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J Hepatol. 2005 Aug;43(2):310-6.

Tumor doubling time predicts recurrence after surgery and describes the histological pattern of hepatocellular carcinoma on cirrhosis.

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Dipartimento di Discipline Chirurgiche, Rianimatorie e dei Trapianti, University of Bologna, Policlinico S.Orsola, Via Massarenti 9, 40138 Bologna, Italy.



Recurrence of hepatocellular carcinoma (HCC) following surgical resection is influenced by parameters detectable on the resection specimen or through a biopsy. The prognostic significance of HCC doubling time (DT) after surgery has never been investigated.


We evaluated 62 patients who underwent curative resection of a single HCC on cirrhosis; tumors were assessed before surgery on two subsequent occasions with the same imaging technique allowing the calculation of DT. The influence of tumor DT, clinical and pathological parameters on recurrence-rate and patients survival was assessed with uni- and multivariate analysis. Relationship between DT and pathological features was also analyzed.


Three-year recurrence rate was 32.3% (20 patients): this was significantly higher in the presence of DT shorter than 100 days (58 versus 18% when equal to or longer; P=0.008), microvascular invasion (59 versus 17% when absent; P=0.008) or tumor undifferentiation (54 versus 25% when well/moderately differentiated; P=0.015). DT was the only independent predictor of recurrence (P=0.005). Patients survival was affected by Child-Pugh class only. DT was significantly shorter in tumors with microvascular invasion (P=0.007), undifferentiation (P=0.003) and high alpha-fetoprotein levels (P=0.011).


DT is easy to estimate and indicates the prognosis of single HCCs prior to liver resection.

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