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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.

BackgroundEndoluminal radiofrequency ablation (RFA) has been promoted as palliative treatment for patients with cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) in order to improve biliary drainage and eventually prolong survival. No high level evidence is, however, available on this technique.DesignIn this randomised controlled study, we compared endoluminal RFA plus stenting with stenting alone (control group) in patients with malignant biliary obstruction; metal stents were primarily placed. Primary outcome was overall survival; secondary outcomes were stent patency, quality of life and adverse events. In a superiority design, survival was assumed to be doubled by RFA as compared with 6.4 months in the control group (n=280).ResultsA total of 161 patients (male:female 90:71, mean age 71±9 years) were randomised before recruitment was terminated for futility after an interim analysis. Eighty-five patients had CCA (73 hilar, 12 distal) and 76 had pancreatic cancer. There was no difference in survival in both subgroups: for patients with CCA, median survival was 10.5 months (95% CI 6.7 to 18.3) in the RFA group vs 10.6 months (95% CI 9.0 to 24.8), p=0.58)) in the control group. In the subgroup with pancreatic cancer, median survival was 6.4 months (95% CI 4.3 to 9.7) for the RFA vs 7.7 months (95% CI 5.6 to 11.3), p=0.73) for the control group. No benefit was seen in the RFA group with regard to stent patency (at 12 months 40% vs 36% in CCA and 66% vs 65% in PDAC), and quality of life was unchanged by either treatment and comparable between the groups. Adverse events occurred in seven patients in each groups.ConclusionA combination of endoluminal RFA and stenting was not superior to stenting alone in prolonging survival or improving stent patency in patients with malignant biliary obstruction.Trial registration number NCT03166436.

PurposeThis study aimed to establish a nomogram based on preoperative magnetic resonance imaging (MRI) features to predict the very early recurrence (VER, less than 6 months) of intrahepatic mass-forming cholangiocarcinoma (IMCC) after R0 resection.MethodsThis study enrolled a group of 193 IMCC patients from our institution between March 2010 and January 2022. Patients were allocated into the development cohort (n = 137) and the validation cohort (n = 56), randomly, and the preoperative clinical and MRI features were collected. Univariate and multivariate stepwise logistic regression assessments were adopted to assess predictors of VER. Nomogram was constructed and certificated in the validation cohort. The performance of the prediction nomogram was evaluated by its discrimination, calibration, and clinical utility. The performance of the nomogram was compared with the T stage of the American Joint Committee on Cancer (AJCC) 8th edition staging system.ResultsFifty-three patients (27.5%) experienced VER of the tumor and 140 patients (72.5%) with non-VER, during the follow-up period. After multivariate stepwise logistic regression, number of lesions, diffuse hypoenhancement on arterial phase, necorsis and suspicious lymph nodes were independently associated with VER. The nomogram demonstrated significantly higher area under the curve (AUC) of 0.813 than T stage (AUC = 0.666, P = 0.006) in the development cohort, whereas in the validation cohort, the nomogram showed better discrimination performance, with an AUC of 0.808 than T stage (0.705) with no significantly difference (P = 0.230). Decision curve analysis reflected the clinical net benefit of the nomogram.ConclusionThe nomogram based on preoperative MRI features is a reliable tool to predict VER for patients with IMCC after R0 resection. This nomogram will be helpful to improve survival prediction and individualized treatment.

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

Backgrounds Stent migration following endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) may sometimes be fatal because there are no adhesions between the biliary tract and stomach. To prevent stent migration and minimize the stent length in the abdominal cavity, we recently performed EUS-HGS using the technique of releasing the stent within the scope channel. Aims To examine the technical feasibility of the intra-scope channel stent release technique. Methods Forty-one consecutive patients who underwent EUS-HGS were enrolled. Between October 2015 and December 2015, EUS-HGS was performed using the extra-scope channel release technique, while the intra-scope channel release technique was performed between January 2016 and March 2016. Results The distance between the hepatic parenchyma and the stomach wall after EUS-HGS in the intra-scope channel stent release group was significantly shorter than that in the extra-scope channel release group (0.66 ± 1.25 vs 2.52 ± 0.97, P  < 0.05). Adverse events, such as biloma or stent migration, were seen in only the extra-scope channel release group. Conclusion In conclusion, although additional cases and randomized controlled studies using metal stents of various lengths are needed, our technique is likely to be clinically useful for the prevention of early and late stent migration.

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.

Background To evaluate the clinical value of plain magnetic resonance (MR) imaging (including magnetic resonance cholangiopancreatography, MRCP) and coronal liver acquisition with volume acceleration (LAVA) technique in the diagnosis and preoperative assessment of malignant low-level biliary obstruction. Methods Forty-one patients with confirmed malignant low-level biliary obstruction were examined by plain MR, MRCP and coronal LAVA techniques. Group 1, plain MR (including MRCP); group 2, coronal LAVA; group 3, plain MR and coronal LAVA. Assessments included positioning, qualitative diagnosis and preoperative evaluation. The results were compared with pathological, endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography results. Results There were 14 pancreatic adenocarcinoma, 12 distal common bile duct carcinoma, 10 ampullary carcinoma, and 5 duodenal carcinoma cases. There was no significant difference in accuracy of the three groups’ positioning diagnoses, 87.8, 90.2, and 92.7 %, respectively. The accuracy of the qualitative diagnoses was lower in group 1 at 78.0 %, but not significantly different in groups 2 and 3 at 92.7 and 95.1 %, respectively ( P  = 0.031, and 0.039, group 1 vs groups 2 and 3, respectively). Thirty-three patients underwent open surgery. There were 19 adjacent organ involvements, 9 vascular involvements, 13 lymph node metastases and 6 liver metastases. 22 patients were verified surgically and histologically for resectable lesions. Plain MR with coronal LAVA imaging showed 85.4 % accuracy, 90.9 % sensitivity, 78.9 % specificity, 83.3 % positive and 88.2 % negative predictive value for resectability. Conclusions Plain MR and coronal LAVA techniques are potential noninvasive tools for diagnosis and preoperative assessment of malignant low-level biliary obstruction.

On the basis of morphological features, we subclassified 189 intrahepatic cholangiocarcinomas into two subtypes: bile duct and cholangiolar. The cholangiolar type is composed of cuboidal to low columnar tumor cells that contain scanty cytoplasm. The bile duct type is composed of tall columnar tumor cells arranged in a large glandular pattern. In this study, 77 (41%) tumors were classified as the cholangiolar type and 112 (59%) tumors were classified as the bile duct type. The cholangiolar-type intrahepatic cholangiocarcinoma was more frequently associated with viral hepatitis, whereas all but one intrahepatic cholangiocarcinoma associated with intrahepatic lithiasis were classified as the bile duct type. Biliary intraepithelial neoplasm or intraductal papillary neoplasm of the bile duct could be identified in 50 bile duct-type intrahepatic cholangiocarcinomas (45%), but in only 3 cholangiolar-type intrahepatic cholangiocarcinomas (4%). Cholangiolar-type intrahepatic cholangiocarcinomas frequently expressed N-cadherin, whereas bile duct intrahepatic cholangiocarcinomas were more likely to express S100P, Trefoil factor 1, and anterior gradient 2. KRAS is mutated in 23 of 98 (23%) bile duct-type intrahepatic cholangiocarcinomas and in only 1 of 76 (1%) cholangiolar-type intrahepatic cholangiocarcinomas. Cholangiolar-type intrahepatic cholangiocarcinomas had a higher frequency of IDH1 or 2 mutations than did the bile duct-type intrahepatic cholangiocarcinomas. The molecular features of the bile duct-type intrahepatic cholangiocarcinoma were similar to those of hilar cholangiocarcinoma. Patients with the cholangiolar-type intrahepatic cholangiocarcinoma had higher 5-year survival rates than those of patients with the bile duct-type intrahepatic cholangiocarcinoma. Our results indicated that intrahepatic cholangiocarcinoma was a heterogeneous tumor. Subclassification of intrahepatic cholangiocarcinomas based on cholangiocytic differentiation divides them into two groups with different etiologies, clinical manifestations, and molecular pathogeneses.

BackgroundHepatectomy is a definitive treatment for hepatolithiasis because it simultaneously removes intrahepatic duct (IHD) stones and biliary tract strictures together with the involved liver region en bloc. Unlike cystic or solid liver tumors, hepatolithiasis is usually associated with alterations of anatomical structures and perihepatic adhesions because of chronic recurrent inflammation. This complicates identification of the target hepatic region and location of biliary strictures.MethodsTo determine the efficacy of near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG), we performed a comparative trial and developed a white-light and near-infrared dual-channel image-guided device (DPM-I) for both open and endoscopic surgery. Forty-four eligible patients were randomly assigned to Group A (NIRF imaging) or Group B (traditional hepatectomy). We injected ICG via peripheral veins for patients in Group A.ResultsThe NIRF imaging method was associated with less blood loss (OR 1.004, 95% CI 0.999–1.010; P = 0.016), briefer hospitalization (OR 1.336, 95% CI 1.016–1.756; P = 0.001), lower rates of margins with dilated bile ducts (OR 1.278, 95% CI 1.030–1.585; P = 0.023), lower postoperative white blood cell counts (OR 1.262, 95% CI 0.931–1.712; P = 0.038), lower procalcitonin levels (OR 1.316, 95% CI 1.020–1.513; P = 0.002), and lower alanine aminotransferase levels (OR 1.013, 95% CI 1.003–1.023; P = 0.002) compared with traditional hepatectomy.ConclusionsThese data demonstrate the efficacy of NIRF imaging with ICG using DPM-I for treating hepatolithiasis.

Background Cholangiocarcinoma can be classified in intrahepatic cholangiocarcinoma (ICC) and perihilar cholangiocarcinoma (PCC). Moreover, PCC includes two different forms: extrahepatic (EH) PCC, which arises from the perihilar EH large ducts, and intrahepatic (IH) PCC, in which a significant liver mass invades the perihilar bile ducts. In this study, we investigated the molecular profile and molecular prognostic factors in EH-PCC, IH-PCC, and ICC submitted to curative surgery. Methods Ninety-one patients with cholangiocarcinoma (38 EH-PCC, 18 IH-PCC, and 35 ICC), who underwent curative surgery in a single tertiary hepatobiliary surgery referral center were assessed for mutational status in 56 cancer-related genes. Results The most frequently mutated genes in EH-PCC were KRAS (47.4 %), TP53 (23.7 %) and ARID1A (15.8 %); in IH-PCC were KRAS (22.2 %), PBRM1 (16.7 %), and PIK3CA (16.7 %); and in ICC were IDH1 (17.1 %), NRAS (17.1 %), and BAP1 (14.3 %). The presence of mutations in ALK , IDH1 , and TP53 genes was significantly associated with poor prognosis in patients with EH-PCC ( p  < 0.001, p  = 0.043, and p  = 0.019, respectively). Mutation of the TP53 gene was significantly associated with poor prognosis in patients with IH-PCC ( p  = 0.049). The presence of mutations in ARID1A , PIK3C2G , STK11 , TGFBR2 , and TP53 genes was significantly associated with poor prognosis in patients with ICC ( p  = 0.012, p  = 0.030, p  = 0.030, p  = 0.011, and p  = 0.011, respectively). Conclusions Mutational gene profiling identified different gene mutations in EH-PCC, IH-PCC, and ICC. Moreover, our study reported specific prognostic genes that can identify patients with poor prognosis after curative surgery who may benefit from traditional or target adjuvant treatments.