Antonio Giorgio

P. Matteucci

Valentina Giorgio

English

Open Access Repository

virus recurrence after liver transplantation. Gastroenterology 2008;134:1890–1899.[4] Gehring AJ, Xue S-A, Ho ZZ, Teoh D, Ruedl C, Chia A, et al. Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellularcarcinoma cell lines. J Hepatol 2011;55:103–110.[5] Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, et al. A practicalapproach to immunotherapy of hepatocellular carcinoma using T cellsredirected against hepatitis B virus. Mol Ther Nucleic Acids 2013;2:e114.[6] Sung W-K, Zheng H, Li S, Chen R, Liu X, Li Y, et al. Genome-wide survey ofrecurrent HBV integration in hepatocellular carcinoma. Nat Genet 2012;44:765–769.[7] Lau C-C, Sun T, Ching AKK, He M, Li J-W, Wong AM, et al. Viral-humanchimeric transcript predisposes risk to liver cancer development andprogression. Cancer Cell 2014;25:335–349.[8] Tang K-W, Alaei-Mahabadi B, Samuelsson T, Lindh M, Larsson E. Thelandscape of viral expression and host gene fusion and adaptation in humancancer. Nat Commun 2013;4:2513.[9] June CH, Blazar BR, Riley JL. Engineering lymphocyte subsets: tools, trials andtribulations. Nat Rev Immunol 2009;9:704–716.[10] Yan H, Yang Y, Zhang L, Tang G, Wang Y, Xue G, et al. Characterization of thegenotype and integration patterns of hepatitis B virus in early- and late-onset hepatocellular carcinoma. Hepatology 2015. http://dx.doi.org/10.1002/hep.27722.Waseem QasimInstitute of Child Health & Great Ormond Street Hospital,University College London, London, UKMaurizia BrunettoHepatology Unit, University Hospital of Pisa, Pisa, ItalyAdam J. GehringMolecular Microbiology and Immunology Department, Saint LouisUniversity School of Medicine, Saint Louis, USAMala K. MainiDivision of Infection & Immunity, Institute of Immunity &Transplantation, University College London, London, UKFerruccio BoninoGeneral Medicine, Liver and Digestive Disease Unit, UniversityHospital of Pisa, Pisa, ItalyHans StaussDivision of Infection & Immunity, Institute of Immunity &Transplantation, University College London, London, UKAntonio Bertoletti⇑Program Emerging Infectious Diseases,Duke-NUS Medical School, SingaporeSingapore Institute for Clinical Sciences, A⁄STAR, SingaporeSchool of Immunity and Infection, College of Medical and DentalScience, University of Birmingham, Edgbaston Birmingham, UK⇑Corresponding author.E-mail address: antonio@duke-nus.edu.sgTWw(alatcvtmiHCpaiiIoMpLetters to the Editor1Poor contrast enhanced ultrasonography! There is no limit to itsdecline in the diagnosis of hepatocellular carcinoma on cirrhosis!o the Editore have read with great interest the article by Forner and co-orkers, who described the use of contrast-enhanced ultrasoundCEUS) to define the priority for diagnostic work-up of hep-tocellular carcinoma (HCC) nodules <2 cm arising in cirrhoticivers during ultrasound (US) surveillance [1].Nevertheless we would like to make some criticismIn their prospective study carried out from 2003 to 2011, theuthors state that fine needle biopsy (FNB) result was consideredhe gold standard for diagnosis of HCC, but that after 2007, theyonsidered only enhanced MRI result as gold standard, as prioryalidated. Our question to the authors is why did they not con-inue to perform FNB to diagnose HCC nodules? It seems to usethodologically incorrect to change the diagnostic method dur-ng the study. Maybe MRI has 100% specificity in diagnosingCC? As far as we know, in a recent meta-analysis comparingEUS and enhanced MRI for diagnosis of HCC [2], including onlyatients diagnosed with percutaneous biopsy [3,4], CEUS showedstatistically better specificity than MRI in the pair-wise compar-sons (0.86 vs. 0.78; p = 0.014), and a statistically better sensitiv-ty than computed tomography [(CT) 0.88 vs. 0.78; p = 0.030] [2].n addition, in a recent work, the specificity of CEUS plus CT and/r MRI was significantly higher than the specificity of CT and/orRI, CEUS, or intraoperative ultrasound [(IOUS) p = 0.004,= 0.002, and p = 0.002, respectively]. The diagnostic accuracyof CEUS plus CT/MRI was higher than that of CT/MRI (p = 0.001)[5].Furthermore, in a specific section, the authors state that FNBwas performed using a 20 G spinal needle, and state that, when‘‘technically feasible because of location and accessibility, a corebiopsy was performed using a 18 G needle biopsy’’. From histology,there were 3 intrahepatic cholangiocarcinomas (ICCs) and 35regenerating nodules or dysplastic nodules and 1 neuroendocrinetumor. It is evident that diagnosis of ICC and dysplastic nodulescan be made only using histology. Another question arises: wereall ICCs and dysplastic nodules and metastasis of endocrine tumorslocated in a ‘‘feasible and accessible location’’ in the liver? It seemsimprobable to us. Moreover, it is probably incorrect to use the termFNB 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 werenot evaluable with CEUS examination. Four out of 5 of them wereHCC. This is quite interesting, and it would be useful to know if allnodules were located in a deep position, since they had been nor-mally detected with conventional US. It would be also interestingto 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 and14 ablations), ‘‘confirming their overt malignant profile’’: how452 Journal of Hepatology 2015 vol. 62 j 1438–1454EOB-DTPA. Z Gastroenterol 2011;49:23–29. http://dx.doi.org/10.1055/s-0029-1245781.[4] Giorgio A, De Stefano G, Coppola C, Ferraioli G, Esposito V, Di Sarno A, et al.Contrast-enhanced sonography in the characterization of small hep-atocellular carcinomas in cirrhotic patients: comparison with contrast-JOURNAL OF HEPATOLOGYcan authors state that recurrence is due to the ‘‘malignant profile’’if nodules had been resected or ablated and ‘‘classified as necro-tic’’? Is it not possible that distant recurrences were due to thewell-known hepatocarcinogenesis of HCC on cirrhosis?Conflict of interestThe authors declared that they do not have anything to discloseregarding funding or conflict of interest with respect to thismanuscript.References[1] Forner A, Vilana R, Bianchi L, Rodríguez-Lope C, Reig M, García-Criado MA,et al. Lack of arterial hypervascularity at contrast-enhanced ultrasoundshould not define the priority for diagnostic work-up of nodules <2 cm. JHepatol 2015;62:150–155. http://dx.doi.org/10.1016/j.jhep.2014.08.028.[2] Floriani I, D’Onofrio M, Rulli E, Chen MH, Li R, Musicco L. Performance ofimaging modalities in the diagnosis of hepatocellular carcinoma: a systematicreview and meta-analysis. Ultraschall Med 2013;34:454–462. http://dx.doi.org/10.1055/s-0032-1330358.[3] Blondin D, Erhardt A, Crynen K, Sagir A, Scherer A, Kröpil P, et al. Diagnosis offocal liver lesions in cirrhotic patients: comparison of contrast-enhancedultrasound using sulphur hexafluoride (SF6) microbubbles and MRI using Gd-enhanced ultrafast magnetic resonance imaging. Anticancer Res2007;27:4263–4269.[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 ofhepatocellular carcinoma and guiding individual treatment. World JGastroenterol 2014;20:12628–12636. http://dx.doi.org/10.3748/wjg.v20.i35.12628.Antonio Giorgio⇑Interventional Ultrasound Unit, Tortorella Clinical Institute,ISSMES Consortium, Salerno, Italy⇑Corresponding author.E-mail address: agiorgio28@gmail.comValentina GiorgioCatholic University of sacred Heart, Rome, ItalyPaolo MatteucciCampus Biomedico University, Rome, ItalyReply to: ‘‘Poor contrast enhanced ultrasonography! There is no limitto its decline in the diagnosis of hepatocellular carcinomaon cirrhosis!’’To the Editor:We would like to thank Giorgio et al. for their interest in ourrecent study about the role of contrast-enhanced ultrasound(CEUS) in the diagnostic process of small nodules detected duringscreening US [1]. In this study, the main conclusion was that theabsence of contrast hyperenhancement during the arterial phaseat CEUS does not predict a less malignant profile and thus, prior-ity for diagnostic work-up and treatment should not differaccording to contrast profile at CEUS. The letter by Giorgio et al.criticised some methodological aspects of our study and theyclaim that CEUS still has an important role in the diagnostic recallstrategy upon the detection of a nodule by screening US. The firstconcern raised in the letter was the use of the non-invasivediagnostic criteria by MRI after 2007 as gold standard for HCCconclusive diagnosis. Since the non-invasive HCC diagnosis byimaging has been extensively and prospectively validated, andfully accepted by the main scientific societies [2,3] and theSpanish guidelines for HCC management [4], Giorgio et al. willsurely agree with us that delaying the HCC diagnosis and treat-ment until histological confirmation is ethically questionable. Inaddition, we would like to highlight that in only 14 out of 119(11.7%) HCC lesions the final diagnosis was based only on imag-ing criteria, and all 18 HCC lesions with absence of arterial con-trast hyperenhancement detection at CEUS were histologicallyconfirmed. Moreover, Giorgio et al. summarize some studiesaimed to evaluate the diagnostic accuracy of CEUS alone orassociated to CT/MRI for HCC diagnosis, emphasizing that CEUSshowed the best diagnostic accuracy. This is not surprising sincethe combination of imaging techniques is always associated withbetter specificity than when just only one imaging technique,whatever one is used. Furthermore, Giorgio et al. questionedthe feasibility of cytology for diagnosing intrahepaticcholangiocarcinoma and dysplastic nodules. However, the sam-ples were processed in cell-block; this allows the assessment ofcyto-histological findings and the use of immunohistochemistrymarkers, which permits the diagnosis of both entities [5,6].Regarding the feasibility of CEUS, in the 5 cases (3%) men-tioned the nodule was deeply located with a poor sonographicwindow and despite that the nodule was previously visualizedby US, a reliable CEUS was not possible. This is not surprising sinceour study was prospective and the inclusion criteria was the iden-tification of a solitary nodule smaller than 2 cm by screening USand not by CEUS exploration, and expert radiologists will agreethat not all US visible nodules can be explored by CEUS.Giorgio et al. also claim data regarding the diagnostic accuracyof MRI. We would like to stress that our study is not aimed toassess the diagnostic accuracy of MRI, or compared it withCEUS, since this information has been previously reported [7,8].As requested, in our cohort of patients, MRI did not identify thetarget nodule in 25 out of 168 patients (14.8%), but only 3 of theseJournal of Hepatology 2015 vol. 62 j 1438–1454 1453

Poor contrast enhanced ultrasonography! There is no limit to its decline in the diagnosis of hepatocellular carcinoma on cirrhosis!

https://www.openaccessrepository.it/record/85969/files/fulltext.pdf

Poor contrast enhanced ultrasonography! There is no limit to its decline in the diagnosis of hepatocellular carcinoma on cirrhosis!

Abstract

Similar works

Full text

Available Versions

Open Access Repository