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Intrahepatic cholangiocarcinoma

Tokio Higaki, Osamu Aramaki, Masamichi Moriguchi, Hisashi Nakayama, Yutaka Midorikawa, Tadatoshi Takayama
Conventional regimens for unresectable intrahepatic cholangiocarcinoma are considered of limited effectiveness. To evaluate the efficacy and toxicity of combination chemotherapy with hepatic arterial infusion of IA-call (a fine-powder formulation of cisplatin) plus oral S-1 in patients with unresectable intrahepatic cholangiocarcinoma. The clinicopathological data and long-term outcome of 12 patients who were received with IA-call plus S-1 were compared with those of 16 patients who were received other treatments, such as radiation therapy, trans-arterial chemoembolization, and systemic chemotherapy...
2018: Bioscience Trends
Liang-Qing Dong, Yang Shi, Li-Jie Ma, Liu-Xiao Yang, Xiao-Ying Wang, Shu Zhang, Zhi-Chao Wang, Meng Duan, Zhao Zhang, Long-Zi Liu, Bo-Hao Zheng, Zhen-Bin Ding, Ai-Wu Ke, Da-Ming Gao, Ke Yuan, Jian Zhou, Jia Fan, Ruibin Xi, Qiang Gao
BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (ICC) is the second-most lethal primary liver cancer. Little is known about intratumoral heterogeneity (ITH) and its impact on ICC progression. We aim to investigate its ITH in hope of helping develop new therapeutic strategies. METHODS: We obtained 69 spatially distinct regions from 6 operable ICCs. Patient-derived primary cancer cells (PDPCs) were established for each region, followed by whole-exome sequencing(WES) and multi-level validation...
March 15, 2018: Journal of Hepatology
Jie Wu, Shigui Yang, Kaijin Xu, Cheng Ding, Yuqing Zhou, Xiaofang Fu, Yiping Li, Min Deng, Chencheng Wang, Xiaoxiao Liu, Lanjuan Li
BACKGROUND & AIMS: We examined temporal trends in liver cancer incidence rates overall and by histological type from the years 1983 through 2007. We predict trends in liver cancer incidence rates through 2030 for selected Eastern and Southeastern Asian countries. METHODS: Data on yearly liver cancer incident cases by age group and sex were drawn from 6 major selected Eastern and Southeastern Asian countries or regions with cancer registries available in the CI5plus database, including China, Japan, Hong Kong Special Administrative Region (SAR), the Philippines, Singapore, and Thailand...
March 13, 2018: Gastroenterology
Keri E Lunsford, Milind Javle, Kirk Heyne, Rachna T Shroff, Reham Abdel-Wahab, Nakul Gupta, Constance M Mobley, Ashish Saharia, David W Victor, Duc T Nguyen, Edward A Graviss, Ahmed O Kaseb, Robert S McFadden, Thomas A Aloia, Claudius Conrad, Xian C Li, Howard P Monsour, A Osama Gaber, Jean-Nicolas Vauthey, R Mark Ghobrial
BACKGROUND: At present, intrahepatic cholangiocarcinoma is a contraindication for liver transplantation. However, previous studies in this field did not preselect patients on the basis of chemosensitivity or disease trajectory after neoadjuvant therapy. Experience with hilar cholangiocarcinoma has indicated that neoadjuvant therapy followed by liver transplantation in patients without disease progression results in a long-term survival benefit. We aimed to establish the potential efficacy of liver transplantation in patients with biologically responsive intrahepatic cholangiocarcinoma who have had sustained tumour stability or regression with neoadjuvant therapy...
March 13, 2018: Lancet. Gastroenterology & Hepatology
Peng Liu, Teng-Fei Zhou, Bao-An Qiu, Ying-Xiang Yang, Yong-Jian Zhu, Yang An, Wen-Chao Zhao, Yin-Tao Wu, Peng-Fei Ma, Jing-Bo Li, Nian-Xin Xia
Cholangiocarcinoma (CCA) is one of the most common hepatic and biliary malignancies, accounting for about 3% of all gastrointestinal tumors. GATA5 is a transcription factor capable of suppressing the development of various human cancer types. Transcriptional inactivation and CpG island (CGI) methylation of GATA3 and GATA5, two members of the GATA family of transcription factors, have been observed in some human cancers. But whether high-density CGI methylation of GATA5 is associated with the clinical course of CCA patients has not been clarified...
March 13, 2018: Translational Oncology
Jingxiao Wang, Mingjie Dong, Zhong Xu, Xinhua Song, Shanshan Zhang, Yu Qiao, Li Che, John Gordan, Kaiwen Hu, Yan Liu, Diego F Calvisi, Xin Chen
Liver cancer comprises a group of malignant tumors, among which hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common. ICC is especially pernicious and associated with poor clinical outcome. Studies have shown that a subset of human ICCs may originate from mature hepatocytes. However, the mechanisms driving the trans-differentiation of hepatocytes into malignant cholangiocytes remain poorly defined. We adopted lineage tracing techniques and an established murine hepatocyte-derived ICC model by hydrodynamic injection of activated forms of AKT (myr-AKT) and Yap (YapS127A) proto-oncogenes...
March 16, 2018: Oncogene
Beng Yang, Rongliang Tong, Hua Liu, Jingbang Wu, Diyu Chen, Zhengze Xue, Chaofeng Ding, Lin Zhou, Haiyang Xie, Jian Wu, Shusen Zheng
Intrahepatic cholangiocarcinoma (ICC) is a fatal, malignant tumor of the liver; effective diagnostic biomarkers and therapeutic targets for ICC have not been identified yet. High expression of H2A histone family member Z (H2A.Z) is a high-risk factor for poor prognosis in patients with breast cancer and primary hepatocellular cancer. However, the significance of H2A.Z and its expression in ICC remains unknown. The present study demonstrated that H2A.Z is overexpressed in ICC and expression of H2A.Z correlated with poor prognosis in patients with ICC...
April 2018: International Journal of Oncology
Julian A Gingold, Dandan Zhu, Dung-Fang Lee, Ahmed Kaseb, Jian Chen
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), the two most common primary liver cancers, represent the second most common cancer-related cause of death worldwide, with most cases being diagnosed at an advanced stage. Recent genome-wide studies have helped to elucidate the molecular pathogenesis and genetic heterogeneity of liver cancers. This review of the genetic landscape of HCC and iCCA discusses the most recent findings from genomic profiling and the current understanding of the pathways involved in the initiation and progression of liver cancer...
March 9, 2018: Trends in Molecular Medicine
Keisuke Kakisaka, Kei Endo, Ryo Sugimoto, Kazuyuki Ishida, Tamotsu Sugai, Yasuhiro Takikawa
Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver cancer, although its occurrence is relatively rare. Budd-Chiari syndrome (BCS) is characterized by outflow obstruction from the liver, with hepatocellular carcinoma being the most common cause of malignant BCS. In this case report, we describe the occurrence of an unrecognized ICC that induced BCS and esophageal achalasia.
March 9, 2018: Internal Medicine
Yi Shi, Jianfeng Bai, Shuwei Guo, Jiandong Wang
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy of the bile duct, representing the second most common primary liver cancer. Wntless (Wls) is a highly conserved transmembrane protein that shuttles palmitoylated Wnt proteins from the endoplasmic reticulum to the plasma membrane. Wls is highly expressed in various types of cancers and is essential for cell proliferation, anti-apoptotic activity, and survival. The profile of Wls expression and its clinical significance has not been well clarified in ICC...
2018: Tohoku Journal of Experimental Medicine
Vindya Abeysinghe, Siva Sundararajan, Luc Delriviere, Jonathan Tibballs
Unresectableintrahepaticcholangiocarcinoma has a very poor prognosis despite various treatment options. The case presented describes the diagnostic challenges of a young pregnant woman with unresectable cholangiocarcinoma. The current treatment options for cholangiocarcinoma have limited evidence and high recurrence rate. Given the young age of this patient, selective internal radiotherapy was trialled with traditional chemotherapy with a clinically significant result. This case highlights the delays when diagnosing cholangiocarcinoma in younger patients and the possibility of selective internal radiation therapy in combination with chemotherapy as a potential first-line treatment for a complete response in unresectable disease...
March 9, 2018: BMJ Case Reports
Jessica L Petrick, Peter T Campbell, Jill Koshiol, Jake E Thistle, Gabriella Andreotti, Laura E Beane-Freeman, Julie E Buring, Andrew T Chan, Dawn Q Chong, Michele M Doody, Susan M Gapstur, John Michael Gaziano, Edward Giovannucci, Barry I Graubard, I-Min Lee, Linda M Liao, Martha S Linet, Julie R Palmer, Jenny N Poynter, Mark P Purdue, Kim Robien, Lynn Rosenberg, Catherine Schairer, Howard D Sesso, Rashmi Sinha, Meir J Stampfer, Marcia Stefanick, Jean Wactawski-Wende, Xuehong Zhang, Anne Zeleniuch-Jacquotte, Neal D Freedman, Katherine A McGlynn
BACKGROUND: While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type. METHODS: The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410)...
March 9, 2018: British Journal of Cancer
David D Lee, Kristopher P Croome, Kaitlyn R Musto, Jose Melendez, Ghassan Tranesh, Raouf Nakhleh, C Burcin Taner, Justin H Nguyen, Tushar Patel, Denise M Harnois
Background While hepatocellular carcinoma (HCC) has become a common indication for liver transplantation (LT), intrahepatic cholangiocarcinoma (ICC) and combined-Hepatocellular-cholangiocarcioma (cHCC-CC) are historically contraindicated due to their aggressive behavior. Based on recent experiences, some groups have proposed a clinical trial investigating the role of LT for patients with early CC, defined as a single lesion ≤ 2cm. The purpose of this study is to assess the clinicopathologic features and outcomes following LT for patients who were initially diagnosed with HCC and subsequently found to have either ICC or cHCC-CC on explant...
March 7, 2018: Liver Transplantation
Xiao-Hong Pu, Qing Ye, Jun Yang, Hong-Yan Wu, Xi-Wei Ding, Jiong Shi, Liang Mao, Xiang-Shan Fan, Jun Chen, Yu-Dong Qiu, Qin Huang
Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer rarely curable by surgery that is increasing rapidly in incidence. Chromosomal translocations and amplifications of the fibroblast growth factor receptor 2 (FGFR2) locus are present in several kinds of tumors including ICC, but their incidence has not been assessed in Chinese patients. Using break-apart probes and by determining the ratios of FGFR2/chromosome enumeration probe (CEP) 10 double-color probes, we evaluated 122 ICCs for the presence of FGFR2 translocations and amplifications, respectively, by fluorescence in situ hybridization (FISH)...
March 4, 2018: Human Pathology
Long-Zi Liu, Liu-Xiao Yang, Bo-Hao Zheng, Ping-Ping Dong, Xin-Yang Liu, Zhi-Chao Wang, Jian Zhou, Jia Fan, Xiao-Ying Wang, Qiang Gao
BACKGROUND AND OBJECTIVES: Frequently aberrant expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) have been observed in several human cancers. In this retrospective study, we aimed at investigating the prognostic significance of CK7 and CK19 in intrahepatic cholangiocarcinoma (ICC). METHODS: Immunohistochemistry was performed to assess CK7 and CK19 expression on tissue microarrays in training cohort enrolling 214 ICC patients and validation cohort comprising 108 ICC patients...
March 7, 2018: Journal of Surgical Oncology
Sivesh K Kamarajah
BACKGROUND: Recently, the AJCC has released its 8th edition changes to the staging system for intrahepatic cholangiocarcinoma (iCCA). This study sought to validate the proposed changes to the 8th edition of AJCC system for T and N classification of iCCA using a population-based data set. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database (1998-2013), patients undergoing resection or non-surgical management for non-metastatic iCCA were identified...
March 7, 2018: Journal of Gastrointestinal Cancer
Tatsuaki Sumiyoshi, Yasuo Shima, Takehiro Okabayashi, Yuji Negoro, Yasuhiro Shimada, Jun Iwata, Manabu Matsumoto, Yasuhiro Hata, Yoshihiro Noda, Kenta Sui, Taijiro Sueda
OBJECTIVE: Surgical resection is the only available treatment for achieving long-term survival in cholangiocarcinoma. The purpose of this study is to elucidate the utility of chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma. METHODS: Unresectable locally advanced cholangiocarcinoma was defined as those in which radical surgery could not be achieved even with aggressive surgical procedure. Fifteen candidates (7 intrahepatic cholangiocarcinomas and 8 hilar cholangiocarcinomas) underwent chemoradiotherapy...
March 6, 2018: World Journal of Surgery
Yu Huang, Yang Kong, Lufei Zhang, Tianyu He, Xiaohu Zhou, Yingcai Yan, Linshi Zhang, Dongkai Zhou, Sinan Lu, Jiarong Zhou, Lin Zhou, Haiyang Xie, Shusen Zheng, Weilin Wang
Integrin subunit alpha 3 (ITGA3) interacts with a beta 1 subunit to form a member of the integrin family. Integrins are heterodimeric integral membrane proteins that serve as cell surface adhesion proteins. In this research, we investigated the biological function of this protein in human intrahepatic cholangiocarcinoma (ICC) for the first time. Here, using Western blotting and immunohistochemistry assays, we discovered that ITGA3 was overexpressed in ICC cell lines and ICC patients. Moreover, we found ITGA3 expression correlated with several clinicopathological features, including tumor size, lymph node metastasis, and the TNM stage...
2018: BioMed Research International
Xiaobo Cai, Jun Li, Xiaodong Yuan, Jingbo Xiao, Steven Dooley, Xinjian Wan, Honglei Weng, Lungen Lu
BACKGROUND: CD133 is a marker of stem cells as well cancer stem cells. This study investigated the association between CD133 expression in cancer cells and the clinical outcome of non-mucin producing intrahepatic cholangiocarcinoma (ICC). METHODS: Fifty-seven non-mucin producing ICC patients were enrolled in this study. Immunohistochemistry (IHC) and immunofluorescence staining for CD133 as well as other cancer-associated proteins, including cytokeratin 19, TGF-β1, p-Smad2 and epithelial-mesenchymal transition (EMT) markers S100A4, E-Cadherin and Vimentin were analyzed...
March 6, 2018: Journal of Translational Medicine
Aude Merdrignac, Gaëlle Angenard, Coralie Allain, Kilian Petitjean, Damien Bergeat, Pascale Bellaud, Allain Fautrel, Bruno Turlin, Bruno Clément, Steven Dooley, Laurent Sulpice, Karim Boudjema, Cédric Coulouarn
Intrahepatic cholangiocarcinoma (iCCA) is a deadly liver primary cancer associated with poor prognosis and limited therapeutic opportunities. Active transforming growth factor beta (TGFβ) signaling is a hallmark of the iCCA microenvironment. However, the impact of TGFβ on the transcriptome of iCCA tumor cells has been poorly investigated. Here, we have identified a specific TGFβ signature of genes commonly deregulated in iCCA cell lines, namely HuCCT1 and Huh28. Novel coding and noncoding TGFβ targets were identified, including a TGFβ-induced long noncoding RNA (TLINC), formerly known as cancer susceptibility candidate 15 (CASC15)...
March 2018: Hepatology Communications
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