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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. Graphical abstract

Extrahepatic cholangiocarcinoma (ECC) is classified into two subtypes based on anatomic origin: distal extrahepatic (DECC) and perihilar (PHCC) cholangiocarcinoma. This study aimed to shed light on its genomic and transcriptomic profiles.The genomic alterations of 99 ECC (47 PHCC and 52 DECC) were investigated by next-generation sequencing of 96 genes. A subgroup of cases, representative of each subtype, was further investigated using transcriptomic analysis. Bioinformatics tools were applied for clustering and pathway analysis and defining the immune composition of the tumor microenvironment.PHCC had more frequent KRAS mutations (p = 0.0047), whereas TP53 mutations were more common in DECC (p = 0.006). Potentially actionable alterations included high-tumor mutational burden and/or microsatellite instability (7.1%), PI3KCA mutations (8.1%), and MYC (10.1%) and ERBB2 amplification (5.1%). The transcriptomic profiles showed the presence of three distinct clusters, which followed the anatomic origin and differed in immune microenvironment. DECC appeared to contain two distinct tumor subgroups, one enriched for druggable alterations and one lacking actionable opportunities.This study provides new insights into the molecular landscape and the actionable alterations of ECC. Our findings represent a step toward improved ECC molecular taxonomy and therapeutic strategies for precision oncology.

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. info:eu-repo/semantics/publishedVersion

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 HCCrecurrence wereexamined. Results: Among 852 patients who underwent resection of HCC, 307 (36.0%) individuals developed a recurrence. The median rAFP level was 8ng/mL (interquartile range 3–100). Among the 307 patients who developed recurrence, 3-year post-recurrence survival was 48.5%. Patients with rAFP > 10ng/mL had worse 3-year post-recurrence survival compared with individuals with rAFP < 10ng/mL (28.7% vs. 65.5%, p < 0.001). rAFP correlated with survival among patients who had early (3-year survival; rAFP > 10 vs. < 10ng/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. < 10ng/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 > 10ng/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.

OBJECTIVE: The objective of the current study was to define surgical outcomes after resection of multinodular hepatocellular carcinoma (HCC) beyond the Milan criteria, and develop a prediction tool to identify which patients likely benefit the most from resection. BACKGROUND: Liver resection for multinodular HCC, especially beyond the Milan criteria, remains controversial. Rigorous selection of the best candidates for resection is essential to achieve optimal outcomes after liver resection of advanced tumors. METHODS: Patients who underwent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Patients were categorized according to Milan criteria status. Pre- and postoperative overall survival (OS) prediction models that included HCC tumor burden score (TBS) among patients with multinodular HCC beyond Milan criteria were developed and validated. RESULTS: Among 1037 patients who underwent resection for HCC, 164 (15.8%) had multinodular HCC beyond the Milan criteria. Among patients with multinodular HCC, 25 (15.2%) patients experienced a serious complication and 90-day mortality was 3.7% (n = 6). Five-year OS after resection of multinodular HCC beyond Milan criteria was 52.8%. A preoperative TBS-based model (5-year OS: low-risk, 73.7% vs intermediate-risk, 45.1% vs high-risk, 13.1%), and postoperative TBS-based model (5-year OS: low-risk, 80.1% vs intermediate-risk, 37.2% vs high-risk, not reached) categorized patients into distinct prognostic groups relative to long-term prognosis (both P < 0.001). Pre- and postoperative models could accurately stratify OS in an external validation cohort (5-year OS; low vs medium vs high risk; pre: 66.3% vs 25.2% vs not reached, P = 0.012; post: 61.4% vs 42.5% vs not reached, P = 0.045) Predictive accuracy of the pre- and postoperative models was good in the training (c-index; pre: 0.68; post: 0.71), internal validation (n = 2000 resamples) (c-index, pre: 0.70; post: 0.72) and external validation (c-index, pre: 0.67; post 0.68) datasets. TBS alone could stratify patients relative to 5-year OS after resection of multinodular HCC beyond Milan criteria (c-index: 0.65; 5-year OS; low TBS: 70.2% vs medium TBS: 54.7% vs high TBS: 16.7%; P < 0.001). The vast majority of patients with low and intermediate TBS were deemed low or medium risk based on both the preoperative (98.4%) and postoperative risk scores (95.3%). CONCLUSION: Prognosis of patients with multinodular HCC was largely dependent on overall tumor burden. Liver resection should be considered among patients with multinodular HCC beyond the Milan criteria who have a low- or intermediate-TBS.

Background and aims We aimed to investigate the impact of vascular resection (VR) on postoperative outcomes and survival of patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). Methods A retrospective analysis of a multi-institutional series of 270 patients with resected ICC was carried out. Patients were divided into three groups: portal vein VR (PVR), inferior vena cava VR (CVR) and no VR (NVR). Univariate and multivariate analysis were applied to define the impact of VR on postoperative outcomes and survival. Results Thirty-one patients (11.5%) underwent VR: 15 (5.6%) to PVR and 16 (5.9%) to CVR. R0 resection rates were 73.6% in NVR, 73.3% of PVR and 68.8% in CVR. The postoperative mortality rate was increased in VR groups: 2.5% in NVR, 6.7% in PVR and 12.5% in CVR. The 5-years overall survival (OS) rates progressively decreased from 38.4% in NVR, to 30.1% in CVR and to 22.2% in PVR, p = 0.030. However, multivariable analysis did not confirm an association between VR and prognosis. The following prognostic factors were identified: size ≥50 mm, patterns of distribution of hepatic nodules (single, satellites or multifocal), lymph-node metastases (N1) and R1 resections. In the VR group the 5-years OS rate in patients without lymph-node metastases undergoing R0 resection (VRR0N0) was 44.4%, while in N1 patients undergoing R1 resection was 20% (p Conclusion Vascular resection (PVR and CVR) is associated with higher operative risk, but seems to be justified by the good survival results, especially in patients without other negative prognostic factors (R0N0 resections).

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. info:eu-repo/semantics/publishedVersion

Although KRAS mutation status is known to affect the prognosis of patients with colorectal liver metastasis, the hierarchical association between other prognostic factors and KRAS status is not fully understood.Patients who underwent a hepatectomy for colorectal liver metastasis were identified in a multi-institutional international database. A classification and regression tree model was constructed to investigate the hierarchical association between prognostic factors and overall survival relative to KRAS status.Among 1,123 patients, 29.9% (n = 336) had a KRAS mutation. Among wtKRAS patients, the classification and regression tree model identified presence of metastatic lymph nodes as the most important prognostic factor, whereas among mtKRAS patients, carcinoembryonic antigen level was identified as the most important prognostic factor. Among patients with wtKRAS, the highest 5-year overall survival (68.5%) was noted among patients with node negative primary colorectal cancer, solitary colorectal liver metastases, size4.3 cm. In contrast, among patients with mtKRAS colorectal liver metastases, the highest 5-year overall survival (57.5%) was observed among patients with carcinoembryonic antigen6 mg/mL. The classification and regression tree model had higher prognostic accuracy than the Fong score (wtKRAS [Akaike's Information Criterion]: classification and regression tree model 3334 vs Fong score 3341; mtKRAS [Akaike's Information Criterion]: classification and regression tree model 1356 vs Fong score 1396).Machine learning methodology outperformed the traditional Fong clinical risk score and identified different factors, based on KRAS mutational status, as predictors of long-term prognosis.

Despite the progress in the treatment of liver cancer, the prognosis of CCA remains poor and the surgical resection remains the only treatment with a potentially curative intent to date. Advances i...

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. 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. 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. 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: 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 anon-MIS approach had longer LoS (> 7days; non-MIS: 55% vs. MIS: 29%), as well as higher morbidity (non-MIS: 42% vs. MIS: 29%) [p

The aim of this study was to analyze the risk factors for surgical infectious complications and the outcomes of patients undergoing surgery for perihilar cholangiocarcinoma according to the microbiological examinations.Patients who underwent surgery for perihilar cholangiocarcinoma in the last decade were enrolled, and all clinical and microbiological data were collected from a retrospective monocentric database. Univariate and multivariate analyses were performed distinguishing patients who developed at least 1 surgical infectious complication (surgical site infections, acute bacterial cholangitis, bacteremia).A total of 98 patients were included. Among patients who developed surgical infectious complications (51%), many preoperative characteristics were significantly more frequent: American Society of Anesthesiologists score ≥3 (P = .026), neutrophil-to-lymphocyte ratio ≥3.4 (P = .001), endoscopic sphincterotomy (P = .032), ≥2 biliary drainage procedures (P = .013), acute cholangitis (P = .012), multidrug resistant (P = .009), and ≥3 microorganisms' detection (P = .042); whereas during the postoperative period, surgical infectious complications were associated to increased incidence of intensive care unit readmission (P = .031), major complications (P.001), posthepatectomy liver failure (P = .005), ascites (P = .008), biliary leakage (P = .008), 90-day readmission (P = .003), and prolonged length of hospital stay (P.001). At the multivariate analysis 3 independent preoperative risk factors for surgical infectious complications were identified: neutrophil-to-lymphocyte ratio ≥3.4 (P = .004), endoscopic sphincterotomy (P = .009), and acute cholangitis (P = .013). The presence of multidrug-resistance in the perioperative biliary cultures was related to postoperative multidrug-resistant species from all cultures (P.001) and organ/space and incisional-surgical site infections (P ≤ .044).Infective complications after surgery for perihilar cholangiocarcinoma worsen the short-term outcomes. A careful microbiological surveillance should be carried out in all cases to prevent and promptly treat surgical infectious complications.

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 info:eu-repo/semantics/publishedVersion

Background: Tumor burden is an important factor in defining prognosis among patients with primary and secondary liver cancers. Although the eighth edition of the American Joint Committee on Cancer staging system has changed the criteria for staging patients with intrahepatic cholangiocarcinoma to better define the effect of tumor burden on prognosis, the impact of intrahepatic cholangiocarcinoma tumor burden on overall survival has not been examined using a machine-learning tool. Methods: Patients who underwent resection of intrahepatic cholangiocarcinoma at 1 of 14 participating international hospitals between 1990 and 2015 were identified. Classical survival models and the Classification and Regression Tree model were used to identify groups of patients with a homogeneous risk of death and investigate the hierarchical association between variables and overall survival. Results: Among 1,116 patients included in the analysis, tumor size was ≤5 cm in 447 (40.1%) patients and >5 cm in 669 (59.9%) patients. Although 82.9% (n = 926) of patients had a single intrahepatic cholangiocarcinoma, 9.9% (n = 110) and 7.2% (n = 80) of patients had 2 and ≥3 tumors, respectively. Patients with intrahepatic cholangiocarcinoma tumors ≤5 cm and >5 cm had a 5-year overall survival of 51.7% and 32.6%, respectively (P < 0.001). Five-year overall survival decreased from 44.6% among patients with a single intrahepatic cholangiocarcinoma to 28.1% and 14.2% among patients with 2 and ≥3 intrahepatic cholangiocarcinomas, respectively (P < 0.001). Among the combinations of tumor size and intrahepatic cholangiocarcinoma tumor number used to estimate tumor burden, logarithmic transformation of tumor size (log tumor size) and intrahepatic cholangiocarcinoma tumor number had the highest concordance index. The Classification and Regression Tree model identified 8 classes of patients with a homogeneous risk of death, illustrating the hierarchical relationship between tumor burden (log tumor size and number of intrahepatic cholangiocarcinomas) and other factors associated with prognosis. Conclusion: Intrahepatic cholangiocarcinoma tumor size and number demonstrated a strong nonlinear association with survival after resection of intrahepatic cholangiocarcinoma. A log-model Classification and Regression Tree–derived tumor burden score may be a better tool to estimate prognosis of patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma.

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. info:eu-repo/semantics/publishedVersion

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. 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. 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). 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 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 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.

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).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.Among the 40,338 patients undergoing resection for CCA, the proportion of patients undergoing surgery at high volume hospitals increased over time (25%-44%, p0.001), while the proportion of patients undergoing surgery at low volume hospitals decreased (30%-15%, p0.001). 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, p0.001) and receipt of care compliant with NCCN guidelines (HR = 0.87, 95% CI: 0.83-0.91, p0.001) were independently associated with improved OS.Both centralization of surgery for CCA to high volume hospitals and increased compliance with NCCN guidelines were associated with significant improvements in overall survival.

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.

Intrahepatic cholangiocarcinoma (ICC) remains an uncommon disease with a rising incidence worldwide. We sought to identify trends in therapeutic approaches and differences in patient outcomes based on facility types. Between January 1, 2004, and December 31, 2015, a total of 27,120 patients with histologic diagnosis of ICC were identified in the National Cancer Database and were enrolled in this study. The incidence of ICC patients increased from 1194 in 2004 to 3821 in 2015 with an average annual increase of 4.16% (p

Background: The impact of tumor burden score (TBS) on conditional survival (CS) among patients undergoing curative-intent resection of hepatocellular carcinoma (HCC) has not been examined to date. Methods: Patients who underwent liver resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS and other clinicopathologic factors on 3-year conditional survival (CS3) was examined. Results: Among 1,040 patients, 263 (25.3%) patients had low TBS, 668 (64.2%) had medium TBS and 109 (10.5%) had high TBS. TBS was strongly associated with OS; 5-year OS was 39.0% among patients with high TBS compared with 61.1% and 79.4% among patients with medium and low TBS, respectively (p < 0.001). While actuarial survival decreased as time elapsed from resection, CS increased over time irrespective of TBS. The largest differences between 3-year actuarial survival and CS3 were noted among patients with high TBS (5-years postoperatively; CS3: 78.7% vs. 3-year actuarial survival: 30.7%). The effect of adverse clinicopathologic factors including high TBS, poor/undifferentiated tumor grade, microvascular invasion, liver capsule involvement, and positive margins on prognosis decreased over time. Conclusions: CS rates among patients who underwent resection for HCC increased as patients survived additional years, irrespective of TBS. CS estimates can be used to provide important dynamic information relative to the changing survival probability after resection of HCC. info:eu-repo/semantics/publishedVersion

The relationship between immune-nutritional status and tumor growth, biological aggressiveness and survival, is still debated. Therefore, this study aimed to evaluate the prognostic performance of different inflammatory and immune-nutritional markers in patients who underwent surgery for biliary tract cancer (BTC). The prognostic role of the following inflammatory and immune-nutritional markers were investigated: Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), Neutrophil to Lymphocyte ratio (NLR), Platelet to Lymphocyte ratio (PLR), Lymphocyte to Monocyte ratio (LMR), Prognostic Nutritional Index (PNI). A total of 282 patients undergoing surgery for BTC were included. According to Cox regression and ROC curves analysis for survival, LMR had the best prognostic performances, with hazard ratio (HR) of 1.656 (p = 0.005) and AUC of 0.652. Multivariable survival analysis identified the following independent prognostic factors: type of BTC (p = 0.002), T stage (p = 0.014), N stage (p &lt, 0.001), histological grading (p = 0.045), and LMR (p = 0.025). Conversely, PNI was related to higher risk of severe morbidity (p &lt, 0.001) and postoperative mortality (p = 0.005). In conclusion, LMR appears an independent prognostic factor of long-term survival, whilst PNI seems associated with worse short-term outcomes.

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. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-09905-z.

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.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.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).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.

Purpose Several multi-omics classifications have been proposed for hepato-pancreato-biliary (HPB) cancers, but these classifications have not proven their role in the clinical practice and been validated in external cohorts. Patients and methods Data from whole-exome sequencing (WES) of The Cancer Genome Atlas (TCGA) patients were used as an input for the artificial neural network (ANN) to predict the anatomical site, iClusters (cell-of-origin patterns) and molecular subtype classifications. The Ohio State University (OSU) and the International Cancer Genome Consortium (ICGC) patients with HPB cancer were included in external validation cohorts. TCGA, OSU and ICGC data were merged, and survival analyses were performed using both the ‘classic’ survival analysis and a machine learning algorithm (random survival forest). Results Although the ANN predicting the anatomical site of the tumour (i.e. cholangiocarcinoma, hepatocellular carcinoma of the liver, pancreatic ductal adenocarcinoma) demonstrated a low accuracy in TCGA test cohort, the ANNs predicting the iClusters (cell-of-origin patterns) and molecular subtype classifications demonstrated a good accuracy of 75% and 82% in TCGA test cohort, respectively. The random survival forest analysis and Cox’ multivariable survival models demonstrated that models for HPB cancers that integrated clinical data with molecular classifications (iClusters, molecular subtypes) had an increased prognostic accuracy compared with standard staging systems. Conclusion The analyses of genetic status (i.e. WES, gene panels) of patients with HPB cancers might predict the classifications proposed by TCGA project and help to select patients suitable to targeted therapies. The molecular classifications of HPB cancers when integrated with clinical information could improve the ability to predict the prognosis of patients with HPB cancer.

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. info:eu-repo/semantics/publishedVersion

Background: The impact of a prolonged time-to-surgery (TTS) among patients with resectable hepatocellular carcinoma (HCC) is not well defined. Methods: Patients who underwent curative-intent hepatectomy for BCLC-0, A and B HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of prolonged TTS on overall survival (OS) and disease-free survival (DFS) was examined. Results: Among 775 patients who underwent resection for HCC, 537 (69.3%) had early surgery (TTS < 90 days) and 238 (30.7%) patients had a delayed surgery (TTS ≥ 90 days). Patient- and tumor-related characteristics were similar between the two groups except for a higher proportion of patients undergoing major liver resection in the early surgery group (31.3% vs. 23.8%, p = .04). The percentage of patients with delayed surgery varied from 8.8% to 59.1% among different centers (p < .001). Patients with TTS < 90 days had similar 5-year OS (63.7% vs. 64.9; p = .79) and 5-year DFS (33.5% vs. 42.4; p = .20) with that of patients with TTS ≥ 90 days. On multivariable analysis, delayed surgery was not associated with neither worse OS (BCLC-0/A: adjusted hazards ratio [aHR] = 0.90; 95% confidence interval [CI]: 0.65-1.25 and BCLC-B: aHR = 0.72; 95%CI: 0.30-1.74) nor DFS (BCLC-0/A: aHR = 0.78; 95%CI: 0.60-1.01 and BCLC-B: aHR = 0.67; 95% CI: 0.36-1.25). Conclusion: Approximately one in three patients diagnosed with resectable HCC had a prolonged TTS. Delayed surgery was not associated with worse outcomes among patients with resectable HCC. info:eu-repo/semantics/publishedVersion

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. info:eu-repo/semantics/publishedVersion

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 5.0cm (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, 84.0months vs < 50% necrosis, 73.6months vs ≥ 50% necrosis: 59.3months; p < 0.001) and RFS (median RFS: no necrosis, 49.6months vs < 50% necrosis, 38.3months vs ≥ 50% necrosis: 26.5months; 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 61.8months; 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 62.4months; 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.

The prognostic impact of colorectal liver metastasis (CRLM) morphologic characteristics relative to KRAS mutational status after hepatic resection remains ill defined.Patients undergoing hepatectomy for CRLM between 2001 and 2018 were identified using an international multi-institutional database. Tumor burden score (TBS) was defined as distance from origin on a Cartesian plane that incorporated maximum tumor size (x-axis) and number of lesions (y-axis). Impact of TBS on overall survival (OS) relative to KRAS status (wild type [wtKRAS] vs mutated [mutKRAS]) was assessed.Among 1,361 patients, the median number of metastatic lesions was 2 (interquartile range [IQR] 1-3), and median size of the largest metastatic lesion was 3.0 cm (IQR 2.0-5.0 cm), resulting in a median TBS of 4.1 (IQR 2.8-6.1); KRAS status was wtKRAS (n = 420, 30.9%), mutKRAS (n = 251, 18.4%), and unknown (n = 690, 50.7%). Overall median and 5-year OS were 49.5 months (95%CI 45.2-53.8) and 43.2%, respectively. In examining the entire cohort, TBS was associated with long-term prognosis (5-year OS, low TBS: 49.4% vs high TBS: 36.7%), as was KRAS mutational status (5-year OS, wtKRAS: 48.2% vs mutKRAS: 31.1%; unknown KRAS: 44.0%)(both p0.01). Among patients with wtKRAS tumors, TBS was strongly associated with improved OS (5-year OS, low TBS: 59.1% vs high TBS: 38.4%, p = 0.002); however, TBS failed to discriminate long-term prognosis among patients with mutKRAS tumors (5-year OS, low TBS: 37.4% vs high TBS: 26.7%, p = 0.19). In fact, patients with high TBS/wtKRAS CRLM had comparable outcomes to patients with low TBS/mutKRAS tumors (5-year OS, 38.4% vs 37.4%, respectively; p = 0.59). On multivariable analysis, while TBS was associated with OS among patients with wtKRAS CRLM (hazard ratio 1.43, 95%CI 1.02-2.00; p = 0.03), TBS was not an independent predictor of survival among patients with mutKRAS CRLM (HR 1.36, 95%CI 0.92-1.99; p = 0.12).While TBS was associated with survival among patients with wtKRAS tumors, CRLM morphology was not predictive of long-term outcomes among patients with mutKRAS CRLM.

Background The objective of this study was to assess trends in the use as well as the outcomes of patients undergoing simultaneous versus staged resection for synchronous colorectal liver metastases. Methods Patients undergoing resection for colorectal liver metastases between 2008 and 2018 were identified using a multi-institutional database. Trends in use and outcomes of simultaneous resection of colorectal liver metastases were examined over time and compared with that of staged resection after propensity score matching. Results Among 1,116 patients undergoing resection for colorectal liver metastases, 690 (61.8%) patients had synchronous disease. Among them, 314 (45.5%) patients underwent simultaneous resection, while 376 (54.5%) had staged resection. The proportion of patients undergoing simultaneous resection for synchronous colorectal liver metastases increased over time (2008: 37.2% vs 2018: 47.4%; ptrend = 0.02). After propensity score matching (n = 201 per group), patients undergoing simultaneous resection for synchronous colorectal liver metastases had a higher incidence of overall (44.8% vs 34.3%; P = .03) and severe complications (Clavien-Dindo ≥III) (16.9% vs 7.0%; P = .002) yet comparable 90-day mortality (3.5% vs 1.0%; P = .09) compared with patients undergoing staged resection. The incidence of severe morbidity decreased over time (2008: 50% vs 2018: 11.1%; ptrend = 0.02). Survival was comparable among patients undergoing simultaneous versus staged resection of colorectal liver metastases (3-year overall survival: 66.1% vs 62.3%; P = .67). Following simultaneous resection, severe morbidity and mortality increased incrementally based on the extent of liver resection and complexity of colectomy. Conclusion While simultaneous resection was associated with increased morbidity, the incidence of severe morbidity decreased over time. Long-term survival was comparable after simultaneous resection versus staged resection of colorectal liver metastases.

Bile acids (BAs) assessments are garnering increasing interest for their potential involvement in development and progression of cholangiocarcinoma (CCA). Since machine learning (ML) algorithms are increasingly used for exploring metabolomic profiles, we evaluated performance of some ML models for dissecting patients with CCA or benign biliary diseases according to their plasma BAs profiles. We used ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) for assessing plasma BAs profile in 112 patients (70 CCA, 42 benign biliary diseases). Twelve normalisation procedures were applied, and performance of six ML algorithms were evaluated (logistic regression, k-nearest neighbors, na&iuml, ve bayes, RBF SVM, random forest, extreme gradient boosting). Na&iuml, ve bayes, using direct bilirubin concentration for normalisation of BAs, was the ML model displaying better performance in the holdout set, with an Area Under Curve (AUC) of 0.95, 0.79 sensitivity, 1.00 specificity. This model, also characterised by 1.00 positive predictive value and 0.73 negative predictive value, displayed a globally excellent accuracy (86.4%). The accuracy of the other five models was lower, and AUCs ranged 0.75&ndash, 0.95. Preliminary results of this study show that application of ML to BAs profile analysis can provide a valuable contribution for characterising bile duct diseases and identifying patients with higher likelihood of having malignant pathologies.

We aimed to investigate the impact of the site of the primary on postoperative and oncological outcomes in patients undergone simultaneous approach for colon (CC) and rectal cancer (RC) with synchronous liver metastases (SCRLM).Of the 220 patients with SCRLM operated on between Mar 2006 and Dec 2017, 169 patients (76.8%) were treated by a simultaneous approach and were included in the study. Two groups were considered according to the location of primary tumor RC-Group (n = 47) and CC-group (n = 122).Multiple liver metastases were observed in 70.2% in RC-Group and 77.0% in CC-Group (p = 0.233), whilst median Tumor Burden Score (TBS) was 4.7 in RC-Group and 5.4 CC-Group (p = 0.276). Severe morbidity (p = 0.315) and mortality at 90 days (p = 0.520) were comparable between RC-Group and CC-Group. The 5-year overall survival (OS) rate was similar comparing RC-Group and CC-Group (48.2% vs. 45.3%; p = 0.709), but it was significantly different when considering left-CC, right-CC and RC separately (54.5% vs. 35.2% vs. 48.2%; p = 0.041). Primary tumor location (right-CC, p = 0.001; RC, p = 0.002), microscopic residual (R1) disease at the primary (p 0.001), TBS ≥6 (p = 0.012), bilobar metastases (p = 0.004), and chemotherapy strategy (preoperative ChT, p = 0.253; postoperative ChT, p = 0.012; and perioperative ChT, p 0.001) resulted to be independent prognostic factors at multivariable analysis.In patients with SCRLM, simultaneous resection of the primary tumor and liver metastases seems feasible and safe and allows satisfactory oncological outcomes both in CC and RC. Right-CC shows a worse prognosis when compared to left-CC and RC.

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. 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. 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. 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 The refusal of blood transfusions compels surgeons to face ethical and clinical issues. A single-institution experience with a dedicated perioperative blood management protocol was reviewed to assess feasibility and short-term outcomes of true bloodless pancreatic surgery. Methods The institutional database was reviewed to identify patients who refused transfusion and were scheduled for elective pancreatic surgery from 2010 through 2018. A protocol to optimize the hemoglobin values by administration of drugs stimulating erythropoiesis was systematically used. Results Perioperative outcomes of 32 Jehovah’s Witnesses patients were included. Median age was 67 years (range, 31–77). Nineteen (59.4%) patients were treated with preoperative erythropoietin. Twenty-four (75%) patients underwent pylorus-preserving pancreaticoduodenectomy, 4 (12.5%) distal pancreatectomy (DP) with splenectomy, 3 (9.4%) spleen-preserving DP, and 1 (3.1%) total pancreatectomy. Median estimated blood loss and surgical duration were 400 mL (range, 100–1000) and 470 min (range, 290–595), respectively. Median preoperative hemoglobin was 13.9 g/dL (range, 11.7–15.8) while median postoperative nadir hemoglobin was 10.5 g/dL (range, 7.1–14.1). The most common histological diagnosis (n = 15, 46.9%) was pancreatic ductal adenocarcinoma. Clavien-Dindo grade I-II complications occurred in fourteen (43.8%) patients while one (3.1%) patient had a Clavien-Dindo grade IIIa complication wich was an abdominal collection that required percutaneous drainage. Six (18.8%) patients presented biochemical leak or postoperative pancreatic fistula grade B. Median hospital stay was 16 days (range, 8–54) with no patient requiring transfusion or re-operation and no 90-day mortality. Conclusions A multidisciplinary approach and specific perioperative management allowed performing pancreatic resections in patients who refused transfusion with good short-term outcomes.

Objective To define and test "Textbook Outcome" (TO)-a composite measure for healthcare quality-among Medicare patients undergoing hepatopancreatic resections. Hospital variation in TO and Medicare payments were analyzed. Background Composite measures of quality may be superior to individual measures for the analysis of hospital performance. 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. TO was defined as: no postoperative surgical complications, no prolonged length of hospital stay, no readmission ≤ 90 days after discharge, and no postoperative mortality ≤ 90 days after surgery. Medicare payments were compared among patients who achieved TO versus patients who did not. Multivariable logistic regression was used to investigate patient factors associated with TO. A nomogram to predict probability of TO was developed and validated. Results TO was achieved in 44% (n = 5919) of 13,467 patients undergoing hepatopancreatic surgery. Adjusted TO rates at the hospital level varied from 11.1% to 69.6% for pancreatic procedures and from 16.6% to 78.7% for liver procedures. Prolonged length of hospital stay represented the major obstacle to achieve TO. Average Medicare payments were substantially higher among patients who did not have a TO. Factors associated with TO on multivariable analysis were age, sex, Charlson comorbidity score, previous hospital admissions, procedure type, and surgical approach (all P > 0.05). Conclusions Less than one-half of Medicare patients achieved a TO following hepatopancreatic procedures with a wide variation in the rates of TO among hospitals. There was a discrepancy in Medicare payments for patients who achieved a TO versus patients who did not. TO could be useful for the public reporting of patient level hospital performance and hospital variation.

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. 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. 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

BACKGROUND AND OBJECTIVES Reducing readmissions is an important quality improvement metric. We sought to investigate patterns of 90-day readmission after hepato-pancreatic (HP) procedures. METHODS The Nationwide Readmissions Database (NRD) was used to identify patients undergoing HP procedures between 2010 and 2014. Patients were stratified according to benign versus malignant HP diagnoses and as index (same hospital as operation) versus non-index (different hospital) readmissions. RESULTS Among the 41 059 patients who underwent HP procedures, 26 563 (65%) underwent a liver resection while 14 496 (35%) pancreatic resection. Among all patients, 11 902 (29%) had a benign diagnosis versus 29 157 (71%) who had a cancer diagnosis. Overall 90-day readmission was 22% (n = 8 998) with a slight increase in readmissions among patients with a malignant (n = 6 655;23%) versus benign (n = 2 343;20%) diagnosis (P

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.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.Not only was FTR less common at HV hospitals, but the management of most major complications was cost-effective at higher volume centers.

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. 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 (cm2), 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, cm2/m2). 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/m2 among men and 27.5 kg/m2 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. 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.

Background The role of routine lymph node dissection (LND) in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) remains controversial. The objective of this study was to investigate the trends of LND use in the surgical treatment of ICC. Methods Patients undergoing curative intent resection for ICC in 2000–2015 were identified from an international multi-institutional database. Use of lymphadenectomy was evaluated over time and by geographical region (West versus East); LND use and final nodal status were analysed relative to AJCC T categories. Results Among the 1084 patients identified, half (535, 49·4 per cent) underwent concomitant hepatic resection and LND. Between 2000 and 2015, the proportion of patients undergoing LND for ICC nearly doubled: 44·4 per cent in 2000 versus 81·5 per cent in 2015 (P < 0·001). Use of LND increased over time among both Eastern and Western centres. The odds of LND was associated with the time period of surgery and the extent of the tumour/T status (referent T1a: OR 2·43 for T2, P = 0·001; OR 2·13 for T3, P = 0·016). Among the 535 patients who had LND, lymph node metastasis (LNM) was noted in 209 (39·1 per cent). Specifically, the incidence of LNM was 24 per cent in T1a disease, 22 per cent in T1b, 42·9 per cent in T2, 48 per cent in T3 and 66 per cent in T4 (P < 0·001). AJCC T3 and T4 categories, harvesting of six or more lymph nodes, and presence of satellite lesions were independently associated with LNM. Conclusion The rate of LNM was high across all T categories, with one in five patients with T1 disease having nodal metastasis. The trend in increased use of LND suggests a growing adoption of AJCC recommendations in the treatment of ICC.

BACKGROUND: The risk of recurrence for patients undergoing curative-intent surgery for non-metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) is currently poorly defined. We sought to develop and validate a nomogram to predict the risk of recurrence after curative-intent resection. METHODS: Using a pseudo-randomization technique, a training set to develop a predictive nomogram and a test set to validate the nomogram were identified. The predictive ability of the nomogram to predict recurrence was assessed using the c-index. RESULTS: Among 1,477 patients, 673 (46%) patients were included in the training set and 804 (54%) patients were included in the test set to validate the nomogram. On multivariable analysis, Ki-67, tumor size, nodal status, and invasion of adjacent organs were independent predictors of DFS. The risk of death increased by 8% for each percentage increase in the Ki-67 index (HR 1.08, 95% CI, 1.05–1.10; p3 lymph node metastasis had a 2.5-fold increased risk of death (HR 2.51, 95% CI, 1.50–4.24; p80%, which correlated with disease free-survival at 10-year of 87%, 68%, 37%, and 0%, respectively. CONCLUSION: A nomogram based on four variables (i.e. Ki-67, tumor size, invasion of adjacent organs and lymph node status) was able to predict the risk of recurrence after surgery for GEP-NET. The nomogram demonstrated a good ability to identify patients at risk of recurrence and can be easily applied in the clinical setting.