Hepatocellular Cancer (Surveillance)

Pathway

Images

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1a		Hepatocellular Carcinoma Image 1a and 1b (Ultrasound): Within segment 6 of the liver, there is an approximately 2cm subcapsular hypoechoic lesion (arrow) which does not demonstrate any increased vascularity.
1b
1c		Image 1c, 1d, 1e and 1f (Triphasic Computed Tomography): CT of the same patient shows a cirrhotic liver with patent hepatic and portal veins as well as ascites. Within segment 6, there is a nodular area which demonstrates slight enhancement corresponding to the lesion identified on ultrasound (arrow). This lesion could represent either a dysplastic cirrhotic nodule or an early hepatocellular carcinoma.
1d
1e
1f
1g		Image 1g, 1h, 1i and 1j (Magnetic Resonance Imaging): MRI of the same patient demonstrates a lesion measuring approximately 2.5 cm in diameter on the inferomedial aspect of segment 5 in a subcapsular location. This is bulging the capsule of the liver at the level of the upper pole of the right kidney. The lesion is essentially isointense to the rest of the liver on T1 weighted imaging (out of phase) but is slightly hyperintense on in-phase imaging suggesting that the rest of the liver has some fatty infiltration. The lesion is slightly hyperintense on first echo T2 but is not clearly visible on more heavily weighted T2 imaging. The lesion shows arterial enhancement but washes out in the portal venous phase, with the rim of the lesion remaining enhanced. The appearances are consistent with a hepatocellular carcinoma.
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1i
1j
2a		Hepatocellular Carcinoma Image 2a and 2b : Hepatectomy specimens showing a multifocal hepatocellular carcinoma with areas of necrosis and haemorrhage arising in a cirrhotic liver.
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2c		Image 2c (H&E, x2.5) and 2d (H&E, x10): Histological sections of a hepatocellular carcinoma arising on a background of cirrhosis. The usual lobular architecture is replaced by irregular and thickened trabeculae of malignant hepatocytes. There is mild nuclear pleomorphism.
2d

Teaching Points

Teaching Points

• In patients with cirrhosis, the risk of developing hepatocellular carcinoma (HCC) is highest with HCV, in Asians and in more advanced stages of cirrhosis 1
• Ultrasonography (US) 6 monthly is recommended as the primary surveillance modality 2-5
• Survival was significantly better in patients who underwent surveillance 18
• The earliest identifiable HCCs often show atypical radiological features 19 and these are the very lesions that need to be diagnosed to enable a higher likelihood of cure
• Sensitivity for detecting hepatocellular carcinoma on US varies with the size of the lesion
• Utilizing contrast enhanced ultrasonography (CEUS) allows for dynamic real-time ultrasound angiogram with greater temporal resolution than contrast-enhanced CT or MRI, in addition to quantitative assessments
• The use of serum alpha-fetoprotein (AFP) alone as a surveillance tool is not recommended
• The use of AFP to complement US surveillance is controversial 31,32

References

References

Date of literature search: June 2015

The search methodology is available on request. Email

References are graded from Level I to V according to the Oxford Centre for Evidence-Based Medicine, Levels of Evidence. Download the document

1. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(5 Suppl 1):S35-50. (Review article). View the reference
2. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020-2. (Review article). View the reference
3. 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(4):908-43. (Guidelines). View the reference
4. Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4(2):439-74. (Guidelines). View the reference
5. Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O, et al. Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis. 2011;29(3):339-64. (Guidelines). View the reference
6. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208-36. (Guidelines). View the reference
7. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001;35(3):421-30. (Review article). View the reference
8. Leoni S, Piscaglia F, Golfieri R, Camaggi V, Vidili G, Pini P, et al. The impact of vascular and nonvascular findings on the noninvasive diagnosis of small hepatocellular carcinoma based on the EASL and AASLD criteria. Am J Gastroenterol. 2010;105(3):599-609. (Level II evidence). View the reference
9. Della Corte C, Colombo M. Surveillance for hepatocellular carcinoma. Semin Oncol. 2012;39(4):384-98. (Review article). View the reference
10. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130(7):417-22. (Level II evidence). View the reference
11. Kansagara D, Papak J, Pasha AS, O'Neil M, Freeman M, Relevo R, et al. Screening for hepatocellular carcinoma in chronic liver disease: a systematic review. Ann Intern Med. 2014;161(4):261-9. (Level I/II evidence). View the reference
12. Trevisani F, Cantarini MC, Labate AM, De Notariis S, Rapaccini G, Farinati F, et al. Surveillance for hepatocellular carcinoma in elderly Italian patients with cirrhosis: effects on cancer staging and patient survival. Am J Gastroenterol. 2004;99(8):1470-6. (Level III evidence). View the reference
13. Trevisani F, De Notariis S, Rapaccini G, Farinati F, Benvegnu L, Zoli M, et al. Semiannual and annual surveillance of cirrhotic patients for hepatocellular carcinoma: effects on cancer stage and patient survival (Italian experience). Am J Gastroenterol. 2002;97(3):734-44. (Level III evidence). View the reference
14. Wong LL, Limm WM, Severino R, Wong LM. Improved survival with screening for hepatocellular carcinoma. Liver Transpl. 2000;6(3):320-5. (Level III evidence). View the reference
15. Yu EW, Chie WC, Chen TH. Does screening or surveillance for primary hepatocellular carcinoma with ultrasonography improve the prognosis of patients? Cancer J. 2004;10(5):317-25. (Level III/IV evidence). View the reference
16. Yuen MF, Cheng CC, Lauder IJ, Lam SK, Ooi CG, Lai CL. Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience. Hepatology. 2000;31(2):330-5. (Level III evidence). View the reference
17. Midorikawa Y, Takayama T, Shimada K, Nakayama H, Higaki T, Moriguchi M, et al. Marginal survival benefit in the treatment of early hepatocellular carcinoma. J Hepatol. 2013;58(2):306-11. (Level III evidence). View the reference
18. Edenvik P, Davidsdottir L, Oksanen A, Isaksson B, Hultcrantz R, Stal P. Application of hepatocellular carcinoma surveillance in a European setting. What can we learn from clinical practice? Liver Int. 2015;35(7):1862-71. (Level III evidence). View the reference
19. Sherman M. The radiological diagnosis of hepatocellular carcinoma. Am J Gastroenterol. 2010;105(3):610-2. (Level IV/V evidence). View the reference
20. Singal A, Volk ML, Waljee A, Salgia R, Higgins P, Rogers MA, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther. 2009;30(1):37-47. (Level I evidence). View the reference
21. Chou R, Cuevas C, Fu R, Devine B, Wasson N, Ginsburg A, et al. Imaging techniques for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Ann Intern Med. 2015;162(10):697-711. (Level I evidence). View the reference
22. Pocha C, Dieperink E, McMaken KA, Knott A, Thuras P, Ho SB. Surveillance for hepatocellular cancer with ultrasonography vs computed tomography -- a randomised study. Aliment Pharmacol Ther. 2013;38(3):303-12. (Level II/III evidence). View the reference
23. Bolondi L, Cillo U, Colombo M, Craxi A, Farinati F, Giannini EG, 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(9):712-23. (Guidelines). View the reference
24. Claudon M, Dietrich CF, Choi BI, Cosgrove DO, Kudo M, Nolsoe CP, 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. Ultrasound Med Biol. 2013;39(2):187-210. (Guidelines). View the reference
25. Barreiros AP, Piscaglia F, Dietrich CF. Contrast enhanced ultrasound for the diagnosis of hepatocellular carcinoma (HCC): comments on AASLD guidelines. J Hepatol. 2012;57(4):930-2. (Level IV/V evidence). View the reference
26. Sangiovanni A, Manini MA, Iavarone M, Romeo R, Forzenigo LV, Fraquelli M, et al. The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis. Gut. 2010;59(5):638-44. (Level III evidence). View the reference
27. Serste T, Barrau V, Ozenne V, Vullierme MP, Bedossa P, Farges O, et al. Accuracy and disagreement of computed tomography and magnetic resonance imaging for the diagnosis of small hepatocellular carcinoma and dysplastic nodules: role of biopsy. Hepatology. 2012;55(3):800-6. (Level III evidence). View the reference
28. Tanaka H, Iijima H, Nouso K, Aoki N, Iwai T, Takashima T, et al. Cost-effectiveness analysis on the surveillance for hepatocellular carcinoma in liver cirrhosis patients using contrast-enhanced ultrasonography. Hepatol Res. 2012;42(4):376-84. (Level III evidence). View the reference
29. Xu HX, Lu MD, Liu LN, Zhang YF, Guo LH, Xu JM, et al. Discrimination between neoplastic and non-neoplastic lesions in cirrhotic liver using contrast-enhanced ultrasound. Br J Radiol. 2012;85(1018):1376-84. (Level III evidence). View the reference
30. Dumitrescu CI, Gheonea IA, Sandulescu L, Surlin V, Saftoiu A, Dumitrescu D. Contrast enhanced ultrasound and magnetic resonance imaging in hepatocellular carcinoma diagnosis. Med Ultrason. 2013;15(4):261-7. (Level IV evidence). View the reference
31. Webb GJ, Wright KV, Harrod EC, Gorard DA, Collier JD, Evans AK. Surveillance for hepatocellular carcinoma in a mixed-aetiology UK cohort with cirrhosis: does alpha-fetoprotein still have a role? Clin Med. 2015;15(2):139-44. (Level III/IV evidence). View the reference
32. El-Serag HB, Kanwal F. Alpha-fetoprotein in hepatocellular carcinoma surveillance: mend it but do not end it. Clin Gastroenterol Hepatol. 2013;11(4):441-3. (Level IV/V evidence). View the reference
33. Chang TS, Wu YC, Tung SY, Wei KL, Hsieh YY, Huang HC, et al. Alpha-fetoprotein measurement benefits hepatocellular carcinoma surveillance in patients with cirrhosis. Am J Gastroenterol. 2015;110(6):836-44. (Level III evidence). View the reference
34. Huang TS, Shyu YC, Turner R, Chen HY, Chen PJ. Diagnostic performance of alpha-fetoprotein, lens culinaris agglutinin-reactive alpha-fetoprotein, des-gamma carboxyprothrombin, and glypican-3 for the detection of hepatocellular carcinoma: a systematic review and meta-analysis protocol. Syst Rev. 2013;2:37. (Level I/II evidence). View the reference
35. Witjes CD, van Aalten SM, Steyerberg EW, Borsboom GJ, de Man RA, Verhoef C, et al. Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta-analysis. Hepatol Int. 2013;7(1):59-64. (Level I evidence). View the reference

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