A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer.

OBJECTIVES: To compare the efficacy and safety of algenpantucel-L [HyperAcute-Pancreas algenpantucel-L (HAPa); IND# 12311] immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: To date, immunotherapy has not been shown to benefit patients with borderline resectable or locally advanced unresectable PDAC. HAPa is a cancer vaccine consisting of allogeneic pancreatic cancer cells engineered to express the murine α(1,3)GT gene. METHODS: A multicenter, phase 3, open label, randomized (1:1) trial of patients with borderline resectable or locally advanced unresectable PDAC. Patients received neoadjuvant SOC chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) followed by chemoradiation (standard group) or the same standard neoadjuvant regimen combined with HAPa immunotherapy (experimental group). The primary outcome was overall survival. RESULTS: Between May 2013 and December 2015, 303 patients were randomized from 32 sites. Median (interquartile range) overall survival was 14.9 (12.2-17.8) months in the standard group (N = 158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) [hazard ratio (HR) 1.02, 95% confidence intervals 0.66-1.58; P = 0.98]. Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% confidence intervals 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05). CONCLUSIONS: Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01836432.

A National Survey of Motor Vehicle Crashes Among General Surgery Residents.

OBJECTIVES: Evaluate the frequency of self-reported, post-call hazardous driving events in a national cohort of general surgery residents and determine the associations between duty hour policy violations, psychiatric well-being, and hazardous driving events. SUMMARY OF BACKGROUND DATA: MVCs are a leading cause of resident mortality. Extended work shifts and poor psychiatric well-being are risk factors for MVCs, placing general surgery residents at risk. METHODS: General surgery residents from US programs were surveyed after the 2017 American Board of Surgery In-Training Examination. Outcomes included self-reported nodding off while driving, near-miss MVCs, and MVCs. Group-adjusted cluster Chi-square and hierarchical regression models with program-level intercepts measured associations between resident- and program-level factors and outcomes. RESULTS: Among 7391 general surgery residents from 260 programs (response rate 99.3%), 34.7% reported nodding off while driving, 26.6% a near-miss MVC, and 5.0% an MVC over the preceding 6 months. More frequent 80-hour rule violations were associated with all hazardous driving events: nodding off while driving {59.8% with ≥5 months with violations vs 27.2% with 0, adjusted odds ratio (AOR) 2.86 [95% confidence interval (CI) 2.21-3.69]}, near-miss MVCs, [53.6% vs 19.2%, AOR 3.28 (95% CI 2.53-4.24)], and MVCs [14.0% vs 3.5%, AOR 2.46 (95% CI 1.65-3.67)]. Similarly, poor psychiatric well-being was associated with all 3 outcomes [eg, 8.0% with poor psychiatric well-being reported MVCs vs 2.6% without, odds ratio 2.55 (95% CI 2.00-3.24)]. CONCLUSIONS: Hazardous driving events are prevalent among general surgery residents and associated with frequent duty hour violations and poor psychiatric well-being. Greater adherence to duty hour standards and efforts to improve well-being may improve driving safety.

Association of Surgical Resident Wellness With Medical Errors and Patient Outcomes.

OBJECTIVES: The aims of this study were to: (1) measure the prevalence of self-reported medical error among general surgery trainees, (2) assess the association between general surgery resident wellness (ie, burnout and poor psychiatric well-being) and self-reported medical error, and (3) examine the association between program-level wellness and objectively measured patient outcomes. SUMMARY OF BACKGROUND DATA: Poor wellness is prevalent among surgical trainees but the impact on medical error and objective patient outcomes (eg, morbidity or mortality) is unclear as existing studies are limited to physician and patient self-report of events and errors, small cohorts, or examine few outcomes. METHODS: A cross-sectional survey was administered immediately following the January 2017 American Board of Surgery In-training Examination to clinically active general surgery residents to assess resident wellness and self-reported error. Postoperative patient outcomes were ascertained using a validated national clinical data registry. Associations were examined using multivariable logistic regression models. RESULTS: Over a 6-month period, 22.5% of residents reported committing a near miss medical error, and 6.9% reported committing a harmful medical error. Residents were more likely to report a harmful medical error if they reported frequent burnout symptoms [odds ratio 2.71 (95% confidence interval 2.16-3.41)] or poor psychiatric well-being [odds ratio 2.36 (95% confidence interval 1.92-2.90)]. However, there were no significant associations between program-level resident wellness and any of the independently, objectively measured postoperative American College of Surgeons National Surgical Quality improvement Program outcomes examined. CONCLUSIONS: Although surgical residents with poor wellness were more likely to self-report a harmful medical error, there was not a higher rate of objectively reported outcomes for surgical patients treated at hospitals with higher rates of burnout or poor psychiatric well-being.

Multi-institution Evaluation of Adherence to Comprehensive Postoperative VTE Chemoprophylaxis.

OBJECTIVES: The aims of this study were to: (1) measure the rate of failure to provide defect-free postoperative venous thromboembolism (VTE) chemoprophylaxis, (2) identify reasons for failure to provide defect-free VTE chemoprophylaxis, and (3) examine patient- and hospital-level factors associated with failure. SUMMARY BACKGROUND DATA: Current VTE quality measures are inadequate. VTE outcome measures are invalidated for interhospital comparison by surveillance bias. VTE process measures (e.g., SCIP-VTE-2) do not comprehensively capture failures throughout patients' entire hospitalization. METHODS: We examined adherence to a novel VTE chemoprophylaxis process measure in patients who underwent colectomies over 18 months at 36 hospitals in a statewide surgical collaborative. This measure assessed comprehensive VTE chemoprophylaxis during each patient's entire hospitalization, including reasons why chemoprophylaxis was not given. Associations of patient and hospital characteristics with measure failure were examined. RESULTS: The SCIP-VTE-2 hospital-level quality measure identified failures of VTE chemoprophylaxis in 0% to 3% of patients. Conversely, the novel measure unmasked failure to provide defect-free chemoprophylaxis in 18% (736/4086) of colectomies. Reasons for failure included medication not ordered (30.4%), patient refusal (30.3%), incorrect dosage/frequency (8.2%), and patient off-unit (3.4%). Patients were less likely to fail the chemoprophylaxis process measure if treated at nonsafety net hospitals (OR 0.62, 95% CI 0.39-0.99, P = 0.045) or Magnet designated hospitals (OR 0.45, 95% CI 0.29-0.71, P = 0.001). CONCLUSIONS: In contrast to SCIP-VTE-2, our novel quality measure unmasked VTE chemoprophylaxis failures in 18% of colectomies. Most failures were due to patient refusals or ordering errors. Hospitals should focus improvement efforts on ensuring patients receive VTE prophylaxis throughout their entire hospitalization.

The Role of Biomarkers in the Management of Colorectal Liver Metastases.

Surgical management combined with improved systemic therapies have extended 5-year overall survival beyond 50% among patients with colorectal liver metastases (CRLM). Furthermore, a multitude of liver-directed therapies has improved local disease control for patients with unresectable CRLM. Unfortunately, a significant portion of patients treated with curative-intent hepatectomy develops disease recurrence. Traditional markers fail to risk-stratify and prognosticate patients with CRLM appropriately. Over the last few decades, advances in molecular sequencing technology have greatly expanded our knowledge of the pathophysiology and tumor microenvironment characteristics of CRLM. These investigations have revealed biomarkers with the potential to better inform management decisions in patients with CRLM. Actionable biomarkers such as RAS and BRAF mutations, microsatellite instability/mismatch repair status, and tumor mutational burden have been incorporated into national and societal guidelines. Other biomarkers, including circulating tumor DNA and radiomic features, are under active investigation to evaluate their clinical utility. Given the plethora of therapeutic modalities and lack of evidence on timing and sequence, reliable biomarkers are needed to assist clinicians with the development of patient-tailored management plans. In this review, we discuss the current evidence regarding biomarkers for patients with CRLM.

Reducing colorectal surgical site infections: a novel, resident-driven, quality initiative.

BACKGROUND: Surgical site infections (SSIs) cause significant patient morbidity and increase costs. This work prospectively examines our institutional effort to reduce SSIs through a resident-driven quality initiative. METHODS: A general surgery resident-championed, evidenced-based care bundle for patients undergoing colorectal surgery at a single academic institution was developed using attending mentorship. National Surgical Quality Improvement Program definitions for SSIs were used. Data were collected prospectively and bundle compliance was monitored using a checklist. The primary outcome compared SSIs before and after implementation. RESULTS: In the 2 years preceding standardization, 489 colorectal surgery cases were performed. SSIs occurred in 68 patients (13.9% SSI rate). Following implementation of the bundle, 212 cases were performed with 10 SSIs (4.7% SSI rate, P < .01). Multivariate logistic regression analysis found a decrease in superficial and overall SSIs (odds ratio .17, 95% confidence interval .05 to .59; odds ratio .31, 95% confidence interval .14 to .68). CONCLUSIONS: These data demonstrate that resident-driven initiatives to improve quality of care can be a swift and effective way to enact change. We observed significantly decreased SSIs with a renewed focus on evidence-based, standardized patient care.