Hepatic Chemoembolization Imaging

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Hepatocellular carcinoma (HCC) is the most common primary liver tumor worldwide, and its incidence is rising. Most HCCs are associated with cirrhosis. The risk of developing HCC appears to be related to the degree of activity of cirrhosis. The risk is high in patients with macronodular cirrhosis secondary to hemochromatosis and lower in those with alcoholic micronodular cirrhosis. Surgery offers the best prospect of cure, but the resectability of HCC is low. Key predictors of tumor response after chemoembolization on unresectable HCC include the tumor’s size, vascularity, and number, as well as portal vein invasion. Factors associated with poor prognosis for overall patient survival include Child-Pugh class B or C, tumor size ≥4 cm, 5 or more tumors, portal vein invasion, and an alpha fetoprotein (AFP) level >83 ng/mL. ^[1]  Conventional and drug-eluting bead chemoembolization have been found to have a limited impact on liver function, and tumor response is not dependent on type of embolization used. ^{[2, 3, 4]}

Diagnostic imaging depicts not only the primary hepatic disease but also ascites, lymph node metastases, and thrombosis of portal or hepatic veins. Confirming portal vein patency is important because portal vein thrombosis is a relative contraindication to chemoembolization. ^{[5, 6]} If portal flow via collateral vessels remains hepatopetal, embolization may be better tolerated. Imaging also plays an important role in evaluating the effectiveness of interventional therapy.

Peptide-receptor radionuclide therapy (PRRT) is a relatively new treatment reserved for treatment of unresectable or metastatic gastroenteropancreatic neuroendocrine tumors (GEP NETs). Campana et al conducted a study to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response. The study concluded that low tumor burden and a low proliferation index represent independent prognostic factors for long progression-free survival, while previous transcatheter arterial chemoembolization (TACE) techniques represent independent prognostic factors for early tumor progression and shorter progression-free survival. The data derived from the study suggest that TACE techniques to reduce the hepatic tumor burden should be avoided. ^[7]

Liu et al retrospectively studied 246 consecutive patients with primary Budd-Chiari syndrome (BCS) with the view to analyze the imaging features of BCS associated HCC and the results of angioplasty/stenting of hepatic veins/inferior vena cava and TACE. The study concluded that BCS patients with inferior vena cava block and stricture of hepatic venous outflow tract seem to be associated with HCC. A single, large, irregular nodule with a peripheral location appears to be HCC. ^[8]

Bile duct strictures are a known complication of TACE. Anastomosis between A1 or A4 and other branches has been shown to be frequently associated with bile duct strictures 2-8 months after TACE of the bile duct branch. ^[9]

A review by Rempp and associates suggested that radiofrequency ablation should be used in patients with early-stage HCC with up to 3 lesions with a tumor diameter of ≤3 cm and for patients with nonresectable liver metastasis. ^[10]

An axial computed tomography (CT) scan of an HCC is seen below.

The imaging strategy in HCC depends on the clinical question to be answered and the treatment options available. Angiography is an essential part of the workup performed prior to embolization or chemoembolization, although most centers proceed to the embolization procedure if no contraindications are present. In patients with a known primary malignancy, such as colorectal cancer or islet cell tumors, an initial investigation includes an ultrasonographic examination followed by spiral or multisection, 3-phase, contrast-enhanced CT scanning. Contrast-enhanced sonography is useful in determining the differences between the grades of HCCs. Using auto-tracking contrast quantification software, the time to peak, contrast-enhanced time, and wash-out time were longer for well-differentiated hepatocellular lesions and the enhancement slope and clearance slope were lower than that of moderately to poorly differentiated carcinomas. ^{[11, 12, 13, 14]}

Magnetic resonance imaging (MRI) and radionuclide scanning are useful in confirming the diagnosis, particularly the diagnosis of benign lesions, such as hemangiomas and focal nodular hyperplasia. These lesions are increasingly encountered in the setting of malignant disease. The multiplanar capability of MRI is particularly helpful in determining the exact anatomic location of the lesions. In the setting of HCC, a protocol similar to that used for liver metastasis is performed.

Follow-up CT scans are obtained approximately 10-14 days after chemoembolization. An early scan may be acquired if complications, such as nontarget embolization, are suspected. Because the chemotherapeutic agent is mixed with lipiodol, CT scans of a tumor reveal dense opacification associated with necrosis (see the image below).  Along with nontarget embolization, CT scans also demonstrate such complications as the development of ascites and pleural effusions. When only polyvinyl alcohol embolization is performed, as in cases of hepatic carcinoid, postembolization CT scans demonstrate only tumor necrosis. ^[15]  In patients with hepatocellular carcinoma (HCC), if the embolization procedure is successful, the postprocedural CT scan will show a lipiodol uptake of greater than 50% in necrotic tumor. In these cases, the embolization is repeated in 6-8 weeks. If the lipiodol uptake is less than 50%, the authors repeat the CT scan in 6-8 weeks. ^{[16, 17, 18]}

MRI and radionuclide scanning are useful in confirming a diagnosis, particularly the diagnosis of benign lesions, such as hemangiomas and focal nodular hyperplasia. These lesions are increasingly encountered in the setting of malignant disease. The multiplanar capability of MRI is particularly helpful in determining the exact anatomic location of the lesions. In the setting of hepatocellular carcinoma, a protocol similar to that used for liver metastasis is performed. ^{[19, 20]}

Angiography is an essential part of the workup performed prior to embolization or chemoembolization, although most centers proceed to the embolization procedure if no contraindications are present. Angiography is usually performed by placing a 5F to 6F catheter through a sheath via the right or left femoral artery. The catheter should be able to accept the insertion of a 3F coaxial microcatheter. A celiac-axis and superior mesenteric angiogram is first obtained to identify common variations in the blood supply to the liver and to check for patency of the portal vein.

Angiograms obtained prior to and after chemoembolization are seen below.

Embolization of parasitized extrahepatic arteries (EHAs) to reestablish intrahepatic arterial inflow to hepatic tumors was found to be safe and effective in a retrospective analysis of 201 patients. ^[21] The procedure successfully delivered yttrium-90 microspheres to tumors previously perfused by parasitized EHAs.

Hu HT, Kim JH, Lee LS, Kim KA, Ko GY, Yoon HK, et al. Chemoembolization for hepatocellular carcinoma: multivariate analysis of predicting factors for tumor response and survival in a 362-patient cohort. J Vasc Interv Radiol. 2011 Jul. 22(7):917-23. [Medline].

Sacco R, Bargellini I, Bertini M, Bozzi E, Romano A, Petruzzi P, et al. Conventional versus Doxorubicin-eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma. J Vasc Interv Radiol. 2011 Nov. 22(11):1545-52. [Medline].

Aljumah AA, Kuriry H, AlZunaitan M, Al Ghobain M, Al Muaikeel M, Al Olayan A, et al. Clinical Presentation, Risk Factors, and Treatment Modalities of Hepatocellular Carcinoma: A Single Tertiary Care Center Experience. Gastroenterol Res Pract. 2016. 2016:1989045. [Medline].

Arslanoglu A, Seyal AR, Sodagari F, Sahin A, Miller FH, Salem R, et al. Current Guidelines for the Diagnosis and Management of Hepatocellular Carcinoma: A Comparative Review. AJR Am J Roentgenol. 2016 Aug 4. W1-W11. [Medline].

Gates J, Hartnell GG, Stuart KE, Clouse ME. Chemoembolization of hepatic neoplasms: safety, complications, and when to worry. Radiographics. 1999 Mar-Apr. 19(2):399-414. [Medline].

Palma LD. Diagnostic imaging and interventional therapy of hepatocellular carcinoma. Br J Radiol. 1998 Aug. 71(848):808-18. [Medline].

Campana D, Capurso G, Partelli S, Nori F, Panzuto F, Tamburrino D. Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence. Eur J Nucl Med Mol Imaging. 2013 Apr 26. [Medline].

Liu FY, Wang MQ, Duan F, Fan QS, Song P, Wang Y. Hepatocellular carcinoma associated with budd-chiari syndrome: imaging features and transcatheter arterial chemoembolization. BMC Gastroenterol. 2013 Jun 24. 13(1):105. [Medline].

Miyayama S, Yamashiro M, Hashimoto M, Hashimoto N, Ikuno M, Okumura K, et al. Blood supply of the main bile duct from the caudate artery and medial subsegmental artery of the hepatic artery: Evaluation using images obtained during transcatheter arterial chemoembolization for hepatocellular carcinoma. Hepatol Res. 2013 Jan 14. [Medline].

Rempp H, Boss A, Helmberger T, Pereira P. The current role of minimally invasive therapies in the management of liver tumors. Abdom Imaging. 2011 Dec. 36(6):635-47. [Medline].

Kim HO, Kim JS, Shin YM, et al. Evaluation of metabolic characteristics and viability of lipiodolized hepatocellular carcinomas using 18F-FDG PET/CT. J Nucl Med. 2010 Dec. 51(12):1849-56. [Medline].

Kouri BE, Abrams RA, Al-Refaie WB, Azad N, Farrell J, Gaba RC, et al. ACR Appropriateness Criteria Radiologic Management of Hepatic Malignancy. J Am Coll Radiol. 2016 Mar. 13 (3):265-73. [Medline].

Yoshimatsu R, Yamagami T, Ishikawa M, Kajiwara K, Aikata H, Chayama K, et al. Change in Imaging Findings on Angiography-Assisted CT During Balloon-Occluded Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma. Cardiovasc Intervent Radiol. 2016 Jun. 39 (6):865-74. [Medline].

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Meyer BC, Frericks BB, Voges M, Borchert M, Martus P, Justiz J, et al. Visualization of hypervascular liver lesions during TACE: comparison of angiographic C-arm CT and MDCT. AJR Am J Roentgenol. 2008 Apr. 190(4):W263-9. [Medline].

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Takada K, Toyoda H, Tada T, Ito T, Hasegawa R, Gotoh T, et al. Accurate and rapid identification of feeding arteries with multidetector-row angiography-assisted computed tomography for transarterial chemoembolization for hepatocellular carcinoma. J Gastroenterol. 2015 Dec. 50 (12):1190-6. [Medline].

Kim I, Kim DJ, Kim KA, Yoon SW, Lee JT. Feasibility of MDCT angiography for determination of tumor-feeding vessels in chemoembolization of hepatocellular carcinoma. J Comput Assist Tomogr. 2014 Sep-Oct. 38 (5):742-6. [Medline].

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Abdelmaksoud MH, Louie JD, Kothary N, Hwang GL, Kuo WT, Hofmann LV, et al. Embolization of Parasitized Extrahepatic Arteries to Reestablish Intrahepatic Arterial Supply to Tumors before Yttrium-90 Radioembolization. J Vasc Interv Radiol. 2011 Oct. 22(10):1355-62. [Medline].

Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR Consultant Radiologist and Honorary Professor, North Manchester General Hospital Pennine Acute NHS Trust, UK

Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR is a member of the following medical societies: American Association for the Advancement of Science, American Institute of Ultrasound in Medicine, British Medical Association, Royal College of Physicians and Surgeons of the United States, British Society of Interventional Radiology, Royal College of Physicians, Royal College of Radiologists, Royal College of Surgeons of England

Disclosure: Nothing to disclose.

Chi-Leung (Eddie) Tam, MBChB, FRCS Consulting Staff, Department of Radiology, Lancaster Royal Infirmary, UK

Chi-Leung (Eddie) Tam, MBChB, FRCS is a member of the following medical societies: Royal College of Radiologists

Disclosure: Nothing to disclose.

Aali J Sheen, MD, MBChB, FRCS Consulting Hepatobiliary Surgeon, HepatoBiliary Unit, Manchester Royal Infirmary, UK

Aali J Sheen, MD, MBChB, FRCS is a member of the following medical societies: British Medical Association, International Hepato-Pancreato-Biliary Association, Royal College of Surgeons of England

Disclosure: Nothing to disclose.

Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand

Disclosure: Nothing to disclose.

Douglas M Coldwell, MD, PhD Professor of Radiology, Director, Division of Vascular and Interventional Radiology, University of Louisville School of Medicine

Douglas M Coldwell, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Heart Association, SWOG, Special Operations Medical Association, Society of Interventional Radiology, American Physical Society, American College of Radiology, American Roentgen Ray Society

Disclosure: Received consulting fee from Sirtex, Inc. for speaking and teaching; Received honoraria from DFINE, Inc. for consulting.

Kyung J Cho, MD, FACR, FSIR William Martel Emeritus Professor of Radiology (Interventional Radiology), Frankel Cardiovascular Center, University of Michigan Health System

Kyung J Cho, MD, FACR, FSIR is a member of the following medical societies: American College of Radiology, American Heart Association, American Medical Association, American Roentgen Ray Society, Association of University Radiologists, Radiological Society of North America

Disclosure: Nothing to disclose.

Anthony Watkinson, MD Professor of Interventional Radiology, The Peninsula Medical School; Consultant and Senior Lecturer, Department of Radiology, The Royal Devon and Exeter Hospital, UK

Anthony Watkinson, MD is a member of the following medical societies: Radiological Society of North America, Royal College of Radiologists, Royal College of Surgeons of England

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, David Sherlock, MBBS, FRCS, and Martin Punter, MBChB, to the development and writing of this article.

Hepatic Chemoembolization Imaging

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