Liver transplantation for small hepatocellular carcinoma: The tumor‐node‐metastasis classification does not have prognostic power

Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors ≤5 cm without vascular invasion, thus avoiding the...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Hepatology (Baltimore, Md.) Md.), 1998-06, Vol.27 (6), p.1572-1577
Hauptverfasser: Llovet, Josep M., Bruix, Jordi, Fuster, Josep, Castells, Antoni, Garcia‐Valdecasas, Juan Carlos, Grande, Lluís, França, Alex, Brú, Concepció, Navasa, Miquel, Ayuso, Maria del, Solé, Manel, Real, Maria Isabel, Vilana, Ramon, Rimola, Antoni, Visa, Josep, Rodés, Joan
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1577
container_issue 6
container_start_page 1572
container_title Hepatology (Baltimore, Md.)
container_volume 27
creator Llovet, Josep M.
Bruix, Jordi
Fuster, Josep
Castells, Antoni
Garcia‐Valdecasas, Juan Carlos
Grande, Lluís
França, Alex
Brú, Concepció
Navasa, Miquel
Ayuso, Maria del
Solé, Manel
Real, Maria Isabel
Vilana, Ramon
Rimola, Antoni
Visa, Josep
Rodés, Joan
description Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors ≤5 cm without vascular invasion, thus avoiding the use of the tumor‐node‐metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 ± 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 ± 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 ± 45.1 days). The pathological tumor‐node‐metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1‐, 3‐, and 5‐year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long‐term prognosis.
doi_str_mv 10.1002/hep.510270616
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_79921694</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>79921694</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4066-c7b60be1f6a403c0187450ca1d5294a13787f33df00242b045ff1c2cf2fd65233</originalsourceid><addsrcrecordid>eNp9kE2LFDEQhoMo6-zq0aOQg3jrNR_dycSbLOuuMKCH9dzUpBMnku60qfQue_Pi3d_oLzHDDONNCBSkHt6qegh5xdklZ0y827n5suNMaKa4ekJWvBO6kbJjT8lq_9sYLs1zco74nTFmWrE-I2dGCSaFWZFfm3DvMi0ZJpwjTAVKSBP1KVMcIUZa46Ek62JcImRqIdswpRHe07udo2UZU_7z8_eUBlfL6ApgfQGpjYAYfLCHwCE5pFMqdAf3js45fZsSlmDpnB5cfkGeeYjoXh7rBfn68fru6rbZfL75dPVh09iWKdVYvVVs67hX0DJpGV_rtmMW-NAJ0wKXeq29lIOvXlqxZW3nPbfCeuEH1QkpL8jbQ25d4MfisPRjwP1tMLm0YK-NEVyZtoLNAbQ5IWbn-zmHEfJjz1m_195XL_1Je-VfH4OX7eiGE330XPtvjn1AC9FX3TbgCROi49roiukD9hCie_z_zP72-su_Bf4Cw5ifnw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>79921694</pqid></control><display><type>article</type><title>Liver transplantation for small hepatocellular carcinoma: The tumor‐node‐metastasis classification does not have prognostic power</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Llovet, Josep M. ; Bruix, Jordi ; Fuster, Josep ; Castells, Antoni ; Garcia‐Valdecasas, Juan Carlos ; Grande, Lluís ; França, Alex ; Brú, Concepció ; Navasa, Miquel ; Ayuso, Maria del ; Solé, Manel ; Real, Maria Isabel ; Vilana, Ramon ; Rimola, Antoni ; Visa, Josep ; Rodés, Joan</creator><creatorcontrib>Llovet, Josep M. ; Bruix, Jordi ; Fuster, Josep ; Castells, Antoni ; Garcia‐Valdecasas, Juan Carlos ; Grande, Lluís ; França, Alex ; Brú, Concepció ; Navasa, Miquel ; Ayuso, Maria del ; Solé, Manel ; Real, Maria Isabel ; Vilana, Ramon ; Rimola, Antoni ; Visa, Josep ; Rodés, Joan</creatorcontrib><description>Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors ≤5 cm without vascular invasion, thus avoiding the use of the tumor‐node‐metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 ± 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 ± 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 ± 45.1 days). The pathological tumor‐node‐metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1‐, 3‐, and 5‐year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long‐term prognosis.</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.510270616</identifier><identifier>PMID: 9620329</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Philadelphia, PA: W.B. Saunders</publisher><subject>Adult ; Biological and medical sciences ; Carcinoma, Hepatocellular - mortality ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - surgery ; Female ; Humans ; Liver Neoplasms - mortality ; Liver Neoplasms - pathology ; Liver Neoplasms - surgery ; Liver Transplantation ; Liver, biliary tract, pancreas, portal circulation, spleen ; Male ; Medical sciences ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the digestive system ; Survival Analysis</subject><ispartof>Hepatology (Baltimore, Md.), 1998-06, Vol.27 (6), p.1572-1577</ispartof><rights>Copyright © 1998 American Association for the Study of Liver Diseases</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4066-c7b60be1f6a403c0187450ca1d5294a13787f33df00242b045ff1c2cf2fd65233</citedby><cites>FETCH-LOGICAL-c4066-c7b60be1f6a403c0187450ca1d5294a13787f33df00242b045ff1c2cf2fd65233</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%2Fhep.510270616$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.510270616$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=2251797$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9620329$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Llovet, Josep M.</creatorcontrib><creatorcontrib>Bruix, Jordi</creatorcontrib><creatorcontrib>Fuster, Josep</creatorcontrib><creatorcontrib>Castells, Antoni</creatorcontrib><creatorcontrib>Garcia‐Valdecasas, Juan Carlos</creatorcontrib><creatorcontrib>Grande, Lluís</creatorcontrib><creatorcontrib>França, Alex</creatorcontrib><creatorcontrib>Brú, Concepció</creatorcontrib><creatorcontrib>Navasa, Miquel</creatorcontrib><creatorcontrib>Ayuso, Maria del</creatorcontrib><creatorcontrib>Solé, Manel</creatorcontrib><creatorcontrib>Real, Maria Isabel</creatorcontrib><creatorcontrib>Vilana, Ramon</creatorcontrib><creatorcontrib>Rimola, Antoni</creatorcontrib><creatorcontrib>Visa, Josep</creatorcontrib><creatorcontrib>Rodés, Joan</creatorcontrib><title>Liver transplantation for small hepatocellular carcinoma: The tumor‐node‐metastasis classification does not have prognostic power</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors ≤5 cm without vascular invasion, thus avoiding the use of the tumor‐node‐metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 ± 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 ± 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 ± 45.1 days). The pathological tumor‐node‐metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1‐, 3‐, and 5‐year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long‐term prognosis.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - surgery</subject><subject>Female</subject><subject>Humans</subject><subject>Liver Neoplasms - mortality</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - surgery</subject><subject>Liver Transplantation</subject><subject>Liver, biliary tract, pancreas, portal circulation, spleen</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis</subject><subject>Prognosis</subject><subject>Recurrence</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the digestive system</subject><subject>Survival Analysis</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2LFDEQhoMo6-zq0aOQg3jrNR_dycSbLOuuMKCH9dzUpBMnku60qfQue_Pi3d_oLzHDDONNCBSkHt6qegh5xdklZ0y827n5suNMaKa4ekJWvBO6kbJjT8lq_9sYLs1zco74nTFmWrE-I2dGCSaFWZFfm3DvMi0ZJpwjTAVKSBP1KVMcIUZa46Ek62JcImRqIdswpRHe07udo2UZU_7z8_eUBlfL6ApgfQGpjYAYfLCHwCE5pFMqdAf3js45fZsSlmDpnB5cfkGeeYjoXh7rBfn68fru6rbZfL75dPVh09iWKdVYvVVs67hX0DJpGV_rtmMW-NAJ0wKXeq29lIOvXlqxZW3nPbfCeuEH1QkpL8jbQ25d4MfisPRjwP1tMLm0YK-NEVyZtoLNAbQ5IWbn-zmHEfJjz1m_195XL_1Je-VfH4OX7eiGE330XPtvjn1AC9FX3TbgCROi49roiukD9hCie_z_zP72-su_Bf4Cw5ifnw</recordid><startdate>199806</startdate><enddate>199806</enddate><creator>Llovet, Josep M.</creator><creator>Bruix, Jordi</creator><creator>Fuster, Josep</creator><creator>Castells, Antoni</creator><creator>Garcia‐Valdecasas, Juan Carlos</creator><creator>Grande, Lluís</creator><creator>França, Alex</creator><creator>Brú, Concepció</creator><creator>Navasa, Miquel</creator><creator>Ayuso, Maria del</creator><creator>Solé, Manel</creator><creator>Real, Maria Isabel</creator><creator>Vilana, Ramon</creator><creator>Rimola, Antoni</creator><creator>Visa, Josep</creator><creator>Rodés, Joan</creator><general>W.B. Saunders</general><general>Wiley</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>199806</creationdate><title>Liver transplantation for small hepatocellular carcinoma: The tumor‐node‐metastasis classification does not have prognostic power</title><author>Llovet, Josep M. ; Bruix, Jordi ; Fuster, Josep ; Castells, Antoni ; Garcia‐Valdecasas, Juan Carlos ; Grande, Lluís ; França, Alex ; Brú, Concepció ; Navasa, Miquel ; Ayuso, Maria del ; Solé, Manel ; Real, Maria Isabel ; Vilana, Ramon ; Rimola, Antoni ; Visa, Josep ; Rodés, Joan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4066-c7b60be1f6a403c0187450ca1d5294a13787f33df00242b045ff1c2cf2fd65233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - mortality</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - surgery</topic><topic>Female</topic><topic>Humans</topic><topic>Liver Neoplasms - mortality</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - surgery</topic><topic>Liver Transplantation</topic><topic>Liver, biliary tract, pancreas, portal circulation, spleen</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Metastasis</topic><topic>Prognosis</topic><topic>Recurrence</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the digestive system</topic><topic>Survival Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Llovet, Josep M.</creatorcontrib><creatorcontrib>Bruix, Jordi</creatorcontrib><creatorcontrib>Fuster, Josep</creatorcontrib><creatorcontrib>Castells, Antoni</creatorcontrib><creatorcontrib>Garcia‐Valdecasas, Juan Carlos</creatorcontrib><creatorcontrib>Grande, Lluís</creatorcontrib><creatorcontrib>França, Alex</creatorcontrib><creatorcontrib>Brú, Concepció</creatorcontrib><creatorcontrib>Navasa, Miquel</creatorcontrib><creatorcontrib>Ayuso, Maria del</creatorcontrib><creatorcontrib>Solé, Manel</creatorcontrib><creatorcontrib>Real, Maria Isabel</creatorcontrib><creatorcontrib>Vilana, Ramon</creatorcontrib><creatorcontrib>Rimola, Antoni</creatorcontrib><creatorcontrib>Visa, Josep</creatorcontrib><creatorcontrib>Rodés, Joan</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>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Llovet, Josep M.</au><au>Bruix, Jordi</au><au>Fuster, Josep</au><au>Castells, Antoni</au><au>Garcia‐Valdecasas, Juan Carlos</au><au>Grande, Lluís</au><au>França, Alex</au><au>Brú, Concepció</au><au>Navasa, Miquel</au><au>Ayuso, Maria del</au><au>Solé, Manel</au><au>Real, Maria Isabel</au><au>Vilana, Ramon</au><au>Rimola, Antoni</au><au>Visa, Josep</au><au>Rodés, Joan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Liver transplantation for small hepatocellular carcinoma: The tumor‐node‐metastasis classification does not have prognostic power</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>1998-06</date><risdate>1998</risdate><volume>27</volume><issue>6</issue><spage>1572</spage><epage>1577</epage><pages>1572-1577</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors ≤5 cm without vascular invasion, thus avoiding the use of the tumor‐node‐metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 ± 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 ± 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 ± 45.1 days). The pathological tumor‐node‐metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1‐, 3‐, and 5‐year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long‐term prognosis.</abstract><cop>Philadelphia, PA</cop><pub>W.B. Saunders</pub><pmid>9620329</pmid><doi>10.1002/hep.510270616</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0270-9139
ispartof Hepatology (Baltimore, Md.), 1998-06, Vol.27 (6), p.1572-1577
issn 0270-9139
1527-3350
language eng
recordid cdi_proquest_miscellaneous_79921694
source MEDLINE; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals
subjects Adult
Biological and medical sciences
Carcinoma, Hepatocellular - mortality
Carcinoma, Hepatocellular - pathology
Carcinoma, Hepatocellular - surgery
Female
Humans
Liver Neoplasms - mortality
Liver Neoplasms - pathology
Liver Neoplasms - surgery
Liver Transplantation
Liver, biliary tract, pancreas, portal circulation, spleen
Male
Medical sciences
Middle Aged
Neoplasm Metastasis
Prognosis
Recurrence
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the digestive system
Survival Analysis
title Liver transplantation for small hepatocellular carcinoma: The tumor‐node‐metastasis classification does not have prognostic power
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T04%3A23%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Liver%20transplantation%20for%20small%20hepatocellular%20carcinoma:%20The%20tumor%E2%80%90node%E2%80%90metastasis%20classification%20does%20not%20have%20prognostic%20power&rft.jtitle=Hepatology%20(Baltimore,%20Md.)&rft.au=Llovet,%20Josep%20M.&rft.date=1998-06&rft.volume=27&rft.issue=6&rft.spage=1572&rft.epage=1577&rft.pages=1572-1577&rft.issn=0270-9139&rft.eissn=1527-3350&rft.coden=HPTLD9&rft_id=info:doi/10.1002/hep.510270616&rft_dat=%3Cproquest_cross%3E79921694%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=79921694&rft_id=info:pmid/9620329&rfr_iscdi=true