Data-Independent Acquisition Phosphoproteomics of Urinary Extracellular Vesicles Enables Renal Cell Carcinoma Grade Differentiation.

Translating 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.

Does larger prostate size provide protection for cancer specific outcomes in localized prostate cancer.

OBJECTIVE: Benign prostatic hyperplasia is common in the aging population and frequently comorbid with localized prostate cancer. Large prostate volume places significant challenges in robotic prostatectomy including reduced mobility and visualization. The goal of this study is to evaluate the effect of prostate volume as a continuous variable on cancer specific outcomes. METHODS: Three thousand four hundred and twenty five patients with localized prostate cancer at a single institution who underwent robotic prostatectomy were retrospectively reviewed. A number of preoperative, operative, and postoperative variables were collected to evaluate cancer specific outcomes including pathologic stage, tissue margins, and biochemical recurrence (BCR). Logistic regression models and univariate and multivariate analyses were implemented for pathologic stage T3 and BCR respectively. RESULTS: The median follow up time was 52 months (IQR 18-95). 37.4% of the patients had a final pathologic stage of T3 or higher, 21.2% experienced positive surgical margins, and 24.7% of patients experienced BCR. Prostate size was a significant predictor of all three outcomes of interest. Increasing prostate size was protective against both higher pathologic stage and positive surgical margins (odds ratio = 0.989, 0.990 respectively, p < 0.001). There was a modest increase in the risk of BCR with increasing gland size (hazard ratio = 1.006, p < 0.001). These results were most significant for patients with Gleason Grade Groups 1 and 2 prostate cancer. CONCLUSION: Prostate size is a commonly determined clinical factor that effects both surgical planning and cancer specific outcomes. Increasing prostate size may offer protection against higher stage disease and positive surgical margins. While surgically challenging, favorable oncologic outcomes can be consistently achieved for patients with low-intermediate risk disease.

Comparing Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prediction of Extraprostatic Extension of Prostate Cancer and Surgical Guidance: A Prospective Nonrandomized Clinical Trial.

PURPOSE: Survivors of surgically managed prostate cancer may experience urinary incontinence and erectile dysfunction. Our aim was to determine if 68Ga-prostate-specific membrane antigen-11 positron emission tomography CT (PSMA-PET) in addition to multiparametric (mp) MRI scans improved surgical decision-making for nonnerve-sparing or nerve-sparing approach. MATERIALS AND METHODS: We prospectively enrolled 50 patients at risk for extraprostatic extension (EPE) who were scheduled for prostatectomy. After mpMRI and PSMA-PET images were read for EPE prediction, surgeons prospectively answered questionnaires based on mpMRI and PSMA-PET scans on the decision for nerve-sparing or nonnerve-sparing approach. Final whole-mount pathology was the reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curves were calculated and McNemar's test was used to compare imaging modalities. RESULTS: The median age and PSA were 61.5 years and 7.0 ng/dL. The sensitivity for EPE along the posterior neurovascular bundle was higher for PSMA-PET than mpMRI (86% vs 57%, P = .03). For MRI, the specificity, positive predictive value, negative predictive value, and area under the curve for the receiver operating characteristic curves were 77%, 40%, 87%, and 0.67, and for PSMA-PET were 73%, 46%, 95%, and 0.80. PSMA-PET and mpMRI reads differed on 27 nerve bundles, with PSMA-PET being correct in 20 cases and MRI being correct in 7 cases. Surgeons predicted correct nerve-sparing approach 74% of the time with PSMA-PET scan in addition to mpMRI compared to 65% with mpMRI alone (P = .01). CONCLUSIONS: PSMA-PET scan was more sensitive than mpMRI for EPE along the neurovascular bundles and improved surgical decisions for nerve-sparing approach. Further study of PSMA-PET for surgical guidance is warranted in the unfavorable intermediate-risk or worse populations. CLINICALTRIALS.GOV IDENTIFIER: NCT04936334.

Preoperative aspirin and anticoagulants do not affect partial nephrectomy bleeding.

INTRODUCTION: Studies have reached mixed conclusions on the role of antiplatelet and anticoagulant agents on postoperative complications of partial nephrectomies. This study examines whether preoperative anticoagulation use affected the risk of hemorrhagic complications after partial nephrectomy. MATERIALS AND METHODS: This is a retrospective chart review of all partial nephrectomies performed between 2017 and 2022 at a single institution. For each operation, preoperative data was gathered on whether the patient was on anticoagulation, the type and dose of anticoagulation, and how many days the anticoagulation was held preoperatively. Bivariate analyses for continuous measures were performed using Student's t-tests when there were two comparison groups and ANOVA models when there were more than two comparison groups and Chi-Square tests were used for categorical variables, with Fisher's Exact being used when expected cell counts were small. RESULTS: In this study, warfarin was held for an average of 5.43 days, clopidogrel was held for an average of 6.60 days, aspirin was held for an average of 7.65 days, and direct oral anticoagulants (DOACs) were held for an average of 4.00 days. There was no significant difference in hemoglobin (Hb) change, rate of intraoperative transfusion, postoperative transfusion, bleeding complication, pseudoaneurysm rate, or additional bleeding processes between patients on prior anticoagulation therapy and those not on therapy. There was no significant difference in intraoperative or postoperative outcomes based on history of aspirin use and continuation of aspirin through the surgery. While estimated blood loss appeared statistically significant initially, this difference was accounted for by the covariates of comorbidities, RENAL score, surgical approach, and type of renorrhaphy. Overall, there was no difference in complication rate based solely on aspirin use or continuation of aspirin through surgery. CONCLUSIONS: No difference in complication rate of partial nephrectomy was determined to be solely due to prior use of anticoagulation or aspirin use alone with appropriate cessation of anticoagulation preoperatively. Overall, patients on anticoagulation are not at a higher risk of intraoperative or postoperative bleeding complications when undergoing partial nephrectomy.

Genetic risk assessment for hereditary renal cell carcinoma: Clinical consensus statement.

BACKGROUND: 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.

Evaluation, diagnosis and surveillance of renal masses in the setting of VHL disease.

This 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.

Plasma-Derived Extracellular Vesicle Phosphoproteomics through Chemical Affinity Purification.

The invasive nature and the pain caused to patients inhibit the routine use of tissue biopsy-based procedures for cancer diagnosis and surveillance. The analysis of extracellular vesicles (EVs) from biofluids has recently gained significant traction in the liquid biopsy field. EVs offer an essential "snapshot" of their precursor cells in real time and contain an information-rich collection of nucleic acids, proteins, lipids, and so on. The analysis of protein phosphorylation, as a direct marker of cellular signaling and disease progression could be an important stepping stone to successful liquid biopsy applications. Here we introduce a rapid EV isolation method based on chemical affinity called EVtrap (extracellular vesicle total recovery and purification) for the EV phosphoproteomics analysis of human plasma. By incorporating EVtrap with high-performance mass spectrometry (MS), we were able to identify over 16 000 unique peptides representing 2238 unique EV proteins from just 5 µL of plasma sample, including most known EV markers, with substantially higher recovery levels compared with ultracentrifugation. Most importantly, more than 5500 unique phosphopeptides representing almost 1600 phosphoproteins in EVs were identified using only 1 mL of plasma. Finally, we carried out a quantitative EV phosphoproteomics analysis of plasma samples from patients diagnosed with chronic kidney disease or kidney cancer, identifying dozens of phosphoproteins capable of distinguishing disease states from healthy controls. The study demonstrates the potential feasibility of our robust analytical pipeline for cancer signaling monitoring by tracking plasma EV phosphorylation.

The Role of Prostate Specific Antigen Monitoring after Holmium Laser Enucleation of the Prostate.

PURPOSE: Prostate specific antigen screening for prostate cancer has recently been challenged due to poor sensitivity. In addition to prostate cancer, a number of conditions elevate prostate specific antigen, of which benign prostatic hyperplasia is most common. The objective of this study was to assess the positive predictive value of prostate specific antigen and prostate specific antigen density for prostate cancer risk following holmium laser enucleation of the prostate. MATERIALS AND METHODS: We queried an institutional review board approved database of holmium laser enucleation of the prostate performed at Indiana University from 1999 to 2018 to identify 1,147 patients with prostate specific antigen data available after holmium laser enucleation. A total of 55 biopsies after enucleation were recorded. Demographics, prostate specific antigen, prostate volume and oncologic details were analyzed. The primary outcome was biopsy proven prostate cancer. RESULTS: A total of 55 patients underwent transrectal ultrasound prostate biopsy for cause after holmium laser enucleation of the prostate. Cancer was identified in more than 90% of biopsied cases. Men with prostate specific antigen above 1 ng/ml at biopsy had a 94% probability of cancer detection and an 80% risk of clinically significant disease. Prostate specific antigen density above 0.1 ng/ml2 was associated with a 95% risk of cancer and an 88% risk of clinically significant cancer. Prostate specific antigen greater than 5.8 ng/ml or prostate specific antigen density greater than 0.17 ng/ml2 was universally associated with biopsy proven cancer. CONCLUSIONS: Prostate specific antigen and prostate specific antigen density have high positive predictive value for prostate cancer risk after holmium laser enucleation of the prostate. Thresholds for biopsy should be lower than in patients who do not undergo holmium laser enucleation. Those who undergo that procedure and have prostate specific antigen above 1 ng/ml or prostate specific antigen density above 0.1 ng/ml2 are at higher risk for harboring clinically significant disease and should undergo biopsy. Referring physicians should be aware of these significant risk shifts.

A Prospective Program to Reduce the Clinical Incidence of Clostridium difficile Colitis Infection after Cystectomy.

PURPOSE: The development of Clostridium difficile infection after cystectomy is associated with significant morbidity and mortality. We implemented a prospective screening program to identify asymptomatic carriers of C. difficile and assessed its impact on clinical C. difficile infection rates compared to historical matched controls. MATERIALS AND METHODS: Prospective C. difficile screening prior to cystectomy began in March 2015. The 380 consecutive patients who underwent cystectomy before the initiation of screening (control cohort) were matched based on 5 clinical factors with the 386 patients who underwent cystectomy from March 2015 to December 2017 (trial cohort). Patients who screened positive were placed in contact isolation and treated prophylactically with metronidazole. Multivariable models were built on an intent to screen basis and an effectiveness of screening basis to determine whether screening reduced the rate of symptomatic C. difficile infection postoperatively. RESULTS: With the implementation of the screening protocol the C. difficile infection rate declined from 9.4% to 5.5% (OR 0.52, p = 0.0268) in patients on the intent to screen protocol and from 9.2% to 4.9% in those on the effectiveness of screening protocol (OR 0.46, p = 0.0174). CONCLUSIONS: C. difficile screening prior to cystectomy is associated with a significant decrease in the rate of clinically symptomatic infection postoperatively. These results should be confirmed in a randomized controlled trial.

Standardized Reporting of Microscopic Renal Tumor Margins: Introduction of the Renal Tumor Capsule Invasion Scoring System.

PURPOSE: Renal tumor enucleation allows for maximal parenchymal preservation. Identifying pseudocapsule integrity is critically important in nephron sparing surgery by enucleation. Tumor invasion into and through the capsule may have clinical implications, although it is not routinely commented on in standard pathological reporting. We describe a system to standardize the varying degrees of pseudocapsule invasion and identify predictors of invasion. MATERIALS AND METHODS: We performed a multicenter retrospective review between 2002 and 2014 at Indiana University Hospital and Loyola University Medical Center. A total of 327 tumors were evaluated following removal via radical nephrectomy, standard margin partial nephrectomy or enucleation partial nephrectomy. Pathologists scored tumors using our i-Cap (invasion of pseudocapsule) scoring system. Multivariate analysis was done to determine predictors of higher score tumors. RESULTS: Tumor characteristics were similar among surgical resection groups. Enucleated tumors tended to have thinner pseudocapsule rims but not higher i-Cap scores. Rates of complete capsular invasion, scored as i-Cap 3, were similar among the surgical techniques, comprising 22% of the overall cohort. Papillary histology along with increasing tumor grade was predictive of an i-Cap 3 score. CONCLUSIONS: A capsule invasion scoring system is useful to classify renal cell carcinoma pseudocapsule integrity. i-Cap scores appear to be independent of surgical technique. Complete capsular invasion is most common in papillary and high grade tumors. Further work is warranted regarding the relevance of capsular invasion depth as it relates to the oncologic outcome for local recurrence and disease specific survival.

Changing USA national trends for adrenalectomy: the influence of surgeon and technique.

OBJECTIVE: To explain differences over time between operative approach and surgeon type for adrenal surgery in the USA. PATIENTS AND METHODS: A retrospective cohort analysis was performed on all patients undergoing adrenalectomy between 2002 and 2011 using the Nationwide Inpatient Sample. Patients undergoing concurrent nephrectomy were excluded. Surgeon specialty was only available for 2003-2009. Descriptive analyses and multivariable logistic regression models were used to assess variables associated with minimally invasive surgery (MIS) and urologist-performed procedures. RESULTS: In all, 58,948 adrenalectomies were identified. A MIS approach was used in 20% of these operations. There was a 4% increase in MIS throughout the study period (P < 0.001). Cases performed at teaching hospitals were more likely to be MIS (odds ratio [OR] 1.47, P < 0.001). We were able to identify surgical specialty in 23,746 cases, of which 60% were performed by urologists. Cases performed in the Midwest compared with Northeast were at increased adjusted odds of being performed by urologists (OR 1.38, P = 0.11). Despite most cases being performed by urologists, adrenalectomy by urologists showed a 15% annual decrease over the analysed period (P < 0.001). CONCLUSIONS: The use of a MIS technique to perform adrenalectomy is increasing at a slower rate compared with most other surgical extirpative procedures. Further investigation to explain the decreased performance of adrenalectomy by urologists is warranted.

Robotic management of genitourinary injuries from obstetric and gynaecological operations: a multi-institutional report of outcomes.

OBJECTIVE: To evaluate the utility of robotic repair of injuries to the ureter or bladder from obstetrical and gynaecological (OBGYN) surgery PATIENTS AND METHODS: A retrospective review of all patients from four different high-volume institutions between 2002 and 2013 that had a robot-assisted (RA) repair by a urologist after an OBGYN genitourinary injury. RESULTS: Of the 43 OBGYN operations, 34 were hysterectomies: 10 open, 10 RA, nine vaginally, and five pure laparoscopic. Nine patients had alternative OBGYN operations: three caesarean sections, three oophorectomies (one open, two laparoscopic), one RA colpopexy, one open pelvic cervical cerclage with mesh and one RA removal of an invasive endometrioma. In all, 49 genitourinary (GU) injuries were sustained: ureteric ligation (26), ureterovaginal fistula (10), ureterocutaneous fistula (one), vesicovaginal fistula (VVF; 10) and cystotomy alone (two). In all, 10 patients (23.3%) underwent immediate urological repair at the time of their OBGYN RA surgery. The mean (range) time between OBGYN injury and definitive delayed repair was 23.5 (1-297) months. Four patients had undergone prior failed repair: two open VVF repairs and two balloon ureteric dilatations with stent placement. In all, 22 ureteric re-implants (11 with ipsilateral psoas hitch) and 15 uretero-ureterostomies were performed. Stents were placed in all ureteric cases for a mean (range) of 32 (1-63) days. In all, 10 VVF repairs and two primary cystotomy closures were performed. Drains were placed in 28 cases (57.1%) for a mean (range) of 4.1 (1-26) days. No case required open conversion. Two patients (4.1%) developed ureteric obstruction after RA repair requiring dilatation and stenting. The mean (range) follow-up of the entire cohort was 16.6 (1-63) months. CONCLUSIONS: RA repair of GU injuries during OBGYN surgery is associated with good outcomes, appears safe and feasible, and can be used successfully immediately after injury recognition or as a salvage procedure after prior attempted repair. RA techniques may improve convalescence in a patient population where quick recovery is paramount.

Robot-assisted renal tumor enucleo-resection in patients with a solitary kidney.

INTRODUCTION: Nephron-sparing surgery is most crucial for patients with a small renal mass in a solitary kidney. Historically, a minimally invasive approach in this setting has been discouraged. Tumor enucleo-resection, long established in the management of hereditary renal tumor syndromes, is currently being evaluated as a viable surgical technique in the sporadic renal cell carcinoma (RCC) population. This approach may significantly reduce or eliminate the need for hilar clamping. We sought to evaluate our experience with robot-assisted enucleo-resection partial nephrectomy (EN-RAPN) in patients with solitary kidneys. MATERIALS AND METHODS: Records of patients with a solitary kidney requiring partial nephrectomy performed with robot-assisted enucleo-resection technique at four academic institutions between 2010 and 2013 were reviewed. Baseline demographic, perioperative and pathological data were collected. Functional and early operative outcomes were analyzed. RESULTS: Twelve patients underwent EN-RAPN with a median age of 68 years (range 55-80) and follow up duration of 12.55 months (IQR: 5.25, 18.88). Median warm ischemia time was 5.5 minutes (IQR: 0, 13.25) with 6/12 (50%) done off-clamp (zero warm ischemia). Ten (83.3%) patients were pT1a and clear cell was the predominant pathology (9 patients, 75%). Surgical margins were negative in all patients. No patient experienced renal loss or required dialysis. Pre and postoperative estimated glomerular filtration rate (eGFR) at last follow up was similar (54.3, 48.9, Δ-7.0%; p = 0.313). CONCLUSIONS: Robot-assisted enucleo-resection partial nephrectomy in patients with a solitary kidney appears safe and feasible in our early experience. This approach may be utilized to maximize renal preservation and minimize hilar clamping in this setting.

Spontaneous resolution of inflammatory myofibroblastic tumor of the kidney.

Inflammatory myofibroblastic tumor (IMT) of the kidney is a rare and benign condition often confused with renal malignancy based on clinical presentation and radiologic evaluation that has commonly been treated with nephrectomy. Utilizing renal mass biopsy to help diagnose and guide therapeutic intervention is increasing but has not been universally adopted to this point. We present a case of an incidentally found atypical renal mass in a 71-year-old female diagnosed as inflammatory myofibroblastic tumor of the kidney after core needle biopsy. This tumor was managed conservatively without surgical intervention and resolved spontaneously.

Outcomes of Robot-Assisted Laparoscopic Pyeloplasty Based on Degree of Obstruction on Preoperative Tc-99 MAG-3 Renal Scintigraphy.

Objective: Management of symptomatic ureteropelvic junction (UPJ) obstruction with hydronephrosis and discordant Tc-99 mercaptoacetyltriglycine (MAG-3) renal scintigraphy is challenging. In this study we describe long-term outcomes of patients who underwent robot-assisted laparoscopic pyeloplasty for the correction of symptomatic UPJ obstruction with discordant preoperative Tc-99m MAG-3 renal scintigraphy. Methods: Patients undergoing robot-assisted laparoscopic pyeloplasty for symptomatic UPJ obstruction at a single academic center from 2009 to 2021 were retrospectively reviewed. Patients were categorized into three groups with varying degrees of obstruction based on preoperative MAG-3 imaging: Group 1: no obstruction (Lasix T1/2 clearance <10 minutes), Group 2: equivocal obstruction (Lasix T1/2 clearance 10-20 minutes), and Group 3: obstruction (Lasix T1/2 clearance >20 minutes. Pyeloplasty success was defined as resolution of symptoms and improvement/stable computed tomography (CT) imaging or MAG-3 scintigraphy. Failure was defined as persistence of symptoms with either obstruction on functional imaging, worsening hydronephrosis, or subsequent intervention. Results: A total of 125 cases were identified, with a median patient age of 35 years. Dismembered pyeloplasty technique was performed in 98.4% of cases. Median preoperative split renal function on MAG-3 scintigraphy was the only statistically significant (p = 0.003) difference in preoperative characteristics between the three groups. There were 15 postoperative complications, with a rate of Clavien-Dindo grade 3 or higher complications of 4.8%. Overall pyeloplasty success was 92.8%, with success rates of 100% (15/15) and 97% (32/33) in the no obstruction and equivocal obstruction groups, respectively. Median time to pyeloplasty failure was 20.4 months. Conclusion: Robot-assisted laparoscopic pyeloplasty is a safe and effective surgical intervention for correcting UPJ obstruction. Patients with symptoms of UPJ obstruction and discordant functional imaging studies demonstrate similar or improved success rates after pyeloplasty compared with patients with documented high-grade obstruction. Based on these findings preoperative renal scan may not be reliable in appropriate selection of candidacy for pyeloplasty.

Identifying Preoperative Predictors of Operative Time and Their Impact on Outcomes in Robot-Assisted Partial Nephrectomy.

Objective: 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.

Human jackstone arms show a protein-rich, X-ray lucent core, suggesting that proteins drive their rapid and linear growth.

Jackstone 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.

Can Retroperitoneal Lymph Node Dissection (RPLND) be feasibly performed to prolong survival in Renal Cell Carcinoma (RCC) with limited lymph node involvement? An Analysis of Recurrence Patterns.

INTRODUCTION: The therapeutic benefit of performing a lymph node dissection (LND) in patients with renal cell carcinoma (RCC) has been controversial. In prior studies, it was thought that a low event rate for nodal metastases affected the ability to draw any conclusions. Here, we opted to select patients that had low burden 1 or 2 nodes positive to study survival outcomes and recurrence patterns based on limited LND or extended LND with a template retroperitoneal lymph node dissection (RPLND). METHODS: We used our single institutional database from 2000 and 2019 and identified 45 patients that had only 1 or 2 nodes positive on final pathology without any other systemic disease. These patients all underwent nephrectomy with limited LND or a template RPLND on the ipsilateral side. RESULTS: We identified 23 patients in the limited LND and 22 in the template RPLND group. Thirty-one patients included in the study had 1 positive lymph node and 14 patients had 2 positive lymph nodes. For patients undergoing a limited LND, a median 4 (IQR 1-11) lymph nodes were resected and for those undergoing template RPLND, 18 (IQR: 13-23) lymph nodes were resected. On Kaplan-Meier analysis, a difference was noted in overall survival (P = 0.04) when comparing limited LND to template RPLND. We also mapped out patterns of recurrence and found that 6 patients had retroperitoneal lymph node recurrences after a limited LND in the ipsilateral node packet. On univariate analysis, pathologic stage was a major factor for survival, but did not remain as significant with the inclusion of template RPLND status and Charlson Comorbidity Index in multivariate analysis. CONCLUSION: We identified specific patients that had RCC with limited lymph node involvement. We found that a select number of patients had durable improvement in survival outcomes with template RPLND. In examining the recurrence patterns, a greater number of patients may have derived benefit for an initial template RPLND.