title: Impact of large regenerative, low grade and high grade dysplastic nodules in hepatocellular carcinoma development.
abstract: OBJECTIVE
  The natural outcome of ultrasound-detected macronodules in cirrhosis is still poorly understood. In this study we assessed the incidence and predictors of malignant transformation in a prospective study of 90 consecutive ultrasound-detected macronodules in cirrhosis.
  
  
  METHODS
  Macronodules classification was based on recently proposed histological criteria. Extranodular large (LCC) and small cell changes were also evaluated. The follow-up included ultrasound and serum alfa-fetoprotein determination every 3 months. Independent predictors of hepatocellular carcinoma were evaluated by Cox proportional hazards regression analysis.
  
  
  RESULTS
  During a mean follow-up of 33 months, 28 (31%) nodules transformed into hepatocellular carcinoma. The incidence of hepatocellular carcinoma per 100 person-years of follow-up was 11.3%, with a malignant transformation rate of 3.5, 15.5, 31 and 48.5% at 1, 2, 3, and 5 years respectively. High-grade dysplastic nodules (HGDN) (hazard risk=2.4; CI 95%=1.1-5.0) and LCC (hazard risk=3.1; CI 95%=1.2-7.8) were independent predictors of malignant transformation. Eight additional hepatocellular carcinomas developed outside the original lesions raising the overall malignant transformation rate to 40% while 15 macronodules (17%) became undetectable at ultrasound (US).
  
  
  CONCLUSIONS
  Macronodules characterize a cirrhotic subpopulation with high risk of hepatocellular carcinoma. HGDN and LCC are strong predictors of malignant transformation; subjects with simultaneous presence of both these two conditions are at highest risk of cancer development. The management of cirrhotics with macronodules should be based on morphologic features detected on liver microsamples.
authors.affiliation: Department of Medicine, Gastroenterology Unit, Ospedale Fatebenefratelli, C.so Porta Nuova 23, 20121, Milan, Italy. maborzio@interfree.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Borzio
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
authors.forename: Franco
authors.initials: F
authors.lastname: Borzio
authors.forename: Anna Ludovica
authors.initials: AL
authors.lastname: Fracanzani
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Croce
authors.forename: Tommaso
authors.initials: T
authors.lastname: Stroffolini
authors.forename: Silvia
authors.initials: S
authors.lastname: Oldani
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Cotichini
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000473:pathology*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors