Risk Factors For Intrahepatic Cholangiocarcinoma Research Articles

FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer and is highly lethal. Clonorchis sinensis (C.sinensis) infection is an important risk factor for iCCA. Here we investigated the clinical impact and underlying molecular characteristics of C.sinensis infection-related iCCA. We performed single-cell RNA sequencing, whole-exome sequencing, RNA sequencing, metabolomics and spatial transcriptomics in 251 patients with iCCA from three medical centers. Alterations in metabolism and the immune microenvironment of C.sinensis-related iCCAs were validated through an invitro co-culture system and in a mouse model of iCCA. We revealed that C.sinensis infection was significantly associated with iCCA patients' overall survival and response to immunotherapy. Fatty acid biosynthesis and the expression of fatty acid synthase (FASN), a key enzyme catalyzing long-chain fatty acid synthesis, were significantly enriched in C.sinensis-related iCCAs. iCCA cell lines treated with excretory/secretory products of C.sinensis displayed elevated FASN and free fatty acids. The metabolic alteration of tumor cells was closely correlated with the enrichment of tumor-associated macrophage (TAM)-like macrophages and the impaired function of T cells, which led to formation of an immunosuppressive microenvironment and tumor progression. Spatial transcriptomics analysis revealed that malignant cells were in closer juxtaposition with TAM-like macrophages in C.sinensis-related iCCAs than non-C.sinensis-related iCCAs. Importantly, treatment with a FASN inhibitor significantly reversed the immunosuppressive microenvironment and enhanced anti-PD-1 efficacy in iCCA mouse models treated with excretory/secretory products from C.sinensis. We provide novel insights into metabolic alterations and the immune microenvironment in C.sinensis infection-related iCCAs. We also demonstrate that the combination of a FASN inhibitor with immunotherapy could be a promising strategy for the treatment of C.sinensis-related iCCAs. Clonorchis sinensis (C.sinensis)-infected patients with intrahepatic cholangiocarcinoma (iCCA) have a worse prognosis and response to immunotherapy than non-C.sinensis-infected patients with iCCA. The underlying molecular characteristics of C.sinensis infection-related iCCAs remain unclear. Herein, we demonstrate that upregulation of FASN (fatty acid synthase) and free fatty acids in C.sinensis-related iCCAs leads to formation of an immunosuppressive microenvironment and tumor progression. Thus, administration of FASN inhibitors could significantly reverse the immunosuppressive microenvironment and further enhance the efficacy of anti-PD-1 against C.sinensis-related iCCAs.

Influence of cirrhosis on outcomes of patients with advanced intrahepatic cholangiocarcinoma receiving chemotherapy.

Cirrhosis is a risk factor for intrahepatic cholangiocarcinoma (iCC). However, its exact prevalence is uncertain and its impact on the management of advanced disease is not established. Retrospective analysis of patients treated with systemic chemotherapy for advanced iCC in the 1st-line setting at 2 tertiary cancer referral centres. Cirrhosis was diagnosed based on at least one element prior to any treatment: pathological diagnosis, baseline platelets <150 × 109/L, portal hypertension and/or dysmorphic liver on imaging. In the cohort of patients (n = 287), 82 (28.6%) had cirrhosis (45 based on pathological diagnosis). Patients with cirrhosis experienced more grade 3/4 haematologic toxicity (44% vs 22%, respectively, P = 0.001), and more grade 3/4 non-haematologic toxicity (34% vs 14%, respectively, P = 0.001) than those without. The overall survival (OS) was significantly shorter in patients with cirrhosis: median 9.1 vs 13.1 months for those without (HR = 1.56 [95% CI: 1.19-2.05]); P = 0.002), confirmed on multivariable analysis (HR = 1.48 [95% CI: 1.04-2.60]; P = 0.028). Cirrhosis was relatively common in patients with advanced iCC and was associated with increased chemotherapy-induced toxicity and shorter OS. Formal assessment and consideration of cirrhosis in therapeutic management is recommended.

Hepatitis B virus-related intrahepatic cholangiocarcinoma originates from hepatocytes

BackgroundHepatitis B virus (HBV) infection is one of the most common risk factors for intrahepatic cholangiocarcinoma (ICC). However, there is no direct evidence of a causal relationship between HBV infection and ICC. In this study, we attempted to prove that ICC may originate from hepatocytes through a pathological study involving ICC tissue-derived organoids.MethodThe medical records and tumor tissue samples of 182 patients with ICC after hepatectomy were collected. The medical records of 182 patients with ICC were retrospectively analyzed to explore the prognostic factors. A microarray of 182 cases of ICC tumor tissue and 6 cases of normal liver tissue was made, and HBsAg was stained by immunohistochemistry (IHC) to explore the factors closely related to HBV infection. Fresh ICC tissues and corresponding adjacent tissues were collected to make paraffin sections and organoids. Immunofluorescence (IF) staining of factors including HBsAg, CK19, CK7, Hep-Par1 and Albumin (ALB) was performed on both fresh tissues and organoids. In addition, we collected adjacent nontumor tissues of 6 patients with HBV (+) ICC, from which biliary duct tissue and normal liver tissue were isolated and RNA was extracted respectively for quantitative PCR assay. In addition, the expression of HBV-DNA in organoid culture medium was detected by quantitative PCR and PCR electrophoresis.ResultsA total of 74 of 182 ICC patients were HBsAg positive (40.66%, 74/182). The disease-free survival (DFS) rate of HBsAg (+) ICC patients was significantly lower than that of HBsAg (−) ICC patients (p = 0.0137). IF and IHC showed that HBsAg staining was only visible in HBV (+) ICC fresh tissues and organoids, HBsAg expression was negative in bile duct cells in the portal area. Quantitative PCR assay has shown that the expression of HBs antigen and HBx in normal hepatocytes were significantly higher than that in bile duct epithelial cells. Combined with the IF and IHC staining, it was confirmed that HBV does not infect normal bile duct epithelial cells. In addition, IF also showed that the staining of bile duct markers CK19 and CK7 were only visible in ICC fresh tissue and organoids, and the staining of hepatocyte markers Hep-Par1 and ALB was only visible in normal liver tissue fresh tissue. Real-time PCR and WB had the same results. High levels of HBV-DNA were detected in the culture medium of HBV (+) organoids but not in the culture medium of HBV (−) organoids.ConclusionHBV-related ICC might be derived from hepatocytes. HBV (+) ICC patients had shorter DFS than HBV (−) ICC patients.

Influence of cirrhosis on outcomes of patients with advanced intrahepatic cholangiocarcinoma receiving chemotherapy.

475 Background: Cirrhosis is a risk factor for intrahepatic cholangiocarcinoma (iCC). However, its impact on the management of advanced disease is not established. Methods: Retrospective analysis of patients (pts) treated with systemic chemotherapy for advanced iCC in the first-line setting at 2 tertiary cancer referral centers, the second center used to validate findings from the first. Cirrhosis was diagnosed based on at least one element among pathological diagnosis, baseline platelet &lt; 150 G/L, portal hypertension and/or dysmorphic liver at imaging. Results: In the first center (n=185), 55 pts (29.7%) had cirrhosis (74.5 % based on pathological diagnosis). Main aetiology of cirrhosis was alcohol for 17 pts (31%), non-alcoolic steato-hepatitis (NASH) for 10 pts (18.2%), and mixed alcohol and NASH for 9 pts (16.4%). 102 (57.0%) pts received gemcitabine-cisplatin, 55 (30.7%) pts received gemcitabine-oxaliplatin, and 11 (6%) pts received gemcitabine, with no difference between cirrhotic and non-cirrhotic pts (p=0.38). Second-line treatment was less frequent in cirrhotic pts (21.8% vs. 50.0%, p=0.001). Cirrhotic pts experienced more grade 3/4 hematologic toxicity than non-cirrhotic pts (38% vs. 20%, respectively, p=0,014), and more grade 3/4 non-hematologic toxicity (28% vs. 15%, respectively, p=0.048). The overall survival (OS) was significantly shorter in cirrhotic pts; median: 9.0 vs. 13.8 months for non-cirrhotic pts (HR = 1.54 [95%CI: 1.09-2.16]; p = 0.014); confirmed on multivariable analysis, adjusted on ALBI-score, ECOG PS, extension of the disease (liver only disease and bilobar) (HR = 1.53 [95% CI: 1.01-2.33]; p=0.046). However, PFS was not significantly shorter in cirrhotic pts: median 9,9 months vs. 11.7 for non-cirrhotics (p = 0.35). In the second center (n=102), similar results were seen: 27 (26.5%) pts had cirrhosis. The cirrhotic pts experienced more grade 3/4 hematologic toxicities than non-cirrhotic pts (55.6% vs. 25.4%, respectively, p=0.005), and more grade 3/4 non-hematologic toxicity (44.4% vs. 12.7%, respectively, p = 0.001). OS was shorter in cirrhotic pts; median 9.1 months vs. 11.7 months for non-cirrhotic pts (HR = 1.81 [95%CI: 1.14-2.87]; p = 0.011). PFS was not significantly shorter in cirrhotic pts: 7.5 months for patients without cirrhosis, and 4.2 months for pts with cirrhosis (p=0.221). Conclusions: Cirrhosis was frequent in pts with advanced iCC, and had a negative impact on patients’ outcomes, with increased chemotherapy-induced toxicity and shorter OS. Formal assessment and consideration of cirrhosis in the therapeutic management should be recommended and could lead to a dose adjustment.

Внутрипеченочная холангиокарцинома на фоне множественного холангиолитиаза как плохо диагностируемая проблема в клинической практике

Intrahepatic cholangiocarcinoma (ICH) is one of the most aggressive malignant neoplasms of the gastrointestinal tract, which accounts for 10–15% of all primary liver tumors. Among the risk factors for ICH in Europe and Russia, diseases accompanied by the formation of concretions in the intrahepatic bile ducts, which include Karoli's disease (KD), are of primary importance. The article presents a clinical observation of HPV that developed against the background of KD, a literature review is conducted.

A Novel Insight into Controversial Risk Factors of Intrahepatic Cholangiocarcinoma: A Mendelian Randomization Study

A Novel Insight into Controversial Risk Factors of Intrahepatic Cholangiocarcinoma: A Mendelian Randomization Study

The role of lymph node dissection and a new N-staging system for intrahepatic cholangiocarcinoma: a study from the SEER database.

BackgroundAlthough the National Comprehensive Cancer Network guidelines recommend routine lymph node dissection (LND) in intrahepatic cholangiocarcinoma (ICC), the role of LND remains controversial, and the node (N) stage is oversimplified.MethodsPatients were identified from the Surveillance, Epidemiology, and End Results research data 18 (SEER 18). Propensity score matching (PSM) was used to reduce bias, and Kaplan–Meier curves and Cox proportional hazards models were used to compare overall survival (OS). The best cutoff values were found using X-tile software.ResultsOf 2037 patients included in SEER 18, 1147 underwent LND (56.3%); 389 (34.3%) had pathologically confirmed lymph node metastasis (LNM), and 316 (27.6%) had at least 6 LNDs. The median OS was worse for LND patients (34 months vs. 40 months, respectively), and this result remained after PSM. Male sex, age ≥60 years, tumor size > 5 cm, and LNM were independent prognostic risk factors for ICC. LNM ≥3 was associated with worse OS.ConclusionsOnly a few LNDs met the requirements per the guidelines. LND does not improve OS in ICC, and the best approach to LND and a better N staging method should be explored further.

A Nomogram in Predicting Risks of Intrahepatic Cholangiocarcinoma After Partial Hepatectomy for Hepatolithiasis

BackgroundHepatolithiasis 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. MethodsData 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. ResultsOf 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. ConclusionsA 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.

Non-Alcoholic Steatohepatitis as a Risk Factor for Intrahepatic Cholangiocarcinoma and Its Prognostic Role.

Simple SummaryThe prevalence of intrahepatic cholangiocarcinoma (iCCA) is rising. About 50% of iCCA arise in patients without known risk factors. We hypothesized that nonalcoholic fatty liver disease (NAFLD) and its most aggressive phenotype (NASH) could be risk factors for iCCA, similarly to other liver malignancies. We verified whether the prevalence of NAFLD and NASH was higher in the peritumor samples of iCCA patients compared with matched healthy controls (liver donors). We found the NASH (but not NAFLD) was over-represented in iCCA patients. Moreover, NASH patients had a shorter survival. Our results demonstrated that NASH is a risk factor for iCCA and underline the importance of dissecting the role of NASH from that of NAFLD as a whole. Prevention protocols for NASH patients should consider also the risk for iCCA and not only HCC. Studies aimed to find a direct pathogenic link between NASH and iCCA could add further relevant information.Non-alcoholic fatty liver disease (NAFLD) and its most aggressive form, non-alcoholic steatohepatitis (NASH), are causing a rise in the prevalence of hepatocellular carcinoma. Data about NAFLD/NASH and intrahepatic cholangiocarcinoma (iCCA) are few and contradictory, coming from population registries that do not correctly distinguish between NAFLD and NASH. We evaluated the prevalence of NAFLD and NASH in peritumoral tissue of resected iCCA (n = 180) and in needle biopsies of matched liver donors. Data of iCCA patients were subsequently analysed to compare NASH-related iCCA (Group A), iCCA arisen in a healthy liver (Group B) or in patients with classical iCCA risk factors (Group C). NASH was found in 22.5% of 129 iCCA patients without known risk factors and in 6.2% of matched controls (risk ratio 3.625, 95% confidence interval 1.723–7.626, p < 0.001), while NAFLD was equally represented in both groups. The overall survival of NASH-related iCCA was inferior to that of patients with healthy liver (38.5 vs. 48.1 months, p = 0.003) and similar to that of patients with known risk factors (31.9 months, p = 0.948), regardless of liver fibrosis. The multivariable Cox regression confirmed NASH as a prognostic factor (hazard ratio 1.773, 95% confidence interval 1.156–2.718, p = 0.009). We concluded that NASH (but not NAFLD) is a risk factor for iCCA and might affect its prognosis. Dissecting NASH from NAFLD by histology is necessary to correctly assess the actual role of these conditions. Prevention protocols for NASH patients should also consider the risk for iCCA and not only HCC. Mechanistic studies aimed to find a direct pathogenic link between NASH and iCCA could add further relevant information.

THU504 - Non-alcoholic steatohepatitis is a risk factor for intrahepatic cholangiocarcinoma and affects its long-time outcome: results from a multicenter international case-control study

THU504 - Non-alcoholic steatohepatitis is a risk factor for intrahepatic cholangiocarcinoma and affects its long-time outcome: results from a multicenter international case-control study

An Integrated Nomogram Combining Clinical Factors and Microtubule-Associated Protein 1 Light Chain 3B Expression to Predict Postoperative Prognosis in Patients with Intrahepatic Cholangiocarcinoma.

PurposeMicrotubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy, which is associated with the progression of carcinoma. Yet, it is still unclear whether LC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aim to explore the predictive value of LC3B on prognosis of ICC, and to establish a novel and available nomogram to predict relapse-free survival (RFS) and overall survival (OS) for these patients after curative-intent hepatectomy.Materials and MethodsFrom August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the Third Affiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolled patients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry.ResultsThe 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariate Cox regression analysis, independent risk factors for 5-year OS were cancer antigen 125, microvascular invasion, LC3B expression and lymph node metastasis. Except for the above 4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factors for 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and 0.747, respectively.ConclusionThe nomograms based on LC3B can be considered as effective models to predict postoperative survival for ICC patients.

741P - Genomic analysis of hepatobiliary lithiasis associated cholangiocarcinoma revealed a distinct subtype feature

BackgroundHepatic stone or lithiasis is a known risk factor for intrahepatic cholangiocarcinoma (ICC) in clinic, however the process and genomic background of the hepatobiliary lithiasis associated cholangiocarcinoma (BCAC) is completely unknown. MethodsHere, we retrospectively collected 81 paired intrahepatic cholangiocarcinoma (ICC) frozen cancerous and adjacent tissues including those patients combining biliary calculi. Whole exome sequence (WES, average 400x) and RNA-seq were applied to characterize this cohort. ResultsAmong them, prognosis of 64 patients from 2011 to 2013 revealed that BCAC had poor overall survival (18.6 months vs 28.6 months, P=0.024, Kaplan-Meier) compared to those of non-stone ICC. WES of 81 ICC patients showed that BCAC displayed a distinct mutation pattern, with EPHA2 and SMAD4 genes significantly enriched in BCAC (P<0.05, Fisher exact test) and epigenetic regulators IDH1, BAP1 and calcium channel RYR1 more enriched in non-calculi ICCs. Transcriptome profile showed that BCAC was different from canonical ICCs. Gene set enrichment analysis revealed that RESPONSE_TO_LIPID and CALCIUM_ION_BINDING were among the top significant changed gene sets, which might play important roles in BCACs. ConclusionsOur results demonstrate that BCAC is a distinct CCAs subtype and biliary calculi might be an independent factor for ICC and result in a poor prognosis. Legal entity responsible for the studyBGI-Shenzhen. FundingShenzhen Science and Technology Innovation Committee. DisclosureAll authors have declared no conflicts of interest.

Short- and Long-Term Outcomes of Liver Resection for Intrahepatic Cholangiocarcinoma Associated with the Metabolic Syndrome.

While the metabolic syndrome (MS) is being recognized as an important risk factor for intrahepatic cholangiocarcinoma (ICC), the outcomes of liver resection in this context remain poorly described. This study aims to report the short- and long-term results of hepatectomy for patients with MS as risk factor for the development of ICC (MS+). All patients undergoing hepatectomy for ICC between 2000 and 2016 at a single center were retrospectively analyzed. The perioperative outcomes of MS+ and ICCpatients without MS (MS-) were compared. Among 115 resected ICC patients, 40 (34.8%) were MS+ and 75 (65.2%) were MS-. MS+ exhibited an increased Charlson comorbidity index (5 ± 2 vs. 2 ± 2, p < 0.001) than MS- patients. While operative characteristics did not differ significantly between the 2 groups, MS+ experienced higher rate of major complications (62.5 vs. 29.3%, p = 0.001). On multivariate analysis, MS+ was an independent risk factor of major complication (HR 2.86, 95% CI 1.07-7.60, p = 0.036) and major cardiorespiratory complication (HR 4.35, 95% CI 1.50-12.62, p = 0.007). Pathological analysis revealed that MS+ displayed higher rates of non-alcoholic fatty liver disease (60.0 vs. 31.1%, p = 0.003) and non-alcoholic steatohepatitis (25 vs. 5.4%, p = 0.005). MS+ was independently associated with decreased risk of recurrence (HR 0.47, 95% CI 0.26-0.85, p = 0.001). MS+ accounts for 35% of resected ICC patients. The existence of significant cardiovascular comorbidities increases postoperative morbidity and requires specific management.

SAT-459-NASH as a risk factor for intrahepatic cholangiocarcinoma and its prognostic role: Case-control study

SAT-459-NASH as a risk factor for intrahepatic cholangiocarcinoma and its prognostic role: Case-control study

Role of nonalcoholic steatohepatitis as a risk factor for intrahepatic cholangiocarcinoma and its role in patients’ prognosis: A case-control study.

224 Background: The prevalence of intrahepatic cholangiocarcinoma (ICC) is rising worldwide. The current epidemics of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) might be partly responsible for this trend. Methods: Case control study investigating the prevalence of histology-confirmed NASH in peritumoral liver of resected ICC patients and controls (pre-explant biopsies of liver donors). Controls were matched for age and sex in a 2:1 fashion. Correlates between NASH, tumor characteristics and overall survival (OS) were also explored in the ICC cohort. Results: Between 2006 and 2017, 84 ICCs were resected in our Institution. Sixty-two (74%) had no apparent risk factors for ICC. Amongst this group, the prevalence of NAFLD and NASH was 45.2% and 24.2%,respectively, compared to 44.3 and 8.9% in the 124 matched liver donors (p = 1.000 and p = 0.007, respectively). The 5-year OS rate was 20.0% in NASH and 57.4% in ICC without either NASH and other risk factors (p = 0.017). Main tumor size, sex and NASH (hazard ratio 2.618 , 95% confidence interval 1.140-6.013, p = 0.023) were independent predictors of the OS at the multivariate Cox regression. Conclusions: NASH (but not NAFLD) acts as a risk factor for ICC and may affect its long-term outcome. A collaborative multicenter approach could confirm and strengthen these data.

Intrahepatic cholangiocarcinoma associated with the metabolic syndrome: characteristics and results of liver resection

Objective: To report short and long-term outcomes after hepatectomy for intrahepatic cholangiocarcinoma (ICC) related to metabolic syndrome (MS). Background: While the metabolic syndrome is being recognized as an important risk factor for ICC, MS-related ICC (MS+) remains poorly described. Methods: All patients undergoing hepatectomy for ICC between 2000-2016 at a single center were retrospectively analyzed. The peri-operative characteristics, pathological analysis and long-term outcomes of MS+ and ICC without MS (MS-) were compared. Results: Among 115 resected ICC patients, 40 (34.8%) were MS+ and 75 (65.2%) were MS-. MS+ patients were more frequently classified ASA>2 (37.5 vs. 5.3%, p=0.001) and exhibited increased Charlson comorbidity index (5±2 vs. 2±2, p< 0.001) than MS- patients. While operative characteristics did not differ significantly between the two groups, MS+ experienced higher rates of major complications (62.5 vs. 29.3%, p=0.001). On multivariate analysis, MS+ was an independent risk factor for both major complications (HR: 2.855, 95% CI: 1.072-7.599, p=0.036) and major cardiorespiratory complications (HR=4.356, 95% CI: 1.503-12.622, p=0.007). Pathological analysis revealed that MS+ displayed higher rates of non-alcoholic fatty liver disease (60.0 vs. 31.1%, p=0.003) and non-alcoholic steatohepatitis (25 vs. 5.4%, p=0.005) but significantly smaller lesions (64 vs. 76 mm, p=0.048). MS+ was independently associated with decreased risk of recurrence (HR: 0.462, 95% CI: 0.241-0.887, p=0.020). Conclusion: MS+ accounts for 35% of resected ICC patients. The prognosis of these patients seems to be more favorable but the existence of significant cardiovascular comorbidities increases postoperative morbidity and requires specific management.

Recurrent pyogenic cholangitis – an independent poor prognostic indicator for resectable intrahepatic cholangiocarcinoma: A propensity score matched analysis

BackgroundRecurrent pyogenic cholangitis (RPC) is a known risk factor for intrahepatic cholangiocarcinoma (ICC), whether it represents a poor prognostic factor remains controversial. The aim of this study was to investigate the post-hepatectomy oncological outcomes of patients with ICC and coexisting RPC. MethodA retrospective analysis with propensity score matching (PSM) was performed for comparison between ICC patient with and without RPC. ResultsThere were 143 patients with ICC with a median follow-up of 21 months. RPC was diagnosed in 18% of patients. The time from RPC diagnosis to ICC diagnosis was 137(47–481) months. The 3-year disease-free (DFS) and overall survival for the whole population was 34% and 43% respectively. Preoperative child score, elevated carcinoembryonic antigen, presence of microvascular invasion, multiple tumours, presence of postoperative complications and RPC were independent factors for DFS and OS. After PSM, 60 ICC patients who did not have RPC were compared with 20 ICC patients with RPC. Patients with RPC had significantly worse median DFS (10 vs 23 months, P = 0.020) and OS (15 vs 45 months, P = 0.004) when compared to the patients without RPC. ConclusionRPC represents a poor prognostic factor affecting outcomes after hepatectomy for patients with ICC.

Prognostic implications of hepatitis B virus infection in intrahepatic cholangiocarcinoma treated with first-line gemcitabine plus cisplatin.

Hepatitis B virus infection is a well-known risk factor for intrahepatic cholangiocarcinoma. However, its prognostic impact has rarely been investigated in advanced intrahepatic cholangiocarcinoma. Between April 2010 and May 2015, 296 patients with unresectable or metastatic intrahepatic cholangiocarcinoma who received gemcitabine plus cisplatin (GemCis) were categorized into a hepatitis B virus group (n=62; 21%) and a non-hepatitis B virus group (n=234; 79%). Clinicopathological features and survival outcomes were retrospectively reviewed and analyzed. The median age of patients was 59 years (range, 27-78). The median overall survival with first-line GemCis was 9.4 months (95% CI 8.4, 10.4). Compared to the non-hepatitis B virus group, the hepatitis B virus group was younger (median age, 57 vs. 61 years, P = 0.001), mainly male (74% vs. 57%, P = 0.02), and had lower frequency of elevated cancer antigen (CA) 19-9 (34% vs. 59%, P = 0.001) and alkaline phosphatase (43% vs. 61%, P = 0.01). In a univariate analysis, the hepatitis B virus infection showed a marginal relationship with poor overall survival compared to the non-hepatitis B virus infection (median, 8.3 vs. 10.0 months; P=0.13). A multivariate analysis of potential prognostic factors revealed a significant association with poor overall survival in the hepatitis B virus group (hazard ratio (HR) =1.50, P = 0.02). Initial metastatic disease (vs. recurrent/unresectable disease; HR=1.50), metastatic sites ⩾ 2 (vs. 0-1; HR=1.51), Eastern Cooperative Oncology Group performance status ⩾ 2 (vs. 0-1; HR=1.93), elevated total bilirubin (vs. normal; HR=1.83), and low albumin (vs. normal; HR=1.52) were significantly related to an unfavorable overall survival. This study suggests that the hepatitis B virus infection may be associated with distinctive clinicopathological characteristics and poor outcome in advanced intrahepatic cholangiocarcinoma treated with GemCis.

Occupational exposure to asbestos and risk of cholangiocarcinoma: a population-based case–control study in four Nordic countries

ObjectivesTo assess the association between occupational exposure to asbestos and the risk of cholangiocarcinoma (CC).MethodsWe conducted a case–control study nested in the Nordic Occupational Cancer (NOCCA) cohort. We studied 1458...

Early obesity and risk of cholangiocarcinoma in the United States.

239 Background: In the United States, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing over the last few decades. Despite the public health problem of obesity and the increasing incidence of ICC, the relationship between early adulthood obesity and ICC has never been examined in the American population. Methods: At the University of Texas MD Anderson Cancer Center we conducted a case-control study aimed at examining relationship between ICC and history of obesity after controlling for the potential confounding of several risk factors. Cases were patients with pathologically confirmed diagnosis of ICC. Controls were healthy subjects recruited from spouses of patients at MD Anderson who had cancers other than liver or gastrointestinal. Each case was frequency matched to 4 controls by age (± 5 years), sex, and race. Case patients and controls were interviewed for risk factors of liver cancer. A self-reported weight and body size pictogram at ages 20, 30, 40, 50, 60 was obtained from each participant. In 2016 we recruited 63 newly diagnosed patients with ICC who were compared to 252 healthy controls. Obesity was defined as body mass index (BMI) ≥ 30.0. Results: There was a significant 3 fold increase in ICC risk for obese individuals compared to those with normal weight. The estimated odds ratio (OR), 95%; confidence interval (CI) was 3.3 (1.3-9.1); P = .02. Obesity at the mid-20s, mid-30s, and mid- 40s was significantly associated with ICC risk; the estimated OR (95% CI) was 7.3 (2.8-19.7), 7 (2.4-20.9), and 4.8 (2-11.4), respectively. In addition, viral hepatitis, heavy alcohol use ( &gt; 40 ml ethanol/day), and family history of cancer were significantly associated with ICC. Underlying radiological, pathological, or clinical evidence of steatosis, fibrosis, and cirrhosis was significantly observed in 25% ICC patients with early obesity. Conclusions: We concluded that early adulthood obesity is a significant risk factor for ICC in USA where underlying fatty liver diseases can be a significant factor for ICC progression. Integration of obesity with other ICC risk factors into a risk model may lead to identify high-risk individuals. Future collaboration with other US institutions is highly warranted to highlight the mechanism of obesity-induced ICC.