{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:26:48Z","timestamp":1791462408186,"version":"4.3.4"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":8370,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,10]]},"abstract":"<jats:title>\n                           <jats:bold>ABSTRACT<\/jats:bold>\n                        <\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Macroregenerative nodules, also called nodules of adenomatous hyperplasia, have been well documented in Japan. Extensive studies support the hypothesis that in the Japanese population these lesions represent a possible pathway for hepatocarcinogenesis. However, reporting of these lesions in non\u2013Japanese populations has so far been rare. We examined 44 sequential cirrhotic hepatectomy specimens from adult patients who underwent orthotopic liver transplantation at our institution. All livers were serially sectioned every 0.5 cm. Macroregenerative nodules were defined as regenerative nodules at least 1 cm in diameter. Forty\u2013eight macroregenerative nodules were found in 11 livers (25% of livers). The antecedent diseases in these livers included hepatitis C (3), alcoholism (2), primary biliary cirrhosis (2) (one with iron overload), cryptogenic cirrhosis (2), hepatitis B (1) and \u03b1<jats:sub>1<\/jats:sub>\u2013antitrypsin deficiency (1). The macroregenerative nodules often differed from the surrounding nodular parenchyma in color, texture or the degree to which they bulged beyond the cut liver surface. Three livers contained grossly apparent hepatocellular carcinomas. Microscopically, macroregenerative nodules could be classified as those with (type 2) and without (type 1) dysplasia. Four livers had type 1 lesions, two had type 2 lesions and five had lesions of both types. We found 36 type 1 lesions in all and 12 type 2 lesions, 3 containing foci of microscopic carcinoma. All hepatocellular carcinomas arose in livers containing macroregenerative nodules (either type). Liver cell dysplasia, large\u2013cell or small\u2013cell, was observed in cirrhotic nodules of 27 livers. Microscopic or macroscopic hepatocellular carcinoma occurred in three livers with large\u2013cell but not small\u2013cell dysplasia and in one liver without dysplasia. We conclude that macroregenerative nodules are common in non\u2013Japanese cirrhotic patients, occur in a wide range of chronic liver diseases and may represent precancerous lesions in this population. (HEPATOLOGY 1993;16:949-955.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840160416","type":"journal-article","created":{"date-parts":[[2007,3,4]],"date-time":"2007-03-04T01:22:37Z","timestamp":1172971357000},"page":"949-955","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":102,"title":["Macroregenerative Nodules and Hepatocellular Carcinoma in Forty\u2013Four Sequential Adult Liver Explants With Cirrhosis"],"prefix":"10.1097","volume":"16","author":[{"given":"Neil D.","family":"Theise","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myron","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swan N.","family":"Thung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840160416-BIB1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/0016-5085(86)90458-0","volume":"91","author":"Arakawa","year":"1986","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840160416-BIB2","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/0046-8177(91)90039-R","volume":"22","author":"Sakamoto","year":"1991","journal-title":"Hum Pathol"},{"key":"10.1002\/hep.1840160416-BIB3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/1097-0142(19880101)61:1<99::AID-CNCR2820610117>3.0.CO;2-U","volume":"62","author":"Furuya","year":"1988","journal-title":"Cancer"},{"key":"10.1002\/hep.1840160416-BIB4","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1002\/1097-0142(19841201)54:11<2487::AID-CNCR2820541129>3.0.CO;2-M","volume":"54","author":"Nagasue","year":"1984","journal-title":"Cancer"},{"key":"10.1002\/hep.1840160416-BIB5","first-page":"520","volume":"39","author":"Grigioni","year":"1989","journal-title":"Acta Pathol Jpn"},{"key":"10.1002\/hep.1840160416-BIB6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2214\/ajr.155.1.1693808","volume":"155","author":"Takayasu","year":"1990","journal-title":"AJR Am J Roentgenol"},{"key":"10.1002\/hep.1840160416-BIB7","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1136\/jcp.26.3.217","volume":"26","author":"Anthony","year":"1973","journal-title":"J Clin Pathol"},{"key":"10.1002\/hep.1840160416-BIB8","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1002\/1097-0142(19830615)51:12<2197::AID-CNCR2820511208>3.0.CO;2-5","volume":"51","author":"Watanabe","year":"1983","journal-title":"Cancer"},{"key":"10.1002\/hep.1840160416-BIB9","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/1097-0142(195405)7:3<462::AID-CNCR2820070308>3.0.CO;2-E","volume":"7","author":"Edmondson","year":"1954","journal-title":"Cancer"},{"key":"10.1002\/hep.1840160416-BIB10","first-page":"418","volume":"84","author":"Terada","year":"1989","journal-title":"Am J Gastroenterol"},{"key":"10.1002\/hep.1840160416-BIB11","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1002\/hep.1840080636","volume":"8","author":"Wada","year":"1988","journal-title":"HEPATOLOGY"},{"key":"10.1002\/hep.1840160416-BIB12","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/0046-8177(89)90101-9","volume":"20","author":"Terada","year":"1989","journal-title":"Hum Pathol"},{"key":"10.1002\/hep.1840160416-BIB13","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/BF00784350","volume":"415","author":"Terada","year":"1989","journal-title":"Virchows Arch Pathol [A]"},{"key":"10.1002\/hep.1840160416-BIB14","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/hep.1840100517","volume":"10","author":"Terada","year":"1989","journal-title":"HEPATOLOGY"},{"key":"10.1002\/hep.1840160416-BIB15","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1002\/1097-0142(19900501)65:9<1994::AID-CNCR2820650919>3.0.CO;2-B","volume":"65","author":"Terada","year":"1990","journal-title":"Cancer"},{"key":"10.1002\/hep.1840160416-BIB16","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1002\/1097-0142(19850515)55:10<2400::AID-CNCR2820551017>3.0.CO;2-B","volume":"55","author":"Nakanuma","year":"1985","journal-title":"Cancer"},{"key":"10.1002\/hep.1840160416-BIB17","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/j.1600-0676.1984.tb00917.x","volume":"4","author":"Nakanuma","year":"1984","journal-title":"Liver"},{"key":"10.1002\/hep.1840160416-BIB18","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/hep.1840120324","volume":"12","author":"Kondo","year":"1990","journal-title":"HEPATOLOGY"},{"key":"10.1002\/hep.1840160416-BIB19","first-page":"53","volume-title":"Primary liver tumors","author":"Altman","year":"1977","unstructured":"Pathology of human liver tumors. 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