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Multidisciplinary perspective of hepatocellular carcinoma: A Pacific Northwest experience

World Journal of Hepatology 2015年第11期7卷 1460-1483页

作者： Matthew M Yeh Raymond S Yeung Smith Apisarnthanarax Renuka Bhattacharya Carlos Cuevas William P Harris tony lim kiat hon Siddharth A Padia James O Park Kevin M Riggle Sayed S Daoud Department of Pathology University of Washington School of Medicine Department of Medicine University of Washington School of Medicine Northwest Liver Research Program Depart-ment of Surgery University of Washington School of Medicine Department of Radiation Oncology University of Washington School of Medicine Department of Radiology University of Washington School of Medicine Seattle Department of Pathology Singapore General Hospital Department of Pharmaceutical Sciences Washington State University Health Sciences

Hepatocellular carcinoma(HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would:(1) greatly facilitate the identification of patients at risk;(2) prompt efforts to decrease risk factors; and(3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC,this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, noninvasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics.

关键词： Genetic alterations Epigenetic alterations Diagnostic pathology Diagnostic imaging Surgicalmodality Liver transplantation Locoregional therapy Sorafenib Hepatocellular carcinoma Liver resection

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Overview of multiplex immunohistochemistry/immunofluorescence techniques in the era of cancer immunotherapy

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Cancer Communications 2020年第4期40卷 135-153页

作者： Wei Chang Colin Tan Sanjna Nilesh Nerurkar Hai Yun Cai Harry Ho Man Ng Duoduo Wu Yu Ting Felicia Wee Jeffrey Chun Tatt lim Joe Yeong tony kiat hon lim Yong Loo Lin School of Medicine National University of SingaporeSingapore169856Singapore Department of Anatomical Pathology Singapore General HospitalSingapore169856Singapore Institute of Molecular Cell Biology(IMCB) Agency of ScienceTechnology and Research(A*STAR)Singapore169856Singapore Singapore Immunology Network Agency of Science(SIgN)Technology and Research(A*STAR)Singapore169856Singapore Duke-NUS Medical School Singapore169856Singapore

Conventional immunohistochemistry(IHC)is a widely used diagnostic technique in tissue ***,this technique is associated with a number of limitations,including high inter-observer variability and the capacity to label only one marker per tissue *** review details various highly multiplexed techniques that have emerged to circumvent these constraints,allowing simultaneous detection of multiple markers on a single tissue section and the comprehensive study of cell composition,cellular functional and cell-cell *** these techniques,multiplex Immunohistochemistry/Immunofluorescence(mIHC/IF)has emerged to be particularly ***/IF provides high-throughput multiplex staining and standardized quantitative analysis for highly reproducible,efficient and cost-effective tissue *** technique has immediate potential for translational research and clinical practice,particularly in the era of cancer immunotherapy.

关键词： immunofluorescence immunohistochemistry immunotherapy multiplex overview

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Hepatic adenoma mimicking a metastatic lesion on computed tomography-positron emission tomography scan

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World Journal of Gastroenterology 2013年第27期19卷 4432-4436页

作者： Darryl lim Ser Yee Lee kiat hon lim Chung Yip Chan Department of General Surgery Singapore General Hospital Department of Hepatopancreatobiliary and Transplant Surgery Singapore General Hospital Department of Surgical Oncology National Cancer Centre Duke-National University of Singapore (NUS) Graduate Medical School Department of Pathology Singapore General Hospital

Positron emission tomography (PET) using 18F-fluorodeoxyglucose ( 18F-FDG) is an imaging modality which reflects cellular glucose metabolism. Most malignant cells accumulate and trap 18F-FDG, allowing the visualisation of increased uptake. It is hence widely used to differentiate malignant from benign lesions. "False positive" findings of hepatic lesions have been described in certain instances such as hepatic abscesses, but are rare in cases involving hepatocellular adenomas. To our knowledge, there have been only 7 reports in the English literature documenting PET-avid hepatocellular adenomas; 6 of the 7 reports were published in the last 3 years with the first report by Patel et al. We report the case of a 44-year-old Chinese female patient with a history of cervical adenocarcinoma, referred for a hepatic lesion noted on a surveillance computed tomography (CT) scan. A subsequent CT-PET performed showed a hypermetabolic lesion (standardized uptake value 7.9) in segment Ⅳb of the liver. After discussion at a multidisciplinary hepato-pancreato-biliary conference, the consensus was that of a metastatic lesion from her previous cervical adenocarcinoma, and a resection of the hepatic lesion was performed. Histology revealed features consistent with a hepatocyte nuclear factor-1 α inactivated steatotic hepatocellular adenoma.

关键词： Hepatic adenoma Positron emission tomography 18F-fluorodeoxyglucose Hepatocellular adenoma Hepatocyte nuclear factor-1 α

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Pancreatic lymphangioma:two case reports from an institutional experience with a rare entity and review of literature

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Journal of Pancreatology 2022年第2期5卷 98-109页

作者： Alfonso Tan-Garcia Ser Yee Lee Jen San Wong Thomas W.T.Ho Keng Sin Ng kiat hon tony lim Division of Pathology Department of Anatomical PathologySingapore General HospitalSingapore Surgical Associates Mount Elizabeth Medical CentreSingapore Department of Hepatopancreatobiliary and Transplant Surgery Singapore General HospitalSingapore Hepatobiliary and Pancreatic Surgery Centre Mount Elizabeth Medical CentreSingapore Digestive Surgical Oncology Department of Diagnostic Imaging Mount Alvernia HospitalSingapore

Pancreatic lymphangiomas are very rare benign cystic lesions that pose a diagnostic dilemma due to their resemblance to other non-neoplastic and neoplastic pancreatic cystic *** such,pancreatic lymphangiomas are frequently diagnosed only after histological examination of the excised *** present 2 cases of pancreatic lymphangioma,determine its prevalence at our institution and perform a detailed review of published literature since *** 1 is a 36-year-old male and case 2 is a 35-year-old female,both of which presented with abdominal *** were the only cases of pancreatic lymphangiomas reported at our institution since *** reviewed 69 cases of pancreatic lymphangiomas from 52 *** affects predominantly females with a median age of 43 and such patients typically present with abdominal pain(58.8%)or are asymptomatic(27.9%).The median size is 8.6 cm,the most common location is the head of pancreas and the most common imaging finding is that of a multilocular *** of patients underwent surgical resection(69.6%).Endoscopic ultrasound-guided fine-needle aspiration features of pancreatic lymphangiomas include chylous cyst fluid,elevated fluid triglyceride levels(15/16 cases)and numerous lymphocytes on *** majority of patients with elevated fluid triglyceride levels(13/15 cases)were managed *** lymphangiomas are rare pancreatic cystic lesions that may be diagnosed preoperatively using a multidisciplinary and multimodal approach involving clinical,radiological,biochemical and cytological features,allowing greater confidence in the selection of patients who can be managed conservatively.

关键词： Case report Cystic Diagnostic features Literature review Lymphangioma management Pancreas Prevalence

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肿瘤免疫治疗时代的多重免疫组织化学/免疫荧光技术

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癌症 2021年第9期40卷 367-387页

常规免疫组织化学(immunohistochemistry,IHC)是组织病理学中广泛应用的诊断技术。但该技术存在诸多局限性,包括观察者间的变异性高,每张组织切片仅能标记一个标志物。本文详细描述了各种多重检测技术,这些技术克服了上述局限性,可在单... 详细信息

常规免疫组织化学(immunohistochemistry,IHC)是组织病理学中广泛应用的诊断技术。但该技术存在诸多局限性,包括观察者间的变异性高,每张组织切片仅能标记一个标志物。本文详细描述了各种多重检测技术,这些技术克服了上述局限性,可在单张切片上同时检测多个标志物,可对细胞组成、细胞功能和细胞间相互作用进行整合研究。在这些技术中,多重免疫组织化学/免疫荧光(multiplex immunohistochemistry/immunofluorescence,mIHC/IF)已成为最具应用前景的技术。mIHC/IF为开展高重复性、高效、高性价比的组织研究提供了高通量多重染色技术和标准化的定量分析。该技术在转化研究和临床实践中,尤其是肿瘤免疫治疗中极具应用价值。

关键词：免疫荧光免疫组织化学免疫治疗多重概述

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Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma:the PLANET study

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National Science Review 2022年第3期9卷 96-109页

作者： Weiwei Zhai Hannah Lai Neslihan Arife Kaya Jianbin Chen Hechuan Yang Bingxin Lu Jia Qi lim Siming Ma Sin Chi Chew Khi Pin Chua Jacob Josiah Santiago Alvarez Pauline Jieqi Chen Mei Mei Chang Lingyan Wu Brian K.P.Goh Alexander Yaw-Fui Chung Chung Yip Chan Peng Chung Cheow Ser Yee Lee Juinn Huar Kam Alfred Wei-Chieh Kow Iyer Shridhar Ganpathi Rawisak Chanwat Jidapa Thammasiri Boon Koon Yoong Diana Bee-Lan Ong Vanessa H.de Villa Rouchelle D.Dela Cruz Tracy Jiezhen Loh Wei Keat Wan Zeng Zeng Anders Jacobsen Skanderup Yin Huei Pang Krishnakumar Madhavan tony kiat-hon lim Glenn Bonney Wei Qiang Leow Valerie Chew Yock Young Dan Wai Leong Tam Han Chong Toh Roger Sik-Yin Foo Pierce Kah-Hoe Chow Genome Institute of Singapore Agency for Science Technology and Research Key Laboratory of Zoological Systematics and Evolution Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences School of Biological Sciences Nanyang Technological University Division of Biosciences Faculty of Life Sciences Division of Surgery and Surgical Oncology National Cancer Centre Department of Hepato-Pancreato-Biliary and Transplant Surgery Singapore General Hospital Division of Hepatobiliary and Pancreatic Surgery Department of Surgery University Surgical Cluster National University Health System Hepato-Pancreato-Biliary Surgery Unit Department of Surgery National Cancer Institute Division of Pathology National Cancer Institute Department of Surgery Faculty of Medicine University of Malaya Department of Surgery and Center for Liver Disease Management and Transplantation The Medical City 13. Department of Laboratories The Medical City Department of Pathology Singapore General Hospital Institute for Infocomm Research ASTAR Department of Pathology National University Health System Translational Immunology Institute (TII) Sing Health Duke-NUS Academic Medical Centre Division of Gastroenterology and Hepatology University Medicine Cluster National University Hospital Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Cancer Science Institute of Singapore National University of Singapore Division of Medical Oncology National Cancer Center Singapore Cardiovascular Research Institute National University of Singapore National University Healthcare System Singhealth-Duke-NUS Academic Surgery Program Duke-NUS Graduate Medical School Institute of Molecular and Cell Biology Agency for Science Technology and Research

Intra-tumor heterogeneity(ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic(transcriptomic and immune)heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma(HCC)with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients(331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage Ⅱ patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

关键词： NADH oxidase H2O2 production oxidative phosphorylation

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Nat Genet:单细胞分析解开结直肠癌细胞的神秘面纱

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现代生物医学进展 2017年第15期17卷 I0003-I0003页

作者： Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan Shyam Prabhakar Elise T Courtois, Yuliana Tan Paul Robson Debarka Sengupta Kok Hao Chen, Jolene Jie Lin Goh Paul Jongjoon Choi Say Li Kong, Axel M Hillmer Iain Beehuat Tan Clarinda Chua Iain Beehuat Tan lim kiat hon Wah Siew Tan Mark Wong Lawrence J K Wee Iain Beehuat Tan Paul Robson Paul Robson Paul Robson Computational and Systems Biology Genome Institute of Singapore Singapore Developmental Cellomics Laboratory Genome Institute of Singapore Singapore Department of Computer Science and Engineering and Center for Computational Biology Indraprastha Institute of Information Technology Delhi India Synthetic Biology Genome Institute of Singapore Singapore Cancer Therapeutics and Stratified Oncology Genome Institute of Singapore Singapore Department of Medical Oncology National Cancer Centre Singapore Singapore Department of Pathology Singapore General Hospital Singapore Department of Colorectal Surgery Singapore General Hospital Singapore Data Analytics Department Institute for Infocomm Research Singapore Program in Cancer and Stem Cell Biology Duke-NUS Medical School Singapore The Jackson Laboratory for Genomic Medicine Farmington Connecticut USA Department of Genetics and Genome Sciences Institute for Systems Genomics University of Connecticut Farmington Connecticut USA Department of Biological Sciences National University of Singapore Singapore.

结合单细胞基因组学和计算机技术，一个研究团队（包括来自杰克逊实验室（JAx）单细胞生物学主任Paul Robson博士在内）鉴定出了11种结直肠癌肿瘤的癌细胞组成及邻近的非癌细胞。这对于更好的肿瘤靶向诊断和治疗很重要。”使用单细胞测... 详细信息

结合单细胞基因组学和计算机技术，一个研究团队（包括来自杰克逊实验室（JAx）单细胞生物学主任Paul Robson博士在内）鉴定出了11种结直肠癌肿瘤的癌细胞组成及邻近的非癌细胞。这对于更好的肿瘤靶向诊断和治疗很重要。”使用单细胞测序。”JAX科学家、这篇发表在Nature Genetics上的文章共同第一作者Elise Courtois说道。”我们可以根据肿瘤中的细胞组成将结直肠癌进一步分类。因为每种亚型的肿瘤病人生存率存在差别，我们的方法将为肿瘤医生提供更多的关于肿瘤预后和治疗的信息。”

关键词：单细胞分析结直肠癌癌细胞 Nat 细胞组成肿瘤病计算机技术细胞生物学

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基因组和转录组测序整合分析揭示混合型肝癌的不同分子亚型

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科学新闻 2020年第2期 47-47页

作者：曾木圣白凡张宁薛瑞栋陈璐张冲藤田征志 Ruoyan Li Shu-Mei Yan Choon kiat Ong Xiwen Liao Qiang Gao Shota Sasagawa Yanmeng Li Jincheng Wang Hua Guo Qi-Tao Huang Qian Zhong Jing Tan Lisha Qi Wenchen Gong Zhixian hong Meng Li Jingmin Zhao Tao Peng Yinying Lu kiat hon tony lim Arnoud Boot Atushi Ono Kazuaki Chayama Zemin Zhang Steve George Rozen Bin Tean Teh Xin Wei Wang Hidewaki Nakagawa 中山大学肿瘤防治中心北京大学生物医学前沿创新中心(BIOPIC)生命科学学院北京大学第一医院北京大学医学部北京大学科研部天津肿瘤医院肝胆外科北京大学生物医学前沿创新中心日本理化研究所

文章简介原发性肝癌每年造成全球约70万病人死亡且过半死亡病例来自中国,其致死率在所有癌种中高居第二。肝癌主要分为3种类型:肝细胞癌(约80%)、肝内胆管癌(约15%)和混合型肝癌(约5%)。混合型肝癌兼具肝细胞癌和胆管细胞癌两种成分,是... 详细信息

文章简介原发性肝癌每年造成全球约70万病人死亡且过半死亡病例来自中国,其致死率在所有癌种中高居第二。肝癌主要分为3种类型:肝细胞癌(约80%)、肝内胆管癌(约15%)和混合型肝癌(约5%)。混合型肝癌兼具肝细胞癌和胆管细胞癌两种成分,是预后最差的一种肝癌。既往对混合型肝癌的基因组学研究较少,混合型肝癌的分子特

关键词：混合型肝癌分子遗传临床样本分子亚型肝细胞癌整合分析基因组

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