Search

This study aimed to develop a tool based on preoperative factors to predict the risk of perioperative complications based on the Comprehensive Complication Index (CCI) and long-term survival outcomes after liver resection for primary liver cancer. Patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent hepatectomy between 1990 and 2020 were identified using a multi-institutional international database. Among 1411 patients who underwent curative-intent hepatic resection (HCC: 997, 70.7%; ICC: 414, 29.3%), median patient age was 66.0 years (IQR, 57.0–73.0), and most patients were male (n = 1001, 70.9%). In the postoperative setting, 699 patients (49.5%) experienced a complication; moreover, 112 patients (7.9%) had major complications. Although most patients had a favorable risk complication-overall survival (CompOS) profile (CCI score > 40 risk of <30% and median survival of >5 years: n = 778, 55.1%), 553 patients (39.2%) had an intermediate-risk profile, and 80 patients (5.7%) had a very unfavorable risk profile (CCI score > 40 risk of ≥30% and/or median survival of ≤1.5 years). The areas under the curve of the test and validation cohorts were 0.73 and 0.76, respectively. The CompOS risk model accurately stratified patients relative to short- and long-term risks, identifying a subset of patients at a high risk of major complications and poor overall survival. [ABSTRACT FROM AUTHOR]

Early-stage intrahepatic cholangiocarcinoma (ICC) is often an indication of curative-intent resection. Although patients with early-stage ICC generally have a better prognosis than individuals with advanced ICC, the incidence and risk factors of recurrence after early-stage ICC remain unclear. A multi-institutional database was used to identify patients who underwent surgery between 2000 and 2018 for ICC with pathologically confirmed stage I disease. Cox regression analysis was used to identify clinicopathological factors associated with recurrence, and an online prediction model was developed and validated. Of 430 patients diagnosed with stage I ICC, approximately one-half of patients (n = 221, 51.4%) experienced recurrence after curative-intent resection. Among patients with a recurrence, most (n = 188, 85.1%) experienced it within 12 months. On multivariable analysis, carcinoembryonic antigen (hazard ratio [HR], 1.011; 95% CI, 1.004–1.018), systemic immune-inflammation index (HR, 1.036; 95% CI, 1.019–1.056), no lymph nodes evaluated (HR, 1.851; 95% CI, 1.276–2.683), and tumor size (HR, 1.101; 95% CI, 1.053–1.151) were associated with greater hazards of recurrence. A predictive model that included these weighted risk factors demonstrated excellent prognostic discrimination in the test (12-month recurrence-free survival [RFS]: low risk, 80.1%; intermediate risk, 60.3%; high risk, 37.7%; P =.001) and validation (12-month RFS: low risk, 84.5%; intermediate risk, 63.5%; high risk, 47.1%; P =.036) datasets. The online predictive model was made available at https://ktsahara.shinyapps.io/stageI%5ficc/. Patients with stage I ICC without vascular invasion or lymph node metastasis had a relatively high incidence of recurrence. An online tool can risk stratify patients relative to recurrence risk to identify individuals best suited for alternative treatment approaches. [ABSTRACT FROM AUTHOR]

Introduction: It is unclear whether the histological glandular differentiation (HGD) score that evaluates the tumor grade of two dominant components is prognostic for survival in patients with intrahepatic cholangiocarcinoma (ICC). Method: We retrospectively analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at 5 university hospitals in the Kansai region of Japan. Results: Survival was statistically significantly stratified by trinal HGD grade (p < 0.05). Median disease-free survival (DFS) of patients with high HGD grade was significantly shorter compared with moderate HGD grade (13.0 vs 31.2 months, respectively; p = 0.004). By Cox proportional hazards regression analysis, HGD grade had the fifth-highest hazard ratio (HR = 1.77, p = 0.002) for DFS after vascular and/or biliary invasion, extrahepatic invasion, lymph node metastasis and multiple tumors. Multivariate logistic regression analysis revealed four predictors of early recurrence after hepatectomy (lymph node metastasis: odds ratio [OR] = 3.74, p = 0.001; tumor size > 50 mm: OR = 2.80, p = 0.002; HGD grade, high: OR = 2.11, p = 0.012; and vascular or biliary tract invasion: OR = 2.11, p = 0.048). Conclusion: Trinal HGD grade had a significant prognostic impact on the survival of patients with ICC after radical hepatectomy. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to determine the impact of lymphadenectomy (LND) on clinical outcomes in ICC patients aged ≥ 70 years. Methods: Four hundred and three eligible patients diagnosed with ICC who underwent hepatectomy between 2004 and 2019 were enrolled in the Surveillance, Epidemiology, and End Results database. The impact of LND on perioperative mortality and overall survival (OS) as well as the optimal total number of lymph nodes examined (TNLE) was estimated. Results: One hundred thirty-nine pairs of patients were matched by propensity score matching. Perioperative mortality was comparable between the LND and non-LND (nLND) groups (0.7% vs. 2.9%, P = 0.367). The median OS in the LND group was significantly longer (44 vs. 32 months, P = 0.045) and LND was identified as an independent protective factor for OS by multivariate analysis (HR 0.65, 95% CI 0.46–0.92, P = 0.014). Patients with the following characteristics were potential beneficiaries of LND: white, female, no/moderate fibrosis, tumor size > 5 cm, solitary tumor, and localized invasion (all P < 0.05). TNLE ≥ 6 had the greatest discriminatory power for identifying lymph node metastasis (area under the curve, 0.704, Youden index, 0.365, P = 0.002). Patients with pathologically confirmed lymph node metastasis are likely to benefit from adjuvant therapy (40 months vs. 4 months, P = 0.052). Conclusions: Advanced age (≥ 70 years) was not a contraindication for LND, which facilitates accurate nodal staging and guides postoperative management. Appropriately selected elderly populations could benefit from LND. [ABSTRACT FROM AUTHOR]

Introduction: Cirrhotic patients with primary liver cancer may undergo curative-intent resection when selected appropriately. Patients with T1 tumors and low-MELD are generally referred for resection. We aim to evaluate whether minimally invasive hepatectomy (MIH) is associated with improved outcomes versus open hepatectomy (OH). Methods: NSQIP hepatectomy database 2014–2021 was used to select patients with T1 Hepatocellular Carcinoma (HCC) or Intra-hepatic Cholangiocarcionoma (IHCC) and low-MELD cirrhosis (MELD ≤ 10) who underwent partial hepatectomy. Propensity score matching was applied between OH and MIH patients, and 30-day postoperative outcomes were compared. Multivariable regression was used to identify predictors of post-hepatectomy liver failure (PHLF) in the selected population. Results: There were 922 patients: 494 (53.6%) OH, 372 (40.3%) MIH, and 56 (6.1%) began MIH converted to OH (analyzed with the OH cohort). We matched 354 pairs of patients with an adequate balance between the groups. MIH was associated with lower rates of bile leak (HR 0.37 [0.19–0.72)], PHLF (HR 0.36 [0.15–0.86]), collections requiring drainage (HR 0.30 [0.15–0.63]), postoperative transfusion (HR 0.36 [0.21–0.61]), major (HR 0.45 [0.27–0.77]), and overall morbidity (HR 0.44 [0.31–0.63]), and a two-day shorter median hospitalization (3 vs. 5 days; HR 0.61 [0.45–0.82]). No difference was noted in operative time, wound, respiratory, and septic complications, or mortality. Regression analysis identified ascites, prior portal vein embolization (PVE), additional hepatectomies, Pringle's maneuver, and OH (vs. MIH) as independent predictors of PHLF. Conclusion: MIH for early-stage HCC/IHCC in low-MELD cirrhotic patients was associated with improved postoperative outcomes over OH. These findings suggest that MIH should be considered an acceptable approach in this population of patients. [ABSTRACT FROM AUTHOR]

Background and Aims: The incidence of intrahepatic cholangiocarcinoma (ICC) in non-alcoholic fatty liver disease (NAFLD) is increasing gradually. The prognosis of NAFLD-ICC has not been well studied. We aim to investigate the prognosis of patients with NAFLD-ICC after curative-intent partial hepatectomy (PH). Methods: Multi-center data from January 2003 to January 2014 were retrospectively analyzed. The prognosis of ICC was analyzed using PSM and compared with hepatitis B virus (HBV)–related ICC. Results: A total of 898 patients with ICC were included in this study. Of them, 199 (22.2%) were NAFLD-ICC, and 699 (77.8%) were HBV-ICC. Multivariate analysis showed that CA19-9 ≥ 37 U/mL, microvascular invasion, tumor size > 5 cm, multiple tumors, and lymph node (LN) metastasis were independent risk factors for early recurrence (ER) in ICC patients. After a 1:1 PSM, NAFLD-ICC has worse 5-year overall survival (OS) (24.0% vs. 48.9%), 5-year recurrence (80.9% vs. 55.0%), and ER (58.5% vs. 30.0%) than that of HBV-ICC (all P < 0.01). Multivariable analysis showed NAFLD was an independent risk factor for OS (hazard ratio [HR] 2.26, 95% CI 1.63–3.13, P < 0.001), tumor recurrence (HR 2.24, 95%CI 1.61–3.10, P < 0.001) and ER (HR 2.23, 95%CI 1.60–3.09, P < 0.001) in patients with ICC after PH. The sensitivity analysis indicated that NAFLD-ICC patients were more likely to experience ER. Conclusion: Compared with HBV-ICC, NAFLD-ICC has a worse prognosis and was more likely to relapse early. More frequent surveillance should be considered. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation (LT) has been considered a potential curative treatment for patients with very early intrahepatic cholangiocarcinoma (ICC) and cirrhosis, yet the survival benefit of LT has not been well defined. This study aimed to compare the long-term survival outcomes of patients who underwent LT with that of individuals who received resection and non-curative intent treatment (non-CIT). Methods: Patients who underwent LT, hepatectomy, and non-CIT between 2004 and 2018 were included in the National Cancer Database. Survival benefits of LT over resection and non-CIT were analyzed relative to overall survival (OS). Results: Among 863 patients, 54 (6.3%) underwent LT, while 342 (39.6%) underwent surgical resection, and 467 (54.1%) received non-CIT, respectively. While the rates of non-CIT increased over time, the percentages of LT remained consistent during the study period. LT patients had similar 5-year OS to individuals who underwent resection (referent, resection: LT, HR 0.95, 95%CI 0.84–1.58, p=0.84). In contrast, 5-year OS was better among patients who underwent LT versus individuals who had non-CIT after controlling other variables using propensity score overlapping weighting (5-year OS, LT 57.1% vs. LR 25.8%, p<0.001). Conclusions: The outcomes of very early ICC patients who underwent LT were similar to individuals who underwent hepatectomy, but better than patients treated with non-CIT. LT should be may be a consideration as a treatment option for patients with early stage ICC who are unsuitable candidates for resection. [ABSTRACT FROM AUTHOR]

Background: This study aims to construct a risk classification system and a nomogram in intrahepatic cholangiocarcinomafor patients (ICC). Methods: Three thousand seven hundred thirty-seven patients diagnosed with ICC between 2010 and 2015 were selected from the Surveillance, Epidemiology and End Results. The consistency index, time-dependent receiver operating characteristic curve, and the calibration plots were adopted to evaluate the effective performance of nomogram. Decision curve analysis (DCA), net reclassification index (NRI), and comprehensive discrimination improvement (IDI) were used to compare the advantages and disadvantages of two models. Kaplan–Meier curve showed the difference in prognosis among different groups. Results: Ten variables were selected to establish the nomogram for ICCA. The C-index (training cohort: 0.765, P < 0.05; validation cohort: 0.776, P < 0.05) and the time-dependent AUCs (the training cohort: the values of 1, 3, 5 years were 0.836, 0.873, and 0.888; the validation cohort: the values of 1, 3, 5 years were 0.833, 0.838, and 0.881) showed satisfactory discrimination. The calibration curves also revealed that the nomogram was consistent with the actual observations. The NRI (training cohort: 1-, 3-, 5-year CSS: 0.879, 0.94, 0.771; validation cohort: 1-, 3-, 5-year CSS: 0.905, 0.945, 0.717) and IDI (training cohort: 1-, 3-, 5-year CSS: 0.24, 0.23, 0.22; validation cohort: 1-, 3-, 5-year CSS: 0.24, 0.46, 0.27) (P < 0.05) (compared with AJCC staging). DCA showed that the new model was more practical and had better recognition than AJCC staging. Conclusions: A new risk stratification system for ICC patients has been developed, which can be a practical tool for patient management. [ABSTRACT FROM AUTHOR]

Background: The prognostic role of tumor burden score (TBS) relative to albumin-bilirubin (ALBI) grade among patients undergoing curative-intent resection of ICC has not been examined. Methods : We identified patients who underwent curative-intent resection for ICC between 1990 and 2017 from a multi-institutional database. Multivariable analysis was performed to assess the effect of TBS relative to ALBI grade on both short- and long-term outcomes. Results: Among 724 patients, 360 (49.7%) patients had low TBS and low ALBI grade, 142 (19.6%) patients had low TBS and high ALBI grade, 138 (19.1%) patients had high TBS and low ALBI grade, and 84 patients (11.6%) had high TBS and high ALBI grade. Decreased tumor burden was associated with better long-term outcomes among patients with both low (5-year OS; low TBS vs. high TBS: 52.4% vs 21.4%; p < 0.001) and high ALBI grade (5-year OS; low TBS vs. high TBS: 40.7% vs 12.0%; p < 0.001). On multivariable analysis, higher ALBI grade was associated with greater odds of an extended hospital LOS (> 10 days) (OR 2.80, 95%CI 1.62–4.82; p < 0.001), perioperative transfusion (OR 2.04, 95%CI 1.25–3.36; p = 0.005), 90-day mortality (OR 2.56, 95%CI 1.12–5.81; p = 0.025), as well as a major complication (OR 1.99, 95%CI 1.13–3.49; p = 0.016) among patients with similar tumor burden. Of note, patients with high TBS and high ALBI grade had markedly worse overall survival compared with patients who had low TBS and low ALBI grade disease (HR 2.27; 95%CI 1.44–3.59; p < 0.001). Importantly, high TBS and high ALBI grade were strongly associated with both early recurrence (88.1%%) and 5-year risk of death (96.4%). Conclusion: Both TBS (i.e., tumor morphology) and ALBI grade (i.e., hepatic function reserve) were strong predictors of outcomes among patients undergoing ICC resection. There was an interplay between TBS and ALBI grade relative to patient prognosis after hepatic resection of ICC with high ALBI grade predicting worse outcomes among ICC patients with different TBS. [ABSTRACT FROM AUTHOR]

Background: Volume-outcome relationships have been described for a variety of surgical procedures. We aimed to define the facility volume threshold at which postoperative mortality after hepatectomy was optimal. Methods: We determined volume percentiles for institutions performing hepatectomy for any primary liver tumor within the National Cancer Database (2004–2017). Marginal structural logistic regression defined the volume percentile (Vmin) at which the odds of 90-day mortality were optimally reduced in patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC). Short-term postoperative and survival outcomes were compared between patients treated at facilities above and below Vmin. Results: Thresholds for the 10th/25th/50th/75th/90th percentiles were 2/7/26/46/59 hepatectomies/year. A total of 17,833 patients underwent resection of HCC or ICC. The 90-day postoperative mortality was optimized at the 75th percentile for all hepatectomies (IP-weighted OR = 0.67, 95% CI = 0.52–0.87) and major hepatectomy (IP-weighted OR = 0.62, 95% CI = 0.49–0.80). Seven of 446 facilities met the Vmin threshold. The odds of 30-day mortality were also reduced for all hepatectomies (IP-weighted OR = 0.55, 95% CI = 0.42–0.73) and major hepatectomy (IP-weighted OR = 0.58, 95% CI = 0.41–0.75). There were no differences in length of stay or 30-day readmission rate. Patients with HCC or ICC treated at facilities ≥ 10th percentile had an associated improvement in overall survival. Conclusions: Resection of HCC and ICC is performed at a large number of facilities. Postoperative mortality is optimally reduced at facilities performing at least 46 liver operations annually. Regionalization of surgical care among patients with primary liver malignancies to high-volume centers may result in improved outcomes. [ABSTRACT FROM AUTHOR]

Background: The Affordable Care Act (ACA) transformed the US healthcare system, expanding healthcare insurance coverage. However, its impact on rare malignancies that lack an established screening strategy such as intrahepatic cholangiocarcinoma (ICC) remains ill-defined.Methods: Patients diagnosed with ICC were identified from the National Cancer Database and divided relative to ACA implementation. Multivariate logistic regression analyses were performed to evaluate association with stage at diagnosis, receipt of surgical and multimodal treatments, and survival.Results: Among the 9095 patients, 5636 (62.0%) were diagnosed before and 3459 (38.0%) after the implementation of the ACA. Across US regions, rates of early-stage diagnosis increased in the post-ACA era (Northeast, 62.9% vs. 85.2%; South, 63.7% vs. 78.5%; Midwest, 62.1% vs. 83.4%; West, 55.5% vs. 75.4%; p < 0.001). On multivariate analyses, the post-ACA era was associated with increased early-stage diagnosis (OR = 2.19; 95% CI 1.79-2.69), and receipt of surgical treatment (OR = 1.19, 95% CI 1.03-1.38) (both p < 0.01). Furthermore, the ACA's Medicaid expansion (ME) was also associated with improved overall survival (HR = 0.89, 95% CI 0.80-0.99, p = 0.038). Of note, although the odds of receiving surgical treatment increased after ACA for non-Hispanic White patients (OR = 1.34; 95% CI 1.20-1.49; p < 0.001), no such effect was observed in non-Hispanic Black (OR = 1.01, 95% CI 0.71-1.45), Hispanic (OR = 1.44, 95% CI 0.99-2.09), or others (OR = 1.43, 95% CI 0.98-2.10) (all p > 0.05).Conclusions: The implementation of the ACA increased rates of early diagnosis and receipt of surgical treatment. Additionally, ME improved short- and long-term outcomes. However, racial and socioeconomic disparities persist, resulting in inequitable access to care and outcomes for patients with ICC. [ABSTRACT FROM AUTHOR]

Background: Intraductal papillary neoplasm of the bile duct (IPNB) has a wide range of histopathology and intra- and extrahepatic tumor locations.Methods: This retrospective single-center study evaluated the clinicopathological features and long-term outcomes of 146 patients with IPNB of the liver (IPNB-L) who underwent hepatic resection between January 2002 and June 2019.Results: The 146 patients included 97 (66.4%) men and 49 (33.6%) women, of mean age 64.3 ± 8.0 years. Seventy-two (49.3%) patients were incidentally diagnosed, with no specific symptoms, and 18 (12.3%) were found to have hepatolithiasis. Sixty-one (41.8%) and two (1.4%) patients underwent concurrent bile duct resection and pancreaticoduodenectomy, respectively, and 130 (89.0%) underwent R0 resection. Low-grade and high-grade intraepithelial neoplasia, and invasive carcinoma were identified in 26 (17.8%), 50 (34.2%), and 70 (47.9%) patients, respectively. Five-year tumor recurrence and patient survival rates were 8.4% and 93.9%, respectively, in patients with high-grade neoplasia; and 41.5% and 72.3%, respectively, in patients with invasive carcinoma. CA19-9 > 37 U/mL and R1 resection were independent risk factors for tumor recurrence and reduced survival in patients with carcinoma. The combination of hypermetabolic fluorodeoxy-glucose-positron emission tomography (FDG-PET) or elevated CA19-9 showed a sensitivity of 91.8% and a specificity of 61.9% for the prediction of IPNB-L with high-grade neoplasia and carcinoma.Conclusions: IPNB-L is a rare type of intrahepatic biliary neoplasm that can range histologically from benign disease to invasive carcinoma. Surgical curability is the most important prognostic factor, thus aggressive resection is highly recommended to achieve R0 resection. [ABSTRACT FROM AUTHOR]

Background: Although lymph node metastasis is a known factor predictive of a poor prognosis after radical surgery for intrahepatic cholangiocarcinoma (ICC), few studies have investigated lymph node dissection (LND) areas for accurate staging. The aim of this study was to identify the optimal LND level for ICC considering lymphatic flow. Methods: Clinical characteristics and pathologic nodal status (presence of metastasis) for 163 patients were reviewed according to tumor location. In the node-positive (N1) group, the distribution of metastatic nodes was described. The coverage of metastatic nodes according to dissection level was assessed, and the minimum dissection level for accurate ICC staging was estimated accordingly. For validation, the node-negative (N0) group was divided into two subgroups according to the estimated dissection level, and survival outcomes were compared. Results: In the N1 group, expanding dissection to stations no. 12 and 8 covered 82.0% (n = 50) of metastatic cases regardless of tumor location. In survival analysis of N0 group, patients who underwent LND covering stations no. 8+12 showed better disease-free survival (DFS) and overall survival (OS), although the differences were not statistically significant (DFS: covering no. 12+8 vs. not covering no. 12+8, 109.0 months [24.2–193.8] vs. 33.0 months [10.3–55.7], p = 0.078; OS: covering no. 12+8 vs. not covering no. 12+8, 180.0 months [21.6–338.4] vs. 73.0 months [42.8–103.2], p = 0.080). Conclusion: LND including at least stations no. 12 (hepatoduodenal ligament) and 8 (common hepatic artery), regardless of tumor location, is recommended for accurate staging in ICC patients. [ABSTRACT FROM AUTHOR]

Background: Multiple tumor foci (MTF) in intrahepatic cholangiocarcinoma (ICC), including satellitosis and true multifocality, is a known negative prognostic factor and can inform pre-operative decision-making. Lack of standardized pre-operative liver staging practices may contribute to undiagnosed MTF and poor outcomes. We sought to investigate the sensitivity of different cross-sectional imaging modalities for MTF at our institution. Methods: We identified n = 52 patients with ICC who underwent curative-intent resection from 2004 to 2017 in a multidisciplinary hepato-pancreato-biliary cancer program. Timing and modality of pre-operative imaging were recorded. Blinded review of imaging was performed and modalities were evaluated for false-negative rate (FNR) in detecting MTF, satellitosis, and true multifocality. Results: Forty-one (79%) patients underwent CT and 20 (38%) underwent MRI prior to hepatectomy. MTF was pre-operatively identified in six (12%) patients. An additional seven patients had MTF discovered on final surgical pathology, despite a median interval from CT/MRI to surgery of 20 days. On blinded review the FNR of MRI compared to CT for multifocality was 0% vs. 38%, 50% vs 80% for satellitosis, and 22% vs 46% for MTF as a whole. Conclusion: CT is inadequate for pre-operative diagnosis of MTF in resectable ICC, even when performed within 30 days of hepatectomy. We recommend liver-protocol MRI as the standard pre-operative imaging modality in non-metastatic ICC. [ABSTRACT FROM AUTHOR]

Background: Hepatolithiasis is associated with the development of intrahepatic cholangiocarcinoma (ICC). This study sought to investigate risk factors of ICC for hepatolithiasis after partial hepatectomy (PH) and to develop a model for predicting ICC risk. Methods: Data on consecutive patients who underwent PH for hepatolithiasis at the Eastern Hepatobiliary Surgery Hospital between January 2009 and December 2011 were reviewed. Independent risk factors of ICC identified by Cox regression model were used to develop a nomogram in predicting ICC after PH for hepatolithiasis. Results: Of 2056 patients, 168 developed ICC at a median follow-up of 7.2 years. The cumulative incidences of ICC at 3, 5, and 8 years after PH for hepatolithiasis were 3.0%, 6.5%, and 12.9%, respectively. Independent risk factors of ICC were identified to be a long duration of hepatolithiasis-related symptoms (hazard ratio, 1.088 [95% confidence interval, 1.057–1.120]), metabolic syndrome (2.036 [1.210–3.425]), a high neutrophil-to-lymphocyte ratio (1.250 [1.009–2.816] for 3–5 vs ≤3; 1.538 [1.048–2.069] for ≥5 vs ≤3), hepatic atrophy (1.711 [1.189–2.462]), segmental intensity differences (1.513 [1.052–2.176]), persistent biliary strictures (2.825 [1.480–5.391]), and residual stone disease (2.293 [1.511–3.481]). By incorporating these factors, a constructed nomogram showed a concordance index of 0.721 to predict ICC. The calibration plots demonstrated good agreement between observed and predicted morbidities. The optimal cutoff point for the nomogram was 48 in differentiating between high and low-risk of ICC. Conclusions: A nomogram for predicting ICC after PH for hepatolithiasis was constructed based on risk factors of developing ICC. Patients with a nomogram point of ≥48 were predicted to have a high risk of ICC. [ABSTRACT FROM AUTHOR]

Background: The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy is controversial, and the T category in the American Joint Committee on Cancer (AJCC) stage for ICC is a topic of debate. Methods: Data from 611 T1-2N0M0 ICC patients classified by the AJCC 8th edition who underwent hepatectomy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database during 1988–2015. Cancer-specific survival was evaluated using Kaplan-Meier analysis. The optimal cutoff value of solitary tumor size was used an adjusted p value approach to discriminating patient survival. Results: In the AJCC 8th staging system, using a 5-cm cut-off value of tumor size for solitary ICC without vascular invasion (S/VI–) was not associated with survival in T1 category (p = 0.201), and multifocal ICC with vascular invasion had a worse survival than solitary ICC with vascular invasion (S/VI+) in T2 category (p = 0.014). Tumor size was a prognostic factor for both S/VI– and S/VI+, the optimal cutoff value of tumor size was obtained 8 cm for S/VI– and 3 cm for S/VI+. S/VI– ≤ 8 cm had a similar survival to S/VI+ ≤ 3 cm (p = 0.126), S/VI– > 8 cm had a similar survival to S/VI+ > 3 cm (p = 0.655), and multifocal ICC had a similar survival with S/VI– > 8 cm (p = 0.159) and S/VI+ > 3 cm (p = 0.196). When the cohort was divided into two groups—new T1 (S/VI– ≤ 8 cm and S/VI+ ≤ 3 cm) and new T2 (S/VI– > 8 cm, S/VI+ > 3 cm and multifocal ICC)—significant survival difference was observed (p < 0.0001). Conclusions: The discriminatory power of the AJCC 8th edition for solitary ICC could be further enhanced by subdividing tumors according to size and vascular invasion (8 cm for S/VI– and 3 cm for S/VI+). [ABSTRACT FROM AUTHOR]

Background: Lymph node (LN) metastasis is one factor indicating a poor prognosis after radical surgery for intrahepatic cholangiocarcinoma (ICC). Although several guidelines have recommended that LN dissection be strongly considered at the time of ICC surgery, no clear evidence regarding the appropriate number of harvested LNs has been established. Thus, we aimed to identify the minimum number of harvested LNs required for ICC by using a Bayesian Weibull model.Methods: Data from 142 patients who underwent radical hepatectomy (R0) for ICC from January 2000 to December 2018 were retrospectively reviewed. A Bayesian Weibull model was developed to analyze the effect of number of harvested LNs on survival of patients without (N0; n = 71) and with (N1; n = 71) metastatic nodes. We also compared the percentage of N1 patients (i.e., the N1 rate) in each of the five subgroups categorized according to the number of harvested LNs (1-4, 5-8, 9-12, 13-16, and ≥ 17).Results: In patients with 5 or more harvested LNs, the hazard ratio (HR) for LN metastasis was above the reference line (the HR with 5 harvested LNs, 1.95 (1.09-3.45)). The N1 rate of the 1-4 harvested LNs subgroup was lower than that of the other subgroups (e.g., 1-4 vs. 5-8; 16.1% vs. 39.4%, p = 0.014).Conclusion: Our results suggest that at least 5 LNs should be harvested in patients who undergo radical surgery for ICC to promote accurate staging. [ABSTRACT FROM AUTHOR]

Background: The AJCC made four changes to T category in the 8th AJCC stage for ICC, but this is a topic of debate. Methods: Data from 820 patients with ICC were extracted from the SEER database. Survival analysis of the 8th AJCC stage was examined. Results: To verify the four T staging changes by survival analysis: prognosis of patients with tumor size > 5 cm was poorer than that with tumor size ≤ 5 cm (P < 0.05); in N0M0 cohort, there was no significant difference in survival between solitary tumor with vascular invasion and multiple tumors (P = 0.092), tumor perforating the visceral peritoneum with and without involving local extrahepatic structures by direct invasion (P = 0.470), and tumor with and without periductal invasion (PI) (P = 0.220). The prognosis of patients with ≥ 4 positive lymph nodes was relatively poor compared with 1–3 positive lymph nodes (P = 0.037) and similar to patients with stage IV (8th AJCC, P = 0.585). Conclusion: This study found that there was no significant difference in survival between tumor perforating the visceral peritoneum with and without involving local extrahepatic structures by direct invasion, whereas other T staging changes were effective. The inclusion of the number of positive lymph nodes in the 8th AJCC stage may improve prognostic discrimination in ICC patients. [ABSTRACT FROM AUTHOR]

Objectives: To assess conditional survival (CS) according to recurrence status, as well as conditional disease-free survival (cDFS) among patients with intrahepatic cholangiocarcinoma (ICC).Methods: CS and cDFS were evaluated among ICC patients who underwent curative-intent resection for ICC by using a multi-institutional database. Five-year CS (CS5) at "x" years was calculated separately for patients who did and did not experience recurrence. The cDFS3 at "x" years was defined as the chance to be disease-free for an additional 3 years after not having experienced a recurrence for "x" years postoperatively.Results: Among 1221 patients, median OS was 36.8 months. While estimated actuarial OS decreased over time, CS5 increased as patients survived over longer periods of time and reached 93.9% at 4 years among 139 patients who did not experience a recurrence. Among the 725 (59.4%) patients who did experience a tumor recurrence, CS5 decreased to 17.7% the first postoperative year; however, CS5 subsequently increased to 79.7% for 81 patients who had survived 4 years after surgery. While actuarial DFS decreased from 54.6% at 1 year to 28.2% at 5 years, estimated cDFS3 following liver resection increased over time. Of note, patients with known risk factors for recurrence had even more marked improvements in cDFS3 over subsequent years versus patients without risk factors for recurrence.Conclusion: CS and cDFS changed over time according to the presence of disease-specific risk factors, as well as the presence of recurrence. [ABSTRACT FROM AUTHOR]

Objectives: The role of laparoscopic hepatectomy (LH) for intrahepatic cholangiocarcinoma (ICC) remains indefinite, though the utilization of this minimally invasive approach has been increasing for ICC. We herein performed a meta-analysis to investigate this issue.Methods: Six retrospective studies including 384 patients who had undergone LH and 2147 patients who had undergone open hepatectomy (OH) for ICC were included. The fixed-effects or random-effects models were utilized for data analysis.Results: Compared with patients who had undergone OH for ICC, patients who had undergone LH for ICC experienced more R0 resections (81.6 versus 73.8%, risk ratio (RR) = 1.08, 95% confidence interval (CI) 1.02-1.14; P = 0.008) but less major hepatectomies (37.7 versus 54.2%, RR = 0.69, 95% CI 0.60-0.79; P < 0.0001), less lymph node dissections (38.0 versus 61.5%, RR = 0.62, 95% CI 0.54-0.70; P < 0.0001), and smaller tumor size resected (4.14 versus 4.94 cm, weighted mean difference = - 0.80 cm, 95% CI - 1.38 to - 0.22 cm; P = 0.007). No significant difference was observed in other perioperative results (all P > 0.05) or overall survival (hazard ratio (HR) = 1.38, 95% CI 0.63-3.02; P = 0.43).Conclusions: LH has comparable safety, feasibility, and oncological efficacy to that of OH for ICC and has superiority in R0 resection over OH. It may be time to consider LH for ICC only if a more thorough effort on lymph node dissection is undertaken in selective patients at experienced centers. [ABSTRACT FROM AUTHOR]

Background: The objective was to clarify the prognostic impact of the 8th edition of American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) of intrahepatic cholangiocarcinoma (ICC).Methods: A total of 103 ICC patients who underwent hepatectomy between 2002 and 2016 were enrolled. The survival impact of AJCC/UICC 8th edition was examined.Results: The 5-year disease-specific survival (DSS) rate was 75.9% in T1a (n = 23), 88.9% in T1b (n = 10), 14.9% in T2 (n = 24), 52.5% in T3 (n = 11), and 15.2% in T4 (n = 35). The DSS was comparable among T2, T3, and T4 (T2 vs. T3; p = 0.345, T3 vs. T4; 0.295). A multivariate analysis identified multiple tumors (hazard ratio [HR] 2.821), periductal infiltrating (HR 2.439), perforation of the visceral peritoneum (HR 1.850), and vascular invasion (HR 1.872) as independent prognostic factors that were associated with the DSS. The optimum tumor size with the greatest difference in the DSS was 2 cm (p = 0.014). The new T classification was developed as follows: T1, size ≤ 2 cm without other factors; T2, size > 2 cm without other factors; T3, vascular invasion or perforation of the visceral peritoneum; and T4, multiple tumors or periductal infiltrating. The 5-year DSS was 100% in T1 (n = 7), 76.6% in T2 (n = 28), 45.1% in T3 (n = 28), and 3.4% in T4 (n = 40). There were differences in the DSS between T2 and T3 (p = 0.035) and between T3 and T4 (p = 0.003).Conclusions: T2, T3, and T4 of AJCC/UICC overlapped with regard to the DSS. The new staging can classify ICC patients with sufficient prognostic differences. [ABSTRACT FROM AUTHOR]

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

Background: The prognostic value of tumor multinodularity in intrahepatic cholangiocarcinoma (ICC) remains debated. We aimed to evaluate the impact of tumor multinodularity according to the presence and distribution of multiples ICC's nodules.Methods: A retrospective review of a prospectively maintained database of patients undergoing resection for ICC from January 1995 to September 2017 was performed. Prognostic factors for survival were assessed by multivariate Cox analysis. Tumoral nodules were defined according to their number (single and multiple) and localization (satellites and contralateral).Results: Out of 120 selected patients, 64 (53%) had single and 56 (47%) had multiple lesions. Multiple lesions included tumors with satellites (n = 40; 71.5%) and tumors with contralateral lesions (n = 16; 28.5%). Patients with multiple tumors had significantly larger mean main lesion size (p = 0.02), required a higher rate of perioperative transfusion (p = 0.04), had a greater rate of lymph node involvement (p < 0.0001), vascular invasion (p = 0.04), and poor differentiation (p = 0.04) than single tumors. Patients with single tumors experienced a 5-year survival significantly longer (40%) than patients with multiple tumors (14%; p = 0.004). Patients having tumors with satellites had inferior median overall survival and 5-year survival rates (20 months, 7%) compared with patients with contralateral tumors (33.6 months, 29%) (p = 0.09). Multivariable analysis identified tumor multinodularity, morbidity, tumor size < 5 cm, poor differentiation, and lymph node involvement as independent prognostic factors for overall survival.Conclusions: Tumor multinodularity represents an independent risk factor for survival in ICCs and identifies a category of patients in need of more effective perioperative treatment. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma is a malignancy of the intrahepatic biliary tree. Although surgical resection is the mainstay of treatment for this tumor, the impact of lymph node dissection during hepatectomy is controversial. In this study, we evaluated the impact of lymph node dissection during surgical resection for intrahepatic cholangiocarcinoma.Methods: Records from 170 patients who underwent radical hepatectomy for intrahepatic cholangiocarcinoma from January 2000 to December 2014 were retrospectively reviewed. Twenty-two patients who underwent R1 resection or had distant metastasis at the time of surgery were excluded. Using propensity score matching (matched factors: differentiation, lymphovascular invasion, perineural invasion, and T stage), the patients were divided into two groups: no dissection (n = 34) or lymph node dissection (n = 34). Disease-free survival and overall survival were compared between groups.Results: There was a marginally significant difference between the two groups with respect to the disease-free survival (no dissection vs. lymph node dissection: 20.0 [4.2-35.8] months vs. 64.0 [27.3-120.8] months, p = 0.077). Overall survival was significantly longer in the lymph node dissection group (no dissection vs. lymph node dissection: 44.0 [31.1-56.9] months vs. 90.0 [51.1-158.9] months, p = 0.027).Conclusion: Radical surgery including an adequate lymph node dissection area and suitable harvested lymph nodes appears to improve oncologic outcomes for intrahepatic cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Surgical management of intrahepatic cholangiocarcinoma routinely includes resection of the hepatic parenchyma, yet the role of lymphadenectomy (LND) is more controversial. The objective of the current study was to define overall utilization, as well as temporal trends, in the utilization of LND among patients undergoing curative-intent hepatectomy for ICC using a nationwide database.Materials and Methods: One thousand four hundred ninety-six patients who underwent curative-intent resection for ICC were identified using the SEER database from 2000 to 2013. The utilization of LND was assessed over time and by geographic region. LND utilization and the incidence of lymph node metastasis (LNM) were evaluated relative to AJCC T categories.Results: At the time of surgery, slightly over one-half of patients (n = 784, 52.4%) had at least one LN evaluated. Specifically, 613 (41.0%) patients had 1-5 LNs evaluated, whereas 171 (11.4%) patients had ≥ 6 LNs evaluated. The proportion of patients who had at least one LN evaluated at the time of surgery did not change with time (2000-2004: 50.5% vs. 2005-2009: 52.0% vs. 2010-2013: 53.7%) (p = 0.636). In contrast, the proportion of patients who had ≥ 6 LNs examined did increase (2000-2004: 6.9% vs. 2005-2009: 10.6% vs. 2009-2013: 14.3%) (p = 0.003). The risk of LNM was higher among patients with advanced T category tumors (Referent T1; T2a: OR 4.2, 95% CI 2.0-8.8, p < 0.001; T2b: OR 2.4, 95% CI 1.1-4.9, p = 0.018; T3: OR 3.6, 95% CI 1.6-7.9, p = 0.001; T4: OR 2.2, 95% CI 1.0-4.9, p = 0.049). In addition, the portion of patients with LNM varied among the different T categories (T1, 23.2%, T2a, 55.3%, T2b, 42.0%, T3, 51.4%, and T4, 39.5%; p = 0.001).Conclusions: Utilization of LND in the surgical management of ICC across the USA remained relatively low and did not change over the last decade. Selective utilization of LND may be problematic as T-stage was not a reliable predictor of nodal status with almost a quarter of patients with early stage disease having LNM. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We intended to investigate the clinicopathological features of intrahepatic intraductal papillary neoplasms of the bile duct (IPNB), especially their malignant features and post-resection prognosis. Forty-three patients who met the definition of IPNB and who underwent liver resection between January 2002 and June 2015 were selected from our institutional database of liver resection cases. The mean age was 63.3 ± 6.9 years and 24 were male. Hepatolithiasis was present in addition in 10 of the patients. Left- and right-sided hepatectomies and concurrent bile duct resection (BDR) were performed in 28, 15, and 10 patients, respectively; R0 resection was performed in 37 patients. The mean tumor diameter was 4.1 ± 2.2 cm. Histological tumor grade was low in 4 cases, intermediate in 6, and malignant in 33. There was no cancer-related recurrence or death in the 10 patients with low-grade or intermediate lesions. In the 33 patients with malignant lesions, rates of tumor recurrence and overall survival were 12.5 and 96.2 % at 1 year, 36.4 and 91.3 % at 3 years, and 47.0 and 68.8 % at 5 years, respectively. Multivariate analysis showed that R1 resection was the only prognostic factor for tumor recurrence and patient survival. BDR was performed in only 2 of 6 patients undergoing R1 resection. Intrahepatic IPNB is a rare type of biliary neoplasm that encompasses a histological spectrum ranging from benign disease to invasive malignancy. Long-term survival was anticipated after curative resection. R1 resection reduced survival outcomes; therefore, we suggest that concurrent BDR should be performed if the resection margin of the bile duct is not reliably free of neoplastic involvement. [ABSTRACT FROM AUTHOR]

Objective: Because noticeable changes were made to the 7th American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging for intrahepatic cholangiocarcinoma (IHCC), we validated the prognostic impact of tumor staging after macroscopic curative resection of IHCC. Methods: A cohort of 659 IHCC patients who underwent R0 ( n = 539) or R1 ( n = 120) resection were selected with exclusion of R2 resection ( n = 111). Study patients were followed up for ≥24 months or until death with no patient lost during survival analysis. Results: Anatomical resection was performed in 599 (90.9 %) and concurrent bile duct resection was conducted in 97 (14.7 %). Median survival periods following R0, R1, and R2 resections were 28, 12, and 3 months, respectively ( p = 0.000). In the R0 resection group, the 1-, 3-, 5-, and 10-year tumor recurrence rates were 36.4 %, 57.9 %, 64.7 %, and 65.0 %, respectively, and the 1-, 3-, 5-, and 10-year patient survival rates were 73.1 %, 44.2 %, 33.0 %, and 23.1 %, respectively. Independent risk factors for tumor recurrence and patient survival were tumor growth type, tumor size > 5 cm, perineural invasion, and lymph node metastasis. According to the 7th AJCC staging system, the prognostic contrast was marginal in stage T2-4 tumors without lymph node metastasis ( p > 0.8). With our redefined staging system with tumor growth types and risk factors including tumor number and perineural/lymphovascular invasion, clear prognostic contrast was achieved among T1-3 stages ( p = 0.000). Conclusion: Growth type of IHCC seems to be essential for determining tumor stage. Although the stratification of the 7th AJCC IHCC staging system seems reasonably established, refinements and further validation could improve prognostic predictability. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a surrogate marker of patient frailty that estimates the physiologic reserve of an individual patient. We sought to investigate the impact of sarcopenia on short- and long-term outcomes in patients having undergone surgical intervention for primary hepatic malignancies. Methods: Ninety-six patients who underwent hepatic resection or liver transplantation for HCC or ICC at the John Hopkins Hospital between 2000 and 2013 met inclusion criteria. Sarcopenia was assessed by the measurement of total psoas major volume (TPV) and total psoas area (TPA). The impact of sarcopenia on perioperative complications and survival was assessed. Results: Mean age was 61.9 years and most patients were men (61.4 %). Mean adjusted TPV was lower in women (23.3 cm/m) versus men (34.9 cm/m) ( P < 0.01); 47 patients (48.9 %) had sarcopenia. The incidence of a postoperative complication was 40.4 % among patients with sarcopenia versus 18.4 % among patients who did not have sarcopenia ( P = 0.01). Of note, all Clavien grade ≥3 complications ( n = 11, 23.4 %) occurred in the sarcopenic group. On multivariable analysis, the presence of sarcopenia was an independent predictive factor of postoperative complications (OR = 3.06). Sarcopenia was not associated with long-term survival (HR = 1.23; P = 0.51). Conclusions: Sarcopenia, as assessed by TPV, was an independent factor predictive of postoperative complications following surgical intervention for primary hepatic malignancies. [ABSTRACT FROM AUTHOR]

The role of lymph node dissection (LND) in the treatment of patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) remains controversial. We sought to systematically review all available evidence to determine the role of LND in patients with HCC and ICC. Studies that reported on LND, lymph node metastasis (LNM), and short- and long-term outcomes for patients with HCC or ICC survival were identified from PubMed, Cochrane, Embase, Scopus, and Web of Science databases. Data were extracted, synthesized, and analyzed using standard techniques. A total of 603 and 434 references were identified for HCC and ICC, respectively. Among HCC patients, the overall prevalence of LND was 51.6 % (95 % confidence interval (CI) 19.7-83.5) with an associated LNM incidence of 44.5 % (95 % CI 27.4-61.7). LNM was associated with a 3- and 5-year survival of 27.5 and 20.8 %, respectively. Among ICC patients, most patients 78.5 % (95 % CI 76.2-80.7) underwent LND; 45.2 % (95 % CI 39.2-51.2) had LNM. Three and 5-year survival among ICC patients with LNM was 0.2 % (95 % CI 0-0.7) and 0 %, respectively. While there are insufficient data to recommend a routine LND in all patients with HCC or ICC, the potential prognostic value of LND suggests that LND should at least be considered at the time of surgery. [ABSTRACT FROM AUTHOR]

The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection is controversial. We sought to define the incidence of major and microscopic vascular invasion relative to ICC tumor size, and identify predictors of microscopic vascular invasion in patients with ICC ≥5 cm. A total of 443 patients undergoing surgical resection for ICC between 1973 and 2011 at one of 11 participating institutions were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. As tumor sized increased, the incidence of microscopic vascular invasion increased: <3 cm, 3.6 %; 3-5 cm, 24.7 %; 5-7 cm, 38.3 %; 7-15 cm, 32.9 %, ≥15 cm, 55.6 %; ( p < 0.001). Increasing tumor size was also found to be associated with worsening tumor grade. The incidence of poorly differentiated tumors increased with increasing ICC tumor size: <3 cm, 9.7 %; 3-5 cm, 19.8 %; 5-7 cm, 24.2 %; 7-15 cm, 21.1 %; >15 cm, 31.6 % ( p = 0.04). The presence of perineural invasion (odds ratio [OR] = 2.98) and regional lymph node metastasis (OR = 4.43) were independently associated with an increased risk of microscopic vascular invasion in tumors ≥5 cm (both p < 0.05). Risk of microscopic vascular invasion and worse tumor grade increased with tumor size. Large tumors likely harbor worse pathologic features; this information should be considered when determining therapy and prognosis of patients with large ICC. [ABSTRACT FROM AUTHOR]

Background: Surgical resection is currently indicated for all potentially resectable intrahepatic cholangiocarcinoma (ICC), but the survival outcomes and the prognostic factors have not been well-documented due to its rarity. This study aims to assess these in a large, consecutive series of patients with ICC treated surgically. Methods: A retrospective study was conducted on 1,333 ICC patients undergoing surgery between January 2007 and December 2011. Surgical results and survival were evaluated and compared among different subgroups of patients. Univariate and multivariate analyses were performed to identify prognostic factors. Results: R0, R1, R2 resection and exploratory laparotomy were obtained in 34.8, 44.9, 16.4, and 3.9 % of the patients, respectively. The overall 1-, 3-, and 5-year survival rates for the entire cohort were 58.2, 25.2, and 17.0 %, respectively, with corresponding rates of 79.1, 42.6, and 28.7 % for patients with R0 resection; 60.5, 20.1, and 13.9 % for patients with R1 resection; 20.5, 7.4, and 0 % for patients with R2 resection; and 3.8, 0, and 0 % for patients with an exploratory laparotomy. Independent factors for poor survival included positive resection margin, lymph node metastasis, multiple tumors, vascular invasion, and elevated CA19-9 and/or CEA, whereas hepatitis B virus infection and cirrhosis were independently favorable prognosis indicators. Conclusions: R0 resection offers the best possibility of long-term survival, but the chance of a R0 resection is low when surgery is performed for potential resectable ICC. Further randomized trials are warranted to refine indications for surgery in the management of ICC. [ABSTRACT FROM AUTHOR]

Objective: The objective of this paper is to evaluate the perioperative outcomes of major hepatectomy for intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis. Methods: We retrospectively evaluated the preoperative, intraoperative, and postoperative findings in 42 consecutive patients with cirrhosis and in 102 patients with normal livers who underwent major hepatectomy for ICC. Results: Preoperative liver function was worse in patients with cirrhosis compared to patients without cirrhosis. Cirrhotic patients had significantly higher intraoperative blood loss, longer operation time, and longer hospital stay than non-cirrhotic patients. However, the two groups had similar overall morbidity and hospital mortality rates and similar rates of liver failure or other complications. Their R0 resection rates, resection margin widths and disease-free survival rates were also similar. Conclusions: Major hepatectomy for ICC can be performed in selected cirrhotic patients with acceptable morbidity and mortality rates, as compared to patients without cirrhosis. [ABSTRACT FROM AUTHOR]

Introduction: The prognostic significance of lymph node dissection (LND), the number and status of harvested lymph nodes (LNs), and the lymph node ratio (LNR) are still under debate in intrahepatic (ICC) and perihilar (PCC) cholangiocarcinoma. The aims of this study were to evaluate the prognostic value of the extent of LN dissection, the number of positive LNs, the distribution of positive LNs along different LN stations, and the LNR in a cohort of patients with ICC and PCC who underwent surgical resection and to compare the different prognostic values of lymph node involvement. Material and Methods: A retrospective analysis was done evaluating extent of LND, number, status, and location of harvested LNs in a cohort of 145 patients with cholangiocarcinoma submitted to surgical resection with curative intent from 1990 to 2012. Results: Seventy patients had ICC and 75 had PCC. The median survival times of patients with N0 and N+ tumors were 42 and 19 months in ICC patients ( p = 0.05) and 42 and 22 months in PCC patients ( p = 0.01). In patients without LN metastases, the median survival times of patients with up to three LNs retrieved and with more than three LNs retrieved were 38 and 69 months in ICC patients ( p = 0.05) and 18 and 43 months in PCC patients ( p = 0.04), respectively. In N+ patients, the location of positive LNs (hepatoduodenal ligament or other regional stations) did not influence overall survival in ICC or PCC patients ( p = 0.6). The median survival times of patients with LNRs of 0 and >0.25 were 43 and 19 months in ICC patients ( p = 0.01); the 0-0.25 group did not reach the value. In PCC patients, median survival of 0, 0-0.25, and >0.25 groups of patients were 42, 23, and 11 months ( p = 0.01), respectively. Conclusions: LN metastasis is a major prognostic factor after surgical resection of cholangiocarcinoma. The number of harvested LNs and the LNR showed a high prognostic value in ICC and PCC. [ABSTRACT FROM AUTHOR]

Background and Aims: The objective of this report was to determine the prevalence of underlying nonalcoholic steatohepatitis in resectable intrahepatic cholangiocarcinoma. Methods: Demographics, comorbidities, clinicopathologic characteristics, surgical treatments, and outcomes from patients who underwent resection of intrahepatic cholangiocarcinoma at one of eight hepatobiliary centers between 1991 and 2011 were reviewed. Results: Of 181 patients who underwent resection for intrahepatic cholangiocarcinoma, 31 (17.1 %) had underlying nonalcoholic steatohepatitis. Patients with nonalcoholic steatohepatitis were more likely obese (median body mass index, 30.0 vs. 26.0 kg/m, p < 0.001) and had higher rates of diabetes mellitus (38.7 vs. 22.0 %, p = 0.05) and the metabolic syndrome (22.6 vs. 10.0 %, p = 0.05) compared with those without nonalcoholic steatohepatitis. Presence and severity of hepatic steatosis, lobular inflammation, and hepatocyte ballooning were more common among nonalcoholic steatohepatitis patients (all p < 0.001). Macrovascular (35.5 vs. 11.3 %, p = 0.01) and any vascular (48.4 vs. 26.7 %, p = 0.02) tumor invasion were more common among patients with nonalcoholic steatohepatitis. There were no differences in recurrence-free (median, 17.0 versus 19.4 months, p = 0.42) or overall (median, 31.5 versus 36.3 months, p = 0.97) survival after surgical resection between patients with and without nonalcoholic steatohepatitis. Conclusions: Nonalcoholic steatohepatitis affects up to 20 % of patients with resectable intrahepatic cholangiocarcinoma. [ABSTRACT FROM AUTHOR]