Utility of Hospital Failure to Rescue for Analyzing Variation in Pediatric Postoperative Mortality.

OBJECTIVES: To evaluate the association between pediatric hospital performances in terms of failure to rescue (FTR), defined as postoperative mortality after a surgical complication, and mortality among patients without a surgical complication. DESIGN: Retrospective cohort study. SETTING: Forty-eight academic, pediatric hospitals; data obtained from Pediatric Health Information System database (Child Health Corporation of America, Shawnee Mission, KS) (2012-2020). PATIENTS: Children who underwent at least one of 57 high-risk operations associated with significant postoperative mortality. EXPOSURES: Hospitals were stratified into quintiles of reliability adjusted FTR (lower than average FTR in quintile 1 [Q1], higher than average FTR in quintile 5 [Q5]). Multivariable hierarchical regression was used to evaluate the association between hospital FTR performance and mortality among patients who did not have a surgical complication. MEASUREMENTS AND MAIN RESULTS: Among 203,242 children treated across 48 academic hospitals, the complication and overall postoperative mortality rates were 8.8% and 2.3%, respectively. Among patients who had a complication, the FTR rate was 8.8%. Among patients who did not have a complication, the mortality rate was 1.7%. There was a 6.5-fold increase in reliability adjusted FTR between the lowest and highest performing hospitals (lowest FTR hospital-2.7%; 95% CI [1.6-3.9]; highest FTR hospital-17.8% [16.8-18.8]). Complex chronic conditions were highly prevalent across hospitals (Q1, 72.7%; Q2, 73.8%; Q3, 72.2%; Q4, 74.0%; Q5, 74.8%; trend test p < 0.01). Relative to Q1 hospitals, the odds of mortality in the absence of a postoperative complication significantly increased by 33% at Q5 hospitals (odds ratio 1.33; 95% CI [1.07-1.66]). This association was consistent when limited to patients with a complex chronic condition and neonates. CONCLUSION: FTR may be a useful and valid surgical quality measure for pediatric surgery, even when considering patients without a postoperative complication. These findings suggest practices and processes for preventing FTR at high performing pediatric hospitals might help mitigate the risk of postoperative mortality even in the absence of a postoperative complication.

Association Between Postoperative Complications and Long-term Survival After Non-cardiac Surgery Among Veterans.

OBJECTIVE: To evaluate the relationship between postoperative complications and long-term survival. SUMMARY AND BACKGROUND: Postoperative complications remain a significant driver of healthcare costs and are associated with increased perioperative mortality, yet the extent to which they are associated with long-term survival is unclear. METHODS: National cohort study of Veterans who underwent non-cardiac surgery using data from the Veterans Affairs Surgical Quality Improvement Program (2011-2016). Patients were classified as having undergone outpatient, low-risk inpatient, or high-risk inpatient surgery. Patients were categorized based on number and type of complications. The association between the number of complications (or the specific type of complication) and risk of death was evaluated using multivariable Cox regression with robust standard errors using a 90-day survival landmark. RESULTS: Among 699,002 patients, complication rates were 3.0%, 6.1%, and 18.3% for outpatient, low-risk inpatient, and high-risk inpatient surgery, respectively. There was a dose-response relationship between an increasing number of complications and overall risk of death in all operative settings [outpatient surgery: no complications (ref); one-hazard ratio (HR) 1.30 (1.23 - 1.38); multiple-HR 1.61 (1.46 - 1.78); low-risk inpatient surgery: one-HR 1.34 (1.26 - 1.41); multiple-HR 1.69 (1.55 - 1.85); high-risk inpatient surgery: one-HR 1.14 (1.10 - 1.18); multiple-HR 1.42 (1.36 - 1.48)]. All complication types were associated with risk of death in at least 1 operative setting, and pulmonary complications, sepsis, and clostridium difficile colitis were associated with higher risk of death across all settings. Conclusions: Postoperative complications have an adverse impact on patients' long-term survival beyond the immediate postoperative period. Although most research and quality improvement initiatives primarily focus on the perioperative impact of complications, these data suggest they also have important longer-term implications that merit further investigation.

Hospital Variation in Mortality After Inpatient Pediatric Surgery.

OBJECTIVE: The aim was to determine the association between risk adjusted hospital perioperative mortality rates, postoperative complications, and failure to rescue (FTR) after inpatient pediatric surgery. BACKGROUND: FTR has been identified as a possible explanatory factor for hospital variation in perioperative mortality in adults. However, the extent to which this may be the case for hospitals that perform pediatric surgery is unclear. METHODS: The Pediatric Health Information System database (2012-2020) was used to identify patients who underwent one of 57 high-risk operations associated with significant perioperative mortality (n=203,242). Academic, pediatric hospitals (n=48) were stratified into quintiles based on risk adjusted inpatient mortality [lower than average, quintile 1 (Q1); higher than average, quintile 5 (Q5)]. Multivariable hierarchical regression was used to evaluate the association between hospital mortality rates, complications, and FTR. RESULTS: Inpatient mortality, complication, and FTR rates were 2.3%, 8.8%, and 8.8%, respectively. Among all patients who died after surgery, only 34.1% had a preceding complication (Q1, 36.1%; Q2, 31.5%; Q3, 34.7%; Q4, 35.7%; Q5, 32.2%; trend test, P =0.49). The rates of observed mortality significantly increased across hospital quintiles, but the difference was <1% (Q1, 1.9%; Q5; 2.6%; trend test, P <0.01). Relative to Q1 hospitals, the odds of complications were not significantly increased at Q5 hospitals [odds ratio (OR): 1.02 (0.87-1.20)]. By comparison, the odds of FTR was significantly increased at Q5 hospitals [OR: 1.60 (1.30-1.96)] with a dose-response relationship across hospital quintiles [Q2-OR: 0.99 (0.80-1.22); Q3-OR: 1.26 (1.03-1.55); Q4-OR: 1.33 (1.09-1.63)]. CONCLUSIONS: The minority of pediatric surgical deaths are preceded by a postoperative complication, but variation in risk adjusted mortality across academic, pediatric hospitals may be partially explained by differences in the recognition and management of postoperative complications. Additional work is needed to identify children at greatest risk of postoperative death from perioperative complications as opposed to those at risk from pre-existing chronic conditions.

Variation in Complications and Mortality According to Infant Diagnosis.

OBJECTIVE: Investigate patterns of infant perioperative mortality, describe the infant diagnoses with the highest mortality burden, and evaluate the association between types of postoperative complications and mortality in infants. BACKGROUND: The majority of mortality events in pediatric surgery occur among infants (ie, children <1 y old). However, there is limited data characterizing patterns of infant perioperative mortality and diagnoses that account for the highest proportion of mortality. METHODS: Infants who received inpatient surgery were identified in the National Surgical Quality Improvement Program-Pediatric database (2012-2019). Perioperative mortality was stratified into mortality associated with a complication or mortality without a complication. Complications were categorized as wound infection, systemic infection, pulmonary, central nervous system, renal, or cardiovascular. Multivariable logistic regression was used to evaluate the association between different complications and complicated mortality. RESULTS: Among 111,946 infants, the rate of complications and perioperative mortality was 10.4% and 1.6%, respectively. Mortality associated with a complication accounted for 38.8% of all perioperative mortality. Seven diagnoses accounted for the highest proportion of mortality events (40.3%): necrotizing enterocolitis (22.3%); congenital diaphragmatic hernia (7.3%); meconium peritonitis (3.8%); premature intestinal perforation (2.5%); tracheoesophageal fistula (1.8%); gastroschisis (1.4%); and volvulus (1.1%). Relative to wound complications, cardiovascular [odds ratio (OR): 19.4, 95% confidence interval (95% CI): 13.9-27.0], renal (OR: 6.88; 4.65-10.2), and central nervous system complications (OR: 6.50; 4.50-9.40) had the highest odds of mortality for all infants. CONCLUSIONS: A small subset of diagnoses account for 40% of all infant mortality and specific types of complications are associated with mortality. These data suggest targeted quality improvement initiatives could be implemented to reduce adverse surgical outcomes in infants.

Treatment Disparities Partially Mediate Socioeconomic- and Race/Ethnicity-Based Survival Disparities in Stage I-II Hepatocellular Carcinoma.

BACKGROUND: Low socioeconomic status (SES) patients with early-stage hepatocellular carcinoma (HCC) receive procedural treatments less often and have shorter survival. Little is known about the extent to which these survival disparities result from treatment-related disparities versus other causal pathways. We aimed to estimate the proportion of SES-based survival disparities that are mediated by treatment- and facility-related factors among patients with stage I-II HCC. METHODS: We analyzed patients aged 18-75 years diagnosed with stage I-II HCC in 2008-2016 using the National Cancer Database. Inverse odds weighting mediation analysis was used to calculate the proportion mediated by three mediators: procedure type, facility volume, and facility procedural interventions offered. Intersectional analyses were performed to determine whether treatment disparities played a larger role in survival disparities among Black and Hispanic patients. RESULTS: Among 46,003 patients, 15.0% had low SES, 71.6% had middle SES, and 13.4% had high SES. Five-year overall survival was 46.9%, 39.9%, and 35.7% among high, middle, and low SES patients, respectively. Procedure type mediated 45.9% (95% confidence interval [CI] 31.1-60.7%) and 36.7% (95% CI 25.7-47.7%) of overall survival disparities for low and middle SES patients, respectively, which was more than was mediated by the two facility-level mediators. Procedure type mediated a larger proportion of survival disparities among low-middle SES Black (46.6-48.2%) and Hispanic patients (92.9-93.7%) than in White patients (29.5-29.7%). CONCLUSIONS: SES-based disparities in use of procedural interventions mediate a large proportion of survival disparities, particularly among Black and Hispanic patients. Initiatives aimed at attenuating these treatment disparities should be pursued.

Association between readmission care fragmentation and outcomes after interventions for peripheral arterial disease.

OBJECTIVE: Lower extremity revascularization (LER) for peripheral artery disease is complicated by the frequent need for readmission. However, it is unclear if readmission to a nonindex LER facility (ie, a facility different from the one where the LER was performed) compared with the index LER facility is associated with worse outcomes. METHODS: This was a national cohort study of older adults who underwent open, endovascular, or hybrid LER for peripheral artery disease (January 1, 2010, to December 31, 2018) in the Vascular Quality Initiative who were readmitted within 90 days of their vascular procedure. This dataset was linked to Medicare claims and the American Hospital Association Annual Survey. The primary outcome was 90-day mortality and the secondary outcome was major amputation at 90 days after LER. The primary exposure was the location of the first readmission after LER (categorized as occurring at the index LER facility vs a nonindex LER facility). Generalized estimating equations logistic regression models were used to assess the association between readmission location and 90-day mortality and amputation. RESULTS: Among 42,429 patients who underwent LER, 33.0% were readmitted within 90 days. Of those who were readmitted, 27.3% were readmitted to a nonindex LER facility, and 42.2% of all readmissions were associated with procedure-related complications. Compared with patients readmitted to the index LER facility, those readmitted to a nonindex facility had a lower proportion of procedure-related reasons for readmission (21.5% vs 50.1%; P < .001). Most of the patients readmitted to a nonindex LER facility lived further than 31 miles from the index LER facility (39.2% vs 19.6%; P < .001) and were readmitted to a facility with a total bed size of <250 (60.1% vs 11.9%; P < .001). Readmission to a nonindex LER facility was not associated with 90-day mortality or 90-day amputation. However, readmission for a procedure-related complication was associated with major amputation (90-day amputation: adjusted odds ratio, 3.33; 95% confidence interval, 2.89-3.82). CONCLUSIONS: Readmission after LER for a procedure-related complication is associated with subsequent amputation. This finding suggests that quality improvement efforts should focus on understanding various types of procedure-related failure after LER and its role in limb salvage.

A Retrospective Cohort Study to Evaluate Adding Biomarkers to the Risk Analysis Index of Frailty.

INTRODUCTION: The Risk Analysis Index (RAI) is a frailty assessment tool associated with adverse postoperative outcomes including 180 and 365-d mortality. However, the RAI has been criticized for only containing subjective inputs rather than including more objective components such as biomarkers. METHODS: We conducted a retrospective cohort study to assess the benefit of adding common biomarkers to the RAI using the Veterans Affairs Surgical Quality Improvement Program (VASQIP) database. RAI plus body mass index (BMI), creatinine, hematocrit, and albumin were evaluated as individual and composite variables on 180-d postoperative mortality. RESULTS: Among 480,731 noncardiac cases in VASQIP from 2010 to 2014, 324,320 (67%) met our inclusion criteria. Frail patients (RAI ≥30) made up to 13.0% of the sample. RAI demonstrated strong discrimination for 180-d mortality (c = 0.839 [0.836-0.843]). Discrimination significantly improved with the addition of Hematocrit (c = 0.862 [0.859-0.865]) and albumin (c = 0.870 [0.866-0.873]), but not for body mass index (BMI) or creatinine. However, calibration plots demonstrate that the improvement was primarily at high RAI values where the model overpredicts observed mortality. CONCLUSIONS: While RAI's ability to predict the risk of 180-d postoperative mortality improves with the addition of certain biomarkers, this only observed in patients classified as very frail (RAI >49). Because very frail patients have significantly elevated observed and predicted mortality, the improved discrimination is likely of limited clinical utility for a frailty screening tool.

Variation in hospital utilization of palliative interventions for patients with advanced gastrointestinal cancer near end of life.

BACKGROUND: Patients with advanced gastrointestinal (GI) cancer often undergo noncurative interventions with palliative intent to relieve high symptom burden near end of life. Hospital-level variation in intervention utilization remains unclear. METHODS: National cohort study of 142 304 patients with stage III or IV GI cancer within the National Cancer Database (2004-2014) who died within 1-year of diagnosis. Hospitals were stratified by palliative intervention utilization (surgery, chemotherapy, radiation, pain management). Multivariable, multinomial regression evaluated the association between patient/hospital factors and palliative intervention utilization. RESULTS: Across 1322 hospitals, median hospital palliative intervention utilization was 12.0% [interquartile range: 0.0%-26.1%]. Utilization increased over time in all but lowest utilizing hospitals. Relative to lowest utilizing hospitals, factors associated with a lower likelihood of care at highest utilizing hospitals included: race (White [ref]; Black-Relative Risk Ratio [RRR] 0.81, 95% confidence interval [0.77-0.85]) and lower income (RRR 0.81 [0.78-0.84]). Factors associated with a higher likelihood included: lower education level (RRR 1.62 [1.55-1.69]) and hospital type (community program [ref]; comprehensive community-RRR 1.33 [1.26-1.41]; academic-RRR 1.88 [1.77-1.99]; integrated network-RRR 1.79 [1.66-1.93]). CONCLUSION: Hospital variation in palliative intervention use is substantial and potentially associated with sociodemographic and hospital characteristics. Future work can examine how differences in hospital care processes translate to quantity/quality of life for cancer patients.

Evaluating the benefit of surgical resection for hepatocellular carcinoma with multifocality or intrahepatic vascular invasion.

BACKGROUND: The role of hepatectomy for hepatocellular carcinoma (HCC) with multifocality or intrahepatic vascular involvement remains ill-defined. Our objective was to evaluate benefits of surgical resection for patients with these high-risk features. METHODS: The National Cancer Database was used to identify HCC patients with vascular involvement and/or multifocality (T2/T3, N-/M-) from 2011 to 2015. Propensity score matching (k-nearest neighbors, no replacement, 1:1) grouped patients by treatment: surgical resection versus non-surgical modalities. Groups were matched using patient, clinical, and liver-specific characteristics. Median overall survival (OS) was calculated using Kaplan-Meier, and adjusted analyses were performed using shared frailty models. RESULTS: 14,557 patients met inclusion criteria, including 1892 (9.4%) treated with surgical resection. Median cohort OS was 20.5 months. After adjustment, surgical resection was associated with survival advantage compared to non-surgical treatment (37.8 versus 15.7 months, log-rank P < .001; adjusted hazard ratio 0.49, 95% confidence interval, 0.45-0.54). Patients with minimal comorbidity, unifocal disease, and age <54 had highest probability of survival one year post-surgery. CONCLUSIONS: Surgical resection is associated with a survival advantage in HCC with multifocality and/or intrahepatic vascular involvement. The presence of these features should not contraindicate consideration of hepatectomy in suitable surgical candidates.

Bayesian Approach to Understand the Association Between Treatment Down-staging and Survival for Patients With Pancreatic Adenocarcinoma.

OBJECTIVE: To evaluate the association between staging concordance, treatment sequencing, and response to neoadjuvant therapy (NAT) on the survival of patients with pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: NAT is increasingly utilized in the management of patients with PDAC, but it is unclear whether its benefit is contingent on tumor down-staging. METHODS: This was a cohort study of stage I-III PDAC patients in the National Cancer Database (2006-2015) treated with upfront resection or NAT followed by surgery. We determined staging concordance using patients' clinical and pathological staging data. For NAT patients, we used Bayesian analysis to ascertain staging concordance accounting for down-staging. RESULTS: Among 16,597 patients treated at 979 hospitals, 13,982 had an upfront resection and 2,615 NAT followed by surgery. Overall survival (OS) at 5-years ranged from 26.0% (95% CI 24.9%-27.1%) among cT1-2N0 patients to 18.6% (17.9%-19.2%) among cT1-3N+ ones. Patients with cT3-4 or cN+ tumors had improved OS after NAT compared to upfront surgery (all p< 0.001), while there was no difference among patients with cT1-2N0 (P = 0.16) disease. Relative to accurately staged cT1-2-3N+ or cT4 patients treated with upfront surgery, NAT was associated with a lower risk of death [HR 0.46 (0.37-0.57) for N+; HR 0.56 (0.40-0.77) for T4 disease], even among those without tumor down-staging [HR 0.81 (0.73-0.90) for N+; HR 0.48 (0.39-0.60) for T4]. CONCLUSIONS: NAT is associated with improved survival for PDAC, particularly for patients with more advanced disease and regardless of down-staging. Consideration should be given to recommending NAT for all PDAC patients.

Complications and Failure to Rescue After Inpatient Pediatric Surgery.

OBJECTIVE: To describe the frequency and patterns of postoperative complications and FTR after inpatient pediatric surgical procedures and to evaluate the association between number of complications and FTR. SUMMARY AND BACKGROUND: FTR, or a postoperative death after a complication, is currently a nationally endorsed quality measure for adults. Although it is a contributing factor to variation in mortality, relatively little is known about FTR after pediatric surgery. METHODS: Cohort study of 200,554 patients within the National Surgical Quality Improvement Program-Pediatric database (2012-2016) who underwent a high (≥ 1%) or low (< 1%) mortality risk inpatient surgical procedures. Patients were stratified based on number of postoperative complications (0, 1, 2, or ≥3) and further categorized as having undergone either a low- or high-risk procedure. The association between the number of postoperative complications and FTR was evaluated with multivariable logistic regression. RESULTS: Among patients who underwent a low- (89.4%) or high-risk (10.6%) procedures, 14.0% and 12.5% had at least 1 postoperative complication, respectively. FTR rates after low- and high-risk procedures demonstrated step-wise increases as the number of complications accrued (eg, low-risk- 9.2% in patients with ≥3 complications; high-risk-36.9% in patients with ≥ 3 complications). Relative to patients who had no complications, there was a dose-response relationship between mortality and the number of complications after low-risk [1 complication - odds ratio (OR) 3.34 (95% CI 2.62-4.27); 2 - OR 10.15 (95% CI 7.40-13.92); ≥3-27.48 (95% CI 19.06-39.62)] and high-risk operations [1 - OR 3.29 (2.61-4.16); 2-7.24 (5.14-10.19); ≥3-20.73 (12.62-34.04)]. CONCLUSIONS: There is a dose-response relationship between the number of postoperative complications after inpatient surgery and FTR, ever after common, "minor" surgical procedures. These findings suggest FTR may be a potential quality measure for pediatric surgical care.

Use of Palliative Interventions at End of Life for Advanced Gastrointestinal Cancer.

BACKGROUND: Despite the well-established benefits of palliative care, little is known about the use of palliative interventions among patients with advanced gastrointestinal (GI) cancer near the end of life (EOL). METHODS: A national cohort study analyzed 142,304 patients with advanced GI cancers (stage 3 or 4) near EOL (death within 1 year of diagnosis) in the National Cancer Database (2004-2014) who received palliative interventions (defined as treatment to relieve symptoms: surgery, radiation, chemotherapy, and/or pain management). The study used multivariable hierarchical regression evaluate the association between the use of palliative interventions, temporal trends, and patient and hospital factors. RESULTS: Overall, 16.5% of the patients were treated with a palliative intervention, and use increased over time (13.4% in 2004 vs 19.8% in 2014; trend test, p < 0.001). Palliative interventions were used most frequently for esophageal cancer (20.6%) and least frequently for gallbladder cancer (13.3%). Palliative interventions were associated with younger age (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98-0.99), recent diagnosis year (OR, 1.05; 95% CI, 1.04-1.06), black race (white [ref]; OR, 1.07; 95% CI, 1.01-1.12), insurance status (no insurance [ref]; private: OR, 0.92; 95% CI ,0.95-0.99), hospital type (community cancer program [ref]; integrated network cancer programs: OR, 1.37; 95% CI ,1.07-1.75), and stage 4 disease (OR, 2.17; 95% CI, 2.07-2.27). Patients in southern and western regions were less likely to receive palliative intervention (Northeast [ref]; OR, 0.76; 95% CI, 0.62-0.94 and OR 0.46; 95% CI, 0.37-0.57, respectively). CONCLUSION: Increased palliative intervention use over time suggests ongoing changes in how care is delivered to GI cancer patients toward EOL. However, sociodemographic and geographic variation suggests opportunities to address barriers to optimal EOL care.

Clinical Understaging, Treatment Response, and Survival Among Esophageal Adenocarcinoma Patients.

INTRODUCTION: Selecting appropriate management for patients with esophageal adenocarcinoma (EA) is predicated on accurate clinical staging information. Inaccurate information could lead to inappropriate treatment and suboptimal survival. We investigated the relationship between staging accuracy, treatment, and survival. METHODS: This was a national cohort study of EA patients in the National Cancer Data Base (2006-2015) treated with upfront resection or neoadjuvant therapy (NAT). Clinical and pathological staging information was used to ascertain staging concordance for each patient. For NAT patients, Bayesian analysis was used to account for potential downstaging. We evaluated the association between staging concordance, receipt of NAT, and survival through hierarchical logistic regression and multivariable Cox regression. RESULTS: Among 7635 EA patients treated at 877 hospitals, 3038 had upfront resection and 4597 NAT followed by surgery. Relative to accurately staged patients, understaging was associated with a lower likelihood (odds ratio [OR] 0.04 95% confidence interval [CI] 0.02-0.05) while overstaging was associated with a greater likelihood of receiving NAT (OR 1.98 [1.53-2.56]). Relative to upfront surgery, treatment of cT1N0 patients with NAT was associated with a higher risk of death (HR 3.08 [2.36-4.02]). For accurately or overstaged cT3-T4 patients, NAT was associated with a lower risk of death whether downstaging occurred (ypN0 disease-HR 0.67 [0.49-0.92]; N+ disease-HR 0.55 [0.45-0.66]) or not (ypN + disease-HR 0.78 [95% CI 0.65-0.93]). CONCLUSIONS: Clinical understaging is associated with receipt of NAT which in turn may have a stage-specific impact on patients' survival regardless of treatment response. Guidelines should account for the possibility of inaccurate clinical staging.

Understanding the association between clinical staging accuracy, treatment response, and survival among gastric cancer patients through Bayesian analysis.

BACKGROUND: Neoadjuvant therapy (NAT) improves survival among patients with locally advanced gastric cancer (GC), but it remains unclear whether its benefit is contingent on treatment response. METHODS: This is a national cohort study of stage Ib-III GC patients in the National Cancer Data Base (2006-2015) treated with upfront resection or NAT followed by surgery. Bayesian analysis was used for NAT patients to ascertain staging concordance and to account for down-staging. We used multivariable Cox regression to evaluate the association between staging concordance, treatment, response to NAT, and survival. RESULTS: The cohort included 13 340 patients treated at 1124 hospitals. Staging concordance ranged from 86.1% for cT3-4N+ to 34.7% for cT2N0 patients. Relative to accurately staged patients treated with upfront surgery, NAT was associated with a decreased risk of death if there was disease down-staging among those with cT1-2N+ (hazard ratio [HR]: 0.43 [0.30-0.61]), cT3-4N0 (HR: 0.69 [0.54-0.88]), and cT3-4N+ (HR: 0.51 [0.48-0.58]) tumors, and in the absence of down-staging among cT3-4N+ patients (HR: 0.83 [0.74-0.92]). Conversely, NAT without down-staging increased the risk of death among those with intermediate-stage disease. CONCLUSIONS: NAT is associated with improved survival for GC, but it seems to be contingent on treatment response among patients with intermediate-stage disease.

Clinical Utility of the Risk Analysis Index as a Prospective Frailty Screening Tool within a Multi-practice, Multi-hospital Integrated Healthcare System.

OBJECTIVE: The goal of this project was to first address barriers to implementation of the Risk Analysis Index (RAI) within a large, multi-hospital, integrated healthcare delivery system, and to subsequently demonstrate its utility for identifying at-risk surgical patients. BACKGROUND: Prior studies demonstrate the validity of the RAI for evaluating preoperative frailty, but they have not demonstrated the feasibility of its implementation within routine clinical practice. METHODS: Implementation of the RAI as a frailty screening instrument began as a quality improvement initiative at the University of Pittsburgh Medical Center in July 2016. RAI scores were collected within a REDCap survey instrument integrated into the outpatient electronic health record and then linked to information from additional clinical datasets. NSQIP-eligible procedures were queried within 90 days following the RAI, and the association between RAI and postoperative mortality was evaluated using logistic regression and Cox proportional hazards models. Secondary outcomes such as inpatient length of stay and readmissions were also assessed. RESULTS: RAI assessments were completed on 36,261 unique patients presenting to surgical clinics across five hospitals from July 1 to December 31, 2016, and 8,172 of these underwent NSQIP-eligible surgical procedures. The mean RAI score was 23.6 (SD 11.2), the overall 30-day and 180-day mortality after surgery was 0.7% and 2.6%, respectively, and the median time required to collect the RAI was 33 [IQR 23-53] seconds. Overall clinic compliance with the recommendation for RAI assessment increased from 58% in the first month of the study period to 84% in the sixth and final month. RAI score was significantly associated with risk of death (HR=1.099 [95% C.I.: 1.091 - 1.106], p < 0.001). At an RAI cutoff of ≥37, the positive predictive values for 30- and 90-day readmission were 14.8% and 26.2%, respectively, and negative predictive values were 91.6% and 86.4%, respectively. CONCLUSIONS: The RAI frailty screening tool can be efficiently implemented within multi-specialty, multi-hospital healthcare systems. In the context of our findings and given the value of the RAI in predicting adverse postoperative outcomes, health systems should consider implementing frailty screening within surgical clinics.

Comparative Effectiveness of Neoadjuvant Therapy and Upfront Resection for Patients with Resectable Pancreatic Adenocarcinoma: An Instrumental Variable Analysis.

BACKGROUND: Neoadjuvant therapy (NAT) is increasingly being used in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC); however, there is a lack of evidence regarding the benefit among these patients. OBJECTIVE: The aim of this study was to evaluate overall survival (OS) in PDAC patients with resectable disease treated with NAT or upfront resection through instrumental variable (IV) analysis. DESIGN: A national cohort study of resectable PDAC patients in the National Cancer Data Base (2007-2015) treated with either upfront surgery or resection after NAT. Using multivariable modeling and IV methods, OS was compared between those treated with NAT and upfront resection. The IV was hospital-level NAT utilization in the most recent year prior to treatment. RESULTS: The cohort included 16,666 patients (14,012 upfront resection; 2654 NAT) treated at 779 hospitals. Among those treated with upfront resection, 59.9% received any adjuvant therapy. NAT patients had higher median (27.9 months, 95% confidence interval [CI] 26.2-29.1) and 5-year OS (24.1%, 95% CI 21.9-26.3%) compared with those treated with upfront surgery (median 21.2 months, 95% CI 20.7-21.6; 5-year survival 20.9%, 95% CI 20.1-21.7%). After multivariable modeling, NAT was associated with an approximately 20% decrease in the risk of death (hazard ratio [HR] 0.78, 95% CI 0.73-0.84), and this effect was magnified in the IV analysis (HR 0.61, 95% CI 0.47-0.79). CONCLUSIONS: In patients with resectable PDAC, NAT is associated with improved survival relative to upfront resection. Given the benefits of multimodality therapy and the challenges in receiving adjuvant therapy, consideration should be given to treating all PDAC patients with NAT.

National Utilization of Imatinib in the Management of Resected Gastrointestinal Stromal Tumors.

BACKGROUND: Imatinib decreases recurrence risk and improves overall survival (OS) in localized gastrointestinal stromal tumors (GISTs); however, the extent to which patients receive appropriate treatment in the US has not been well characterized. METHODS: Patients with non-metastatic, resectable GIST were included in this study (National Cancer Database, 2010-2015). Those with a low-risk of recurrence were classified as receiving overtreatment or guideline-concordant treatment, while those with a high-risk of recurrence were classified as receiving undertreatment or guideline-concordant treatment. Multivariable logistic regression was used to determine factors associated with non-concordant treatment. The association between non-concordant treatment and OS was evaluated using multivariable Cox regression and propensity score matching. RESULTS: Among 3088 patients with high-risk GIST, 41% were undertreated, and among 3908 patients with low-risk GIST, 18.8% were overtreated. For patients with high-risk GIST, age > 60 years, African American race, and treatment at a community or comprehensive cancer program were associated with undertreatment. Among low-risk patients, small bowel primary, tumor size > 2 cm, and tumors with > 1 mitotic figure per 50 high-power fields were more likely to be overtreated. After propensity score matching, guideline-concordant therapy was associated with an 8.8% improvement in 5-year OS (81.9% vs. 73.1%, p = 0.002) for those with high-risk GIST and decreased risk of death (hazard ratio 0.63, 95% confidence interval 0.47-0.84). There was no statistically significant difference in survival for patients with low-risk GIST with the addition of imatinib overtreatment (overtreatment 93.9% vs. 89.6%, p = 0.053). CONCLUSIONS: Nearly 30% of GIST patients do not receive guideline-concordant treatment and future work is needed to understand the factors driving non-concordant treatment.

Time to Rethink Upfront Surgery for Resectable Intrahepatic Cholangiocarcinoma? Implications from the Neoadjuvant Experience.

BACKGROUND: While surgery is a mainstay of curative-intent treatment for patients with intrahepatic cholangiocarcinoma (IHC), the role of neoadjuvant therapy (NT) has not been well-established. We sought to describe trends in NT utilization, characterize associated factors, and evaluate association with overall survival (OS). METHODS: Retrospective cohort study of 4456 surgically resected IHC patients within National Cancer Data Base (2006-2016). NT included chemotherapy alone and/or (chemo)radiation. Descriptive statistics used to describe the cohort. Multivariable hierarchical logistic regression models were used to examine factors associated with NT administration. Analyses conducted comparing OS among upfront surgery patients and NT patients using propensity matching using nearest-neighbor methodology and adjustment using inverse probability of treatment weighting (IPTW). Association between NT and risk of death evaluated using multivariable Cox shared frailty modeling. RESULTS: Utilization of NT did not significantly increase over time (11%-2006 to 16%-2016, trend test p = 0.07) but did increase among patients with clinical nodal involvement (cN+, 13% to 36%, p = 0.002). Factors associated with NT use include cN+ disease (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.31-2.15) and advanced clinical T stage: T2 (OR 1.65, 95% CI 1.33-2.06); T3 (OR 1.51, 95% CI 1.13-2.02). After propensity matching, NT associated with a 23% decreased risk of death relative to upfront surgery (hazard ratio [HR] 0.77, 95% CI 0.61-0.97). Findings were similar after IPTW (HR 0.83, 95% CI 0.78-0.88). CONCLUSIONS: NT is increasingly used for the management of IHC patients with characteristics indicating aggressive tumor biology and is associated with decreased risk of death. These data suggest need for prospective studies of NT in management of patients with potentially resectable IHC.

Comparative Effectiveness of Risk-adjusted Cumulative Sum and Periodic Evaluation for Monitoring Hospital Perioperative Mortality.

BACKGROUND: National surgical quality improvement (QI) programs use periodic, risk-adjusted evaluation to identify hospitals with higher than expected perioperative mortality. Rapid, accurate identification of poorly performing hospitals is critical for avoiding potentially preventable mortality and represents an opportunity to enhance QI efforts. METHODS: Hospital-level analysis using Veterans Affairs (VA) Surgical Quality Improvement Program data (2011-2016) to compare identification of hospitals with excess, risk-adjusted 30-day mortality using observed-to-expected (O-E) ratios (ie, current gold standard) and cumulative sum (CUSUM) with V-mask. Various V-mask slopes and radii were evaluated-slope of 2.5 and radius of 1.0 was used as the base case. RESULTS: Hospitals identified by CUSUM and quarterly O-E were identified midway into a quarter [median 47 days; interquartile range (IQR): 24-61 days before quarter end] translating to a median of 129 (IQR: 60-187) surgical cases and 368 (IQR: 145-681) postoperative inpatient days occurring after a CUSUM signal, but before the quarter end. At hospitals identified by CUSUM but not O-E, a median of 2 deaths within a median of 5 days triggered a signal. In some cases, these clusters extended beyond CUSUM identification date with as many as 8 deaths undetected using O-E. Sensitivity and negative predictive values for CUSUM relative to O-E were 71.9% (95% confidence interval: 66.2%-77.1%) and 95.5% (94.4%-96.4%), respectively. CONCLUSIONS: CUSUM evaluation identifies hospitals with clusters of mortality in excess of expected more rapidly than periodic analysis. CUSUM represents an analytic tool national QI programs could utilize to provide participating hospitals with data that could facilitate more proactive implementation of local interventions to help reduce potentially avoidable perioperative mortality.

Relationship Between Perioperative Outcomes Used for Profiling Hospital Noncardiac Surgical Quality.

BACKGROUND: Risk-adjusted morbidity and mortality are commonly used by national surgical quality improvement (QI) programs to measure hospital-level surgical quality. However, the degree of hospital-level correlation between mortality, morbidity, and other perioperative outcomes (like reoperation) collected by contemporary surgical QI programs has not been well-characterized. MATERIALS AND METHODS: Veterans Affairs (VA) Surgical Quality Improvement Program (VASQIP) data (2015-2016) were used to evaluate hospital-level correlation in performance between risk-adjusted 30-d mortality, morbidity, major morbidity, reoperation, and 2 composite outcomes (1- mortality, major morbidity, or reoperation; 2- mortality or major morbidity) after noncardiac surgery. Correlation between outcomes rates was evaluated using Pearson's correlation coefficient. Correlation between hospital risk-adjusted performance rankings was evaluated using Spearman's correlation. RESULTS: Based on a median of 232 [IQR 95-331] quarterly surgical cases abstracted by VASQIP, statistical power for identifying 30-d mortality outlier hospitals was estimated between 3.3% for an observed-to-expected ratio of 1.1 and 45.7% for 3.0. Among 230,247 Veterans who underwent a noncardiac operation at 137 VA hospitals, there were moderate hospital-level correlations between various risk-adjusted outcome rates (highest r = 0.40, mortality and composite 1; lowest r = 0.32, mortality and morbidity). When hospitals were ranked based on performance, there was low-to-moderate correlation between rankings on the various outcomes (highest ρ = 0.47, mortality and composite 1; lowest ρ = 0.37, mortality and major morbidity). CONCLUSIONS: Modest hospital-level correlations between perioperative outcomes suggests it may be difficult to identify high (or low) performing hospitals using a single measure. Additionally, while composites of currently measured outcomes may be an efficient way to improve analytic sample size (relative to evaluations based on any individual outcome), further work is needed to understand whether they provide a more robust and accurate picture of hospital quality or whether evaluating performance across a portfolio of individual measures is most effective for driving QI.