Poor contrast enhanced ultrasonography! There is no limit to its decline in the diagnosis of hepatocellular carcinoma on cirrhosis!
Authors: Antonio Giorgio, Valentina Giorgio, Paolo Matteucci
Journal: Journal of Hepatology (2015)

Lack of arterial hypervascularity at contrast-enhanced ultrasound should not define the priority for diagnostic work-up of nodules <2 cmJournal of HepatologyVol. 62Issue 1PreviewCurrent guidelines recommend diagnostic work-up for nodules >1 cm detected during screening for hepatocellular carcinoma (HCC). This implies that patients with benign conditions may undergo unnecessary evaluation and those with small nodules may be intervened too early, leading to overdiagnosis. Since increased arterial vascularization is the hallmark of malignancy, its detection by contrast-enhanced ultrasound (CEUS) could become the signal to proceed with diagnosis confirmation. The aim was to assess if HCCs <2 cm without arterial hyperenhancement by baseline CEUS have a benign evolutionary profile, suggesting that diagnosis and invasive treatment could be delayed until detection of an overt malignant profile, associated with increased vascularization. Full-Text PDF Reply to: ‘‘Poor contrast enhanced ultrasonography! There is no limit to its decline in the diagnosis of hepatocellular carcinoma on cirrhosis!’’Journal of HepatologyVol. 62Issue 6PreviewWe would like to thank Giorgio et al. for their interest in our recent study about the role of contrast-enhanced ultrasound (CEUS) in the diagnostic process of small nodules detected during screening US [1]. In this study, the main conclusion was that the absence of contrast hyperenhancement during the arterial phase at CEUS does not predict a less malignant profile and thus, priority for diagnostic work-up and treatment should not differ according to contrast profile at CEUS. The letter by Giorgio et al. Full-Text PDF Open Access We have read with great interest the article by Forner and co-workers, who described the use of contrast-enhanced ultrasound (CEUS) to define the priority for diagnostic work-up of hepatocellular carcinoma (HCC) nodules <2 cm arising in cirrhotic livers during ultrasound (US) surveillance [[1]Forner A. Vilana R. Bianchi L. Rodríguez-Lope C. Reig M. García-Criado M.A. et al.Lack of arterial hypervascularity at contrast-enhanced ultrasound should not define the priority for diagnostic work-up of nodules <2 cm.J Hepatol. 2015; 62: 150-155https://doi.org/10.1016/j.jhep.2014.08.028Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar]. Nevertheless we would like to make some criticism In their prospective study carried out from 2003 to 2011, the authors state that fine needle biopsy (FNB) result was considered the gold standard for diagnosis of HCC, but that after 2007, they considered only enhanced MRI result as gold standard, as priory validated. Our question to the authors is why did they not continue to perform FNB to diagnose HCC nodules? It seems to us methodologically incorrect to change the diagnostic method during the study. Maybe MRI has 100% specificity in diagnosing HCC? As far as we know, in a recent meta-analysis comparing CEUS and enhanced MRI for diagnosis of HCC [[2]Floriani I. D’Onofrio M. Rulli E. Chen M.H. Li R. Musicco L. Performance of imaging modalities in the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis.Ultraschall Med. 2013; 34: 454-462https://doi.org/10.1055/s-0032-1330358Crossref PubMed Scopus (15) Google Scholar], including only patients diagnosed with percutaneous biopsy [3Blondin D. Erhardt A. Crynen K. Sagir A. Scherer A. Kröpil P. et al.Diagnosis of focal liver lesions in cirrhotic patients: comparison of contrast-enhanced ultrasound using sulphur hexafluoride (SF6) microbubbles and MRI using Gd-EOB-DTPA.Z Gastroenterol. 2011; 49: 23-29https://doi.org/10.1055/s-0029-1245781Crossref PubMed Scopus (12) Google Scholar, 4Giorgio A. De Stefano G. Coppola C. Ferraioli G. Esposito V. Di Sarno A. et al.Contrast-enhanced sonography in the characterization of small hepatocellular carcinomas in cirrhotic patients: comparison with contrast-enhanced ultrafast magnetic resonance imaging.Anticancer Res. 2007; 27: 4263-4269PubMed Google Scholar], CEUS showed a statistically better specificity than MRI in the pair-wise comparisons (0.86 vs. 0.78; p = 0.014), and a statistically better sensitivity than computed tomography [(CT) 0.88 vs. 0.78; p = 0.030] [[2]Floriani I. D’Onofrio M. Rulli E. Chen M.H. Li R. Musicco L. Performance of imaging modalities in the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis.Ultraschall Med. 2013; 34: 454-462https://doi.org/10.1055/s-0032-1330358Crossref PubMed Scopus (15) Google Scholar]. In addition, in a recent work, the specificity of CEUS plus CT and/or MRI was significantly higher than the specificity of CT and/or MRI, CEUS, or intraoperative ultrasound [(IOUS) p = 0.004, p = 0.002, and p = 0.002, respectively]. The diagnostic accuracy of CEUS plus CT/MRI was higher than that of CT/MRI (p = 0.001) [[5]Zhang Xiao-Yun Luo Yan Wen Tian-Fu Jiang Li Li Chuan Zhong Xiao-Fei et al.Contrast-enhanced ultrasound: Improving the preoperative staging of hepatocellular carcinoma and guiding individual treatment.World J Gastroenterol. 2014; 20: 12628-12636https://doi.org/10.3748/wjg.v20.i35.12628Crossref PubMed Scopus (14) Google Scholar]. Furthermore, in a specific section, the authors state that FNB was performed using a 20 G spinal needle, and state that, when “technically feasible because of location and accessibility, a core biopsy was performed using a 18 G needle biopsy”. From histology, there were 3 intrahepatic cholangiocarcinomas (ICCs) and 35 regenerating nodules or dysplastic nodules and 1 neuroendocrine tumor. It is evident that diagnosis of ICC and dysplastic nodules can be made only using histology. Another question arises: were all ICCs and dysplastic nodules and metastasis of endocrine tumors located in a “feasible and accessible location” in the liver? It seems improbable to us. Moreover, it is probably incorrect to use the term FNB when two different needles are used for performing biopsies, since the 18 G needle is not definable as “fine”, as it is >1 mm. In addition, 3% of cases (5 cases) of US detected nodules were not evaluable with CEUS examination. Four out of 5 of them were HCC. This is quite interesting, and it would be useful to know if all nodules were located in a deep position, since they had been normally detected with conventional US. It would be also interesting to know if any MRI resulted unfeasible in the study. Finally, in the results section, authors reported that 10/18 (55.6%) CEUS un-enhanced patients with final diagnosis of HCC, experienced tumor recurrence after treatment (4 resections and 14 ablations), “confirming their overt malignant profile”: how can authors state that recurrence is due to the “malignant profile” if nodules had been resected or ablated and “classified as necrotic”? Is it not possible that distant recurrences were due to the well-known hepatocarcinogenesis of HCC on cirrhosis? The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.