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Review

Ongoing challenges in the diagnosis of hepatocellular carcinoma

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Pages 451-463 | Received 30 Jul 2015, Accepted 23 Nov 2015, Published online: 19 Dec 2015

References

  • Parente DB, Perez RM, Eiras-Araujo A, et al. MR imaging of hypervascular lesions in the cirrhotic liver: a diagnostic dilemma. Radiographics. 2012;32:767–787.
  • Clinical Practice Guidelines for Hepatocellular Carcinoma Differ between Japan, United States, and Europe. Liver Cancer, 2015;4:85–95.
  • Bota S, Piscaglia F, Marinelli S, et al. Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma. Liver Cancer. 2012;1:190–200.
  • European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–943.
  • Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–1022.
  • Kudo M. Surveillance, diagnosis, treatment, and outcome of liver cancer in Japan. Liver Cancer. 2015;4:39–50.
  • Omata M, Lesmana LA, Tateishi R, et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4:439–474.
  • Kokudo N, Hasegawa K, Akahane M, et al. Evidence-based clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol Res. 2015;45:123–127.
  • Bolondi L, Cillo U, Colombo M, et al. Position paper of the Italian Association for the Study of the Liver (AISF): the multidisciplinary clinical approach to hepatocellular carcinoma. Dig Liver Dis. 2013;45:712–723.
  • Bremner KE, Bayoumi AM, Sherman M, et al. Management of solitary 1 cm to 2 cm liver nodules in patients with compensated cirrhosis: a decision analysis. Can J Gastroenterol. 2007;21:491–500.
  • Bolondi L, Gaiani S, Celli N, et al. Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma. Hepatology. 2005;42:27–34.
  • Forner A, Vilana R, Ayuso C, et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology. 2008;47:97–104.
  • Sangiovanni A, Manini MA, Iavarone M, et al. The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis. Gut. 2010;59:638–644.
  • Leoni S, Piscaglia F, Granito A, et al. Characterization of primary and recurrent nodules in liver cirrhosis using contrast-enhanced ultrasound: which vascular criteria should be adopted? Ultraschall Med. 2013;34:280–287.
  • Golfieri R, Grazioli L, Orlando E, et al. Which is the best MRI marker of malignancy for atypical cirrhotic nodules: hypointensity in hepatobiliary phase alone or combined with other features? Classification after Gd-EOB-DTPA administration. J Magn Reson Imaging. 2012;36:648–657.
  • Granito A, Galassi M, Piscaglia F, et al. Impact of gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance on the non-invasive diagnosis of small hepatocellular carcinoma: a prospective study. Aliment Pharmacol Ther. 2013;37:355–363.
  • Ringe KI, Husarik DB, Sirlin CB, et al. Gadoxetate disodium-enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. AJR Am J Roentgenol. 2010;195:13–28.
  • Fidler J, Hough D. Hepatocyte-specific magnetic resonance imaging contrast agents. Hepatology. 2011;53:678–682.
  • Hsu C, Chen BB, Chen CH, et al. Consensus development from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014). Liver Cancer. 2015;4:96–105.
  • Hyodo T, Murakami T, Imai Y, et al. Hypovascular nodules in patients with chronic liver disease: risk factors for development of hypervascular hepatocellular carcinoma. Radiology. 2013;266:480–490.
  • Inoue T, Hyodo T, Murakami T, et al. Hypovascular hepatic nodules showing hypointense on the hepatobiliary-phase image of Gd-EOB-DTPA-enhanced MRI to develop a hypervascular hepatocellular carcinoma: a nationwide retrospective study on their natural course and risk factors. Dig Dis. 2013;31:472–479.
  • Kumada T, Toyoda H, Tada T, et al. Evolution of hypointense hepatocellular nodules observed only in the hepatobiliary phase of gadoxetate disodium-enhanced MRI. AJR Am J Roentgenol. 2011;197:58–63.
  • Ichikawa S, Ichikawa T, Motosugi U, et al. Was hypervascular hepatocellular carcinoma visible on previous gadoxetic acid-enhanced magnetic resonance images? Liver Cancer. 2015;4:154–162.
  • Rimola J, Forner A, Tremosini S, et al. Non-invasive diagnosis of hepatocellular carcinoma </= 2 cm in cirrhosis. Diagnostic accuracy assessing fat, capsule and signal intensity at dynamic MRI. J Hepatol. 2012;56:1317–1323.
  • Tsai YY, Lu SN, Changchien CS, et al. Combined cytologic and histologic diagnosis of liver tumors via one-shot aspiration. Hepatogastroenterology. 2002;49:644–647.
  • Durand F, Regimbeau JM, Belghiti J, et al. Assessment of the benefits and risks of percutaneous biopsy before surgical resection of hepatocellular carcinoma. J Hepatol. 2001;35:254–258.
  • Huang GT, Sheu JC, Yang PM, et al. Ultrasound-guided cutting biopsy for the diagnosis of hepatocellular carcinoma – a study based on 420 patients. J Hepatol. 1996;25:334–338.
  • John TG, Garden OJ. Needle track seeding of primary and secondary liver carcinoma after percutaneous liver biopsy. HPB Surg. 1993;6:199–203; discussion 203-194.
  • Kim SH, Lim HK, Lee WJ, et al. Needle-tract implantation in hepatocellular carcinoma: frequency and CT findings after biopsy with a 19.5-gauge automated biopsy gun. Abdom Imaging. 2000;25:246–250.
  • Ohlsson B, Nilsson J, Stenram U, et al. Percutaneous fine-needle aspiration cytology in the diagnosis and management of liver tumours. Br J Surg. 2002;89:757–762.
  • Caturelli E, Solmi L, Anti M, et al. Ultrasound guided fine needle biopsy of early hepatocellular carcinoma complicating liver cirrhosis: a multicentre study. Gut. 2004;53:1356–1362.
  • Mullhaupt B, Durand F, Roskams T, et al. Is tumor biopsy necessary? Liver Transpl. 2011;17(Suppl 2):S14–25.
  • The International Consensus Group for Hepatocellular Neoplasia. Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology, 2009;49:658–664.
  • Kojiro M. Pathological diagnosis at early stage: reaching international consensus. Oncology. 2010;78(Suppl 1):31–35.
  • Kojiro M. Diagnostic discrepancy of early hepatocellular carcinoma between Japan and West. Hepatol Res. 2007;37(Suppl 2):S121–124.
  • Di Tommaso L, Franchi G, Park YN, et al. Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis. Hepatology. 2007;45:725–734.
  • Tremosini S, Forner A, Boix L, et al. Prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma. Gut. 2012;61:1481–1487.
  • Colagrande S, Centi N, La Villa G, et al. Transient hepatic attenuation differences. AJR Am J Roentgenol. 2004;183:459–464.
  • Lupescu IG, Grasu M, Capsa R, et al. Hepatic perfusion disorders: computer-tomographic and magnetic resonance imaging. J Gastrointestin Liver Dis. 2006;15:273–279.
  • Catalano O, Sandomenico F, Nunziata A, et al. Transient hepatic echogenicity difference on contrast-enhanced ultrasonography: sonographic sign and pitfall. J Ultrasound Med. 2007;26:337–345.
  • Shah S, Shukla A, Paunipagar B. Radiological features of hepatocellular carcinoma. J Clin Exp Hepatol. 2014;4:S63–66.
  • Llovet JM, Hernandez-Gea V. Hepatocellular carcinoma: reasons for phase III failure and novel perspectives on trial design. Clin Cancer Res. 2014;20:2072–2079.
  • Santoro A, Rimassa L, Borbath I, et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol. 2013;14:55–63.
  • Nault JC, Mallet M, Pilati C, et al. High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions. Nat Commun. 2013;4:2218.
  • Nault JC, Zucman-Rossi J. Genetics of hepatocellular carcinoma: the next generation. J Hepatol. 2014;60:224–226.
  • Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329–338.
  • Lim HY, Heo J, Choi HJ, et al. A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma. Clin Cancer Res. 2014;20:5976–5985.
  • Tardy I, Pochon S, Theraulaz M, et al. Ultrasound molecular imaging of VEGFR2 in a rat prostate tumor model using BR55. Invest Radiol. 2010;45:573–578.
  • Baron Toaldo M, Salvatore V, Marinelli S, et al. Use of VEGFR-2 targeted ultrasound contrast agent for the early evaluation of response to sorafenib in a mouse model of hepatocellular carcinoma. Mol Imaging Biol. 2015;17:29–37.
  • Salvatore V, Borghi A, Piscaglia F. Contrast-enhanced ultrasound for liver imaging: recent advances. Curr Pharm Des. 2012;18:2236–2252.
  • Vilana R, Forner A, Bianchi L, et al. Intrahepatic peripheral cholangiocarcinoma in cirrhosis patients may display a vascular pattern similar to hepatocellular carcinoma on contrast-enhanced ultrasound. Hepatology. 2010;51:2020–2029.
  • Lu Q, Xue LY, Wang WP, et al. Dynamic enhancement pattern of intrahepatic cholangiocarcinoma on contrast-enhanced ultrasound: the correlation with cirrhosis and tumor size. Abdom Imaging. 2015;40(6):1558–1566.
  • Li R, Yuan MX, Ma KS, et al. Detailed analysis of temporal features on contrast enhanced ultrasound may help differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma in cirrhosis. PLoS One. 2014;9:e98612.
  • Yuan MX, Li R, Zhang XH, et al. Factors affecting the enhancement patterns of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and their pathological correlations in patients with a single lesion. Ultraschall Med. 2015. [Epub ahead of print]
  • Wildner D, Bernatik T, Greis C, et al. CEUS in hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma in 320 patients – early or late washout matters: a subanalysis of the DEGUM multicenter trial. Ultraschall Med. 2015;36:132–139.
  • Galassi M, Iavarone M, Rossi S, et al. Patterns of appearance and risk of misdiagnosis of intrahepatic cholangiocarcinoma in cirrhosis at contrast enhanced ultrasound. Liver Int. 2013;33:771–779.
  • Barreiros AP, Piscaglia F, Dietrich CF. Contrast enhanced ultrasound for the diagnosis of hepatocellular carcinoma (HCC): comments on AASLD guidelines. J Hepatol. 2012;57:930–932.
  • Kim JH, Won HJ, Shin YM, et al. Radiofrequency ablation for the treatment of primary intrahepatic cholangiocarcinoma. AJR Am J Roentgenol. 2011;196:W205–209.
  • Park YH, Hwang S, Ahn CS, et al. Long-term outcome of liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma. Transplant Proc. 2013;45:3038–3040.
  • Salgia RJ, Singal AG, Fu S, et al. Improved post-transplant survival in the United States for patients with cholangiocarcinoma after 2000. Dig Dis Sci. 2014;59:1048–1054.
  • Sapisochin G, de Lope CR, Gastaca M, et al. Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study. Ann Surg. 2012;259:944–952.
  • Manini MA, Sangiovanni A, Fornari F, et al. Clinical and economical impact of 2010 AASLD guidelines for the diagnosis of hepatocellular carcinoma. J Hepatol. 2014;60:995–1001.
  • SonoVue (sulphur hexafluoride microbubbles) – contrast agent for contrast enhanced ultrasound imaging of the liver. [ Last modified August 2012]. Available from: http://publications.nice.org.uk/dg5.
  • Barr RG. Off-label use of ultrasound contrast agents for abdominal imaging in the United States. J Ultrasound Med. 2013;32:7–12.
  • Hatanaka K, Kudo M, Minami Y, et al. Differential diagnosis of hepatic tumors: value of contrast-enhanced harmonic sonography using the newly developed contrast agent, Sonazoid. Intervirology. 2008;51(Suppl 1):61–69.
  • Boozari B, Soudah B, Rifai K, et al. Grading of hypervascular hepatocellular carcinoma using late phase of contrast enhanced sonography – a prospective study. Dig Liver Dis. 2011;43:484–490.
  • Nicolau C, Catala V, Vilana R, et al. Evaluation of hepatocellular carcinoma using SonoVue, a second generation ultrasound contrast agent: correlation with cellular differentiation. Eur Radiol. 2004;14:1092–1099.
  • Liu GJ, Xu HX, Lu MD, et al. Correlation between enhancement pattern of hepatocellular carcinoma on real-time contrast-enhanced ultrasound and tumour cellular differentiation on histopathology. Br J Radiol. 2007;80:321–330.
  • Sugimoto K, Moriyasu F, Saito K, et al. Comparison of Kupffer-phase Sonazoid-enhanced sonography and hepatobiliary-phase gadoxetic acid-enhanced magnetic resonance imaging of hepatocellular carcinoma and correlation with histologic grading. J Ultrasound Med. 2012;31:529–538.
  • Hatanaka K, Kudo M, Minami Y, et al. Sonazoid-enhanced ultrasonography for diagnosis of hepatic malignancies: comparison with contrast-enhanced CT. Oncology. 2008;75(Suppl 1):42–47.
  • Suzuki K, Okuda Y, Ota M, et al. Diagnosis of hepatocellular carcinoma nodules in patients with chronic liver disease using contrast-enhanced sonography: usefulness of the combination of arterial- and kupffer-phase enhancement patterns. J Ultrasound Med. 2015;34:423–433.
  • Wakui N, Takayama R, Matsukiyo Y, et al. A case of poorly differentiated hepatocellular carcinoma with intriguing ultrasonography findings. Oncol Lett. 2012;4:393–397.
  • Goto E, Masuzaki R, Tateishi R, et al. Value of post-vascular phase (Kupffer imaging) by contrast-enhanced ultrasonography using Sonazoid in the detection of hepatocellular carcinoma. J Gastroenterol. 2012;47:477–485.
  • Claudon M, Dietrich CF, Choi BI, et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver–update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultraschall Med. 2013;34:11–29.
  • Nanashima A, Tobinaga S, Abo T, et al. Usefulness of sonazoid-ultrasonography during hepatectomy in patients with liver tumors: a preliminary study. J Surg Oncol. 2011;103:152–157.
  • Joshita S, Ichijo T, Suzuki F, et al. A case of well-differentiated cholangiolocellular carcinoma visualized with contrast-enhanced ultrasonography using Sonazoid. Hepatol Res. 2009;39:207–212.
  • Personeni N, Bozzarelli S, Pressiani T, et al. Usefulness of alpha-fetoprotein response in patients treated with sorafenib for advanced hepatocellular carcinoma. J Hepatol. 2012;57:101–107.
  • Riaz A, Ryu RK, Kulik LM, et al. Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival. J Clin Oncol. 2009;27:5734–5742.
  • Tsai MC, Wang JH, Hung CH, et al. Favorable alpha-fetoprotein decrease as a prognostic surrogate in patients with hepatocellular carcinoma after radiofrequency ablation. J Gastroenterol Hepatol. 2010;25:605–612.
  • Vora SR, Zheng H, Stadler ZK, et al. Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma. Oncologist. 2009;14:717–725.
  • Toyoda H, Kumada T, Tada T, et al. Prognostic significance of a combination of pre- and post-treatment tumor markers for hepatocellular carcinoma curatively treated with hepatectomy. J Hepatol. 2012;57:1251–1257.
  • Rich N, Singal AG. Hepatocellular carcinoma tumour markers: current role and expectations. Best Pract Res Clin Gastroenterol. 2014;28:843–853.
  • Volk ML, Hernandez JC, Su GL, et al. Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3. Cancer Biomark. 2007;3:79–87.
  • Gupta S, Bent S, Kohlwes J. Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. A systematic review and critical analysis. Ann Intern Med. 2003;139:46–50.
  • Ge T, Shen Q, Wang N, et al. Diagnostic values of alpha-fetoprotein, dickkopf-1, and osteopontin for hepatocellular carcinoma. Med Oncol. 2015;32:59.
  • Marrero JA, Romano PR, Nikolaeva O, et al. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol. 2005;43:1007–1012.
  • Jia X, Liu J, Gao Y, et al. Diagnosis accuracy of serum glypican-3 in patients with hepatocellular carcinoma: a systematic review with meta-analysis. Arch Med Res. 2014;45:580–588.
  • Hussein MM, Ibrahim AA, Abdella HM, et al. Evaluation of serum squamous cell carcinoma antigen as a novel biomarker for diagnosis of hepatocellular carcinoma in Egyptian patients. Indian J Cancer. 2008;45:167–172.
  • Giannelli G, Fransvea E, Trerotoli P, et al. Clinical validation of combined serological biomarkers for improved hepatocellular carcinoma diagnosis in 961 patients. Clin Chim Acta. 2007;383:147–152.
  • Mao Y, Yang H, Xu H, et al. Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut. 2010;59:1687–1693.
  • Daniele B, Annunziata M, Barletta E, et al. Cancer of the Liver Italian Program (CLIP) score for staging hepatocellular carcinoma. Hepatol Res. 2007;37(Suppl 2):S206–209.
  • Chevret S, Trinchet JC, Mathieu D, et al. A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire. J Hepatol. 1999;31:133–141.
  • Leung TW, Tang AM, Zee B, et al. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients. Cancer. 2002;94:1760–1769.
  • Yang JD, Kim WR, Park KW, et al. Model to estimate survival in ambulatory patients with hepatocellular carcinoma. Hepatology. 2012;56:614–621.
  • Toyoda H, Kumada T, Osaki Y, et al. Staging hepatocellular carcinoma by a novel scoring system (BALAD score) based on serum markers. Clin Gastroenterol Hepatol. 2006;4:1528–1536.
  • Budhu A, Jia HL, Forgues M, et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology. 2008;47:897–907.
  • Jiang J, Gusev Y, Aderca I, et al. Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res. 2008;14:419–427.
  • Tan Y, Ge G, Pan T, et al. A serum microRNA panel as potential biomarkers for hepatocellular carcinoma related with hepatitis B virus. PLoS One. 2014;9:e107986.
  • Zhang J, Chong CC, Chen GG, et al. A seven-microRNA expression signature predicts survival in hepatocellular carcinoma. PLoS One. 2015;10:e0128628.

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