|
1
|
Samarasinghe SM, Hewage AS, Siriwardana RC, Tennekoon KH, Niriella MA, De Silva S, Abeysuriya V. Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort. BMC Gastroenterol 2025; 25:151. [PMID: 40065199 PMCID: PMC11892176 DOI: 10.1186/s12876-025-03738-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Single nucleotide polymorphisms (SNPs) in patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2) and membrane bound O-acyltransferase domain containing 7 (MBOAT7) genes were reported to be strongly associated with non-alcoholic fatty liver disease (NAFLD) pathogenicity among different populations. We investigated whether these SNPs are associated with prognostic factors and genetic biomarkers of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) in the Sri Lankan context. METHODS We conducted an exploratory study to evaluate the prevalence of five SNPs (PNPLA3 rs738409, PNPLA3 rs2281135, PNPLA3 rs2294918, TM6SF2 rs58542926 and MBOAT7 rs641738) as genetic risk factors for NASH-HCC pathogenicity. We genotyped 48 NASH-HCC patient samples collected at a clinical setting using a minisequencing method. Impact of each SNP with tumor prognostic factors such as nodularity, tumor size and AFP (alpha-feto protein) level was analyzed using chi square test. We also analyzed the expression of micro RNA-122 (miR-122) in serum and leukocyte telomere length via quantitative real-time PCR. Associations between each SNP with micro RNA-122 (miR-122) expression level and leukocyte telomere length of NASH-HCC patients were analyzed using one-way analysis of variance (ANOVA) test and independent t test. Relationships among tested SNPs and some well-established HCC risk factors such as age, BMI, gender, diabetes status and the cirrhotic stage were also analyzed using chi square test, independent t-test and One-way ANOVA test. RESULTS Our analyses demonstrated significant associations between PNPLA3 rs2281135 variant and tumor nodularity. Also, PNPLA3 rs2281135 and PNPLA3 rs2294918 variants were significantly associated with miR-122 expression levels of NASH-HCC patients. Further, age and body mass index (BMI) were significantly associated with PNPLA3 rs2281135 variant in our study cohort. CONCLUSION We found that in the Sri Lankan NASH-related HCC cohort, some PNPLA3 variants (rs2281135 and rs2294918) correlate with tumor nodularity, higher miR-122 expression, and distinct demographic features such as age and BMI. Our work highlights the role of specific SNPs in tumor aggressiveness, contributing to the precision screening for HCC in NASH patients.
Collapse
Affiliation(s)
- Saumya Madushani Samarasinghe
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, No 90, Cumarathunga Munidasa Mawatha, Colombo 03, Sri Lanka
| | - Asanka Sudeshini Hewage
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, No 90, Cumarathunga Munidasa Mawatha, Colombo 03, Sri Lanka.
| | | | - Kamani Hemamala Tennekoon
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, No 90, Cumarathunga Munidasa Mawatha, Colombo 03, Sri Lanka
| | - Madunil Anuk Niriella
- Colombo North Center for Liver Diseases, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
| | - Sumadee De Silva
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, No 90, Cumarathunga Munidasa Mawatha, Colombo 03, Sri Lanka
| | - Visula Abeysuriya
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, No 90, Cumarathunga Munidasa Mawatha, Colombo 03, Sri Lanka
| |
Collapse
|
|
2
|
Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e82-e158. [PMID: 39919781 DOI: 10.1055/a-2460-6347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
3
|
Tang H, Zhang W, Cao J, Cao Y, Bi X, Zhao H, Zhang Z, Liu Z, Wan T, Lang R, Sun W, Du S, Yang Y, Lu Y, Zeng D, Wu J, Duan B, Lin D, Li F, Meng Q, Zhou J, Xing B, Tian X, Zhu J, Gao J, Hao C, Wang Z, Duan F, Wang Z, Wang M, Liang B, Chen Y, Xu Y, Li K, Li C, Hu M, Wang Z, Cai S, Ji W, Xia N, Zheng W, Wang H, Li G, Zhu Z, Huang Z, Zhang W, Tao K, Liang J, Zhang K, Dai C, Li J, Qiu Q, Guo Y, Wu L, Ding W, Zhu Z, Gu W, Cao J, Wang Z, Tian L, Ding H, Li G, Zeng Y, Wang K, Yang N, Jin H, Chen Y, Yang Y, Xiu D, Yan M, Wang X, Han Q, Jiao S, Tan G, Wang J, Liu L, Song J, Liao J, Zhao H, Li P, Song T, Wang Z, Yuan J, Hu B, Yuan Y, Zhang M, Sun S, Zhang J, Wang W, Wen T, Yang J, Du X, Peng T, Xia F, Liu Z, Niu W, Liang P, Xu J, Zhao X, Zhu M, et alTang H, Zhang W, Cao J, Cao Y, Bi X, Zhao H, Zhang Z, Liu Z, Wan T, Lang R, Sun W, Du S, Yang Y, Lu Y, Zeng D, Wu J, Duan B, Lin D, Li F, Meng Q, Zhou J, Xing B, Tian X, Zhu J, Gao J, Hao C, Wang Z, Duan F, Wang Z, Wang M, Liang B, Chen Y, Xu Y, Li K, Li C, Hu M, Wang Z, Cai S, Ji W, Xia N, Zheng W, Wang H, Li G, Zhu Z, Huang Z, Zhang W, Tao K, Liang J, Zhang K, Dai C, Li J, Qiu Q, Guo Y, Wu L, Ding W, Zhu Z, Gu W, Cao J, Wang Z, Tian L, Ding H, Li G, Zeng Y, Wang K, Yang N, Jin H, Chen Y, Yang Y, Xiu D, Yan M, Wang X, Han Q, Jiao S, Tan G, Wang J, Liu L, Song J, Liao J, Zhao H, Li P, Song T, Wang Z, Yuan J, Hu B, Yuan Y, Zhang M, Sun S, Zhang J, Wang W, Wen T, Yang J, Du X, Peng T, Xia F, Liu Z, Niu W, Liang P, Xu J, Zhao X, Zhu M, Wang H, Kuang M, Shen S, Cui X, Zhou J, Liu R, Sun H, Fan J, Chen X, Zhou J, Cai J, Lu S. Chinese expert consensus on sequential surgery following conversion therapy based on combination of immune checkpoint inhibitors and antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2024 edition). Biosci Trends 2025; 18:505-524. [PMID: 39721704 DOI: 10.5582/bst.2024.01394] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2024]
Abstract
Up to half of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage, for which effective treatment options are lacking, resulting in a poor prognosis. Over the past few years, the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has proven highly efficacious in treating advanced HCC, significantly extending patients' survival and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy, patients can receive long-term survival benefits. In order to improve the long-term survival rate of the overall population with liver cancer and achieve the goal of a 15% increase in the overall 5-year survival rate outlined in the Healthy China 2030 blueprint, the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association, Chinese Society of Liver Cancer, and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts in the field. These discussions focused on the latest progress since the release of the Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2021 Edition) and resulted in a new consensus on the modifications and supplements to related key points. This consensus aims to further guide clinical practice, standardize medical care, and promote the development of the discipline.
Collapse
Affiliation(s)
- Haowen Tang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Wenwen Zhang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Junning Cao
- Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Shandong, China
| | - Yinbiao Cao
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Ze Zhang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Zhe Liu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Tao Wan
- Faculty of Hepato-Pancreato-Biliary Surgery, the Eighth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Wenbing Sun
- Department of Hepatobiliary Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Yongping Yang
- Senior Department of Hepatology, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Yinying Lu
- Comprehensive Liver Cancer Center, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Daobing Zeng
- Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jushan Wu
- Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Binwei Duan
- Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Dongdong Lin
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Fei Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Qinghua Meng
- Department of Medical Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jun Zhou
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Baocai Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiaodong Tian
- Department of General Surgery, Peking University First Hospital, Beijing, China
| | - Jiye Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China
| | - Jie Gao
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China
| | - Chunyi Hao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Sarcoma Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhiqiang Wang
- Department of Hepatobiliary and Pancreatic Surgery, Qinghai Red Cross Hospital, Qinghai, China
| | - Feng Duan
- Department of Interventional Radiology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Zhijun Wang
- Department of Interventional Radiology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Maoqiang Wang
- Department of Interventional Radiology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Bin Liang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Yongwei Chen
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Yinzhe Xu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Kai Li
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Chengang Li
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Minggen Hu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Zhaohai Wang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Shouwang Cai
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Wenbin Ji
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Nianxin Xia
- Faculty of Hepato-Pancreato-Biliary Surgery, the Sixth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Wenheng Zheng
- Department of Interventional Therapy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China
| | - Hongguang Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gong Li
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Ziman Zhu
- Faculty of Hepato-Pancreato-Biliary Surgery, the Fourth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Zhiyong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Wanguang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Kaishan Tao
- Department of Hepatobiliary Surgery, Xijing Hosptial, the Fourth Military Medical University, Shanxi, China
| | - Jun Liang
- Department of Medical Oncology, Peking University International Hospital, Beijing, China
| | - Keming Zhang
- Department of Hepatobiliary Surgery, Peking University International Hospital, Beijing, China
| | - Chaoliu Dai
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Jiangtao Li
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China
| | - Qiu Qiu
- Department of Gastroenterology, People's Hospital of Chongqing Hechuan, Chongqing, China
| | - Yuan Guo
- Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Shandong, China
| | - Liqun Wu
- Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Shandong, China
| | - Weibao Ding
- Department of Hepatobiliary Surgery, Weifang People's Hospital, Shandong, China
| | - Zhenyu Zhu
- Hepatobiliary Surgery Center, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Wanqing Gu
- Chinese Journal of Hepatobiliary Surgery, Beijing, China
| | - Jingyu Cao
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Shandong China
| | - Zusen Wang
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Shandong China
| | - Lantian Tian
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Shandong China
| | - Huiguo Ding
- Department of Hepatology and Gastroenterology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Guangming Li
- Department of Liver Transplantation Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yongyi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, China
| | - Kui Wang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Ning Yang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Haosheng Jin
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong, China
| | - Yajin Chen
- Department of Hepatobiliopancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong, China
| | - Yinmo Yang
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, China
| | - Dianrong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Maolin Yan
- Department of Hepatobiliary and Pancreatic Surgery, Fujian Provincial Hospital, Fujian, China
| | - Xiaodong Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Interventional Therapy, Peking UniversityCancer Hospital & Institute, Beijing, China
| | - Quanli Han
- Department of Medical Oncology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Shunchang Jiao
- Department of Medical Oncology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Guang Tan
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Liaoning, China
| | - Jizhou Wang
- Department of Hepatobiliary Surgery and Organ Transplantation Center, The First Affiliated Hospital of USTC, Division of Life Science andMedicine, University of Science and Technology of China, Anhui, China
| | - Lianxin Liu
- Department of Hepatobiliary Surgery and Organ Transplantation Center, The First Affiliated Hospital of USTC, Division of Life Science andMedicine, University of Science and Technology of China, Anhui, China
| | - Jinghai Song
- Department of General Surgery, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of MedicalSciences, Beijing, China
| | - Jiajie Liao
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Peng Li
- The Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Tianqiang Song
- Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical ResearchCenter for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory ofDigestive Cancer, Tianjin, China
| | - Zhanbo Wang
- Department of Pathology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Jing Yuan
- Department of Pathology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Bingyang Hu
- Department of General Surgery, Beijing Shijingshan Hospital, Beijing, China
| | - Yufeng Yuan
- Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Hubei, China
| | - Meng Zhang
- Department of Hepatobiliary Surgery, the Fourth Hospital of Hebei Medical University, Hebei, China
| | - Shuyang Sun
- Department of Gastroenterology, Beijing Chest Hospital, Capital Medical University, Beijing, China
| | - Jialin Zhang
- Department of Radiology, the First Hospital of China Medical University, Liaoning, China
| | - Wentao Wang
- Department of Liver Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Tianfu Wen
- Department of Liver Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Jiayin Yang
- Department of Liver Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Xilin Du
- Department of General Surgery, Tangdu Hospital, the Fourth Military Medical University, Shanxi, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Feng Xia
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Zuojin Liu
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Weibo Niu
- Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Shandong, China
| | - Ping Liang
- Department of Interventional Ultrasound, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Jianming Xu
- Department of Gastrointestinal Oncology, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Xiao Zhao
- Department of Immunology and National Center for Biomedicine Analysis, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing,China
| | - Min Zhu
- Department of Transplant Surgery, Qilu Hospital of Shandong University, Shandong, China
| | - Huaizhi Wang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing, China
| | - Ming Kuang
- Center of Hepato Pancreato Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangdong, China
| | - Shunli Shen
- Center of Hepato Pancreato Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangdong, China
| | - Xing Cui
- Department of Oncology and Hematology, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong,China
| | - Jinxue Zhou
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan,China
| | - Rong Liu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Huichuan Sun
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry ofEducation, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital,Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry ofEducation, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital,Fudan University, Shanghai, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry ofEducation, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital,Fudan University, Shanghai, China
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shichun Lu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| |
Collapse
|
|
4
|
Hoang MTQ, Koh YX, Sultana R, Allen JC, Moris D, Cheow PC, Chung AY, Jeyaraj PR, Mack POP, Ooi LLPJ, Tan EK, Teo JY, Kam JH, Moe FN, Chua JS, Ng AW, Goh JS, Goh BKP, Zani S, Chow PKH. Metroticket approach in a retrospective cohort study to predict overall survival after surgical resection for hepatocellular carcinoma. Int J Surg 2024; 110:7058-7066. [PMID: 39248314 PMCID: PMC11573095 DOI: 10.1097/js9.0000000000001868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 06/06/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND Surgical resection is a curative therapy for early-stage hepatocellular carcinoma (HCC) patients meeting the Milan criteria as well as a widely used therapy in intermediate-stage HCC. However, intermediate-stage HCC encompasses a wide spectrum of disease and there is a lack of good predictive models for the long-term clinical outcome of HCC patients currently. Here, the authors adopt Mazzaferro's Metroticket 2.0 to create a robust survival prediction model for intermediate-stage HCC patients undergoing surgical resection. Our algorithm considers age, AFP levels, ALBI score, and nodule size/number to generate survival estimates in an accessible graph format. Importantly, their model surpasses the American Joint Committee on Cancer staging model and was validated with independent US patient data. METHODS The authors conducted a retrospective analysis of OS and RFS in early- and intermediate-stage HCC patients treated with liver resection, including a training cohort in Singapore and a validation cohort in North Carolina, USA. RESULTS The authors recorded 278 deaths (35.0%) and 428 patients (53.9%) in the first 5 years after surgical resection; higher ALBI score, higher lnAFP, more advanced age and higher tumour burden index were identified as significant parameters. The overall predictive capability of our model, with the inclusion of AFP, is reflected with a UNO's C-statistic of 0.655, which is 1.11 times better than the 0.5895 C-statistic of the 8th AJCC TNM Staging model. CONCLUSIONS The authors' modified Metroticket model allows for more granular and better-informed prognostication. This will help surgeons and patients make accurate comparisons between the clinical outcomes of surgical resection and other non-surgical treatments.
Collapse
Affiliation(s)
- Marjorie T. Q. Hoang
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - Rehena Sultana
- Centre for Quantitative Medicine, Duke-NUS Medical School
| | - John C. Allen
- Centre for Quantitative Medicine, Duke-NUS Medical School
| | - Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Peng Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - Alexander Y.F. Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - Prema Raj Jeyaraj
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - Peter O. P. Mack
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - London Lucien P. J. Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - Ek Khoon Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - Jin Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - Fiona N.N. Moe
- Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Centre Singapore, Singapore
| | - Jacelyn S.S. Chua
- Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Centre Singapore, Singapore
| | - Ashley W.Y. Ng
- Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Centre Singapore, Singapore
| | - Jade S.Q. Goh
- Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Centre Singapore, Singapore
| | - Brian K. P. Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
| | - Sabino Zani
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Pierce K. H. Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore
- Duke-NUS Medical School
- Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Centre Singapore, Singapore
| |
Collapse
|
|
5
|
Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e213-e282. [PMID: 38364849 DOI: 10.1055/a-2189-8567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein, Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg
| | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
6
|
Kumar A, Acharya SK, Singh SP, Duseja A, Madan K, Shukla A, Arora A, Anand AC, Bahl A, Soin AS, Sirohi B, Dutta D, Jothimani D, Panda D, Saini G, Varghese J, Kumar K, Premkumar M, Panigrahi MK, Wadhawan M, Sahu MK, Rela M, Kalra N, Rao PN, Puri P, Bhangui P, Kar P, Shah SR, Baijal SS, Shalimar, Paul SB, Gamanagatti S, Gupta S, Taneja S, Saraswat VA, Chawla YK. 2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations. J Clin Exp Hepatol 2024; 14:101269. [PMID: 38107186 PMCID: PMC10724697 DOI: 10.1016/j.jceh.2023.08.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 08/12/2023] [Indexed: 12/19/2023] Open
Abstract
Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.
Collapse
Affiliation(s)
- Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Kaushal Madan
- Clinical Hepatology, Max Hospitals, Saket, New Delhi, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | - Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Anil C. Anand
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
| | - Ankur Bahl
- Department of Medical Oncology, Fortis Memorial Research Institute, Sector - 44, Opp. HUDA City Center, Gurugram, 122002, India
| | - Arvinder S. Soin
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, CH Baktawar Singh Road, Sector 38, Gurugram, Haryana, 122 001, India
| | - Bhawna Sirohi
- Medical Oncology, BALCO Medical Centre, Raipur Chattisgarh, 493661, India
| | - Debnarayan Dutta
- Radiation Oncology, Amrita Institute of Medical Sciences, Ponekkara, AIMS (P.O.), Kochi, 682041, India
| | - Dinesh Jothimani
- Department of Hepatology, Dr. Rela Institute & Medical Centre, #7, CLC Works Road, Chromepet, Chennai, 600044, India
| | - Dipanjan Panda
- Department of Medical Oncology, Apollo Cancer Centre, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, 110076, India
| | - Gagan Saini
- Radiation Oncology, Max Institute of Cancer Care, Max Super-Speciality Hospital, W-3, Ashok Marg, near Radisson Blu Hotel, Sector-1, Vaishali, Ghaziabad, 201012, India
| | - Joy Varghese
- Department of Hepatology & Transplant Hepatology, Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600100, India
| | - Karan Kumar
- Department of HPB Sciences and Liver Transplantation, Mahatma Gandhi Medical College and Hospital, RIICO Institutional Area, Sitapura, Tonk Road, Jaipur, 302022, Rajasthan, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Manas K. Panigrahi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, 751019, Odisha, India
| | - Manav Wadhawan
- Liver & Digestive Diseases Institute, Institute of Liver & Digestive Diseases, BLK Max Hospital, Delhi, 110 005, India
| | - Manoj K. Sahu
- Department of Medical Gastroenterology, IMS & SUM Hospital, K8 Kalinga Nagar, Shampur, Bhubaneswar, Odisha 751 003, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, #7, CLC Works Road, Chromepet, Chennai, 600044, India
| | - Naveen Kalra
- Department of Radio Diagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Padaki N. Rao
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, No. 6-3-661, Punjagutta Road, Somajiguda, Hyderabad, Telangana, 500 082, India
| | - Pankaj Puri
- Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Heart Institute & Research Centre, Okhla Road, New Delhi, 110025, India
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, CH Baktawar Singh Road, Sector 38, Gurugram, Haryana, 122 001, India
| | - Premashis Kar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
| | - Samir R. Shah
- Department of Hepatology and Liver Intensive Care, Institute of Liver Disease, HPB Surgery and Transplant Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | - Sanjay S. Baijal
- Diagnostic and Interventional Radiology, Medanta The Medicity, CH Baktawar Singh Road, Sector 38, Gurugram, Haryana, 122 001, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Shashi B. Paul
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Shivanand Gamanagatti
- Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Heart Institute & Research Centre, Okhla Road, New Delhi, 110025, India
| | - Subash Gupta
- Centre for Liver & Biliary Sciences, Liver Transplant and Biliary Sciences, Robotic Surgery, Max Super Speciality Hospital, No. 1, 2, Press Enclave Road, Mandir Marg, Saket Institutional Area, Saket, New Delhi, Delhi, 110017, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Vivek A. Saraswat
- Department of Gastroenterology and Hepatology, Mahatma Gandhi Medical College and Hospital, RIICO Institutional Area, Sitapura, Tonk Road, Jaipur, 302022, Rajasthan, India
| | - Yogesh K. Chawla
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
| |
Collapse
|
|
7
|
Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e67-e161. [PMID: 38195102 DOI: 10.1055/a-2189-6353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V.(AWMF), Berlin
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V.(AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
8
|
Sindayigaya R, Tzedakis S, Tribillon E, Gavignet C, Mazzotta A, Nassar A, Marchese U, Soubrane O, Fuks D. Assessing textbook outcome after single large hepatocellular carcinoma resection. HPB (Oxford) 2023; 25:1093-1101. [PMID: 37208281 DOI: 10.1016/j.hpb.2023.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/27/2023] [Accepted: 05/01/2023] [Indexed: 05/21/2023]
Abstract
BACKGROUND This study aimed to investigate the impact and predictors of an ideal surgical care following SLHCC resection. METHODS SLHCC patients who underwent LR in two tertiary hepatobiliary centers between 2000 and 2021 were retrieved from prospectively maintained databases. The quality of surgical care was measured by the textbook outcome (TO). Tumor burden was defined by the tumor burden score (TBS). Factors associated with TO were determined on multivariate analysis. The impact of TO on oncological outcomes was assessed using Cox regressions. RESULTS Overall, 103 SLHCC patients were included. Laparoscopic approach was considered in 65 (63.1%) patients and 79 (76.7%) patients presented with moderate TBS. TO was achieved in 54 (52.4%) patients. Laparoscopic approach was independently associated with TO (OR 2.57; 95% CI 1.03-6.64; p = 0.045). Within 19 (6-38) months of median follow up, patients who achieved TO had better OS compared to non-TO patients (1-year OS: 91.7% vs. 66.9%; 5-year OS: 83.4% vs. 37.0%, p < 0.0001). On multivariate analysis, TO was independently associated with improved OS, especially in non-cirrhotic patients (HR 0.11; 95% CI 0.02-0.52, p = 0.005). CONCLUSIONS TO achievement could be a relevant surrogate marker of improved oncological care following SLHCC resection in non-cirrhotic patients.
Collapse
Affiliation(s)
- Rémy Sindayigaya
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, Assistance Publique - Hôpitaux de Paris (APHP), 75014, Paris, France; Université Paris Cité, Faculté de Médecine, 75006, Paris, France.
| | - Stylianos Tzedakis
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, Assistance Publique - Hôpitaux de Paris (APHP), 75014, Paris, France; Université Paris Cité, Faculté de Médecine, 75006, Paris, France
| | - Ecoline Tribillon
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, 75014, Paris, France
| | - Chloé Gavignet
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, Assistance Publique - Hôpitaux de Paris (APHP), 75014, Paris, France
| | - Alessandro Mazzotta
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, 75014, Paris, France
| | - Alexandra Nassar
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, Assistance Publique - Hôpitaux de Paris (APHP), 75014, Paris, France
| | - Ugo Marchese
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, Assistance Publique - Hôpitaux de Paris (APHP), 75014, Paris, France
| | - Olivier Soubrane
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, 75014, Paris, France
| | - David Fuks
- Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, Assistance Publique - Hôpitaux de Paris (APHP), 75014, Paris, France; Université Paris Cité, Faculté de Médecine, 75006, Paris, France
| |
Collapse
|
|
9
|
Wong LL, Landsittel DP, Kwee SA. Liver Transplantation vs Partial Hepatectomy for Stage T2 Multifocal Hepatocellular Carcinoma <3 cm Without Vascular Invasion: A Propensity Score-Matched Survival Analysis. J Am Coll Surg 2023; 237:568-577. [PMID: 37102575 DOI: 10.1097/xcs.0000000000000725] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
Abstract
BACKGROUND Multifocal hepatocellular carcinoma (HCC) differs biologically and immunologically from single-nodule HCC. Asian and European guidelines consider liver transplantation (LT) and partial hepatectomy (PH) as effective for T2 multifocal HCC, with preference toward LT, but few US studies compare these treatments directly. This propensity score-based observational study uses an established national cancer outcomes registry to compare overall survival in patients undergoing PH and LT for multifocal HCC. STUDY DESIGN Data from the 2020 National Cancer Database were obtained on patients who underwent LT or PH for multifocal stage 2 HCC within Milan criteria and without vascular invasion. Propensity score matching and Cox regression analysis was applied to evaluate overall survival in an observational cohort balanced by age, sex, treatment facility type, treatment year, prothrombin time, α-fetoprotein, comorbidity burden, liver fibrosis severity, and pretreatment creatinine and bilirubin levels. RESULTS Of 21,248 T2 HCC patients identified, 6,744 had multifocal tumors with largest tumor diameter <3 cm without major vascular invasion, with 1,267 and 181 having undergone LT and PH, respectively. Propensity score-matched Cox regression analysis associated LT with a hazard ratio of 0.39 (95% CI 0.30 to 0.50) relative to PH. Landmark analyses to account for a longer interval to LT demonstrated survival benefits of similar magnitude. CONCLUSIONS Although early-stage HCC can be effectively treated with either LT or PH, propensity score-matched analysis comparatively shows a survival benefit for LT in patients with multifocal HCC who are within the Milan criteria.
Collapse
Affiliation(s)
- Linda L Wong
- From the Department of Surgery, University of Hawaii, John A Burns School of Medicine, Honolulu, HI (Wong)
- Translational Cancer Research Program, University of Hawaii Cancer Center, Honolulu, HI (Wong, Kwee)
| | - Douglas P Landsittel
- Department of Epidemiology and Biostatistics, Indiana University, School of Public Health, Bloomington, IN (Landsittel)
| | - Sandi A Kwee
- Translational Cancer Research Program, University of Hawaii Cancer Center, Honolulu, HI (Wong, Kwee)
- Queen's Medical Center, Honolulu, HI (Kwee)
| |
Collapse
|
|
10
|
Pandrowala S, Patkar S, Goel M, Mirza D, Mathur SK. Surgical resection for large hepatocellular carcinoma and those beyond BCLC: systematic review with proposed management algorithm. Langenbecks Arch Surg 2023; 408:144. [PMID: 37041364 DOI: 10.1007/s00423-023-02881-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 04/02/2023] [Indexed: 04/13/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) accounts for the sixth most common cancer and ranks third in mortality worldwide with inhomogeneity in terms of resection for advanced-stage disease. METHODS A systematic review of published literature using the PubMed, Medline, and Google Scholar databases from 1995 to 2020 was conducted to identify studies that reported outcomes of resection for solitary HCC > 10 cm, BCLC B/C, and multinodular HCC. Our aim was to assess overall survival for resection, identify poor prognostic factors, and to compare it to trans-arterial chemotherapy (TACE) where data was available. RESULTS Eighty-nine articles were included after a complete database search in the systematic review as per our predefined criteria. Analysis revealed a 5-year overall survival of 33.5% for resection of HCC > 10 cm, 41.7% for BCLC B, 23.3% for BCLC C, and 36.6% for multinodular HCC. Peri-operative mortality ranged from 0 to 6.9%. Studies comparing resection versus TACE for BCLC B/C had a survival of 40% versus 17%, respectively. CONCLUSION Our systematic review justifies hepatic resection wherever feasible for hepatocellular carcinomas > 10 cm, BCLC B, BCLC C, and multinodular tumors. In addition, we identified and proposed an algorithm with five poor prognostic criteria in this group of patients who may benefit from adjuvant TACE.
Collapse
Affiliation(s)
- Saneya Pandrowala
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Shraddha Patkar
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Mahesh Goel
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India.
| | - Darius Mirza
- Hepato-Pancreato-Biliary and Transplant Surgery, University Hospital Birmingham and Birmingham Children's Hospital, Birmingham, UK
| | - S K Mathur
- Zen Digestive Disease Center, Zen Hospital, Mumbai, India
| |
Collapse
|
|
11
|
Bitzer M, Groß S, Albert J, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Kautz A, Krug D, Fougère CL, Lang H, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e92-e156. [PMID: 37040776 DOI: 10.1055/a-2026-1240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/13/2023]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | | | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschrirugie, Eberhard-Karls Universität, Tübingen
| | | | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
12
|
Preoperative Predictors of Early Recurrence After Liver Resection for Multifocal Hepatocellular Carcinoma. J Gastrointest Surg 2023:10.1007/s11605-023-05592-1. [PMID: 36857014 DOI: 10.1007/s11605-023-05592-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/07/2023] [Indexed: 03/02/2023]
Abstract
BACKGROUND Liver transplantation remains the optimal treatment for multifocal hepatocellular carcinoma (HCC). However, due to resource constrains, other therapeutic modalities such as liver resection (LR), are frequently utilized. LR, however, has to be balanced against potential morbidity and mortality along with the risks of early recurrence leading to futile surgery. In this study, we evaluated preoperative factors, including inflammatory indices, in predicting early (< 1 year) recurrence in patients who underwent LR for multifocal HCC. METHODS This was a post hoc analysis of 250 consecutive patients with multifocal HCC who underwent LR. RESULTS After exclusion of 10 patients with 30-day/in-hospital mortality, 240 were included of which 134 (55.8%) developed early recurrence. Hepatitis B/C aetiology, 3/ > more hepatic nodules and elevated alpha-fetoprotein (AFP) ≥ 200 ng/ml were significant independent preoperative predictors of early recurrence. The early recurrence rate was 72.1% when 2 out of 3 significant predictive factors were present. The conglomerate of all 3 factors predicted early recurrence of 100% with a statistically significant association between number of predictive factors and early recurrence (p < 0.001). CONCLUSION Better patient selection via the use of preoperative predictive factors of early recurrence such as hepatitis B/C aetiology, ≥ 3 nodules and elevated AFP ≥ 200 ng/ml may assist in identifying patients in whom LR is deemed futile and improve resource allocation.
Collapse
|
|
13
|
Tan LLY, Chew VTW, Syn N, Tan EK, Koh YX, Teo JY, Cheow PC, Jeyaraj PR, Chow PKH, Chan CY, Chung AYF, Ooi LLPJ, Goh BKP. Intraoperative blood transfusion does not impact overall and recurrence-free survival after curative hepatectomy for hepatocellular carcinoma: A propensity-score-matched and inverse probability of treatment-weighted study. J Surg Oncol 2023; 127:598-606. [PMID: 36354172 DOI: 10.1002/jso.27141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/24/2022] [Accepted: 10/03/2022] [Indexed: 11/11/2022]
Abstract
INTRODUCTION Our primary objective was to determine if receiving intraoperative blood transfusion was a significant prognostic factor for overall and recurrence-free survival after curative resection of hepatic cellular carcinoma (HCC). METHODOLOGY Between 2001 and 2018, 1092 patients with histologically proven primary HCC who underwent curative liver resection were retrospectively reviewed. Primary study endpoints were recurrence-free survival (RFS) and overall survival (OS). The main analysis was undertaken using propensity-score matching (PSM) to minimize confounding and selection biases in the comparison of patients with or without transfusion. RESULTS There were 220 patients who received and 666 patients who did not receive intraoperative blood transfusion. The PSM cohort consisted of 163 pairs of patients. After PSM, the only perioperative outcome that appeared to significantly affect whether patients would receive blood transfusion was median blood loss (p = 0.001). In the PSM cohort, whether patients received blood transfusion was neither associated with OS (p = 0.759) nor RFS (p = 0.830). When the volume of blood transfusion was analyzed as a continuous variable, no significant dose-response relationship between blood transfusion volume and HR for OS and RFS was noted. CONCLUSION Intraoperative blood transfusion had no significant impact on the survival outcomes in patients who receive curative resection in primary HCC.
Collapse
Affiliation(s)
- Laura L Y Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Ministry of Health Holdings, Singapore, Singapore
| | - Valerie T W Chew
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Ministry of Health Holdings, Singapore, Singapore
| | - Nicholas Syn
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Ministry of Health Holdings, Singapore, Singapore
| | - Ek-Khoon Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore, Singapore
| | - Ye-Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore, Singapore.,Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Jin-Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Peng-Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore, Singapore.,Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Prema Raj Jeyaraj
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore, Singapore.,Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Pierce K H Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Chung-Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore, Singapore.,Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore, Singapore.,Duke-National University of Singapore Medical School, Singapore, Singapore
| | - London L P J Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore, Singapore.,Duke-National University of Singapore Medical School, Singapore, Singapore
| |
Collapse
|
|
14
|
Shi H, Zhang W, Hu B, Wang Y, Zhang Z, Sun Y, Mao G, Li C, Lu S. Whole-exome sequencing identifies a set of genes as markers of hepatocellular carcinoma early recurrence. Hepatol Int 2022; 17:393-405. [PMID: 36550350 DOI: 10.1007/s12072-022-10457-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 11/12/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is characterized by a high recurrence rate and poor prognosis. In recent years, the therapeutic regimen of programmed cell death protein 1 (PD-1) antibody combined with multi-targeted tyrosine kinase inhibitors (mTKIs) has achieved better results in the clinical application of hepatocellular carcinoma. Whole-exome sequencing can reflect the mutational characteristics of patients' exons and guide the clinical selection of molecular targeting drugs more accurately, which is in line with the concept of precision medicine. METHODS We performed exome sequencing on 63 patients with HCC treated with radical surgery at our hospital and collected their clinical indexes and postoperative follow-up data. Using machine learning, a prediction model for recurrence within 1 year was constructed and the model was presented in a nomogram. Patients treated with PD-1 antibodies in combination with mTKIs after relapse were grouped by prognosis, and the valuable mutated genes were screened according to whole-exome sequencing data. The tumor tissue immune cells were analyzed using the UCSC Xena database. The expressions of target proteins were verified by Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC), respectively, on commercial HCC cell lines and pathological specimens of hepatocellular carcinoma collected clinically. RESULTS The proportion of patients who relapsed within a year was 41% and the prognosis of those patients was poor. The characteristic exon mutation profile with a high frequency of variants in multiple mucin genes was present in Chinese HCC patients. Multiple nidi and 30 exon variants were brought into the prediction model with an area under the curve (AUC) = 0.94. MUC6 gene mutation was obvious in patients with an early recurrence, and MUC3A and MUC4 gene mutations were evident in patients with poorer responses to PD-1 antibodies combined with mTKIs. Those three mucins were negatively correlated with immune infiltrating cells. CONCLUSIONS We depicted the exon characteristics of hepatocellular carcinoma in the Chinese population and established a predictive model for recurrence within 1 year after radical surgical treatment. Moreover, we found that mucins were worthy targets of hepatocellular carcinoma.
Collapse
Affiliation(s)
- Huizhong Shi
- Medical School of China PLA, Beijing, China
- The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, China
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
| | - Wenwen Zhang
- The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, China
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
| | - Bingyang Hu
- The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, China
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
| | - Yafei Wang
- The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, China
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
- Medical College of Nankai University, Tianjin, China
| | - Ze Zhang
- Medical School of China PLA, Beijing, China
- The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, China
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
| | - Ying Sun
- GenomiCare Biotechnology (Shanghai) Co., Ltd., Shanghai, China
| | - Guankun Mao
- The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, China
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
| | - Chonghui Li
- The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, China
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China
- Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China
| | - Shichun Lu
- The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, China.
- Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China.
- Key Laboratory of Digital Hepatobiliary Surgery, PLA, Beijing, China.
| |
Collapse
|
|
15
|
Wee IJY, Moe FNN, Sultana R, Ang RWT, Quek PPS, Goh BKP, Chan CY, Cheow PC, Chung AYF, Jeyaraj PR, Koh YX, Mack POP, Ooi LLPJ, Tan EK, Teo JY, Kam JH, Chua JSS, Ng AWY, Goh JSQ, Chow PKH. Extending Surgical Resection for Hepatocellular Carcinoma Beyond Barcelona Clinic for Liver Cancer (BCLC) Stage A: A Novel Application of the Modified BCLC Staging System. J Hepatocell Carcinoma 2022; 9:839-851. [PMID: 35999856 PMCID: PMC9393033 DOI: 10.2147/jhc.s370212] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 08/07/2022] [Indexed: 11/23/2022] Open
Abstract
Objective We aimed to prognosticate survival after surgical resection of HCC stratified by stage with amalgamation of the modified Barcelona Clinic Liver Cancer (BCLC) staging system and location of tumour. Methods This single-institutional retrospective cohort study included patients with HCC who underwent surgical resection between 1st January 2000 to 30th June 2016. Participants were divided into 6 different subgroups: A-u) Within MC with Unilobar lesions; A-b) Within MC + Bilobar lesions; B1-u) Out of MC + within Up-To-7 + Unilobar lesions; B1-b) Out of MC + within Up-to-7 + Bilobar lesions; B2-u) Out of MC + Out of Up-To-7 + Unilobar lesions; B2-b) Out of MC + Out of Up-To-7 + Bilobar lesions. A separate survival analysis was conducted for solitary HCC lesions according to three subgroups: A-S (Within MC); B1-S (Out of MC + within Up-To-7); B2-S (Out of MC + out of Up-To-7). Results A total of 794 of 1043 patients with surgical resection for HCC were analysed. Groups A-u (64.6%), A-b (58.4%) and B1-u (56.2%) had 5-year cumulative overall survival (OS) rates above 50% after surgical resection and median OS exceeding 60 months (P = 0.0001). The 5-year cumulative recurrence-free survival rates (RFS) were 40.4% (group A-u), 38.2% (group A-b), 36.3% (group B1-u), 24.6% (group B2-u), and 7.3% (group B2-b)(P=0.0001). For solitary lesions, the 5-year OS for the subgroups were A-S (65.1%), B1-S (56.0%) and B2-S (47.1%) (P = 0.0003). Compared to A-S, there was also a significant trend towards relatively poorer OS as the lesion sizes increased in B1-S (HR 1.46, 95% CI 1.03–2.08) and B2-S (HR 1.65, 95% CI 1.25–2.18). Conclusion We adopted a novel approach combining the modified BCLC B sub-classification and dispersion of tumour to show that surgical resection in intermediate stage HCC can be robustly prognosticated. We found that size prognosticates resection outcomes in solitary tumours.
Collapse
Affiliation(s)
- Ian J Y Wee
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Fiona N N Moe
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Rehena Sultana
- Center of Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore
| | - Reiko W T Ang
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | | | - Brian Kim Poh Goh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Chung Yip Chan
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Peng Chung Cheow
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Prema Raj Jeyaraj
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Peter O P Mack
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - London Lucien P J Ooi
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Ek Khoon Tan
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Jin Yao Teo
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Jacelyn S S Chua
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Ashley W Y Ng
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Jade S Q Goh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Pierce K H Chow
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.,Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| |
Collapse
|
|
16
|
Tan LLY, Chew VTW, Syn N, Tan EK, Koh YX, Teo JY, Cheow PC, Jeyaraj PR, Chow PKH, Chan CY, Chung AYF, Ooi LLPJ, Goh BKP. Effect of age on the short- and long-term outcomes of patients undergoing curative liver resection for HCC. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1339-1347. [PMID: 34972621 DOI: 10.1016/j.ejso.2021.12.027] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 11/17/2021] [Accepted: 12/21/2021] [Indexed: 02/09/2023]
Abstract
BACKGROUND Few studies have evaluated the outcomes of curative liver resection (LR) in octogenarian patients, analysed cancer-specific survival (CSS) with HCC-related death or explored the age-varying effect of HCC-related death in elderly patients undergoing LR. We aim to determine the effect of age on the short and long-term outcomes of LR for HCC. METHODOLOGY Between 2000 and 2018, 1,092 patients with primary HCC who underwent LR with curative intent were retrospectively reviewed. The log-rank test and Gray's test were used to assess the equality of survivor functions and competing risk-adjusted cumulative incidence functions between patients in the three age categories respectively. Regression adjustment was used to control for confounding bias via a Principal Component Analysis. Quantile, Firth logistic, Cox, and Fine-Gray competing risk regression were used to analyse continuous, binary, time-to-event, and cause-specific survival respectively. Restricted cubic splines were used to illustrate the dose-effect relationship between age and patient outcomes. RESULTS The study comprised of 764 young patients (<70 years), 278 septuagenarians (70-79 years old) and 50 octogenarians (≥80 years). Compared to young patients, octogenarians had significantly lower 5-year OS(62.1% vs 37.7%, p < 0.001). However, there was no significant difference in 1-year RFS(73.1% vs 67.0%, p = 0.774) or 5-year CSS (5.4% vs 15.2%, p = 0.674). Every 10-year increase in age was significantly associated with an increase length of stay (p < 0.001), postoperative complications (p = 0.004) and poorer OS(p = 0.018) but not significantly associated with major complications (p = 0.279), CSS(p = 0.338) or RFS(p = 0.941). CONCLUSION Age by itself was associated with OS after LR for HCC but was not a significant risk factor for HCC-related death.
Collapse
Affiliation(s)
- Laura L Y Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Ministry of Health Holdings, Singapore
| | - Valerie T W Chew
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Ministry of Health Holdings, Singapore
| | - Nicholas Syn
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Ministry of Health Holdings, Singapore
| | - Ek-Khoon Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Ye-Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Jin-Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Peng-Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Prema Raj Jeyaraj
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Pierce K H Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Chung-Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - London L P J Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Liver Transplant Service, Singhealth Duke-National University of Singapore Transplant Center, Singapore; Duke-National University of Singapore Medical School, Singapore.
| |
Collapse
|
|
17
|
Sabrina V, Michael B, Jörg A, Peter B, Wolf B, Susanne B, Thomas B, Frank D, Matthias E, Markus F, Christian LF, Paul F, Andreas G, Eleni G, Martin G, Elke H, Thomas H, Ralf-Thorsten H, Wolf-Peter H, Peter H, Achim K, Gabi K, Jürgen K, David K, Frank L, Hauke L, Thomas L, Philipp L, Andreas M, Alexander M, Oliver M, Silvio N, Huu Phuc N, Johann O, Karl-Jürgen O, Philipp P, Kerstin P, Philippe P, Thorsten P, Mathias P, Ruben P, Jürgen P, Jutta R, Peter R, Johanna R, Ulrike R, Elke R, Barbara S, Peter S, Irene S, Andreas S, Dietrich VS, Daniel S, Marianne S, Alexander S, Andreas S, Nadine S, Christian S, Andrea T, Anne T, Jörg T, Ingo VT, Reina T, Arndt V, Thomas V, Hilke V, Frank W, Oliver W, Heiner W, Henning W, Dane W, Christian W, Marcus-Alexander W, Peter G, Nisar M. S3-Leitlinie: Diagnostik und Therapie des hepatozellulären Karzinoms. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e56-e130. [PMID: 35042248 DOI: 10.1055/a-1589-7568] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Voesch Sabrina
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Bitzer Michael
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Albert Jörg
- Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Stuttgart
| | | | - Bechstein Wolf
- Klinik für Allgemein-, Viszeral-, Transplantations- und Thoraxchirurgie, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Brunner Thomas
- Klinik für Strahlentherapie, Universitätsklinikum Magdeburg A. ö. R., Magdeburg
| | - Dombrowski Frank
- Institut für Pathologie, Universitätsmedizin Greifswald, Greifswald
| | | | - Follmann Markus
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | | | | | - Geier Andreas
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg
| | - Gkika Eleni
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg, Freiburg
| | | | - Hammes Elke
- Lebertransplantierte Deutschland e. V., Ansbach
| | - Helmberger Thomas
- Institut für Radiologie, Neuroradiologie und minimal-invasive Therapie, München Klinik Bogenhausen, München
| | | | - Hofmann Wolf-Peter
- Gastroenterologie am Bayerischen Platz, medizinisches Versorgungszentrum, Berlin
| | | | | | - Knötgen Gabi
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Körber Jürgen
- Klinik Nahetal, Fachklinik für onkologische Rehabilitation und Anschlussrehabilitation, (AHB), Bad Kreuznach
| | - Krug David
- Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Kiel
| | | | - Lang Hauke
- Klinik für Allgemein-, Viszeral und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz
| | - Langer Thomas
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | - Lenz Philipp
- Universitätsklinikum Münster, Zentrale Einrichtung Palliativmedizin, Münster
| | - Mahnken Andreas
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Meining Alexander
- Medizinische Klinik und Poliklinik II des Universitätsklinikums Würzburg, Würzburg
| | - Micke Oliver
- Klinik für Strahlentherapie und Radioonkologie, Franziskus Hospital Bielefeld, Bielefeld
| | - Nadalin Silvio
- Universitätsklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Oldhafer Karl-Jürgen
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Semmelweis Universität, Asklepios Campus Hamburg, Hamburg
| | - Paprottka Philipp
- Abteilung für interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München, München
| | - Paradies Kerstin
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Pereira Philippe
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, Klinikum am Gesundbrunnen, SLK-Kliniken Heilbronn GmbH, Heilbronn
| | - Persigehl Thorsten
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln, Köln
| | | | | | - Pohl Jürgen
- Interventionelles Endoskopiezentrum und Schwerpunkt Gastrointestinale Onkologie, Asklepios Klinik Altona, Hamburg
| | - Riemer Jutta
- Lebertransplantierte Deutschland e. V., Bretzfeld
| | - Reimer Peter
- Institut für diagnostische und interventionelle Radiologie, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe
| | - Ringwald Johanna
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | - Roeb Elke
- Medizinische Klinik II, Universitätsklinikum Gießen und Marburg GmbH, Gießen
| | - Schellhaas Barbara
- Medizinische Klinik I, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen
| | - Schirmacher Peter
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg
| | - Schmid Irene
- Zentrum Pädiatrische Hämatologie und Onkologie, Dr. von Haunersches Kinderspital, Klinikum der Universität München, München
| | | | | | - Seehofer Daniel
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig
| | - Sinn Marianne
- Medizinische Klinik II, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | | | - Stengel Andreas
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Tannapfel Andrea
- Institut für Pathologie der Ruhr-Universität Bochum am Berufsgenossenschaftlichen Universitätsklinikum Bergmannsheil, Bochum
| | - Taubert Anne
- Kliniksozialdienst, Universitätsklinikum Heidelberg, Bochum
| | - Trojan Jörg
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Tholen Reina
- Deutscher Verband für Physiotherapie e. V., Köln
| | - Vogel Arndt
- Klinik für Gastroenterologie, Hepatologie, Endokrinologie der Medizinischen Hochschule Hannover, Hannover
| | - Vogl Thomas
- Universitätsklinikum Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, Frankfurt
| | - Vorwerk Hilke
- Klinik für Strahlentherapie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Wacker Frank
- Institut für Diagnostische und Interventionelle Radiologie der Medizinischen Hochschule Hannover, Hannover
| | - Waidmann Oliver
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | - Wedemeyer Heiner
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie Medizinische Hochschule Hannover, Hannover
| | - Wege Henning
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - Wildner Dane
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Lauf an der Pegnitz
| | | | | | - Galle Peter
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Mainz, Mainz
| | - Malek Nisar
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| |
Collapse
|
|
18
|
Kabir T, Tan ZZ, Syn NL, Wu E, Lin JD, Zhao JJ, Tan AYH, Hui Y, Kam JH, Goh BKP. Laparoscopic versus open resection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Br J Surg 2021; 109:21-29. [PMID: 34757385 DOI: 10.1093/bjs/znab376] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 09/29/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The exact role of laparoscopic liver resection (LLR) in patients with hepatocellular carcinoma (HCC) and underlying liver cirrhosis (LC) is not well defined. In this meta-analysis, both long- and short-term outcomes following LLR versus open liver resection (OLR) were analysed. METHODS PubMed, EMBASE, Scopus and Web of Science databases were searched systematically for randomised controlled trials (RCTs) and propensity-score matched (PSM) studies reporting outcomes of LLR versus OLR of HCC in patients with cirrhosis. Primary outcome was overall survival (OS). This was analysed using one-stage (individual participant data meta-analysis) and two-stage (aggregate data meta-analysis) approaches. Secondary outcomes were operation duration, blood loss, blood transfusion, Pringle manoeuvre utilization, overall and major complications, length of hospital stay (LOHS), 90-day mortality and R0 resection rates. RESULTS Eleven studies comprising 1618 patients (690 LLR versus 928 OLR) were included for analysis. In the one-stage meta-analysis, an approximately 18.7 per cent lower hazard rate (HR) of death in the LLR group (random effects: HR 0.81, 95 per cent confidence interval [C.I.] 0.68 to 0.96; P = 0.018) was observed. Two-stage meta-analysis resulted in a pooled HR of 0.84 (95 per cent C.I. 0.74 to 0.96; P = 0.01) in the overall LLR cohort. This indicated a 16-26 per cent reduction in the HR of death for patients with HCC and cirrhosis who underwent LLR. For secondary outcomes, LLR was associated with less blood loss (mean difference [MD] -99 ml, 95 per cent C.I. -182 to -16 ml), reduced overall complications (odds ratio 0.49, 95 per cent C.I. 0.37 to 0.66) and major complications (odds ratio 0.45, 95 per cent C.I. 0.26 to 0.79), and shorter LOHS (MD -3.22 days, 95 per cent C.I. -4.38 to -2.06 days). CONCLUSION Laparoscopic resection of HCC in patients with cirrhosis is associated with improved survival and perioperative outcomes.
Collapse
Affiliation(s)
- Tousif Kabir
- Department of General Surgery, Sengkang General Hospital, Singapore.,Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Zoe Z Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | | | - Eric Wu
- Yong Loo Lin School of Medicine, Singapore
| | | | | | - Alvin Y H Tan
- Department of General Surgery, Sengkang General Hospital, Singapore
| | - Yong Hui
- Department of General Surgery, Sengkang General Hospital, Singapore.,Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Juinn H Kam
- Department of General Surgery, Sengkang General Hospital, Singapore.,Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.,Duke NUS Medical School, Singapore
| |
Collapse
|
|
19
|
Goh BKP, Chua DW, Koh YX, Tan EK, Kam JH, Teo JY, Cheow PC, Jeyaraj PR, Chow PKH, Chan CY, Chung AYF, Ooi LLPJ. Continuous improvements in short and long-term outcomes after partial hepatectomy for hepatocellular carcinoma in the 21st century: Single institution experience with 1300 resections over 18 years. Surg Oncol 2021; 38:101609. [PMID: 34126522 DOI: 10.1016/j.suronc.2021.101609] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/16/2021] [Accepted: 05/22/2021] [Indexed: 01/10/2023]
Abstract
INTRODUCTION To investigate the changing trends in short- and long-term outcomes after partial hepatectomy(PH) for hepatocellular carcinoma(HCC) performed in the 21st century. METHODS A retrospective review was conducted on 1300 consecutive patients who underwent PH for HCC. The study cohort was divided into 3 time periods(P): P1(2000-2005), P2(2006-2011) and P3(20012-2017). RESULTS Comparison between the patients' baseline demographic features across the 3 periods demonstrated that patients were significantly older, had decreasing frequency of hepatitis B, increasing non-alcoholic fatty liver disease, lower alpha-feto protein(AFP) level, lower creatinine levels, less likely to undergo emergency surgery, less likely to undergo major hepatectomy, more likely to undergo repeat resection and minimally-invasive surgery. There was also an increase in operation time, decrease in blood loss, increase frequency in the use of Pringles manoeuvre, decrease liver failure, decrease length of stay and decrease postoperative mortality. HCC resected were of smaller size, less likely to demonstrate microvascular invasion and less likely to have close margins. This was associated with significant improvement in overall survival and recurrence free interval over time. Period of resection was an independent predictor of 90-day mortality and OS on multivariate analysis. CONCLUSION We observed a continuous improvement in postoperative outcomes including postoperative mortality and long-term survival after PH for HCC over the past 18 years.
Collapse
Affiliation(s)
- Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore.
| | - Darren W Chua
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Ye-Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Ek-Khoon Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Juinn-Huar Kam
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Jin-Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Peng-Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Prema Raj Jeyaraj
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Pierce K H Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Chung-Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - London L P J Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| |
Collapse
|
|
20
|
Romano F, Chiarelli M, Garancini M, Scotti M, Zago M, Cioffi G, De Simone M, Cioffi U. Rethinking the Barcelona clinic liver cancer guidelines: Intermediate stage and Child-Pugh B patients are suitable for surgery? World J Gastroenterol 2021; 27:2784-2794. [PMID: 34135554 PMCID: PMC8173387 DOI: 10.3748/wjg.v27.i21.2784] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 02/24/2021] [Accepted: 04/29/2021] [Indexed: 02/06/2023] Open
Abstract
According to Barcelona Clinic Liver Cancer recommendations, intermediate stage hepatocellular carcinomas (stage B) are excluded from liver resection and are referred to palliative treatment. Moreover, Child-Pugh B patients are not usually candidates for liver resection. However, many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection, maintaining that hepatic resection is not contraindicated in selected patients with non-early-stage hepatocellular carcinoma and without normal liver function. Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification, and this treatment gives good results in the setting of multinodular, large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis. In this review we explore this controversial topic, and we show through the literature analysis how liver resection may improve the short- and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients. However, other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.
Collapse
Affiliation(s)
- Fabrizio Romano
- Department of Surgery, School of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Marco Chiarelli
- Emergency and Robotic Surgery, A. Manzoni Hospital, ASST Lecco, Lecco 23900, Italy
| | - Mattia Garancini
- Department of General Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Mauro Scotti
- Department of General Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Mauro Zago
- Emergency and Robotic Surgery, A. Manzoni Hospital, ASST Lecco, Lecco 23900, Italy
| | - Gerardo Cioffi
- Department of Sciences and Technologies, Università degli Studi del Sannio di Benevento, Benevento 82100, Italy
| | | | - Ugo Cioffi
- Department of Surgery, University of Milan, Milano 20122, Italy
| |
Collapse
|
|
21
|
Chen YS, Hsieh PM, Lin HY, Hung CM, Lo GH, Hsu YC, Lu IC, Lee CY, Wu TC, Yeh JH, Hsiao P, Li YC, Wang YC, Hsieh KC, Lin CW. Surgical resection significantly promotes the overall survival of patients with hepatocellular carcinoma: a propensity score matching analysis. BMC Gastroenterol 2021; 21:220. [PMID: 33990184 PMCID: PMC8120780 DOI: 10.1186/s12876-021-01807-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 05/06/2021] [Indexed: 12/15/2022] Open
Abstract
Background The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.
Methods Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. Results
In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0–96) months for the total cohort and was subdivided into 52 (8–96), 32 (1–96), 19 (0–84), and 12 (0–79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child–Pugh (C–P) class; (3) SR, hepatitis B virus (HBV) infection, and C–P class; and (4) SR, HBV infection, and C–P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values < 0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages. Conclusions SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-021-01807-4.
Collapse
Affiliation(s)
- Yaw-Sen Chen
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Pei-Min Hsieh
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Hung-Yu Lin
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Chao-Ming Hung
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Yao-Chun Hsu
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - I-Cheng Lu
- Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Chih-Yuan Lee
- Department of Surgery, National Taiwan University Hospital, Taipei, 100, Taiwan, ROC
| | - Tsung-Chin Wu
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 807, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Jen-Hao Yeh
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 807, Taiwan, ROC.,Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Pojen Hsiao
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 807, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Yu-Chan Li
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Ya-Chin Wang
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 807, Taiwan, ROC.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Kun-Chou Hsieh
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 807, Taiwan, ROC. .,Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC. .,Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, 824, Taiwan, ROC. .,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 824, Taiwan, ROC. .,School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404, Taiwan, ROC. .,Research Center for Traditional Chinese Medicine, China Medical University Hospital, Taichung, 404, Taiwan, ROC.
| |
Collapse
|
|
22
|
Key Enzymes in Pyrimidine Synthesis, CAD and CPS1, Predict Prognosis in Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:cancers13040744. [PMID: 33670206 PMCID: PMC7916936 DOI: 10.3390/cancers13040744] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 02/05/2021] [Indexed: 02/06/2023] Open
Abstract
Patients with hepatocellular carcinoma (HCC) have a highly variable clinical course. Therefore, there is an urgent need to identify new prognostic markers to determine prognosis and select specific therapies. Recently, it has been demonstrated that dysregulation of the urea cycle (UC) is a common phenomenon in multiple types of cancer. Upon UC dysregulation, nitrogen is diverted toward the multifunctional enzyme carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD), and increases pyrimidine synthesis. In this study, we investigated the role of CAD and carbamoyl-phosphate synthetase 1 (CPS1), a rate-limiting enzyme of the UC highly expressed in hepatocytes, in HCC. We created a tissue microarray to analyze expression of both enzymes by immunohistochemistry in a large and well-characterized overall cohort of 871 HCCs of 561 patients that underwent surgery. CAD was induced in recurrent HCCs, and high expression predicted shorter overall survival. CPS1 was downregulated in HCC and further reduced in recurrent tumors and distant metastases. Additionally, low CPS1 was associated with short overall survival. A combined score of both enzymes was an independent prognostic marker in a multivariate Cox regression model (HR = 1.37, 95% confidence interval 1.06-1.75, p = 0.014). Inhibition of pyrimidine synthesis may represent a novel therapeutic strategy for HCC.
Collapse
|
|
23
|
Otto G, Pitton MB, Hoppe-Lotichius M, Weinmann A. Liver transplantation and BCLC classification: Limitations impede optimum treatment. Hepatobiliary Pancreat Dis Int 2021; 20:6-12. [PMID: 33349607 DOI: 10.1016/j.hbpd.2020.12.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 12/01/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The Barcelona Clinic Liver Cancer (BCLC) system has been endorsed by international guidelines as a staging algorithm of hepatocellular carcinoma. This analysis was performed to assess the outcome of liver transplantation in patients treated against the BCLC recommendations. METHODS The data of 198 patients who underwent liver transplantation for hepatocellular carcinoma were extracted from a prospectively maintained database to classify the patients according to the BCLC system. RESULTS BCLC staging was as follows: 0, n = 5; A, n = 77; B, n = 41; C, n = 53; and D, n = 22. Accordingly, liver transplantation was performed in the majority of patients against BCLC recommendations. Surgery (n = 16), radiofrequency ablation (n = 15) and transarterial chemoembolization (n = 151) preceded liver transplantation in 182 patients. Sixteen patients were transplanted without pretreatment. The1-, 5- and 10-year survival rates were 83.8%, 62.4% and 45.9%, and 1-, 5-, and 10-year recurrence rates were 7.7%, 22.7% and 26.7%. The BCLC classification did neither impact survival (P = 0.796) nor recurrence (P = 0.693). In the Cox analysis, RECIST tumor progression and initial alpha fetoprotein were independent predictors of outcome. CONCLUSIONS Neither the oncological nor the functional stratification imposed by the BCLC system was of importance for outcome. Lack of flexibility and disregard of biological parameters hamper its clinical applicability in liver transplantation.
Collapse
Affiliation(s)
- Gerd Otto
- (Former) Department of Hepatobiliary and Transplant Surgery, University Medical Center, Mainz, Germany.
| | - Michael B Pitton
- Department of Diagnostic and Interventional Radiology, University Medical Center, Mainz, Germany
| | - Maria Hoppe-Lotichius
- (Former) Department of Hepatobiliary and Transplant Surgery, University Medical Center, Mainz, Germany; Department of General, Abdominal and Transplant Surgery, University Medical Center, Mainz, Germany
| | - Arndt Weinmann
- Department of Internal Medicine I, University Medical Center, Mainz, Germany
| |
Collapse
|
|
24
|
Kabir T, Syn NL, Tan ZZX, Tan HJ, Yen C, Koh YX, Kam JH, Teo JY, Lee SY, Cheow PC, Chow PKH, Chung AYF, Ooi LL, Chan CY, Goh BKP. Predictors of post-operative complications after surgical resection of hepatocellular carcinoma and their prognostic effects on outcome and survival: A propensity-score matched and structural equation modelling study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1756-1765. [PMID: 32345496 DOI: 10.1016/j.ejso.2020.03.219] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 01/31/2020] [Accepted: 03/23/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Although hepatectomy is the mainstay of curative therapy for hepatocellular carcinoma (HCC), post-operative complications remain high. Presently there is conflicting data on the impact of morbidity on oncologic outcomes. We sought to identify predictors for the occurrence of post-hepatectomy complications, as well as to analyse the impact on overall survival (OS) and recurrence-free survival (RFS). MATERIALS AND METHODS We performed a retrospective review of 888 patients who underwent resection for HCC from 2001 to 2016 in our institution. RESULTS A total of 237 patients (26.7%) developed 254 complications of Clavien-Dindo Grade ≥2. Hepatitis B (p = 0.0397), elevated ASA score (p = 0.0002), higher platelet counts (p = 0.0277), raised pre-operative APRI scores (p = 0.0105) and bloodloss (p < 0.0001) were independently associated with the development of complications. After propensity-score matching, 458 patients were compared in a 1:1 ratio (229 with complications versus 229 without). Patients with complications had significantly longer median length of stay (9 days [IQR 7-15] versus 6 days [IQR 5-8], p < 0.0001), higher 90-day mortality rates as well as inferior OS (p = 0.0139), but there was no difference in RFS (p = 0.4577). Age (p = 0.0006), elevated Child Pugh points (p < 0.0001), microvascular invasion (p = 0.0002), multifocal tumours (p = 0.0002), R1 resection (p = 0.0443) and development of complications (p = 0.0091) were independent predictors of inferior OS. CONCLUSION Post-operative morbidity affected both short-term and OS outcomes after hepatectomy for HCC. Hepatitis B, higher ASA scores, elevated preoperative APRI and increased blood loss were found to predict a higher likelihood of developing complications. This may potentially be mitigated by careful patient selection and adopting strict measures to minimise intraoperative bleeding.
Collapse
Affiliation(s)
- Tousif Kabir
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Department of General Surgery, Sengkang General Hospital, Singapore
| | | | - Zoe Z X Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Hiang-Jin Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Clarence Yen
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Ye-Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke NUS Medical School, Singapore
| | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Department of General Surgery, Sengkang General Hospital, Singapore
| | - Jin-Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Ser-Yee Lee
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke NUS Medical School, Singapore
| | - Peng-Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Pierce K H Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke NUS Medical School, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke NUS Medical School, Singapore
| | - London L Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Department of General Surgery, Sengkang General Hospital, Singapore; Yong Loo Lin School of Medicine, Singapore; Duke NUS Medical School, Singapore
| | - Chung-Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke NUS Medical School, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke NUS Medical School, Singapore.
| |
Collapse
|
|
25
|
Allaire M, Goumard C, Lim C, Le Cleach A, Wagner M, Scatton O. New frontiers in liver resection for hepatocellular carcinoma. JHEP Rep 2020; 2:100134. [PMID: 32695968 PMCID: PMC7360891 DOI: 10.1016/j.jhepr.2020.100134] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 04/23/2020] [Accepted: 05/15/2020] [Indexed: 02/08/2023] Open
Abstract
Liver resection is one of the main curative options for early hepatocellular carcinoma (HCC) in patients with cirrhosis and is the treatment of choice in non-cirrhotic patients. However, careful patient selection is required to balance the risk of postoperative liver failure and the potential benefit on long-term outcomes. In the last decades, improved surgical techniques and perioperative management, as well as better patient selection, have enabled the indications for liver resection to be expanded. In this review, we aim to describe the main indications for liver resection in the management of HCC, its role compared to percutaneous ablation and liver transplantation in the therapeutic algorithm, as well as the recent advances in liver surgery that could be used to improve the prognosis of patients with HCC.
Collapse
Key Words
- ALPPS, associating liver partition and portal vein ligation for staged hepatectomy
- BCLC, Barcelona Clinic liver cancer
- CSPH, clinically significant portal hypertension
- DFS, disease-free survival
- GSA, galactosyl serum albumin
- HCC
- HCC, hepatocellular carcinoma
- HVGP, hepatic venous pression gradient
- ICG, indocyanine green
- ICG-R15, hepatic clearance of ICG 15 minutes after its intravenous administration
- IL-6, interleukin 6
- LR, liver resection
- LSM, liver stiffness measurement
- Laparoscopy
- Liver resection
- MELD, model for end-stage liver disease
- NAFLD, non-alcoholic fatty liver disease
- OS, overall survival
- PVL, portal vein ligation
- PVTT, tumour-related portal vein thrombosis
- RFA, radiofrequency ablation
- SSM, spleen stiffness measurement
- Surgery
- TACE, transarterial chemoembolisation
Collapse
Affiliation(s)
- Manon Allaire
- Sorbonne Université, Service d'Hépatologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
- Inserm U1149, Centre de Recherche sur l'Inflammation, France Faculté de Médecine Xavier Bichat, Université Paris Diderot, Paris, France
| | - Claire Goumard
- Sorbonne Université, CRSA, Service de chirurgie digestive, hépato-biliaire et transplantation hépatique, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| | - Chetana Lim
- Sorbonne Université, CRSA, Service de chirurgie digestive, hépato-biliaire et transplantation hépatique, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| | - Aline Le Cleach
- Sorbonne Université, Service d'Hépatologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| | - Mathilde Wagner
- Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale (LIB), Service de Radiologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| | - Olivier Scatton
- Sorbonne Université, CRSA, Service de chirurgie digestive, hépato-biliaire et transplantation hépatique, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| |
Collapse
|
|
26
|
Li C, Zhang W, Yang H, Xiang J, Wang X, Wang J. Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals potential lncRNA biomarkers for human hepatocellular carcinoma. PeerJ 2020; 8:e8758. [PMID: 32201648 PMCID: PMC7071826 DOI: 10.7717/peerj.8758] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 02/16/2020] [Indexed: 12/16/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis and a high incidence. The molecular changes and novel biomarkers of HCC need to be identified to improve the diagnosis and prognosis of this disease. We investigated the current research concentrations of HCC and identified the transcriptomics-related biomarkers of HCC from The Cancer Genome Atlas (TGCA) database. Methods We investigated the current research concentrations of HCC using literature metrology analysis for studies conducted from 2008 to 2018. We identified long noncoding RNAs (lncRNAs) that correlated with the clinical features and survival prognoses of HCC from The Cancer Genome Atlas (TGCA) database. Differentially expressed genes (lncRNAs, miRNAs, and mRNAs) were also identified by TCGA datasets in HCC tumor tissues. A lncRNA competitive endogenous RNA (ceRNA) network was constructed from lncRNAs based on intersected lncRNAs. Survival times and the association between the expression levels of the key lncRNAs of the ceRNA network and the clinicopathological characteristics of HCC patients were analyzed using TCGA. Real-time polymerase chain reaction (qRT-PCR) was used to validate the reliability of the results in tissue samples from 20 newly-diagnosed HCC patients. Results Analysis of the literature pertaining to HCC research revealed that current research is focused on lncRNA functions in tumorigenesis and tumor development. A total of 128 HCC dysregulated lncRNAs were identified; 66 were included in the co-expressed ceRNA network. We analyzed survival times and the associations between the expression of 66 key lncRNAs and the clinicopathological features of the HCC patients identified from TCGA. Twenty-six lncRNAs were associated with clinical features of HCC (P < 0.05) and six key lncRNAs were associated with survival time (log-rank test P < 0.05). Six key lncRNAs were selected for the validation of their expression levels in 20 patients with newly diagnosed HCC using qRT-PCR. Consistent fold changes in the trends of up and down regulation between qRT-PCR validation and TCGA proved the reliability of our bioinformatics analysis. Conclusions We used integrative bioinformatics analysis of the TCGA datasets to improve our understanding of the regulatory mechanisms involved with the functional features of lncRNAs in HCC. The results revealed that lncRNAs are potential diagnostic and prognostic biomarkers of HCC.
Collapse
Affiliation(s)
- Chengyun Li
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Gansu province, China
| | - Wenwen Zhang
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Gansu province, China
| | - Hanteng Yang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu province, China
| | - Jilian Xiang
- Department of gastroenterology, Third People's Hospital of Gansu province, Lanzhou, Gansu province, China
| | - Xinghua Wang
- Department of gastrointestinal surgery, Gansu Wuwei Tumor Hospital, Wuwei, Gansu province, China
| | - Junling Wang
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Gansu province, China
| |
Collapse
|
|
27
|
Chagas AL, Mattos AAD, Carrilho FJ, Bittencourt PL, Vezozzo DCP, Horvat N, Rocha MDS, Alves VAF, Coral GP, Alvares-DA-Silva MR, Barros FMDR, Menezes MR, Monsignore LM, Coelho FF, Silva RFD, Silva RDCMA, Boin IDFSF, D Albuquerque LAC, Garcia JHP, Felga GEG, Moreira AM, Braghiroli MIFM, Hoff PMG, Mello VBD, Dottori MF, Branco TP, Schiavon LDL, Costa TDFA. BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF HEPATOCELLULAR CARCINOMA. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:1-20. [PMID: 32294682 DOI: 10.1590/s0004-2803.202000000-20] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 12/19/2019] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.
Collapse
Affiliation(s)
- Aline Lopes Chagas
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Angelo Alves de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | - Flair José Carrilho
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Natally Horvat
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Manoel de Souza Rocha
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
| | - Venâncio Avancini Ferreira Alves
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Gabriela Perdomo Coral
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | | | | | - Marcos Roberto Menezes
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Lucas Moretti Monsignore
- Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, São Paulo, SP, Brasil
| | | | - Renato Ferreira da Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | - Rita de Cássia Martins Alves Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | | | | | | | | | - Airton Mota Moreira
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | - Paulo Marcelo Gehm Hoff
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Tiago Pugliese Branco
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | |
Collapse
|
|
28
|
Oncul S, Karakaya G, Dilsiz Aytemir M, Ercan A. A kojic acid derivative promotes intrinsic apoptotic pathway of hepatocellular carcinoma cells without incurring drug resistance. Chem Biol Drug Des 2019; 94:2084-2093. [PMID: 31495064 DOI: 10.1111/cbdd.13615] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 06/09/2019] [Accepted: 08/03/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Selin Oncul
- Department of Biochemistry Faculty of Pharmacy Hacettepe University Ankara Turkey
| | - Gulsah Karakaya
- Department of Pharmaceutical Chemistry Faculty of Pharmacy Hacettepe University Ankara Turkey
| | - Mutlu Dilsiz Aytemir
- Department of Pharmaceutical Chemistry Faculty of Pharmacy Hacettepe University Ankara Turkey
| | - Ayse Ercan
- Department of Biochemistry Faculty of Pharmacy Hacettepe University Ankara Turkey
| |
Collapse
|
|
29
|
Kubota K, Aoki T, Kumamaru H, Shiraki T, Miyata H, Seto Y, Kakeji Y, Yamamoto M. Use of the National Clinical Database to evaluate the association between preoperative liver function and postoperative complications among patients undergoing hepatectomy. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2019:jhbp.644. [DOI: 10.1002/jhbp.644] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Affiliation(s)
- Keiichi Kubota
- Second Department of Surgery Dokkyo Medical University Tochigi Japan
| | - Taku Aoki
- Second Department of Surgery Dokkyo Medical University Tochigi Japan
| | - Hiraku Kumamaru
- Department of Healthcare Quality Assessment The University of Tokyo 880 Kitakobayashi, Mibu Tochigi321-0293Japan
| | - Takayuki Shiraki
- Second Department of Surgery Dokkyo Medical University Tochigi Japan
| | - Hiroaki Miyata
- Department of Health Policy and Management School of Medicine Keio University Tokyo Japan
| | - Yasuyuki Seto
- The Japanese Society of Gastroenterological Surgery Tokyo Japan
| | - Yoshihiro Kakeji
- Database Committee The Japanese Society of Gastroenterological Surgery Tokyo Japan
| | - Masakazu Yamamoto
- The Japanese Society of Hepato‐Biliary‐Pancreatic Surgery Tokyo Japan
| |
Collapse
|
|
30
|
Li GX, Ding ZY, Wang YW, Liu TT, Chen WX, Wu JJ, Xu WQ, Zhu P, Zhang BX. Integrative analysis of DNA methylation and gene expression identify a six epigenetic driver signature for predicting prognosis in hepatocellular carcinoma. J Cell Physiol 2019; 234:11942-11950. [PMID: 30536816 DOI: 10.1002/jcp.27882] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Accepted: 11/12/2018] [Indexed: 12/12/2022]
Abstract
DNA methylation is a crucial regulator of gene transcription in the etiology and pathogenesis of hepatocellular carcinoma (HCC). Thus, it is reasonable to identify DNA methylation-related prognostic markers. Currently, we aimed to make an integrative epigenetic analysis of HCC to identify the effectiveness of epigenetic drivers in predicting prognosis for HCC patients. By the software pipeline TCGA-Assembler 2, RNA-seq, and methylation data were downloaded and processed from The Cancer Genome Atlas. A bioconductor package MethylMix was utilized to incorporate gene expression and methylation data on all 363 samples and identify 589 epigenetic drivers with transcriptionally predictive. By univariate survival analysis, 72 epigenetic drivers correlated with overall survival (OS) were selected for further analysis in our training cohort. By the robust likelihood-based survival model, six epi-drivers (doublecortin domain containing 2, flavin containing monooxygenase 3, G protein-coupled receptor 171, Lck interacting transmembrane adaptor 1, S100 calcium binding protein P, small nucleolar RNA host gene 6) serving as prognostic markers was identified and then a DNA methylation signature for HCC (MSH) predicting OS was identified to stratify patients into low-risk and high-risk groups in the training cohort (p < 0.001). The capability of MSH was also assessed in the validation cohort (p = 0.002). Furthermore, a receiver operating characteristic curve confirmed MSH as an effective prognostic model for predicting OS in HCC patients in training area under curve (AUC = 0.802) and validation (AUC = 0.691) cohorts. Finally, a nomogram comprising MSH and pathologic stage was generated to predict OS in the training cohort, and it also operated effectively in the validation cohort (concordance index: 0.674). In conclusion, MSH, a six epi-drivers based signature, is a potential model to predict prognosis for HCC patients.
Collapse
Affiliation(s)
- Gan-Xun Li
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ze-Yang Ding
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu-Wei Wang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tong-Tong Liu
- Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei-Xun Chen
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing-Jing Wu
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei-Qi Xu
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Peng Zhu
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bi-Xiang Zhang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
31
|
Giovanardi F, Lai Q, Bertacco A, Vitale A. Resection for hepatocellular cancer: overpassing old barriers. Transl Gastroenterol Hepatol 2018; 3:64. [PMID: 30363682 PMCID: PMC6182022 DOI: 10.21037/tgh.2018.09.13] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 09/11/2018] [Indexed: 01/27/2023] Open
Abstract
Several recent studies have shown that the selection limits commonly used for patients with hepatocellular cancer (HCC) potentially requiring a liver resection (LR) are too restrictive. The present review aims at investigating the studies showing that LR is no longer a treatment suitable only for highly selected patients, but also for patients selectively presenting one-to-more negative factors. Several specific variables have been investigated, none of them showing to be an absolute contraindication for LR: age; single vs. multiple diseases; the dimension of the nodule; hyperbilirubinemia; clinically relevant portal hypertension; Child-Pugh status; macrovascular invasion. As a consequence, LR for the treatment of HCC-on-cirrhosis is a safe and effective procedure not only in "ideal cases", but also for selected patients presenting risk factors. The presence of only one of these factors does not represent an absolute contraindication for LR. On the opposite, the contemporaneous presence of risk factors should contraindicate the procedure. Further studies investigating the "borderline" cases are required, mainly looking at the possible decisive role of laparoscopy in this setting.
Collapse
Affiliation(s)
- Francesco Giovanardi
- General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Alessandra Bertacco
- Department of Surgery, Oncology and Gastroenterology, Padua University, Padua, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Padua University, Padua, Italy
| |
Collapse
|