[Show abstract][Hide abstract] ABSTRACT: To address the need to study frozen clinical specimens using next-generation RNA, DNA, chromatin immunoprecipitation (ChIP) sequencing and protein analyses, we developed a bio-bank work flow to prospectively collect biospecimens from patients with renal cell carcinoma (RCC). We describe our standard operating procedures and work flow to annotate pathologic results and clinical outcomes. We report quality control outcomes and nucleic acid yields of our RCC submissions (N=16) to The Cancer Genome Atlas (TCGA) project, as well as newer discovery platforms, by describing mass spectrometry analysis of albumin oxidation in plasma and 6 ChIP sequencing libraries generated from nephrectomy specimens after histone H3 lysine 36 trimethylation (H3K36me3) immunoprecipitation. From June 1, 2010, through Janu-ary 1, 2013, we enrolled 328 patients with RCC. Our mean (SD) TCGA RNA integrity numbers (RINs) were 8.1 (0.8) for papillary RCC, with a 12.5% overall rate of sample disqualification for RIN <7. Banked plasma had significantly less albumin oxidation (by mass spectrometry analysis) than plasma kept at 25°C (P<.001). For ChIP sequencing, the FastQC score for average read quality was at least 30 for 91% to 95% of paired-end reads. In parallel, we analyzed frozen tissue by RNA sequencing; after genome alignment, only 0.2% to 0.4% of total reads failed the default quality check steps of Bowtie2, which was comparable to the disqualification
[Show abstract][Hide abstract] ABSTRACT: Mutations in SETD2, a histone H3 lysine trimethyltransferase, have been identified in clear cell renal cell carcinoma (ccRCC); however it is unclear if loss of SETD2 function alters the genomic distribution of histone 3 lysine 36 trimethylation (H3K36me3) in ccRCC. Furthermore, published epigenomic profiles are not specific to H3K36me3 or metastatic tumors. To determine if progressive SETD2 and H3K36me3 dysregulation occurs in metastatic tumors, H3K36me3, SETD2 copy number (CN) or SETD2 mRNA abundance was assessed in two independent cohorts: metastatic ccRCC (n=71) and the Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma data set (n=413). Although SETD2 CN loss occurs with high frequency (>90%), H3K36me3 is not significantly impacted by monoallelic loss of SETD2. H3K36me3-positive nuclei were reduced an average of ~20% in primary ccRCC (90% positive nuclei in uninvolved vs 70% positive nuclei in ccRCC) and reduced by ~60% in metastases (90% positive in uninvolved kidney vs 30% positive in metastases) (P<0.001). To define a kidney-specific H3K36me3 profile, we generated genome-wide H3K36me3 profiles from four cytoreductive nephrectomies and SETD2 isogenic renal cell carcinoma (RCC) cell lines using chromatin immunoprecipitation coupled with high-throughput DNA sequencing and RNA sequencing. SETD2 loss of methyltransferase activity leads to regional alterations of H3K36me3 associated with aberrant RNA splicing in a SETD2 mutant RCC and SETD2 knockout cell line. These data suggest that during progression of ccRCC, a decline in H3K36me3 is observed in distant metastases, and regional H3K36me3 alterations influence alternative splicing in ccRCC.Oncogene advance online publication, 22 June 2015; doi:10.1038/onc.2015.221.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this article was to review the relationship of postoperative CO2 levels to the risk of complications after radical cystectomy. In this review, we summarize the existing body of literature on the topic as well as metabolic complications after urinary diversion. Currently, there are no studies that specifically examine CO2 levels in the context of complications after radical cystectomy; therefore, we also present our own institutional data which demonstrate that a drop in postoperative CO2 levels is highly predictive of complications, the most common of which is failure to thrive. These data indicate that significant changes in CO2 levels prior to discharge after a radical cystectomy may be a harbinger of forthcoming complications.
Current Urology Reports 05/2015; 16(5):499. DOI:10.1007/s11934-015-0499-5 · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Image-based renal morphometry scoring systems are used to predict the potential difficulty of partial nephrectomy (PN), but they are centered entirely on tumor-specific factors and neglect other patient-specific factors that may complicate the technical aspects of PN. Adherent perinephric fat (APF) is one such factor known to make PN difficult.
To develop an accurate image-based nephrometry scoring system to predict the presence of APF encountered during robot-assisted partial nephrectomy (RAPN).
Design, setting, and participants
We prospectively analyzed 100 consecutive RAPNs performed by one surgeon and defined APF as the need for subcapsular renal dissection to isolate the renal tumor for RAPN.
Outcome measurements and statistical analysis
The scoring algorithm to predict the presence of APF was developed with a multivariable logistic regression model using a forward selection approach with a focus on improvement in the area under the receiver operating characteristic curve.
Results and limitations
Thirty patients (30%; 95% confidence interval, 21–40) had APF. Single-variable analysis noted an increased likelihood of APF in male patients (p < 0.001), higher body mass index (p = 0.003), greater posterior perinephric fat thickness (p < 0.001), greater lateral perinephric fat thickness (p < 0.001), and those with perirenal fat stranding (p < 0.001). Two of these variables, posterior perinephric fat thickness and stranding, were most highly predictive of APF in multivariable analysis and were therefore used to create a risk score, termed Mayo Adhesive Probability (MAP) and ranging from 0 to 5, to predict the presence of APF. We observed APF in 6% of patients with a MAP score of 0, 16% with a score of 1, 31% with a score of 2, 73% with a score of 3–4, and 100% of patients with a score of 5.
MAP score accurately predicts the presence of APF in patients undergoing RAPN. Prospective validation of the MAP score is required.
The Mayo Adhesive Probability score that we we developed is an accurate system that predicts whether or not adherent perinephric, or “sticky,” fat is present around the kidney that would make partial nephrectomy difficult.
European Urology 12/2014; 66(6). DOI:10.1016/j.eururo.2014.08.054 · 12.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To determine whether on-clamp partial nephrectomy (ON-PN) has any significant impact on long-term renal function in a two kidney model. Methods: From November 1999 to July 2013, 607 patients underwent partial nephrectomy at our institution. After excluding patients with solitary kidneys, multiple renal masses, and follow-up less than 90 days, 331 remained. Patient demographics were assessed, as was renal function based on pre- and postoperative MAG-3 renal scans and change in estimated glomerular filtration rate (eGFR) using the preoperative and most recent recorded creatinine levels. Results: There were a total of 236 patients who underwent ON-PN and 95 who underwent off-clamp partial nephrectomy (OFF-PN) during the study period. The longest follow-up was 12.6 years with mean follow-up of 3 years. Mean ischemia time of patients undergoing ON-PN was 25 minutes (ranging from 8 to 63 minutes). No differences were noted between the ON-PN and OFF-PN cohorts with respect to estimated change in eGFR (ON-PN: -6.07 mL/min/1.73 m2 vs OFF-PN: -6.00 mL/min/1.73 m2, p=0.69). No differences were noted in the % change in the MAG-3 renal scans (ON-PN: -0.77% vs OFF-PN: -1.1%, p=0.94). A post-hoc sensitivity analysis of the same two variables stratified by age revealed no differences in change in estimated GFR or % change in differential function on renal scan. Conclusions: In the two kidney model, ischemia does not appear to affect long-term renal function outcomes after partial nephrectomy. These data provide evidence that ON-PN is perfectly acceptable in the appropriately selected patient with two kidneys.
Journal of endourology / Endourological Society 09/2014; 29(4). DOI:10.1089/end.2014.0476 · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE To evaluate the long-term safety of a novel continuous infusion of ketorolac vs placebo after laparoscopic donor nephrectomy. METHODS We performed a secondary analysis of a previously reported randomized controlled trial conducted from October 7, 2008, to July 21, 2010. Patients aged 18-75 years received a continuous infusion of either ketorolac (treatment [n = 7]) or normal saline (control [n = 4]) for 24 hours immediately after laparoscopic donor nephrectomy. Serum creatinine levels were measured at 1- and 1.5-year follow-ups. Glomerular filtration rate was calculated preoperatively, postoperatively, and at 1- and 1.5-year follow-ups using the Chronic Kidney Disease Epidemiology Collaboration equation. Glomerular filtration rates were compared between treatment and control groups using 2-sample t tests. RESULTS Data analysis for the 111 donor nephrectomy patients showed that glomerular filtration rates decreased in both groups over time, but changes were not clinically significant. No difference was found in glomerular filtration rates (in mL/min/1.73 m(2)) between treatment and control groups at 1-year follow-up (89.29 vs 87.94 mL/min/1.73 m(2); P = .58) or at 1.5-year follow-up (88.54 vs 90.25 mL/min/1.73 m(2); P = .51). CONCLUSION The novel provision of continuous steady-state ketorolac is safe for postoperative pain control in patients after donor nephrectomy, with no change in glomerular filtration rates between treatment and control groups acutely and at up to 1.5-year follow-up. (C) 2014 Elsevier Inc.
[Show abstract][Hide abstract] ABSTRACT: Objective
To determine if massive renal size should be a contraindication for attempting a laparoscopic approach to bilateral native nephrectomies in patients with autosomal dominant polycystic kidney disease (ADPKD).Patients and Methods
We retrospectively reviewed all laparoscopic bilateral nephrectomies performed for ADPKD at our institution from 1 January 2000 to 31 December 2012. We stratified patients by kidney weight (with or without at least one kidney weighing >2500 g) and compared perioperative data, complications, and status of kidney allografts. Additionally, the subset of patients with at least one kidney weighing >3500 g was compared with the rest of the cohort.ResultsWe identified 68 patients; mean (range) individual kidney weight was 1984 (197-5042) g. In all, 24 patients had at least one kidney weighing >2500 g, yet patients in this group were not significantly different from the rest of the cohort for complications, estimated blood loss, transfusion rate, or duration of hospitalisation. For those who underwent simultaneous renal allotransplantation, native kidney size was not associated with graft outcomes. Additionally, of the six patients with at least one kidney weighing >3500 g, only one required a blood transfusion, and the group had no intraoperative or postoperative Clavien grade ≥3 complications. None of the cohort required conversion to open surgery.Conclusion
Massive size of polycystic kidneys is not a contraindication to attempting a laparoscopic approach to bilateral nephrectomies in an experienced, high-volume centre.
BJU International 06/2014; 115(5). DOI:10.1111/bju.12821 · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Few data on the perioperative outcomes of cystectomy after neoadjuvant chemotherapy (NAC) exist. In this study, we evaluated whether patients who had previously received NAC were at higher risk of developing perioperative complications.
The Canadian Journal of Urology 06/2014; 21(3):7259-7265. · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To evaluate outcomes of the first 18 patients treated with robot-assisted retroperitoneal lymph node dissection (RA-RPLND) for non-seminomatous germ cell tumours (NSGCT) and paratesticular rhabdomyosarcoma (RMS) at our institution.Patients and Methods
Between March 2008 and May 2013, 17 patients underwent RA-RPLND for NSGCT and one for paratesticular RMS. Data were collected retrospectively on patient demographics, preoperative tumour characteristics, and perioperative outcomes including open conversion rate, lymph node (LN) yield, rate of positive LNs, operative time, estimated blood loss (EBL), and length of stay (LOS). Perioperative outcomes were compared between patients receiving primary RA-RPLND vs post-chemotherapy RA-RPLND. Medium-term outcomes of tumour recurrence rate and maintenance of antegrade ejaculation were recorded.ResultsRA-RPLND was completed robotically in 15 of 18 (83%) patients. LNs were positive in eight of 18 patients (44%). The mean LN yield was 22 LNs. For cases completed robotically, the mean operative time was 329 min, EBL was 103 mL, and LOS was 2.4 days. At a mean (range) follow-up of 22 (1-58) months, there were no retroperitoneal recurrences and two of 17 (12%) patients with NSGCT had pulmonary recurrences. Antegrade ejaculation was maintained in 91% of patients with a nerve-sparing approach. Patients receiving primary RA-RPLND had shorter operative times compared with those post-chemotherapy (311 vs 369 min, P = 0.03). There was no significant difference in LN yield (22 vs 18 LNs, P = 0.34), EBL (100 vs 313 mL, P = 0.13), or LOS (2.75 vs 2.2 days, P = 0.36).Conclusion
This initial selected case series of RA-RPLND shows that the procedure is safe, reproducible, and feasible for stage I-IIB NSGCT and RMS in the hands of experienced robotic surgeons. Larger studies are needed to confirm the diagnostic and therapeutic utility of this technique.
BJU International 05/2014; 115(1). DOI:10.1111/bju.12804 · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the rates of deep venous thromboembolism (DVT) and pulmonary embolism (PE) after common urologic procedures in the United States.
The National Surgical Quality Improvement Program (NSQIP) database was used to identify common urologic procedures performed between January 1, 2005, and December 31, 2011. A total of 82,808 patients were included.
A total of 633 (0.76%, n=82,808) DVTs occurred within 30 days of surgery in this cohort of patients undergoing common urologic procedures. Among cases performed at least 500 times, the rates of DVT were highest among patients undergoing cystectomy/urinary diversion (3.96% [71/1,792]), partial cystectomy (2.35% [17/722]), and open radical nephrectomy (1.67% [45/2,702]). The rates of DVT were lowest among patients undergoing laparoscopic colpopexy (0.00% [0/707]), placement of a female sling (0.08% [9/10,648]), and hydrocelectomy/spermatocelectomy/varicocelectomy (0.13% [3/2,333]). A total of 349 (0.42%) PEs occurred in this cohort with cystectomy/urinary diversion having the highest rate overall (2.85% [51/1792]). Multivariable logistic regression revealed that age >60, functional status, history of disseminated cancer, CHF, anesthesia time >120 minutes and chronic steroid use were independently associated with DVT/PE formation. A limitation to the study is that no data is available on thromboembolic prophylaxis.
While DVTs and PEs are uncommon after urologic surgery, this is the first study to provide a comprehensive comparison of DVT/PE rates across a full spectrum of various urologic procedures among American patients. This should give the reader a better understanding of the exact risk faced by the patient when undergoing common urologic procedures.
The Journal of urology 03/2014; 192(3). DOI:10.1016/j.juro.2014.02.092 · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To examine whether racial disparities in survival exist among black, Hispanic, and Asian patients compared with white patients with clinically localized prostate cancer (CLPC) after adjustment for the effects of treatment.
Patients and Methods
We performed a retrospective cohort study of patients with CLPC diagnosed from January 1, 1995, through December 31, 2003, as documented in the Surveillance, Epidemiology, and End Results registry. Treatment-stratified, risk-adjusted Cox proportional hazards models were constructed.
During the study period, CLPC was diagnosed in 294,160 patients. Of these patients, 123,850 (42.1%) underwent surgery and 101,627 (34.5%) underwent radiotherapy, whereas 68,683 (23.3%) received no treatment. Overall 5-year and 10-year survival rates for Asians (85.6% and 67.6%, respectively), Hispanics (85.9% and 69.0%, respectively), and whites (83.9% and 65.7%, respectively) were higher than for blacks (81.5% and 61.7%, respectively) (P<.001). Prostate cancer–specific survival also varied significantly by race (P<.001). A risk-adjusted model stratified by primary treatment modality revealed that blacks had worse overall survival than whites (hazard ratio, 1.37; 95% CI, 1.33-1.41; P<.001), whereas Asians had better survival compared with whites (hazard ratio, 0.79; 95% CI, 0.76-0.83; P<.001). After the effects of treatment were accounted for, Hispanics had similar overall survival compared with whites (hazard ratio, 0.97; 95% CI, 0.94-1.01; P=.10).
Blacks with CLPC have poorer survival than whites, whereas Asians have better survival, even after risk adjustment and stratification by treatment. These data may be relevant to US regions with large underserved populations that have limited access to health care.
Mayo Clinic Proceedings 03/2014; 89(3):300–307. DOI:10.1016/j.mayocp.2013.11.001 · 5.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
The purpose of the RAZOR study is to compare open versus robotic radical cystectomy, pelvic lymph node dissection and urinary diversion regarding oncologic outcomes, complications and quality of life measures with a primary endpoint of 2-year progression free survival. Patients and MethodsRAZOR is a multi-institutional, randomized, non-inferior, phase 3 trial that will enroll at least 320 patients with T1-T4, N0-1, M0 bladder cancer with approximately 160 patients in both robotic and open arms at a total of 15 participating institutions.Data will be collected prospectively at each institution regarding cancer outcomes, complications from surgery and quality of life measures and then submitted to trial data management services, Cancer Research and Biostatistics (CRAB) for final analyses. Results306 patients have been randomized to date and accrual to the RAZOR trial is expected to conclude in 2014.In this study, we report RAZOR trial experimental design, objectives, data safety and monitoring and accrual update. Conclusions
The RAZOR trial is a landmark study in urological oncology, randomizing T1-T4, N0-N1, M0 bladder cancer patients to open versus robotic radical cystectomy, pelvic lymph node dissection and urinary diversion.RAZOR is a multi-institutional, non-inferiority trial evaluating cancer outcomes, surgical complications and quality of life measures of open versus robotic cystectomy with a primary endpoint of 2-year progression free survival.Full data from the RAZOR trial are not expected until 2016—2017.
BJU International 02/2014; 115(2). DOI:10.1111/bju.12699 · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Robotic surgery offers three-dimensional visualization and precision of movement that could be of great value to hepatobiliary surgeons. Previous reports of robotic choledochocele resections in adults have detailed extracorporeal jejunojejunostomies. We describe a total robotic excision of a choledochal cyst with hepaticojejunostomy and intracorporeal Roux-en-Y anastomosis.
A 58-year-old woman underwent a robotic excision of a small choledochocele with hepaticojejunostomy and intracorporeal Roux-en-Y.
Port placement was determined via collaborative surgical discussion and previously reported robotic right hepatectomies. Total operative time was 386 min and total robot working time was 330 min. The hepaticojejunostomy was performed using 5-0 PDS suture with parachute-style back wall and running front wall sutures. The jejunojejunostomy was a stapled anastomosis. Estimated blood loss was less than 100 mL. The patient was ambulating and tolerating oral intake on post-operative day 1, and was discharged home on post-operative day 2.
Robotic resection of choledochal cyst with intracorporeal Roux-en-Y anastomosis is feasible, with advantages over open surgery such as superior visualization, precision, and post-operative patient recovery.
Journal of Robotic Surgery 01/2014; 8(1). DOI:10.1007/s11701-012-0389-5
[Show abstract][Hide abstract] ABSTRACT: Objective
To evaluate the long-term safety of a novel continuous infusion of ketorolac vs placebo after laparoscopic donor nephrectomy.
We performed a secondary analysis of a previously reported randomized controlled trial conducted from October 7, 2008, to July 21, 2010. Patients aged 18-75 years received a continuous infusion of either ketorolac (treatment [n = 57]) or normal saline (control [n = 54]) for 24 hours immediately after laparoscopic donor nephrectomy. Serum creatinine levels were measured at 1- and 1.5-year follow-ups. Glomerular filtration rate was calculated preoperatively, postoperatively, and at 1- and 1.5-year follow-ups using the Chronic Kidney Disease Epidemiology Collaboration equation. Glomerular filtration rates were compared between treatment and control groups using 2-sample t tests.
Data analysis for the 111 donor nephrectomy patients showed that glomerular filtration rates decreased in both groups over time, but changes were not clinically significant. No difference was found in glomerular filtration rates (in mL/min/1.73 m2) between treatment and control groups at 1-year follow-up (89.29 vs 87.94 mL/min/1.73 m2; P = .58) or at 1.5-year follow-up (88.54 vs 90.25 mL/min/1.73 m2; P = .51).
The novel provision of continuous steady-state ketorolac is safe for postoperative pain control in patients after donor nephrectomy, with no change in glomerular filtration rates between treatment and control groups acutely and at up to 1.5-year follow-up.
[Show abstract][Hide abstract] ABSTRACT: To examine the impact of body mass index, as a measure of obesity, on the surgical outcomes of cystectomy.
The American College of Surgeons National Surgical Quality Improvement Program database was used to acquire data on 1293 cystectomies carried out from 2005 to 2011. Patients were divided into two groups: body mass index <30 kg/m(2) and ≥30 kg/m(2) . A propensity score-matched analysis of perioperative outcomes was carried out.
A total of 869 patients had a body mass index <30, whereas 424 had a body mass index ≥30. Unadjusted comparisons showed higher rates of superficial surgical site infections (8.7% vs 5.3%, P = 0.04), renal insufficiency (4.0% vs 1.7%, P = 0.01) and increased operative times (365.7 min vs 338.6 min, P = 0.0004) in the obese patients, but interestingly lower rates of pneumonia (2.4% vs 4.8, P = 0.03) and cerebral vascular accidents (0.0% vs 0.9%, P = 0.05). However, the latter two observations might be explained by more tobacco use among non-obese patients (26.6 mean pack-years vs 20.0 mean pack-years, P = 0.004). Notably, no differences in 30-day mortality were noted. After adjusting for preoperative demographic and clinical data using propensity score-matching methods, there were no observed differences between the two cohorts except for operative time (P = 0.04).
Obesity is not independently associated with an increased risk of perioperative complications or 30-day mortality after cystectomy.
International Journal of Urology 11/2013; 21(5). DOI:10.1111/iju.12340 · 1.80 Impact Factor