Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B-positive patients with hepatocellular carcinoma
Background and Objectives Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis‐B or ‐C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising l...
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| Veröffentlicht in: | Journal of surgical oncology 2015-06, Vol.111 (7), p.862-867 |
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| container_title | Journal of surgical oncology |
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| creator | Wang, Xiaojin Bayer, Michael E. Chen, Xiaosong Fredrickson, Craig Cornforth, Andrew N. Liang, Greg Cannon, Jessica He, Jia Fu, Qingchun Liu, Jia Nistor, Gabriel I. Cao, Wei Chen, Chengwei Dillman, Robert O. |
| description | Background and Objectives
Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis‐B or ‐C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long‐term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high‐risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis.
Methods
Previously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC‐TC. After one course of trans‐arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC‐TC suspended in granulocyte‐macrophage colony stimulating factor were administered. Patients were monitored for eight weeks.
Results
HCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA.
Conclusion
Autologous DC‐TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned. J. Surg. Oncol. 2015 111:862–867. © 2014 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/jso.23897 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6220948</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3667991641</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5517-2f01e3e9f987046cd04218124676d673865986285724e086afbd2b609972fce03</originalsourceid><addsrcrecordid>eNp1kstu1DAUhi0EotPCghdAltjAIq3jOL5skKCiF6hoESCWlsdxGg9JHGyn7bwdj4YzmY64iJUln-___Z_jA8CzHB3mCOGjVXCHuOCCPQCLHAmaCST4Q7BINZwRJtAe2A9hhRASgpLHYA-XnBWkLBfg51WjgoHnMHqrWuhqqHS0NwaGwWhbWw1t1429i43xaljDWxsbqMboWnftxgAr01fexsRp07YBDmMbTPUPZr1XlVUxleLYOQ9DNN1WYnvYmEHF5BLg22xwwW4STFemj2E22yBuUoyt8lArr23vOvUEPKpVevPp9jwAX0_efTk-yy4uT8-P31xkuixzluEa5aYwohacIUJ1hQjOeY4JZbSirOC0FJxiXjJMDOJU1csKL2kaGMO1Nqg4AK9n32FcdqbSKZlXrRy87ZRfS6es_LPS20ZeuxtJMUaC8GTwcmvg3Y_RhCg7G6Z-VG_SiGROGSsY5lwk9MVf6MqNvk_tTRTFgpBiSvRqprR3IXhT78LkSE57IdNeyM1eJPb57-l35P0iJOBoBm5ta9b_d5LvP1_eW2azwqa_vNsplP8u0zxZKb99PJVX_IR9OPvEZFn8Apwx1qQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1676294430</pqid></control><display><type>article</type><title>Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B-positive patients with hepatocellular carcinoma</title><source>MEDLINE</source><source>Wiley Online Library Journals</source><creator>Wang, Xiaojin ; Bayer, Michael E. ; Chen, Xiaosong ; Fredrickson, Craig ; Cornforth, Andrew N. ; Liang, Greg ; Cannon, Jessica ; He, Jia ; Fu, Qingchun ; Liu, Jia ; Nistor, Gabriel I. ; Cao, Wei ; Chen, Chengwei ; Dillman, Robert O.</creator><creatorcontrib>Wang, Xiaojin ; Bayer, Michael E. ; Chen, Xiaosong ; Fredrickson, Craig ; Cornforth, Andrew N. ; Liang, Greg ; Cannon, Jessica ; He, Jia ; Fu, Qingchun ; Liu, Jia ; Nistor, Gabriel I. ; Cao, Wei ; Chen, Chengwei ; Dillman, Robert O.</creatorcontrib><description>Background and Objectives
Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis‐B or ‐C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long‐term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high‐risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis.
Methods
Previously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC‐TC. After one course of trans‐arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC‐TC suspended in granulocyte‐macrophage colony stimulating factor were administered. Patients were monitored for eight weeks.
Results
HCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA.
Conclusion
Autologous DC‐TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned. J. Surg. Oncol. 2015 111:862–867. © 2014 Wiley Periodicals, Inc.</description><identifier>ISSN: 0022-4790</identifier><identifier>EISSN: 1096-9098</identifier><identifier>DOI: 10.1002/jso.23897</identifier><identifier>PMID: 25873455</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Carcinoma, Hepatocellular - immunology ; Carcinoma, Hepatocellular - therapy ; Carcinoma, Hepatocellular - virology ; dendritic cell vaccine ; Dendritic Cells - immunology ; Dendritic Cells - transplantation ; Female ; Follow-Up Studies ; hepatitis B ; Hepatitis B - immunology ; Hepatitis B - therapy ; Hepatitis B - virology ; Hepatitis B virus - isolation & purification ; hepatocellular carcinoma ; Humans ; Immunotherapy ; Liver Neoplasms - immunology ; Liver Neoplasms - therapy ; Liver Neoplasms - virology ; Male ; Middle Aged ; Neoplasm Staging ; Neoplastic Stem Cells - immunology ; Neoplastic Stem Cells - transplantation ; Prognosis ; therapeutic cancer vaccines ; Transplantation, Autologous ; tumor stem cells</subject><ispartof>Journal of surgical oncology, 2015-06, Vol.111 (7), p.862-867</ispartof><rights>2015 The Authors. Published by Wiley Periodicals, Inc.</rights><rights>2015 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5517-2f01e3e9f987046cd04218124676d673865986285724e086afbd2b609972fce03</citedby><cites>FETCH-LOGICAL-c5517-2f01e3e9f987046cd04218124676d673865986285724e086afbd2b609972fce03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjso.23897$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjso.23897$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25873455$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xiaojin</creatorcontrib><creatorcontrib>Bayer, Michael E.</creatorcontrib><creatorcontrib>Chen, Xiaosong</creatorcontrib><creatorcontrib>Fredrickson, Craig</creatorcontrib><creatorcontrib>Cornforth, Andrew N.</creatorcontrib><creatorcontrib>Liang, Greg</creatorcontrib><creatorcontrib>Cannon, Jessica</creatorcontrib><creatorcontrib>He, Jia</creatorcontrib><creatorcontrib>Fu, Qingchun</creatorcontrib><creatorcontrib>Liu, Jia</creatorcontrib><creatorcontrib>Nistor, Gabriel I.</creatorcontrib><creatorcontrib>Cao, Wei</creatorcontrib><creatorcontrib>Chen, Chengwei</creatorcontrib><creatorcontrib>Dillman, Robert O.</creatorcontrib><title>Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B-positive patients with hepatocellular carcinoma</title><title>Journal of surgical oncology</title><addtitle>J. Surg. Oncol</addtitle><description>Background and Objectives
Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis‐B or ‐C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long‐term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high‐risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis.
Methods
Previously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC‐TC. After one course of trans‐arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC‐TC suspended in granulocyte‐macrophage colony stimulating factor were administered. Patients were monitored for eight weeks.
Results
HCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA.
Conclusion
Autologous DC‐TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned. J. Surg. Oncol. 2015 111:862–867. © 2014 Wiley Periodicals, Inc.</description><subject>Adult</subject><subject>Aged</subject><subject>Carcinoma, Hepatocellular - immunology</subject><subject>Carcinoma, Hepatocellular - therapy</subject><subject>Carcinoma, Hepatocellular - virology</subject><subject>dendritic cell vaccine</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - transplantation</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>hepatitis B</subject><subject>Hepatitis B - immunology</subject><subject>Hepatitis B - therapy</subject><subject>Hepatitis B - virology</subject><subject>Hepatitis B virus - isolation & purification</subject><subject>hepatocellular carcinoma</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Liver Neoplasms - immunology</subject><subject>Liver Neoplasms - therapy</subject><subject>Liver Neoplasms - virology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Neoplastic Stem Cells - immunology</subject><subject>Neoplastic Stem Cells - transplantation</subject><subject>Prognosis</subject><subject>therapeutic cancer vaccines</subject><subject>Transplantation, Autologous</subject><subject>tumor stem cells</subject><issn>0022-4790</issn><issn>1096-9098</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kstu1DAUhi0EotPCghdAltjAIq3jOL5skKCiF6hoESCWlsdxGg9JHGyn7bwdj4YzmY64iJUln-___Z_jA8CzHB3mCOGjVXCHuOCCPQCLHAmaCST4Q7BINZwRJtAe2A9hhRASgpLHYA-XnBWkLBfg51WjgoHnMHqrWuhqqHS0NwaGwWhbWw1t1429i43xaljDWxsbqMboWnftxgAr01fexsRp07YBDmMbTPUPZr1XlVUxleLYOQ9DNN1WYnvYmEHF5BLg22xwwW4STFemj2E22yBuUoyt8lArr23vOvUEPKpVevPp9jwAX0_efTk-yy4uT8-P31xkuixzluEa5aYwohacIUJ1hQjOeY4JZbSirOC0FJxiXjJMDOJU1csKL2kaGMO1Nqg4AK9n32FcdqbSKZlXrRy87ZRfS6es_LPS20ZeuxtJMUaC8GTwcmvg3Y_RhCg7G6Z-VG_SiGROGSsY5lwk9MVf6MqNvk_tTRTFgpBiSvRqprR3IXhT78LkSE57IdNeyM1eJPb57-l35P0iJOBoBm5ta9b_d5LvP1_eW2azwqa_vNsplP8u0zxZKb99PJVX_IR9OPvEZFn8Apwx1qQ</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Wang, Xiaojin</creator><creator>Bayer, Michael E.</creator><creator>Chen, Xiaosong</creator><creator>Fredrickson, Craig</creator><creator>Cornforth, Andrew N.</creator><creator>Liang, Greg</creator><creator>Cannon, Jessica</creator><creator>He, Jia</creator><creator>Fu, Qingchun</creator><creator>Liu, Jia</creator><creator>Nistor, Gabriel I.</creator><creator>Cao, Wei</creator><creator>Chen, Chengwei</creator><creator>Dillman, Robert O.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>BSCLL</scope><scope>24P</scope><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>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150601</creationdate><title>Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B-positive patients with hepatocellular carcinoma</title><author>Wang, Xiaojin ; Bayer, Michael E. ; Chen, Xiaosong ; Fredrickson, Craig ; Cornforth, Andrew N. ; Liang, Greg ; Cannon, Jessica ; He, Jia ; Fu, Qingchun ; Liu, Jia ; Nistor, Gabriel I. ; Cao, Wei ; Chen, Chengwei ; Dillman, Robert O.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5517-2f01e3e9f987046cd04218124676d673865986285724e086afbd2b609972fce03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Carcinoma, Hepatocellular - immunology</topic><topic>Carcinoma, Hepatocellular - therapy</topic><topic>Carcinoma, Hepatocellular - virology</topic><topic>dendritic cell vaccine</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - transplantation</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>hepatitis B</topic><topic>Hepatitis B - immunology</topic><topic>Hepatitis B - therapy</topic><topic>Hepatitis B - virology</topic><topic>Hepatitis B virus - isolation & purification</topic><topic>hepatocellular carcinoma</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Liver Neoplasms - immunology</topic><topic>Liver Neoplasms - therapy</topic><topic>Liver Neoplasms - virology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Neoplastic Stem Cells - immunology</topic><topic>Neoplastic Stem Cells - transplantation</topic><topic>Prognosis</topic><topic>therapeutic cancer vaccines</topic><topic>Transplantation, Autologous</topic><topic>tumor stem cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xiaojin</creatorcontrib><creatorcontrib>Bayer, Michael E.</creatorcontrib><creatorcontrib>Chen, Xiaosong</creatorcontrib><creatorcontrib>Fredrickson, Craig</creatorcontrib><creatorcontrib>Cornforth, Andrew N.</creatorcontrib><creatorcontrib>Liang, Greg</creatorcontrib><creatorcontrib>Cannon, Jessica</creatorcontrib><creatorcontrib>He, Jia</creatorcontrib><creatorcontrib>Fu, Qingchun</creatorcontrib><creatorcontrib>Liu, Jia</creatorcontrib><creatorcontrib>Nistor, Gabriel I.</creatorcontrib><creatorcontrib>Cao, Wei</creatorcontrib><creatorcontrib>Chen, Chengwei</creatorcontrib><creatorcontrib>Dillman, Robert O.</creatorcontrib><collection>Istex</collection><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xiaojin</au><au>Bayer, Michael E.</au><au>Chen, Xiaosong</au><au>Fredrickson, Craig</au><au>Cornforth, Andrew N.</au><au>Liang, Greg</au><au>Cannon, Jessica</au><au>He, Jia</au><au>Fu, Qingchun</au><au>Liu, Jia</au><au>Nistor, Gabriel I.</au><au>Cao, Wei</au><au>Chen, Chengwei</au><au>Dillman, Robert O.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B-positive patients with hepatocellular carcinoma</atitle><jtitle>Journal of surgical oncology</jtitle><addtitle>J. Surg. Oncol</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>111</volume><issue>7</issue><spage>862</spage><epage>867</epage><pages>862-867</pages><issn>0022-4790</issn><eissn>1096-9098</eissn><abstract>Background and Objectives
Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis‐B or ‐C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long‐term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high‐risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis.
Methods
Previously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC‐TC. After one course of trans‐arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC‐TC suspended in granulocyte‐macrophage colony stimulating factor were administered. Patients were monitored for eight weeks.
Results
HCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA.
Conclusion
Autologous DC‐TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned. J. Surg. Oncol. 2015 111:862–867. © 2014 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25873455</pmid><doi>10.1002/jso.23897</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Carcinoma, Hepatocellular - immunology Carcinoma, Hepatocellular - therapy Carcinoma, Hepatocellular - virology dendritic cell vaccine Dendritic Cells - immunology Dendritic Cells - transplantation Female Follow-Up Studies hepatitis B Hepatitis B - immunology Hepatitis B - therapy Hepatitis B - virology Hepatitis B virus - isolation & purification hepatocellular carcinoma Humans Immunotherapy Liver Neoplasms - immunology Liver Neoplasms - therapy Liver Neoplasms - virology Male Middle Aged Neoplasm Staging Neoplastic Stem Cells - immunology Neoplastic Stem Cells - transplantation Prognosis therapeutic cancer vaccines Transplantation, Autologous tumor stem cells |
| title | Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B-positive patients with hepatocellular carcinoma |
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