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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., (© 2020 Wiley Periodicals LLC.)

Background: The aim of the current study was to develop an online calculator to predict survival after liver resection for intrahepatic cholangiocarcinoma (ICC) based on the "metro-ticket" paradigm., Methods: Between 1990 and 2016, patients who underwent liver resection for ICC were identified in an international multi-institutional database. The final multivariable model of survival was used to develop an online prognostic calculator of survival., Results: Among 643 patients, actual 5-year overall survival (OS) after resection for ICC was 42.7%. On multivariable analysis, CA19-9 > 200 (hazard ratio (HR), 2.62; 95% CI, 2.01-3.42), sum of the number and largest tumor size >7 (HR, 1.88; 95% CI, 1.46-2.42), N1 disease (HR, 2.87; 95% CI, 1.98-4.16), R1 resection (HR, 1.72; 95% CI, 1.21-2.46), poor/undifferentiated tumor grade (HR, 1.74; 95% CI, 1.25-2.44), major vascular invasion (HR, 1.47; 95% CI, 1.03-2.10), and adjuvant chemotherapy (HR, 0.64; 95% CI, 0.45-0.89) were significantly associated with survival and were included in the online calculator. The predictive accuracy of the model was good to very good as the C-statistics to predict 5-year OS was 0.696 in the training dataset and 0.672 with bootstrapping resamples (n = 5000) in the test dataset., Conclusion: A novel, online calculator was developed to estimate the 5-year survival probability for patients undergoing resection for ICC. This tool could help provide useful information to guide treatment decision-making and inform conversations about prognosis., (© 2019 Wiley Periodicals, Inc.)

Background: The objective of the current study was to define the impact of albumin-bilirubin (ALBI) grade on short- as well as long-term outcomes among patients with intrahepatic cholangiocarcinoma (ICC)., Methods: Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified using an international multi-institutional database. Clinicopathologic factors including ALBI score were assessed using bivariate and multivariable analyses, as well as standard survival analyses., Results: Among 706 patients, 453 (64.2%) patients had ALBI grade 1, 231 (32.7%) ALBI grade 2, and 22 (3.1%) had ALBI grade 3. After adjusting for all competing factors, patients with ALBI grade 2/3 had higher odds of a prolonged length-of-stay (>10 days, odds ratio [OR] = 2.37, 95% confidence interval [CI]:1.47-3.80), perioperative transfusion (OR = 2.15, 95% CI:1.45-3.18) and 90-day mortality (OR = 2.50, 95% CI:1.16-5.38). Median and 5-year overall survival (OS) for the entire cohort was 41.5 months (IQR:15.7-107.8) and 39.8%, respectively. Of note, median OS incrementally worsened with increased ALBI grade: grade 1, 49.6 months (IQR:18.3-NR) vs grade 2, 29.6 months (IQR:12.6-98.4) vs grade 3, 16.9 months (IQR:6.5-32.4; P < 0.001). On multivariable analysis, higher ALBI grade remained associated with higher hazards of death (grade 2/3: hazard ratio = 1.36, 95% CI:1.04-1.78)., Conclusion: The ALBI score was associated with both short- and long-term outcomes following resection for ICC and could prove a useful surrogate marker to identify patients at risk for adverse outcomes., (© 2019 Wiley Periodicals, Inc.)

Background: We sought to define the management of mixed hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC) as well as characterize short- and long-term outcomes of patients with mixed HCC-ICC., Methods: Patients diagnosed with HCC-ICC, HCC, or ICC between 2004 and 2015 were identified from the National Cancer Data Base using the International Classification of Diseases for Oncology codes. Short- and long-term outcomes were assessed using univariate and multivariate analyses., Results: Among 174 454 patients, 86.8% had HCC, 12.1% ICC, and 1.1% HCC-ICC. The incidence of lymphadenectomy was 55.6% among ICC patients vs 15.1% and 34.2% for HCC and HCC-ICC patients, respectively (P < 0.001). A 90-day mortality was comparable among patients with HCC (9.1%), ICC (8.8%), and HCC-ICC (10.5%) (all P > 0.2). While 42.0% of ICC patients received adjuvant chemotherapy, adjuvant chemotherapy among HCC and HCC-ICC patients was 13.1% and 27.4%, respectively (P < 0.001). A 5-year survival was 43.5% (95% CI, 42.5-44.5), 33.3% (95% CI, 31.4-35.3), 34.4% (95% CI, 29.1-39.8) for HCC, ICC, and HCC-ICC patients, respectively., Conclusion: Patients who underwent resection of mixed HCC-ICC had a prognosis that was comparable to ICC, yet worse than HCC. Utilization of lymphadenectomy and adjuvant therapy were low. HCC-ICC remains a rare disease with a guarded prognosis that should be treated in a multidisciplinary setting., (© 2018 Wiley Periodicals, Inc.)

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy. We sought to examine the association between preoperative prognostic nutritional index (PNI) and long-term overall survival among patients with ICC who underwent curative-intent resection., Methods: Patients who underwent hepatectomy for ICC between 1990 and 2015 were identified using an international multi-institutional database. Clinic-pathological characteristics and long-term outcomes of patients with PNI ≥ 40 and <40 were compared using univariable and multivariable analyses., Results: Among 637 patients, 53 patients had PNI < 40 (8.3%) and 584 patients had PNI ≥ 40 (91.7%). While there was no difference between PNI groups with regard to tumor size (P = .87), patients with PNI < 40 were more likely to have multifocal disease (PNI < 40, n = 16, 30.2% vs PNI ≥ 40, n = 65, 11.1%; P < 0.001), poorly differentiated or undifferentiated ICC (PNI < 40, n = 13, 25.5% vs PNI ≥ 40, n = 75, 13.1%; P = 0.020) and T2/T3/T4 disease vs patients with PNI ≥ 40 (PNI < 40, n = 38, 71.7% vs PNI ≥ 40, n = 265, 45.4%; P < 0.001). Patients with PNI ≥ 40 had better OS vs patients with PNI < 40 (5-year OS: PNI ≥ 40: 47.5%, 95% CI, 42.2 to 52.6% vs PNI < 40: 24.6%, 95% CI, 12.1 to 39.6%; P < 0.001). On multivariable analysis, PNI < 40 remained associated with increase risk of death (HR, 1.71; 95% CI, 1.15 to 2.53; P = 0.008)., Conclusion: A low preoperative PNI was associated with a more aggressive ICC phenotype. After controlling for these factors, PNI remained independently associated with a markedly worse prognosis., (© 2018 Wiley Periodicals, Inc.)

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 < 0.001). Readmission to an index hospital was more common (n = 7 316 81%) versus a non-index hospital (n = 1 682 19%). Non-index hospital readmissions were more frequent among patients with malignant HP diagnoses (OR, 1.41;P  = 0.001)., Conclusions: Up to one in four patients were readmitted after HP surgery. Late readmission was more common among patients with a cancer-diagnosis. While most readmissions occurred at the index hospital, 19% of all readmissions occurred at a non-index hospital and were more frequent among patients with malignant diagnoses., (© 2018 Wiley Periodicals, Inc.)

Background: The effect of the histological subtype on the prognosis of patients undergoing surgery for colon cancer (CC) is not completely understood., Methods: The Surveillance, Epidemiology, and End Results (SEER) 2004-2014 database was used to compare the long-term outcomes of patients undergoing colon resection for classical adenocarcinoma (CA), mucinous adenocarcinoma (MUC), and signet-cell adenocarcinoma (SC)., Results: A total of 153 317 (89%) patients had CA, 16 660 (10%) MUC while 1810 (1%) patients had SC subtype. Patients with MUC and SC more frequently had a poorly differentiated CC and were more likely to present with advanced disease compared with CA patients (P < 0.001). Patients with CA had a 5-year OS of 62% versus 55% and 34% for patients with MUC and SC subtypes, respectively (P = 0.001). On multivariable analysis, site of cancer, tumor grade, and TNM stage were associated with prognosis (all P < 0.001). After controlling for these risk factors, patients with MUC (HR, 1.09, P < 0.001) and SC (HR, 1.47, P < 0.001) had a roughly 10% and 50% increased hazard of death, respectively, compared with CA patients., Conclusions: MUC and SC are distinct subtypes of CC associated with a worse prognosis. These data can help inform discussion about prognosis and possibly direct adjuvant management., (© 2018 Wiley Periodicals, Inc.)

Background: The risk of recurrence after resection of non-metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) is poorly defined. We developed/validated a nomogram to predict risk of recurrence after curative-intent resection., Methods: A training set to develop the nomogram and test set for validation were identified. The predictive ability of the nomogram was assessed using c-indices., Results: Among 1477 patients, 673 (46%) were included in the training set and 804 (54%) in y the test set. 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; P < 0.001). GEP-NET invading adjacent organs had a HR of 1.65 (95% CI, 1.03-2.65; P = 0.038), similar to tumors ≥3 cm (HR 1.67, 95% CI, 1.11-2.51; P = 0.014). Patients with 1-3 positive nodes and patients with >3 positive nodes had a HR of 1.81 (95% CI, 1.12-2.87; P = 0.014) and 2.51 (95% CI, 1.50-4.24; P < 0.001), respectively. The nomogram demonstrated good ability to predict risk of recurrence (c-index: training set, 0.739; test set, 0.718)., Conclusion: The nomogram was able to predict the risk of recurrence and can be easily applied in the clinical setting., (© 2018 Wiley Periodicals, Inc.)

Introduction: We sought to validate the commonly used prognostic models and staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi-center patient cohort., Methods: The overall (OS) and disease free survival (DFS) prognostic discriminatory ability of various commonly used models were assessed in a large retrospective cohort. Harrell's concordance index (c-index) was used to determine accuracy of model prediction., Results: Among 1054 ICC patients, median OS was 37.7 months and 1-, 3-, and 5-year survival, were 78.8%, 51.5%, and 39.3%, respectively. Recurrence of disease occurred in 454 (43.0%) patients with a median DFS of 29.6 months. One-, 3- and 5- year DFS were 64.6%, 46.5 % and 44.4%, respectively. The prognostic models associated with the best OS prediction were the Wang nomogram (c-index 0.668) and the Nathan staging system (c-index 0.639). No model was proficient in predicting DFS. Only the Wang nomogram exceeded a c-index of 0.6 for DFS (c-index 0.602). The c-index for the AJCC staging system was 0.637 for OS and 0.582 for DFS., Conclusions: While the Wang nomogram had the best discriminatory ability relative to OS and DFS, no ICC staging system or nomogram demonstrated excellent prognostic discrimination. The AJCC staging for ICC performed reasonably, although its overall discrimination was only modest-to-good., (© 2017 Wiley Periodicals, Inc.)

Background: The objective of this study was to assess the prognostic performance of American Joint Committee on Cancer (AJCC) 8th edition in patients with intrahepatic cholangiocarcinoma (ICC) using a cancer registry., Methods: The Surveillance, Epidemiology, and End Results (SEER) cancer registry was queried to identify 1008 patients who underwent surgical resection of ICC during 1998-2013. Kaplan-Meier method and Cox proportional hazards regression models were used to analyze long-term survival. The relative discriminative abilities were assessed using the Harrell's concordance index., Results: Median patient age was 62 years and 47.6% of the patients were male. Most tumors were T1 or T2 (n = 413, 41.0% and n = 329, 32.6%, respectively) and 22.1% of patients had lymph node (LN) metastasis. Median tumor size was 5.5 cm. With a median follow-up of 18 months, median survival was 27 months and 5-year OS was 30.6%. The OS c-index for the AJCC 8th staging system was 0.669, which was comparable with the c-index for the 7th edition AJCC staging system (c-index: 0.667); the AJCC 8th-edition did provide more discrete stratification of patients., Conclusions: The new AJCC 8th-edition staging system for ICC was largely comparable to the 7th-edition version and did not provide a marked improvement in overall prognostic discrimination., (© 2017 Wiley Periodicals, Inc.)

Objective: We sought to characterize the treatment, as well as define the long-term outcomes, of patients with recurrent neuroendocrine liver metastasis (NELM)., Methods: Between 1990 and 2014, 322 patients undergoing curative intent liver surgery for NELM were identified from a multi-institutional database. Recurrences were classified as intrahepatic, extrahepatic, and both intra- and extra-hepatic., Results: Overall, median, 1-, 5-, 10-year DFS were 3.1 years, 75.5%, 40.4%, and 32.1%, respectively. After curative intent liver surgery, 209 patients (64.9%) recurred within a median follow-up of 4.5 years, while 113 (35.1%) patients were alive without disease with a follow-up time ≥3 years. The site of recurrence was intrahepatic only (n = 111, 65.7%), extrahepatic only (n = 19, 11.2%), or intra- and extra-hepatic (n = 39, 23.1%). Compared with intrahepatic only recurrence, extrahepatic only, and combined intra- and extra-hepatic recurrence were associated with a worse long-term outcome (10-year OS: intrahepatic only, 42.5%, 95%CI, 24.9-59.0 vs extrahepatic only, 0% and combined intra- and extra-hepatic, 21.5%, 95%CI, 5.3-44.0) (P < 0.001). Most patients were treated with repeat surgery (n = 49, 36.6%), while 34 (23.5%) patients received a somatostatin analogue, 27 (18.6%) systemic cytotoxic chemotherapy, and 27 (21.4%) patients had intra-arterial therapy. Ten-year OS among patients who underwent repeat surgery or intra-arterial treatments was 60.3% (95%CI, 34.1-78.8) and 52.0% (95%CI, 30.6-69.9), respectively. Patients who received somatostatin analogues (45.9% 95%CI, 22.3-66.9) or systemic chemotherapy (0%) had a shorter long-term survival (P = 0.001)., Conclusion: Recurrence after surgery for NELM occurred among half of patients. Repeat liver resection for recurrence may offer a reasonable 5-year survival benefit., (© 2017 Wiley Periodicals, Inc.)

Background and Objective: Neuroendocrine liver metastasis tumors (NELM) are a heterogeneous group of neoplasms with varied histologic features and a wide range of clinical behaviors. We aimed to identify the fraction of patients cured after liver surgery for NELM., Methods: Cure fraction models were used to analyze 376 patients who underwent hepatectomy with curative intent for NELM., Results: The median and 5-year disease-free survival (DFS) were 4.5 years and 46%, respectively. The probability of being cured from NELM by liver surgery was 44%; the time to cure was 5.1 years. In a multivariable cure model, type of neuroendocrine tumor (NET), grade of tumor differentiation, and rate of liver involvement resulted as independent predictors of cure. The cure fraction for patients with well differentiated NELM from gastrointestinal NET or a functional pancreatic NET, and with <50% of liver-involvement was 95%. Patients who had moderately/poorly differentiated NELM from a non-functional pancreatic NET, and with <50% of liver-involvement was 43%. In the presence of all the three unfavorable prognostic factors (nonfunctional PNET, liver involvement >50%, moderately/poorly differentiation), the cure fraction was 8%., Conclusions: Statistical cure after surgery for NELM is possible, and allow for a more accurate prediction of long-term outcome among patients with NELM undergoing liver resection., (© 2017 Wiley Periodicals, Inc.)

Background: We sought to evaluate and validate the 8th edition of the AJCC classification using a multi-institutional cohort of patients with intrahepatic cholangiocarcinoma (ICC)., Methods: Patients undergoing curative-intent hepatic resection for ICC between 1990 and 2015 at 14 major hepatobiliary centers were included and were staged according to 7th and 8th editions AJCC criteria., Results: A total of 1154 patients underwent liver resection for ICC. When patients were staged using the AJCC 7th edition, T2a, T2b, and T4 patients had a higher hazard ratio (HR) of death compared with T1 (T2a, HR 1.43, P = 0.004; T2b, HR 1.99, P < 0.001; T4, HR 2.20, P < 0.001). T3 patients had a higher HR of death compared with T1 patients (HR 1.30, P = 0.029) but lower than T2a and T2b. According to AJCC 8th edition, T1b, T2, and T4 patients were at higher risk of death compared with T1a patients (T1b, HR 1.91, P < 0.001; T2, HR 2.29, P < 0.001; T4, HR 4.16, P < 0.001). As in the AJCC 7th edition, AJCC 8th edition T3 patients had a higher HR of death compared with T1 patients (HR 1.65, P  = 0.001) but lower than T1b and T2. AJCC 8th edition. T-category performed slightly better than AJCC 7th edition with a C-index of 0.609 versus 0.590., Conclusions: A staging system that perfectly discriminates between stages has not yet been developed, but the AJCC 8th edition was able to better stratify the risk of death of Stage III and T3 patients., (© 2017 Wiley Periodicals, Inc.)

Background: Little is known regarding postoperative outcomes of elderly patients undergoing liver surgery for intrahepatic cholangiocarcinoma (ICC)., Methods: Five hundred and eighty-four patients undergoing liver resection for ICC between 1990 and 2015 were identified. Perioperative morbidity, mortality, overall survival (OS), and disease-free survival (DFS) were compared between elderly (>70 year, n = 129) and non-elderly (≤70 years, n = 455) patients., Results: Older patients had a higher incidence of complications (elderly vs. non-elderly; 52.7% vs. 42.6%; P = 0.03), as well as major complications (elderly vs. non-elderly; 24.0% vs. 14.9%; P = 0.01); 30-day (0.1% vs. 3.3%; P > 0.05), and 90-day mortality (2.3% vs. 5.5%; P > 0.05) were comparable. Five-year OS and DFS were comparable between the elderly and non-elderly patients (OS, 13.3% vs. 24.4%; and DFS; 7.3% vs. 12.0%; P > 0.05). On propensity score matching, DFS and OS were also comparable among non-elderly versus elderly patients. Poor tumor grade was associated with worse DFS among elderly patients (HR = 1.6, 95%CI 1.0-2.6; P = 0.04), whereas periductal invasion (HR = 1.9, 95% CI 1.1-3.5; P = 0.03) and nodal disease (HR = 2.3, 95% CI 1.3-3.9; P = 0.003) were predictive of shorter DFS among non-elderly patients., Conclusion: Elderly patients undergoing liver surgery for ICC demonstrated an increased risk of perioperative complications, but comparable long-term DFS and OS compared with younger patients. Rather, tumor characteristics were more predictive of worse long-term outcomes. J. Surg. Oncol. 2016;113:420-426. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: The systemic inflammatory response may be associated with tumor progression. We sought to analyze the impact of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on recurrence-free survival (RFS) and disease-specific survival (DSS) among patients who underwent surgery for adrenocortical carcinoma (ACC)., Methods: Patients undergoing surgery for ACC were identified from a multi-center database. Cut-off values of 5 and 190 were defined as elevated NLR and PLR, respectively, and long-term outcome was assessed., Results: Among 84 patients with ACC, 29 (34.%) had NLR > 5 while 32 (40.5%) had PLR > 190. NLR and PLR were associated with larger tumors (NLR > 5: ≤ 5 cm, 0% vs. >5 cm, 39.7%; PLR > 190: ≤ 5cm, 0% vs. >5 cm, 45.7%), as well as need to resect of other organs (NLR > 5: other organ resected 48.8% vs. not resected 20.9%; PLR > 190: other organ resected 25.0% vs. not resected 56.4%)(all P < 0.05). Five-year RFS was associated with an elevated NLR (NLR ≤ 5, 14.2% vs. NLR> 5, 10.5%) and PLR (PLR ≤ 190: 19.4% vs. PLR > 190: 5.2%) (both P < 0.05). On multivariate survival analyses, PLR remained a predictor of RFS (HR 1.72), while NLR was associated with both DSS (HR 2.21) and RFS (HR 1.99) (both P < 0.05)., Conclusions: Immune markers such as NLR and PLR may be useful to stratify patients with regards to prognosis following surgery for ACC., (© 2015 Wiley Periodicals, Inc.)