Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: While lower socioeconomic status has been shown to correlate with worse outcomes in cancer care, data correlating neighborhood-level metrics with outcomes are scarce. We aim to explore the association between neighborhood disadvantage and both short- and long-term postoperative outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed 243 patients who underwent resection for PDAC at a single institution between 1 January 2010 and 15 September 2021. To measure neighborhood disadvantage, the cohort was divided into tertiles by Area Deprivation Index (ADI). Short-term outcomes of interest were minor complications, major complications, unplanned readmission within 30 days, prolonged hospitalization, and delayed gastric emptying (DGE). The long-term outcome of interest was overall survival. Logistic regression was used to test short-term outcomes; Cox proportional hazards models and Kaplan-Meier method were used for long-term outcomes. RESULTS: The median ADI of the cohort was 49 (IQR 32-64.5). On adjusted analysis, the high-ADI group demonstrated greater odds of suffering a major complication (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.26-6.40; p = 0.01) and of an unplanned readmission (OR, 3.09; 95% CI, 1.16-9.28; p = 0.03) compared with the low-ADI group. There were no significant differences between groups in the odds of minor complications, prolonged hospitalization, or DGE (all p > 0.05). High ADI did not confer an increased hazard of death (p = 0.63). CONCLUSIONS: We found that worse neighborhood disadvantage is associated with a higher risk of major complication and unplanned readmission after pancreatectomy for PDAC.

Colon Cancer Survival Among South Asian Americans: A Cross-Sectional Analysis of a National Dataset.

INTRODUCTION: Colon cancer (CC) is one of the most common cancers among South Asian Americans (SAAs). The objective of this study was to measure differences in risk-adjusted survival among SAAs with CC compared to non-Hispanic Whites (NHWs) using a representative national dataset from the United States. METHODS: A retrospective analysis of patients with CC in the National Cancer Database (2004-2020) was performed. Differences in presentation, management, median overall survival (OS), three-year survival, and five-year survival between SAAs and NHWs were compared. Kaplan-Meier analysis and multivariable Cox regression were used to assess differences in survival outcomes, adjusting for demographics, presentation, and treatments received. RESULTS: Data from 2873 SAA and 639,488 NHW patients with CC were analyzed. SAAs were younger at diagnosis (62.2 versus 69.5 y, P < 0.001), higher stage (stage III [29.0% versus 26.2%, P = 0.001] or Stage IV [21.4% versus 20.0%, P = 0.001]), and experienced delays to first treatment (SAA 5.9% versus 4.9%, P = 0.003). SAAs with CC had higher OS (median not achieved versus 68.1 mo for NHWs), three-year survival (76.3% versus 63.4%), and five-year survival (69.1% versus 52.9%). On multivariable Cox regression, SAAs with CC had a lower risk of death across all stages (hazard ratio: 0.64, P < 0.001). CONCLUSIONS: In this national study, SAA patients with CC presented earlier in life with more advanced disease, and a higher proportion experienced treatment delay compared to NHW patients. Despite these differences, SAAs had better adjusted OS than NHW, warranting further exploration of tumor biology and socioeconomic determinants of cancer outcomes in SAAs.

Neighborhood-Level Socioeconomic Disadvantage Predicts Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignancy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves survival in select patients with peritoneal metastases (PM), but the impact of social determinants of health on CRS/HIPEC outcomes remains unclear. PATIENTS AND METHODS: A retrospective review was conducted of a multi-institutional database of patients with PM who underwent CRS/HIPEC in the USA between 2000 and 2017. The area deprivation index (ADI) was linked to the patient's residential address. Patients were categorized as living in low (1-49) or high (50-100) ADI residences, with increasing scores indicating higher socioeconomic disadvantage. The primary outcome was overall survival (OS). Secondary outcomes included perioperative complications, hospital/intensive care unit (ICU) length of stay (LOS), and disease-free survival (DFS). RESULTS: Among 1675 patients 1061 (63.3%) resided in low ADI areas and 614 (36.7%) high ADI areas. Appendiceal tumors (n = 1102, 65.8%) and colon cancer (n = 322, 19.2%) were the most common histologies. On multivariate analysis, high ADI was not associated with increased perioperative complications, hospital/ICU LOS, or DFS. High ADI was associated with worse OS (median not reached versus 49 months; 5 year OS 61.0% versus 28.2%, P < 0.0001). On multivariate Cox-regression analysis, high ADI (HR, 2.26; 95% CI 1.13-4.50; P < 0.001), cancer recurrence (HR, 2.26; 95% CI 1.61-3.20; P < 0.0001), increases in peritoneal carcinomatosis index (HR, 1.03; 95% CI 1.01-1.05; P < 0.001), and incomplete cytoreduction (HR, 4.48; 95% CI 3.01-6.53; P < 0.0001) were associated with worse OS. CONCLUSIONS: Even after controlling for cancer-specific variables, adverse outcomes persisted in association with neighborhood-level socioeconomic disadvantage. The individual and structural-level factors leading to these cancer disparities warrant further investigation to improve outcomes for all patients with peritoneal malignancies.

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.

Interpreting the risk analysis index of frailty in the context of surgical oncology.

BACKGROUND AND OBJECTIVES: The Risk Analysis Index (RAI) accurately predicts adverse postoperative outcomes but the inclusion of cancer status in the RAI has raised two key concerns about its suitability for use in surgical oncology: (1) the potential over classification of cancer patients as frail, and (2) the potential overestimation of postoperative mortality for patients with surgically curable cancers. METHODS: We performed a retrospective cohort analysis to assess the RAI's power to appropriately identify frailty and predict postoperative mortality in cancer patients. We assessed discrimination for mortality and calibration across five RAI models-the complete RAI and four variants that removed different cancer-related variables. RESULTS: We found that the presence of disseminated cancer was a key variable driving the RAI's power to predict postoperative mortality. The model including only this variable [RAI (disseminated cancer)] was similar to the complete RAI in the overall sample (c = 0.842 vs. 0.840) and outperformed the complete RAI in the cancer subgroup (c = 0.736 vs 0.704, respectively, p < 0.0001, Max R2 = 19.3% vs. 15.1%, respectively). CONCLUSION: The RAI demonstrates somewhat less discrimination when applied exclusively to cancer patients, but remains a strong predictor of postoperative mortality, especially in the setting of disseminated cancer.

Rethinking Routine Intensive Care After Cytoreductive Surgery With Heated Intraperitoneal Chemotherapy: The Fiscal Argument.

BACKGROUND: Patients undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) are frequently admitted to the intensive care unit (ICU) for mitigation of potential complications, although ICU length of stay (LOS) is a significant driver of cost. This study asked whether a fiscal argument could be made for the selective avoidance of ICU admission after CRS/HIPEC. METHODS: Prospective data for select low-risk patients (e.g., lower peritoneal cancer index [PCI]) admitted to the intermediate care unit (IMC) instead of the ICU after CRS/HIPEC were matched with a historic cohort routinely admitted to the ICU. Cohort comparisons and the impact of the intervention on cost were assessed. RESULTS: The study matched 81 CRS/HIPEC procedures to form a cohort of 49 pre- and 15 post-intervention procedures for patients with similar disease burdens (mean PCI, 8 ± 6.7 vs. 7 ± 5.1). The pre-intervention patients stayed a median of 1 day longer in the ICU (1 day [IQR, 1-1 day] vs. 0 days [IQR, 0-0 days]) and had a longer LOS (8 days [IQR, 7-11 days] vs. 6 days [IQR, 5.5-9 days]). Complications and complication severity did not differ statistically. The median total hospital cost was lower after intervention ($30,845 [IQR, $30,181-$37,725] vs. $41,477 [IQR, $33,303-$51,838]), driven by decreased indirect fixed cost ($8984 [IQR, $8643-$11,286] vs. $14,314 [IQR, $12,206-$18,266]). In a weighted multiple variable linear regression analysis, the intervention was associated with a savings of $2208.68 per patient. CONCLUSIONS: Selective admission to the IMC after CRS/HIPEC was associated with $2208.68 in savings per patient without added risk. In this era of cost-conscious practice of medicine, these data highlight an opportunity to decrease cost by more than 5% for patients undergoing CRS/HIPEC.

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.

The Correlation Between Case Total Work Relative Value Unit, Operative Stress, and Patient Frailty: Retrospective Cohort Study.

OBJECTIVE: Assess the relationships between case total work relative value units (wRVU), patient frailty, and the physiologic stress of surgical interventions. SUMMARY OF BACKGROUND DATA: Surgeon reimbursement is frequently apportioned by wRVU. These subjective, procedure-specific valuations generated by physician survey estimate the intensity and time for typical patient care services. We hypothesized wRVU would not adequately account for patient-specific factors, such as frailty, that modify the required physician work, regardless of procedural complexity. METHODS: Using National and Veterans Affairs Surgical Quality Improvement Programs (2015-2018), we evaluated the correlation between case total wRVU, patient frailty (risk analysis index) and physiologic surgical stress (operative stress score). RESULTS: Of 4,111,371 (86%) cases, the correlation between total wRVU and operative stress was moderate [ρs = 0.587 (95% confidence interval, 0.586-0.587)], but negligible with frailty ρ = 0.177 (95% confidence interval, 0.176-0.178)]. Very high operative stress procedures [n = 34,047 (1%)] generated a mean total wRVU of 55.1 (standard deviation, 12.9), comprising 7%, 2%, and 1% of thoracic, vascular, and general surgical cases, respectively. Very frail patients [n = 152,535 (4%)] accounted for 9% of thoracic, 9% of vascular, 4% of general, 5% of urologic, and 4% of neurologic surgical cases, generating 21.0 (standard deviation, 12.4) mean total wRVU. Some nonfrail patients undergoing low operative stress procedures [n = 60,128 (2%)] nonetheless generated the highest quintile wRVU; these comprised >15% of plastic, gynecologic, and urologic surgical cases. CONCLUSIONS: Surgeon reimbursement correlates with operative stress but not patient frailty. The total wRVU does not adequately reflect patient-specific factors that increase the physician workload required to render optimal care to complex patients.

Leveraging Decision Curve Analysis to Improve Clinical Application of Surgical Risk Calculators.

BACKGROUND: Surgical risk calculators (SRCs) have been developed for estimation of postoperative complications but do not directly inform decision-making. Decision curve analysis (DCA) is a method for evaluating prediction models, measuring their utility in guiding decisions. We aimed to analyze the utility of SRCs to guide both preoperative and postoperative management of patients undergoing hepatopancreaticobiliary surgery by using DCA. METHODS: A single-institution, retrospective review of patients undergoing hepatopancreaticobiliary operations between 2015 and 2017 was performed. Estimation of postoperative complications was conducted using the American College of Surgeons SRC [ACS-SRC] and the Predictive OpTimal Trees in Emergency Surgery Risk (POTTER) calculator; risks were compared with observed outcomes. DCA was used to model optimal patient selection for risk prevention strategies and to compare the relative performance of the ACS-SRC and POTTER calculators. RESULTS: A total of 994 patients were included in the analysis. C-statistics for the ACS-SRC prediction of 12 postoperative complications ranged from 0.546 to 0.782. DCA revealed that an ACS-SRC-guided readmission prevention intervention, when compared with an all-or-none approach, yielded a superior net benefit for patients with estimated risk between 5% and 20%. Comparison of SRCs for venous thromboembolism intervention demonstrated superiority of the ACS-SRC for thresholds for intervention between 2% and 4% with the POTTER calculator performing superiorly between 4% and 8% estimated risk. CONCLUSIONS: SRCs can be used not only to predict complication risk but also to guide risk prevention strategies. This methodology should be incorporated into external validations of future risk calculators and can be applied for institution-specific quality improvement initiatives to improve patient outcomes.

Recalibration and External Validation of the Risk Analysis Index: A Surgical Frailty Assessment Tool.

OBJECTIVE AND BACKGROUND: The Risk Analysis Index (RAI) predicts 30-, 180-, and 365-day mortality based on variables constitutive of frailty. Initially validated, in a single-center Veteran hospital, we sought to improve model performance by recalibrating the RAI in a large, veteran surgical registry, and to externally validate it in both a national surgical registry and a cohort of surgical patients for whom RAI was measured prospectively before surgery. METHODS: The RAI was recalibrated among development and confirmation samples within the Veterans Affairs Surgical Quality Improvement Program (VASQIP; 2010-2014; N = 480,731) including major, elective noncardiac surgery patients to create the revised RAI (RAI-rev), comparing discrimination and calibration. The model was tested externally in the American College of Surgeons National Surgical Quality Improvement Program dataset (NSQIP; 2005-2014; N = 1,391,785), and in a prospectively collected cohort from the Nebraska Western Iowa Health Care System VA (NWIHCS; N = 6,856). RESULTS: Recalibrating the RAI significantly improved discrimination for 30-day [c = 0.84-0.86], 180-day [c = 0.81-0.84], and 365-day mortality [c = 0.78-0.82] (P < 0.001 for all) in VASQIP. The RAI-rev also had markedly better calibration (median absolute difference between observed and predicted 180-day mortality: decreased from 8.45% to 1.23%). RAI-rev was highly predictive of 30-day mortality (c = 0.87) in external validation with excellent calibration (median absolute difference between observed and predicted 30-day mortality: 0.6%). The discrimination was highly robust in men (c = 0.85) and women (c = 0.89). Discrimination also improved in the prospectively measured cohort from NWIHCS for 180-day mortality [c = 0.77 to 0.80] (P < 0.001). CONCLUSIONS: The RAI-rev has improved discrimination and calibration as a frailty-screening tool in surgical patients. It has robust external validity in men and women across a wide range of surgical settings and available for immediate implementation for risk assessment and counseling in preoperative patients.

Interferon regulatory factor 1-Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury.

The role and regulators of extracellular vesicle (EV) secretion in hepatic ischemia/reperfusion (IR) injury have not been defined. Rab27a is a guanosine triphosphatase known to control EV release. Interferon regulatory factor 1 (IRF-1) is a transcription factor that plays an important role in liver IR and regulates certain guanosine triphosphatases. However, the relationships among IRF-1, Rab27a, and EV secretion are largely unknown. Here, we show induction of IRF-1 and Rab27a both in vitro in hypoxic hepatocytes and in vivo in warm IR and orthotopic liver transplantation livers. Interferon γ stimulation, IRF-1 transduction, or IR promoted Rab27a expression and EV secretion. Meanwhile, silencing of IRF-1 decreased Rab27a expression and EV secretion. Rab27a silencing decreased EV secretion and liver IR injury. Ten putative IRF-1 binding motifs in the 1,692-bp Rab27a promoter region were identified. Chromatin immunoprecipitation and electrophoretic mobility shift assay verified five functional IRF-1 binding motifs, which were confirmed by a Rab27a promoter luciferase assay. IR-induced EVs contained higher oxidized phospholipids (OxPL). OxPLs on the EV surface activated neutrophils through the toll-like receptor 4 pathway. OxPL-neutralizing E06 antibody blocked the effect of EVs and decreased liver IR injury. CONCLUSION: These findings provide a novel mechanism by which IRF-1 regulates Rab27a transcription and EV secretion, leading to OxPL activation of neutrophils and subsequent hepatic IR injury. (Hepatology 2018;67:1056-1070).

Neutrophil extracellular traps promote inflammation and development of hepatocellular carcinoma in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a progressive, inflammatory form of fatty liver disease. It is the most rapidly rising risk factor for the development of hepatocellular carcinoma (HCC), which can arise in NASH with or without cirrhosis. The inflammatory signals promoting the progression of NASH to HCC remain largely unknown. The propensity of neutrophils to expel decondensed chromatin embedded with inflammatory proteins, known as neutrophil extracellular traps (NETs), has been shown to be important in chronic inflammatory conditions and in cancer progression. In this study, we asked whether NET formation occurs in NASH and contributes to the progression of HCC. We found elevated levels of a NET marker in serum of patients with NASH. In livers from STAM mice (NASH induced by neonatal streptozotocin and high-fat diet), early neutrophil infiltration and NET formation were seen, followed by an influx of monocyte-derived macrophages, production of inflammatory cytokines, and progression of HCC. Inhibiting NET formation, through treatment with deoxyribonuclease (DNase) or using mice knocked out for peptidyl arginine deaminase type IV (PAD4-/- ), did not affect the development of a fatty liver but altered the consequent pattern of liver inflammation, which ultimately resulted in decreased tumor growth. Mechanistically, we found that commonly elevated free fatty acids stimulate NET formation in vitro. CONCLUSION: Our findings implicate NETs in the protumorigenic inflammatory environment in NASH, suggesting that their elimination may reduce the progression of liver cancer in NASH. (Hepatology 2018).

Does robotic pancreaticoduodenectomy improve outcomes in patients with high risk morphometric features compared to the open approach.

BACKGROUND: We sought to investigate whether robotic pancreatoduodenectomy (RPD) mitigates adverse outcomes in patients with high-risk morphometric features compared to the open approach (OPD). METHODS: Morphometric parameters for RPD and OPDs were measured by two blinded radiologists. The morphometric parameter best correlating with adverse outcomes was identified and used in multivariable models to evaluate the impact of surgical approach (open vs. robotic) on outcomes of patients with high-risk morphometric features. RESULTS: Of 282 PDs available for morphometric analysis, 134 (47.5%) underwent RPD. Average Psoas Density demonstrated the most frequent association with adverse outcomes, with correlations to prolonged LOS (ρ= -0.154, p=0.01), severe complications (ρ= -0.159, p=0.007), readmission (ρ= -0.16, p=0.007), and discharge to home (ρ= 0.2, p<0.001). On multivariable analysis of patients with high-risk morphometric features (defined as APD ≤ 50th percentile), RPD was associated with a reduction in the likelihood of prolonged LOS (OR 0.27, p = 0.015) and a trend towards discharge home versus a rehab facility or nursing home (OR 2.26, p = 0.061). CONCLUSION: This study confirms the association between morphometrics and outcomes following PD, and suggests that the robotic approach may be associated with improved outcomes in PD patients with high-risk morphometric features.

Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response.

BACKGROUND: Tumour-derived exosomes (TEXs) have a potential for application in cancer vaccines. Whether TEXs after induction by interferon regulatory factor 1 (IRF-1) are capable of enhancing the antitumour response remains to be determined. METHODS: Exosomes released by tumour cells infected with IRF-1-expressing adenovirus (IRF-1-Exo) or treated with interferon-γ (IFN-Exo) were isolated via ultracentrifugation. The IRF-1 target proteins IL-15Rα and MHC class I (MHC-I) were analysed by western blot. Exosomes along with CpG adjuvant were injected into tumour models to assess the antitumour effects. Tumours were harvested for immunofluorescence staining. Splenocytes from tumour-bearing mice were co-cultured with tumour cells. The IFNγ-positive and granzyme B-positive CD8α+ splenocyte cells were quantified by flow cytometry. RESULTS: The IRF-1-Exo or IFN-Exo displayed increased IL-15Rα and MHC-I expression. Injection of IRF-1-Exo or IFN-Exo combined with CpG had improved antitumour effects in mice. This effect may be a result of increased infiltration of tumours by CD4+ and CD8α+ T cells. Antibody-mediated depletion of CD4+ or CD8+ T cells abrogated the antitumour effects. Splenocytes isolated from CpG+IRF-1-Exo-injected Hepa 1-6 tumour mice had increased IFNγ-positive and granzyme B-positive CD8+ cells after co-culturing with Hepa 1-6 cells as compared with MC38 cells. CONCLUSIONS: The IRF-1 priming of TEXs enhances antitumour immune response.

Race and Health Disparities in Patient Refusal of Surgery for Early-Stage Pancreatic Cancer: An NCDB Cohort Study.

AIM: To identify factors associated with refusal of surgery in patients with early-stage pancreatic cancer and estimate the impact of this decision on survival. METHODS: Using the National Cancer Data Base, 26,358 patients were identified with potentially resectable tumors (pretreatment clinical stage I: T1 or T2 N0M0). Multivariate models were employed to identify factors predicting failure to undergo surgery and assess the impact on survival. RESULTS: Of early-stage patients who were recommended surgery, 7.8% (N = 992) refused surgery for resectable early-stage pancreatic cancer. On multivariable analysis, patients were more likely to refuse surgery if they were older [odds ratio (OR) = 1.18; 95% confidence interval (CI) 1.16-1.19], female (OR = 1.52; 95% CI 1.33-1.73), African American (vs White, OR = 1.79; 95% CI 1.37-2.34), on Medicare/Medicaid (vs private, OR = 2.75; 95% CI 1.54-4.92) or had higher Charlson-Deyo score (2 vs 0, OR = 1.33; 95% CI 1.03-1.72). Patients were also significantly more likely to refuse surgery if they were seen at a center that is not an academic/research program (OR 1.9; 95% CI 1.6-2.27). Patients who were recommended surgery but refused had significantly worse survival than those with stage I who received surgery [median survival 6.8 vs 24 months, Cox hazard ratio (HR) 3.41; 95% CI 3.12-3.60]. CONCLUSIONS: The percentage of patients refusing surgery for operable early-stage pancreatic cancer has been decreasing in the last decade but remains a significant issue that affects survival. Disparities in refusal of surgery are independently associated with several variables including gender, race, and insurance. To mitigate national disparities in surgical care, future studies should focus on exploring potential reasons for refusal and developing communication interventions.

Dissemination of Minimally Invasive Liver Resection for Primary Malignancy: Reevaluating Effectiveness.

BACKGROUND: Experiences at specialized hepatobiliary centers have demonstrated efficacy of minimally invasive liver resection, but concerns exist regarding whether these procedures would remain effective once disseminated to a broad range of clinical practices. We sought to present the first comparison of MILR and open liver resection (OLR) for primary liver malignancy from a nationally representative cancer registry. METHODS: Cases of liver and intrahepatic bile duct cancer were identified from the National Cancer Data Base Participant Use File. Mixed effects logistic regression and stratified Cox proportional hazards regression were used for analysis. A propensity score matched cohort was used as an alternative form of analysis to evaluate the robustness of results. RESULTS: A total of 3236 cases were analyzed from 2010 to 2011 with 2581 OLR (80%) and 655 MILR (20%). Of the variation in patient selection for MILR 28.5% was related to treatment at a specific treatment center; however, the proportion of MILR was similar among low-, medium-, and high-volume centers. Overall 90-day mortality was lower at high-volume centers (odds ratio [OR] 0.58; 95% confidence interval [CI] 0.40-0.85) compared with low-volume centers. MILR was similar to OLR in both 90-day mortality and overall survival (OR 0.9; 95% CI 0.62-1.10) and hazard ratio [HR] 0.88 (95% CI 0.72-1.07), regardless of treatment center volume. CONCLUSIONS: MILR for primary liver malignancy is used across a variety of practice settings, with similar outcomes to OLR. While volume is associated with short-term outcomes of liver resection as a whole, this relationship is not explained by adoption of MILR at low-volume centers.

Radioembolization for Hepatocellular Carcinoma: A Nationwide 10-Year Experience.

PURPOSE: To examine the US nationwide experience with transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) in the years 2003-2012 and the prognostic factors associated with overall survival. MATERIALS AND METHODS: A retrospective cohort study from the National Cancer Database included 110,139 adult patients with HCC between 2003 and 2012, of whom 1,222 received TARE. Primary outcome of interest was mortality after treatment. Univariate and multivariate analyses for factors predicting mortality were performed for 961 patients treated between 2003 and 2011. Overall survival was estimated by Kaplan-Meier method. RESULTS: There was a steady increase in utilization of TARE in the past decade. Most patients were white men with median age of 64 years. Of those patients, 67% received treatment at an academic institution, 42% were American Joint Committee on Cancer stage I or II, and 10% had metastatic disease at the time of treatment. Median overall survival was 13.3 months. Overall survival varied by patient and tumor characteristics. Female patients with tumors < 5 cm or stage I or II disease benefited the most from treatment. Outcomes were the same across all age groups. Patients who were African American or had metastatic disease tended to have worse outcomes. CONCLUSIONS: Use of TARE in patients with HCC has been increasing. Several factors are significantly associated with a less favorable outcome after TARE, including male sex, large tumors, and extrahepatic disease. These data can be used for designing future radioembolization trials.

Bayesian estimation of direct and correlated responses to selection on linear or ratio expressions of feed efficiency in pigs.

BACKGROUND: This study aimed at (1) deriving Bayesian methods to predict breeding values for ratio (i.e. feed conversion ratio; FCR) or linear (i.e. residual feed intake; RFI) traits; (2) estimating genetic parameters for average daily feed consumption (ADFI), average daily weight gain (ADG), lean meat percentage (LMP) along with the derived traits of RFI and FCR; and (3) deriving Bayesian estimates of direct and correlated responses to selection on RFI, FCR, ADG, ADFI, and LMP. Response to selection was defined as the difference in additive genetic mean of the selected top individuals, expected to be parents of the next generation, and the total population after integrating genetic trends out of the posterior distribution of selection responses. Inferences were based on marginal posterior distributions obtained from the Bayesian method for integration over unknown population parameters and "fixed" environmental effects and for appropriate handling of ratio traits. Terminal line pigs (n = 3724) were used for a multi-variate model for ADFI, ADG, and LMP. RFI was estimated from the conditional distribution of ADFI given ADG and LMP, using either genetic (RFIG) or phenotypic (RFIP) partial regression coefficients. The posterior distribution of the FCR's breeding values was derived from the posterior distribution of "fixed" environmental effects and additive genetic effects on ADFI and ADG. RESULTS: Posterior means of heritability were 0.32, 0.26, 0.56, 0.20, and 0.15 for ADFI, ADG, LMP, RFIP, and RFIG, respectively. Selection against RFIG showed a direct response of - 0.16 kg/d and correlated responses of - 0.16 kg/kg for FCR and - 0.15 kg/d for ADFI, with no effect on other production traits. Selection against FCR resulted in a direct response of - 0.17 kg/kg and correlated responses of - 0.14 kg/d for RFIG, - 0.18 kg/d for ADFI, and 0.98% for LMP. CONCLUSIONS: The Bayesian methodology developed here enables prediction of breeding values for FCR and RFI from a single multi-variate model. In addition, we derived posterior distributions of direct and correlated responses to selection. Genetic parameter estimates indicated a genetic basis for the studied traits and that genetic improvement through selection was possible. Direct selection against FCR or RFIP resulted in unexpected responses in production traits.

Preoperative risk analysis index for frailty predicts short-term outcomes after hepatopancreatobiliary surgery.

BACKGROUND: The Risk Analysis Index (RAI) for frailty is a rapid survey for comorbidities and performance status, which predicts mortality after general surgery. We aimed to validate the RAI in predicting outcomes after hepatopancreatobiliary surgery. METHODS: Associations of RAI, determined in 162 patients prior to undergoing hepatopancreatobiliary surgery, with prospectively collected 30-day post-operative outcomes were analyzed with multivariate logistic and linear regression. RESULTS: Patients (age 62 ± 14, 51% female) had a median RAI of 7, range 0-25. With every unit increase in RAI, length of stay increased by 5% (95% CI: 2-7%), odds of ICU admission increased by 10% (0-20%), ICU length of stay increased by 21% (9-34%), and odds of discharge to a nursing facility increased by 8% (0-17%) (all P < 0.05). Particularly in patients who suffered a first post-operative complication, RAI was associated with additional complications (1.6 unit increase in Comprehensive Complication Index per unit increase in RAI, P = 0.002). In a direct comparison in a subset of 74 patients, RAI and the ACS-NSQIP Risk Calculator performed comparably in predicting outcomes. CONCLUSION: While RAI and ACS-NSQIP Risk Calculator comparatively predicted short-term outcomes after HPB surgery, RAI has been specifically designed to identify frail patients who can potentially benefit from preoperative prehabilitation interventions.