Sonya Cnossen

Change in Adverse Events After Enrollment in the National Surgical Quality Improvement Program: A Systematic Review and Meta-Analysis.

Background The American College of Surgeons’ National Surgical Quality Improvement Program (NSQIP) is the first nationally validated, risk-adjusted, outcomes-based program to measure and compare the quality of surgical care across North America. Participation in this program may provide an opportunity to reduce the incidence of adverse events related to surgery. Study Design A systematic review of the literature was performed. MedLine, EMBASE and PubMed were searched for studies relevant to NSQIP. Patient characteristics, intervention, and primary outcome measures were abstracted. The intervention was participation in NSQIP and monitoring of Individual Site Summary Reports with or without implementation of a quality improvement program. The outcomes of interest were change in peri-operative adverse events and mortality represented by pooled risk ratios (pRR) and 95% confidence intervals (CI). Results Eleven articles reporting on 35 health care institutions were included. Nine (82%) of the eleven studies implemented a quality improvement program. Minimal improvements in superficial (pRR 0.81; 95% CI 0.72–0.91), deep (pRR 0.82; 95% CI0.64–1.05) and organ space (pRR 1.15; 95% CI 0.96–1.37) infections were observed at centers that did not institute a quality improvement program. However, centers that reported formal interventions for the prevention and treatment of infections observed substantial improvements (superficial pRR 0.55, 95% CI 0.39–0.77; deep pRR 0.61, 95% CI 0.50–0.75, and organ space pRR 0.60, 95% CI 0.50–0.71). Studies evaluating other adverse events noted decreased incidence following NSQIP participation and implementation of a formal quality improvement program. Conclusions These data suggest that NSQIP is effective in reducing surgical morbidity. Improvement in surgical quality appears to be more marked at centers that implemented a formal quality improvement program directed at the reduction of specific morbidities.

The Risks and Benefits of Cavernous Neurovascular Bundle Sparing during Radical Prostatectomy: A Systematic Review and Meta-Analysis

Purpose: We summarize published data on associations between cavernous neurovascular bundle preservation (nerve sparing) during prostatectomy and positive surgical margins, erectile function, urinary function and other patient reported outcomes. Materials and Methods: A systematic literature search of MEDLINE®, Embase® and Cochrane Reviews databases was performed for interventional or observational studies published between 2000 and 2014. English language articles that compared clinical outcomes of patients undergoing nerve sparing and nonnerve sparing radical prostatectomy were included. Meta‐analyses were performed to calculate pooled relative risk estimates for positive surgical margins, erectile dysfunction and urinary incontinence in nerve sparing and nonnerve sparing groups. Sensitivity analyses compared outcomes among unilateral and bilateral nerve sparing vs nonnerve sparing groups. Results: Of the 1,883 articles identified, 124 studies (73,448 patients) were included in the analysis. Nerve sparing did not increase the risk of positive surgical margins in patients with pT2 (RR 0.92, 95% CI 0.75–1.13) or pT3 disease (RR 0.83, 95% CI 0.71–0.96), potentially due to appropriate patient selection. The risk of incontinence was lower in nerve sparing cases (RR 0.75, 95% CI 0.65–0.85 and RR 0.61, 95% CI 0.44–0.84) at 3 and 12 months, respectively. The relative risk of erectile dysfunction with nerve sparing was 0.77 (95% CI 0.70–0.85) at 3 months and 0.53 (95% CI 0.39–0.71) at 12 months. Subgroup analyses of unilateral and bilateral nerve sparing approaches demonstrated similar results. Conclusions: Among cohort studies nerve sparing was not associated with worse cancer outcomes. Nerve sparing is associated with better urinary and erectile function. These results should be interpreted with caution given the potential for selection bias and unadjusted confounding factors.

Reducing the Harm of Prostate Cancer Screening: Repeated Prostate-Specific Antigen Testing

OBJECTIVE To determine if repeating a prostate-specific antigen (PSA) test in men with an elevated PSA level is associated with a decreased risk of prostate biopsy and cancer diagnosis. PATIENTS AND METHODS A cohort of patients referred to the Ottawa Regional Prostate Cancer Assessment Clinic from April 1, 2008, through May 31, 2013, who had referral PSA levels between 4 and 10 ng/mL were included in the study. Univariate and multivariate associations between a normal result on repeated PSA testing and the risk of prostate biopsy, cancer diagnosis, and Gleason score of 7 or higher were examined. RESULTS The study cohort included 1268 patients. Repeated PSA test results were normal in 315 patients (24.8%). Men with normal results on repeated PSA testing were younger (mean ± SD age, 61.5±8.2 years vs 65.2±8.2 years; P<.001) and had lower referral PSA levels (mean ± SD, 5.5±1.4 ng/mL vs 6.6±1.5 ng/mL; P<.001) than men with an abnormal repeated PSA result. In multivariate analysis, men with normal results on repeated PSA testing were less likely to undergo prostate biopsy (relative risk [RR], 0.42; 95% CI, 0.34-0.50) and were at lower risk for cancer diagnosis (RR, 0.22; 95% CI, 0.14-0.34) and Gleason score of 7 or higher (RR, 0.16; 95% CI, 0.08-0.34) compared with men who had an abnormal repeated PSA test result. CONCLUSION Routinely repeating a PSA test in patients with an elevated PSA level is independently associated with decreased risk of prostate biopsy and prostate cancer diagnosis. Men with an elevated PSA level should be given a repeated PSA test before proceeding to biopsy.

Active surveillance in Canadian men with low-grade prostate cancer

Background: Recent guidelines recommend against routine screening for prostate cancer, partly because of the risks associated with overtreatment of clinically indolent tumours. We aimed to determine the proportion of patients whose low-grade prostate cancer was managed by active surveillance instead of immediate treatment. Methods: We reviewed data for patients who were referred to the Ottawa regional Prostate Cancer Assessment Clinic with abnormal results for prostate-specific antigen (PSA) or prostate examination between Apr. 1, 2008, and Jan. 31, 2013. Patients with subsequent biopsy-proven low-grade (Gleason score 6) cancer were included. Active surveillance was defined a priori as monitoring by means of PSA, digital rectal examination and repeat biopsies, with the potential for curative-intent treatment in the event of disease progression. Results: Of 477 patients with low-grade cancer, active surveillance was used for 210 (44.0%), and the annual proportion increased from 32% (11/34) in 2008 to 67% (20/30) in 2013. Factors associated with immediate treatment were palpable tumour, PSA density above 0.2 ng/mL2 and more than 2 positive biopsy cores. Factors associated with surveillance were age over 70 years and higher Charlson comorbidity index. Of 173 men who received immediate surgical treatment, 103 (59.5%) had higher-grade or advanced-stage disease on final pathologic examination. Of the 210 men with active surveillance, 62 (29.5%) received treatment within a median of 1.3 years, most commonly (52 [84%]) because of upgrading of disease on the basis of surveillance biopsy. Interpretation: Active surveillance has become the most common management strategy for men with low-grade prostate cancer at our regional diagnostic centre. Factors associated with immediate treatment reflected those that increase the risk of higher-grade tumours.

The Safety and Efficacy of Lysine Analogues in Cancer Patients: A Systematic Review and Meta-Analysis

Lysine analogues are effective agents used for the reduction of blood loss and transfusion. However, the safety of lysine analogues in cancer patients remains in question due to a potential risk of venous thromboembolism (VTE). The objective of our review is to investigate safety and efficacy of lysine analogue administration in the patients with cancer. Medline, Embase, and The Cochrane Library were searched from inception to June, 2016. Reference lists of retrieved studies were searched to identify additional publications. We included randomized clinical trials in adult cancer patients for which a lysine analogue was administered for the purpose of blood loss reduction. Abstract and full-text selection as well as data extraction and risk of bias assessment was done by 2 independent reviewers. The primary outcome was venous thromboembolic events. Secondary outcomes were other adverse events, blood transfusion, and blood loss. Overall, 11studies involving 1177 patients evaluated at least one of the primary or secondary outcomes. Nine studies evaluated the effects of tranexamic acid, one study evaluated the effects of aminocaproic acid and one study examined both agents. No increased risk of venous thromboembolism was observed for patients who received lysine analogues compared to control (Peto OR 0.58; 95% CI 0.26-1.28). The administration of a lysine analogue significantly decreased both transfusion risk (pooled RR 0.52, 95% CI 0.34-0.80) and blood loss (SMD -1.57, 95% CI -2.21 to -0.92). Among 3 eligible studies, no increased risk was observed for mortality (Peto OR 1.01; 95% CI 0.14-7.18) or infection (OR 0.58; 95% CI 0.27-1.27). The safety of lysine analogues in cancer patients has not been extensively studied. Based on the available literature, lysine analogue use has not been associated with increased risk of venous thromboembolism or other adverse events, while being effective in reducing blood loss and subsequent transfusion.

Laparoscopic nephroureterectomy is associated with higher risk of adverse events compared to laparoscopic radical nephrectomy.

INTRODUCTION Laparoscopic radical nephrectomy (LRN) and laparoscopic nephroureterectomy (LNU) are similar procedures and some surgeons may believe the perioperative risks are the same. The purpose of this study is to characterize and compare complications following LRN and LNU. METHODS A historical cohort of patients who received either LRN or LNU between 2006 and 2012 was reviewed from the National Surgical Quality Improvement Program (NSQIP) database. Patient characteristics, surgical characteristics, and perioperative outcomes up to 30 days postoperatively were abstracted. Unadjusted and adjusted associations between procedure (LRN or LNU) and any adverse event were determined. RESULTS During the study period, 4904 patients met study inclusion criteria; 4159 (84.8%) received a LRN while 745 (15.2%) received a LNU. Overall, 651 (13.3%) patients experienced at least one postoperative complication. LNU was associated with more complications than LRN (21% and 12%, respectively, p value <0.01). The most common complications were: bleeding requiring blood transfusion (9.0% LNU vs. 6.0% LRN), urinary tract infection (4.6% LNU vs. 1.5% LRN), wound infection (1.3% LNU vs. 1.8% LRN), and unplanned intubation (2.3% LNU vs. 0.9% LRN). After adjusting for potential confounders, LNU was associated with higher risk of any complication compared to LRN (relative risk [RR] 1.41, 95% confidence interval [CI] 1.16-1.72). Other variables independently associated with an increased risk of complications included: increasing patient age (RR 1.01, 95% CI 1.01-1.02), American Society of Anesthesiologists (ASA) classification ≥3 (RR 1.34, 95% CI 1.10-1.63), higher preoperative creatinine (RR 1.11, 95% CI 1.06-1.17), >4 units of blood transfused within 72 hours before surgery (RR 1.93, 95% CI 1.29-2.86), and operative time >6 hours (RR 2.17, 95% CI 1.71-2.75). CONCLUSIONS Postoperative complications within 30 days of surgery are common after LNU and LRN. Despite having technical similarities, LNU carries a significantly higher risk of developing short-term complications compared to LRN. This information should be considered when counseling patients prior to surgery. Notable limitations of this study included the lack of information on tumour stage and management of the distal ureter.

Needs Assessment Survey for the Management of Kidney Cancer

Introduction: In this study we determined self‐perceived knowledge gaps and continuing medical education preferences among Canadian urologists and medical oncologists related to the treatment of patients with kidney cancer. Methods: A needs assessment survey was created by the Quality Initiative group of the Kidney Cancer Research Network of Canada using an iterative feedback process. The survey determined knowledge gaps and continuing medical education preferences pertaining to 23 previously validated quality indicators of kidney cancer care. Topics included screening, diagnosis, prognosis, surgical management, systemic therapies and followup care. The survey was distributed via e‐mail to Canadian urologists and medical oncologists. Results: Among the 164 respondents 121 (74%) were urologists and 43 (26%) were medical oncologists. The majority of respondents practice in academic (72, 57%) or large urban community centers (40, 32%). Of the 23 quality indicators examined 14 were designated as priority continuing medical education topics based on perceived inadequate knowledge or high interest in the topic. Priority topics were similar for urologists and medical oncologists, and covered the spectrum of kidney cancer care with an emphasis on hereditary kidney cancer and management of advanced disease. Most respondents preferred that continuing medical education be delivered through in person, case based group discussions. Conclusions: Canadian urologists and medical oncologists report similar knowledge gaps and continuing medical education preferences regarding kidney cancer care. Priority topics include screening for hereditary kidney cancer and management of advanced disease.

The effect of wide resection during radical prostatectomy on surgical margins

INTRODUCTION The impact of nerve-sparing on positive surgical margins during radical prostatectomy (RP) remains unclear. The objective of this study was to determine the incidence of positive surgical margins with a wide resection compared to a nerve-sparing technique. METHODS A consecutive, single-surgeon patient cohort treated between August 2010 and November 2014 was reviewed. A standardized surgical approach of lobe-specific nerve-spare or wide resection was performed. Lobe-specific margin status and tumour stage were obtained from pathology reports. Univariable and multivariable associations between nerve management technique and lobe-specific positive surgical margin were determined. RESULTS Of 388 prostate lobes, wide resection was performed in 105 (27%) and nerve-sparing in 283 (73%). In 273 lobes without extra-prostatic extension (EPE), 0 of 52 (0%) had a positive margin when wide resection was performed compared to 20 of 221 (9%) if nerve-sparing was performed (p=0.02). In 115 lobes with EPE, 11 of 53 (21%) had a positive margin if wide resection was performed compared to 28 of 62 (45%) if nerve-sparing was performed (p=0.006). In multivariable analysis, the risk of a positive margin was decreased among patients who received wide resection as compared to nerve-spare (RR 0.43, 95% CI 0.26-0.71; p=0.001). CONCLUSIONS Surgical techniques to reduce positive surgical margins have become increasingly important as more patients with high-risk cancer are selecting surgery. The risk of a positive margin was greatly reduced using a standardized wide resection technique compared to nerve-sparing.

Are renal tumour scoring systems better than clinical judgement at predicting partial nephrectomy complexity

INTRODUCTION We aimed to determine how renal tumour scoring systems, such as RENAL, PADUA, and Centrality (C)-index, compare to clinical judgement at predicting time required for tumour removal and kidney reconstruction during partial nephrectomy. METHODS A consecutive cohort of partial nephrectomy patients treated at The Ottawa Hospital, a tertiary care uro-oncological centre, was retrospectively reviewed. Preoperative axial images were reviewed by four experienced urological oncologists who independently rated the complexity of a partial nephrectomy from 1-10 to generate a clinical judgement score. Two independent reviewers determined the RENAL, PADUA, and C-index scores. The time to complete tumour resection and renal reconstruction during partial nephrectomy was prospectively recorded. RESULTS During the study period, 104 partial nephrectomies were performed. The mean partial nephrectomy complexity score based on clinical judgement was 3.4 (standard deviation [SD] 2.1) out of 10. There was good agreement between surgeons in assessing tumour complexity (intraclass correlation coefficient 0.72; 95% confidence interval [CI] 0.65, 0.78). The mean RENAL score was 6.7 (SD 1.6) out of a maximum of 12, the mean PADUA score was 8.5 (SD 1.5) out of a maximum of 14, and the mean C-index score was 3.8 (SD 2). Mean resection and reconstruction time was 24 minutes (SD 10 minutes). The correlation between clinical judgement score and time was 0.27 (p=0.005). The correlation between renal tumour scoring systems and time was 0.20 (p=0.04) for RENAL, 0.21 (p=0.03) for C-index, and 0.26 (p=0.007) for PADUA. RENAL and PADUA scores were significantly associated with surgical and total complications. CONCLUSIONS The majority of variance in ischemia time is not explained by clinical judgement or renal tumour scoring systems. Renal tumour scoring systems were not better than the clinical judgement of urological oncologists at predicting ischemia time during partial nephrectomy.

MP68-19 FACTORS ASSOCIATED WITH SURGICAL SITE INFECTIONS FOLLOWING RADICAL CYSTECTOMY

INTRODUCTION AND OBJECTIVES: The Cancer Genome Atlas (TCGA) project recently published a global analysis of urothelial carcinoma that provided insight into the pathogenesis of urothelial carcinoma. However, the molecular correlates to clinical parameters associated with patient outcomes have yet to be fully characterized. In this study, we use RNA-seq data from TCGA to evaluate expression changes in the primary tumor of patients with and without lymph node metastasis stratified by T stage. METHODS: Raw count RNA-seq data was downloaded from the Broad Institute Firehose Pipeline (http://gdac.broadinstitute.org/) for all patients with associated clinical data. Pathology reports were reviewed and we recorded the T stage, N stage, and number of lymph nodes examined. Raw counts were imported into R v 3.12 and analyzed with the edgeR package. Data was stratified according to T stage (T2, T3, T4) for further analysis and all patients with negative lymph nodes who had less than 15 nodes examined were excluded. Exploratory data analysis was performed using Minus Average (MA) plots. Differential gene expression was performed evaluating differences between the primary tumors of lymph node positive and lymph node negative patients stratified by T stage. Pathway analysis was performed using iPathwayGuide. RESULTS: There were a total of 176 patients with pathologic information. A total of 106 patients met inclusion criteria: 23 T2 (8 Nþ, 15 N-), 64 T3 (30 Nþ, 34 N-), 19 T4 (15 Nþ, 4 N-). MAplots comparing Nþ and Npatients showed increasing variability with increasing T stage (Figure 1). There were a total of 4, 744, and 84 differentially expressed genes for T2, T3, and T4 tumors, respectively (p<0.01, q<0.05). There were only 8 differentially expressed genes that overlapped between T3 and T4 tumors; no genes overlapped all three groups. Pathway analysis showed involvement of PIK3-Akt pathway in T2 tumors, the MAPK signaling pathway in T3 tumors, and GnRH signaling in T4 tumors. CONCLUSIONS: There appears to be an increase in differential gene expression between tumors that have the biological capacity to spread to lymph nodes and those that do not, as T stage increases. Each T stage is associated with enrichment in unique pathways. This may shed light on the biologic heterogeneity in bladder cancer and potential differential pathways to metastasis.