prostate cancer were excluded. Multivariable logistic regression assessed variables associated with identification of prostate cancer on HoLEP specimens and Gleason 7 or higher prostate cancer among the malignant cases. The Gleason grade was used as a proxy for disease severity. Each of the models was adjusted for age, preoperative prostate-specific antigen (PSA), and HoLEP specimen weight. Results: The cohort comprised 1272 patients, of whom 103 (8.1%) had prostate cancer identified. Prostate cancer cases had higher pre-HoLEP PSA (p=0.06) but lower HoLEP specimen weight (p=0.01). On multivariate logistic regression, age and preoperative PSA were associated with increased odds of prostate cancer being present (p<0.01 each), while increasing HoLEP specimen weight was associated with decreased odds of prostate cancer (p<0.001). Men older than 80 had 20% predicted probability of being diagnosed with prostate cancer. Seventy-eight percent of prostate cancer cases were Gleason 6 or less. The pre-HoLEP PSA was associated with increased adjusted odds of intermediate- or high-grade prostate cancer. Conclusion: Prostate cancer identified by HoLEP is not uncommon, but is generally a low-risk disease. Older patients with smaller prostate glands have the highest odds of prostate cancer identification.Item Comparing oncologic outcomes in patients undergoing surgery for oncocytic neoplasms, conventional oncocytoma, and chromophobe renal cell carcinoma(Elsevier, 2019-11) Flack, Chandra K.; Calaway, Adam C.; Miller, Brady L.; Picken, Maria M.; Gondim, Dibson D.; Idrees, Muhammad T.; Abel, E. Jason; Gupta, Gopal N.; Boris, Ronald S.; Urology, School of MedicineIntroduction Oncocytic neoplasms are renal tumors similar to oncocytoma, but their morphologic variations preclude definitive diagnosis. This somewhat confusing diagnosis can create treatment and surveillance challenges for the treating urologist. We hypothesize that these subtle morphologic variations do not drastically affect the malignant potential of these tumors, and we sought to demonstrate this by comparing clinical outcomes of oncocytic neoplasms to those of classic oncocytoma and chromophobe. Methods We gathered demographic and outcomes data for patients with variant oncocytic tumors. Oncologic surveillance was conducted per institutional protocol in accordance with NCCN guidelines. Descriptive statistics were used to compare incidence of metastasis and death against those for patients with oncocytoma and chromophobe. Three hundred and fifty-one patients were analyzed: 164 patients with oncocytoma, 28 with oncocytic neoplasms, and 159 with chromophobe tumors. Results Median follow-up time for the entire cohort was 32.4 months, (interquartile range 9.2–70.0). Seventeen total patients (17/351, 4.9%) died during the course of the study. In patients with oncocytoma or oncocytic neoplasm, none were known to metastasize or die of their disease. Only chromophobe tumors >6 cm in size in our series demonstrated metastatic progression and approximately half of these metastasized tumors demonstrated sarcomatoid changes. Conclusion Variant oncocytic neoplasms appear to have a natural course similar to classic oncocytoma. These tumors appear to have no metastatic potential, and oncologic surveillance may not be indicated after surgery.Item Data-Independent Acquisition Phosphoproteomics of Urinary Extracellular Vesicles Enables Renal Cell Carcinoma Grade Differentiation(Elsevier, 2023) Hadisurya, Marco; Lee, Zheng-Chi; Luo, Zhuojun; Zhang, Guiyuan; Ding, Yajie; Zhang, Hao; Iliuk, Anton B.; Pili, Roberto; Boris, Ronald S.; Tao, W. Andy; Urology, School of MedicineTranslating the research capability and knowledge in cancer signaling into clinical settings has been slow and ineffective. Recently, extracellular vesicles (EVs) have emerged as a promising source for developing disease phosphoprotein markers to monitor disease status. This study focuses on the development of a robust data-independent acquisition (DIA) using mass spectrometry to profile urinary EV phosphoproteomics for renal cell cancer (RCC) grades differentiation. We examined gas-phase fractionated library, direct DIA (library-free), forbidden zones, and several different windowing schemes. After the development of a DIA mass spectrometry method for EV phosphoproteomics, we applied the strategy to identify and quantify urinary EV phosphoproteomes from 57 individuals representing low-grade clear cell RCC, high-grade clear cell RCC, chronic kidney disease, and healthy control individuals. Urinary EVs were efficiently isolated by functional magnetic beads, and EV phosphopeptides were subsequently enriched by PolyMAC. We quantified 2584 unique phosphosites and observed that multiple prominent cancer-related pathways, such as ErbB signaling, renal cell carcinoma, and regulation of actin cytoskeleton, were only upregulated in high-grade clear cell RCC. These results show that EV phosphoproteome analysis utilizing our optimized procedure of EV isolation, phosphopeptide enrichment, and DIA method provides a powerful tool for future clinical applications.Item Development and Validation of an Objective Scoring Tool for Robot-Assisted Partial Nephrectomy: Scoring for Partial Nephrectomy(Mary Ann Liebert, 2021) Iqbal, Umar; Jing, Zhe; Ahmed, Youssef; Elsayed, Ahmed S.; Rogers, Craig G.; Boris, Ronald S.; Porter, James Robert; Allaf, Mohamad E.; Badani, Ketan K.; Stifelman, Michael D.; Kaouk, Jihad; Terakawa, Tomoaki; Hinata, Nobuyuki; Aboumohamed, Ahmed; Kauffman, Eric; Li, Qiang; Abaza, Ronney; Guru, Khurshid A.; Hussein, Ahmed; Eun, Daniel; Urology, School of MedicineObjective: To develop a structured and objective scoring tool for assessment of robot-assisted partial nephrectomy (RAPN): Scoring for Partial Nephrectomy (SPaN). Materials and Methods:Content development: RAPN was deconstructed into 6 domains by a multi-institutional panel of 10 expert robotic surgeons. Performance on each domain was represented on a Likert scale of 1 to 5, with specific descriptions of anchors 1, 3, and 5. Content validation: The Delphi methodology was utilized to achieve consensus about the description of each anchor for each domain in terms of appropriateness of the skill assessed, objectiveness, clarity, and unambiguous wording. The content validity index (CVI) of ≥0.75 was set as cutoff for consensus. Reliability: 15 de-identified videos of RAPN were utilized to determine the inter-rater reliability using linearly weighted percent agreement, and Construct validation of SPaN was described in terms of median scores and odds ratios. Results: The expert panel reached consensus (CVI ≥0.75) after 2 rounds. Consensus was achieved for 36 (67%) statements in the first round and 18 (33%) after the second round. The final six-domain SPaN included Exposure of the kidney; Identification and dissection of the ureter and gonadal vessels; Dissection of the hilum; Tumor localization and exposure; Clamping and tumor resection; and Renorrhaphy. The linearly weighted percent agreement was >0.75 for all domains. There was no difference between median scores for any domain between attendings and trainees. Conclusion: Despite the lack of significant construct validity, SPaN is a structured, reliable, and procedure-specific tool that can objectively assesses technical proficiency for RAPN.Item Evaluation, diagnosis and surveillance of renal masses in the setting of VHL disease(SpringerLink, 2021-07) Chahoud, Jad; McGettigan, Melissa; Parikh, Nainesh; Boris, Ronald S.; Iliopoulos, Othon; Rathmell, W. Kimryn; Daniels, Anthony B.; Jonasch, Eric; Spiess, Philippe E.; Urology, School of MedicineThis brief report focuses on the evaluation and diagnosis of clinically localized renal masses in children and adults with Von Hippel–Lindau (VHL) disease. Counseling considerations pertinent to the urologists, medical oncologists, and multidisciplinary teams involved in the care of these patients are addressed. As practice patterns regarding the evaluation and management of VHL tumors can vary considerably, this report aims to provide guidance on some of the controversies associated with the diagnostic evaluation and initial management of localized renal masses in VHL patients.Item Genetic Risk Assessment for Hereditary Renal Cell Carcinoma: Clinical Consensus Statement(Wiley, 2021) Bratslavsky, Gennady; Mendhiratta, Neil; Daneshvar, Michael; Brugarolas, James; Ball, Mark W.; Metwalli, Adam; Nathanson, Katherine L.; Pierorazio, Phillip M.; Boris, Ronald S.; Singer, Eric A.; Carlo, Maria I.; Daly, Mary B.; Henske, Elizabeth P.; Hyatt, Colette; Middleton, Lindsay; Morris, Gloria; Jeong, Anhyo; Narayan, Vivek; Rathmell, W. Kimryn; Vaishampayan, Ulka; Lee, Bruce H.; Battle, Dena; Hall, Michael J.; Hafez, Khaled; Jewett, Michael A.S.; Karamboulas, Christina; Pal, Sumanta K.; Hakimi, A. Ari; Kutikov, Alexander; Iliopoulos, Othon; Linehan, W. Marston; Jonasch, Eric; Srinivasan, Ramaprasad; Shuch, Brian; Urology, School of MedicineBackground: Although renal cell carcinoma (RCC) is believed to have a strong hereditary component, there is a paucity of published guidelines for genetic risk assessment. A panel of experts was convened to gauge current opinions. Methods: A North American multidisciplinary panel with expertise in hereditary RCC, including urologists, medical oncologists, clinical geneticists, genetic counselors, and patient advocates, was convened. Before the summit, a modified Delphi methodology was used to generate, review, and curate a set of consensus questions regarding RCC genetic risk assessment. Uniform consensus was defined as ≥85% agreement on particular questions. Results: Thirty-three panelists, including urologists (n = 13), medical oncologists (n = 12), genetic counselors and clinical geneticists (n = 6), and patient advocates (n = 2), reviewed 53 curated consensus questions. Uniform consensus was achieved on 30 statements in specific areas that addressed for whom, what, when, and how genetic testing should be performed. Topics of consensus included the family history criteria, which should trigger further assessment, the need for risk assessment in those with bilateral or multifocal disease and/or specific histology, the utility of multigene panel testing, and acceptance of clinician-based counseling and testing by those who have experience with hereditary RCC. Conclusions: In the first ever consensus panel on RCC genetic risk assessment, 30 consensus statements were reached. Areas that require further research and discussion were also identified, with a second future meeting planned. This consensus statement may provide further guidance for clinicians when considering RCC genetic risk assessment. Lay summary: The contribution of germline genetics to the development of renal cell carcinoma (RCC) has long been recognized. However, there is a paucity of guidelines to define how and when genetic risk assessment should be performed for patients with known or suspected hereditary RCC. Without guidelines, clinicians struggle to define who requires further evaluation, when risk assessment or testing should be done, which genes should be considered, and how counseling and/or testing should be performed. To this end, a multidisciplinary panel of national experts was convened to gauge current opinion on genetic risk assessment in RCC and to enumerate a set of recommendations to guide clinicians when evaluating individuals with suspected hereditary kidney cancer.Item Human jackstone arms show a protein-rich, X-ray lucent core, suggesting that proteins drive their rapid and linear growth(Springer, 2022) Canela, Victor Hugo; Dzien, Cornelius; Bledsoe, Sharon B.; Borofsky, Michael S.; Boris, Ronald S.; Lingeman, James E.; El-Achkar, Tarek M.; Williams, James C., Jr.; Anatomy, Cell Biology and Physiology, School of MedicineJackstone calculi, having arms that extend out from the body of the stone, were first described over a century ago, but this morphology of stones has been little studied. We examined 98 jackstones from 50 different patient specimens using micro-computed tomography (micro CT) and infrared (IR) spectroscopy. Micro CT showed that jackstone arms consisted of an X-ray lucent core within each arm. This X-ray lucent core frequently showed sporadic, thin layers of apatite arranged transversely to the axis of the arm. The shells of the jackstones were always composed of calcium oxalate (CaOx), and with the monohydrate form the majority or sole mineral. Study of layering in the shell regions by micro CT showed that growth lines extended from the body of the stone out onto jack arms and that the thickness of the shell covering of jack arms often thinned with distance from the stone body, suggesting that the arms grew at a faster radial rate than did the stone body. Histological cross-sections of decalcified jackstone arms showed the core to be more highly autofluorescent than was the CaOx shell, and immunohistochemistry showed the core to be enriched in Tamm-Horsfall protein. We hypothesize that the protein-rich core of a jack arm might preferentially bind more protein from the urine and resist deposition of CaOx, such that the arm grows in a linear manner and at a faster rate than the bulk of the stone. This hypothesis thus predicts an enrichment of certain urine proteins in the core of the jack arm, a theory that is testable by appropriate analysis.Item Identifying Preoperative Predictors of Operative Time and Their Impact on Outcomes in Robot-Assisted Partial Nephrectomy(Liebert, 2022-01) Krishnan, Naveen K.; Zappia, Jason; Calaway, Adam C.; Nagle, Ramzy T.; Sundaram, Chandru P.; Boris, Ronald S.; Urology, School of MedicineObjective: To identify preoperative characteristics in patients with renal masses that influence operative time during robot-assisted partial nephrectomy (RAPN) and evaluate the relationship between operative time and length of stay (LOS), complication rates, and overall outcome. Materials and Methods: We queried our institutional database to identify a cohort of patients who underwent RAPN by two experienced robotic surgeons between 2012 and 2019. A multivariable regression model was developed to analyze operative time, LOS, and any grade complication within 30 days postoperatively using the bootstrap resampling technique. Results: A total of 392 patients were included. On multivariable analyses, prior abdominal surgery (p = 0.001) was associated with 22 minutes of increase in operating room time, as well as adhesive perirenal fat (22 minutes, p = 0.001). For each one unit increase in nephrometry score, there was a 4-minute increase in operating room time (p = 0.028), and for each one-cm increase in tumor size, there was an associated 12-minute increase in operating room time (p < 0.001). For each 1 year increase in age, there was an associated 0.024-day increase in LOS [odds ratio (OR) (0.013–0.035)]; in addition, for every one-cm increase in tumor size there was a 0.18-day associated increase in LOS [OR (0.070–0.28)]. Each 1-hour increase in operating room time was associated with a 0.25-day increased LOS [OR (0.092–0.41)]. Only tumor size was found to be associated with any grade complication. Conclusions: Patients with a history of abdominal surgery, larger complex tumors, and significant Gerota's fat undergoing robotic partial nephrectomy should anticipate longer operative times. Older patients with larger tumors and longer operative times can anticipate a longer LOS. Tumor size appears to be the common determinant of all three outcomes: operative time, LOS, and any grade Clavien complication.Item A novel preoperative model to predict 90-day surgical mortality in patients considered for renal cell carcinoma surgery(Elsevier, 2018-10) Calaway, Adam C.; Monn, M. Francesca; Bahler, Clinton D.; Cary, Clint; Boris, Ronald S.; Urology, School of MedicineIntroduction Surgical benefits for renal cell carcinoma must be weighed against competing causes of mortality, especially in the elderly patient population. We used a large cancer registry to evaluate the impact of patient and cancer-specific factors on 90-day mortality (90DM). A nomogram to predict the odds of short-term mortality was created. Materials and Methods The National Cancer Database was queried to identify all patients with clinically localized, nonmetastatic disease treated with partial or radical nephrectomy. Using a random sample of 60%, multiple logistic regression with 90DM outcomes were performed to identify preoperative variables associated with mortality. Variables included age, sex, race, co-morbidity score, tumor size, and presence of a thrombus. A nomogram was created and tested on the remaining 40% of patients to predict 90DM. Results 183,407 patients met inclusion criteria. Overall 90DM for the cohort was 1.9%. All preoperative variables significantly influenced the risk of 90DM. Patient age was by far the strongest predictor. Nomogram scores ranged from 0 to 12. Compared to patients with 0 to 1 points, those with 2 to 3 (odds ratio [OR] 2.89, 2.42–3.46; P < 0.001), 4 to 5 (OR 6.25, 5.26–7.43; P < 0.001), and >6 (OR 12.86, 10.83–15.27; P < 0.001) were at incrementally significantly higher odds of 90DM. Being >80 years of age alone placed patients into the highest risk of surgical mortality. Conclusions Management of localized kidney cancer must consider competing causes of mortality, especially in elderly patients with multiple co-morbidities. We present a preoperative tool to calculate risk of surgical short-term mortality to aid surgeon–patient counseling.Item Oncologic outcomes and prognostic impact of urothelial recurrences in patients undergoing segmental and total ureterectomy for upper tract urothelial carcinoma(Canadian Urological Association, 2015-04-13) Pedrosa, Jose A.; Masterson, Timothy A.; Rice, Kevin R.; Kaimakliotis, Hristos Z.; Monn, M. Francesca; Bihrle, Richard; Koch, Michael O.; Boris, Ronald S.; Department of Urology, IU School of MedicineINTRODUCTION: We evaluated the impact of urothelial recurrences in a cohort of patients undergoing segmental (SU) and total ureterectomy (TU) as an alternative to nephroureterectomy (NU) for upper tract urothelial carcinoma. METHODS: Between 1999 and 2012, patients who underwent SU, TU and NU for treatment of upper tract urothelial carcinoma were evaluated. Demographic, surgical, pathologic and oncologic data were collected. Recurrence-free (RFS) and disease-specific survival (DSS) were analyzed using Kaplan-Meier and multivariable Cox methods. RESULTS: A total 141 patients were evaluated, 35 underwent SU, 10 TU and 96 NU. Patients who underwent TU were more likely to have bilateral disease (p < 0.01), solitary kidney (p < 0.01), and multifocal disease (p = 0.01). Organ-confined (p < 0.01) and low-grade disease (p < 0.01) were more common in the TU and SU groups compared with NU. At a median follow-up of 56.9 months (range: 0.2-181.1) disease relapse occurred in 88 (55.3%) patients. Localized recurrence occurred in 31.1% of SU/TU group compared to 27.1% (p = 0.62) of the NU group. Neither total nor segmental ureterectomy demonstrated significantly worse RFS (p = 0.26 and p = 0.81), CSS (p = 0.96 and p = 0.52) or overall survival (p = 0.59 and p = 0.55) compared with complete NU. Localized urothelial recurrence did not confer increased risk of cancer-specific (p = 0.73) or overall mortality (p = 0.39). The paper's most important limitations include its retrospective nature and its relatively small number of patients. CONCLUSION: No significant survival differences were demonstrated between surgical approaches for upper tract urothelial cancer. Localized urothelial recurrence after surgical treatment for upper tract urothelial cancer does not affect mortality in this population. TU with ileal-substitution may provide an alternative option for patients with extensive ureteral disease and poor renal function.