Continuous flow local anesthetic wound infusion for post-operative analgesia following kidney transplantation.

BACKGROUND: Some patients with end stage renal disease are or will become narcotic-dependent. Chronic narcotic use is associated with increased graft loss and mortality following kidney transplantation. We aimed to compare the efficacy of continuous flow local anesthetic wound infusion pumps (CFLAP) with patient controlled analgesia pumps (PCA) in reducing inpatient narcotic consumption in patients undergoing kidney transplantation. MATERIALS AND METHODS: In this single-center, retrospective analysis of patients undergoing kidney transplantation, we collected demographic and operative data, peri-operative outcomes, complications, and inpatient oral morphine milligram equivalent (OME) consumption. RESULTS: Four hundred and ninety-eight patients underwent kidney transplantation from 2020 to 2022. 296 (59%) historical control patients received a PCA for postoperative pain control and the next 202 (41%) patients received a CFLAP. Median age [53.5 vs. 56.0 years, p = .08] and BMI [29.5 vs. 28.9 kg/m2, p = .17] were similar. Total OME requirement was lower in the CFLAP group [2.5 vs. 34 mg, p < .001]. Wound-related complications were higher in the CFLAP group [5.9% vs. 2.7%, p = .03]. Two (.9%) patients in the CFLAP group experienced cardiac arrhythmia due to local anesthetic toxicity and required lipid infusion. CONCLUSIONS: Compared to PCA, CFLAP provided a 93% reduction in OME consumption with a small increase in the wound-related complication rate. The utility of local anesthetic pumps may also be applicable to patients undergoing any unilateral abdominal or pelvic incision.

A Comprehensive Review of the Current State of Robot-assisted Laparoscopic Salvage Prostatectomy.

BACKGROUND AND OBJECTIVE: Salvage robot assisted radical prostatectomy (sRARP) is performed for patients with biochemical or biopsy proven, localized prostate cancer recurrences after radiation or ablative therapies. Traditionally, sRARP has been avoided by lower volume surgeons due to technical demand and high complication rates. Post-radiation sRARP outcomes studies exist but remain few in number. With increasing use of whole gland and focal ablative therapies, updates on sRARP in this setting are needed. The aim of this narrative review is to provide an overview of recently reviewed studies on the oncologic outcomes, functional outcomes, and complications after post-radiation and post-ablative sRARP. Tips and tricks are provided to guide surgeons who may perform sRARP. MATERIALS AND METHODS: We performed a non-systematic literature search of PubMed and MEDLINE for the most relevant articles pertaining to the outlined topics from 2010-2022 without limitation on study design. Only case reports, editorial comments, letters, and manuscripts in non-English languages were excluded. Key Content and Findings: Salvage robotic radical prostatectomy is performed in cases of biochemical recurrence after radiation or ablative therapies. Oncologic outcomes after sRARP are worse compared to primary surgery (pRARP) though improvements have been made with the robotic approach when compared to open salvage prostatectomy. Higher pre-sRARP PSA levels and more advanced pathologic stage portend worse oncologic outcomes. Patients meeting low-risk, EAU-biochemical recurrence criteria have improved oncologic outcomes compared to those with high-risk BCR. While complication rates in sRARP are higher compared to pRARP, Retzius sparing approaches may reduce complication rates, particularly rectal injuries. In comparison to the traditional open approach, sRARP is associated with a lower rate of bladder neck contracture. In terms of functional outcomes, potency rates after sRARP are poor and continence rates are low, though Retzius sparing approaches demonstrate acceptable recovery of urinary continence by 1 year, post-operatively. CONCLUSIONS: Advances in the robotic platform and improvement in robotic experience have resulted in acceptable complication rates after sRARP. However, oncologic and functional outcomes after sRARP in both the post-radiation and post-ablation settings are worse compared to pRARP. Thus, when engaging in shared decision making with patients regarding the initial management of localized prostate cancer, patients should be educated regarding oncologic and functional outcomes and complications in the case of biochemically recurrent prostate cancer that may require sRARP.

Less is more: single dose versus extended antibiotic prophylaxis for transperineal prostate biopsy.

INTRODUCTION: There is an ongoing debate as to the appropriate regimen of antibiotic prophylaxis with transperineal (TP) biopsy. The objective of this study was to report the rate of infection following TP biopsy at a high-volume institution and assess the impact of single dose antibiotics at the time of biopsy versus outpatient antibiotics in preventing postprocedural infections. MATERIALS AND METHODS: Records of men undergoing TP prostate biopsy from 2012 to 2022 were reviewed. Patients were divided into two groups, those who received single dose intravenous (IV) antibiotics at the time of biopsy (n = 440) and those who received both IV antibiotics at the time of biopsy and outpatient antibiotics before/after biopsy (n = 327). Post biopsy infection was defined as at least one of the following: fever (≥ 38.3°C) with/without symptoms of urinary tract infection or positive urine culture (> 105 colony forming units) within 72 hours post biopsy. The rates of infection were compared between the two groups. RESULTS: A total of 767 biopsies were included in the study. Infection rate post TP biopsy was 1.83% (n = 14). The infection rate for patients with single dose prophylaxis was 2.05% (n = 9) and 1.53% (n = 5) for those that received the extended antibiotic regimen. No significant difference in infection rates between the different antibiotic regimens was found (p = 0.597). CONCLUSIONS: Overall rates of infection after TP prostate biopsy are very low. Our data indicate that single dose and extended regimen of antibiotic prophylaxis show similar infection rates. These findings support antibiotic stewardship and encourage further research into the appropriate regimen of prophylaxis for TP prostate biopsy.

Syntaxin 6-mediated exosome secretion regulates enzalutamide resistance in prostate cancer.

Prostate cancer (PCa) deaths are typically the result of metastatic castration-resistant PCa (mCRPC). Recently, enzalutamide (Enz), an oral androgen receptor inhibitor, was approved for treating patients with mCRPC. Invariably, all PCa patients eventually develop resistance against Enz. Therefore, novel strategies aimed at overcoming Enz resistance are needed to improve the survival of PCa patients. The role of exosomes in drug resistance has not been fully elucidated in PCa. Therefore, we set out to better understand the exosome's role in the mechanism underlying Enz-resistant PCa. Results showed that Enz-resistant PCa cells (C4-2B, CWR-R1, and LNCaP) secreted significantly higher amounts of exosomes (2-4 folds) compared to Enz-sensitive counterparts. Inhibition of exosome biogenesis in resistant cells by GW4869 and dimethyl amiloride strongly decreased their cell viability. Mechanistic studies revealed upregulation of syntaxin 6 as well as its increased colocalization with CD63 in Enz-resistant PCa cells compared to Enz-sensitive cells. Syntaxin 6 knockdown by specific small interfering RNAs in Enz-resistant PCa cells (C4-2B and CWR-R1) resulted in reduced cell number and increased cell death in the presence of Enz. Furthermore, syntaxin 6 knockdown significantly reduced the exosome secretion in both Enz-resistant C4-2B and CWR-R1 cells. The Cancer Genome Atlas analysis showed increased syntaxin 6 expressions associated with higher Gleason score and decreased progression-free survival in PCa patients. Importantly, IHC analysis showed higher syntaxin 6 expression in cancer tissues from Enz-treated patients compared to Enz naïve patients. Overall, syntaxin 6 plays an important role in the secretion of exosomes and increased survival of Enz-resistant PCa cells.

Neoadjuvant Chemotherapy is Not Associated with Adverse Perioperative Outcomes after Robot-Assisted Radical Cystectomy: A Case for Increased Use from the IRCC.

PURPOSE: We sought to determine the trend of neoadjuvant chemotherapy use for nonmetastatic muscle invasive urothelial bladder cancer and whether it is associated with adverse perioperative morbidity after robot-assisted radical cystectomy. MATERIALS AND METHODS: We retrospectively reviewed the IRCC (International Robotic Cystectomy Consortium) database between 2006 and 2017. After excluding patients with nonmuscle invasive bladder cancer the patients were divided into 2 groups, including those who did vs did not receive neoadjuvant chemotherapy. Data were reviewed for demographics, preoperative, operative and 90-day perioperative outcomes. We used the Cochran-Armitage trend test to assess trends of neoadjuvant chemotherapy associations with high grade and overall complications with time. Multivariate stepwise regression analyses were done to determine whether neoadjuvant chemotherapy was associated with prolonged operative time, 90-day postoperative complications, readmissions, reoperations and mortality after robot-assisted radical cystectomy. RESULTS: A total of 298 patients (26%) received neoadjuvant chemotherapy. These patients were younger (age 67 vs 69 years, p=0.01) and more frequently had an ASA™ (American Society of Anesthesiologists™) score of 3 or greater (62% vs 55%, p=0.02) and pathological T3 stage or greater disease (28% vs 22%, p=0.04). The use of neoadjuvant chemotherapy increased significantly from 10% in 2006 to 2007 to 42% in 2016 to 2017 (p <0.01). On multivariate analysis neoadjuvant chemotherapy was not significantly associated with prolonged operative time, hospital stay, 90-day postoperative complications, reoperation or mortality. Neoadjuvant chemotherapy was associated with 90-day readmissions after robot-assisted radical cystectomy (OR 5.90, 95% CI 3.30-10.90, p <0.01). CONCLUSIONS: Neoadjuvant chemotherapy utilization has significantly increased in the last decade. It was not associated with perioperative surgical morbidity after robot-assisted radical cystectomy.

Selective clamping during robot-assisted partial nephrectomy in patients with a solitary kidney: is it safe and does it help?

OBJECTIVES: To obtain the most accurate assessment of the risks and benefits of selective clamping in robot-assisted partial nephrectomy (RAPN) we evaluated outcomes of this technique vs those of full clamping in patients with a solitary kidney undergoing RAPN. PATIENTS AND METHODS: Data from institutional review board-approved retrospective and prospective databases from 2006 to 2019 at multiple institutions with sharing agreements were evaluated. Patients with a solitary kidney were identified and stratified based on whether selective or full renal artery clamping was performed. Both groups were analysed with regard to demographics, risk factors, intra-operative complications, and postoperative outcomes using chi-squared tests, Fisher's exact tests, t-tests and Mann-Whitney U-tests. RESULTS: Our initial cohort consisted of 4112 patients, of whom 72 had undergone RAPN in a solitary kidney (51 with full clamping and 21 with selective clamping). There were no significant differences in demographics, tumour size, baseline estimated glomerular filtration rate (eGFR), or warm ischaemia time (WIT) between the groups (Table 1). Intra-operative outcomes, including estimated blood loss, operating time, and intra-operative complications were similar in the two groups. Short- and long-term postoperative percentage change in eGFR, frequency of acute kidney injury (AKI), and frequency of de novo chronic kidney disease (CKD) were also not significantly different between the two techniques. CONCLUSION: In a large cohort of patients with solitary kidney undergoing RAPN, selective clamping resulted in similar intra-operative and postoperative outcomes compared to full clamping and conferred no additional risk of harm. However, selective clamping did not appear to provide any functional advantage over full clamping as there was no difference observed in the frequency of AKI, CKD or change in eGFR. Short WIT in both groups (<15 min) may have prevented identification of benefits in the selective clamping group; a similar study analysing cases with longer WIT may elucidate any beneficial effects of selective clamping.

Do patients with Stage 3-5 chronic kidney disease benefit from ischaemia-sparing techniques during partial nephrectomy?

OBJECTIVE: To analyse whether selective arterial clamping (SAC) and off-clamp (OC) techniques during robot-assisted partial nephrectomy (RPN) are associated with a renal functional benefit in patients with Stage 3-5 chronic kidney disease (CKD). PATIENTS AND METHODS: The change in estimated glomerular filtration rate (eGFR) over time was compared between 462 patients with baseline CKD 3-5 that underwent RPN with main arterial clamping (MAC) (n = 375, 81.2%), SAC (n = 48, 10.4%) or OC (n = 39, 8.4%) using a multivariable linear mixed-effects model. All follow-up eGFRs, including baseline and follow-up between 3 and 24 months, were included in the model for analysis. The median follow-up was 12.0 months (interquartile range 6.7-16.5; range 3.0-24.0 months). RESULTS: In the multivariable linear mixed-effects model adjusting for characteristics including tumour size and the R.E.N.A.L. (Radius; Exophytic/Endophytic; Nearness; Anterior/Posterior; Location) Nephrometry Score, the change in eGFR over time was not significantly different between SAC and MAC RPN (ß = -1.20, 95% confidence interval [CI] -5.45, 3.06; P = 0.582) and OC and MAC RPN (ß = -1.57, 95% CI -5.21, 2.08; P = 0.400). Only 20 (15 MAC, two SAC, three OC) patients overall had progression of their CKD stage at last follow-up. The mean ischaemia time was 17 min for MAC and 15 min for SAC. There was no benefit to SAC or OC in terms of blood loss, perioperative complications, length of stay, or surgical margins. CONCLUSION: SAC and OC techniques during RPN were not associated with benefit in preservation of eGFR in patients with baseline CKD.

A comparative propensity score-matched analysis of perioperative outcomes of intracorporeal vs extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

OBJECTIVE: To compare the perioperative outcomes of intracorporeal (ICUD) vs extracorporeal urinary diversion (ECUD) after robot-assisted radical cystectomy (RARC). PATIENTS AND METHODS: We retrospectively reviewed the prospectively maintained International Robotic Cystectomy Consortium (IRCC) database. A total of 972 patients from 28 institutions who underwent RARC were included. Propensity score matching was used to match patients based on age, gender, body mass index (BMI), American Society of Anesthesiologists Score (ASA) score, Charlson Comorbidity Index (CCI) score, prior radiation and abdominal surgery, receipt of neoadjuvant chemotherapy, and clinical staging. Matched cohorts were compared. Multivariate stepwise logistic and linear regression models were fit to evaluate variables associated with receiving ICUD, operating time, 90-day high-grade complications (Clavien-Dindo Classification Grade ≥III), and 90-day readmissions after RARC. RESULTS: Utilisation of ICUD increased from 0% in 2005 to 95% in 2018. The ICUD patients had more overall complications (66% vs 58%, P = 0.01) and readmissions (27% vs 17%, P = 0.01), but not high-grade complications (21% vs 24%, P = 0.22). A more recent RC era and ileal conduit diversion were associated with receiving an ICUD. Higher BMI, ASA score ≥3, and receiving a neobladder were associated with longer operating times. Shorter operating time was associated with male gender, older age, ICUD, and centres with a larger annual average RC volume. Longer intensive care unit stay was associated with 90-day high-grade complications. Higher CCI score, prior radiation therapy, neoadjuvant chemotherapy, and ICUD were associated with a higher risk of 90-day readmissions. CONCLUSIONS: Utilisation of ICUD has increased over the past decade. ICUD was associated with more overall complications and readmissions compared to ECUD, but not high-grade complications.

Management of low-risk prostate cancer in patients with enlarged glands and lower urinary tract symptoms: robotic total prostatectomy, a novel technique.

PURPOSE: Low-risk prostate cancer (PCa) is primarily managed with Active Surveillance (AS). A subset of these patients have significantly enlarged glands and lower urinary tract symptoms (LUTS) recalcitrant to medical therapy. Radical treatment in this patient population risks compromise to both erectile function and continence. Therefore, our primary aim is to introduce a novel surgical technique, robotic total prostatectomy (RTP), for the management of severely enlarged prostate hyperplasia with concomitant suspicion of low-risk prostate cancer. METHODS: After IRB approval and patient consultation/education, we performed RTP on 12 consecutive patients who presented with low-risk PCa and significantly enlarged prostate glands with LUTS. Inclusion criteria included patients with suspicion of low-risk malignancy, subjective/objective complaint of LUTS, and pre-operative prostate size > 60 g. Preoperative, perioperative and postoperative variables were studied in the following domains: surgical, oncologic, continence and erectile function. RESULTS: A total of 12 patients underwent RTP. Mean preoperative prostate volume and PSA was estimated at 96.96 g and 8.79, respectively. Surgical time, EBL and LOS was estimated at 180.8 min, 189.6 ml, and 2 days, respectively. Post-operative variables confirmed resolution of LUTS (mean PVR 41.78/IPSS 8.3) and efficient oncologic control (mean PSA 0.04), with minimal compromise of sexual function. 100% continence was achieved at 3 months. CONCLUSION: RTP is a novel, efficient surgical procedure for the treatment of patients with at-risk for low-grade malignancy and symptomatic LUTS in an enlarged gland. Expanding the indication to patients with low-risk malignancy, irrespective of prostate size may alleviate the adverse effects of radical treatment in this select subset of patients.

A novel Bayesian continuous piecewise linear log-hazard model, with estimation and inference via reversible jump Markov chain Monte Carlo.

We present a reversible jump Bayesian piecewise log-linear hazard model that extends the Bayesian piecewise exponential hazard to a continuous function of piecewise linear log hazards. A simulation study encompassing several different hazard shapes, accrual rates, censoring proportion, and sample sizes showed that the Bayesian piecewise linear log-hazard model estimated the true mean survival time and survival distributions better than the piecewsie exponential hazard. Survival data from Wake Forest Baptist Medical Center is analyzed by both methods and the posterior results are compared.

Ten-Year Oncologic Outcomes Following Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

PURPOSE: Radical cystectomy is the gold standard for nonmetastatic muscle invasive bladder cancer and for refractory nonmuscle invasive disease. Compared to open radical cystectomy, robot-assisted radical cystectomy has been shown to provide comparable early oncologic outcomes and improved perioperative outcomes. However, there is a paucity of data on long-term oncologic outcomes and concerns about a higher incidence of local recurrence after robot-assisted radical cystectomy. We report 10-year oncologic outcomes following robot-assisted radical cystectomy using a multinational database. MATERIALS AND METHODS: We retrospectively reviewed the prospective International Robotic Cystectomy Consortium database. Consecutive patients who underwent robot-assisted radical cystectomy 10 years ago or earlier were included in analysis. Data were reviewed for demographics, and perioperative, pathological and oncologic outcomes. Kaplan-Meier curves were used to depict recurrence-free, disease specific and overall survival. Multivariate stepwise Cox regression models were applied to identify variables associated with recurrence-free, disease specific and overall survival. RESULTS: We identified 446 patients with a median age of 67 years (IQR 59-76). Of the patients 10% received neoadjuvant chemotherapy, 51% experienced any complication, 23% had high grade complications and 4% died within 3 months of robot-assisted radical cystectomy. Disease was pT3 or greater in 43% of patients and pN+ in 24% while a positive soft tissue surgical margin was observed in 7%. At a median followup of 5 years (IQR 2-10, maximum 14) local and distant recurrence had developed in 15% and 29% of patients, respectively. Ten-year recurrence-free, disease specific and overall survival rates were 59%, 65% and 35%, respectively. Patients with pT3 or greater and pN+ disease showed worse recurrence-free, disease specific and overall survival. CONCLUSIONS: Long-term oncologic outcomes, and recurrence rates and patterns after robot-assisted radical cystectomy seem comparable to those in open series. Advanced disease stage and positive surgical margins remain the main determinants of survival after radical cystectomy.

A National Cancer Database-based nomogram to predict lymph node metastasis in penile cancer.

OBJECTIVE: To evaluate the predictive nature of several clinicopathological variables by developing a nomogram predictive for lymph node-positive disease using the National Cancer Database cohort of patients with squamous cell carcinoma of the penis. METHODS: Stepwise logistic regression was used to find the best-fit model; remaining clinical variables were used to create a nomogram to predict the probability of lymph node-positive disease. RESULTS: On multivariate analysis, high pathological grade (3-4 vs 1: odds ratio [OR] 3.27, 95% confidence interval [CI] 1.70-6.29; 2 vs 1: OR 2.58, 95% CI 1.39-4.79 [P = 0.002]), lymphovascular invasion (OR 2.49, 95% CI 1.61-3.84 [P < 0.001]), and positive clinical lymph node status (N1 vs N0: OR 20.0, 95% CI 11.4-35.7; N2 vs N0: OR 27.8, 95% CI 14.1-55.6; N3 vs N0: OR 49.2, 95% CI 14.8-162.8 [P < 0.001]) were predictors of lymph node metastasis in penile cancer. The bootstrap-corrected concordance index of this nomogram was 0.880. CONCLUSION: Using tumour grade, tumour lymphovascular invasion and clinical lymph node status, we developed a nomogram highly predictive of pathologial lymph node metastasis that, after further external validation, could be helpful in the surgical decision-making process.

Hypertension and diabetes mellitus are not associated with worse renal functional outcome after partial nephrectomy in patients with normal baseline kidney function.

OBJECTIVE: To analyze the association of hypertension and/or diabetes mellitus on renal function after partial nephrectomy in patients with normal baseline kidney function. METHODS: We identified 453 patients with baseline estimated glomerular filtration rate ≥60 that underwent robotic partial nephrectomy for a cT1 renal mass from 2008 to 2014 using a multi-institutional database. The association between estimated glomerular filtration rate and time (pre-partial nephrectomy to 24 months post-partial nephrectomy) was compared between 269 (59.4%) patients with preoperative hypertension and/or diabetes mellitus and 184 (40.6%) patients with neither hypertension nor diabetes mellitus using a multivariable model adjusting for confounders. RESULTS: The estimated glomerular filtration rate significantly decreased over time for both groups compared with baseline (average units/month: 1.8974 hypertension/diabetes mellitus, 1.2163 no hypertension/diabetes mellitus; P < 0.0001), and the estimated glomerular filtration rate decrease per month reduced over time (P < 0.0001). The estimated glomerular filtration rate began to increase at approximately 12 months for the hypertension/diabetes mellitus group, and at approximately 18 months for the no hypertension/diabetes mellitus group. Although a greater initial decline in the estimated glomerular filtration rate after partial nephrectomy was observed for the hypertension/diabetes mellitus group (0.68 units/month), this was not statistically significant (P = 0.0842); and while the rate of recovery from this decline was faster for the hypertension/diabetes mellitus group, this also was not statistically significant (P = 0.0653). The predicted estimated glomerular filtration rate was similar (83 mL/min/1.73 m2 ) for both groups 24 months after partial nephrectomy. CONCLUSIONS: There seems to be no significant association between hypertension, diabetes mellitus and renal functional outcome after partial nephrectomy in patients with normal baseline glomerular filtration rate. Renal function declines after partial nephrectomy, but then it recovers, irrespective of the presence of hypertension or diabetes mellitus.

Exosomes secreted by placental stem cells selectively inhibit growth of aggressive prostate cancer cells.

The current paradigm in the development of new cancer therapies is the ability to target tumor cells while avoiding harm to noncancerous cells. Furthermore, there is a need to develop novel therapeutic options against drug-resistant cancer cells. Herein, we characterized the placental-derived stem cell (PLSC) exosomes (PLSCExo) and evaluated their anti-cancer efficacy in prostate cancer (PCa) cell lines. Nanoparticle tracking analyses revealed the size distribution (average size 131.4 ±â€¯0.9 nm) and concentration of exosomes (5.23 × 1010±1.99 × 109 per ml) secreted by PLSC. PLSCExo treatment strongly inhibited the viability of enzalutamide-sensitive and -resistant PCa cell lines (C4-2B, CWR-R1, and LNCaP cells). Interestingly, PLSCExo treatment had no effect on the viability of a non-neoplastic human prostate cell line (PREC-1). Mass spectrometry (MS) analyses showed that PLSCExo are loaded with 241 proteins and mainly with saturated fatty acids. Further, Ingenuity Pathway Analysis analyses of proteins loaded in PLSCExo suggested the role of retinoic acid receptor/liver x receptor pathways in their biological effects. Together, these results suggest the novel selective anti-cancer effects of PLSCExo against aggressive PCa cells.

Outcomes of Intracorporeal Urinary Diversion after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

PURPOSE: This study aimed to provide an update and compare perioperative outcomes and complications of intracorporeal and extracorporeal urinary diversion following robot-assisted radical cystectomy using data from the multi-institutional, prospectively maintained International Robotic Cystectomy Consortium database. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,125 patients from a total of 26 institutions. Intracorporeal urinary diversion was compared with extracorporeal urinary diversion. Multivariate logistic regression models using stepwise variable selection were fit to evaluate preoperative, operative and postoperative predictors of intracorporeal urinary diversion, operative time, high grade complications and 90-day hospital readmissions after robot-assisted radical cystectomy. RESULTS: In our cohort 1,094 patients (51%) underwent intracorporeal urinary diversion. These patients demonstrated shorter operative time (357 vs 400 minutes), less blood loss (300 vs 350 ml) and fewer blood transfusions (4% vs 19%, all p <0.001). They experienced more high grade complications (13% vs 10%, p = 0.02). Intracorporeal urinary diversion use increased from 9% of all urinary diversions in 2005 to 97% in 2015. Complications after this procedure decreased significantly with time (p <0.001). On multivariable analysis higher annual cystectomy volume (OR 1.02, 95% CI 1.01-1.03, p <0.002), year of robot-assisted radical cystectomy (2013-2016 OR 68, 95% CI 44-105, p <0.001) and American Society of Anesthesiologists® score less than 3 (OR 1.75, 95% CI 1.38-2.22, p <0.001) were associated with undergoing intracorporeal urinary diversion. The procedure was associated with a shorter operative time of 27 minutes (p = 0.001). CONCLUSIONS: The use of intracorporeal urinary diversion has increased in the last decade. A higher annual institutional volume of robot-assisted radical cystectomy was associated with intracorporeal urinary diversion as well as with shorter operative time. Although intracorporeal urinary diversion was associated with higher grade complications than extracorporeal urinary diversion, they decreased with time.

Robot-assisted partial nephrectomy for large renal masses: a multi-institutional series.

OBJECTIVES: To compare peri-operative outcomes after robot-assisted partial nephrectomy (RAPN) for cT2a (7 to <10 cm) to cT1 tumours. MATERIALS AND METHODS: Patients with a cT1a (n = 1 358, 76.4%), cT1b (n = 379, 21.3%) or cT2a (n = 41, 2.3%) renal mass were identified from a multi-institutional RAPN database. Intra- and postoperative outcomes were compared for cT2a masses vs cT1a and cT1b masses using multivariable regression models (linear, logistic, Poisson etc.), adjusting for operating surgeon and a modified R.E.N.A.L. nephrometry score that excluded the radius component. RESULTS: The median sizes for cT1a, cT1b and cT2a tumours were 2.5, 5.0 and 8.0 cm, respectively (P < 0.001) with modified R.E.N.A.L. nephrometry scores being 6.0, 6.5 and 7.0, respectively (cT1a, P < 0.001; cT1b, P = 0.105). RAPN for cT2a vs cT1a masses was associated with a 12% increase in operating time (P < 0.001), a 32% increase in estimated blood loss (P < 0.001), a 7% increase in ischaemia time (P = 0.008), a 3.93 higher odds of acute kidney injury at discharge (95% confidence interval [CI] 1.33, 8.76; P = 0.009) and a higher risk of recurrence (hazard ratio [HR] 10.9, 95% CI 1.31, 92.2; P = 0.027). RAPN for cT2a vs cT1b masses was associated with a 12% increase in blood loss (P = 0.036), a 5% increase in operating time (P = 0.062) and a marginally higher risk of recurrence (HR 11.2, 95% CI 0.77, 11.5; P = 0.059). RAPN for cT2a tumours was not associated with differences in complications (cT1a, P = 0.535; cT1b, P = 0.382), positive margins (cT1a, P = 0.972; cT1b, P = 0.681), length of stay (cT1a, P = 0.507; cT1b, P = 0.513) or renal function decline up to 24 months post-RAPN (cT1a, P = 0.124; cT1b, P = 0.467). CONCLUSION: For T2a tumours RAPN is a feasible treatment option in a select patient population when performed by experienced surgeons in institutions equipped to manage postoperative complications. Although RAPN was associated with greater blood loss and longer operating and ischaemia time in T2a tumours, it was not associated with greater complication or positive surgical margin rates compared with T1 tumours. Renal function preservation rates were equivalent for up to 24 months postoperatively; however, 12-month recurrence-free survival was significantly lower in the T2a group. Extended follow-up is required to further evaluate long-term survival.

JC polyoma viruria associates with protection from chronic kidney disease independently from apolipoprotein L1 genotype in African Americans.

Background: Viral infections can trigger chronic kidney disease (CKD) and the urine virome may inform risk. The Natural History of APOL1-Associated Nephropathy Study (NHAANS) reported that urine JC polyomavirus (JCPyV) associated with a lower risk of APOL1-associated nephropathy in African Americans. Herein, association was assessed between urine JCPyV with CKD in African Americans independent from the APOL1 genotype. Methods: Quantitative polymerase chain reaction was performed for urinary detection of JCPyV and BK polyoma virus (BKPyV) in 200 newly recruited nondiabetic African Americans. A combined analysis was performed in these individuals plus 300 NHAANS participants. Results: In the 200 new participants, urine JCPyV was present in 8.8% of CKD cases and 45.8% of nonnephropathy controls (P = 3.0 × 10-8). In those with APOL1 renal-risk genotypes, JCPyV was detected in 5.1% of cases and 40.0% of controls (P = 0.0002). In those lacking APOL1 renal-risk genotypes, JCPyV was detected in 12.2% of cases and 48.8% of controls (P = 8.5 × 10-5). BKPyV was detected in 1.3% of cases and 0.8% of controls (P = 0.77). In a combined analysis with 300 NHAANS participants (n = 500), individuals with urine JCPyV had a 63% lower risk of CKD compared with those without urine JCPyV (odds ratio 0.37; P = 4.6 × 10-6). RNA fluorescence in situ hybridization confirmed the presence of JCPyV genomic DNA and JCPyV messenger RNA (mRNA) in nondiseased kidney. Conclusions: Inverse relationships exist between JCPyV viruria and non-diabetic CKD. Future studies should determine whether renal inflammation associated with CKD is less permissive for JCPyV reactivation/replication or whether JCPyV is a marker of reduced host immune responsiveness that diminishes immune pathologic contributions to CKD.

Nonhuman primate model of persistent erectile and urinary dysfunction following radical prostatectomy: Feasibility of minimally invasive therapy.

OBJECTIVE: Persistent urinary incontinence (UI) and/or erectile dysfunction (ED) occur in 30-50% of post-radical prostatectomy patients regardless of nerve sparing approaches. Identification of potential treatment options for these patients will require testing in an animal model that develops these chronic conditions. The objective was to characterize a nonhuman primate (NHP) model of persistent post-prostatectomy ED and UI and then test the feasibility of periurethral injection of the chemokine CXCL-12. METHODS: Ten adult male cynomolgus monkeys were used. Two were used for study of normal male nonhuman primate genitourinary anatomy. Five were used for measures of sexual behavior, peak intra-corporal pressure (ICP), abdominal leak point pressures (ALPP) 3 and 6-months post open radical prostatectomy (ORP). Three additional ORP animals received ultrasound-guided peri-urethral injection of chemokine CXCL12 6 weeks after ORP, and UI/ED evaluated for up to 3 months. RESULTS: The anatomy, innervation, and vascular supply to the prostate and surrounding tissues of these male NHPs are substantially similar to those of human beings. ORP resulted in complete removal of the prostate gland along with both neurovascular bundles and seminal vesicles while permitting stable restoration of vesico-urethral patency. ORP produced sustained (6 months) decreases in ALPP, ICP's, and sexual function. Transurethral injection of chemokine CXCL12 was feasible and had beneficial effects on erectile and urinary function. CONCLUSIONS: ORP in NHPs produced persistent erectile and urinary tract dysfunction. Periurethral injection of CXCL-12 was feasible and improved both urinary incontinence and erectile dysfunction and suggests that this model can be used to test new approaches for both conditions.

APOL1 Renal-Risk Variants Induce Mitochondrial Dysfunction.

APOL1 G1 and G2 variants facilitate kidney disease in blacks. To elucidate the pathways whereby these variants contribute to disease pathogenesis, we established HEK293 cell lines stably expressing doxycycline-inducible (Tet-on) reference APOL1 G0 or the G1 and G2 renal-risk variants, and used Illumina human HT-12 v4 arrays and Affymetrix HTA 2.0 arrays to generate global gene expression data with doxycycline induction. Significantly altered pathways identified through bioinformatics analyses involved mitochondrial function; results from immunoblotting, immunofluorescence, and functional assays validated these findings. Overexpression of APOL1 by doxycycline induction in HEK293 Tet-on G1 and G2 cells led to impaired mitochondrial function, with markedly reduced maximum respiration rate, reserve respiration capacity, and mitochondrial membrane potential. Impaired mitochondrial function occurred before intracellular potassium depletion or reduced cell viability occurred. Analysis of global gene expression profiles in nondiseased primary proximal tubule cells from black patients revealed that the nicotinate phosphoribosyltransferase gene, responsible for NAD biosynthesis, was among the top downregulated transcripts in cells with two APOL1 renal-risk variants compared with those without renal-risk variants; nicotinate phosphoribosyltransferase also displayed gene expression patterns linked to mitochondrial dysfunction in HEK293 Tet-on APOL1 cell pathway analyses. These results suggest a pivotal role for mitochondrial dysfunction in APOL1-associated kidney disease.