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
Hauptverfasser: WONG, I. H. N, LAU, W. Y, LEUNG, T, YEO, W, JOHNSON, P. J
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creator WONG, I. H. N
LAU, W. Y
LEUNG, T
YEO, W
JOHNSON, P. J
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.
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H. N ; LAU, W. Y ; LEUNG, T ; YEO, W ; JOHNSON, P. J</creator><creatorcontrib>WONG, I. H. N ; LAU, W. Y ; LEUNG, T ; YEO, W ; JOHNSON, P. J</creatorcontrib><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). 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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. 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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. 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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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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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