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Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The use of a drain to detect and evacuate anastomotic urine leakage after radical prostatectomy is a common clinical practice. The use of such drains, traditionally, attempts to avoid the short-term risks of urinoma, ileus, and infection, but little is known on the long-term complications of such leakage on functional outcomes, such as erectile function, continence, and bladder neck contracture. This study shows that after a mean of two years of follow-up, patients with clinically detected anastomotic urine leakage after robotic-assisted laparoscopic radical prostatectomy do not have worse erectile function, incontinence or risk of bladder neck contracture than patients who had no clinical evidence of leakage. OBJECTIVE • To determine whether patients with postoperative clinically detected anastomotic urine leaks are at increased risk for poorer erectile function, urinary incontinence and bladder neck contracture (BNC) after robotic-assisted laparoscopic radical prostatectomy. PATIENTS AND METHODS • A retrospective review of all patients undergoing RALRP from October 2005 until December 2009 by a single surgeon (R.B.N.) was conducted. Clinically detected anastomotic urine leak was defined as drain output consistent with urine at more than 24 h postoperatively. The presence of BNC was identified on cystoscopy. • Erectile function was measured with the Sexual Healthy Inventory for Men (SHIM) questionnaire. Incontinence was measured by patient-reported daily pad use. • Univariate and multivariate analyses were performed. Outcomes were assessed at the most recent follow-up. RESULTS • Among 213 patients eligible for inclusion, 27 experienced an anastomotic urine leak (12.7%). • At a mean long-term follow-up of 24.2 months, there was no difference in SHIM scores (7.0 vs 13.1; P= 0.101), continence rates (87.5% vs 85.2%; P= 0.999) or risk of BNC (7.4% vs 3.2%; P= 0.268) between patients with and without postoperative anastomotic urine leaks, respectively. • The results did not change after controlling for covariates in a multivariate analysis. CONCLUSION • The present study suggests that patients with clinically detected postoperative anastomotic urine leaks do not necessarily have worse long-term outcomes of erectile function, continence and risk of BNC. [ABSTRACT FROM AUTHOR]

Haywood S, Abecassis M, Levitsky J. The renal benefit of mycophenolate mofetil after liver transplantation. Clin Transplant 2011: 25: E88-E95. © 2010 John Wiley & Sons A/S. The risk and benefit of adding mycophenolate mofetil (MMF) to a standard immunosuppressive regimen at the time of liver transplantation (LT) is not well described. We performed a retrospective case-control analysis comparing one-yr outcomes of all LT recipients at our institution treated with post-operative tacrolimus (TAC), MMF, and steroids vs. TAC and steroids. A total of 101 LT recipients (50:51 case:control) were analyzed. Despite more renal dysfunction at LT, the MMF + TAC group had similar serum creatinine (Cr) and glomerular filtration rate (GFR) as the TAC group one-yr post-LT. In this time period, Cr decreased (1.57-1.22 mg/dL, p = 0.04) and GFR increased (57.5-65.1 mL/min per 1.73 m, p = 0.05) in the MMF + TAC group, while Cr increased (1.11-1.35, p < 0.01) and GFR declined (73.5-60.1, p < 0.001) in the TAC group. These findings occurred without a difference in absolute rejection episodes, hospitalizations, infections, deaths, or time to above events (p > 0.05). Subgroup analysis of patients stratified by pre-transplant renal dysfunction (Cr ≥ 1.2 mg/dL) supported the previous. MMF was reasonably well tolerated with a low rate of discontinuation. The use of adjunctive MMF immediately after LT may protect against calcineurin inhibitor nephrotoxicity, potentially without the need for dose reduction or increased risk of adverse events. [ABSTRACT FROM AUTHOR]

This study tests the hypothesis that lipids could act as an alternative fuel source in the brain during insulin-induced hypoglycemia. Male Sprague-Dawley rats were subjected to hyperinsulinemic (5 mU∙kg[sup-1]∙min[sup-1]) hypoglycemic (∼50 mg/dl) clamps. In protocol 1, intralipid (IL), a fat emulsion, was infused intravenously to prevent the fall in free fatty acid levels that occurs in response to hyperinsulinemic hypoglycemia. Intravenous lipid infusion did not alter the counterregulatory responses to hypoglycemia. To test whether IL could have central effects in mediating the counterregulatory response to hypoglycemia, in protocol 2 the brains of precannulated rats were intracerebroventricularly (icy) infused with IL or artificial cerebrospinal fluid (aCSF) as control. Unexpectedly, the epinephrine and glucagon response to hypoglycemia was significantly augmented with icy IL infusion. To determine whether central IL infusion could restore defective counterregulation, in protocol 3 rats were made recurrently hypoglycemic (RH) for 3 days and on the 4th day underwent hyperinsulinemic hypoglycemic clamps with icy IL or aCSF infusion. RH rats had the expected impaired epinephrine response to hypoglycemia, and icy IL infusion again significantly augmented the epinephrine response in RH rats to normal. With regard to our experimental model of hypoglycemic counterregulation, we conclude that 1) systemic lipid infusion did not alter the counterregulatory response to hypoglycemia, 2) the icy infusion of lipids markedly increased CSF FFA levels and paradoxically augmented the epinephrine and glucagon responses, and 3) the blunted sympathoadrenal response in recurrently hypoglycemic rats was completely normalized with the icy lipid infusion. It is concluded that, in the setting of insulin-induced hypoglycemia, increased brain lipids can enhance the sympathoadrenal response. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusion To investigate whether preoperative body morphometry analysis can identify patients at risk of parastomal hernia (PH), which is a common complication after radical cystectomy (RC).All patients who underwent RC between 2010 and 2020 with available cross‐sectional imaging preoperatively and at 1 and 2 years postoperatively were included. Skeletal muscle mass and total fat mass (FM) were determined from preoperative axial computed tomography images obtained at the level of the L3 vertebral body using Aquarius Intuition software. Sarcopenia and obesity were assigned based on consensus definitions of skeletal muscle index (SMI) and FM index (FMI). PH were graded using both the Moreno‐Matias and European Hernia Society criteria. Binary logistic regression and recursive partitioning were used to identify patients at risk of PH. The Kaplan–Meier method with log‐rank and Cox proportional hazards models included clinical and image‐based parameters to identify predictors of PH‐free survival.A total of 367 patients were included in the final analysis, with 159 (43%) developing a PH. When utilising binary logistic regression, high FMI (odds ratio [OR] 1.63, P < 0.001) and low SMI (OR 0.96, P = 0.039) were primary drivers of risk of PH. A simplified model that only relied upon FMI, SMI, and preoperative albumin improved the classification of patients at risk of PH. On Kaplan–Meier analysis, patients who were obese or obese and sarcopenic had significantly worse PH‐free survival (P < 0.001).Body morphometry analysis identified FMI and SMI to be the most consistent predictors of PH after RC. [ABSTRACT FROM AUTHOR]

Objective: To automate the generation of three validated nephrometry scoring systems on preoperative computerised tomography (CT) scans by developing artificial intelligence (AI)‐based image processing methods. Subsequently, we aimed to evaluate the ability of these scores to predict meaningful pathological and perioperative outcomes. Patients and Methods: A total of 300 patients with preoperative CT with early arterial contrast phase were identified from a cohort of 544 consecutive patients undergoing surgical extirpation for suspected renal cancer. A deep neural network approach was used to automatically segment kidneys and tumours, and then geometric algorithms were used to measure the components of the concordance index (C‐Index), Preoperative Aspects and Dimensions Used for an Anatomical classification of renal tumours (PADUA), and tumour contact surface area (CSA) nephrometry scores. Human scores were independently calculated by medical personnel blinded to the AI scores. AI and human score agreement was assessed using linear regression and predictive abilities for meaningful outcomes were assessed using logistic regression and receiver operating characteristic curve analyses. Results: The median (interquartile range) age was 60 (51–68) years, and 40% were female. The median tumour size was 4.2 cm and 91.3% had malignant tumours. In all, 27% of the tumours were high stage, 37% high grade, and 63% of the patients underwent partial nephrectomy. There was significant agreement between human and AI scores on linear regression analyses (R ranged from 0.574 to 0.828, all P < 0.001). The AI‐generated scores were equivalent or superior to human‐generated scores for all examined outcomes including high‐grade histology, high‐stage tumour, indolent tumour, pathological tumour necrosis, and radical nephrectomy (vs partial nephrectomy) surgical approach. Conclusions: Fully automated AI‐generated C‐Index, PADUA, and tumour CSA nephrometry scores are similar to human‐generated scores and predict a wide variety of meaningful outcomes. Once validated, our results suggest that AI‐generated nephrometry scores could be delivered automatically from a preoperative CT scan to a clinician and patient at the point of care to aid in decision making. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusions To rigorously evaluate the impact of the percentage of parenchymal volume preserved (PPVP) and how well the preserved parenchyma recovers from ischaemia (Recischaemia) on functional outcomes after partial nephrectomy (PN) using an accurate and objective software‐based methodology for estimating parenchymal volumes and split renal function (SRF). A secondary objective was to assess potential predictors of the PPVP.A total of 894 PN patients with available studies (2011–2014) were evaluated. The PPVP was measured from cross‐sectional imaging at ≤3 months before and 3–12 months after PN using semi‐automated software. Pearson correlation evaluated relationships between continuous variables. Multivariable linear regression evaluated predictors of ipsilateral glomerular filtration rate (GFR) preserved and the PPVP. Relative‐importance analysis was used to evaluate the impact of the PPVP on ipsilateral GFR preserved. Recischaemia was defined as the percentage of ipsilateral GFR preserved normalised by the PPVP.The median tumour size and R.E.N.A.L. nephrometry score were 3.4 cm and 7, respectively. In all, 49 patients (5.5%) had a solitary kidney. In all, 538 (60%)/251 (28%)/104 (12%) patients were managed with warm/cold/zero ischaemia, respectively. The median pre/post ipsilateral GFRs were 40/31 mL/min/1.73 m2, and the median (interquartile range [IQR]) percentage of ipsilateral GFR preserved was 80% (71–88%). The median pre/post ipsilateral parenchymal volumes were 181/149 mL, and the median (IQR) PPVP was 84% (76–92%). In all, 330 patients (37%) had a PPVP of <80%, while only 34 (4%) had a Recischaemia of <80%. The percentage of ipsilateral GFR preserved correlated strongly with the PPVP (r = 0.83, P < 0.01) and loss of parenchymal volume accounted for 80% of the loss of ipsilateral GFR. Multivariable analysis confirmed that the PPVP was the strongest predictor of ipsilateral GFR preserved. Greater tumour size and endophytic and nearness properties of the R.E.N.A.L. nephrometry score were associated with a reduced PPVP (all P ≤ 0.01). Solitary kidney and cold ischaemia were associated with an increased PPVP (all P < 0.05).A reduced PPVP predominates regarding functional decline after PN, although a low Recischaemia can also contribute. Tumour‐related factors strongly influence the PPVP, while surgical efforts can improve the PPVP as observed for patients with solitary kidneys. [ABSTRACT FROM AUTHOR]

Background: CC-115, a dual mTORC1/2 and DNA-PK inhibitor, has promising antitumour activity when combined with androgen receptor (AR) inhibition in pre-clinical models. Methods: Phase 1b multicentre trial evaluating enzalutamide with escalating doses of CC-115 in AR inhibitor-naive mCRPC patients (n = 41). Primary endpoints were safety and RP2D. Secondary endpoints included PSA response, time-to-PSA progression, and radiographic progression. Results: Common adverse effects included rash (31.7% Grades 1–2 (Gr); 31.7% Gr 3), pruritis (43.9% Gr 1–2), diarrhoea (37% Gr 1–2), and hypertension (17% Gr 1–2; 9.8% Gr 3). CC-115 RP2D was 5 mg twice a day. In 40 evaluable patients, 80% achieved ≥50% reduction in PSA (PSA50), and 58% achieved ≥90% reduction in PSA (PSA90) by 12 weeks. Median time-to-PSA progression was 14.7 months and median rPFS was 22.1 months. Stratification by PI3K alterations demonstrated a non-statistically significant trend towards improved PSA50 response (PSA50 of 94% vs. 67%, p = 0.08). Exploratory pre-clinical analysis suggested CC-115 inhibited mTOR pathway strongly, but may be insufficient to inhibit DNA-PK at RP2D. Conclusions: The combination of enzalutamide and CC-115 was well tolerated. A non-statistically significant trend towards improved PSA response was observed in patients harbouring PI3K pathway alterations, suggesting potential predictive biomarkers of response to a PI3K/AKT/mTOR pathway inhibitor. Clinical trial registration: ClinicalTrials.gov identifier: NCT02833883. [ABSTRACT FROM AUTHOR]

Background: Tension-free abdominal closure is a primary tenet of laparotomy. But this concept neglects the baseline tension of the abdominal wall. Ideally, abdominal closure should be tailored to restore native physiologic tension. We sought to quantify the tension needed to re-establish the linea alba in patients undergoing exploratory laparotomy. Methods: Patients without ventral hernias undergoing laparotomy at a single institution were enrolled from December 2021 to September 2022. Patients who had undergone prior laparotomy were included. Exclusion criteria included prior incisional hernia repair, presence of an ostomy, large-volume ascites, and large intra-abdominal tumors. After laparotomy, a sterilizable tensiometer measured the quantitative tension needed to bring the fascial edge to the midline. Outcomes included the force needed to bring the fascial edge to the midline and the association of BMI, incision length, and prior lateral incisions on abdominal wall tension. Results: This study included 86 patients, for a total of 172 measurements (right and left for each patient). Median patient BMI was 26.4 kg/m2 (IQR 22.9;31.5), and median incision length was 17.0 cm (IQR 14;20). Mean tension needed to bring the myofascial edge to the midline was 0.97 lbs. (SD 1.03). Mixed-effect multivariable regression modeling found that increasing BMI and greater incision length were associated with higher abdominal wall tension (coefficient 0.04, 95% CI [0.01,0.07]; p = 0.004, coefficient 0.04, 95% CI [0.01,0.07]; p = 0.006, respectively). Conclusion: In patients undergoing laparotomy, the tension needed to re-establish the linea alba is approximately 1.94 lbs. A quantitative understanding of baseline abdominal wall tension may help surgeons tailor abdominal closure in complex scenarios, including ventral hernia repairs and open or burst abdomens. [ABSTRACT FROM AUTHOR]

To determine whether we can surpass the traditional R.E.N.A.L. nephrometry score (H-score) prediction ability of pathologic outcomes by creating artificial intelligence (AI)-generated R.E.N.A.L.+ score (AI+ score) with continuous rather than ordinal components. We also assessed the AI+ score components' relative importance with respect to outcome odds. This is a retrospective study of 300 consecutive patients with preoperative computed tomography scans showing suspected renal cancer at a single institution from 2010 to 2018. H-score was tabulated by three trained medical personnel. Deep neural network approach automatically generated kidney segmentation masks of parenchyma and tumor. Geometric algorithms were used to automatically estimate score components as ordinal and continuous variables. Multivariate logistic regression of continuous R.E.N.A.L. components was used to generate AI+ score. Predictive utility was compared between AI+, AI, and H-scores for variables of interest, and AI+ score components' relative importance was assessed. Median age was 60 years (interquartile range 51-68), and 40% were female. Median tumor size was 4.2 cm (2.6-6.12), and 92% were malignant, including 27%, 37%, and 23% with high-stage, high-grade, and necrosis, respectively. AI+ score demonstrated superior predictive ability over AI and H-scores for predicting malignancy (area under the curve [AUC] 0.69 vs 0.67 vs 0.64, respectively), high stage (AUC 0.82 vs 0.65 vs 0.71, respectively), high grade (AUC 0.78 vs 0.65 vs 0.65, respectively), pathologic tumor necrosis (AUC 0.81 vs 0.72 vs 0.74, respectively), and partial nephrectomy approach (AUC 0.88 vs 0.74 vs 0.79, respectively). Of AI+ score components, the maximal tumor diameter ("R") was the most important outcomes predictor. AI+ score was superior to AI-score and H-score in predicting oncologic outcomes. Time-efficient AI+ score can be used at the point of care, surpassing validated clinical scoring systems. [ABSTRACT FROM AUTHOR]

Objective: To identify factors associated with longitudinal ipsilateral functional decline after partial nephrectomy (PN). Patients and Methods: Of 1140 patients managed with PN (2012–2014), 349 (31%) had imaging/serum creatinine levels pre‐PN, 1–12 months post‐PN (new baseline), and >3 years later necessary for inclusion. Parenchymal‐volume analysis was used to determine split renal function. Patients were grouped as having significant renal comorbidity (CohortSRC: diabetes mellitus with insulin‐dependence or end‐organ damage, refractory hypertension, or severe pre‐existing chronic kidney disease) vs not having significant renal comorbidity (CohortNoSRC) preoperatively. Multivariable regression was used to identify predictors of annual ipsilateral parenchymal atrophy and functional decline relative to new baseline values post‐PN, after the kidney had healed. Results: The median follow‐up was 6.3 years with 87/226/36 patients having cold/warm/zero ischaemia. The median cold/warm ischaemia times were 32/22 min. Overall, the median tumour size was 3.0 cm. The preoperative glomerular filtration rate (GFR) and new baseline GFR (NBGFR) were 81 and 71 mL/min/1.73 m2, respectively. After establishment of the NBGFR, the median loss of global and ipsilateral function was 0.7 and 0.4 mL/min/1.73 m2/year, respectively, consistent with the natural ageing process. Overall, the median ipsilateral parenchymal atrophy was 1.2 cm3/year and accounted for a median of 53% of the annual functional decline. Significant renal comorbidity, age, and warm ischaemia were independently associated with ipsilateral parenchymal atrophy (all P < 0.01). Significant renal comorbidity and ipsilateral parenchymal atrophy were independently associated with annual ipsilateral functional decline (both P < 0.01). Annual median ipsilateral parenchymal atrophy and functional decline were both significantly increased for CohortSRC compared to CohortNoSRC (2.8 vs 0.9 cm3, P < 0.01 and 0.90 vs 0.30 mL/min/1.73 m2/year, P < 0.01, respectively). Conclusions: Longitudinal renal function following PN generally follows the normal ageing process. Significant renal comorbidities, age, warm ischaemia, and ipsilateral parenchymal atrophy were the most important predictors of ipsilateral functional decline following establishment of NBGFR. [ABSTRACT FROM AUTHOR]

Objectives: To provide a more rigorous assessment of factors affecting functional recovery after partial nephrectomy (PN) using novel tools that allow for analysis of more patients and improved accuracy for assessment of parenchymal volume loss, thereby revealing the potential impact of secondary factors such as ischaemia. Patients and Methods: Of 1140 patients managed with PN (2012–2014), 670 (59%) had imaging and serum creatinine levels measured before and after PN necessary for inclusion. Recovery from ischaemia was defined as the ipsilateral glomerular filtration rate (GFR) saved normalised by parenchymal volume saved. Acute kidney injury was assessed through Spectrum Score, which quantifies the degree of acute ipsilateral renal dysfunction due to exposure to ischaemia that would otherwise be masked by the contralateral kidney. Multivariable regression was used to identify predictors of Spectrum Score and Recovery from Ischaemia. Results: In all, 409/189/72 patients had warm/cold/zero ischaemia, respectively, with median (interquartile range [IQR]) ischaemia times for cold and warm ischaemia of 30 (25–42) and 22 (18–28) min, respectively. The median (IQR) global preoperative GFR and new baseline GFR (NBGFR) were 78 (63–92) and 69 (54–81) mL/min/1.73 m2, respectively. The median (IQR) ipsilateral preoperative GFR and NBGFR were 40 (33–47) and 31 (24–38) mL/min/1.73 m2, respectively. Functional recovery correlated strongly with parenchymal volume preserved (r = 0.83, P < 0.01). The median (IQR) decline in ipsilateral GFR associated with PN was 7.8 (4.5–12) mL/min/1.73 m2 with loss of parenchyma accounting for 81% of this loss. The median (IQR) recovery from ischaemia was similar across the cold/warm/zero ischaemia groups at 96% (90%–102%), 95% (89%–101%), and 97% (91%–102%), respectively. Independent predictors of Spectrum Score were ischaemia time, tumour complexity, and preoperative global GFR. Independent predictors of recovery from ischaemia were insulin‐dependent diabetes mellitus, refractory hypertension, warm ischaemia, and Spectrum Score. Conclusions: The main determinant of functional recovery after PN is parenchymal volume preservation. A more robust and rigorous evaluation allowed us to identify secondary factors including comorbidities, increased tumour complexity, and ischaemia‐related factors that are also independently associated with impaired recovery, although altogether these were much less impactful. [ABSTRACT FROM AUTHOR]

Objectives: To provide a more rigorous assessment of factors affecting functional recovery after partial nephrectomy (PN) using novel tools that allow for analysis of more patients and improved accuracy for assessment of parenchymal volume loss, thereby revealing the potential impact of secondary factors such as ischaemia. Patients and Methods: Of 1140 patients managed with PN (2012–2014), 670 (59%) had imaging and serum creatinine levels measured before and after PN necessary for inclusion. Recovery from ischaemia was defined as the ipsilateral glomerular filtration rate (GFR) saved normalised by parenchymal volume saved. Acute kidney injury was assessed through Spectrum Score, which quantifies the degree of acute ipsilateral renal dysfunction due to exposure to ischaemia that would otherwise be masked by the contralateral kidney. Multivariable regression was used to identify predictors of Spectrum Score and Recovery from Ischaemia. Results: In all, 409/189/72 patients had warm/cold/zero ischaemia, respectively, with median (interquartile range [IQR]) ischaemia times for cold and warm ischaemia of 30 (25–42) and 22 (18–28) min, respectively. The median (IQR) global preoperative GFR and new baseline GFR (NBGFR) were 78 (63–92) and 69 (54–81) mL/min/1.73 m2, respectively. The median (IQR) ipsilateral preoperative GFR and NBGFR were 40 (33–47) and 31 (24–38) mL/min/1.73 m2, respectively. Functional recovery correlated strongly with parenchymal volume preserved (r = 0.83, P < 0.01). The median (IQR) decline in ipsilateral GFR associated with PN was 7.8 (4.5–12) mL/min/1.73 m2 with loss of parenchyma accounting for 81% of this loss. The median (IQR) recovery from ischaemia was similar across the cold/warm/zero ischaemia groups at 96% (90%–102%), 95% (89%–101%), and 97% (91%–102%), respectively. Independent predictors of Spectrum Score were ischaemia time, tumour complexity, and preoperative global GFR. Independent predictors of recovery from ischaemia were insulin‐dependent diabetes mellitus, refractory hypertension, warm ischaemia, and Spectrum Score. Conclusions: The main determinant of functional recovery after PN is parenchymal volume preservation. A more robust and rigorous evaluation allowed us to identify secondary factors including comorbidities, increased tumour complexity, and ischaemia‐related factors that are also independently associated with impaired recovery, although altogether these were much less impactful. [ABSTRACT FROM AUTHOR]

To assess how IsoPSA, a structure-based serum assay which has been prospectively validated in detecting clinically significant prostate cancer (csPCa), can help the biopsy decision process when combined with the prostate imaging reporting and data systems (PI-RADS). This was a single-center retrospective review of prospectively collected data on patients receiving IsoPSA testing for elevated PSA (>4.0ng/mL). Patients were included if they had received an IsoPSA test and prostate MRI within 1 year of IsoPSA testing, and subsequently underwent prostate biopsy. Multivariable logistic regression was used to identify predictors of (csPCa, ie, GG ≥ 2) on biopsy. Predictive probabilities for csPCa at biopsy were generated using IsoPSA and various PI-RADS scores. Two hundred and 7 patients were included. Twenty-two percent had csPCa. Elevated IsoPSA ratio (defined as ≥6.0) (OR: 5.06, P =.015) and a PI-RADS 4-5 (OR: 6.37, P <.001) were significant predictors of csPCa. The combination of elevated IsoPSA ratio and PI-RADS 4-5 lesion had the highest area under the curve (AUC) (AUC: 0.83, P <.001). The predicted probability of csPCa when a patient had a negative or equivocal MRI (PI-RADS 1-3) and a low IsoPSA ratio (≤6) was <5%. The combination of PI-RADS with IsoPSA ratios may help refine the biopsy decision-making process. In our cohort, a negative or equivocal MRI with a low IsoPSA may provide a low enough predicted probability to omit biopsy in such patients. [ABSTRACT FROM AUTHOR]

Partial prostatectomy using a novel single-port robotic transvesical approach is safe and feasible with minimal postoperative pain, shortened Foley catheter duration, and full recovery of urine control and potency within few weeks postoperatively in carefully selected patients with localized low- and intermediate-risk prostate cancer. Partial prostatectomy has been described as an alternative to focal therapy for the management of localized low- and intermediate-risk prostate cancer. To describe early outcomes and technique for single-port (SP) transvesical partial prostatectomy. A retrospective analysis was performed for nine patients with low-volume, localized, low- to intermediate-risk prostate cancer (Gleason ≤7) undergoing SP transvesical partial prostatectomy replicating the inclusion criteria for focal therapy by a single surgeon from November 2020 to March 2022. The daVinci SP access port was inserted percutaneously into the bladder and pnuemovesicum was achieved. The camera, robotic instruments, assistant port, and flexible suction tubing were introduced through the access port. The Koelis transrectal ultrasound with preoperative prostate magnetic resonance imaging fusion was used for intraoperative guidance. Demographic information, intraoperative variables, and postoperative outcomes were collected in an institutional review board–approved database, and a descriptive statistical analysis was performed. All cases were completed without requiring extra ports or conversion. No intraoperative complications were noted, and all patients were discharged on the day of surgery. Pathology showed Gleason scores of 3 + 3 = 6 in one case, 3 + 4 = 7 in seven cases, and 4 + 3 = 7 in one case, all with negative intraoperative margin assessment. At 6 wk, the median prostate-specific antigen was 0.5 and the median Sexual Health Inventory for Men score was 17.5 from 23 preoperatively. All patients were continent at 6 wk. The limitations include a small number of patients, short follow-up, and single-surgeon experience. We demonstrated the feasibility of the SP robotic transvesical partial prostatectomy. Early functional outcomes show impressive time to continence and erectile function. Continued follow-up will evaluate long-term oncologic outcomes. We performed partial prostatectomies in selected patients as an alternative to focal therapy using a novel transvesical single-port approach. Our approach was safe and feasible, with fewer complications and promising initial return to continence and erectile function. [ABSTRACT FROM AUTHOR]

While it is well known that peripheral actions of insulin cause hypoglycemia, several studies suggest that insulin action in the brain may paradoxically protect against severe hypoglycemia by augmenting the sympathoadrenal (SA) response to hypoglycemia. Since the mediobasal hypothalamus has been identified as a key site for both glucose sensing and insulin action in the brain, we hypothesized that a direct infusion of insulin into this area would amplify the SA response to hypoglycemia. Nine week-old male Sprague-Dawley rats were implanted with bilateral intrahypothalamic (IH) cannulas and subsequent jugular vein and carotid artery catheters. After a one week recovery and an overnight fast, insulin (15 mU in 30 µd) or aCSF (control) was infused bilaterally into the mediobasal hypothalamus over 5 hours. During the final two hours of the IH infusion, we measured the SA response to either a hyperinsulinemic (5 mU/kg/min) hypoglycemic (∼50 mg/dl) clamp or to a single 600 mg/kg IV bolus of 2-deoxy-glucose (2-DG). The 2-DG experiments were designed to selectively increase IH insulin in the absence of marked peripheral hyperinsulinemia. Proper placement of the IH cannulas was confirmed by injection of Evan's Blue dye. In response to insulin-induced hypoglycemia, epinephrine (E) rose more than 60-fold in both the IH-control and the IH-insulin groups (3768±472 vs. 3224±313 pg/ml, P=NS), and norepinephrine (NE) increased more than 4-fold (850±97 vs. 653±79 pg/ml, P=NS). Similarly, in response to 2-DG-induced glucoprivation, E rose more than 60-fold in both the IH-control and IH-insulin groups (3920±580 vs. 3802±364 pg/ml, P=NS), and NE increased more than 4 fold (807±79 vs. 757±79 pg/ml, P=NS). In summary, we were surprised to find that IH insulin did not augment the SA response to insulin-induced hypoglycemia nor to 2-DG-induced glucoprivation in male Sprague-Dawley rats. We propose that the previously noted acute actions of insulin to augment the sympathoadrenal response to hypoglycemia are likely mediated via extrahypothalamic mechanisms. [ABSTRACT FROM AUTHOR]

Pathologic overread following transurethral resection of bladder tumor (TURBT) is a common practice at our tertiary care center, however its value in terms of how often management is impacted remains largely unknown. As the treatment of non-muscle invasive bladder cancer (NMIBC) is primarily determined by AUA risk stratification, we sought to determine how pathologic re-review of TURBT performed at an outside institution changed histologic grade, clinical T (cT) stage and risk stratification. A total of 113 patients with

Micropapillary (MP) variant urothelial carcinoma is associated with poor response to intravesical therapy and increased risk of occult lymph node (LN) metastasis at radical cystectomy (RC). To date, evidence regarding whether the percentage of MP variant present within transurethral resection (TUR) samples impacts these outcomes is lacking. Our objective is to evaluate the impact of percentage MP variant on TUR on rates of lymph node metastasis and survival outcomes. A total of 70 patients with MP variant on TUR were identified from a prospectively maintained database of patients undergoing RC at our institution between 2007 and 2022. TUR samples were rereviewed by an expert GU pathologist with over ten years of experience. Presence and percent MP component, LVI, CIS, grade, and clinical stage were evaluated.;Pathologic outcomes were collected from subsequent RC specimens, and recurrence free (RFS) and overall survival (OS) were estimated via the Kaplan-Meier method. Associations between percent MP and lymph node metastasis, RFS, and OS were assessed with univariate and multivariate logistic regression and Cox survival analyses as appropriate. 67 of 70 TUR samples were confirmed to contain MP variant urothelial carcinoma on rereview. 34 of 67 (50.6%) patients underwent RC for cT1 disease, while the remainder harbored cT2+ disease. 17 of 33 (51.5%) patients with cT2+ disease underwent neoadjuvant chemotherapy (NAC). Percent MP was 34.7% in cT1 patients and 27.6% in cT2 patients (p = 0.25).; On univariate analysis, both MP ≥ 30% (Odds Ratio (OR) 3.24, p = 0.025) and clinical T stage 2+ (OR 3.09, p = 0.03) were significant predictors of nodal metastasis at RC. On multivariate analysis, both MP ≥ 30% (Odds Ratio (OR) 3.79, p = 0.017) and clinical T stage 2+ (OR 3.63, p = 0.021) remained significant predictors of pathologic node positive disease. The lowest pN+ rate was found in patients with cT1 disease and MP <30% (3/16, 18.7%), versus the highest in cT2+ disease and MP ≥ 30% (12/16, 75%). Percent MP component on TURBT is associated with increased risk of occult lymph node metastasis at subsequent radical cystectomy. Routine pathologic evaluation of percent MP component has the potential to help select which patients with MP might be reasonable candidates for intravesical therapy. [ABSTRACT FROM AUTHOR]

Objective: To understand the mechanistic basis for reduced infectious complications in transperineal (TP) prostate biopsy, we sought to determine whether TP prostate biopsy is associated with a lower degree of pathogen introduction into the prostate relative to transrectal (TR) biopsy.Materials and Methods: In men scheduled for prostate biopsy for standard clinical indications, rectal and perineal skin swabs, and 2 extra biopsy cores, were obtained. Specimens underwent DNA extraction followed by next-generation sequencing and standard laboratory culture. Microbial quantity and composition were determined and compared between prostate core biopsy tissue from individuals who underwent TP vs TR biopsy.Results: Twenty-three men were accrued to the study. Biopsy core tissue from the TP group had less microbial diversity (15.0 vs 25.8 phylogenetic clades/sample, P = .0004) and had a lower quantity of known pathogens (36.3 vs 104.2 normalized counts of pathogens/sample, P = .018) relative to the TR group. TP group tissue core flora was more attributable to the perineal than rectal source (P = .047). Viable Escherichia coli was isolated from 45% of the TR group cores, but none in the TP group (P = .014).Conclusion: Biopsy tissue from individuals who undergo TP biopsy harbors a lower human pathogenic bacterial load than those who undergo TR biopsy, with a minimal risk of viable E. coli. Our results elucidate a possible mechanism for reduced infectious risk associated with TP biopsy relative to TR biopsy and a rational basis for widespread implementation of TP biopsy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between intraoperative anaesthetic parameters, primarily intraoperative hypotension, and postoperative renal function in patients undergoing nephrectomy. Patients and Methods: We reviewed data from 3240 consecutive patients who underwent nephrectomy between 2010 and 2018. Anaesthetic parameters evaluated included duration of hypotension, tachycardia, hypothermia, volatile anaesthetic use and mean arterial pressure in the post‐anaesthesia care unit. Outcomes included acute kidney injury (AKI) and estimated glomerular filtration rate (eGFR) within the first year after nephrectomy. Associations between anaesthetic parameters and outcomes were evaluated with multivariable logistic regression and generalised estimating equation, respectively, adjusted for predictors of renal function after nephrectomy. Results: Before nephrectomy, 677 (21%) patients had moderate–severe chronic kidney disease. A quarter of patients (n = 809) had postoperative AKI and 35% (n = 746) had Stage ≥3 chronic kidney disease 12‐months after surgery. Only 12% of patients (n = 386) had >5 min of intraoperative hypotension. While not statistically significant, longer duration of intraoperative hypotension was associated with slightly higher rates of AKI (odds ratio [OR] per 10‐min 1.14, 95% confidence interval [CI] 0.98, 1.32). Prolonged hypothermia was associated with increased rate of AKI (OR per 10‐min 1.02, 95% CI 1.00, 1.04), and decreased eGFR (change in eGFR per 10‐min −0.19, 95% CI −0.27, −0.12); however, these results have limited clinical significance. Conclusions: Under current practice, intraoperative anaesthetic parameters are tightly maintained, restricting the significance of their effect on postoperative renal function. Future studies should evaluate whether haemodynamic parameters during the early postoperative period, when they are monitored less frequently, are associated with renal functional outcome. [ABSTRACT FROM AUTHOR]

• Most renal tumors merely displace nephrons while others can obliterate/replace them. • Parenchymal volume replacement (PVR) by RCC negatively impacts preoperative GFR. • PVR correlates with aggressive tumor features and reduced recurrence-free survival. • PVR is a cost-effective, quantifiable, reproducible parameter. • PVR can improve oncologic risk stratification and counseling for RCC patients. Most renal tumors merely displace nephrons while others can obliterate parenchyma in an invasive manner. Substantial parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) may have oncologic implications; however, studies regarding PVR remain limited. Our objective was to evaluate the oncologic implications associated with PVR using improved methodology including more accurate and objective tools. A total of 1,222 patients with non-metastatic renal tumors managed with partial nephrectomy (PN) or radical nephrectomy (RN) at Cleveland Clinic (2011-2014) with necessary studies were retrospectively evaluated. Parenchymal volume analysis via semiautomated software was used to estimate split renal function and preoperative parenchymal volumes. Using the contralateral kidney as a control, %PVR was defined: (parenchymal volume contralateral –parenchymal volume ipsilateral) normalized by parenchymal volume contralateral x100%. PVR was determined preoperatively and not altered by management. Patients were grouped by degree of PVR: minimal (<5%, N = 566), modest (5%-25%, N = 414), and prominent (≥25%, N = 142). Kaplan-Meier was used to evaluate survival outcomes relative to degree of PVR. Multivariable Cox-regression models evaluated predictors of recurrence-free survival (RFS). Of 1,122 patients, 801 (71%) were selected for PN and 321 (29%) for RN. Overall, median tumor size was 3.1 cm and 6.8 cm for PN and RN, respectively, and median follow-up was 8.6 years. Median %PVR was 15% (IQR = 6%-29%) for patients selected for RN and negligible for those selected for PN. %PVR correlated inversely with preoperative ipsilateral GFR (r = -0.49, P < 0.01) and directly with advanced pathologic stage, high tumor grade, clear cell histology, and sarcomatoid features (all P < 0.01). PVR≥25% associated with shortened recurrence-free, cancer-specific, and overall survival (all P < 0.01). Male sex, ≥pT3a, tumor grade 4, positive surgical margins, and PVR≥25% independently associated with reduced RFS (all P < 0.02). Obliteration of normal parenchyma by RCC substantially impacts preoperative renal function and patient selection. Our data suggests that increased PVR is primarily driven by aggressive tumor characteristics and independently associates with reduced RFS, although further studies will be needed to substantiate our findings. [ABSTRACT FROM AUTHOR]

Bacillus Calmette-Guerin (BCG) has been the gold-standard intravesical agent for the management of intermediate and high-risk non-muscle invasive bladder cancer (NMIBC). However, the presence of variant histology (VH) in NMIBC patients is considered an especially high-risk feature for which up-front radical cystectomy (RC) should be offered. Limited data exists on oncologic outcomes in NMIBC patients with VH who are managed with intravesical therapy. Therefore, the goal of the present study was to examine oncologic outcomes for NMIBC with VH managed with intravesical therapy at a high-volume tertiary care center. A retrospective review of an IRB-approved bladder cancer database was performed. Patients with a history of NMIBC with VH present on transurethral resection of bladder tumor (TURBT) treated with either BCG or chemotherapy were identified. Patients were required to have underwent both initial and a restaging TURBT and had re-review of pathology specimens by a fellowship-trained genitourinary pathologist. If multiple variants were present, the variant to have the highest percentage present in the specimen was recorded. The primary outcome was recurrence within the bladder (bladder RFS), which was defined as any evidence of recurrence on cystoscopy that was confirmed on TURBT. Other endpoints included progression to muscle invasive disease (MIBC RFS) and metastasis free survival (MFS). Survival time was defined from date of initiation of intravesical therapy to date of event or censoring. The Kaplan-Meier method with log rank was used to estimate oncologic outcomes among the various VH sub-populations. Ninety patients were included for the final analysis with a median follow-up of 38 months. The following VHs were included: glandular (26%), squamous differentiation (26%), giant cell (15%), micropapillary (13%), nested (9%), plasmacytoid (7%), sarcomatoid (2%), and lymphoepithelioma-like (2%). The majority of patients had T1 disease (72%) and received BCG (83%). At 5 years, 48 patients (53%) had experienced a recurrence with a median RFS of 24 months (95% Confidence Interval: 2-46 months). Five-year rates of progression to MIBC or metastasis were low at 14%. When stratifying by VH, patients with sarcomatoid or plasmacytoid had significantly worse oncologic outcomes, which is consistent with prior literature. Twenty-six patients (29%) proceeded to radical cystectomy with cystectomy free survival of 14 months (95% CI: 7-24 months). In a series of highly selected patients with NMBIC and VH, bladder-sparing treatment with intravesical therapy demonstrated acceptable oncologic outcomes for most VH. Therefore, through shared medical decision making, this may be a possible treatment alternative for NMIBC patients who are not suitable cystectomy candidates or who would prefer to pursue bladder-sparing treatment. [ABSTRACT FROM AUTHOR]

Radical cystectomy is the gold standard treatment for muscle-invasive bladder cancer, and neoadjuvant chemotherapy (NAC) with cisplatin-based regimens can improve outcomes. However, administering NAC to patients with borderline estimated glomerular filtration rates (eGFR) poses challenges, often leading to dose modification or early discontinuation. Prior studies have indicated that serum creatinine-based glomerular filtration rate (GFR) calculations may over-estimate renal function in non-weight bearing patients with reduced muscle mass. Given the prevalence of sarcopenia among bladder cancer patients, we hypothesized that Cr-based GFR estimations may overestimate renal function in patients with diminished muscle mass, potentially leading to an increased incidence of NAC dose modification or early discontinuation. We retrospectively reviewed patients who underwent radical cystectomy with borderline preoperative eGFR (40-59 mL/min/1.73 m2) between 2010-2022 at our institution. Sarcopenia was determined using computed tomography scans (figure 1) and validated criteria according to the gender-specific cutoff values of skeletal muscle index (SMI) and skeletal muscle density (SMD). The incidence of NAC dose modification or early discontinuation was evaluated along with patient demographics and outcome measures. 140 patients who underwent radical cystectomy in our cohort and were noted to have borderline eGFR were included in our final analyses. The median patient age was 70.7 years. Among radical cystectomy patients with borderline eGFR, 81.4% (114/140) had clinical parameters diagnostic of sarcopenia on computed tomography. Only 44.3% (62/140) of patients received neoadjuvant chemotherapy of which 53/62 were sarcopenic. In this patient cohort, lower;SMD was significantly associated with NAC completion that required dose reduction or medication changes (e.g. cisplatin to carboplatin, p=0.03397). For patients that did not complete their chemotherapy regimen, the number of cycles completed was not dependent on age, BMI, presence of comorbidities (diabetes;and/or hypertension), eGFR, or SMI. Sarcopenia is highly prevalent in patients with borderline renal function and muscle-invasive bladder cancer undergoing radical cystectomy. Lower skeletal muscle density was significantly associated with a greater likelihood of dose reduction in chemotherapy regimen or change in medication (e.g. cisplatin to carboplatin) in this cohort. Further research is needed to validate these findings and explore the impact of sarcopenia on GFR calculations and determining cisplatin eligibility in this patient population. [ABSTRACT FROM AUTHOR]

• At a high-volume tertiary care referral center, non-muscle invasive bladder cancer (NMIBC) with a diverse array of divergent differentiation or variant histology had comparable oncologic outcomes when treated with intravesical BCG or chemotherapy. • Known aggressive variants such as plasmacytoid, sarcomatoid, and micropapillary had poorer outcomes and should always be offered upfront radical cystectomy. • For all other variant histologies, it may feasible to trial a bladder sparing approach if cystectomy is contraindicated or patient does not wish to pursue. There is limited data on oncologic outcomes in nonmuscle invasive bladder cancer (NMIBC) with variant histology (VH) managed with intravesical therapy. We sought to evaluate oncologic outcomes for this cohort at a high-volume center. A retrospective review of an IRB-approved bladder cancer database was performed. Patients with a history of NMIBC with VH present on transurethral resection of bladder tumor (TURBT) treated with intravesical therapy (BCG or chemotherapy) were identified. Outcomes of interest included recurrence within the bladder, progression to muscle-invasive bladder cancer (MIBC), metastatic progression, cancer-specific, and overall survival. Survival time was computed from the date of initiation of intravesical therapy to the date of event or censoring. For patients who underwent radical cystectomy, recurrence-free, cancer-specific, and overall survival were also computed. The Kaplan-Meier method with log rank was utilized to compare survival time between VH sub-groups. Ninety patients were included in the final cohort with a median follow-up of 38 months. The majority of patients had T1 disease (72%) and received intravesical BCG (83%) as their only form of intravesical therapy. The most commonly represented VH in this series were glandular and squamous differentiation (26%). Forty-eight patients (53%) experienced recurrence within the bladder with a median recurrence-free survival of 24 months (95% Confidence Interval [CI]: 2–46 months). Five-year rates of progression to MIBC and distant metastasis were both 14% respectively. Twenty-six patients (28%) eventually required cystectomy. When stratifying by VH, patients with sarcomatoid, plasmacytoid, and micropapillary had significantly worse oncologic outcomes. In this series of highly-selected patients with NMIBC and VH, bladder-sparing treatment with intravesical therapy demonstrated acceptable oncologic outcomes for most VHs. This may be an acceptable treatment option for patients without plasmacytoid, sarcomatoid, or micropapillary features who are not suitable cystectomy candidates or who prioritize bladder-sparing treatment. [ABSTRACT FROM AUTHOR]

Background: Myeloid derived suppressor cells (MDSC) are heterogeneous immunosuppressive cells with potential predictive and prognostic roles in cancer. The association between MDSC, clinicopathologic factors, and pathologic response in patients with bladder urothelial carcinoma (UC) was explored.Methods: Peripheral blood or tissue were collected from patients with UC undergoing definitive surgery. MDSCs levels were measured in peripheral blood mononuclear cells and fresh tumor tissue. MDSCs were identified by flow cytometry and defined as total MDSC (T-MDSC) CD33+/HLADR-. From this population, 3 subsets were identified: polymorphonuclear-MDSC (PMN-MDSC) defined as CD33+/HLADR-/CD15+/CD14-, monocytic-MDSC (M-MDSC) defined as CD33+/HLADR-/CD15-/CD14+, and immature-MDSC (I-MDSC) defined as CD33+/HLADR-/CD15-/CD14-. MDSC populations were presented as % of live nucleated blood cells. Spearman correlations (r) and Wilcoxon rank sum test were used to assess correlations between MDSC populations, clinicopathologic factors, and pathologic complete response (pCR).Results: 85 patients scheduled to undergo cystectomy from February 2015 through Dec 2016 were included. All patients had blood drawn for analysis and 23 patients had residual tumor tissue collected for analysis at the time of surgery. Of these 85, 74 (87%) were men with a median age at diagnosis of 68 (range: 44-87). Pure UC was the most common histology (75%); 28 (35%) patients had prior treatment with intravesical therapy and 36 (42%) were treated with neoadjuvant chemotherapy, primarily gemcitabine plus cisplatin (n = 24). On surgical pathology, 18 (21%) of the patients had pCR, 11 (13%) had positive lymph nodes, and 20 patients (24%) had lymphovascular invasion. Statistically significant associations were found between circulating MDSC levels and pCR rates (P<0.01), absolute neutrophil-lymphocyte ratio (P = 0.008), and histology (P = 0.01). Tumor % M-MDSCs were negatively associated with lymphovascular invasion (P = 0.04). There were no significant correlations between peripheral blood mononuclear cells and tumor MDSC subtypes.Conclusions: Blood and tissue MDSC levels correlate with several clinicopathologic factors and may predict for pCR. Future studies are needed to highlight the role of MDSC in predicting long-term outcomes and to determine the clinical implications of these findings. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between absence of disease on confirmatory biopsy and risk of pathologic reclassification in men on active surveillance (AS).Materials and Methods: Men with grade groups 1 and 2 disease on AS between 2002 and 2015 were identified who received a confirmatory biopsy within 1 year of diagnosis and ≥3 biopsies overall. The primary outcomes were pathologic reclassification by grade (any increase in primary Gleason pattern or Gleason score) or volume (>33% of sampled cores involved or increase in the number of cores with >50% involvement). The effect of a negative confirmatory biopsy survival was evaluated using Kaplan-Meier analysis and a Cox proportional hazards modeling.Results: Out of 635 men, 224 met inclusion criteria (median follow-up: 55.8 months). A total of 111 men (49.6%) had a negative confirmatory biopsy. Decreased grade reclassification (69.7% vs 83.9%; P = .01) and volume reclassification (66.3% vs 87.4%; P = .004) was seen at 5 years for men with a negative confirmatory biopsy compared with those with a positive biopsy. On adjusted analysis, a negative confirmatory biopsy was associated with a decreased risk of grade reclassification (hazard ratio, 0.51; 95% confidence interval, 0.28-0.94; P = .03) and volume reclassification (hazard ratio, 0.32; 95% confidence interval, 0.17-0.61; P = .0006) at a median of 4.7 years.Conclusion: Absence of cancer on the confirmatory biopsy is associated with a significant decrease in rate of grade and volume reclassification among men on AS. This information may be used to better counsel men on AS. [ABSTRACT FROM AUTHOR]