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Cholangiocarcinoma BTC

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https://read.qxmd.com/read/30682771/mtor-inhibitors-in-advanced-biliary-tract-cancers
#1
REVIEW
Chao-En Wu, Ming-Huang Chen, Chun-Nan Yeh
Patients with advanced biliary tract cancers (BTCs), including cholangiocarcinoma (CCA), have poor prognosis so novel treatment is warranted for advanced BTC. In current review, we discuss the limitations of current treatment in BTC, the importance of mTOR signalling in BTC, and the possible role of mTOR inhibitors as a future treatment in BTC. Chemotherapy with gemcitabine-based chemotherapy is still the standard of care and no targeted therapy has been established in advanced BTC. PI3K/AKT/mTOR signaling pathway linking to several other pathways and networks regulates cancer proliferation and progression...
January 24, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30675238/an-atlas-for-clinical-target-volume-definition-including-elective-nodal-irradiation-in-definitive-radiotherapy-of-biliary-cancer
#2
Silvia Bisello, Matteo Renzulli, Milly Buwenge, Lucia Calculli, Giuseppina Sallustio, Gabriella Macchia, Francesco Deodato, Giancarlo Mattiucci, Silvia Cammelli, Alessandra Arcelli, Lucia Giaccherini, Francesco Cellini, Giovanni Brandi, Sara Guerri, Savino Cilla, Rita Golfieri, Lorenzo Fuccio, Alessio G Morganti, Alessandra Guido
Radiotherapy (RT) is a treatment option for advanced biliary tract cancer (BTC), often combined with sequential and/or concurrent chemotherapy. The use of modern RT techniques requires accurate clinical target volume (CTV) definition and delineation. However, guidelines for CTV delineation in BTC are lacking. Therefore, the aim of this study was to propose a computer tomography (CT) atlas for CTV definition of BTC. We previously proposed guidelines to define the nodal CTV (CTV-N) in BTC. In this study, based on a literature analysis, we defined the margins to be added to the gross tumor volume (GTV; subclinical and microscopic disease) to define the primary tumor CTV (CTV-T)...
February 2019: Oncology Letters
https://read.qxmd.com/read/30659304/molecular-targeting-of-her2-overexpressing-biliary-tract-cancer-cells-with-trastuzumab-emtansine-an-antibody-cytotoxic-drug-conjugate
#3
Yoriko Yamashita-Kashima, Yasushi Yoshimura, Takaaki Fujimura, Sei Shu, Mieko Yanagisawa, Keigo Yorozu, Koh Furugaki, Ryota Higuchi, Junichi Shoda, Naoki Harada
PURPOSE: Trastuzumab emtansine (T-DM1) provides clinical benefit in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2). However, its efficacy against biliary tract cancers (BTC) has not been evaluated. In this study, the effectiveness of T-DM1 in various BTC cell lines and xenograft models with different levels of HER2 expression was investigated. METHODS: HER2 expression status in xenografts and patient tissue microarrays was assessed by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)...
January 18, 2019: Cancer Chemotherapy and Pharmacology
https://read.qxmd.com/read/30645774/biliary-tract-cancer-incidence-and-trends-in-the-united-states-by-demographic-group-1999-2013
#4
Alison L Van Dyke, Meredith S Shiels, Gieira S Jones, Ruth M Pfeiffer, Jessica L Petrick, Jennifer L Beebe-Dimmer, Jill Koshiol
BACKGROUND: Biliary tract cancers (BTCs) are rare but deadly cancers (gallbladder cancer [GBC], intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], and ampulla of Vater cancer [AVC]). A recent US study reported increasing GBC incidence among people younger than 45 years and blacks; however, it did not examine trends for other biliary tract sites. METHODS: This study characterized demographic differences in BTC incidence rates and time trends by anatomic site...
January 15, 2019: Cancer
https://read.qxmd.com/read/30602096/somatic-mutations-from-whole-exome-sequencing-analysis-of-the-patients-with-biliary-tract-cancer
#5
Kyong-Ah Yoon, Sang Myung Woo, Yun-Hee Kim, Sun-Young Kong, Sung-Sik Han, Sang-Jae Park, Woo Jin Lee
Biliary tract cancer (BTC) is one of the rare cancers and associated with poor prognosis. To understand genetic characteristics of BTC, we analyzed whole exome sequencing (WES) data and identified somatic mutations in the patients with BTC. Tumors and matched blood or normal samples were obtained from seven patients with cholangiocarcinoma who were underwent surgical resection. We discovered inactivating mutations of tumor suppressor genes including APC, TP53, and ARID1A genes in three patients. Activating mutations of KRAS and NRAS were also identified...
December 2018: Genomics & Informatics
https://read.qxmd.com/read/30448774/statin-use-and-reduced-risk-of-biliary-tract-cancers-in-the-uk-clinical-practice-research-datalink
#6
Zhiwei Liu, Rotana Alsaggaf, Katherine A McGlynn, Lesley A Anderson, Huei-Ting Tsai, Bin Zhu, Yue Zhu, Sam M Mbulaiteye, Shahinaz M Gadalla, Jill Koshiol
OBJECTIVE: To evaluate the association between statin use and risk of biliary tract cancers (BTC). DESIGN: This is a nested case-control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time and years of enrolment in the general practice using incidence density sampling...
November 17, 2018: Gut
https://read.qxmd.com/read/30419338/pharmacologic-il-6r%C3%AE-inhibition-in-cholangiocarcinoma-promotes-cancer-cell-growth-and-survival
#7
Florian Kleinegger, Eva Hofer, Christina Wodlej, Nicole Golob-Schwarzl, Anna Maria Birkl-Toeglhofer, Alexander Stallinger, Johannes Petzold, Anna Orlova, Stefanie Krassnig, Robert Reihs, Tobias Niedrist, Harald Mangge, Young Nyun Park, Michael Thalhammer, Ariane Aigelsreiter, Sigurd Lax, Christoph Garbers, Peter Fickert, Stefan Rose-John, Richard Moriggl, Beate Rinner, Johannes Haybaeck
Biliary tract cancer (BTC) represents a malignant tumor of the biliary tract including cholangiocarcinoma (CCA) and the carcinoma of the gallbladder (GBC) with a 5-year survival rate between 5 and 18% due to late diagnosis and rapid disease progression. Chronic inflammation is one of the main risk factors for CCA and GBC in particular. IL-6, as a mediator of inflammation, can act through a membrane-bound receptor alpha-chain (mIL-6R, "IL-6 classic signaling") or via soluble forms (sIL-6R, "IL-6 trans-signaling")...
November 9, 2018: Biochimica et biophysica acta. Molecular basis of disease
https://read.qxmd.com/read/30335866/the-her3-pathway-as-a-potential-target-for-inhibition-in-patients-with-biliary-tract-cancers
#8
Angela Lamarca, Salvatore Galdy, Jorge Barriuso, Sharzad Moghadam, Elizabeth Beckett, Jane Rogan, Alison Backen, Catherine Billington, Mairéad G McNamara, Richard A Hubner, Angela Cramer, Juan W Valle
INTRODUCTION: Expression of human epidermal growth factor receptor (HER)2 and HER3 have been investigated in small BTC studies using variable scoring systems. METHODS: HER2 and HER3 overexpression/amplification were explored following internationally agreed guidelines using immunohistochemistry (IHC) and fluorescent in-situ hybridisation (FISH), respectively. Logistic regression and survival analysis (Kaplan Meier, Log rank test and Cox Regression) were used for statistical analysis...
2018: PloS One
https://read.qxmd.com/read/30325974/methylated-promoter-dna-of-cdo1-gene-and-preoperative-serum-ca19-9-are-prognostic-biomarkers-in-primary-extrahepatic-cholangiocarcinoma
#9
Shuji Nakamoto, Yusuke Kumamoto, Kazuharu Igarashi, Yoshiki Fujiyama, Nobuyuki Nishizawa, Shigenori Ei, Hiroshi Tajima, Takashi Kaizu, Masahiko Watanabe, Keishi Yamashita
BACKGROUND: Promoter DNA methylation of Cysteine dioxygenase type1 (CDO1) gene has been clarified as a molecular diagnostic and prognostic indicator in various human cancers. The aim of this study is to investigate the clinical relevance of CDO1 methylation in primary biliary tract cancer (BTC). METHODS: CDO1 DNA methylation was assessed by quantitative methylation-specific PCR in 108 BTC tumor tissues and 101 corresponding normal tissues. BTC was composed of extrahepatic cholangiocarcinoma (EHCC) (n = 81) and ampullary carcinoma (AC) (n = 27)...
2018: PloS One
https://read.qxmd.com/read/30218788/biliary-tract-cancer-state-of-the-art-and-potential-role-of-dna-damage-repair
#10
REVIEW
Angela Lamarca, Jorge Barriuso, Mairéad G McNamara, Juan W Valle
Biliary tract cancers (BTCs), including cholangiocarcinoma, gallbladder cancer and ampullary cancers, are poor-prognosis malignancies. Most patients are diagnosed with advanced disease, when treatment is limited to palliative chemotherapy. First line chemotherapy is usually administered in the form of cisplatin and gemcitabine. Benefit from second line chemotherapy is still to be confirmed. Even though new systemic treatment targets have been recognised, especially in patients with intrahepatic cholangiocarcinoma (e...
November 2018: Cancer Treatment Reviews
https://read.qxmd.com/read/29934122/the-role-of-sex-in-the-outcomes-of-patients-with-biliary-tract-cancers-remains-unclear-a-population-based-study
#11
Madeline Lemke, Yvonne DeWit, Sulaiman Nanji, Christopher M Booth, Jennifer A Flemming
BACKGROUND: Differences in outcomes between males and females with biliary tract cancer (BTC) has been previously reported but not studied. METHODS: This was a population-based retrospective cohort study of patients undergoing BTC resection in Ontario between 2002 and 2012. Descriptive statistics on patient, disease, and treatment-related factors in each BTC subtype were reported. Kaplan Meier Curves and Cox Proportional Hazards analysis were used to examine the univariate relationship between sex and overall survival...
June 19, 2018: American Journal of Surgery
https://read.qxmd.com/read/29707118/identification-of-a-serum-biomarker-panel-for-the-differential-diagnosis-of-cholangiocarcinoma-and-primary-sclerosing-cholangitis
#12
Joy Cuenco, Natascha Wehnert, Oleg Blyuss, Anna Kazarian, Harry J Whitwell, Usha Menon, Anne Dawnay, Michael P Manns, Stephen P Pereira, John F Timms
The non-invasive differentiation of malignant and benign biliary disease is a clinical challenge. Carbohydrate antigen 19-9 (CA19-9), leucine-rich α2-glycoprotein (LRG1), interleukin 6 (IL6), pyruvate kinase M2 (PKM2), cytokeratin 19 fragment (CYFRA21.1) and mucin 5AC (MUC5AC) have reported utility for differentiating cholangiocarcinoma (CCA) from benign biliary disease. Herein, serum levels of these markers were tested in 66 cases of CCA and 62 cases of primary sclerosing cholangitis (PSC) and compared with markers of liver function and inflammation...
April 3, 2018: Oncotarget
https://read.qxmd.com/read/29572828/the-prognostic-impact-of-differentiation-at-the-invasive-front-of-biliary-tract-cancer
#13
Satoshi Okubo, Shuichi Mitsunaga, Yuichiro Kato, Motohiro Kojima, Motokazu Sugimoto, Naoto Gotohda, Shinichiro Takahashi, Ryuichi Hayashi, Masaru Konishi
BACKGROUND: The invasive front of tumor can provide prognostic information in many cancers. We investigated the prognostic morphological factors at the invasive front including tumor differentiation (Difinv ) and tumor budding (Bud) in biliary tract cancer (BTC). METHODS: The resected specimen from the 299 BTC patients were examined. Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer were found in 16%, 48%, 17%, and 19%, respectively...
May 2018: Journal of Surgical Oncology
https://read.qxmd.com/read/29507708/survival-rates-are-higher-in-married-patients-with-biliary-tract-cancer-a-population-based-study
#14
Wei Song, Dong-Liu Miao, Lei Chen
Marital status has been identified as a prognostic factor in multiple malignancies. In this study, we assessed the prognostic value of marital status in 24,035 patients from the Surveillance, Epidemiology, and End Results database diagnosed with biliary tract cancer (BTC) between 2004 and 2014. Widowed patients were more likely to be women, elderly (> 60 years), have gallbladder cancer, and have localized SEER Stage disease than all other patients. Marital status was identified as an independent prognostic factor in both univariate and multivariate analyses, and cause-specific survival (CSS) rates were higher in married patients than unmarried patients...
February 6, 2018: Oncotarget
https://read.qxmd.com/read/29448202/the-correlation-between-serum-chemokines-and-clinical-outcome-in-patients-with-advanced-biliary-tract-cancer
#15
Su Jin Lee, Jung Eun Kim, Seung Tae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Won Ki Kang, Young Suk Park, Ho Yeong Lim
BACKGROUND: Biliary tract cancers (BTCs) are known to have a dismal prognosis. A number of chemokines play important roles in the progress of BTCs. However, the serum levels of chemokines in BTCs have not yet been explored. METHODS: The sera of healthy donors (n = 8) and patients with BTCs who were enrolled in second line sunitinib trials (n = 27) were collected. The concentrations of three kinds of chemokines (CXCL5, CXCL8 and CXCL12) were measured using ELISA assay...
April 2018: Translational Oncology
https://read.qxmd.com/read/29360550/genomic-characterization-of-biliary-tract-cancers-identifies-driver-genes-and-predisposing-mutations
#16
Christopher P Wardell, Masashi Fujita, Toru Yamada, Michele Simbolo, Matteo Fassan, Rosa Karlic, Paz Polak, Jaegil Kim, Yutaka Hatanaka, Kazuhiro Maejima, Rita T Lawlor, Yoshitsugu Nakanishi, Tomoko Mitsuhashi, Akihiro Fujimoto, Mayuko Furuta, Andrea Ruzzenente, Simone Conci, Ayako Oosawa, Aya Sasaki-Oku, Kaoru Nakano, Hiroko Tanaka, Yujiro Yamamoto, Kubo Michiaki, Yoshiiku Kawakami, Hiroshi Aikata, Masaki Ueno, Shinya Hayami, Kunihito Gotoh, Shun-Ichi Ariizumi, Masakazu Yamamoto, Hiroki Yamaue, Kazuaki Chayama, Satoru Miyano, Gad Getz, Aldo Scarpa, Satoshi Hirano, Toru Nakamura, Hidewaki Nakagawa
BACKGROUND & AIMS: Biliary tract cancers (BTCs) are clinically and pathologically heterogeneous and respond poorly to treatment. Genomic profiling can offer a clearer understanding of their carcinogenesis, classification and treatment strategy. We performed large-scale genome sequencing analyses on BTCs to investigate their somatic and germline driver events and characterize their genomic landscape. METHODS: We analyzed 412 BTC samples from Japanese and Italian populations, 107 by whole-exome sequencing (WES), 39 by whole-genome sequencing (WGS), and a further 266 samples by targeted sequencing...
May 2018: Journal of Hepatology
https://read.qxmd.com/read/29352306/prognostic-and-predictive-role-of-egfr-pathway-alterations-in-biliary-cancer-patients-treated-with-chemotherapy-and-anti-egfr
#17
RANDOMIZED CONTROLLED TRIAL
Caterina Peraldo-Neia, Giuliana Cavalloni, Elisabetta Fenocchio, Celeste Cagnazzo, Loretta Gammaitoni, Stefano Cereda, Guglielmo Nasti, Maria Antonietta Satolli, Giuseppe Aprile, Michele Reni, Antonio Avallone, Rosella Spadi, Tiziana Venesio, Vittoria Martin, Claudio Doglioni, Milo Frattini, Massimo Aglietta, Francesco Leone
The association of anti-EGFR to gemcitabine and oxaliplatin (GEMOX) chemotherapy did not improve survival in biliary tract carcinoma (BTC) patients. Multiple mechanisms might be involved in the resistance to anti-EGFR. Here, we explored the mutation profile of EGFR extracellular domain (ECD), of tyrosine kinase domain (TKD), and its amplification status. EGFR mutational status of exons 12, 18-21 was analyzed in 57 tumors by Sanger sequencing. EGFR amplification was evaluated in 37 tumors by Fluorescent In Situ Hybridization (FISH)...
2018: PloS One
https://read.qxmd.com/read/29238914/clinical-and-genetic-implications-of-dna-mismatch-repair-deficiency-in-biliary-tract-cancers-associated-with-lynch-syndrome
#18
Jordan M Cloyd, Yun Shin Chun, Naruhiko Ikoma, Jean Nicolas Vauthey, Tlhomas A Aloia, Amanda Cuddy, Miguel A Rodriguez-Bigas, Y Nancy You
PURPOSE: Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS. METHODS: A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2...
March 2018: Journal of Gastrointestinal Cancer
https://read.qxmd.com/read/29164423/successful-radical-surgical-resection-of-initially-unresectable-intrahepatic-cholangiocarcinoma-by-downsizing-chemotherapy-with-gemcitabine-plus-cisplatin-a-case-report
#19
Ryosuke Takayanagi, Shigetsugu Takano, Kensuke Sugiura, Hideyuki Yoshitomi, Katsunori Furukawa, Tsukasa Takayashiki, Satoshi Kuboki, Atsushi Kato, Masaru Miyazaki, Masayuki Ohtsuka
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a subtype of biliary tract cancer (BTC). Recently, downsizing chemotherapy has been applied to initially unresectable BTCs, including ICC. CASE PRESENTATION: We report a case of liver resection in a 23-year-old woman who was diagnosed with initially unresectable ICC attached to the inferior vena cava, with portal vein (PV) cavernous transformation. Positron emission tomography (PET) showed fluorodeoxyglucose (FDG) uptake in the para-aortic lymph nodes...
November 21, 2017: Surgical Case Reports
https://read.qxmd.com/read/29113399/dck-expression-a-potential-predictive-biomarker-in-the-adjuvant-gemcitabine-chemotherapy-for-biliary-tract-cancer-after-surgical-resection-results-from-a-phase-ii-study
#20
Sang Myung Woo, Kyong-Ah Yoon, Eun Kyung Hong, Weon Seo Park, Sung-Sik Han, Sang-Jae Park, Jungnam Joo, Eun Young Park, Ju Hee Lee, Yun-Hee Kim, Tae Hyun Kim, Woo Jin Lee
The role of adjuvant therapy following resection of biliary tract cancer (BTC) remains unclear. We therefore evaluated the feasibility and toxicity of adjuvant gemcitabine in patients with BTC. This clinical phase II trial was an open-label, single center, single-arm study. Within 8 weeks after gross complete resection of BTC, patients were started on intravenous infusions of gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of every 28-day cycle. Intratumoral expression of cytidine deaminase (CDA), human equilibrative transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit 1 (RRM1) was measured by immunohistochemistry...
October 6, 2017: Oncotarget
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