Hematogenous Dissemination of Hepatocytes and Tumor Cells after Surgical Resection of Hepatocellular Carcinoma: A Quantitative Analysis
The only hope of long-term survival for patients with hepatocellular carcinoma (HCC) is surgical resection or liver transplantation. However, recurrence or metastasis formation is common after surgery. We aim to assess whether surgical resection leads to hematogenous dissemination of malignant and n...
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Veröffentlicht in: | Clinical cancer research 1999-12, Vol.5 (12), p.4021-4027 |
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description | The only hope of long-term survival for patients with hepatocellular carcinoma (HCC) is surgical resection or liver transplantation.
However, recurrence or metastasis formation is common after surgery. We aim to assess whether surgical resection leads to
hematogenous dissemination of malignant and nontumor hepatocytes and determine the quantity and timing of hepatocyte shedding
into the circulation. Using semiquantitative reverse transcription-PCR for α-fetoprotein ( afp ) and albumin ( alb ) mRNAs, we measured the mass of malignant and nontumor hepatocytes in 53 peripheral blood samples collected preoperatively,
intraoperatively, and postoperatively from 13 HCC patients. We compared these data with those in 54 control samples collected
from 24 healthy subjects and patients with chronic hepatitis/cirrhosis and 10 hepatocellular adenoma patients who underwent
resection. Clinicopathological information of HCC patients was obtained during 3-year follow-up. In 100% (23 of 23) of HCC
and adenoma patients, alb mRNA levels increased 10–10 6 -fold intraoperatively and then markedly declined within 8 weeks after operation. Levels of afp mRNA increased 5–7600-fold preoperatively in 8% (1 of 13) and postoperatively in 70% (9 of 13) of HCC patients. All five
HCC patients with persistently elevated afp mRNA levels died from intrahepatic/extrahepatic metastasis, liver recurrence, or persistent HCC within 1 year after surgery.
The absence/clearance of afp mRNA in 75% (six of eight) of survivors was strongly associated with the absence of metastasis/recurrence ( P = 0.02). We present evidence that alb- expressing hepatocytes are released intraoperatively into the circulation, and afp -expressing tumor cells are disseminated mostly postoperatively that may potentially be the source of recurrence or metastasis.
Sequential quantification of both alb and afp mRNAs may provide insights for risk assessment and prognostic indication. |
format | Article |
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However, recurrence or metastasis formation is common after surgery. We aim to assess whether surgical resection leads to
hematogenous dissemination of malignant and nontumor hepatocytes and determine the quantity and timing of hepatocyte shedding
into the circulation. Using semiquantitative reverse transcription-PCR for α-fetoprotein ( afp ) and albumin ( alb ) mRNAs, we measured the mass of malignant and nontumor hepatocytes in 53 peripheral blood samples collected preoperatively,
intraoperatively, and postoperatively from 13 HCC patients. We compared these data with those in 54 control samples collected
from 24 healthy subjects and patients with chronic hepatitis/cirrhosis and 10 hepatocellular adenoma patients who underwent
resection. Clinicopathological information of HCC patients was obtained during 3-year follow-up. In 100% (23 of 23) of HCC
and adenoma patients, alb mRNA levels increased 10–10 6 -fold intraoperatively and then markedly declined within 8 weeks after operation. Levels of afp mRNA increased 5–7600-fold preoperatively in 8% (1 of 13) and postoperatively in 70% (9 of 13) of HCC patients. All five
HCC patients with persistently elevated afp mRNA levels died from intrahepatic/extrahepatic metastasis, liver recurrence, or persistent HCC within 1 year after surgery.
The absence/clearance of afp mRNA in 75% (six of eight) of survivors was strongly associated with the absence of metastasis/recurrence ( P = 0.02). We present evidence that alb- expressing hepatocytes are released intraoperatively into the circulation, and afp -expressing tumor cells are disseminated mostly postoperatively that may potentially be the source of recurrence or metastasis.
Sequential quantification of both alb and afp mRNAs may provide insights for risk assessment and prognostic indication.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 10632334</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adenoma - blood ; Adenoma - metabolism ; Adenoma - pathology ; Adenoma - surgery ; Adult ; Aged ; alpha-Fetoproteins - biosynthesis ; alpha-Fetoproteins - genetics ; alpha-Fetoproteins - metabolism ; Biological and medical sciences ; Carcinoma, Hepatocellular - blood ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - surgery ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Hepatectomy - adverse effects ; Humans ; Intraoperative Period ; Liver Neoplasms - blood ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Liver Neoplasms - surgery ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Middle Aged ; Neoplastic Cells, Circulating - pathology ; Postoperative Period ; Preoperative Care ; RNA, Messenger - metabolism ; Serum Albumin - biosynthesis ; Serum Albumin - genetics ; Serum Albumin - metabolism ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Clinical cancer research, 1999-12, Vol.5 (12), p.4021-4027</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1234816$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10632334$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WONG, I. H. N</creatorcontrib><creatorcontrib>LAU, W. Y</creatorcontrib><creatorcontrib>LEUNG, T</creatorcontrib><creatorcontrib>YEO, W</creatorcontrib><creatorcontrib>JOHNSON, P. J</creatorcontrib><title>Hematogenous Dissemination of Hepatocytes and Tumor Cells after Surgical Resection of Hepatocellular Carcinoma: A Quantitative Analysis</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>The only hope of long-term survival for patients with hepatocellular carcinoma (HCC) is surgical resection or liver transplantation.
However, recurrence or metastasis formation is common after surgery. We aim to assess whether surgical resection leads to
hematogenous dissemination of malignant and nontumor hepatocytes and determine the quantity and timing of hepatocyte shedding
into the circulation. Using semiquantitative reverse transcription-PCR for α-fetoprotein ( afp ) and albumin ( alb ) mRNAs, we measured the mass of malignant and nontumor hepatocytes in 53 peripheral blood samples collected preoperatively,
intraoperatively, and postoperatively from 13 HCC patients. We compared these data with those in 54 control samples collected
from 24 healthy subjects and patients with chronic hepatitis/cirrhosis and 10 hepatocellular adenoma patients who underwent
resection. Clinicopathological information of HCC patients was obtained during 3-year follow-up. In 100% (23 of 23) of HCC
and adenoma patients, alb mRNA levels increased 10–10 6 -fold intraoperatively and then markedly declined within 8 weeks after operation. Levels of afp mRNA increased 5–7600-fold preoperatively in 8% (1 of 13) and postoperatively in 70% (9 of 13) of HCC patients. All five
HCC patients with persistently elevated afp mRNA levels died from intrahepatic/extrahepatic metastasis, liver recurrence, or persistent HCC within 1 year after surgery.
The absence/clearance of afp mRNA in 75% (six of eight) of survivors was strongly associated with the absence of metastasis/recurrence ( P = 0.02). We present evidence that alb- expressing hepatocytes are released intraoperatively into the circulation, and afp -expressing tumor cells are disseminated mostly postoperatively that may potentially be the source of recurrence or metastasis.
Sequential quantification of both alb and afp mRNAs may provide insights for risk assessment and prognostic indication.</description><subject>Adenoma - blood</subject><subject>Adenoma - metabolism</subject><subject>Adenoma - pathology</subject><subject>Adenoma - surgery</subject><subject>Adult</subject><subject>Aged</subject><subject>alpha-Fetoproteins - biosynthesis</subject><subject>alpha-Fetoproteins - genetics</subject><subject>alpha-Fetoproteins - metabolism</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - blood</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - surgery</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepatectomy - adverse effects</subject><subject>Humans</subject><subject>Intraoperative Period</subject><subject>Liver Neoplasms - blood</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - surgery</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplastic Cells, Circulating - pathology</subject><subject>Postoperative Period</subject><subject>Preoperative Care</subject><subject>RNA, Messenger - metabolism</subject><subject>Serum Albumin - biosynthesis</subject><subject>Serum Albumin - genetics</subject><subject>Serum Albumin - metabolism</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0FtLwzAUB_AiipvTryB5EPGlkFtvvo15mTAQdT6Xs_R0jbTpTFJln8CvbWQTwacknN9Jcv4H0ZglSRYLniaHYU-zPKZS8FF04twbpUwyKo-jEaOp4ELIcfQ1xw58v0bTD47caOew0wa87g3pazLHTaiqrUdHwFRkOXS9JTNs23CuPVryMti1VtCSZ3So_vUFN7QQGsAqbfoOrsmUPA1gvPbhjQ8kUwPt1ml3Gh3V0Do826-T6PXudjmbx4vH-4fZdBE3PC18rPJMKFYBMFUUiViBRJljKmpZJxVySelK0UKxjGLCBFdFVbMqBYY5z3MGUkyiy929G9u_D-h82Wn3808wGBIo00IUGc-TAM_3cFh1WJUbqzuw2_I3ugAu9gBcmL-2YJR2f44LmbM0sKsda_S6-dQWSxUgWhviCqk0ZRJoKSln4hu2noiZ</recordid><startdate>19991201</startdate><enddate>19991201</enddate><creator>WONG, I. H. N</creator><creator>LAU, W. Y</creator><creator>LEUNG, T</creator><creator>YEO, W</creator><creator>JOHNSON, P. J</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19991201</creationdate><title>Hematogenous Dissemination of Hepatocytes and Tumor Cells after Surgical Resection of Hepatocellular Carcinoma: A Quantitative Analysis</title><author>WONG, I. H. N ; LAU, W. Y ; LEUNG, T ; YEO, W ; JOHNSON, P. J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h269t-c873c1daa1c9953ba4e48e63f4f5de2400bc09c170e5132c9df1d6a1e82881a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adenoma - blood</topic><topic>Adenoma - metabolism</topic><topic>Adenoma - pathology</topic><topic>Adenoma - surgery</topic><topic>Adult</topic><topic>Aged</topic><topic>alpha-Fetoproteins - biosynthesis</topic><topic>alpha-Fetoproteins - genetics</topic><topic>alpha-Fetoproteins - metabolism</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - blood</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - surgery</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepatectomy - adverse effects</topic><topic>Humans</topic><topic>Intraoperative Period</topic><topic>Liver Neoplasms - blood</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - surgery</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplastic Cells, Circulating - pathology</topic><topic>Postoperative Period</topic><topic>Preoperative Care</topic><topic>RNA, Messenger - metabolism</topic><topic>Serum Albumin - biosynthesis</topic><topic>Serum Albumin - genetics</topic><topic>Serum Albumin - metabolism</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WONG, I. H. N</creatorcontrib><creatorcontrib>LAU, W. Y</creatorcontrib><creatorcontrib>LEUNG, T</creatorcontrib><creatorcontrib>YEO, W</creatorcontrib><creatorcontrib>JOHNSON, P. J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WONG, I. H. N</au><au>LAU, W. Y</au><au>LEUNG, T</au><au>YEO, W</au><au>JOHNSON, P. J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hematogenous Dissemination of Hepatocytes and Tumor Cells after Surgical Resection of Hepatocellular Carcinoma: A Quantitative Analysis</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>1999-12-01</date><risdate>1999</risdate><volume>5</volume><issue>12</issue><spage>4021</spage><epage>4027</epage><pages>4021-4027</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>The only hope of long-term survival for patients with hepatocellular carcinoma (HCC) is surgical resection or liver transplantation.
However, recurrence or metastasis formation is common after surgery. We aim to assess whether surgical resection leads to
hematogenous dissemination of malignant and nontumor hepatocytes and determine the quantity and timing of hepatocyte shedding
into the circulation. Using semiquantitative reverse transcription-PCR for α-fetoprotein ( afp ) and albumin ( alb ) mRNAs, we measured the mass of malignant and nontumor hepatocytes in 53 peripheral blood samples collected preoperatively,
intraoperatively, and postoperatively from 13 HCC patients. We compared these data with those in 54 control samples collected
from 24 healthy subjects and patients with chronic hepatitis/cirrhosis and 10 hepatocellular adenoma patients who underwent
resection. Clinicopathological information of HCC patients was obtained during 3-year follow-up. In 100% (23 of 23) of HCC
and adenoma patients, alb mRNA levels increased 10–10 6 -fold intraoperatively and then markedly declined within 8 weeks after operation. Levels of afp mRNA increased 5–7600-fold preoperatively in 8% (1 of 13) and postoperatively in 70% (9 of 13) of HCC patients. All five
HCC patients with persistently elevated afp mRNA levels died from intrahepatic/extrahepatic metastasis, liver recurrence, or persistent HCC within 1 year after surgery.
The absence/clearance of afp mRNA in 75% (six of eight) of survivors was strongly associated with the absence of metastasis/recurrence ( P = 0.02). We present evidence that alb- expressing hepatocytes are released intraoperatively into the circulation, and afp -expressing tumor cells are disseminated mostly postoperatively that may potentially be the source of recurrence or metastasis.
Sequential quantification of both alb and afp mRNAs may provide insights for risk assessment and prognostic indication.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>10632334</pmid><tpages>7</tpages></addata></record> |
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source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
subjects | Adenoma - blood Adenoma - metabolism Adenoma - pathology Adenoma - surgery Adult Aged alpha-Fetoproteins - biosynthesis alpha-Fetoproteins - genetics alpha-Fetoproteins - metabolism Biological and medical sciences Carcinoma, Hepatocellular - blood Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - surgery Female Gastroenterology. Liver. Pancreas. Abdomen Hepatectomy - adverse effects Humans Intraoperative Period Liver Neoplasms - blood Liver Neoplasms - metabolism Liver Neoplasms - pathology Liver Neoplasms - surgery Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Middle Aged Neoplastic Cells, Circulating - pathology Postoperative Period Preoperative Care RNA, Messenger - metabolism Serum Albumin - biosynthesis Serum Albumin - genetics Serum Albumin - metabolism Tumor Cells, Cultured Tumors |
title | Hematogenous Dissemination of Hepatocytes and Tumor Cells after Surgical Resection of Hepatocellular Carcinoma: A Quantitative Analysis |
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