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Background: To define the chronological changes of long-term survival among patients with non-hepatitis-related hepatocellular carcinoma (Non-Hep-HCC) versus hepatitis C-related HCC (HCV-HCC) over the last two decades., Methods: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Overall (OS) and recurrence-free survival (RFS) were analyzed and compared among Non-Hep-HCC versus HCV-HCC patients. Propensity score matching (PSM) was utilized to mitigate residual bias., Results: Among 617 patients, 196 (31.8%) patients had HCV-HCC, whereas 421 (68.2%) patients had Non-Hep-HCC. While patients with HCV-HCC had an improvement in OS over time (5-year OS, 2000-2009 55% vs. 2010-2017 67%, p = 0.034), OS among patients with Non-Hep-HCC remain unchanged (5-year OS, 2000-2009 53% vs. 2010-2017 52%, p = 0.905). In the matched cohort, patients with HCV-HCC had a worse OS versus patients with Non-Hep-HCC during 2000 and 2009 (5-year OS, 12% vs. 63%, p = 0.029), but significantly better OS from 2010 to 2017 than patients with Non-Hep-HCC (5-year OS, 86% vs. 73%, p = 0.035). The recurrence timing, patterns and re-treatments were comparable among Non-Hep-HCC and HCV-HCC patients., Conclusion: While OS of patients with HCV-HCC improved over time, the long-term survival of patients with Non-Hep-HCC patients remained unchanged and was more unfavorable., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Composite measures such as "Textbook Outcome" (TO) may be superior to individual quality metrics to assess surgical care and hospital performance. However, the incidence and factors associated with TO after resection of HCC remain poorly defined., Methods: Hospital variation in the rates of TO, factors associated with achieving a TO and the impact of TO on long-term survival following resection for HCC were examined using an international multi-institutional database., Results: Among 605 patients who underwent curative-intent resection of HCC, the unadjusted incidence of TO ranged from 50.9% to 77.7%. While achievement of each individual quality metric was relatively high (range, 74.5-98.0%), an overall TO was achieved among only 62.3% (n = 377) of patients. At the hospital level, TO ranged from 54.3% to 72.9%. Patients with BCLC-0 HCC (referent BCLC-B/C; OR: 4.17, 95%CI: 1.62-10.7) and ALBI grade 1 (referent ALBI grade 2/3; OR: 1.49, 95%CI: 1.06-2.11) had higher odds of achieving a TO. On multivariable analysis, TO was associated with improved overall survival (HR: 0.60, 95% CI: 0.42-0.85)., Conclusion: Roughly 6 in 10 patients achieved a TO following resection for HCC. When achieved, TO was associated with better long-term outcomes. TO is a simple composite measure of both short- and long-term outcomes among patients undergoing resection for HCC., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Two recent studies based on multi-omics data analysis identified distinct subtypes of bile-duct cancers (BDC) with important implications in terms of disease classification and patients' treatment., Methods: Patients with mutations in KRAS, NRAS, TP53, and ARID1A genes were classified in KRAS/TP53 group while patients with mutations in IDH1-2, BAP1, and PBRM1 were classified in IDH1-2/BAP1/PBRM1 group. The aim of this study was to define long-term outcomes among patients stratified by patterns of genes mutated., Results: Among 105 patients who underwent surgical resection for BDCs, 71 (68%) patients were classified in two groups based on patterns of genes mutated. While in IDH1-2/BAP1/PBRM1 group there were 58%, 22%, and 10% of patients with intrahepatic-cholangiocarcinoma (ICC), perihilar-cholangiocarcinoma (PHCC), and gallbladder cancer (GBC), in KRAS/TP53 group there were 42%, 78%, and 90% of patients with ICC, PHCC, and GBC (p = 0.003), respectively. Patients in IDH1-2/BAP1/PBRM1 group had a 5-year OS of 40% compared with 13% for KRAS/TP53 group (p = 0.032). In a multivariable model adjusted for margins, lymph-node status, microvascular invasion, and tumor grade, patients in KRAS/TP53 group had a 2.1-fold increased risk of death compared with patients in IDH1-2/BAP1/PBRM1 group (p = 0.028)., Conclusions: Genetic data were able to overcome the clinical based staging system in predicting patients' prognosis., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. All rights reserved.)

Background: Progression of colorectal liver metastasis (CRLM) on preoperative chemotherapy has been associated with a worse prognosis compared with patients who have responsive disease. Defining response can be challenging as traditional criteria largely assess only tumor size., Methods: Patients who underwent hepatectomy between 2010 and 2017 were identified using a multi-centric database. This study aimed to define the impact of preoperative chemotherapy response relative to initial tumor burden score (TBS) and determine impact of clinico-pathological variables on overall survival (OS)., Results: Among 784 patients who received preoperative chemotherapy, the regimen was oxaliplatin- (66%) or irinotecan-based (34%). Among patients with a TBS<6 at diagnosis, genetic status was the most important prognostic variable. Patients with a TBS<6, 5-year OS was 55%, 35%, and 0% for patients with KRAS/NRAS/BRAF wild-type, KRAS/NRAS, and BRAF mutations, respectively. Among patients who presented with CRLM with a TBS≥6, only Δ-TBS was prognostically important and patients with a Δ-TBS ≥ -10% had a 5-year OS of 27% compared with 49% for patients with a Δ-TBS < -10%., Conclusions: Prognostic stratification of patients with CRLM receiving preoperative chemotherapy should be multi-faceted and include consideration of initial tumor burden, change in tumor burden due to chemotherapy, and tumor genetic status., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The best achievable short-term outcomes after liver surgery have not been identified. Several factors may influence the post-operative course of patients undergoing hepatectomy increasing the risk of post-operative complications. We sought to identify risk-adjusted benchmark values [BMV] for liver surgery., Methods: The National Surgery Quality Improvement Program (NSQIP) database was used to develop Bayesian models to estimate risk-adjusted BMVs for overall and liver related (post-hepatectomy liver failure [PHLF], biliary leakage [BL]) complications. A separate international multi-institutional database was used to validate the risk-adjusted BMVs., Results: Among the 11,243 patients included in the NSQIP database, the incidence of complications, PHLF, and BL was 36%, 5%, and 8%, respectively. The risk-adjusted BMVs for complication (range, 16-72%), PHLF (range, 1%-20%), and BL (range, 4%-22%) demonstrated a high variability based on patients characteristics. When tested using an international database including nine institutes, the risk-adjusted BMVs for complications ranged from 26% (Institute-4) to 43% (Institute-1), BMVs for PHLF between 3% (Institute-3) and 12% (Institute-5), while BMVs for BL ranged between 5% (Institute-4) and 9% (Institute-7)., Conclusions: Multiple factors influence the risk of complications following hepatectomy. Risk-adjusted BMVs are likely much more applicable and appropriate in assessing "acceptable" benchmark outcomes following liver surgery., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: A retrospective study was performed to characterize trends in centralization of care and compliance with National Comprehensive Cancer Network (NCCN) guidelines for resected cholangiocarcinoma (CCA), and their impact on overall survival (OS)., Methods: Using the National Cancer Database (NCDB) 2004-2015 we identified patients undergoing resection for CCA. Receiver Operating Characteristic (ROC) analyses identified time periods and hospital volume groups for comparison. Propensity score matching provided case-mix adjusted patient cohorts. Cox hazard analysis identified risk factors for OS., Results: Among the 40,338 patients undergoing resection for CCA, the proportion of patients undergoing surgery at high volume hospitals increased over time (25%-44%, p < 0.001), while the proportion of patients undergoing surgery at low volume hospitals decreased (30%-15%, p < 0.001). Using ROC analyses, a hospital volume of 14 operations/year was the most sensitive and specific value associated with mortality. Surgery at high volume hospitals [HR] = 0.92, 95% CI: 0.88-0.97, p < 0.001) and receipt of care compliant with NCCN guidelines (HR = 0.87, 95% CI: 0.83-0.91, p < 0.001) were independently associated with improved OS., Conclusions: Both centralization of surgery for CCA to high volume hospitals and increased compliance with NCCN guidelines were associated with significant improvements in overall survival., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: We sought to characterize epidural analgesia (EA) use among Medicare patients undergoing hepatopancreatic (HP) procedures, identify factors associated with EA use and asses perioperative outcomes., Methods: Patients undergoing HP surgery were identified using the Inpatient Standard Analytic Files. Logistic regression was utilized to identify factors associated with EA receipt, and assess associations of EA with in-hospital outcomes and Medicare expenditures., Results: Among 20,562 patients included in the study, 6.7% (n =1362) had EA. There was no difference in the odds of complications (OR 1.05, 95% CI 0.93-1.19) or blood transfusions (OR 0.90, 95% CI 0.79-1.03) with EA versus conventional analgesia (CA). The odds of prolonged LOS (OR 1.16, 95% CI 1.03-1.30) were higher with EA; the odds of in-hospital mortality were higher with conventional analgesia (OR 1.90, 95% CI 1.28-2.83). Medicare payments for liver surgery were comparable among EA ($19,500) versus conventional analgesia ($19,300, p = 0.85) and slightly higher for EA ($23,600) versus conventional analgesia ($22,000, p < 0.001) for pancreatic procedures., Conclusion: EA utilization among Medicare patients undergoing HP was low. While EA was not associated with morbidity, it resulted in an average additional one day LOS and slightly higher expenditures in pancreatic surgery., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The objective of the current study was to compare outcomes among patients combined colon (CR) and liver resection (LR) for the treatment of simultaneous colorectal liver metastasis (CRLM) versus patients undergoing two-stage CR and LR., Methods: Patients undergoing surgery for CRLM between 2004 and 2014 were identified using the Nationwide Inpatient Sample (NIS). Propensity-score matching was used to compare patients undergoing CR + LR with patients undergoing two-stage CR and LR., Results: Among 83,410 patients, CR + LR was performed in 5659 (6.7%), stage C + LR was performed in 5659 (6.7%), while isolated CR and LR was performed in 70,177 (84.0%) and 7574 (9.3%) patients, respectively. The number of patients undergoing CR + LR increased from 423 in 2004 to 580 in 2014 (Δ = +37%). Patients undergoing CR + LR had lower postoperative morbidity (CR + LR vs. two-staged CR and LR: 38.5% vs. 61.2%), shorter LOS (median LOS: 8 days [IQR: 7-12] vs. 14 days [IQR: 10-21]), and lower postoperative mortality (3.1% vs. 5.9%) versus patients undergoing two-stage CR and LR. Compared with patients undergoing two-staged CR and LR, median hospital costs were $13,093 lower for patients undergoing CR + LR (median costs: $36,775 [IQR: 26,416-54,245] vs. $23,682 [IQR: 16,299-32,996])., Conclusion: CR + LR was increasingly performed for treatment of CRLM. Compared with two-staged CR and LR, CR + LR was associated with improved outcomes and lower costs., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Objectives were to determine the causes of readmission and assess the cost-effectiveness of high (HQ) and low quality (LQ) hospitals in performing pancreatic resection, by using readmission rates as the measure of quality., Methods: We identified 53,572 pancreatic resection cases from National Readmission Database from 2010 through 2014. Hospitals were risk adjusted and ranked based on readmission. Top 20% HQ hospitals having the lowest readmission rates were compared to the bottom 20% LQ hospitals with the highest readmission rates., Results: The 90-day readmission rate was 27.2% (HQ: 25.7%, LQ: 30.9%, p < 0.001). Compared to LQ, HQ hospitals had lower mortality (2.1% vs 10.2%, p < 0.001) and major complication (10.5% vs 53%, p < 0.001). Major complication during index operation was a major predictor of readmission (RR: 1.6, 95% CI: 1.6-1.7, p < 0.001). The optimal cut point of hospital volume associated with low mortality was 70 or more cases/year. Per year of survival benefit at HQ hospitals, the costs were lower by $9,293 with cost-savings of $6.98 million/year., Conclusion: HQ hospitals were cost-effective at performing pancreatic resection and achieved substantial cost-savings by avoiding major complications during index operation and having lower rates of readmissions. Hospital readmission rate is a strong marker of quality of care., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The relationship of expenditures related to rescuing patients from complications and hospital quality has not been well characterized. We sought to examine the relationship between payments for treating post-operative complications after liver and pancreas surgery and hospital quality., Methods: A retrospective cohort study of patients who underwent hepatopancreatic surgery was performed using claims data from 2013 to 2015 in the Medicare Provider Analysis and Review (MEDPAR) database. Medicare payments for index hospitalization and readmissions, as well as perioperative clinical outcomes were analyzed. Hospitals were stratified using average payments for patients who were rescued from complications (cost-of-rescue)., Results: A total of 13,873 patients and 737 hospitals were included in the analyses. Patient characteristics were similar across hospitals. Risk-adjusted rates of overall complications were higher at the highest cost-of-rescue hospitals (relative risk [RR], 1.35, 95% confidence interval [CI] 1.16-1.58), as well as rates of serious complications (RR, 1.78, 95% CI 1.51-2.09), 30-day readmission (RR 1.21 95% CI 1.06-1.39), 90-day mortality (RR, 1.29, 95% CI 1.01-1.64), and rates of failure-to-rescue (RR, 1.50, 95% CI 1.14-1.97)., Conclusion: Highest cost-of-rescue hospitals demonstrated worse quality metrics, including higher rates of serious complications, failure-to-rescue, 30-day readmission, and 90-day mortality., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Intraductal-growth (IG) type of intrahepatic cholangiocarcinoma (ICC) may be associated with a favorable prognosis compared with mass-forming (MF) and periductal-infiltrating (PI) ICC., Methods: The clinico-pathological characteristics and long-term outcomes of 1206 patients undergoing liver resection for ICC were compared based on the ICC morphological classification., Results: Compared with MF patients, IG patients had a higher incidence of poor/un-differentiated tumor, lympho-vascular, and perineural invasion (poor/un-differentiated: MF, 18% vs. IG, 24%; lympho-vascular invasion: MF, 30% vs. IG, 35%; perineural invasion: MF, 17% vs. IG, 33%; all p > 0.05). The pattern of recurrence was different among MF patients (intrahepatic only: 63%; extrahepatic only: 22%; both intra- and extrahepatic: 16%) versus IG patients (intrahepatic only: 46%; extrahepatic: 25%; both intra- and extrahepatic: 29%) (p < 0.001). Moreover, while 78% of patients with MF had an early recurrence (<18 months from surgery), 59% of IG patients had and early recurrence (p = 0.039). On multivariable analysis, after controlling for competing risk factors, IG patients had a similar prognosis as MF patients (HR 0.90, p = 0.69)., Conclusion: While IG patients more frequently presented with more adverse pathological characteristics, the prognosis of IG patients was comparable with MF patients after controlling for all these adverse factors., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: While several prognostic models have been developed to predict long-term outcomes in resectable intrahepatic cholangiocarcinoma (ICC), their prognostic discrimination remains limited. The addition of tumor markers might improve the prognostic power of the classification schemas proposed by the AJCC 8th edition and the Liver Cancer Study Group of Japan (LCSGJ)., Methods: The prognostic discrimination of the AJCC and the LCSGJ were compared before and after the addition of CA 19-9 and CEA, using Harrell's C-index, net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) in an international, multi-institutional cohort., Results: Eight hundred and five surgically treated patients with ICC that met the inclusion criteria were identified. On multivariable analysis, CEA5 ng/mL, 100IU/mL CA 19-9< 500IU/mL and CA 19-9500 IU/mL were associated with worse overall survival. The C-index of the AJCC and the LCSGJ improved from 0.540 to 0.626 and 0.553 to 0.626, respectively following incorporation of CA 19-9 and CEA. The NRI and IDI metrics confirmed the superiority of the modified AJCC and LCSGJ, compared to the original versions., Conclusion: The inclusion of preoperative CA 19-9 and CEA in the AJCC and LCSGJ staging schemas may improve prognostic discrimination among surgically treated patients with ICC., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: It is unclear how either the successful or failed rescue of hepato-pancreato-biliary (HPB) patients from complications impacts costs., Methods: A retrospective cohort study of HPB surgical patients was performed using claims data from 2013 to 2015 in the Medicare Provider Analysis and Review (MEDPAR) database. Patient demographics, characteristics, outcomes and risk-adjusted Medicare payments were compared., Results: 11,596 patients were identified. Over half of the patients (n = 5,810, 50.1%) underwent liver surgery, while 42% (n = 4892) had pancreatic and 8% (n = 894) had biliary operations. The overall complication rate varied (liver: 19.6%; pancreas: 20.3%; biliary: 25.2%, p = 0.001). In general, both minor and serious complications resulted in higher Medicare payments. Failed rescue led to higher average Medicare payments during index hospitalization compared to successful rescue ($53,476 versus $44,636, p < 0.001). The reverse was true on readmission; successful rescue was associated with higher average Medicare payments ($25,746 versus $15,654, p < 0.001). Taken together (index plus readmission), total hospitalization payments were higher for failed compared to successful rescue ($66,604 versus $52,143, p < 0.001)., Conclusion: Following HPB surgery, there is a significant cost associated with both rescue and failure-to-rescue from perioperative complications. Total hospitalization cost was highest for patients who experienced failure-to-rescue., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The benefit of adjuvant chemotherapy for resected intrahepatic cholangiocarcinoma (ICC) is unclear. The aim of the current study was to investigate the impact of adjuvant chemotherapy on survival among patients undergoing resection of ICC using a multi-institutional database., Methods: 1154 ICC patients undergoing curative-intent hepatectomy between 1990 and 2015 were identified from 14 institutions. Cox proportional hazard modeling was used to determine the impact of adjuvant chemotherapy on overall survival (OS)., Results: Following resection, 347 (30%) patients received adjuvant chemotherapy, most commonly a gemcitabine-based regimen (n = 184, 52%). Patients with T2/T3/T4 disease were more likely to receive adjuvant therapy compared with patients with T1a/T1b disease (OR 2.5, 95%CI 1.89-3.23; P < 0.001). Among patients who did and did not receive adjuvant therapy, patients with T2/T3/T4 tumors had a 5-year OS of 37% (95%CI 28.9-44.4) versus 30% (95%CI 23.8-35.6), respectively (p = 0.006). Similarly patients with N1 disease who received adjuvant chemotherapy tended to have improved 5-year OS (18.3%, 95%CI 9.0-30.1 vs. no adjuvant therapy 12%, 95%CI 3.9-24.4; P = 0.050)., Conclusions: While adjuvant chemotherapy did not influence the prognosis of all ICC patients following surgical resection, it was associated with a potential survival benefit in subgroups of patients at increased risk for recurrence, such as those with advanced tumors., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)