Identification and Adjudication of Adverse Events Following Rectal Cancer Surgery: Observational Case Series in a Region of Ontario, Canada.

BACKGROUND: For patients undergoing rectal cancer surgery, we evaluated whether suboptimal preoperative surgeon evaluation of resection margins is a latent condition factor-a factor that is common, unrecognized, and may increase the risk of certain adverse events, including local tumour recurrence, positive surgical margin, nontherapeutic surgery, and in-hospital mortality. METHODS: In this observational case series of patients who underwent rectal cancer surgery during 2016 in Local Health Integrated Network 4 region of Ontario (population 1.4 million), chart review and a trigger tool were used to identify patients who experienced the adverse events. An expert panel adjudicated whether each event was preventable or nonpreventable and identified potential contributing factors to adverse events. RESULTS: Among 173 patients, 25 (14.5%) had an adverse event and 13 cases (7.5%) were adjudicated as preventable. Rate of surgeon awareness of preoperative margin status was low at 50% and similar among cases with and without an adverse event (p = 0.29). Suboptimal surgeon preoperative evaluation of surgical margins was adjudicated a contributing factor in all 11 preventable local recurrence, positive margin, and nontherapeutic surgery cases. Failure to rescue was judged a contributing factor in the two cases with preventable in-hospital mortality. CONCLUSIONS: Suboptimal surgeon preoperative evaluation of surgical margins in rectal cancer is likely a latent condition factor. Optimizing margin evaluation may be an efficient quality improvement target.

High-Intensity vs Low-Intensity Knowledge Translation Interventions for Surgeons and Their Association With Process and Outcome Measures Among Patients Undergoing Rectal Cancer Surgery.

Importance: Surgeon-directed knowledge translation (KT) interventions for rectal cancer surgery are designed to improve patient measures, such as rates of permanent colostomy and in-hospital mortality, and to improve survival. Objective: To evaluate the association of sustained, iterative, integrated KT rectal cancer surgery interventions directed at all surgeons with process and outcome measures among patients undergoing rectal cancer surgery in a geographic region. Design, Setting, and Participants: This quality improvement study used administrative data from patients who underwent rectal cancer surgery from April 1, 2004, to March 31, 2015, in 14 health regions in Ontario, Canada. Follow-up was completed on March 31, 2020. Exposures: Surgeons in 2 regions were offered intensive KT interventions, including annual workshops, audit and feedback sessions, and, in 1 of the 2 regions, operative demonstrations, from 2006 to 2012 (high-intensity KT group). Surgeons in the remaining 12 regions did not receive these interventions (low-intensity KT group). Main Outcomes and Measures: Among patients undergoing rectal cancer surgery, proportions of preoperative pelvic magnetic resonance imaging (MRI), preoperative radiotherapy, and type of surgery were evaluated, as were in-hospital mortality and overall survival. Logistic regression models with an interaction term between group and year were used to assess whether process measures and in-hospital mortality differed between groups over time. Results: A total of 15 683 patients were included in the analysis (10 052 [64.1%] male; mean [SD] age, 65.9 [12.1] years), of whom 3762 (24.0%) were in the high-intensity group (2459 [65.4%] male; mean [SD] age, 66.4 [12.0] years) and 11 921 (76.0%) were in the low-intensity KT group (7593 [63.7%] male; mean [SD] age, 65.7 [12.1] years). A total of 1624 patients (43.2%) in the high-intensity group and 4774 (40.0%) in the low-intensity KT group underwent preoperative MRI (P < .001); 1321 (35.1%) and 4424 (37.1%), respectively, received preoperative radiotherapy (P = .03); and 967 (25.7%) and 2365 (19.8%), respectively, received permanent stoma (P < .001). In-hospital mortality was 1.6% (59 deaths) in the high-intensity KT group and 2.2% (258 deaths) in the low-intensity KT group (P = .02). Differences remained significant in multivariable models only for permanent stoma (odds ratio [OR], 1.67; 95% CI, 1.24-2.24; P < .001) and in-hospital mortality (OR, 0.67; 95% CI, 0.51-0.87; P = .003). In both groups over time, significant increases in the proportion of patients undergoing preoperative MRI (from 6.3% to 67.1%) and preoperative radiotherapy (from 16.5% to 44.7%) occurred, but there were no significant changes for permanent stoma (25.4% to 25.3% in the high-intensity group and 20.0% to 18.3% in the low-intensity group) and in-hospital mortality (0.8% to 0.8% in the high-intensity group and 2.2% to 1.8% in the low-intensity group). Time trends were similar between groups for measures that did or did not change over time. Patient overall survival was similar between groups (hazard ratio, 1.00; 95% CI, 0.90-1.11; P = .99). Conclusions and Relevance: In this quality improvement study, between-group differences were found in only 2 measures (permanent stoma and in-hospital mortality), but these differences were stable over time. High-intensity KT group interventions were not associated with improved patient measures and outcomes. Proper evaluation of KT or quality improvement interventions may help avoid opportunity costs associated with ineffective strategies.

A method to audit and score implementation of knowledge translation (KT) interventions in large health regions - an observational pilot study using rectal cancer surgery in Ontario.

BACKGROUND: Across Ontario, since the year 2006 various knowledge translation (KT) interventions designed to improve the quality of rectal cancer surgery have been implemented by the provincial cancer agency or by individual researchers. Ontario is divided administratively into 14 health regions. We piloted a method to audit and score for each region of the province the KT interventions implemented to improve the quality of rectal cancer surgery. METHODS: We interviewed stakeholders to audit KT interventions used in respective regions over years 2006 to 2014. Results were summarized into narrative and visual forms. Using a modified Delphi approach, KT experts reviewed these data and then, for each region, scored implementation of KT interventions using a 20-item KT Signature Assessment Tool. Scores could range from 20 to 100 with higher scores commensurate with greater KT intervention implementation. RESULTS: There were thirty interviews. KT experts produced scores for each region that were bimodally distributed, with an average score for 2 regions of 78 (range 73-83) and for 12 regions of 30.5 (range 22-38). CONCLUSION: Our methods efficiently identified two groups with similar KT Signature scores. Two regions had relatively high scores reflecting numerous KT interventions and the use of sustained iterative approaches in addition to those encouraged by the provincial cancer agency, while 12 regions had relatively low scores reflecting minimal activities outside of those encouraged by the provincial cancer agency. These groupings will be used for future comparative quantitative analyses to help determine if higher KT signature scores correlate with improved measures for quality of rectal cancer surgery.

Role of the status of the mesorectal fascia in the selection of patients with rectal cancer for preoperative radiation therapy: a retrospective cohort study

Background: Patients with rectal cancer in whom the mesorectal fascia is threatened by tumour are more likely than all patients with stage II/III disease to benefit from preoperative radiotherapy (RT). The objective of this study was to assess whether the status of the mesorectal fascia versus a stage II/III designation can best inform the use of preoperative RT in patients undergoing major rectal cancer resection. Methods: We reviewed the charts of consecutive patients with primary rectal cancer treated by a single surgeon at McMaster University, Hamilton, Ontario, between March 2006 and December 2012. The status of the mesorectal fascia was assessed by digital rectal examination, pelvic computed tomography and, when needed, pelvic magnetic resonance imaging (MRI). Patients whose mesorectal fascia was threatened or involved by tumour received preoperative RT. The study outcomes were rates of positive circumferential radial margin (CRM) and local tumour recurrence. Results: A total of 153 patients were included, of whom 76 (49.7%) received preoperative RT because of concerns of a compromised mesorectal fascia. The median length of follow-up was 4.5 years. The number of CRM-positive cases in the RT and no-RT groups was 16 (22%) and 1 (1%), respectively (p < 0.01), and the number of cases of local tumour recurrence was 5 (7%) and 2 (3%), respectively (p = 0.2). Rates were similar when only patients with stage II/III tumours were included. Overall, 26 patients (17.0%) received MRI. Conclusion: The status of the mesorectal fascia, not tumour stage, may best identify patients for preoperative RT.

Contexte: Plus que tous les patients présentant une maladie de stade II/III, les patients atteints d'un cancer du rectum dont le fascia mésorectal est menacé par la tumeur sont de bons candidats à la radiothérapie (RT) préopératoire. L'objectif de cette étude était d'évaluer ce qui, entre l'état du fascia mésorectal et une désignation de stade II/III, permet le mieux de confirmer le bien-fondé d'une RT préopératoire chez les patients qui doivent subir une résection majeure pour cancer du rectum. Méthodes: Nous avons passé en revue les dossiers de patients consécutifs atteints d'un cancer rectal primaire traités par un seul chirurgien à l'Université McMaster, à Hamilton, en Ontario, entre mars 2006 et décembre 2012. L'état du fascia mésorectal a été évalué par toucher rectal, tomodensitométrie pelvienne et, au besoin, imagerie par résonnance magnétique (IRM) pelvienne. Les patients dont le fascia mésorectal était menacé ou affecté par la tumeur ont reçu une RT préopératoire. Les paramètres de l'étude étaient : taux de positivité de la marge radiale circonférentielle (MRC) et récurrence de la tumeur locale. Résultats: En tout, 153 patients ont été inclus, dont 76 (49,7 %) ont reçu une RT préopératoire en raison d'une atteinte du fascia mésorectal. La durée moyenne du suivi a été de 4,5 ans. Dans les groupes soumis et non soumis à la RT, les nombres de cas MRC-positifs ont été respectivement de 16 (22 %) et de 1 (1 %), (p < 0,01), et les nombres de cas de récurrence de la tumeur locale ont été respectivement de 5 (7 %) et de 2 (3 %) (p = 0,2). Les taux étaient similaires lorsque seuls les patients présentant des tumeurs de stade II/III étaient inclus. Globalement, 26 patients (17,0 %) ont subi l'IRM. Conclusion: C'est l'état du fascia mésorectal et non le stade de la tumeur qui peut le mieux permettre d'identifier les candidats à une RT préopératoire.

Quality of preoperative pelvic computed tomography (CT) and magnetic resonance imaging (MRI) for rectal cancer in a region in Ontario: A retrospective population-based study.

BACKGROUND AND OBJECTIVES: Treatment decisions for rectal cancer rely on preoperative staging with CT and MRI scans. We assessed the quality of such scans in a region of Ontario. METHODS: We retrospectively collected data for patients undergoing rectal cancer surgery between July 2011 and December 2014. We measured three aspects of quality: use; comprehensiveness of reporting T-category, N-category, mesorectal fascia (MRF) status; and in non-radiated patients sensitivity and specificity of reports for relevant elements. RESULTS: A total of 559 patients underwent major rectal cancer surgery. Preoperative staging with CT and MRI was performed in 93% and 50% of patients. CT scan reports provided information on T-category, N-category, and MRF status in 41%, 92%, and 16% of cases. These same elements were reported on MRI in 88%, 93%, and 62% of cases. CT scan sensitivity and specificity was 80% and 80% for T-category, and 85% and 39% for N-category. MRI sensitivity and specificity was 75% and 81% for T-category, 79% and 37% for N-category, and 33% and 89% for MRF status. CONCLUSION: In this region of Ontario, pre-operative MRI was underutilized, CT reporting of MRF status was low, and when reported sensitivity and specificity of T- and N-category were similar for CT and MRI.

The Need for Consensus and Transparency in Assessing Population-Based Rates of Positive Circumferential Radial Margins in Rectal Cancer: Data from Consecutive Cases in a Large Region of Ontario, Canada.

BACKGROUND: A positive circumferential radial margin (CRM) after rectal cancer surgery is an important predictor of local recurrence. The definition of a positive CRM differs internationally, and reported rates vary greatly in the literature. This study used time-series population-based data to assess positive CRM rates in a region over time and to inform future methods of CRM analysis in a defined geographic area. METHODS: Chart reviews provided relevant data from consecutive patients undergoing rectal cancer surgery between 2006 and 2012 in all hospitals of the authors' region. Outcomes included rates for pathologic examination of CRM, CRM distance reporting, and positive CRM. The rate of positive CRM was calculated using various definitions. The variations included positive margin cutoffs of CRM at 1 mm or less versus 2 mm or less and inclusion or exclusion of cases without CRM assessment. RESULTS: In this study, 1222 consecutive rectal cancer cases were analyzed. The rate for pathology reporting of CRM distance increased from 54.7 to 93.2 % during the study. Depending on how the rate of positive CRM was defined, its value varied 8.5 to 19.4 % in 2006 and 6.0 to 12.5 % in 2012. Using a pre-specified definition, the rate of positive CRM decreased over time from 14.0 to 6.3 %. CONCLUSIONS: A marked increase in CRM distance reporting was observed, whereas the rates of positive CRM dropped, suggesting improved pathologist and surgeon performance over time. Changing definitions greatly influenced the rates of positive CRM, indicating the need for more transparency when such population-based rates are reported in the literature.

An Internet-Based Collaborative Cancer Conference for Rectal Cancer Influenced Surgeon Treatment Recommendations.

INTRODUCTION: In many jurisdictions geographic and resource constraints are barriers to multidisciplinary cancer conference review of all patients undergoing cancer surgery. We piloted an internet-based collaborative cancer conference (I-CCC) for rectal cancer to overcome these barriers in the LHIN4 region of Ontario (population 1.4 million). METHODS: Surgeons practicing at one of 10 LHIN4 hospitals were invited to participate in I-CCC reviews. A secure internet audio and visual link facilitated review of cross-sectional images and case details. Before review, referring surgeons detailed initial treatment plans. Main treatment options included preoperative radiation, straight to surgery, and plan uncertain. Changes were noted following I-CCC review from initial to final treatment plan. Major changes included: redirect patient to preoperative radiation from straight to surgery or plan uncertain; and redirect patient to straight to surgery from preoperative radiation or plan uncertain. Minor changes included: change type of neoadjuvant therapy; request additional tests (e.g., pelvic MRI); or formal MCC review. RESULTS: From November 2010 to May 2012, 20 surgeons (7 academic and 13 community) submitted 57 rectal cancer cases for I-CCC review. After I-CCC review, 30 of 57 (53 %) cases had treatment plan changes: 17 major and 13 minor. No patient or tumour factors predicted for treatment plan change. CONCLUSIONS: An I-CCC for rectal cancer in a large geographic region was feasible and influenced surgeon treatment recommendations in 53 % of cases. Because no factor predicted for treatment plan change, it is likely prudent that all rectal cancer patients undergo some form of collaborative review.

Quality improvement in colorectal cancer in local health integration network 4 (LHIN 4) project (QICC-L4): integrated knowledge translation in a large geographic region.

BACKGROUND: Stakeholders suggest that integrating end users into the planning and execution of quality improvement interventions may more effectively close quality gaps. We tested if such an approach could improve the quality of colorectal cancer surgery in a large geographic region (i.e., LHIN4) in Ontario, Canada. METHODS: All LHIN4 surgeons who provide colorectal cancer surgery were invited to an October 2006 inaugural QICC-L4 workshop and subsequent workshops in 2008, 2010, and 2012. At workshops, surgeons selected clinically relevant quality markers for targeted improvement and interventions to achieve improvements. Selected markers included rates of colon and rectal radiology imaging, rate of pathology reporting of rectal radial margin distance, and rate of positive rectal radial margins. To date, implemented interventions have included audit and feedback, tailoring interviews to identify barriers and facilitators to optimal quality, and preoperative internet-based patient reviews. Hospital and regional cancer centre charts provide audit data for annual feedback reports to surgeons. RESULTS: Participating surgeons at workshops and surgeon participants in preoperative reviews treated approximately 70 % of all LHIN4 patients undergoing colorectal surgery. For years 2006-2012, the rate of radiology imaging for colon and rectal cases increased from 70 to 91 % and from 71 to 91 %, respectively. For rectal cases, the rate of reporting radial margins increased (55-93 %), and the rate of positive radial margins decreased (14-6 %). CONCLUSIONS: Initiation of the integrated knowledge translation QICC-L4 project in a large geographic region was associated with marked improvements in relevant colorectal cancer surgery quality markers.

O-GlcNAc-glycosylation of beta-catenin regulates its nuclear localization and transcriptional activity.

Beta-catenin plays a role in intracellular adhesion and regulating gene expression. The latter role is associated with its oncogenic properties. Phosphorylation of beta-catenin controls its intracellular expression but mechanism/s that regulates the nuclear localization of beta-catenin is unknown. We demonstrate that O-GlcNAc glycosylation (O-GlcNAcylation) of beta-catenin negatively regulates its levels in the nucleus. We show that normal prostate cells (PNT1A) have significantly higher amounts of O-GlcNAcylated beta-catenin compared to prostate cancer (CaP) cells. The total nuclear levels of beta-catenin are higher in the CaP cells than PNT1A but only a minimal fraction of the nuclear beta-catenin in the CaP cells are O-GlcNAcylated. Increasing the levels of O-GlcNAcylated beta-catenin in the CaP cells with PUGNAc (O- (2-acetamido-2-deoxy-d-gluco-pyranosylidene) amino-N-phenylcarbamate) treatment is associated with a progressive decrease in the levels of beta-catenin in the nucleus. TOPFlash reporter assay and mRNA expressions of beta-catenin's target genes indicate that O-GlcNAcylation of beta-catenin results in a decrease in its transcriptional activity. We define a novel modification of beta-catenin that regulates its nuclear localization and transcriptional function.