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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. info:eu-repo/semantics/publishedVersion

Background: The objective of the current study was to characterize patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent surgery with discordant preoperative and postoperative prediction scores and determine factors associated with prediction discrepancy. Methods: Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified in a multi-institutional international database. Preoperative and postoperative prognostic models were designed and discordant prognostic scores were identified. A multivariable logistic regression analysis was completed to determined factors associated with score discordance. Results: Among 1149 patients, those who had concordant prediction scores were older (median age, 60 vs 56), and more likely to have a smaller median tumor size (6.0 vs 7.5 cm) (all P

BackgroundLittle is known regarding postoperative outcomes of elderly patients undergoing liver surgery for intrahepatic cholangiocarcinoma (ICC). MethodsFive 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. ResultsOlder 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. ConclusionElderly 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. (c) 2016 Wiley Periodicals, Inc.

BACKGROUNDA patient can be considered statistically cured from a specific disease when their mortality rate returns to the same level as that of the general population. In the current study, the authors sought to assess the probability of being statistically cured from intrahepatic cholangiocarcinoma (ICC) by hepatic resection. METHODSA total of 584 patients who underwent surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. A nonmixture cure model was adopted to compare mortality after hepatic resection with the mortality expected for the general population matched by sex and age. RESULTSThe median, 1-year, 3-year, and 5-year disease-free survival was 10 months, 44%, 18%, and 11%, respectively; the corresponding overall survival was 27 months, 75%, 37%, and 22%, respectively. The probability of being cured of ICC was 9.7% (95% confidence interval, 6.1%-13.4%). The mortality of patients undergoing surgery for ICC was higher than that of the general population until year 10, at which time patients alive without tumor recurrence can be considered cured with 99% certainty. Multivariate analysis demonstrated that cure probabilities ranged from 25.8% (time to cure, 9.8 years) in patients with a single, well-differentiated ICC measuring 5 cm that was without vascular/periductal invasion and lymph nodes metastases versus

BACKGROUND: The impact of postoperative complications on the long-term outcomes of patients undergoing surgery for cancer is unclear. The objective of the current study was to define the incidence of complications among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) and identify the association between morbidity and long-term outcomes. METHODS: A total of 583 patients undergoing surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. The association between the occurrence and severity of postoperative complications on long-term survival was analyzed. RESULTS: The median age of the patients was 59.9 years and the majority of patients were male (52.3%). A total of 91 patients (15.6%) and 153 patients (26.2%) developed a major and minor postoperative complication, respectively; 18 patients (3.5%) died within 90 days of surgery. Median, 1-year, 3-year, and 5-year recurrence-free survival were 10.0 months, 43.3%, 16.7%, and 11.1%, respectively. Postoperative complications (hazard ratio [HR], 1.37, 95% confidence interval [95% CI], 1.08-1.73 [P=.01]) and severity of complications (major vs none: HR, 1.55; 95% CI, 1.14-2.11 [P=.01]; minor vs none: HR, 1.30; 95% CI, 0.99-1.70 [P=.06]) independently predicted shorter recurrence-free survival. Median, 1-year, 3-year, and 5-year overall survival was 27.8 months, 76.8%, 39.0%, and 23.4%, respectively. Postoperative complications (HR, 1.64; 95% CI, 1.30-2.08 [P

Background The presence of extra-hepatic disease (EHD) is no longer an absolute contraindication to surgery in patients with colorectal liver metastases (CRLM). Recently, a novel prognostic model predicting overall survival in such patients was proposed using five risk factors (EHD other than isolated lung metastases, CEA10ng/ml, >5 liver metastases, right colon as the primary CRC location, and diagnosis of EHD concomitant to CRLM recurrence). A bi-institutional database was used to perform an external validation of this model. Methods Ninety-seven patients operated for CRLM and EHD between 1982 and 2011 in two institutions was analyzed. The proposed prognostic model was validated in this cohort using Cox proportional hazards models and the concordance index (c). Results Of the five proposed risk factors, only EHD other than isolated lung metastases was found to independently predict overall survival [Hazards Ratio (HR)=2.10 (95% CI: 1.014.40)]. Although, the number of risk factors was marginally associated with overall survival in univariate analysis (P=0.049), the performance of the proposed prognostic model was poor when applied to our cohort (c=0.64). Conclusion The examined prognostic model of survival in patients with CRLM and EHD had poor performance. Further research is warranted to delineate the subset of patients who will benefit from surgery. J. Surg. Oncol. 2013;107:481485. (c) 2012 Wiley Periodicals, Inc.

Potential differences in presentation and outcome of patients with gastric cardia adenocarcinoma (GCA) and non-cardia adenocarcinoma may exist. The aim of the present study was to compare the clinicopathological characteristics and the prognosis of GCA versus non-cardia adenocarcinoma.Patients with gastric adenocarcinoma who underwent gastric resection between 2000-2012 were identified. Clinicopathological characteristics and outcomes were analyzed based on tumor site using a 1:2 matched-control, as well as a multivariable Cox model.Among 743 patients, 80 (10.7%) patients were diagnosed with GCA. Patients with GCA were more likely to have intestinal tumor type (GCA: 80.4% versus non-cardia: 64.2%, P = 0.04) or advanced AJCC T stage tumors (GCA 71.8% versus non-cardia 59.2%, P = 0.03). GCA patients more likely underwent a total gastrectomy (GCA: 85.7% vs. non-cardia: 39.8%) and had a longer length-of-stay (GCA: 10 days vs. non-cardia: 8 days) (both P 0.05). Outcomes in early stage I patients were worse among GCA (disease-free survival, 44.2%; overall survival, 42.3%) versus non-GCA (disease-free survival, 60.8%; overall survival, 63.0%) patients(both P 0.05).In general, disease-free survival and overall survival were similar between patients with GCA versus non-cardia adenocarcinoma. However, long-term outcome was worse among patients with GCA and early stage disease.

Data on outcomes after liver-directed therapy for intrahepatic cholangiocarcinoma (ICC) are limited due to the rarity of the disease. We sought to define overall utilization and temporal trends of liver-directed therapy for ICC.We identified 5,388 patients with ICC using the Surveillance Epidemiology and End Results (SEER) database between 1983 and 2010. Patients were characterized based on the type of liver-directed therapy received: surgical resection, ablation therapy, and radiation therapy.The majority of patients did not undergo liver-directed therapy (n = 4,156, 77.1%). Among those undergoing liver-directed therapy, surgical resection was most commonly performed (n = 672, 54.5%) and its utilization increased threefold over time (P = 0.001). The use of ablation therapy alone was used in 5.2% of patients and increased nearly sixfold over time (P = 0.39) whereas the use of radiation therapy alone decreased by nearly half (P 0.001). Overall median survival was 10 months. Poor predictors of survival include tumor-based factors such as regional and distant disease, as well as poorly differentiated and large tumors (5 cm).There was a moderate improvement in overall survival in patients with ICC between 1983 and 2010. The majority of patients with ICC are not undergoing liver-directed therapy. Among those who do undergo liver-directed therapy, the use of ablation therapy and surgery are increasing with nearly three in five patients undergoing resection.

Objective. We sought to evaluate the utilization of lymphadenectomy (LND) and the incidence of lymph node metastasis (LNM) among different morphologic types of intrahepatic cholangiocarcinoma (ICC). Methods. Clinical data of patients undergoing curative-intent resection for ICC between 1990 and 2017 were collected and analyzed. The preoperative nodal status was evaluated by imaging studies, and the morphologic and lymph node (LN) status was collected on final pathology report. Results. Overall, 1032 patients had a mass-forming (MF) or intraductal growth (IG) ICC subtype, whereas 150 patients had a periductal infiltrating (PI) or MF+PI subtype. Among the 924 patients with MF/IG ICC subtype who had nodal assessment on preoperative imaging, 747 (80.8%) were node-negative, whereas 177 (19.2%) patients were suspicious for metastatic nodal disease. On final pathological analysis, 71 of 282 (25.2%) patients who had preoperative node-negative disease ultimately had LNM. In contrast, 79 of 135 (58.5%) patients with preoperative suspicious/metastatic LNs had pathologically confirmed LNM (odds ratio [OR] 4.2, p

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: Management of neuroendocrine liver metastasis (NELM) in the setting of unresectable disease is poorly defined and the role of debulking remains controversial. The objective of the current study was to define outcomes following non-curative intent liver-directed therapy (debulking) among patients with NELM. METHODS: 612 patients were identified who underwent liver-directed therapy of NELM from a multi-institutional database. Outcomes were stratified according to curative (R0/R1) versus non-curative ≥ 80% debulking (R2). RESULTS: 179 (29.2%) patients had an R2/debulking procedure. Patients undergoing debulking more commonly had more aggressive high-grade tumors (R0/R1: 12.8% vs. R2: 35.0%; P < 0.001) or liver disease burden that was bilateral (R0/R1: 52.8% vs. R2: 75.6%; P < 0.001). After a median follow-up of 51 months, median (R0/R1: not reached vs. R2: 87 months; P < 0.001) and 5-year survival (R0/R1: 85.2% vs. R2: 60.7%; P < 0.001) was higher among patients who underwent an R0/R1 resection compared with patients who underwent a debulking operation. Among patients with ≥50% NELM liver involvement, median and 5-year survival following debulking was 55.4 months and 40.6%, respectively. CONCLUSION: Debulking operations for NELM provided reasonable long-term survival. Hepatic debulking for patients with NELM is a reasonable therapeutic option for patients with grossly unresectable disease that may provide a survival benefit. info:eu-repo/semantics/publishedVersion

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

BACKGROUND: The consequences of lymphadenectomy (LND) on cirrhotic patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) have not been investigated. We sought to analyze the impact of LND on morbidity among patients undergoing resection for ICC. METHODS: A total of 1005 patients who underwent hepatectomy for ICC at one of the 14 participating institutions between 1990 and 2015 were identified. A propensity score match analysis was performed to reduce confounding biases between cirrhosis and non-cirrhosis groups. RESULTS: Cirrhosis was diagnosed in 118 (11.7%) patients. Among non-cirrhotic patients, 63% underwent major liver resection versus only 20% among patients with cirrhosis (p < 0.001). LND was also less common among cirrhotic versus non-cirrhotic patients (19 vs. 50%, p < 0.001). The incidence of complications was 41 and 30% among patients who did not and did have cirrhosis, respectively (p = 0.022). The propensity-matched cohort included 150 patients. The incidence of complications was 71% among patients who underwent lymphadenectomy versus 23% among patients who did not undergo lymphadenectomy (OR 8.39) (p < 0.001). In the propensity-matched analysis, the median HLN was comparable among patients independent of cirrhosis status (median HLN: non-cirrhosis, 2.5 vs. cirrhosis, 2) (p = 0.95). While lymphadenectomy was associated with a higher risk of infections (non-cirrhosis, 0% vs. cirrhosis, 21%, p < 0.001) among patients with cirrhosis, infections were not associated with lymphadenectomy among non-cirrhotic patients (p = 0.19). CONCLUSION: Lymphadenectomy was associated with an increased risk of complications among patients with cirrhosis undergoing surgery for ICC. The benefit of lymphadenectomy in cirrhotic patients should be considered in light of the higher risk of postoperative complications compared with non-cirrhotic patients. info:eu-repo/semantics/publishedVersion

Background: Intrahepatic cholangiocarcinoma with hepatic hilus involvement has been either classified as intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma. The present study aimed to investigate the clinicopathologic characteristics and short- and long-term outcomes after curative resection for hilar type intrahepatic cholangiocarcinoma in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma. Methods: A total of 912 patients with mass-forming peripheral intrahepatic cholangiocarcinoma, 101 patients with hilar type intrahepatic cholangiocarcinoma, and 159 patients with hilar cholangiocarcinoma undergoing curative resection from 2000 to 2015 were included from two multi-institutional databases. Clinicopathologic characteristics and short- and long-term outcomes were compared among the 3 groups. Results: Patients with hilar type intrahepatic cholangiocarcinoma had more aggressive tumor characteristics (eg, higher frequency of vascular invasion and lymph nodes metastasis) and experienced more extensive resections in comparison with either peripheral intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma patients. The odds of lymphadenectomy and R0 resection rate among patients with hilar type intrahepatic cholangiocarcinoma were comparable with hilar cholangiocarcinoma patients, but higher than peripheral intrahepatic cholangiocarcinoma patients (lymphadenectomy incidence, 85.1% vs 42.5%, P < .001; R0 rate, 75.2% vs 88.8%, P < .001). After curative surgery, patients with hilar type intrahepatic cholangiocarcinoma experienced a higher rate of technical-related complications compared with peripheral intrahepatic cholangiocarcinoma patients. Of note, hilar type intrahepatic cholangiocarcinoma was associated with worse disease-specific survival and recurrence-free survival after curative resection versus peripheral intrahepatic cholangiocarcinoma (median disease-specific survival, 26.0 vs 54.0 months, P < .001; median recurrence-free survival, 13.0 vs 18.0 months, P = .021) and hilar cholangiocarcinoma (median disease-specific survival, 26.0 vs 49.0 months, P = .003; median recurrence-free survival, 13.0 vs 33.4 months, P < .001). Conclusion: Mass-forming intrahepatic cholangiocarcinoma with hepatic hilus involvement is a more aggressive type of cholangiocarcinoma, which showed distinct clinicopathologic characteristics, worse long-term outcomes after curative resection, in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma. (C) 2018 Elsevier Inc. All rights reserved.

BACKGROUND: Accurate prediction of prognosis for patients with intrahepatic cholangiocarcinoma (ICC) remains a challenge. We sought to define a preoperative risk tool to predict long-term survival after resection of ICC. STUDY DESIGN: Patients who underwent hepatectomy for ICC at 1 of 16 major hepatobiliary centers between 1990 and 2015 were identified. Clinicopathologic data were analyzed and a prognostic model was developed based on the regression beta-coefficients on data in training set. The model was subsequently assessed using a validation set. RESULTS: Among 538 patients, most patients had a solitary tumor (median tumor number 1; interquartile range 1 to 2) and median tumor size was 5.7 cm (interquartile range 4.0 to 8.0 cm). Median and 5-year overall survival was 39.0 months and 39.0%, respectively. On multivariable analyses, preoperative factors associated with long-term survival included tumor size (hazard ratio [HR] 1.12; 95% CI 1.06 to 1.18), natural logarithm carbohydrate antigen 19-9 level (HR 1.33; 95% CI 1.22 to 1.45), albumin level (HR 0.76; 95% CI 0.55 to 0.99), and neutrophil to lymphocyte ratio (HR 1.05; 95% CI 1.02 to 1.09). A weighted composite prognostic score was constructed based on these factors: [9 + (1.12 x tumor size) + (2.81 x natural logarithm carbohydrate antigen 19-9) + (0.50 x neutrophil to lymphocyte ratio) + (-2.79 x albumin)]. The model demonstrated good performance in the testing (area under the curve 0.696) and validation (0.691) datasets. The model performed better than both the T categories (area under the curve 0.532) and the cumulative stage classifications in the American Joint Committee on Cancer staging manual, 8th edition (area under the curve 0.559). When assessing risk of death within 1 year of operation, a risk score >= 25 had a positive predictive value of 59.8% compared with a positive predictive value of 35.3% for American Joint Committee on Cancer staging manual, 8th edition T4 disease and 31.8% for stage IIIB disease. CONCLUSIONS: Postsurgical long-term outcomes could be predicted using a composite weighted scoring system based on preoperative clinical parameters. The preoperative risk model can be used to inform patient to provider conversations and expectations before operation. (C) 2017 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.

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

BACKGROUND: We sought to investigate the prognosis of patients following curative-intent surgery for intrahepatic cholangiocarcinoma (ICC) stratified by hepatitis B (HBV-ICC), hepatolithiasis (Stone-ICC), and no identifiable cause (conventional ICC) etiologic subtype. METHODS: 986 patients with HBV-ICC (n = 201), stone-ICC (n = 103), and conventional ICC (n = 682) who underwent curative-intent resection were identified from a multi-institutional database. Propensity score matching (PSM) was used to mitigate residual bias. RESULTS: HBV-ICC patients more often had cirrhosis, earlier stage tumors, a mass-forming lesion, well-to-moderate tumor differentiation, and an R0 resection versus stone-ICC or conventional ICC patients. Five-year recurrence-free survival among HBV-ICC and conventional ICC patients was 23.9 and 17.8%, respectively, versus a recurrence-free of only 8.3% among patients with stone-ICC. Similarly, 5-year overall survival among patients with stone-ICC was only 18.3% compared with 48.9 and 38.0% for patients with HBV-ICC and conventional ICC, respectively. On PSM, patients with stone-ICC group had equivalent long-term outcomes as HBV-ICC patients. In contrast, on PSM, stone-ICC patients had a median overall survival of only 18.0 months versus 44.0 months for patients with conventional ICC. Median overall survival after intrahepatic-only recurrence among patients who had stone-ICC (6.0 months) was worse than OS among HBV-ICC (13.0 months) or conventional ICC (12.0 months) (p = 0.006 and p = 0.082, respectively). CONCLUSIONS: While HBV-ICC had a better prognosis on unadjusted analyses, these differences were mitigated on PSM suggesting no stage-for-stage differences in outcomes compared with stone-ICC or conventional ICC. In contrast, patients with stone-ICC had worse long-term outcomes. These data highlight the relative importance of ICC etiology relative to established clinicopathological factors in the prognosis of patients with ICC. info:eu-repo/semantics/publishedVersion

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

Background Major vascular involvement (IVC or portal vein) for intrahepatic cholangiocarcinoma (ICC) has traditionally been considered a contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing hepatectomy with major vascular resection in a large international multi-institutional database. Methods A total of 1087 ICC patients who underwent curative-intent hepatectomy between 1990 and 2016 were identified from 13 institutions. Multivariable logistic and cox regressions were used to determine the impact of major vascular resection on perioperative and survival outcomes. Results Of 1087 patients who underwent resection, 128 (11.8%) also underwent major vascular resection (21 [16.4%] IVC resections, 98 [76.6%] PV resections, 9 [7.0%] combined resections). Despite more advanced disease, major vascular resection was not associated with the risk of any complication (OR = 0.68, 95%CI 0.32-1.45) or major complications (OR = 0.95, 95%CI 0.49-2.00). Post-operative mortality was also comparable between groups (OR = 1.05, 95%CI 0.32-3.47). In addition, median recurrence-free (14.0 vs 14.7 months, HR = 0.737, 95%CI 0.49-1.10) and overall (33.4 vs 40.2 months, HR = 0.71, 95%CI 0.359-1.40) survival were similar among patients who did and did not undergo major vascular resection (both P > 0.05). Conclusion Among patients with ICC, major vascular resection was not associated with worse perioperative or oncologic outcomes. Concurrent major vascular resection should be considered in appropriately selected patients with ICC undergoing hepatectomy.

BACKGROUND: The objective of the current study was to investigate both short- and long-term outcomes of patients undergoing curative-intent resection for intrahepatic cholangiocarcinoma (ICC) stratified by extent of hepatic resection relative to overall final pathological margin status. METHODS: One thousand twenty-three patients with ICC who underwent curative-intent resection were identified from a multi-institutional database. Demographic, clinicopathological, and operative data, as well as overall (OS) and recurrence-free survival (RFS) were compared among patients undergoing major and minor resection before and after propensity score matching. RESULTS: Overall, 608 (59.4%) patients underwent major hepatectomy, while 415 (40.6%) had a minor resection. Major hepatectomy was more frequently performed among patients who had large, multiple, and bilobar tumors. Roughly half of patients (n = 294, 48.4%) developed a postoperative complication following major hepatectomy versus only one fourth of patients (n = 113, 27.2%) after minor resection (p < 0.001). In the propensity model, patients who underwent major hepatectomy had an equivalent OS and RFS versus patients who had a minor hepatectomy (median OS, 38 vs. 37 months, p = 0.556; and median RFS, 20 vs. 18 months, p = 0.635). Patients undergoing major resection had comparable OS and RFS with wide surgical margin (≥10 and 5-9 mm), but improved RFS when surgical margin was narrow (1-4 mm) versus minor resection in the propensity model. In the Cox regression model, tumor characteristics and surgical margin were independently associated with long-term outcome. CONCLUSIONS: Major hepatectomy for ICC was not associated with an overall survival benefit, yet was associated with increased perioperative morbidity. Margin width, rather than the extent of resection, affected long-term outcomes. Radical parenchymal-sparing resection should be advocated if a margin clearance of ≥5 mm can be achieved. info:eu-repo/semantics/publishedVersion

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

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. info:eu-repo/semantics/publishedVersion

IMPORTANCE: Composite measures may be superior to individual measures for the analysis of hospital performance and quality of surgical care. OBJECTIVE: To determine the incidence of a so-called textbook outcome, a composite measure of the quality of surgical care, among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma. DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved an analysis of a multinational, multi-institutional cohort of patient from 15 major hepatobiliary centers in North America, Europe, Australia, and Asia who underwent curative-intent resection of intrahepatic cholangiocarcinoma between 1993 and 2015. Data analysis was conducted from April 2018 to May 2018. MAIN OUTCOMES AND MEASURES: Hospital variation in the composite end point of textbook outcome, defined as negative margins, no perioperative transfusion, no postoperative surgical complications, no prolonged length of stay, no 30-day readmissions, and no 30-day mortality. Secondary end points were factors associated with achieving textbook outcomes. RESULTS: Among 687 patients (of whom 370 [53.9%] were men; median patient age, 61 [range, 18-86] years) undergoing curative-intent resection of intrahepatic cholangiocarcinoma, a textbook outcome was achieved in 175 patients (25.5%). Being 60 years or younger (odds ratio [OR], 1.61 [95% CI, 1.04-2.49]; P = .03), absence of preoperative jaundice (OR, 4.40 [95% CI, 1.28-15.15]; P = .02), no neoadjuvant chemotherapy (OR, 2.57 [95% CI, 1.05-6.29]; P = .04), T1a/T1b-stage disease (OR, 1.58 [95% CI, 1.01-2.49]; P = .049), N0 status (OR, 3.89 [95% CI, 1.77-8.54]; P = .001), and no bile duct resection (OR, 2.46 [95% CI, 1.25-4.84]; P = .009) were independently associated with achieving a textbook outcome after resection. A prolonged length of stay had the greatest negative association with a textbook outcome. A nomogram to assess the probability of textbook outcome was developed and had good accuracy in both the training data set (area under the curve, 0.755) and validation data set (area under the curve, 0.763). CONCLUSIONS AND RELEVANCE: In this study, while hepatic resection for intrahepatic cholangiocarcinoma was performed with less than 5% mortality in specialized centers, a textbook outcome was achieved in only approximately 26% of patients. A textbook outcome may be useful for the reporting of patient-level hospital performance and hospital variation, leading to quality improvement efforts after resection of intrahepatic cholangiocarcinoma.

BACKGROUND The objective of the current study was to identify the risk of early vs late recurrence of well-differentiated (G1) neuroendocrine liver metastasis (NELM) after curative-intent resection. METHODS Patients who underwent curative-intent resection for well-differentiated NELM were identified from a multi-institutional database. Clinicopathological details, as well as the long-term overall (OS) and recurrence free survival (RFS) were obtained and compared. The optimal cutoff value to differentiate early and late recurrence was determined to be 1 year based on trend curve analysis. RESULTS Among the 548 patients undergoing curative resection for NELM, 162 patients had a well-differentiated NELM. After a median follow-up of 69 months, 59 (36.4%) patients had tumor recurrence; 23 (39.0%) patients recurred within 1 year (early recurrence) after surgery, while 36 (61.0%) recurred after 1 year (late recurrence). Early recurrence was associated with worse outcome vs late recurrence (5-year OS, 72.4% vs 92.0%; P = 0.020) and no recurrence (5-year OS, 72.4% vs 100.0%; P

Background: Neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio may be host factors associated with prognosis. We sought to determine whether neutrophil-to-lymphocyte and platelets-to lymphocyte ratio were associated with overall survival among patients undergoing surgery for intrahepatic cholangiocarcinoma. Methods: Patients who underwent resection for intrahepatic cholangiocarcinoma between 1990 and 2015 were identified from 12 major centers. Clinicopathologic factors and overall survival were compared among patients stratified by neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio. Risk factors identified on multivariable analysis were included in a prognostic model and the discrimination was assessed using Harrell's concordance index (C index). Results: A total of 991 patients were identified. Median neutrophil-to-lymphocyte ratio and platelets-to lymphocyte ratio were 2.7 (interquartile range PORI: 2.0-4.0) and 109.6 (IQR: 72.4-158.8), respectively. Preoperative neutrophil-to-lymphocyte ratio was elevated (>= 5) in 100 patients (10.0%) and preoperative platelets-to-lymphocyte ratio (>= 190) in 94 patients (15.2%). Patients with low and high neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio generally had similar baseline characteristics with regard to tumor characteristics. Overall survival was 37.7 months (95% confidence interval [CI]: 32.7-42.6); 1-, 3-, and 5-year overall survival was 78.8%, 51.6%, and 39.3%, respectively. Patients with an neutrophil-to-lymphocyte ratio = 5 (P=.001). In contrast, patients who had a platelets-to-lymphocyte ratio = 190 had comparable long-term survival (P > .05). On multivariable analysis, an elevated neutrophil-to-lymphocyte ratio was independently associated with decreased overall survival (hazard ratio: 1.04, 95% CI: 1.01-1.07; P=.002). Patients could be stratified into low- versus high-risk groups based on standard tumor-specific factors such as lymph node status, tumor size, number, and vascular invasion (C index 0.62). When neutrophil-to-lymphocyte ratio was added to the prognostic model, the discriminatory ability of the model improved (C index 0.71). Conclusion: Elevated neutrophil-to-lymphocyte ratio was independently associated with worse overall survival and improved the prognostic estimation of long-term survival among patients with intrahepatic cholangiocarcinoma undergoing resection. (C) 2018 Elsevier Inc. All rights reserved.

Background The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. Methods Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. Results A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). Conclusion Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.

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

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

INTRODUCTION: The role of routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal staging. We sought to define outcome and risk of death among patients who were staged with ≥6 HLNs versus

BACKGROUND: Reliable criteria to predict mortality after hepatectomy remain poorly defined. We sought to identify factors associated with 90-day mortality, as well as validate the "50-50" and peak bilirubin of >7 mg/dL prediction rules for mortality after liver resection. In addition, we propose a novel integer-based score for 90-day mortality using a large cohort of patients. STUDY DESIGN: Data from 2,056 patients who underwent liver resection at 2 major hepatobiliary centers between 1990 and 2011 were identified. Perioperative laboratory data, as well as surgical and postoperative details, were analyzed to identify factors associated with liver-related 90-day death. RESULTS: Indications for liver resection included colorectal metastasis (39%), hepatocellular carcinoma (19%), benign mass (17%), or noncolorectal metastasis (14%). Most patients had normal underlying liver parenchyma (71%) and resection involved >= 3 segments (36%). Overall morbidity and mortality were 19% and 2%, respectively. Only 1 patient fulfilled the 50-50 criteria; this patient survived and was discharged on day 8. Twenty patients had a peak bilirubin concentration >7 mg/dL and 5 died within 90 days; the sensitivity and specificity of the > 7-mg/dL rule were 25% and 99.3%, respectively, but overall accuracy was poor (area under the curve 0.574). Factors associated with 90-day mortality included international normalized ratio (odds ratio = 11.87), bilirubin (odds ratio = 1.16), and serum creatinine (odds ratio = 1.87) on postoperative day 3, as well as grade of postoperative complications (odds ratio = 5.08; all p < 0.05). Integer values were assigned to each factor to develop a model that predicted 90-day mortality (area under the curve 0.89). A score of >= 11 points had a sensitivity and specificity of 83.3% and 98.8%, respectively. CONCLUSIONS: The 50-50 and bilirubin > 7-mg/dL rules were not accurate in predicting 90-day mortality. Rather, a composite integer-based risk score based on postoperative day 3 international normalized ratio, bilirubin, creatinine, and complication grade more accurately predicted 90-day mortality after hepatectomy. (J Am Coll Surg 2013; 216: 1049-1056. (C) 2013 by the American College of Surgeons)

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

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival. METHODS: Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS 5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (

Introduction Management of neuroendocrine liver metastasis (NELM) in the presence of extrahepatic disease (EHD) is controversial. We sought to examine outcomes of patients undergoing liver-directed therapy (resection, ablation, or both) for NELM in the presence of EHD using a large international cohort of patients. Methods 612 patients who underwent liver-directed therapy were identified from eight institutions. Postoperative outcomes, as well as and overall (OS) were compared among patients with and without EHD. Results Most primary tumors were located in the pancreas (N = 254;41.8%) or the small bowel (N = 188;30.9%). Patients underwent surgery alone (N = 471;77.0%), ablation alone (N = 15;2.5%), or a combined approach (N = 126;20.6%). Patients with EHD had more high-grade tumors (EHD: 44.4% vs no EHD: 16.1%; P

INTRODUCTION: While preoperative chemotherapy (pCT) is utilized in many intra-abdominal cancers, the use of pCT among patients with intrahepatic cholangiocarcinoma (ICC) remains ill defined. As such, the objective of the current study was to examine the impact of pCT among patients undergoing curative-intent resection for ICC. METHODS: Patients who underwent hepatectomy for ICC were identified from a multi-institutional international cohort. The association between pCT with peri-operative and long-term clinical outcomes was assessed. RESULTS: Of the 1 057 patients who were identified and met the inclusion criteria, 62 patients (5.9%) received pCT. These patients were noticed to have more advanced disease. Median OS (pCT:46.9 months vs no pCT:37.4 months; P = 0.900) and DFS (pCT: 34.1 months vs no pCT: 29.1 months; P = 0.909) were similar between the two groups. In a subgroup analysis of propensity-score matched patients, there was longer OS (pCT:46.9 months vs no pCT:29.4 months) and DFS (pCT:34.1 months vs no pCT:14.0 months); however this did not reach statistical significance (both P > 0.05). CONCLUSION: In conclusion, pCT utilization among patients with ICC was higher among patients with more advanced disease. Short-term post-operative outcomes were not affected by pCT use and receipt of pCT resulted in equivalent OS and DFS following curative-intent resection. info:eu-repo/semantics/publishedVersion

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.

BACKGROUND: The surgical management of hepatocellular carcinoma in patients with well-compensated cirrhosis is controversial. The purpose of the current study was to compare the outcome of patients with well-compensated cirrhosis and early stage hepatocellular carcinoma treated with initial hepatic resection versus transplantation. METHODS: Between 1985 and 2008, 245 patients underwent hepatic resection, and 134 patients underwent liver transplantation for early stage hepatocellular carcinoma. All patients had well-compensated cirrhosis. Prognostic factors were evaluated using univariate and multivariate analyses; survival was calculated using the Kaplan-Meier method. RESULTS: Compared with transplantation, patients undergoing resection had larger tumors and a higher incidence of microscopic vascular invasion. Transplantation was associated with better 5-year disease-free and overall survival compared with resection. Hepatitis status, presence of microscopic vascular invasion, and tumor size were predictors for recurrence, while the presence of microscopic vascular invasion and tumor size conferred an increased risk of death. The disease-free survival advantage with transplantation was more pronounced in hepatitis C patients compared with non-hepatitis and hepatitis B patients. The overall survival advantage with transplantation persisted in cases of solitary lesions < or = 3 cm, but was attenuated in patients with a MELD score < or = 8. CONCLUSION: In well-compensated cirrhotic patients with early stage hepatocellular carcinoma, transplantation was associated with longer disease-free and overall survival. Patients undergoing resection did, however, have tumors with more advanced pathologic features. Patients best suited for initial resection as the treatment of hepatocellular carcinoma were those with a MELD score

The objective of the current study was to define the incidence of 30-day readmission after hepatic resection for intrahepatic cholangiocarcinoma (ICC). In particular, we sought to identify risk factors associated with a higher risk of readmission among patients undergoing resection for ICC. Patients who underwent hepatic resection for ICC at 12 major hepatobiliary centers in the USA, Europe, Australia, and Asia between 1990 and 2013 were identified. Thirty-day readmission and clinicopathologic characteristics associated with higher risk of readmission were examined. Among 602 patients, 401 (68.3 %) patients underwent a major hepatectomy and 256 (43.3 %) experienced at least one post-operative complication. Overall 30-day readmission was 7.8 % (n = 47). Risk factors associated with readmission included pre-operative jaundice (odds ratio (OR) 2.45) and the presence of a major complication (OR 3.38). In fact, 95.7 % of readmitted patients had experienced a post-operative complication versus only 38.8 % of non-readmitted patients (P < 0.001). Among patients who were readmitted, repeat hospitalization was associated with a median LOS of 6.5 days (interquartile range (IQR) 4.0-11.5) and one patient died during readmission. Readmission after hepatic resection for ICC occurred in 1 in 13 patients. Patients with pre-operative jaundice and those who experienced a complication had over a threefold higher risk of being readmitted.

BACKGROUND: Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. METHODS: Patients who underwent surgery for ICC from 1990 to 2013 were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence, and recurrence-related management were recorded and analyzed. RESULTS: A total of 563 patients undergoing curative-intent hepatic resection for ICC who met the inclusion criteria were identified. With a median follow-up of 19 months, 400 (71.0 %) patients developed a recurrence. At initial surgery, treatment was resection only (98.8 %) or resection + ablation (1.2 %). Overall 5-year survival was 23.6 %; 400 (71.0 %) patients recurred with a median disease-free survival of 11.2 months. First recurrence site was intrahepatic only (59.8 %), extrahepatic only (14.5 %), or intra- and extrahepatic (25.7 %). Overall, 210 (52.5 %) patients received best supportive care (BSC), whereas 190 (47.5 %) patients received treatment, such as systemic chemotherapy-only (24.2 %) or repeat liver-directed therapy ± systemic chemotherapy (75.8 %). Repeat liver-directed therapy consisted of repeat hepatic resection ± ablation (28.5 %), ablation alone (18.7 %), and intra-arterial therapy (IAT) (52.8 %). Among patients who recurred, median survival from the time of the recurrence was 11.1 months (BSC 8.0 months, systemic chemotherapy-only 16.8 months, liver-directed therapy 18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 9.6 months for patients who had IAT (p < 0.001). CONCLUSIONS: Recurrence following resection of ICC was common, occurring in up to two-thirds of patients. When there is recurrence, prognosis is poor. Only 9 % of patients underwent repeat liver resection after recurrence, which offered a modest survival benefit. info:eu-repo/semantics/publishedVersion

IMPORTANCE Whereas conventional actuarial overall survival (OS) estimates rely exclusively on static factors determined around the time of surgery, conditional survival (CS) estimates take into account the years that a patient has already survived. OBJECTIVE To define the CS of patients following liver resection for intrahepatic cholangiocarcinoma (ICC). DESIGN, SETTING, AND PARTICIPANTS Between January 1, 1990, and December 31, 2013, a total of 535 patients who underwent resection of ICC were identified from an international multi-institutional database. In this retrospective international study conducted from January to June 2014, clinicopathological characteristics, operative details, and long-term survival data were analyzed. Conditional survival estimates were calculated as the probability of survival for an additional 3 years. INTERVENTION Resection of ICC. MAIN OUTCOMES AND MEASURES Overall survival and CS. RESULTS While actuarial OS decreased over time from 39% at 3 years to 16% at 8 years (P = .002), the 3-year CS (CS3) increased over time among those patients who survived. The CS3 at 5 years-the probability of surviving to postoperative year 8 after having already survived to postoperative year 5-was 65% compared with 8-year OS of 16%(P = .002). Factors that were associated with worse OS included larger tumor size (hazard ratio [HR], 1.02; 95% CI, 1.00-1.05; P = .05), multifocal disease (HR, 1.49; 95% CI, 1.19-1.86; P = .01), lymph node metastasis (HR, 2.21; 95% CI, 1.67-2.93; P < .01), and vascular invasion (HR, 1.39; 95% CI, 1.10-1.75; P = .006). The calculated CS3 exceeded the actuarial survival for all high-risk subgroups. For example, patients with lymph node metastasis had an actuarial OS of 11% at 6 years vs a CS3 of 49% at 3 years (Delta 38%). Similarly, patients with vascular invasion had an actuarial OS of 15% at 6 years compared with a CS3 of 50% at 3 years (Delta 35%). CONCLUSIONS AND RELEVANCE Conditional survival estimates may provide critical quantitative information about the changing probability of survival over time among patients undergoing liver resection for ICC. Therefore, such estimates can be of significant value to patients and health care professionals.

IMPORTANCE Choledochal cysts (CCs) are rare, with risk of infection and cancer. OBJECTIVE To characterize the natural history, management, and long-term implications of CC disease. DESIGN, SETTING, AND PARTICIPANTS A total of 394 patients who underwent resection of a CC between January 1, 1972, and April 11, 2014, were identified from an international multi-institutional database. Patients were followed up through September 27, 2014. Clinicopathologic characteristics, operative details, and outcome data were analyzed from May 1, 2014, to October 14, 2014. INTERVENTION Resection of CC. MAIN OUTCOMES AND MEASURES Management, morbidity, and overall survival. RESULTS Among 394 patients, there were 135 children (34.3%) and 318 women (80.7%). Adults were more likely to present with abdominal pain (71.8% vs 40.7%; P < .001) and children were more likely to have jaundice (31.9% vs 11.6%; P < .001). Preoperative interventions were more commonly performed in adults (64.5% vs 31.1%; P < .001), including endoscopic retrograde pancreatography (55.6% vs 27.4%; P < .001), percutaneous transhepatic cholangiography (17.4% vs 5.9%; P < .001), and endobiliary stenting (18.1% vs 4.4%; P < .001)). Type I CCs were more often seen in children vs adults (79.7% vs 64.9%; P = .003); type IV CCs predominated in the adult population (23.9% vs 12.0%; P = .006). Extrahepatic bile duct resection with hepaticoenterostomy was the most frequently performed procedure in both age groups (80.3%). Perioperative morbidity was higher in adults (35.1% vs 16.3%; P < .001). On pathologic examination, 10 patients (2.5%) had cholangiocarcinoma. After a median follow-up of 28 months, 5-year overall survival was 95.5%. On follow-up, 13 patients (3.3%), presented with biliary cancer. CONCLUSIONS AND RELEVANCE Presentation of CC varied between children and adults, and resection was associated with a degree of morbidity. Although concomitant cancer was uncommon, it occurred in 3.0% of the patients. Long-term surveillance is indicated given the possibility of future development of biliary cancer after CC resection.

The role of surgical resection for patients with large or multifocal intrahepatic cholangiocarcinoma (ICC) remains unclear. This study evaluated the long-term outcome of patients who underwent hepatic resection for large (a parts per thousand yen7 cm) or multifocal (a parts per thousand yen2) ICC. Between 1990 and 2013, 557 patients who underwent liver resection for ICC were identified from a multi-institutional database. Clinicopathologic characteristics, operative details, and long-term survival data were evaluated. Of the 557 patients, 215 (38.6 %) had a small, solitary ICC (group A) and 342 (61.4 %) had a large or multifocal ICC (group B). The patients in group B underwent an extended hepatectomy more frequently (16.9 vs. 30.4 %; P < 0.001). At the final pathology exam, the patients in group B were more likely to show evidence of vascular invasion (22.5 vs. 38.5 %), direct invasion of contiguous organs (6.5 vs. 12.9 %), and nodal metastasis (13.3 vs. 21.0 %) (all P < 0.05). Interestingly, the incidences of postoperative complications (39.3 vs. 46.8 %) and hospital mortality (1.1 vs. 3.7 %) were similar between the two groups (both P > 0.05). The group A patients had better rates for 5-year overall survival (OS) (30.5 vs. 18.7 %; P < 0.05) and disease-free survival (DFS) (22.6 vs. 8.2 %; P < 0.05) than the group B patients. For the patients in group B, the factors associated with a worse OS included more than three tumor nodules [hazard ratio (HR), 1.56], nodal metastasis (HR, 1.47), and poor differentiation (HR, 1.48). Liver resection can be performed safely for patients with large or multifocal ICC. The long-term outcome for these patients can be stratified on the basis of a prognostic score that includes tumor number, nodal metastasis, and poor differentiation.