Lipiodol® Ultra-Fluid
(Iodinated ethyl esters of fatty acids of poppy seed oil)  

Scroll down on the page to access the HCC Treatment, Vascular Anomalies Embolization, and the Lymphography procedure’s guidelines.

HCC Treatment Guidelines

Lipiodol® Ultra-Fluid (Iodinated ethyl esters of fatty acids of poppy seed oil) use in TACE efficacy is recognized and endorsed by guidelines worldwide


AASLD (American Association for the Study of Liver Disease) – 2018 (1)

The AASLD recommends locoregional therapy over no treatment in adults with cirrhosis and HCC (T2 or T3, no vascular involvement) who are not candidates for resection or transplantation. (Quality/Certainty of Evidence for TACE = moderate).

A meta-analysis comparing TACE with placebo:  

  • identified 7 RCTs on TACE versus placebo with a total of 545 patients,
  • establishing TACE as an effective strategy for unresectable multinodular HCC occurring in patients with compensated cirrhosis.

The analysis demonstrated improvement in 2-year survival for patients treated with TACE vs placebo (41% vs 27%; OR, 0.53; P = 0.017).

A meta-analysis specifically comparing DEB-TACE with conventional TACE treatment performed (3) identified 4 RCTs and 8 observational trials. Non-significant trends were noted in 1-, 2-, and 3-year survival in favor of DEB-TACE compared with conventional TACE. Pooled analysis of objective response and of complications showed no difference between the two therapies.


NCCN (National Comprehensive Cancer Network) – 2021 (2)

TACE is distinguished from TAE (transarterial embolization) in that,

  • in addition to arterial blockade, the goal is to also deliver a highly concentrated dose of chemotherapy to tumor cells,
  • prolong the contact time between the chemotherapeutic agents and the cancer cells,
  • and minimize systemic toxicity of chemotherapy.

The results of 2 RCTs and one retrospective case-control study have shown a survival benefit for TACE compared with supportive care in patients with unresectable HCC.


Arterially directed therapy (including TACE) is recommended in patients:

  • Potentially resectable or transplantable operable by performance status or comorbidity (Child-Pugh class A – B no portal hypertension, suitable tumor location, adequate liver reserve, suitable liver remnant)
  • Unresectable (Inadequate hepatic reserver, tumor location) and not a transplant candidate
  • Liver-confined disease, inoperable by performance status, comorbidity or with minimal or uncertain extrahepatic disease

BCLC (Barcelona Clinic Liver Cancer) – 2022 (3)

The BCLC recommends TACE for intermediate stage (B: multinodular, preserved liver function, performance status = 0), with well-defined nodules, preserved portal flow and selective access: expected survival > 2.5 years.

TACE might be performed using chemotherapy emulsified in lipiodol followed by gelfoam or any other material injection (conventional TACE) or using drug-eluting microspheres (DEB-TACE).

Response rates and survival are not different between the technique.

TACE is also recommended in not feasible or failure of ablation / resection / ablation / transplant of

- very early stages (0) : Single < 2 cm, preserved liver function, performance status = 0),

- early stage (A: single or < 3 nodules each < 3 cm, preserved liver function, performance status = 0): expected survival > 5 years.

For early stage (A: single or < 3 nodules each < 3cm preserved liver function, performance status = 0), upon enlisting patients for liver transplantation (LT) and if the expected waiting time exceeds 6 months, it is recommended to consider treatment to prevent tumour progression that could rule out LT. Ablation, chemoembolization and transarterial radioembolization are the most widely used options for this purpose.

BCLC staging and treatment strategy


EASL (European Association for the Study of the Liver) – 2018 (4)

TACE is recommended for patients with BCLC stage B and should be carried out in a selective manner (evidence high; recommendation strong).

The use of drug-eluting beads has shown similar benefit to conventional TACE (cTACE; gelfoam-Lipiodol® particles) and either of the two can be utilised (evidence high; recommendation strong).


TACE should not be used in patients with decompensated liver disease, advanced liver and/or kidney dysfunction, macroscopic vascular invasion or extrahepatic spread (evidence high; recommendation



There is insufficient evidence to recommend bland embolization, selective intra-arterial chemotherapy and lipiodolization (evidence moderate).


Recently, a systematic review on conventional TACE has included 101 articles , with a total of 10,108 patients.

The objective response rate was 52.5% (95% CI 43.6–61.5), and the overall survival (OS) was 70.3% at one year, 51.8% at two years, 40.4% at three years, and 32.4% at five years with a median OS of 19.4 months (95% CI 16.2–22.6).


The five most common adverse events were:  

  • liver enzyme abnormalities (18.1%), fever (17.2%), haematological/bone marrow toxicity (13.5%), pain (11%), and vomiting (6%), which are related to the occurrence of postembolization syndrome

A retrospective study has shown that biliary injuries, intrahepatic bilioma, and global hepatic damage were significantly higher following DEB-TACE than with conventional TACE, especially in patients with advanced cirrhosis.

Modified BCLC staging system and treatment strategy






ESMO (European Society of Medical Oncology) – 2018 (5) / update 2021(6)

The benefit of TACE in prolonging OS was demonstrated in selected asymptomatic patients with maintained liver function that belong to the BCLC A stage to early intermediate BCLC B stage, who had a small tumor burden but were not amenable to surgery or local ablation [I, A: strong evidence for efficacy].


Median OS (mOS) of 30– 45 months can be expected in this population. Shorter median survival of < 20 months has been reported in real life cohorts when patients with no proven benefit are treated including those in Child-Pugh B stage, with portal vein invasion, large tumor burden or deteriorating liver function under TACE.


The text has been updated to include a level of evidence and grade of recommendation for selective internal radiotherapy (SIRT)


BCLC staging and treatment options according to level of evidence and approval status

RPC Flag

Hepatocarcinoma Guidelines in China – 2019 (7)

TACE is currently recognized as one of the most commonly used nonsurgical treatments

for HCC (level 1 evidence).


Lipiodol emulsion (containing chemotherapy drugs), standardized gelatin sponge particles, blank microspheres, and polyvinyl alcohol particles are often used in conventional TACE (also known as cTACE).


Indications for TACE:

  • Patients with CNLC stage IIb and IIIa HCC and a proportion of patients with Stage IIIb disease, with Child-Pugh grade A or B and a PS score of 0–2;
  • Patients with resectable CNLC Stage Ib and IIa HCC who are unable or unwilling to receive surgery for other reasons such as older age and severe cirrhosis;
  • Patients with incomplete obstruction of the main portal vein or formation of abundant compensatory collateral branches of the portal vein or recanalized portal vein by portal vein stenting despite complete obstruction;
  • Patients with portal hypertension related bleeding as a result of hepatic artery−portal venous shunt;
  • Digital substaction angiography can be performed for early detection of residual cancer or recurrent lesions following liver resection and TACE can be performed as appropriate.

China clinical staging and treatment pathway for HCC



Japan Society of Hepatology Consensus statements & recommendations update – 2021(8)


  • is mainly indicated in patients with hyper vascular HCCs classified as Child-Pugh class A or B, with 2–3 tumors of ≥3 cm in diameter or ≥4 tumors,
  • may be indicated for some patients with minor vascular invasion.


For localized tumors, superselective infusion of Lipiodol® mixed with anticancer agents followed by gelatin sponge injection with visualization of portal branch improves the local treatment efficacy (20).


According to the 20th Nation-wide Follow-up Survey Report on Primary Liver Cancer, cTACE using Lipiodol® and gelatin sponge was performed as a first-line treatment in 27.5% (n = 5,083) of 18,458 initially diagnosed HCC cases and 39.3% (n = 2,627) of 6,687 recurrent cases of HCC, making it the most commonly used treatment for HCC.


Although TACE using drug-eluting beads (DEB) was introduced in Japan in 2014, cTACE remains the mainstream treatment for HCC, and the improved outcomes of cTACE have directly translated into prolonged survival of HCC patients.


The most recent meta-analysis, which was reported in 2016, included 1,449 patients from 4 randomized controlled trials and 8 observational studies. The results showed no significant difference between DEB-TACE and cTACE in terms of response rate, overall survival, or adverse events.



  1. Heimbach JK, Kulik LM, Finn RS, et al. AASLD Guidelines for the treatment of hepatocellular carcinoma. 2018; 67(1): 358 – 380.


  1. Benson AB, D’Angelica MI, Abott DE, et al. Hepatobiliary cancers, Clinical practice guidelines in oncology. Version 2.2021. Journal of the National Comprehensive Cancer Network. 2021; 19(5): 541 – 565


  1. Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. Journal of Hepatology. 2022; 76: 681 – 693.


  1. European Association for the Study of the Liver (EASL) clinical practice guidelines: Management of hepatocellular carcinoma. Journal of Hepatology. 2018; 69: 182 - 236


  1. Vogel A, Cervantes A, Chau I, et al. Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow up Annals of Oncology. 2018; 29(4): 238 – 255.


  1. Vogel A, Martinelli E. Updated treatment recommendations for hepatocellular carcinoma (HCC) from ESMO clinical practice guidelines. Annals of Oncology. 2021; 32(6): 801 – 804.


  1. Zhou J, Sun H, Wang Z, et al. Guidelines for the diagnosis and treatment of hepatocellular carcinoma (2019 edition). Liver cancer. 2020; 9: 682 – 720.


  1. Kudo M, Kawamura Y, Hasegawa K, et al. Management of hepatocellular carcinoma in Japan: JSH consensus statements and recommendations 2021 update. Liver Cancer. 2021; 10: 181 – 223

Vascular Anomalies Embolization Guidelines

Lipiodol® Ultra-Fluid (Iodinated ethyl esters of fatty acids of poppy seed oil) & N-butyl cyanoacrylate glue (NBCA) endorsed by international guidelines


Japanese Guidelines(6)

« The optimal volume, injection speed, and ratio of the NBCA-Lipiodol® mixture should be determined to facilitate successful vascular embolization. […] NBCA is radiolucent, and therefore, is usually mixed with radiopaque materials such as Lipiodol ®…»

« Lipiodol® is an oily contrast medium. Its generic name is ethyl ester of iodinated poppy-seed oil fatty acids. In Japan, it has been used during hysterosalpingography and lymphangiography. When NBCA is mixed with Lipiodol®, the NBCA becomes radiopaque, and its polymerization time is increased…»


American Guidelines(7)

« Cyanoacrylate glue is a liquid that may be mixed with Lipiodol® , an oily contrast agent, before injection. Mixing cyanoacrylate glues with Lipiodol® slows the rate of solidification, […] It also allows visualization of the injected varix on fluoroscopy. Various ratios of glue and Lipiodol® are used, ranging from 1:1 to 1:1.6.»


Consensus Guidelines -International Union of Angiology(8)

« […] NBCA is a clear free flowing adhesive liquid that will polymerize on contact with any ionic solution. NBCA must be combined with ethiodized oil to reduce the polymerization time and to add radiopacity. The more ethiodized oil used the slower the polymerization time…»

Lymphography procedure’s guidelines

Lymphography – Detecting lymphatic system impairment recommended by International Clinical Guidelines


International Union IUA Guideline (International Union of Angiology)(9)

« Oil contrast standard Lymphangiography /Lymphography
LAG* is still advantageously employ in selected patients with chylous dysplasia and gravitational reflux disorders in order to define more clearly the extension of the pathologic alteration and site of lymphatic and chylous leak. These are the only diagnostic investigation that can clearly demonstrate pathologies of chylous vessels, chylous cyst and thoracic duct in cases of chylothorax, chylous ascites, protein losing enteropathy.»

*LAG: Lymphangiography


American APTA Guideline(10) (American Physical Therapy Association)

« …Lymphography may be used to detect lymphatic system impairment… Diagnostic accuracy in patients with known lymphedema demonstrated a sensitivity of 1.0 and a specificity of 1.0 when compared with CT and MRI…»

Lipiodol® Ultra-Fluid (Iodinated ethyl esters of fatty acids of poppy seed oil) used for lymphangiography/lymphography endorsed by international guideline


International Union IUA Guideline(9) (International Union of Angiology)

« A lipid-soluble ultrafluid contrast medium (Lipiodol® Ultra fluid) is injected into lymphatic vessel after isolation and cannulation of the lymphatics of the dorsum of foot with microsurgical technique so that the lymphatic network and lymph nodes can be seen.

…When this conventional oil contrast lymphangiography is coupled with CT scan, it allows a more accurate assessment of disease extension, as well as the site of the obstacle and source of chylous leakage.
The main indications for the use of direct oil contrast lymphangiography are represented by the pre-operative assessment of patients affected by lymphatic and chylostatic disorders: chyloperitoneum chylothorax, chyluria, chylo-colpometrorrhea, and chylous joint effusion.»

Clinical cases & Publications

Learn more about the clinical cases related to interventional radiology

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1.EASL-EORTC Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma. J. Hepatol. 2018

2.ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (eUpdate), 2020,

3.US Guidelines: Bruix J. AASLD Practice Guidelines; American Association for Study of the Liver Diseases; Hepatology 2011; Vol. 53, No. 3.

4.Japanese Guidelines: Hepatology Research 2010; 40 (Suppl. 1): 96–112.

5.Chinese guidelines 2011 edition, Chin. Clin. Oncol. 2012; 1:10.

6.Takeuchi Y. et al., Guidelines for the use of NBCA in vascular embolization devised by the Committee of Practice Guidelines of the Japanese Society of Interventional Radiology (CGJSIR), 2012 edition, Jpn J Radiol, 2014; 32:500–517.

7.American Society for Gastrointestinal Endoscopy. Tissue adhesives: cyanoacrylate glue and fibrin sealant, Gastrointestinal Endoscopy, 2013;78: 2. 209-215.

8.LEE BB. et al., Consensus Document of the International Union of Angiology (IUA)-2013 Current concepts on the management of arterio-venous malformations, International Angiology, 2013;32(1):11-36.

9.Lee BB, et al., IUA-ISVI consensus for diagnosis guideline of chronic lymphedema of the limbs, Edizioni Minerva Medica, 2014,

10.Kimberly Levenhagen, et al., Diagnosis of Upper-Quadrant Lymphedema Secondary to Cancer: Clinical Practice Guideline From the Oncology Section of APTA, American Physical Therapy Association, Phys Ther, 2017;97: 729–745