title: Diagnosis of hepatocellular carcinoma nodules in patients with chronic liver disease using contrast-enhanced sonography: usefulness of the combination of arterial- and kupffer-phase enhancement patterns.
abstract: OBJECTIVE
  To determine the usefulness of contrast-enhanced sonography using the perfluorobutane contrast agent Sonazoid (Daiichi-Sankyo, Tokyo, Japan) for establishing the diagnosis and cellular differentiation of hepatocellular carcinoma in patients with chronic liver disease.
  
  
  METHODS
  Patients with chronic liver disease in whom hepatic nodules were detected during screening for hepatocellular carcinoma were examined by imaging modalities, including contrast-enhanced computed tomography (CT), contrast-enhanced sonography, and contrast-enhanced magnetic resonance imaging. Nodules with negative imaging findings were further investigated with core biopsy or followed at our hospital. Between April 2007 and March 2011, all patients with hepatic nodules who underwent core biopsy of the nodules or hepatic resection for hepatocellular carcinoma were reviewed. Fifty-nine nodules from 47 patients with 42 contrast-enhanced sonographic findings and 41 contrast-enhanced CT findings were examined. Arterial- and Kupffer-phase enhancement patterns of the nodules on contrast-enhanced sonography were compared with the diagnosis and cellular differentiation of hepatocellular carcinoma. Arterial- and late-phase enhancement patterns on contrast-enhanced CT were also compared with histologic findings.
  
  
  RESULTS
  The combination of hyperenhancement in the arterial phase and hypoenhancement in the Kupffer phase on contrast-enhanced sonography (n = 11) correlated with moderately differentiated hepatocellular carcinoma (P = .0028, Fisher exact test). The combination of hypoenhancement in the arterial phase and isoenhancement in the Kupffer phase on contrast-enhanced sonography (n = 14) correlated with well-differentiated hepatocellular carcinoma (P = .0006, Fisher exact test). The combination of high density in the arterial phase and low density in the late phase on contrast-enhanced CT (n = 21) correlated with moderately differentiated hepatocellular carcinoma (P = .0059, Fisher exact test), but no enhancement pattern combination on contrast-enhanced CT correlated with well-differentiated hepatocellular carcinoma.
  
  
  CONCLUSIONS
  Sonazoid contrast-enhanced sonography is useful for diagnosis of well-differentiated hepatocellular carcinoma.
authors.affiliation: Departments of Gastroenterology (K.S., Y.O., M.O., M.H.) and Pathology (F.K.), Saiseikai Senri Hospital, Osaka, Japan. suzuki003kuni@senri.saiseikai.or.jp.
authors.forename: Kunio
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Departments of Gastroenterology (K.S., Y.O., M.O., M.H.) and Pathology (F.K.), Saiseikai Senri Hospital, Osaka, Japan.
authors.forename: Yorihide
authors.initials: Y
authors.lastname: Okuda
authors.affiliation: Departments of Gastroenterology (K.S., Y.O., M.O., M.H.) and Pathology (F.K.), Saiseikai Senri Hospital, Osaka, Japan.
authors.forename: Makiyo
authors.initials: M
authors.lastname: Ota
authors.affiliation: Departments of Gastroenterology (K.S., Y.O., M.O., M.H.) and Pathology (F.K.), Saiseikai Senri Hospital, Osaka, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Kojima
authors.affiliation: Departments of Gastroenterology (K.S., Y.O., M.O., M.H.) and Pathology (F.K.), Saiseikai Senri Hospital, Osaka, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Horimoto
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000000981:diagnostic imaging*; D003287:Contrast Media / Q000008:administration & dosage; D003937:Diagnosis, Differential; D058625:End Stage Liver Disease / Q000000981:diagnostic imaging* / Q000209:etiology; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage; D006499:Hepatic Artery / Q000000981:diagnostic imaging; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007501:Iron / Q000008:administration & dosage; D007728:Kupffer Cells / Q000000981:diagnostic imaging; D008113:Liver Neoplasms / Q000150:complications / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014463:Ultrasonography / Q000379:methods*
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D010087:Oxides; C069727:Sonazoid; D007501:Iron
keywords: cellular differentiation; contrast media; contrast-enhanced sonography; gastrointestinal ultrasound; hepatocellular carcinoma; perfluorobutane