Adapting the Utility of Lipiodol CT in Treating Small Hepatocellular Carcinoma

Abstract

Introduction

Multiphase MRI liver is the gold-standard imaging modality for staging hepatocellular carcinoma (HCC) in patients with cirrhosis. Often, small HCCs diagnosed on multiphase MRI are occult on B-mode ultrasound and multiphase CT (MPCT) and thus pose a challenge for loco-regional therapy. We adapted the technique of lipiodol CT in treating two such patients of small HCC.

Methods

Lipiodol-CT involved an intra-arterial lipiodol injection through the hepatic artery followed by a noncontrast CT liver. CT delineated small, hyperdense, lipiodol-laden hepatic nodules, which served as a target for executing ablation of the nodule and also revealed the true disease stage by depicting the additional number of tumors in the liver.

Results

Case one was a 51-year female, known case of chronic hepatitis C who presented with ascites for two months. She was diagnosed with a small HCC (LI-RADS-4) in a cirrhotic liver on multiphase MRI. Percutaneous radiofrequency ablation was planned, but the mass was not located on ultrasound or multiphase CT. Lipiodol-CT was undertaken, which delineated the lipiodol-laden small HCC, which served as a target for executing ablation. Case 2 was a 55-year male, Child-Pugh A cirrhotic, who had undergone right extended hepatectomy for hepatitis B-related HCC. Follow-up MRI revealed a 5 mm segment III nodule, which had increased in size on repeat MRI at 3 months (LI-RADS-4). This nodule, too, was occult on both ultrasound and MPCT. Lipiodol CT revealed additional multiple, variable-sized lipiodol-laden nodules in the liver remnant. Treatment of trans-arterial chemoembolization was performed at one month. Both patients showed complete response to treatment. Conclusion: Lipiodol CT can be safely used in a new role of facilitating treatment of small HCCs diagnosed on MRI but occult on ultrasonography and MPCT.

Lipiodol (Lipiodol, Guerbet, Roissy-Charles de Gaulle, France)) is an iodized poppy seed oil that has been used as a contrast medium for various imaging techniques, including the hepatic applications since 1966 onwards.¹ The technique of lipiodol CT entails performing a CT scan of the liver after injection of lipiodol through the hepatic artery. Following intra-arterial injection, lipiodol gets selectively retained within the hepatic tumor cells for weeks to months, and on subsequent CT, these lipiodol-laden tumors are seen as hyperdense nodules within the liver.² Detection of hepatocellular carcinoma (HCC) as small as 2 mm and even tiny satellite nodules around the tumor is possible with the use of this technique. For HCCs less than 1 cm size, the detection rate of lipiodol CT is much higher compared to B mode ultrasound, conventional CT, MRI, or digital subtraction angiography.³ The prolonged use of this technique has established its utility not only for preoperative staging of HCC but also for administering various intra-arterial therapies for HCC.^3,4

Barcelona Clinic Liver Cancer (BCLC) classification is currently used for staging and treatment allocation of patients of HCC.⁵ Number of hepatic tumors and their size form a vital component of this staging classification. The vast majority of our patients with HCC often present to the hospital only when symptomatic. Thus, presentation with advanced disease at the outset makes them ineligible for the available curative surgical options.⁶ As a result, loco-regional treatment of percutaneous ablation and intra-arterial therapies have become the mainstay of therapy for HCC.

With the advent of newer and faster imaging scanners and the availability of hepatobiliary contrast media, multiphase contrast-enhanced CT (MPCT) and MRI have become the recommended noninvasive diagnostic modalities for HCC.⁷ MRI has higher diagnostic accuracy than CT, particularly for the detection of lesions less than 2 cm size.⁸ Hence, multiphase MRI has become an essential modality for staging of HCC, particularly for patients with chronic liver disease. Thus, many additional small HCCs are often detected on multiphase MRI, which may not be picked up on MPCT or B-mode ultrasound. The size of the nodule, location, and enhancement characteristics are some of the important factors affecting the detection of these lesions on imaging; delineation of the tumor on either ultrasonography or MPCT for planning and executing the treatment of percutaneous ablation. Small HCCs that are occult on these commonly used imaging techniques often pose a therapeutic challenge to the interventional radiologist. We report two such cases, which were successfully treated by using the technique of lipiodol CT.

Material and methods

Both patients were part of the ongoing study at our center, for which Institute Ethics Committee approval and written informed consent had been obtained.

Technique of Lipiodol CT

Under fluoroscopic guidance (Artis zee fluoroscopy system, Siemens Healthcare, Erlangen, Germany), using local anesthesia, the right common femoral artery was punctured, and superior mesenteric artery and celiac axis arteriograms were obtained using 5F RC1 (Rosch Curve, Cook, Bloomington, IN, USA) or C1 (Cobra, Cook, Bloomington, IN, USA) angiographic catheters and a 0.035-inch j-tip Terumo guidewire (Terumo Corporation, Tokyo, Japan). A selective hepatic artery angiogram was performed, and an intra-arterial contrast injection was given to identify the tumor blush in the liver. About 5 ml lipiodol was injected into the feeding artery, following which a noncontrast CT (Somatom Definition Flash, Siemens Healthcare, Erlangen, Germany) was undertaken to look for lipiodol-laden hyperdense hepatic tumor nodules.

Results

Case 1

A fifty-one-year-old lady, on treatment for chronic hepatitis C for 7 months, reported to us with ascites for two months. Investigations revealed Child-Pugh class B cirrhosis, performance status score of 1, elevated alpha-fetoprotein (AFP) of 461.42 ng/ml, and grade II esophageal varices. Multiphase MRI Liver revealed a small, 1.9 cm HCC in segment VI (Figure 1a), which as per the Liver Imaging Reporting and Data System [LI-RADS (LR)],⁹ was categorized as LR -4. The underlying liver had features of chronic liver disease. Percutaneous radiofrequency ablation (RFA) using a bipolar RFA system (Celon power system, Olympus Medical Systems, Tokyo, Japan) was planned for her. On pre-ablation evaluation, this mass was not located on ultrasound and MPCT. A hepatic artery angiogram was then performed, which showed a tumor blush in segment VI (Figure 1b), following which 5 ml lipiodol was injected into the feeding artery. There were no complications encountered during or after the procedure. The patient was discharged with the instructions to report for RFA after one month. Noncontrast CT of the liver at one month showed lipiodol-laden HCC in segment VI (Figure 1c). Under local anesthesia, using CT guidance, the hyperdense lipiodol-laden tumor was targeted by the RFA electrode, and ablation was performed Figure 1d). Follow up MRI at one month showed the complete response of the tumor. Thereafter, the patient continued to do well and remained disease free as per the last follow-up MRI done at 4 years.

Figure 1.

Lipiodol-CT for guiding percutaneous tumor ablation. (a) Axial arterial phase image of multiphase MRI of the liver shows a homogenously enhancing nodule in segment VI of the liver (arrow), with washout in the venous phase (not shown). The liver shows features of chronic liver disease. This hepatic nodule was not seen on USG and multiphase CT. (b) Hepatic artery angiogram showing tumor blush in segment VI (arrow), following which 5 ml lipiodol was injected into the feeding artery. (c) Post-injection axial noncontrast CT image confirms the lipiodol deposition within the mass (arrow). (d) Radiofrequency ablation was performed (arrow) under CT guidance targeting the Lipiodol deposit.

Case 2

A fifty-year-old man with chronic hepatitis B-related Child-Pugh A cirrhosis had undergone right extended hepatectomy for non-AFP producing HCC. On his follow up at six months, multiphase MRI revealed a small, 5 mm nodule in segment III of the liver, seen only in the arterial phase of the study (Figure 2a) categorized as LR-3. Repeat MRI at three months was done, which depicted an increase in the size of the same segment III nodules, confirming the malignant nature of the nodule (Figure 2b) and categorized as LR-4. On further evaluation, this nodule was found to be occult on ultrasound and MPCT. Again, lipiodol CT was performed after a month for planning management. After the selective left hepatic artery angiogram and lipiodol injection (Figure 2c), noncontrast CT revealed multiple, small, variable-sized nodules scattered in the liver in addition to the earlier diagnosed segment III nodule (Figure 2d) depicting homogenously hyperdense lipiodol pattern deposition. In view of multifocal lesions in a post hepatectomy patient, TACE was performed at one month using an intra-arterial injection of the mixture of 60 mg epirubicin, 10 ml nonionic contrast, and 20 ml lipiodol, followed by gel-foam embolization. The patient was discharged without any complications. Subsequently, the patient developed extrahepatic disease, deteriorated, and succumbed to death after 8 months.

Figure 2.

Detection of occult lesions by lipiodo-CT. (a) Axial arterial phase MRI image of liver showing a peripherally located, 5 mm enhancing lesion in segment III (arrow). (b) Repeat arterial phase MRI done after 3 months shows >50% increase in the size of the lesion (arrow), suggesting interval growth. This lesion was not seen on USG or CT. (c) Spot radiograph performed after the injection of lipiodol following selective left hepatic artery catheterization shows multiple foci of lipiodol deposition (arrows). (d) Axial noncontrast CT of liver performed after a week shows multiple, small, variable-sized, lipiodol-laden hepatic nodules (arrows) scattered in the entire left lobe.

Discussion

Accurate diagnosis and prompt therapy for HCC are essential for prolonging survival of patients of HCC. The number of liver tumors is vital not only for planning surgery but also for executing treatment by loco-regional therapies to achieve disease-free status.

Small HCCs diagnosed on MRI but occult on other imaging techniques pose a huge therapeutic challenge. The technique of contrast-enhanced ultrasound (CEUS) of the liver is a useful modality and scores over conventional B-mode ultrasound in the detection of small hepatic nodules. It also has the additional advantage of providing guidance for undertaking subsequent ablation of the tumor. However, CEUS has numerous limitations as well. It has a very short imaging window period (arterial phase lasting only 30–45 s), which is often inadequate for any procedure. There is limited penetration of ultrasound waves in the presence of hepatic steatosis or fibrosis. Moreover, sub-diaphragmatic lesions and those less than 5–10 mm in size are difficult to evaluate.¹⁰

We adapted the utility of a well-established technique of lipiodol CT for treating these challenging lesions. Lipiodol-laden small HCC seen on the CT liver not only served as a guide for targeting for ablation but also helped in the accurate staging and management of our second patient.

Our first patient had compromised liver function, as suggested by her history of repeated hepatic decompensation prior to reporting to us. Thus, RFA was a preferred option for her. Noncontrast CT performed one month after lipiodol injection confirmed the diagnosis and facilitated accurate targeting of the lesion by the RFA electrode using CT guidance.

For managing the second patient, this technique proved useful on two accounts. Following hepatectomy, the true stage of the disease was revealed. The detection of additional, multiple small nodules scattered throughout the liver led to appropriate, timely treatment of the patient as per the revised BCLC staging.

Lipiodol CT has a sensitivity of 96% for detecting small HCCs below 5 cm and 93% for those below 2 cm.¹¹ False negatives may be encountered if the nodule is avascular, necrotic, or fibrotic and fails to take up lipiodol. In case the catheter gets mispositioned, all areas of the liver may not be perfused. Even cases of focal nodular hyperplasia (FNH), hemangioma, and metastatic lesions may sometimes be misleading. Thus, the pattern of lipiodol deposition within these small hepatic nodules needs familiarity. A homogeneously hyperdense pattern is typical of HCC, although it may rarely be seen in FNH as well. Patchy lipiodol points towards either FNH, hemangioma, or metastasis.¹¹ Moreover, the duration of lipiodol deposition is a vital clue. Benign nodules have lipiodol retention for a shorter duration as compared to the malignant nodules. Thus, detailed history and follow-up CT becomes extremely important.

To conclude, Lipiodol CT can be safely used in a new role of facilitating percutaneous ablative therapy for small HCCs diagnosed on MRI but occult on ultrasonography and MPCT.

CRediT authorship contribution statement

Shashi B. Paul: Investigation, Data curation, Validation, Writing – original draft. Shivanand R. Gamanagatti: Investigation, Validation, Writing – review & editing. Ekta Dhamija: Visualization, Writing – review & editing. Vishnu P. Pulappadi: Writing – original draft, Writing – review & editing. Shalimar: Validation, Writing – review & editing, Supervision. Subrat K. Acharya: Conceptualization, Supervision.

Conflicts of interest

The authors have none to declare.

FUNDING

None.