This week’s blog will focus on examining the detection of hepatocellular carcinoma (HCC) on patients with cirrhosis. It is inspired by last week’s lecture on imaging the hepato-biliary system.
According to The European Association of the Study of the Liver (EASL) (2012), HCC is the sixth most common cancer worldwide and the third most common cause of cancer related death. It develops from cells in the liver called hepatocytes hence why it is called a primary cancer. It is also more common in men than women and the risk increases with age, the peak being at the age of 70 (Cancer Research UK, 2015). Ethnicity is also a factor as the mean age of tumour manifestation is significantly younger within Asian and Black African population in the world. It also has a different pattern of occurrence in the world with the highest incidence rates found in East Asia, sub-Saharan Africa and Melanesia. 85 % of the cases in the world are found in these regions (EASL, 2012). Cirrhosis is a major risk factor, which is why adults with cirrhosis are offered 6-monthly surveillance for HCC (National Institute for Health and Care Excellence, 2017). Long-term survival is predicted by tumour stage at diagnosis, which is why early detection and accurate diagnosis is essential (Farrell et al. 2017; Cross et al., 2015).
Finding the best suited imaging technique for detection and characterisation of liver lesions on the background of cirrhotic liver is still a challenge (Kurucay et al. 2017). Farrell et al. (2017) did a review of the recall surveillance program for HCC detection in cirrhotic patients in a tertiary-referral centre in the UK. They acknowledge the lack of strong evidence for the efficacy of surveillance programs for HCC. This contradicts the guidelines published by the EASL (2012) which state it being cost-effective and helpful in excluding some patients from further surveillance. It is also not in line with NICE guidelines (2017) which recommend ultrasound surveillance, as HCC can remain asymptomatic while it advances. The reason behind the statement by Farrell et al. (2017) is most likely the lack of organisational support for surveillance programs and the poor provision of the service they found in their study. They continue to say that there is significant benefit to this program, provided they are given the same support as screening programs for other diseases such as breast and colon cancer (Farrell et al. 2017).
There is evidence in literature to say that accurate diagnosis requires contrast-enhanced CT and dynamic MRI with gadolinium (Kurucay et al. 2017; Hennedige and Venkatesh, 2012; EASL, 2012). While a biopsy was needed before, now radiological method is acceptable for diagnosis, provided there are imaging characteristics present (Hennedige and Venkatesh, 2012). This is ideal from patient management perspective as they do not need aftercare and are able to leave after the procedure.
The significant marker seems to be the vascular pattern of the tumour and this requires contrast-enhanced imaging methods (Hennedige and Venkatesh, 2012; EASL, 2012). The European Association of the Study of the Liver (2012) recommends the following guidelines in order to diagnose HCC. Lesions greater than 1 cm with a typical vascular pattern on dynamic contrast enhanced CT or MR should be treated as HCC. If a lesion has an atypical vascular pattern then further imaging is required for diagnosis. However, if a lesion is smaller than 1 cm with atypical vascular pattern then next step is to do a biopsy or an enhanced surveillance with MRI or CT. Lesions greater than 2 cm with atypical vascular patterns may be considered as HCC, provided the level of alpha-fetoprotein is above 200 ng/ml (AFP). High level of AFP is a strong indication of the presence of HCC.
Here, two articles discussing the diagnostic accuracy of CT and MRI for HCC, will be examined. The first one is a review by Kurucay et al. (2017), which examines the imaging parameters derived from perfusion CT (PCT) and gadoxetic acid-enhanced MRI in patients with HCC. The review was done in at one site in Germany with 36 cirrhotic patients with a diagnosis of HCC-suspected liver lesions. There were 67 lesions in total between the 36 patients. Perfusion CT quantified the blood flow within the liver with values for arterial liver perfusion (ALP), mean/max blood flow (BF), blood volume (BV), portal venous perfusion (PVP) and hepatic perfusion index (HPI). They found that HCC is associated with high HPI (> 96 %) and high values of BF in the tissue. Hennedige and Venkatesh (2012) agree with this, saying PCT quantifies arterial flow in the liver and can show the perfusion parameters, which differ significantly from between HCC tissue and normal liver parenchyma.
With regards to MRI, Kurucay et al. (2017) showed that six out of 67 HCCs were missed in T1 weighted images. 59 of the 67 lesions were detected in hepato-biliary phase images; 11 of the 67 lesions were missed on fat-saturated T2 weighted images. The conclusion showed that information from all applied imaging sequences were needed to equal the sensitivity of PCT. PCT also made clear the margins of the tumours, due to the high HPI value. Hennedige and Venkatesh (2012) agree and say that HCC has variable appearances on MRI. It seems to support the results found in the Kurucay et al (2017) study and can explain, why some lesions were missed in certain sequences. Hennedige and Venkatesh (2012) also add that diffusion-weighted imaging may be particularly useful in initial screening, as 70-95 % of lesions appear hyperintense.
The readers used in the study by Kurucay et al (2017) had the combined experience of more than 24 years in reading oncological CTs and MRIs. This was divided, with one reader having 4 years of experience and the other had more than 20 years. They may have done this to compare the effect of experience on lesion detection and characterisation, however they did not mention this in the article. It was mentioned that there were some disagreement with seven cases, however they were resolved in the end. The disagreement only occurred with the MRI scans and the steps that lead to the agreement were not explained. It would have been beneficial to include that information as it could be useful in managing reporting workload effectively within clinical imaging departments.
Kurucay et al. (2017) used only Siemens equipment with both CT and MRI, which suggests that results may differ between manufacturers. This means further studies need to be done with other equipment to compare their performance. The information is useful when departments consider purchasing new scanners. The MRI scanners used had different strength of magnets; one being 1.5 Tesla (T) and the other 3.0 T. This could have had an impact on the results as well. Also with regards to patient management the CT protocol was more patient-friendly, requiring only two scans with one injection of contrast. The MRI protocol included GRE T1-weighted, axial respiratory gated T2-weighted, diffusion weighted and fat suppressed T1 weighted VIBE sequences before the contrast was given. This was followed by four fat suppressed T1 weighted VIBE sequences. The time used is extensive and with issues experienced in these scans, such as claustrophobia and sensitivity to the noise of the machine, it is not the most patient friendly option. However, it is an recommended option because of the use of non-ionising radiation. The dose received from PCT varied between 9 and 14 mSv depending on the scan length. This is significant amount as it is around the range of CT scan of the whole spine, which is 10 mSv (Public Health England, 2011).
Sadly the 3 year survival rate of HCC can be as low as 10 %. Farrell et al. (2017) review showed that 16 of the 22 patients diagnosed with HCC died by June 2016. The review was conducted between 2009 and 2013. Low survival rates coupled with the rising incidence rates of HCC, shows the need for research in improving screening methods as well as diagnostic imaging technology for early detection (EASL, 2012).
Cancer Research UK (2015) Liver cancer – types. Available at: http://www.cancerresearchuk.org/about-cancer/liver-cancer/types [Accessed 09 November 2017].
Cross, T.J., Villaneuva, A., Shetty, S., Wilkes, E., Collins, P., Adair, A., Jones, R.L., Foxton, M.R., Meyer, T., Stern, N., Warshow, U., Khan, N., Prince, M., Khakoo, S., Alexander, G.J., Khan, S., Reeves, H., Marshall, A., Williams, R. (2015) A national survey of the provision of ultrasound surveillance for the detection of hepatocellular carcinoma. BMJ Journals [online] 7 (2) [Accessed 09 November 2017].
European Association for the Study of the Liver (2012) EASL Clinical Practice Guidelines on the management of hepato-cellular carcinoma. Available at: http://www.easl.eu/research/our-contributions/clinical-practice-guidelines/detail/management-of-hepatocellular-carcinoma-easl-eortc-clinical-practice-guidelines/report/4 [Accessed 12 November 2017].
Farrell, C., Halpen, A., Cross, T.J.S., Richardson, P.D., Johnson, P., Joekes, E.C. (2017) Ultrasound surveillance for hepatocellular carcinoma: service evaluation of a radiology-led recall system in a tertiary-referral centre for liver diseases in the UK. Clinical Radiology [online] 72 (4) p 338.e11 – 338.e17 [Accessed 12 November 2017].
Hennedige, T., Venkatesh, S.K. (2012) Imaging of hepatocellular carcinoma: diagnosis, staging and treatment monitoring. Cancer Imaging [online] 12 (3) pp. 530-547 [Available 12 November 2017].
Kurucay, M., Kloth, C., Kaufmann, S., Nikolau, K., Bosmuller, H., Horger, M., Thaiss, W.M. (2017) Multiparametric imaging for detection and characterization of hepatocellular carcinoma using gadodetix acid-enhanced MRI and perfusion-CT: which parameters work best? Cancer Imaging [online] 17 pp. 1-8 [Accessed 12 November 2017].
National Institute for Health and Care Excellence (2017) Liver disease quality standard [QS152]. Available at: https://www.nice.org.uk/guidance/qs152/chapter/Quality-statement-4-Surveillance-for-hepatocellular-carcinoma [Accessed 12 November 2017].
Public Health England (2011) Ionising radiation: dose comparisons. Available at: https://www.gov.uk/government/publications/ionising-radiation-dose-comparisons/ionising-radiation-dose-comparisons [Accessed 12 November 2017].