2 Whereas two contrast imaging techniques with concordant wash-in/wash-out patterns are required for the diagnosis of ≤2 cm tumors, contrast-enhanced US (CE-US), spiral computed tomography (CT), or dynamic magnetic resonance imaging (MRI) alone suffices to diagnose >2 cm nodules.2, 3 In a validation study performed by Forner and colleagues,4 the concurrent application of CE-US and gadolinium MRI showed 33.3% sensitivity and 100% specificity for the diagnosis of 0.5- to 2-cm HCCs using histology with fine-needle biopsy (FNB) as a diagnostic gold standard. In that study, CE-US was combined

with gadolinium MRI, because previous investigations by the same group in explanted livers showed better diagnostic find more performance of MRI than see more CT scan in the identification of small HCC nodules.5 Recently, the accuracy of CE-US has been questioned owing to a discrete number of false positive diagnoses of HCC in patients with an intrahepatic cholangiocarcinoma, a tumor that is increasingly seen

in patients with HCV-related cirrhosis and, at variance with HCC, is a contraindication for orthotopic liver transplantation.6, 7 Because HCC growth depends not only on the rate of arterial vascularization, which accounts for the pathognomonic pattern of HCC on contrast imaging, but also on tumor grade,8 we wondered whether the diagnostic accuracy of dynamic contrast imaging techniques could be influenced by the degree of tumor cell differentiation, as well. To address this question, we assessed tumor grade in the liver cores of de novo HCC nodules that were consecutively diagnosed in 59 patients with compensated Thymidylate synthase cirrhosis who were under surveillance

and were concurrently examined with CE-US, dynamic gadolinium MRI, and contrast CT. AFP, alpha-fetoprotein; CE-US, contrast-enhanced ultrasound; CT, computed tomography; FNB, fine-needle biopsy; HCC, hepatocellular carcinoma; MRI, magnetic resonance imaging; US, ultrasound. This study was a subanalysis of a previous independent, investigator-driven, prospective study aimed to compare the accuracy of CE-US, CT, and MRI in the diagnosis of de novo HCC nodules in patients with compensated cirrhosis who were under surveillance with US.9 Between April 2006 and December 2009, all patients with Child-Pugh class A or B cirrhosis with a de novo liver nodule detected during surveillance were investigated consecutively. Excluded were patients with a pre-existing liver nodule, poor liver function (Child-Pugh C) indicating liver transplantation independently on HCC, or an echo-coarse US pattern of the liver without a well-defined liver nodule. After giving informed consent, patients underwent a detailed medical history, physical examination, and complete blood count and biochemical tests, including serum alpha-fetoprotein (AFP; normal, ≤ 20 ng/mL) (IRMA; Abbott, North Chicago, IL) and markers for viral hepatitis and autoimmunity.