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Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma
Background Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied...
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| Published in: | Annals of surgical oncology 2017-07, Vol.24 (7), p.1843-1851 |
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| creator | Aravinthan, Aloysious D. Bruni, Silvio G. Doyle, Adam C. Thein, Hla-Hla Goldaracena, Nicolas Issachar, Assaf Lilly, Leslie B. Selzner, Nazia Bhat, Mamatha Sreeharsha, Boraiah Selzner, Markus Ghanekar, Anand Cattral, Mark S. McGilvray, Ian D. Greig, Paul D. Renner, Eberhard L. Grant, David R. Sapisochin, Gonzalo |
| description | Background
Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT).
Methods
All patients listed in the Toronto liver transplantation program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiologic images were reviewed by two independent radiologists. The primary end point was patient survival.
Results
Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (
p
= 0.02) and tumor burden (
p
|
| doi_str_mv | 10.1245/s10434-017-5789-3 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1865527911</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1903807874</sourcerecordid><originalsourceid>FETCH-LOGICAL-c415t-e3cc37590a5b84b02666d3aecb23dde7579defaff261137b239590a7968e73183</originalsourceid><addsrcrecordid>eNp1kc2OFCEUhYnRODOtD-DGkLhxUwpF8VPLTkedSTpxEts1oahbDhMaSqDazN4Hl06Nxpi4Au797gHOQegVJe9o2_H3mZKOdQ2hsuFS9Q17gi4pr5VOKPq07olQTd8KfoGucr4nFWSEP0cXraKCUCYv0c-9O0HCh2RCnr0JxRQXA3YZG3ybYIJkBg946wukUHsnwCXiW-O9W0-Hu4rMD3iKCX8BD7bAWPvFQSgZ_3DlDm_Hkwm2lq9hNiVa8H7xJuGdSdaFeDQv0LPJ-AwvH9cN-vrxw2F33ew_f7rZbfeN7SgvDTBrmeQ9MXxQ3UBaIcTIDNihZeMIkst-hMlMUyto_Vyt9mdY9kKBZFSxDXq76s4pfl8gF310-fwcEyAuWVMlOG9lX6c36M0_6H1cqgO-Uj1hikglu0rRlbIp5lzt0nNyR5MeNCX6HJFeI9LVeX2OSLM68_pReRmOMP6Z-J1JBdoVyLUVvkH66-r_qv4CaFudPQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1903807874</pqid></control><display><type>article</type><title>Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma</title><source>Springer Link</source><creator>Aravinthan, Aloysious D. ; Bruni, Silvio G. ; Doyle, Adam C. ; Thein, Hla-Hla ; Goldaracena, Nicolas ; Issachar, Assaf ; Lilly, Leslie B. ; Selzner, Nazia ; Bhat, Mamatha ; Sreeharsha, Boraiah ; Selzner, Markus ; Ghanekar, Anand ; Cattral, Mark S. ; McGilvray, Ian D. ; Greig, Paul D. ; Renner, Eberhard L. ; Grant, David R. ; Sapisochin, Gonzalo</creator><creatorcontrib>Aravinthan, Aloysious D. ; Bruni, Silvio G. ; Doyle, Adam C. ; Thein, Hla-Hla ; Goldaracena, Nicolas ; Issachar, Assaf ; Lilly, Leslie B. ; Selzner, Nazia ; Bhat, Mamatha ; Sreeharsha, Boraiah ; Selzner, Markus ; Ghanekar, Anand ; Cattral, Mark S. ; McGilvray, Ian D. ; Greig, Paul D. ; Renner, Eberhard L. ; Grant, David R. ; Sapisochin, Gonzalo</creatorcontrib><description>Background
Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT).
Methods
All patients listed in the Toronto liver transplantation program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiologic images were reviewed by two independent radiologists. The primary end point was patient survival.
Results
Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (
p
= 0.02) and tumor burden (
p
< 0.001). The majority of those listed underwent LT (
n
= 69, 72%). Both tumor progression on waiting list (hazard ratio [HR] 4.973; range1.599–15.464;
p
= 0.006) and peak alpha-fetoprotein (AFP) at 400 ng/ml or higher (HR, 4.604; range 1.660–12.768;
p
= 0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% of the patients (
n
= 24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (
p
= 0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93, 71, and 66%.
Conclusion
Liver transplantation provides significantly better survival rates than palliation for patients with selected advanced HCC.</description><identifier>ISSN: 1068-9265</identifier><identifier>EISSN: 1534-4681</identifier><identifier>DOI: 10.1245/s10434-017-5789-3</identifier><identifier>PMID: 28160137</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - surgery ; Female ; Follow-Up Studies ; Hepatobiliary Tumors ; Hepatocellular carcinoma ; Humans ; Immunology ; Liver cancer ; Liver Neoplasms - pathology ; Liver Neoplasms - surgery ; Liver Transplantation ; Liver transplants ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Oncology ; Palliation ; Palliative Care ; Patient Selection ; Retrospective Studies ; Surgery ; Surgical Oncology ; Survival Rate ; Treatment Outcome ; Tumor Burden</subject><ispartof>Annals of surgical oncology, 2017-07, Vol.24 (7), p.1843-1851</ispartof><rights>Society of Surgical Oncology 2017</rights><rights>Annals of Surgical Oncology is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-e3cc37590a5b84b02666d3aecb23dde7579defaff261137b239590a7968e73183</citedby><cites>FETCH-LOGICAL-c415t-e3cc37590a5b84b02666d3aecb23dde7579defaff261137b239590a7968e73183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28160137$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aravinthan, Aloysious D.</creatorcontrib><creatorcontrib>Bruni, Silvio G.</creatorcontrib><creatorcontrib>Doyle, Adam C.</creatorcontrib><creatorcontrib>Thein, Hla-Hla</creatorcontrib><creatorcontrib>Goldaracena, Nicolas</creatorcontrib><creatorcontrib>Issachar, Assaf</creatorcontrib><creatorcontrib>Lilly, Leslie B.</creatorcontrib><creatorcontrib>Selzner, Nazia</creatorcontrib><creatorcontrib>Bhat, Mamatha</creatorcontrib><creatorcontrib>Sreeharsha, Boraiah</creatorcontrib><creatorcontrib>Selzner, Markus</creatorcontrib><creatorcontrib>Ghanekar, Anand</creatorcontrib><creatorcontrib>Cattral, Mark S.</creatorcontrib><creatorcontrib>McGilvray, Ian D.</creatorcontrib><creatorcontrib>Greig, Paul D.</creatorcontrib><creatorcontrib>Renner, Eberhard L.</creatorcontrib><creatorcontrib>Grant, David R.</creatorcontrib><creatorcontrib>Sapisochin, Gonzalo</creatorcontrib><title>Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma</title><title>Annals of surgical oncology</title><addtitle>Ann Surg Oncol</addtitle><addtitle>Ann Surg Oncol</addtitle><description>Background
Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT).
Methods
All patients listed in the Toronto liver transplantation program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiologic images were reviewed by two independent radiologists. The primary end point was patient survival.
Results
Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (
p
= 0.02) and tumor burden (
p
< 0.001). The majority of those listed underwent LT (
n
= 69, 72%). Both tumor progression on waiting list (hazard ratio [HR] 4.973; range1.599–15.464;
p
= 0.006) and peak alpha-fetoprotein (AFP) at 400 ng/ml or higher (HR, 4.604; range 1.660–12.768;
p
= 0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% of the patients (
n
= 24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (
p
= 0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93, 71, and 66%.
Conclusion
Liver transplantation provides significantly better survival rates than palliation for patients with selected advanced HCC.</description><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - surgery</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Hepatobiliary Tumors</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Immunology</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - surgery</subject><subject>Liver Transplantation</subject><subject>Liver transplants</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Palliation</subject><subject>Palliative Care</subject><subject>Patient Selection</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Survival Rate</subject><subject>Treatment Outcome</subject><subject>Tumor Burden</subject><issn>1068-9265</issn><issn>1534-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp1kc2OFCEUhYnRODOtD-DGkLhxUwpF8VPLTkedSTpxEts1oahbDhMaSqDazN4Hl06Nxpi4Au797gHOQegVJe9o2_H3mZKOdQ2hsuFS9Q17gi4pr5VOKPq07olQTd8KfoGucr4nFWSEP0cXraKCUCYv0c-9O0HCh2RCnr0JxRQXA3YZG3ybYIJkBg946wukUHsnwCXiW-O9W0-Hu4rMD3iKCX8BD7bAWPvFQSgZ_3DlDm_Hkwm2lq9hNiVa8H7xJuGdSdaFeDQv0LPJ-AwvH9cN-vrxw2F33ew_f7rZbfeN7SgvDTBrmeQ9MXxQ3UBaIcTIDNihZeMIkst-hMlMUyto_Vyt9mdY9kKBZFSxDXq76s4pfl8gF310-fwcEyAuWVMlOG9lX6c36M0_6H1cqgO-Uj1hikglu0rRlbIp5lzt0nNyR5MeNCX6HJFeI9LVeX2OSLM68_pReRmOMP6Z-J1JBdoVyLUVvkH66-r_qv4CaFudPQ</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Aravinthan, Aloysious D.</creator><creator>Bruni, Silvio G.</creator><creator>Doyle, Adam C.</creator><creator>Thein, Hla-Hla</creator><creator>Goldaracena, Nicolas</creator><creator>Issachar, Assaf</creator><creator>Lilly, Leslie B.</creator><creator>Selzner, Nazia</creator><creator>Bhat, Mamatha</creator><creator>Sreeharsha, Boraiah</creator><creator>Selzner, Markus</creator><creator>Ghanekar, Anand</creator><creator>Cattral, Mark S.</creator><creator>McGilvray, Ian D.</creator><creator>Greig, Paul D.</creator><creator>Renner, Eberhard L.</creator><creator>Grant, David R.</creator><creator>Sapisochin, Gonzalo</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20170701</creationdate><title>Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma</title><author>Aravinthan, Aloysious D. ; Bruni, Silvio G. ; Doyle, Adam C. ; Thein, Hla-Hla ; Goldaracena, Nicolas ; Issachar, Assaf ; Lilly, Leslie B. ; Selzner, Nazia ; Bhat, Mamatha ; Sreeharsha, Boraiah ; Selzner, Markus ; Ghanekar, Anand ; Cattral, Mark S. ; McGilvray, Ian D. ; Greig, Paul D. ; Renner, Eberhard L. ; Grant, David R. ; Sapisochin, Gonzalo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-e3cc37590a5b84b02666d3aecb23dde7579defaff261137b239590a7968e73183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - surgery</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Hepatobiliary Tumors</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Immunology</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - surgery</topic><topic>Liver Transplantation</topic><topic>Liver transplants</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Palliation</topic><topic>Palliative Care</topic><topic>Patient Selection</topic><topic>Retrospective Studies</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Survival Rate</topic><topic>Treatment Outcome</topic><topic>Tumor Burden</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aravinthan, Aloysious D.</creatorcontrib><creatorcontrib>Bruni, Silvio G.</creatorcontrib><creatorcontrib>Doyle, Adam C.</creatorcontrib><creatorcontrib>Thein, Hla-Hla</creatorcontrib><creatorcontrib>Goldaracena, Nicolas</creatorcontrib><creatorcontrib>Issachar, Assaf</creatorcontrib><creatorcontrib>Lilly, Leslie B.</creatorcontrib><creatorcontrib>Selzner, Nazia</creatorcontrib><creatorcontrib>Bhat, Mamatha</creatorcontrib><creatorcontrib>Sreeharsha, Boraiah</creatorcontrib><creatorcontrib>Selzner, Markus</creatorcontrib><creatorcontrib>Ghanekar, Anand</creatorcontrib><creatorcontrib>Cattral, Mark S.</creatorcontrib><creatorcontrib>McGilvray, Ian D.</creatorcontrib><creatorcontrib>Greig, Paul D.</creatorcontrib><creatorcontrib>Renner, Eberhard L.</creatorcontrib><creatorcontrib>Grant, David R.</creatorcontrib><creatorcontrib>Sapisochin, Gonzalo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aravinthan, Aloysious D.</au><au>Bruni, Silvio G.</au><au>Doyle, Adam C.</au><au>Thein, Hla-Hla</au><au>Goldaracena, Nicolas</au><au>Issachar, Assaf</au><au>Lilly, Leslie B.</au><au>Selzner, Nazia</au><au>Bhat, Mamatha</au><au>Sreeharsha, Boraiah</au><au>Selzner, Markus</au><au>Ghanekar, Anand</au><au>Cattral, Mark S.</au><au>McGilvray, Ian D.</au><au>Greig, Paul D.</au><au>Renner, Eberhard L.</au><au>Grant, David R.</au><au>Sapisochin, Gonzalo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma</atitle><jtitle>Annals of surgical oncology</jtitle><stitle>Ann Surg Oncol</stitle><addtitle>Ann Surg Oncol</addtitle><date>2017-07-01</date><risdate>2017</risdate><volume>24</volume><issue>7</issue><spage>1843</spage><epage>1851</epage><pages>1843-1851</pages><issn>1068-9265</issn><eissn>1534-4681</eissn><abstract>Background
Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT).
Methods
All patients listed in the Toronto liver transplantation program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiologic images were reviewed by two independent radiologists. The primary end point was patient survival.
Results
Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (
p
= 0.02) and tumor burden (
p
< 0.001). The majority of those listed underwent LT (
n
= 69, 72%). Both tumor progression on waiting list (hazard ratio [HR] 4.973; range1.599–15.464;
p
= 0.006) and peak alpha-fetoprotein (AFP) at 400 ng/ml or higher (HR, 4.604; range 1.660–12.768;
p
= 0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% of the patients (
n
= 24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (
p
= 0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93, 71, and 66%.
Conclusion
Liver transplantation provides significantly better survival rates than palliation for patients with selected advanced HCC.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>28160137</pmid><doi>10.1245/s10434-017-5789-3</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1068-9265 |
| ispartof | Annals of surgical oncology, 2017-07, Vol.24 (7), p.1843-1851 |
| issn | 1068-9265 1534-4681 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1865527911 |
| source | Springer Link |
| subjects | Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - surgery Female Follow-Up Studies Hepatobiliary Tumors Hepatocellular carcinoma Humans Immunology Liver cancer Liver Neoplasms - pathology Liver Neoplasms - surgery Liver Transplantation Liver transplants Male Medicine Medicine & Public Health Middle Aged Oncology Palliation Palliative Care Patient Selection Retrospective Studies Surgery Surgical Oncology Survival Rate Treatment Outcome Tumor Burden |
| title | Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma |
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