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Introduction: In the last decade, several difficulty scoring systems (DSS) have been proposed to predict technical difficulty in laparoscopic liver resections (LLR). The present study aimed to investigate the ability of four DSS for LLR to predict operative, short-term, and textbook outcomes., Methods: Patients who underwent LLR at a single tertiary referral center from January 2014 to June 2020 were included in the present study. Four DSS for LLR (Halls, Hasegawa, Kawaguchi, and Iwate) were investigated to test their ability to predict operative and postoperative complications. Machine learning algorithms were used to identify the most important DSS associated with operative and short-term outcomes., Results: A total of 346 patients were included in the analysis, 28 (8.1%) patients were converted to open surgery. A total of 13 patients (3.7%) had severe (Clavien-Dindo ≥ 3) complications; the incidence of prolonged length of stay (> 5 days) was 39.3% (n = 136). No patients died within 90 days after the surgery. According to Halls, Hasegawa, Kawaguchi, and Iwate scores, 65 (18.8%), 59 (17.1%), 57 (16.5%), and 112 (32.4%) patients underwent high difficulty LLR, respectively. In accordance with a random forest algorithm, the Kawaguchi DSS predicted prolonged length of stay, high blood loss, and conversions and was the best performing DSS in predicting postoperative outcomes. Iwate DSS was the most important variable associated with operative time, while Halls score was the most important DSS predicting textbook outcomes. No one of the DSS investigated was associated with the occurrence of complication., Conclusions: According to our results DDS are significantly related to surgical complexity and short-term outcomes, Kawaguchi and Iwate DSS showed the best performance in predicting operative outcomes, while Halls score was the most important variable in predicting textbook outcome. Interestingly, none of the DSS showed any correlation with or importance in predicting overall and severe postoperative complications., (© 2022. The Author(s).)

Objectives: To identify the preoperative risk factors for prediction of non-transplantable recurrence (NTR) after tumor resection for early-stage hepatocellular carcinoma (HCC) to assist in patient selection relative to upfront liver resection (LR) versus liver transplantation (LT)., Methods: Patients who underwent curative resection for transplantable HCC and chronic liver disease were identified from an international multi-institutional database. NTR was defined as recurrence beyond the Milan or UCSF criteria, and the preoperative risk factors of NTR were investigated., Results: Among 293 patients with transplantable HCC within Milan criteria and 320 within UCSF criteria, 113 (38.6%) and 131 (40.9%) patients developed tumor recurrence, respectively. Among patients who recurred, NTR was present in 32 (28.3%) patients within Milan and 35 (26.7%) within UCSF criteria. When either Milan or UCSF criteria was adopted, three preoperative risk factors including liver cirrhosis, tumor size > 3 cm, and multiple lesions were consistently identified as risk factors associated with NTR after curative resection. By summing up the three factors, a scoring model was established and the incidence of NTR among patients with 0, 1 or ≥ 2 risk factors incrementally increased from 4.5%, 13.3% to 20.5% when Milan criteria was used, and from 4.5%, 12.4% to 33.9% when UCSF criteria was adopted. The model demonstrated very good discriminatory power on internal validation (n = 5,000) (c-index 0.689 for Milan criteria, and 0.715 for UCSF criteria)., Conclusions: Whereas surgical resection may be optimal first-line treatment for patients with no or one risk factor, patients with ≥ 2 risk factors should be considered for upfront liver transplantation., (© 2021. The Society for Surgery of the Alimentary Tract.)

Background: Postoperative infectious complications may be associated with a worse long-term prognosis for patients undergoing surgery for a malignant indication. The current study aimed to characterize the impact of postoperative infectious complications on long-term oncologic outcomes among patients undergoing resection for hepatocellular carcinoma (HCC)., Methods: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The relationship between postoperative infectious complications, overall survival (OS), and recurrence-free survival (RFS) was analyzed., Results: Among 734 patients who underwent HCC resection, 269 (36.6%) experienced a postoperative complication (Clavien-Dindo grade 1 or 2 [n = 197, 73.2%] vs grade 3 and 4 [n = 69, 25.7%]). An infectious complication was noted in 81 patients (11.0%) and 188 patients (25.6%) had non-infectious complications. The patients with infectious complications had worse OS (median: infectious complications [46.5 months] vs no complications [106.4 months] [p < 0.001] and non-infectious complications [85.7 months] [p < 0.05]) and RFS (median: infectious complications [22.1 months] vs no complications [45.5 months] [p < 0.05] and non-infectious complications [38.3 months] [p = 0.139]) than the patients who had no complication or non-infectious complications. In the multivariable analysis, infectious complications remained an independent risk factor for OS (hazard ratio [HR], 1.7; p = 0.016) and RFS (HR, 1.6; p = 0.013). Among the patients with infectious complications, patients with non-surgical-site infection (SSI) had even worse OS and RFS than patients with SSI (median OS: 19.5 vs 70.9 months [p = 0.010]; median RFS: 12.8 vs 33.9 months [p = 0.033])., Conclusion: Infectious complications were independently associated with an increased long-term risk of tumor recurrence and death. Patients with non-SSI versus SSI had a particularly worse oncologic outcome., (© 2021. Society of Surgical Oncology.)

Introduction: Although preoperative α-fetoprotein (AFP) has been recognized as an important tumor marker among patients with hepatocellular carcinoma (HCC), the predictive value of AFP levels at the time of recurrence (rAFP) on post-recurrence outcomes has not been well examined., Methods: Patients undergoing curative-intent resection of HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of rAFP on post-recurrence survival, as well as the impact of rAFP relative to the timing and treatment of HCC recurrence were examined., Results: Among 852 patients who underwent resection of HCC, 307 (36.0%) individuals developed a recurrence. The median rAFP level was 8 ng/mL (interquartile range 3-100). Among the 307 patients who developed recurrence, 3-year post-recurrence survival was 48.5%. Patients with rAFP > 10 ng/mL had worse 3-year post-recurrence survival compared with individuals with rAFP < 10 ng/mL (28.7% vs. 65.5%, p < 0.001). rAFP correlated with survival among patients who had early (3-year survival; rAFP > 10 vs. < 10 ng/mL: 30.1% vs. 60.2%, p < 0.001) or late (18.0% vs. 78.7%, p = 0.03) recurrence. Furthermore, rAFP levels predicted 3-year post-recurrence survival among patients independent of the therapeutic modality used to treat the recurrent HCC (rAFP > 10 vs. < 10 ng/mL; ablation: 41.1% vs. 76.0%; intra-arterial therapy: 12.9% vs. 46.1%; resection: 37.5% vs. 100%; salvage transplantation: 60% vs. 100%; all p < 0.05). After adjusting for competing risk factors, patients with rAFP > 10 ng/mL had a twofold higher hazard of death in the post-recurrence setting (hazard ratio 1.96, 95% confidence interval 1.26-3.04)., Conclusion: AFP levels at the time of recurrence following resection of HCC predicted post-recurrence survival independent of the secondary treatment modality used. Evaluating AFP levels at the time of recurrence can help inform post-recurrence risk stratification of patients with recurrent HCC., (© 2021. Society of Surgical Oncology.)

Background: Although Bismuth-Corlette (BC) type 4 perihilar cholangiocarcinoma (pCCA) is no longer considered a contraindication for curative surgery, few data are available from Western series to indicate the outcomes for these patients. This study aimed to compare the short- and long-term outcomes for patients with BC type 4 versus BC types 2 and 3 pCCA undergoing surgical resection using a multi-institutional international database., Methods: Uni- and multivariable analyses of patients undergoing surgery at 20 Western centers for BC types 2 and 3 pCCA and BC type 4 pCCA., Results: Among 1138 pCCA patients included in the study, 826 (73%) had BC type 2 or 3 disease and 312 (27%) had type 4 disease. The two groups demonstrated significant differences in terms of clinicopathologic characteristics (i.e., portal vein embolization, extended hepatectomy, and positive margin). The incidence of severe complications was 46% for the BC types 2 and 3 patients and 51% for the BC type 4 patients (p = 0.1). Moreover, the 90-day mortality was 13% for the BC types 2 and 3 patients and 12% for the BC type 4 patients (p = 0.57). Lymph-node metastasis (N1; hazard-ratio [HR], 1.62), positive margins (R1; HR, 1.36), perineural invasion (HR, 1.53), and poor grade of differentiation (HR, 1.25) were predictors of survival (all p ≤0.004), but BC type was not associated with prognosis. Among the N0 and R0 patients, the 5-year overall survival was 43% for the patients with BC types 2 and 3 pCCA and 41% for those with BC type 4 pCCA (p = 0.60)., Conclusions: In this analysis of a large Western multi-institutional cohort, resection was shown to be an acceptable curative treatment option for selected patients with BC type 4 pCCA although a more technically challenging surgical approach was required., (© 2021. The Author(s).)

Backgrounds: Extrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection is associated with unfavorable prognosis. The objectives of the current study were to identify the risk factors and develop a nomogram for the prediction of extrahepatic recurrence after initial curative surgery., Methods: A total of 635 patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The clinicopathological characteristics, risk factors, and long-term survival of patients with extrahepatic recurrence were analyzed. A nomogram for the prediction of extrahepatic recurrence was established and validated in 144 patients from an external cohort., Results: Among the 635 patients in the derivative cohort, 283 (44.6%) experienced recurrence. Among patients who recurred, 80 (28.3%) patients had extrahepatic ± intrahepatic recurrence, whereas 203 (71.7%) had intrahepatic recurrence only. Extrahepatic recurrence was associated with more advanced initial tumor characteristics, early recurrence, and worse prognosis versus non-extrahepatic recurrence. A nomogram for the prediction of extrahepatic recurrence was developed using the β-coefficients from the identified risk factors, including neutrophil-to-lymphocyte ratio, multiple lesions, tumor size, and microvascular invasion. The nomogram demonstrated good ability to predict extrahepatic recurrence (c-index: training cohort 0.786; validation cohort: 0.845). The calibration plots demonstrated good agreement between estimated and observed extrahepatic recurrence (p = 0.658)., Conclusions: An externally validated nomogram was developed with good accuracy to predict extrahepatic recurrence following curative-intent resection of HCC. This nomogram may help identify patients at high risk of extrahepatic recurrence and guide surveillance protocols as well as adjuvant treatments., (© 2021. Society of Surgical Oncology.)

Background: The impact of tumor necrosis relative to prognosis among patients undergoing curative-intent resection for hepatocellular carcinoma (HCC) remains ill-defined., Methods: Patients who underwent curative-intent resection for HCC without any prior treatment between 2000 and 2017 were identified from an international multi-institutional database. Tumor necrosis was graded as absent, moderate (< 50% area), or extensive (≥ 50% area) on histological examination. The relationship between tumor necrosis, clinicopathologic characteristics, and long-term survival were analyzed., Results: Among 919 patients who underwent curative-intent resection for HCC, the median tumor size was 5.0 cm (IQR, 3.0-8.5). Tumor necrosis was present in 367 (39.9%) patients (no necrosis: n = 552, 60.1% vs < 50% necrosis: n = 256, 27.9% vs ≥ 50% necrosis: n = 111, 12.1%). Extent of tumor necrosis was also associated with more advanced tumor characteristics. HCC necrosis was associated with OS (median OS: no necrosis, 84.0 months vs < 50% necrosis, 73.6 months vs ≥ 50% necrosis: 59.3 months; p < 0.001) and RFS (median RFS: no necrosis, 49.6 months vs < 50% necrosis, 38.3 months vs ≥ 50% necrosis: 26.5 months; p < 0.05). Patients with T1 tumors with extensive ≥ 50% necrosis had an OS comparable to patients with T2 tumors (median OS, 62.9 vs 61.8 months; p = 0.645). In addition, patients with T2 disease with necrosis had long-term outcomes comparable to patients with T3 disease (median OS, 61.8 vs 62.4 months; p = 0.713)., Conclusion: Tumor necrosis was associated with worse OS and RFS, as well as T-category upstaging of patients. A modified AJCC T classification that incorporates tumor necrosis should be considered in prognostic stratification of HCC patients.

Background: To define early versus late recurrence based on post-recurrence survival (PRS) among patients undergoing curative resection for hepatocellular carcinoma (HCC)., Methods: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The optimal cut-off time point to discriminate early versus late recurrence was determined relative to PRS., Results: Among 1004 patients, 443 (44.1%) patients experienced recurrence with a median recurrence-free survival time of 12 months. A cut-off time point of 8 months was defined as the optimal threshold based on sensitivity analyses relative to PRS for early (n = 165, 37.2%) versus late relapse (n = 278, 62.8%) (p = 0.008). Early recurrence was associated with worse PRS (median PRS, 27.0 vs. 43.0 months, p = 0.019), as well as overall survival (OS) (median OS, 32.0 versus 74.0 months, p < 0.001) versus late recurrence. In addition, patients who recurred early were more likely to recur at extra- ± intrahepatic (35.5% vs. 19.8%, p = 0.003) sites and were less likely to have the recurrence treated with curative intent (33.8% vs. 45.7%, p = 0.08). Patients undergoing curative re-treatment of late recurrence had a comparable OS with patients who had no recurrence (median OS, 139.0 vs. 140.0 months); patients with early recurrence had inferior OS after curative re-treatment versus patients with no recurrence (median OS, 69.0 vs. 140.0 months, p = 0.036), yet still better than patients who received palliative treatment for early recurrence (median OS, 69.0 vs. 21.0 months, p < 0.001)., Conclusions: Eight months was identified as the cut-off value to differentiate early versus late recurrence. Curative-intent treatment for recurrent intrahepatic tumors was associated with reasonable long-term outcomes.

Background: There has been a dramatic increase in worldwide health care spending over the last several decades. Operative procedures and perioperative care in the USA represent some of the most expensive episodes per patient. In view of both the rising cost of health care in general and the rising cost of surgical care specifically, policymakers and stakeholders have sought to identify ways to increase the value-improving quality of care while controlling (or diminishing) costs. In this context, we reviewed data relative to achieving the "value proposition" in the delivery of gastrointestinal surgical care., Methods: The National Library of Medicine online repository (PubMed) was text searched for human studies including "cost," "quality," "outcomes," "health care," "surgery," and "value." Results from this literature framed by the Donabedian conceptual model (identifying structures, processes, and outcomes), and the resulting impact of efforts to improve quality on costs., Results: The relationship between quality and costs was nuanced. Better quality care, though associated with better outcomes, was not always reported as concomitant with low costs. Moreover, some centers reported higher costs of surgical care commensurate with higher quality. Conversely, higher costs in health care delivery were not always linked to improved outcomes. While higher quality surgical care can lead to lower costs, higher costs of care were not necessarily associated with better outcomes. Strategies to improve quality, reduce cost, or achieve both simultaneously included regionalization of complex operations to high-volume centers of excellence, overall reduction in complications, introducing evidence-based improvements in perioperative care pathways including as enhanced recovery after surgery (ERAS), and elimination of inefficient or low-value care., Conclusions: The relationship between quality and cost following gastrointestinal surgical procedure is complex. Data from the current study should serve to highlight the various means available to improve the value proposition related to surgery, as well as encourage surgeons to become more engaged in the national conversation around the Triple Aim of better health care quality, lower costs, and improved health care outcomes.

Background: Surgical resection of hepatic metastases remains the only potentially curative treatment option for patients with colorectal liver metastases (CRLM). Widely adopted prognostic tools may oversimplify the impact of model parameters relative to long-term outcomes., Methods: Patients with CRLM who underwent a hepatectomy between 2001 and 2018 were identified in an international, multi-institutional database. Bootstrap resampling methodology used in tandem with multivariable mixed-effects logistic regression analysis was applied to construct a prediction model that was validated and compared with scores proposed by Fong and Vauthey., Results: Among 1406 patients who underwent hepatic resection of CRLM, 842 (59.9%) had recurrence. The full model (based on age, sex, primary tumor location, T stage, receipt of chemotherapy before hepatectomy, lymph node metastases, number of metastatic lesions in the liver, size of the largest hepatic metastases, carcinoembryonic antigen [CEA] level and KRAS status) had good discriminative ability to predict 1-year (area under the receiver operating curve [AUC], 0.693; 95% confidence interval [CI], 0.684-0.704), 3-year (AUC, 0.669; 95% CI, 0.661-0.677), and 5-year (AUC, 0.669; 95% CI, 0.661-0.679) risk of recurrence. Studies analyzing validation cohorts demonstrated similar model performance, with excellent model accuracy. In contrast, the AUCs for the Fong and Vauthey scores to predict 1-year recurrence were only 0.527 (95% CI, 0.514-0.538) and 0.525 (95% CI, 0.514-0.533), respectively. Similar trends were noted for 3- and 5-year recurrence., Conclusion: The proposed clinical score, derived via machine learning, which included clinical characteristics and morphologic data, as well as information on KRAS status, accurately predicted recurrence after CRLM resection with good discrimination and prognostic ability.

Background: Patients with hepatocellular carcinoma (HCC) and portal vein hypertension assessed with platelet count (PVH-PLT; platelet count < 100,000/mL) are often denied surgery even when the disease is technically resectable. Short- and long-term outcomes of patients undergoing minimally invasive surgery (MIS) versus open resection for HCC and PVH-PLT were compared., Methods: Propensity score matching (PSM) was used to balance the clinicopathological differences between MIS and non-MIS patents. Univariate comparison and standard survival analyses were utilized., Results: Among 1974 patients who underwent surgery for HCC, 13% had a PVH-PLT and 33% underwent MIS. After 1:1 PSM, 407 MIS and 407 non-MIS patients were analyzed. Incidence of complications and length-of-stay (LoS) were higher among non-MIS versus MIS patients (both p ≤ 0.002). After PSM, among 178 PVH-PLT patients (89 MIS and 89 non-MIS), patients who underwent a non-MIS approach had longer LoS (> 7 days; non-MIS: 55% vs. MIS: 29%), as well as higher morbidity (non-MIS: 42% vs. MIS: 29%) [p <0.001]. In contrast, long-term oncological outcomes were comparable, including 3-year overall survival (non-MIS: 66.2% vs. MIS: 72.9%) and disease-free survival (non-MIS: 47.3% vs. MIS: 50.2%) [both p ≥ 0.08]., Conclusion: An MIS approach was associated with improved short-term outcomes, but similar long-term outcomes, compared with open liver resection for patients with HCC and PVH-PLT. An MIS approach for liver resection should be considered for patients with HCC, even those individuals with PVH-PLT.

Background: Surgical resection is the only potentially curative treatment for patients with colorectal, liver, and pancreatic cancers. Although these procedures are performed with low mortality, rates of complications remain relatively high following hepatopancreatic and colorectal surgery., Methods: The American College of Surgeons (ACS) National Surgical Quality Improvement Program was utilized to identify patients undergoing liver, pancreatic and colorectal surgery from 2014 to 2016. Decision tree models were utilized to predict the occurrence of any complication, as well as specific complications. To assess the variability of the performance of the classification trees, bootstrapping was performed on 50% of the sample., Results: Algorithms were derived from a total of 15,657 patients who met inclusion criteria. The algorithm had a good predictive ability for the occurrence of any complication, with a C-statistic of 0.74, outperforming the ASA (C-statistic 0.58) and ACS-Surgical Risk Calculator (C-statistic 0.71). The algorithm was able to predict with high accuracy thirteen out of the seventeen complications analyzed. The best performance was in the prediction of stroke (C-statistic 0.98), followed by wound dehiscence, cardiac arrest, and progressive renal failure (all C-statistic 0.96). The algorithm had a good predictive ability for superficial SSI (C-statistic 0.76), organ space SSI (C-statistic 0.76), sepsis (C-statistic 0.79), and bleeding requiring transfusion (C-statistic 0.79)., Conclusion: Machine learning was used to develop an algorithm that accurately predicted patient risk of developing complications following liver, pancreatic, or colorectal surgery. The algorithm had very good predictive ability to predict specific complications and demonstrated superiority over other established methods.

Background: Preoperative portal vein embolization (PVE) is utilized to induce growth of the future liver remnant volume (FLRV) among patients at elevated risk of post-hepatectomy liver failure (PHLF)., Methods: The American College of Surgery National Surgical Quality Improvement Program (ACS-NSQIP) database was used to compare short-term outcomes of PVE versus non-PVE patients. A propensity score match (PSM) was used to compare short-term outcomes among PVE and non-PVE patients., Results: Among the 11,243 patients included in the study, 462 (4.1%) patients had a PVE. Postoperatively, patients who underwent PVE had a higher incidence of overall (PVE, 44% vs. non-PVE, 23%) and liver-specific complications (biliary leak PVE, 16% vs. non-PVE, 7%; post-hepatectomy liver failure [PHLF] PVE, 17% vs. non-PVE, 5%), as well as a longer length of stay (> 7 days PVE, 39% vs. non-PVE, 22%) compared with the non-PVE group (all p < 0.001). After PSM, no differences in mortality or LOS were observed among PVE and non-PVE patients. PVE patients remained more likely to have a bile leak, organ/surgical-site infection, and PHLF versus non-PVE patients (all p < 0.05)., Conclusion: Among patients who underwent PVE before hepatectomy, the risk of postoperative complications was 1.6-fold higher than non-PVE patients. After PSM, PVE patients still had an increased risk of complications.

Introduction: Although a positive surgical margin is a known prognostic factor for recurrence, the optimal surgical margin width in the context of an R0 resection for early-stage hepatocellular carcinoma (HCC) is still debated. The aim of the current study was to examine the impact of wide (> 1 cm) versus narrow (< 1 cm) surgical margin status on the incidence and recurrence patterns among patients with T1 HCC undergoing an R0 hepatectomy., Methods: Between 1998 and 2017, patients with T1 HCC who underwent R0 hepatectomy for stage T1 HCC were identified using an international multi-institutional database. Recurrence-free survival (RFS) was estimated, and recurrence patterns were examined based on whether patients had a wide versus narrow resection margins., Results: Among 404 patients, median patient age was 66 years (IQR: 58-73). Most patients (n = 326, 80.7%) had surgical margin < 1 cm, while 78 (19.3%) patients had a > 1 cm margin. The majority of patients had early recurrences (< 24 months) in both margin width groups (< 1 cm: 70.3% vs > 1 cm: 85.7%, p = 0.141); recurrence site was mostly intrahepatic (< 1 cm: 77% vs > 1 cm: 61.9%, p = 0.169). The 1-, 3-, and 5-year RFS among patients with margin < 1 cm were 77%, 48.9%, and 35.3% versus 81.7%, 65.8%, and 60.7% for patients with margin > 1 cm, respectively (p = 0.02). Among patients undergoing anatomic resection, resection margin did not impact RFS (3-year RFS: < 1 cm: 49.2% vs > 1 cm: 58.9%, p = 0.169), whereas in the non-anatomic resection group, margin width > 1 cm was associated with a better 3-year RFS compared to margin < 1 cm (86.7% vs 47.3%, p = 0.017). On multivariable analysis, margin > 1 cm remained protective against recurrence (HR = 0.50, 95%CI 0.28-0.89), whereas Child-Pugh B (HR = 2.13, 95%CI 1.09-4.15), AFP > 20 ng/mL (HR = 1.71, 95%CI 1.18-2.48), and presence of microscopic lymphovascular invasion (HR = 1.48, 95%CI 1.01-2.18) were associated with a higher hazard of recurrence., Conclusion: Resection margins > 1 cm predicted better RFS among patients undergoing R0 hepatectomy for T1 HCC, especially small (< 5 cm) HCC. Although resection margin width did not influence outcomes after anatomic resection, wider margins were more important among patients undergoing non-anatomic liver resections.

Background: Several investigators have advocated for extending the Barcelona Clinic Liver Cancer (BCLC) resection criteria to select patients with BCLC-B and even BCLC-C hepatocellular carcinoma (HCC). The objective of the current study was to define the outcomes and recurrence patterns after resection within and beyond the current resection criteria., Patients and Methods: Patients who underwent resection for HCC within (i.e., BCLC 0/A) and beyond (i.e. BCLC B/C) the current resection criteria between 2005 and 2017 were identified from an international multi-institutional database. Overall survival (OS), disease-free survival (DFS), as well as patterns of recurrence of patients undergoing HCC resection within and beyond the BCLC guidelines were examined., Results: Among 756 patients, 602 (79.6%) patients were BCLC 0/A and 154 (20.4%) were BCLC B/C. Recurrences were mostly intrahepatic (within BCLC: 74.3% versus beyond BCLC: 70.8%, p = 0.80), with BCLC B/C patients more often having multiple tumors at relapse (69.6% versus 49.4%, p = 0.001) and higher rates of early (< 2 years) recurrence (88.0% versus 75.5%, p = 0.011). During the first postoperative year, annual recurrence was 38.3% and 21.3% among BCLC B/C and BCLC 0/A patients, respectively; 5-year OS among BCLC 0/A and BCLC B/C patients was 76.9% versus 51.6% (p = 0.003). On multivariable analysis, only a-fetoprotein (AFP) > 400 ng/mL (HR = 1.84, 95% CI 1.07-3.15) and R1 resection (HR = 2.36, 95% CI 1.32-4.23) were associated with higher risk of recurrence among BCLC B/C patients., Conclusions: Surgery can provide acceptable outcomes among select patients with BCLC B/C HCC. The data emphasize the need to further refine the BCLC treatment algorithm as well as highlight the need for surveillance protocols with a particular focus on the liver, especially for patients undergoing resection outside the BCLC criteria.

Background: Accurate risk stratification and patient selection is necessary to identify patients who will benefit the most from surgery or be better treated with other non-surgical treatment strategies. We sought to identify which patients in the preoperative setting would likely derive the most or least benefit from resection of intrahepatic cholangiocarcinoma (ICC)., Methods: Patients who underwent curative-intent resection for ICC between 1990 and 2017 were identified from an international multi-institutional database. A machine-based classification and regression tree (CART) was used to generate homogeneous groups of patients relative to overall survival (OS) based on preoperative factors., Results: Among 1146 patients, CART analysis revealed tumor number and size, albumin-bilirubin (ALBI) grade and preoperative lymph node (LN) status as the strongest prognostic factors associated with OS among patients undergoing resection for ICC. In turn, four groups of patients with distinct outcomes were generated through machine learning: Group 1 (n = 228): single ICC, size ≤ 5 cm, ALBI grade I, negative preoperative LN status; Group 2 (n = 708): (1) single tumor > 5 cm, (2) single tumor ≤ 5 cm, ALBI grade 2/3, and (3) single tumor ≤ 5 cm, ALBI grade 1, metastatic/suspicious LNs; Group 3 (n = 150): 2-3 tumors; Group 4 (n = 60): ≥ 4 tumors. 5-year OS among Group 1, 2, 3, and 4 patients was 60.5%, 35.8%, 27.5%, and 3.8%, respectively (p < 0.001). Similarly, 5-year disease-free survival (DFS) among Group 1, 2, 3, and 4 patients was 47%, 27.2%, 6.8%, and 0%, respectively (p < 0.001)., Conclusions: The machine-based CART model identified distinct prognostic groups of patients with distinct outcomes based on preoperative factors. Survival decision trees may be useful as guides in preoperative patient selection and risk stratification.

Background: The aim of the current study was to re-evaluate the role of minimally invasive liver resection (MILR) among patients with early-stage (stage I or II) hepatocellular carcinoma (HCC) undergoing partial hepatectomy., Methods: A retrospective analysis of the National Cancer Database (NCDB) was conducted to identify patients with early-stage HCC who underwent partial hepatectomy in the USA from 2010 to 2013. Overall survival (OS) was compared in three cohorts: crude; stabilized inverse probability of treatment propensity score weighting (IPTW); and propensity score matching (PSM)., Results: Among 4027 patients included in the study, only 11.7%, (n = 473) underwent MILR. In the stabilized IPTW cohort, patients who underwent MILR versus open resection were more likely to have tumors greater than 3 cm (63.9%, n = 285 vs. 51.4%, n = 228, p < 0.001) and poorly/undifferentiated tumors (21.5%, n = 96 vs. 12.9%, n = 57, p < 0.001). Within the crude cohort, a 5-year OS was superior among patients in the open surgical group (67.8%) compared with patients who underwent MILR (56.6%) (p < 0.001). After classic PSM analysis, the 5-year OS of patients undergoing MILR and open surgery were noted to be comparable (57.3% vs 63.8%, p = 0.17; HR 1.16, 95% CI 0.92-1.45). In contrast, after applying IPTW, the 5-year OS of patients who underwent MILR (55.5%) was worse compared with patients who had an open resection (67.5%) (HR 1.46, 95% CI 1.15-1.84; p < 0.001)., Conclusions: Long-term outcomes of patients undergoing MILR were comparable with patients who had open surgery when assessed by standard PSM. The use of IPTW resulted in more unbalanced groups leading to residual confounding and bias.

Background: There is an ongoing debate about expanding the resection criteria for hepatocellular carcinoma (HCC) beyond the Barcelona Clinic Liver Cancer (BCLC) guidelines. We sought to determine the factors that held the most prognostic weight in the pre- and postoperative setting for each BCLC stage by applying a machine learning method., Methods: Patients who underwent resection for BCLC-0, A and B HCC between 2000 and 2017 were identified from an international multi-institutional database. A Classification and Regression Tree (CART) model was used to generate homogeneous groups of patients relative to overall survival (OS) based on pre- and postoperative factors., Results: Among 976 patients, 63 (6.5%) had BCLC-0, 745 (76.3%) had BCLC-A, and 168 (17.2%) had BCLC-B HCC. Five-year OS among BCLC-0/A and BCLC-B patients was 64.2% versus 50.2%, respectively (p = 0.011). The preoperative CART model selected α-fetoprotein (AFP) and Charlson comorbidity score (CCS) as the first and second most important preoperative factors of OS among BCLC-0/A patients, whereas radiologic tumor burden score (TBS) was the best predictor of OS among BCLC-B patients. The postoperative CART model revealed lymphovascular invasion as the best postoperative predictor of OS among BCLC-0/A patients, whereas TBS remained the best predictor of long-term outcomes among BCLC-B patients in the postoperative setting. On multivariable analysis, pathologic TBS independently predicted worse OS among BCLC-0/A (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.02-1.07) and BCLC-B patients (HR 1.13, 95% CI 1.06-1.19) undergoing resection., Conclusion: Prognostic stratification of patients undergoing resection for HCC within and beyond the BCLC resection criteria should include assessment of AFP and comorbidities for BCLC-0/A patients, as well as tumor burden for BCLC-B patients.

Background: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator (SRC) aims to help predict patient-specific risk for morbidity and mortality. The performance of the SRC among an elderly population undergoing curative-intent hepatectomy for hepatocellular carcinoma (HCC) remains unknown., Methods: Patients > 70 years of age who underwent hepatectomy for HCC between 1998 and 2017 were identified using a multi-institutional international database. To estimate the performance of SRC, 12 observed postoperative outcomes were compared with median SRC-predicted risk, and C-statistics and Brier scores were calculated., Results: Among 500 patients, median age was 75 years (IQR 72-78). Most patients (n = 324, 64.8%) underwent a minor hepatectomy, while 35.2% underwent a major hepatectomy. The observed incidence of venous thromboembolism (VTE) (3.2%) and renal failure (RF) (4.4%) exceeded the median predicted risk (VTE, 1.8%; IQR 1.5-3.1 and RF, 1.0%; IQR 0.5-2.0). In contrast, the observed incidence of 30-day readmission (7.0%) and non-home discharge (2.5%) was lower than median-predicted risk (30-day readmission, 9.4%; IQR 7.4-12.8 and non-home discharge, 5.7%; IQR 3.3-11.7). Only 57.8% and 71.2% of patients who experienced readmission (C-statistic, 0.578; 95%CI 0.468-0.688) or mortality (C-statistic, 0.712; 95%CI 0.508-0.917) were correctly identified by the model., Conclusion: Among elderly patients undergoing hepatectomy for HCC, the SRC underestimated the risk of complications such as VTE and RF, while being no better than chance in estimating the risk of readmission. The ACS SRC has limited clinical applicability in estimating perioperative risk among elderly patients being considered for hepatic resection of HCC.

Background: The Alliance of Dedicated Cancer Centers (DCCs) is comprised of 11 institutions that are exempt from the prospective payment system utilized by Medicare for hospital reimbursement., Objective: The aim of this study was to compare short- and long-term outcomes of patients undergoing liver and pancreatic surgery for cancer at DCCs versus non-DCCs., Methods: Patients who underwent a liver or pancreatic operation for a malignant indication between 2013 and 2015 were identified using the Medicare Inpatient Standard Analytic Files. Regression analyses and the Kaplan-Meier method were used to assess short- and long-term outcomes of patients at DCCs versus non-DCCs., Results: Among 13,256 patients, 7.0% of patients were treated at a DCC. Median patient age and complexity of surgical procedures were comparable among DCCs and non-DCCs (all p > 0.05). Overall complications (16.5% vs. 23.6%), 90-day readmission (26.2% vs. 30.2%), and 90-day mortality (3.0% vs. 8.7%) were lower at DCCs compared with non-DCCs (all p < 0.001). In addition, long-term hazards of death among patients undergoing hepatectomy [hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.54-0.75] and pancreatectomy (HR 0.66, 95% CI 0.56-0.78) were lower among patients treated at DCCs (both p <  0.05). While Medicare payments for patients undergoing pancreatic surgery (DCC: $22,200 vs. non-DCC: $22,100; p = 0.772) were comparable among DCC and non-DCC hospitals, Medicare payments for liver resection at DCCs were 13.9% lower than non-DCCs (DCC: $16,700 vs. non-DCC: $19,400; p < 0.001)., Conclusions: Patients undergoing hepatopancreatic surgery at DCCs had better short- and long-term outcomes for the same/lower level of Medicare expenditure as non-DCC hospitals. DCCs provide higher-value surgical care for patients undergoing liver and pancreatic cancer operations.

Background: Multiple tumor foci of intrahepatic cholangiocarcinoma (ICC) are often considered a contra-indication for resection. We sought to define long-term outcomes after resection of ICC in patients with multiple foci., Methods: Patients who underwent resection for ICC between 1990 and 2017 were identified from 12 major HPB centers. Outcomes of patients with solitary lesions, multiple lesions (ML), and oligometastases (OM) were compared. OM were defined as extrahepatic metastases spread to a single organ., Results: One thousand thirteen patients underwent resection of ICC. On final pathology, 185 patients (18.4%) had ML and 27 (2.7%) had OM. Median survival of patients with a solitary tumor was 43.2 months, while the median survival of patients with 2 tumors was 21.2 months; the median survival of patients with 3 or more tumors was 15.3 months (p < 0.001). Five-year survival was 43.3%, 28.0%, and 8.6%, respectively. The median survival of patients without OM was 37.8 months versus 14.9 months among patients with OM (p < 0.001); estimated 5-year survival was 39.3% and 10.6%, respectively. In multivariable analysis, the presence of two lesions was not an independent poor prognostic factor for OS (HR 1.19; 95%CI 0.90-1.57; p = 0.229). However, the presence of three or more tumors was an independent poor prognostic factor for OS (HR 1.97; 95%CI 1.48-2.64; p < 0.001)., Conclusion: Resection of multiple liver tumors for patients with ICC did not preclude 5-year survival: in particular, estimated 5-year OS for resection of two tumors was 28.0%.

Background: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have questioned the prognostic stratification of this classification schema, as well as the proposed treatment allocation of patients with a single large tumor., Methods: Patients who underwent curative-intent hepatectomy for histologically proven hepatocellular carcinoma (HCC) between 1998 and 2017 were identified using an international multi-institutional database. Overall survival (OS) among patients with BCLC stage 0, A, and B was examined. Patients with a single large tumor were classified as BCLC stage A1 and were independently assessed., Results: Among 814 patients, 68 (8.4%) were BCLC-0, 310 (38.1%) were BCLC-A, 279 (34.3%) were BCLC-A1, and 157 (19.3%) were BCLC-B. Five-year OS among patients with BCLC stage 0, A, A1, and B HCC was 86.2%, 69.0%, 56.9%, and 49.9%, respectively (p < 0.001). Among patients with very early- and early-stage HCC (BCLC 0, A, and A1), patients with BCLC stage A1 had the worst OS (p = 0.0016). No difference in survival was noted among patients undergoing surgery for BCLC stage A1 and B HCC (5-year OS: 56.9% vs. 49.9%; p = 0.259) even after adjusting for competing factors (hazard ratio 0.83, 95% confidence interval 0.54-1.28; p = 0.40)., Conclusion: Prognosis following liver resection among patients with BCLC-A1 HCC was similar to patients presenting with BCLC-B tumors. Surgery provided acceptable long-term outcomes among select patients with BCLC-B HCC. Designation into BCLC stage B should not be considered an a priori contraindication to surgery.

Background: Although lymph node metastasis (LNM) is an important prognostic indicator for patients with intrahepatic cholangiocarcinoma (ICC), the benefit and indication for lymphadenectomy remain unclear., Methods: Patients diagnosed with ICC between 1990 and 2016 were identified in the international multi-institutional dataset. To determine the survival benefit from lymphadenectomy, the therapeutic index was calculated by multiplying the frequency of LNM in a particular group of patients by the 3-year cancer-specific survival (CSS) rate of patients with LNM in that subgroup., Results: Among 471 patients who met the inclusion criteria, approximately half had LNM (n = 205, 43.5%). The median number of resected and metastatic LNs were 4 [interquartile range (IQR) 2-8] and 0 (IQR 0-1), respectively. Three-year CSS in the entire cohort was 29.9%, reflecting a therapeutic index value of 13.0. The therapeutic index was lower among patients with major vascular invasion (5.4), preoperative carcinoembryonic antigen (CEA) > 5.0 (8.2), and LNM in areas other than the hepatoduodenal ligament (5.2). Of note, a therapeutic index difference of more than 10 points was noted only when examining the number of LNs harvested [1-2 (4.1) vs. 3-6 (16.1) vs. ≥ 7 (17.8)]., Conclusion: The survival benefit derived from lymphadenectomy was poor among patients with major vascular invasion, CEA > 5.0, and LNM in areas other than the hepatoduodenal ligament. Resection of three or more LNs was associated with the highest therapeutic value among patients with LNM.

Background and Aims: The role of lymph node dissection (LND) in patients with small intrahepatic cholangiocarcinoma (ICC) is still under debate. The aims of this study were to compare the lymph node (LN) status and its correlation with survival among patients with ICC stratified by tumor size., Methods: A retrospective analysis of a multi-institutional series of 259 patients undergoing curative-intent surgery was carried out. Patients were stratified into Small-ICC (≤ 3 cm) and Large-ICC (> 3 cm) based on tumor size., Results: There were 53 and 206 patients in Small-ICC and Large-ICC groups, respectively. The incidence of LND was 62% among Small-ICC patients and 78% among Large-ICC patients (p = 0.016). LN metastases were identified in 30.3% and 38.5% of Small-ICC and Large-ICC patients, respectively (p = 0.37). No differences in terms of number of harvested LN and LN metastases were identified comparing Small- and Large-ICC patients. The 5-year overall survival (OS) was 52.6% for Small-ICC and 36.2% for Large-ICC (p = 0.024). The 5-year OS according to the LN status (N0 vs N+) was 84.8% and 36.0% (p = 0.032) in Small-ICC, and 45.7% and 12.1% in Large-ICC (p < 0.001), respectively., Conclusion: While Small-ICC patients with no LN metastasis had a good long-term survival, the LN resulted in an important variable associated with survival also for patients in this group. Moreover, the incidence of LN metastasis did not differ when comparing Small-ICC and Large-ICC patients, suggesting that LND is mandatory in the surgical treatment of ICC regardless of tumor size.

Introduction: The Center for Medicare and Medicaid Services (CMS) has identified readmission as an important quality metric. With an increased emphasis on regionalization of complex hepato-pancreato-biliary (HPB) surgery to high-volume centers, care of readmitted HPB patients may be fragmented if readmission occurs at a non-index hospital. We sought to define the proportion of HPB readmissions, as well as evaluate outcomes, that occur at an index versus non-index hospitals and to identify factors associated with non-index hospital readmission., Methods: The National Readmissions Database (NRD) was used to identify patients who underwent major HPB surgery between 2010 and 2015. Factors associated with readmission at 30 and 90 days at index versus non-index hospitals were analyzed. Differences in mortality and complications were analyzed among patients readmitted to index versus non-index hospitals., Results: A total of 49,080 patients underwent HPB surgery (liver n = 27,081, 55%; pancreas n = 14,787, 30%; biliary n = 7212, 15%). Overall, 6643 (14%) and 11,709 (24%) patients were readmitted within 30 and 90 days, respectively. Among all first readmissions, 18 and 21% were to a non-index hospital within the first 30 and 90 days, respectively. On multivariable analysis, factors associated with readmission to a non-index hospital included age (OR 1.19, 95% CI 1.05, 1.34), pancreatic cancer (OR 1.40, 95% CI 1.14, 1.34) and ≥ 3 comorbidities (OR 1.34, 95% CI 1.10, 1.63), while procedures on the pancreas (OR 0.69, 95% CI 0.61, 0.80), private insurance (OR 0.77, 95% CI 0.68, 0.87), initial admission at a large hospital (OR 0.77, 95% CI 0.65, 0.91), and initial admission length of stay > 7 days (OR 0.77, 95% CI 0.69, 0.86) were associated with decreased odds of a non-index hospital readmission (all p < 0.05). Patients readmitted to a non-index hospital had higher inpatient mortality (3.7 vs. 2.7%, p = 0.010)., Conclusions: Roughly 1 in 5 patients were readmitted to a non-index hospital where the initial HPB operation had not taken place. Readmission to a non-index hospital was associated with higher overall in-hospital mortality. The impact of regionalization of HPB care relative to site of subsequent readmission may have important implications for patients.

Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend chemotherapy for patients with inoperable biliary tract cancers (BTC), as well as patients following resection of BTC with lymph node metastasis (N1)/positive margins (R1). We sought to define overall adherence, as well as long-term outcomes, with the NCCN guidelines for BTC using the National Cancer Database (NCDB)., Methods: A total of 176,536 patients diagnosed with BTC at a hospital participating in the NCDB between 2004 and 2015 were identified., Results: Among all patients, 63% of patients received medical therapy (chemotherapy or best supportive care), 11% underwent surgical palliation, and 26% underwent curative-intent surgery. According to the NCCN guidelines, 86% (n = 152,245) of patients were eligible for chemotherapy, yet, only 42.2% (n = 64,615) received chemotherapy. Factors associated with a lower adherence with NCCN guidelines included patient age (> 65 years: OR = 1.02), ethnicity (Black: OR = 1.14, Hispanic: OR = 1.21, Asian: OR = 1.24), and insurance status (non-private: OR = 1.45, all p < 0.001). A smaller subset of patients was either recommended chemotherapy but refused (n = 9269, 10.6%) or had medical factors that contraindicated chemotherapy (n = 8275, 9.4%). On multivariable analysis, adjusting for clinical and tumor-specific factors, adherence with NCCN guidelines was associated with a survival benefit for patients receiving medical therapies (HR = 0.74) or undergoing curative-intent surgery (HR = 0.73, both p < 0.001)., Conclusion: Less than half of patients with BTC received systemic chemotherapy in adherence with NCCN guidelines. While a subset of patients had contraindications or refused chemotherapy, other factors such as insurance status and ethnicity were associated with adherence. Adherence with chemotherapy guidelines may influence long-term outcomes.

Background: Liver resection in patients with neuroendocrine liver metastasis (NELM) provides a survival benefit, yet the optimal extent of resection remains unknown. We sought to examine outcomes of patients undergoing non-anatomic (NAR) versus anatomic liver resection (AR) for NELM using a large international cohort of patients., Methods: Two hundred and fifty-eight patients who underwent curative intent liver resection from January 1990 to December 2016 were identified from eight institutions. Patients were excluded if they underwent concurrent ablation, had extrahepatic disease, underwent a debulking operation, or had mixed anatomic and non-anatomic resections. Overall (OS) and recurrence-free (RFS) survival were compared among patients based on the extent of liver resection (AR vs. NAR)., Results: Most primary tumors were located in the pancreas (n = 117, 45.4%) or the small intestine (n = 65, 25.2%). Liver resection consisted of NAR (n = 126, 48.8%) or AR (n = 132, 51.2%) resection. The overwhelming majority of patients who underwent NAR had an estimated liver involvement of < 50% (NAR 109, 97.3% vs. AR n = 82, 65.6%; P < 0.001). Patients who underwent NAR also had higher rates of primary tumor lymph node metastasis (NAR n = 79, 71.2% vs. AR n = 37, 33.6%; P < 0.001) and microscopically positive margins (R1) (NAR n = 29, 25.7% vs. AR n = 16, 12.5%; P = 0.009). After a median follow-up of 47.7 months, 48 (18.6%) patients died and 37.0% (n = 95) had evidence of disease recurrence. Patients who underwent AR had both longer median OS (not reached) and RFS (not reached) versus patients who underwent NAR (median OS 138.3 months; median RFS 31.3 months) (both P < 0.01). After controlling for patient and disease-related factors, extent of liver resection was independently associated with an increased risk of recurrence (HR 2.39, 95% CI 1.04-5.48; P = 0.04) but not death (HR 1.92, 95% CI 0.40-9.28; P = 0.42)., Conclusion: NAR was independently associated with a higher incidence of recurrence versus patients who undergo a formal anatomic hepatectomy among patients with NELM.

Background: The role of liver transplant (LT) for neuroendocrine liver metastasis (NELM) has not been completely defined. While international guidelines included LT as a potential treatment for highly selected patients with advanced NELM, recently, LT has been proposed as an alternative curative treatment for NELM for patients meeting restrictive criteria (Milan criteria)., Methods: Using a multi-institutional cohort of patients undergoing liver resection for NELM, the long-term outcomes of patients meeting Milan criteria (resected NET drained by the portal system, stable disease/response to therapies for at least 6 months, metastatic diffusion to < 50% of the total liver volume, a confirmed histology of low-grade, and ≤ 60 years) were investigated., Results: Among the 238 patients included in the study, 28 (12%) patients met the Milan criteria for LT with a 5-year OS of 83%. Furthermore, among patients meeting Milan criteria, subsets of patients with favorable clinic-pathological characteristics had 5-year OS rates greater than 90% including G1 patients (5-year OS, 92%), patients undergoing minor liver resection (5-year OS, 94%), patients with low number of NELM (1-2 NELM), and small tumor size (< 3 cm) (for both groups of patients, 5-year OS, 100%)., Conclusions: In our series, only 12% of patients met Milan criteria, and the 5-year OS after liver resection for this small selected group of patients was comparable with that reported in the literature for patients undergoing LT for NELM within Milan criteria. While LT might be the optimal treatment for patients with unresectable NELM, surgical resection should be the first option for patients with resectable NELM.

Introduction: Minimally invasive surgery (MIS) has become standard of care for many gastrointestinal surgical procedures. Despite possible clinical benefits, MIS may be underutilized in some populations. The aim of this study was to access the utilization of MIS among Medicare patients undergoing hepatopancreatic procedures and define clinical outcomes, as well as costs, of minimally invasive techniques compared with the conventional open approach., Methods: The Medicare Provider Analysis and Review (MEDPAR) Inpatient Files were reviewed to identify Medicare patients who underwent pancreatic and liver procedures between 2013 and 2015. Primary outcomes of the analysis included perioperative clinical outcomes such as rates of complications, index hospitalization length-of-stay (LOS), failure-to-rescue, rates, and causes of 90-day readmission, as well as 90-day mortality. Secondary outcomes were Medicare payments for index hospitalization and readmission. Multivariable logistic regression was used to investigate the impact of MIS on clinical outcomes and health expenditures., Results: A total of 13,716 (90.6%) patients underwent open resection, while MIS was performed in 1424 (9.4%) patients. LOS was shorter among patients undergoing MIS (mean 7.3 ± SD 7.3) versus open (mean 9.3 ± SD 9.1) surgery (p < 0.001). The incidence of perioperative complications was lower following MIS (open 25.5%, n = 3492 vs. MIS 17.2%, n = 245) (p < 0.001). Rates of failure-to-rescue were similar among patients undergoing an open versus MIS pancreatic procedure (open 19.4%, n = 271 vs. MIS 13.4%, n = 17) (p = 0.09). In contrast, 90-day readmission (open 31.1%, n = 1630 vs. MIS 24.1%, n = 201, p < 0.001), as well as 90-day mortality (open 7.7%, n = 404 vs. MIS 4.2%, n = 35, p < 0.001) were lower among patients undergoing pancreatic resections via an MIS approach. In contrast, failure-to-rescue and readmission, as well as mortality, were all comparable among patients undergoing a liver resection, regardless as to whether the operation was performed open or via an MIS approach (all p > 0.05). Mean total payments for open pancreatic surgery were on average $1421 higher in the open versus MIS pancreatic group (p = 0.01); in contrast, there was no difference in the overall payment for hepatic resection (p > 0.05)., Conclusion: The MIS approach was underutilized among patients undergoing liver and pancreatic procedures. MIS was associated with lower complication and readmission and shorter LOS, as well as comparable/slightly lower Medicare payments, compared with the open approach. The MIS approach should strongly be considered among older patients undergoing liver and pancreatic procedures.

Objective: We aimed to compare the clinicopathological features and survival after surgery of patients with intrahepatic cholangiocarcinoma (ICC) according to the patterns of distribution of hepatic nodules., Methods: A retrospective analysis of a multi-institutional series of 259 patients with resected ICC was carried out. Patients were further classified according to the pattern of distribution of hepatic nodules: single tumors (type I), single tumors with satellites in the same liver segment (type II), or multifocal tumors (type III)., Results: Overall, 64.5% of patients had type I, 21.9% had type II, and 13.5% had type III. The 5-year overall survival rate was 49.4, 34.2, and 9.9% for types I, II, and III, respectively (p < 0.001). A multivariate survival analysis identified the following independent prognostic factors: pattern types II and III (p = 0.001 and p = 0.001, respectively), size ≥ 50 mm (p = 0.021), lymph node (LN) metastases (p = 0.005), and R1 resections (p = 0.019). We stratified survival for each type of pattern according to the other prognostic factors identified in the multivariate analysis. N0 and R0 patients with type II and III tumors had encouraging long-term results. Conversely, patients with LN metastases and R1 resections had poor prognosis, particularly patients with type III tumors., Conclusion: ICC has distinct patterns of distribution with different prognoses that should be considered when making therapeutic decisions. Patients with type III tumors had a significantly worse prognosis, and the benefits of upfront surgery should be carefully evaluated.

Objective: To estimate the cost of rescue and cost of failure and determine cost-effectiveness of rescue from major complications at high-volume (HV) and low-volume (LV) centers METHODS: Ninety-six thousand one hundred seven patients undergoing liver resection were identified from the Nationwide Inpatient Sample (NIS) between 2002 and 2011. The incremental cost of rescue and cost of FTR were calculated. Using propensity-matched cohorts, a cost-effectiveness analysis was performed to determine the incremental cost-effectiveness ratio (ICER) between HV and LV hospitals., Results: Ninety-six thousand one hundred seven patients were identified in NIS. The overall mortality was 2.3% and was lowest in HV centers (HV 1.4% vs. MV 2.1% vs. LV 2.6%; p < 0.001). Major complications occurred in 14.9% of hepatectomies and were comparable regardless of volume (HV 14.2% vs. MV 14.3% vs. LV 15.4%; p < 0.001). The FTR rate was substantially lower among HV centers (HV 7.7%, MV 11%, LV 12%; p < 0.001). At a willingness to pay benchmark of $50,000 per year of life saved, both HV (ICER = $3296) and MV (ICER = $4182) centers were cost-effective at rescuing patients from a major complication compared to LV hospitals., Conclusion: Not only was FTR less common at HV hospitals, but the management of most major complications was cost-effective at higher volume centers.

Background: Data on the interaction effect of multiple concurrent postoperative complications relative to the risk of short-term mortality following hepatopancreatic surgery have not been reported. The objective of the current study was to define the interaction effect of postoperative complications among patients undergoing HP surgery on 30-day mortality., Methods: Using the ACS-NSQIP Procedure Targeted Participant Use Data File, patients who underwent HP surgery between 2014 and 2016 were identified. Hazard ratios (HRs) for 30-day mortality were estimated using Cox proportional hazard models. Two-way interaction effects assessing combinations of complications relative to 30-day mortality were calculated using the relative excess risk due to interaction (RERI) in separate adjusted Cox models., Results: Among 26,824 patients, 10,886 (40.5%) experienced at least one complication. Mortality was higher among patients who experienced at least one complication versus patients who did not experience a complication (3.0 vs 0.1%, p < 0.001). The most common complications were blood transfusion (16.9%, n = 4519), organ space infection (12.2%, n = 3273), and sepsis/septic shock (8.2%, n = 2205). Combinations associated with additive effect on mortality included transfusion + renal dysfunction (RERI 12.3, 95% CI 5.2-19.4), pulmonary dysfunction + renal dysfunction (RERI 60.9, 95% CI 38.6-83.3), pulmonary dysfunction + cardiovascular complication (RERI 144.1, 95% CI 89.3-199.0), and sepsis/septic shock + renal dysfunction (RERI 11.5, 95% CI 4.4-18.7)., Conclusion: Both the number and specific type of complication impacted the incidence of postoperative mortality among patients undergoing HP surgery. Certain complications interacted in a synergistic manner, leading to a greater than expected increase in the risk of short-term mortality.

Introduction: Biliary tract cancers (BTC) are aggressive malignancies that require complex surgical procedures. Patients with BTC can present with skeletal muscle depletion, yet the effects of muscle wasting (sarcopenia) on outcomes have not been well studied. The objective of the current study was to define the impact of sarcopenia on survival among patients undergoing resection of BTC., Methods: Patients who underwent exploration for BTC who had a pre-operative CT scan available for review were identified. Body composition variables including total and psoas muscle area (cm 2 ), muscle density (Hounsfield units), visceral fat area, subcutaneous fat area, and waist-to-hip ratio were analyzed at the level of L3. Outcomes were assessed according to the presence or absence of sarcopenia defined using sex- and BMI-specific threshold values for Psoas Muscle Index (PMI, cm 2 /m 2 )., Results: Among 117 patients with BTC, 78 (67%) underwent curative-intent resection and 39 (33%) were explored but did not undergo resection due to metastatic/locally advanced disease. Tumor type included distal cholangiocarcinoma (n = 18, 15.4%), hilar cholangiocarcinoma (n = 27, 23.1%), gallbladder carcinoma (n = 52, 44.4%), and intrahepatic cholangiocarcinoma (n = 20, 17.1%). Median patient age was 65.6 years and 43.6% were male. Mean patient BMI was 26.1 kg/m 2 among men and 27.5 kg/m 2 among women. Overall, 41 (35.0%) patients had sarcopenia. Sarcopenia was associated with an increased risk of death among patients who underwent resection (HR 3.52, 95%CI 1.60-7.78, p = 0.002), which was comparable to patients with unresectable metastatic disease. Other factors such as low serum albumin (HR 3.17, 95% CI 1.30-7.74, p = 0.011) and low psoas density (HR 2.96, 95% CI 1.21-7.21, p = 0.017) were also associated with increased risk of death. Survival was stratified based on sarcopenia, psoas density, and serum albumin. The presence of each variable was associated with an incremental increased risk of death (0 variables ref.; 1 variable HR 3.8, 95% CI 1.0-14, p = 0.043; 2 variables HR 13.1, 95% CI 3.0-57.7, p = 0.001; 3 variables HR 14.6, 95% CI 2.5-87.1, p = 0.003). Patients who had no adverse prognostic factors had a 3-year OS of 67% versus no survival among patients with all 3 factors., Conclusions: Sarcopenia was common among patients undergoing resection of BTC, occurring in 1 of every 3 patients. Sarcopenia was associated with poor survival after resection, particularly among patients who experienced a recurrence. Body composition metrics such as sarcopenia and low psoas muscle density in addition to low albumin level were able to stratify patients into different prognostic categories.

Objective: Decreasing hospital length-of-stay (LOS) may be an effective strategy to reduce costs while also improving outcomes through earlier discharge to the non-hospital setting. The objective of the current study was to define the impact of discharge timing on readmission, mortality, and charges following hepatopancreatobiliary (HPB) surgery., Methods: The Nationwide Readmissions Database (NRD) was used to identify patients undergoing HPB procedures between 2010 and 2014. Length of stay (LOS) was categorized as early discharge (4-5 days), routine discharge (6-9 days), and late discharge (10-14 days). Univariable and multivariable analyses were utilized to identify factors associated with 90-day readmission., Results: A total of 28,114 patients underwent HPB procedures. Overall median LOS was 7 days (IQR 5-11); 10,438 (37.1%) patients had an early discharge, while 13,665 (48.6%) and 4011 (14.3%) patients had a routine or late discharge. The probability of early discharge increased over time (referent 2010: 2011-4% (OR 1.04, 95% CI 0.96-1.15) vs. 2012-10% (OR 1.10, 95% CI 1.01-1.20) vs. 2013-21% (OR 1.21, 95% CI 1.11-1.32) vs. 2014-32% (OR 1.32, 95% CI 1.21-1.44)) (p < 0.001). Early discharge was associated with insurance status, diagnosis (benign vs. malignant disease), general health, and overall hospital volume (all p < 0.05). Among patients who had an early discharge, 30- and 90-day readmission was 11.5 and 17.4%, respectively. In contrast, 30- and 90-day readmission was 16.9 and 24.7%, respectively, among patients who had a routine discharge group (p < 0.001). Among patients readmitted within 90 days, in-hospital mortality was similar among patients who had early (n = 43, 2.4%) versus routine discharge (n = 65, 1.9%). Median charges were lower among patients who had an early versus routine versus late discharge ($54,476 [IQR 40,053-79,100] vs. $75,192 [IQR 53,296-113,123] vs. $115,061 [IQR 79,162-171,077], respectively) (p < 0.001)., Conclusions: Early discharge after HPB surgery was not associated with increased 30- or 90-day readmission. Overall 90-day in-hospital mortality following a readmission was comparable among patients with an early, routine, and late discharge, while median charges were lower in the early discharge group.

Background: The relationship between the post-discharge settings and the risk of readmission has not been well examined. We sought to identify the association between discharge destinations and readmission rates after liver and pancreas surgery., Methods: The 2013-2015 Medicare-Provider Analysis and Review (MEDPAR) database was reviewed to identify liver and pancreas surgical patients. Patients were subdivided into three groups based on discharge destination: home/self-care (HSC), home with home health assistance (HHA), and skilled nursing facility (SNF). The association between post-acute settings, readmission rates, and readmission causes was assessed., Results: Among 15,141 liver or pancreas surgical patients, 60% (n = 9046) were HSC, 26.9% (n = 4071) were HHA, and 13.4% (n = 2024) were SNF. Older, female patients and patients with ≥ 2 comorbidities, ≥ 2 previous admissions, an emergent index admission, an index complication, and ≥ 5-day length of stay were more likely to be discharged to HHA or SNF compared to HSC (all P < 0.001). Compared to HSC, HHA and SNF patients had a 34 and a 67% higher likelihood of 30-day readmission, respectively. The HHA and SNF settings were also associated with a 33 and a 69% higher risk of 90-day readmission. There was no association between discharge destination and readmission causes., Conclusion: Among liver and pancreas surgical patients, HHA and SNF patients had a higher risk of readmission within 30 and 90 days. There was no difference in readmission causes and discharge settings. The association between discharge setting and the higher risk of readmission should be further evaluated as the healthcare system seeks to reduce readmission rates after surgery.

Purpose: Introduction of effective neoadjuvant therapy for pancreas cancer has resulted in complex and aggressive operations involving vasculature resection. This results in complicated postoperative CT appearance of vasculature, which in addition to high rate of recurrence makes interpretation of imaging difficult. The aim of this study was to identify patterns of postoperative appearance of portal vein-superior mesenteric vein complex (PV-SMV)., Methods: A retrospective study was conducted on patients undergoing pancreaticoduodenectomy with PV-SMV resection and reconstruction (PVR) between 2004 and 2014. Clinicopathological data were collected from a prospectively maintained database. Postoperative CT scans were reviewed to identify patterns of venous and perivenous features., Results: The mean age, of 70 patients included in the study, was 63.0 ± 12.2 years and 37 (52.9%) were males. The median time between surgery and postoperative scan was 10 days (IQR 7-25). Tangential resection with PVR via primary closure or use of a patch was performed in 37 (52.9%) patients while the rest underwent segmental resection with PVR via end-to-end anastomosis or use of a graft. Postoperative patterns of PV-SMV included concentric narrowing (N = 40, 57.1%), eccentric narrowing (N = 19, 27.1%) or partial venous thrombosis (N = 7, 10.0%). Perivenous features included perivenous fluid collection and induration (N = 57, 81.4%) and mass-like soft tissue thickening (N = 13, 18.6%). Long-term follow-up was available on 44 (62.9%) patients of which 28 (63.6%) demonstrated no recurrence of disease., Conclusion: This is a novel study that identifies and categorizes postoperative features of PV-SMV after PVR. These features overlap with those of disease recurrence and their better understanding can results in an accurate interpretation of postoperative imaging.

Background: The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA., Methods: Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status., Results: Among 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p > 0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5 months and 7.9%, respectively, for patients with an R1 resection (p = 0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p = 0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0-1.7; p = 0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4-2.3; p = 0.829)., Conclusions: Additional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA.

Background: The ability to provide accurate prognostic data after hepatectomy for intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and validate a nomogram to predict survival, as well as investigate the clinical implications of underestimating patients' risk of recurrence., Methods: Patients undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major hepatobiliary centers were included. Variables significant on multivariable analysis were used to construct a nomogram to predict disease-free survival (DFS). The nomogram assigned a score to each variable included in the model and calculated the risk of recurrence., Results: Eight hundred ninety-seven patients are included in the analytic cohort. On multivariable Cox regression analysis, tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13; p < 0.001), multifocal ICC (HR 1.64, 95% CI 1.32-2.03; p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25-2.11; p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89; p < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09-1.83; p = 0.008) were independent adverse risk factors associated with decreased DFS. The Harrell's c-index for the nomogram was 0.633 (with n = 5000 bootstrapping resamples) and the plot comparing predicted and actuarial DFS demonstrated a good calibration of the model. A subset of patients (n = 282) had a DFS worse than predicted (ΔPredicted DFS - Actuarial DFS > 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered "favorable.", Conclusion: A nomogram based on standard clinicopathologic characteristics was suboptimal in its ability to predict accurately risk of recurrence among patients with ICC after curative-intent liver resection. Particularly, the risk of underestimating patient risk of recurrence was highest among patients with historically favorable characteristics. Over one third of patients recurred > 6 months earlier than the DFS predicted by the nomogram.

Introduction: The role of routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal staging. We sought to define outcome and risk of death among patients who were staged with ≥6 HLNs versus <6 HLNs., Materials and Methods: Patients undergoing hepatectomy for ICC between 1990 and 2015 at 1 of the 14 major hepatobiliary centers were identified., Results: Among 1154 patients undergoing hepatectomy for ICC, 515 (44.6%) had lymphadenectomy. On final pathology, 200 (17.3%) patients had metastatic lymph node (MLN), while 315 (27.3%) had negative lymph node (NLN). Among NLN patients, HLN was associated with 5-year OS (p = 0.098). While HLN did not impact 5-year OS among MLN patients (p = 0.71), the number of MLN was associated with 5-year OS (p = 0.02). Among the 317 (27.5%) patients staged according the AJCC eighth edition staging system, N1 patients had a 3-fold increased risk of death compared with N0 patients (hazard ratio 3.03; p < 0.001)., Conclusion: Only one fourth of patients undergoing hepatectomy for ICC had adequate nodal staging according to the AJCC eighth edition. While the six HLN cutoff value impacted prognosis of N0 patients, the number of MLN rather than HLN was associated with long-term survival of N1 patients.

Background: Neuroendocrine tumors typically arise from pancreatic (PNET) vs. gastrointestinal or thoracic origins (non-PNET). The impact of primary tumor site on long-term prognosis following resection of neuroendocrine liver metastasis (NELM) remains poorly defined. The objective of the current study was to define the association of primary tumor location on prognosis of patients undergoing curative intent liver resection for NELM., Methods: Between 1990 and 2014, 421 patients who underwent resection of NELM were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified and analyzed by location of the primary tumor (PNET vs. non-PNET). A propensity score-matched analysis was utilized to assess the impact of primary tumor location on long-term survival., Results: Among the 421 patients, 197 (46.8%) patients had NELM from a PNET primary while 224 (53.2%) had a non-PNET primary (small bowel, n = 145; rectal, n = 10; bronchial, n = 22; other, n = 47). There were no differences in tumor burden and tumor site, while presence of extrahepatic disease was more common among patients with non-PNET NELM (extrahepatic disease, PNET NELM, n = 11 27.5% vs. non-PNET NELM, n = 29 72.5%; p = 0.010). Patients with PNET NELM were more likely to have non-functional disease compared with patients who had non-PNET NELM (non-functional, PNET NELM, n = 117 54.9% vs. non-PNET NELM, n = 96 45.1%; p = 0.011). On the final pathological specimen of the resected NELM, patients with PNET NELM were more likely to have a moderately differentiated tumor (59.3%), while patients with non-PNET NELM were more likely to have a poorly differentiated tumor (67.8%) (p = 0.005). Patients with PNET NELM had a worse 5-year DFS and 5-year OS compared with patients who had non-PNET NELM (DFS, PNET 36.2% vs. non-PNET 55.2%; p = 0.001 and OS, PNET 79.5% vs. non-PNET 83.4%; p = 0.008). After propensity score matching, both 5-year DFS and 5-year OS of the PNET and non-PNET groups were comparable (DFS, PNET 46.2% vs. non-PNET 55.9%; p = 0.22 and OS, PNET 81.5% vs. non-PNET 84.3%; p = 0.19)., Conclusion: PNET patients more often present with non-functional NELM and moderately differentiated tumors. On propensity-matched analysis, factors such as extrahepatic disease and tumor grade, but not primary tumor location, were associated with prognosis of patients undergoing curative intent liver surgery for NELM.

Background: Early tumor recurrence after curative resection typically indicates a poor prognosis. The objective of the current study was to investigate the risk factors, treatment, and prognosis of early recurrence of neuroendocrine tumor (NET) liver metastasis (NELM) after hepatic resection., Methods: A total of 481 patients who underwent curative-intent resection for NELM were identified from a multi-institutional database. Data on clinicopathological characteristics, intraoperative details, and outcomes were documented. The optimal cutoff value to differentiate early and late recurrence was determined to be 3 years based on linear regression., Results: With a median follow-up of 60 months, 223 (46.4%) patients developed a recurrence, including 158 (70.9%) early and 65 (29.1%) late recurrences. On multivariable analysis, pancreatic NET, primary tumor lymph node metastasis, and a microscopic positive surgical margin were independent risk factors for early intrahepatic recurrence. While recurrence patterns and treatments were comparable among patients with early and late recurrences, early recurrence was associated with worse disease-specific survival than late recurrences (10-year NELM-specific survival, 44.5 vs 75.8%, p < 0.001). Among the 34 (21.5%) patients who underwent curative treatment for early recurrence, post-recurrence disease-specific survival was better than non-curatively treated patients (10-year NELM-specific survival, 54.2 vs 26.3%, p = 0.028), yet similar to patients with late recurrences treated with curative intent (10-year NELM-specific survival, 54.2 vs 37.4%, p = 0.519)., Conclusions: Early recurrence after surgery for NELM was associated with the pancreatic type, primary lymph node metastasis, and extrahepatic disease. Re-treatment with curative intent prolonged survival after recurrence, and therefore, operative intervention even for early recurrences of NELM should be considered.

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival., Methods: Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS < 5)., Results: Among the 1154 patients who underwent liver resection for ICC, 5- and 10-year OS were 39.6 and 20.3% while the actual LT survival rate was 13.3%. After excluding 475 patients who survived < 5 years, as well as patients were alive yet had < 5 years of follow-up, 153 patients (22.5%) who survived ≥ 5 years were included in the LT group, while 526 patients (77.5%) who died < 5 years from the date of surgery were included in the non-LT group. Factors associated with not surviving to 5 years included perineural invasion (OR 4.78, 95% CI, 1.92-11.8; p = 0.001), intrahepatic metastasis (OR 3.75, 95% CI, 0.85-16.6, p = 0.082), satellite lesions (OR 2.12, 95% CI, 1.15-3.90, p = 0.016), N1 status (OR 4.64, 95% CI, 1.77-12.2; p = 0.002), ICC > 5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (< 10%) who had these pathological characteristics were LT., Conclusion: While ICC is generally associated with a poor prognosis, some patients will be LT. In fact, even a subset of patients with traditional adverse prognostic factors survived long term.