Chemical Shift MRI Monitoring of Chemoembolization Delivery for Hepatocellular Carcinoma: Multicenter Feasibility of Initial Clinical Translation.

Purpose To demonstrate the feasibility of using chemical shift fat-water MRI methods to visualize and measure intrahepatic delivery of ethiodized oil to liver tumors following conventional transarterial chemoembolization (cTACE). Materials and Methods Twenty-eight participants (mean age, 66 years ± 8 [SD]; 22 men) with hepatocellular carcinoma (HCC) treated with cTACE were evaluated with follow-up chemical shift MRI in this Health Insurance Portability and Accountability Act-compliant prospective, institutional review board-approved study. Uptake of ethiodized oil was evaluated at 1-month follow-up chemical shift MRI. Measurements of tumor size (MRI and CT), attenuation and enhancement (CT), fat content percentage, and tumor:normal ratio (MRI) were compared by lesion for responders versus nonresponders, as assessed with modified Response Evaluation Criteria in Solid Tumors and European Association for the Study of the Liver (EASL) criteria. Adverse events and overall survival by the Kaplan-Meier method were secondary end points. Results Focal tumor ethiodized oil retention was 46% (12 of 26 tumors) at 24 hours and 47% (18 of 38 tumors) at 1 month after cTACE. Tumor volume at CT did not differ between EASL-defined responders and nonresponders (P = .06). Tumor ethiodized oil volume measured with chemical shift MRI was statistically significantly higher for EASL-defined nonresponders (P = .02). Doxorubicin dosing (P = .53), presence of focal fat (P = .83), and a combined end point of focal fat and low doxorubicin dosing (P = .97) did not stratify overall survival after cTACE. Conclusion Chemical shift MRI allowed for assessment of tumor delivery of ethiodized oil out to 1 month after cTACE in participants with HCC and demonstrated tumor ethiodized oil volume as a potential tool for stratification of tumor response by EASL criteria. Keywords: MRI, Chemical Shift Imaging, CT, Hepatic Chemoembolization, Ethiodized Oil Clinicaltrials.gov registration no.: NCT02173119 Supplemental material is available for this article. © RSNA, 2023.

Two Cases of Management of Coronary Artery Perforation During Percutaneous Coronary Intervention Using Injection of Combined Histoacryl (n-Butyl-2-Cyanoacrylate) and Lipiodol (Ethiodized Oil).

BACKGROUND Coronary artery perforation is a rare complication of percutaneous coronary intervention for coronary artery occlusion. This report is of 2 cases of coronary artery perforation during percutaneous coronary intervention that were managed successfully using injection of combined Histoacryl (n-Butyl-2-Cyanoacrylate) and Lipiodol (ethiodized oil). CASE REPORT Case 1 was a 51-year-old man with a past medical history of hypertension, dyslipidemia, and multivessel coronary disease. He was admitted to our hospital with inferior wall myocardial infarction, and a stent was placed in the proximal right coronary artery. He also had chronic total occlusion (CTO) of the left anterior descending artery (LAD). The planned LAD CTO intervention was complicated by balloon-induced coronary perforation and was managed successfully with intracoronary injection of Histoacryl-Lipiodol mixtures via microcatheter. He was discharged in stable condition without any serious consequences. Case 2 was a 72-year-old man with underlying hypertension who was admitted to the hospital with diagnosis of unstable angina. The diagnostic angiography showed occlusion of the LAD, CTO of the left circumflex artery, and minor atherosclerosis in right coronary artery. A stent was placed in the mid-LAD without any complications. Subsequently, a planned left circumflex artery CTO intervention was complicated by wire-induced coronary perforation, which was treated successfully with injection of Histoacryl-Lipiodol mixture. The patient was discharged in good condition. CONCLUSIONS Histoacryl and Lipiodol injection was a rapid and effective management method in 2 rare cases of coronary artery perforation during percutaneous coronary intervention.

Safety and Efficacy of Glass Membrane Pumping Emulsification Device in Transarterial Chemoembolization for Hepatocellular Carcinoma: First Clinical Outcomes.

AIM: Novel glass membrane pumping emulsification devices (GMDs) enable the formation of a high-percentage water-in-oil emulsion with homogeneous and stable droplets. Although GMDs are expected to improve therapeutic effects in transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC), clinical outcomes are not yet available. PATIENTS AND METHODS: A total of 26 patients with unresectable HCC who underwent TACE using a GMD were analyzed retrospectively. Ethiodized oil was mixed with epirubicin solution using a GMD. The emulsion was injected into the tumor-feeding artery, followed by embolization. RESULTS: The median size of HCCs was 28 (range=15-60) mm, and 15 nodules were solitary. Overall treatment effects were complete response in 18 cases (90%) and partial response in two (10%). The local recurrence rate at 6 months was 24.2%. No major complication was observed except for grade 4 elevations of liver enzymes in one case. CONCLUSION: TACE using a GMD is effective and safe in clinical practice.

Spinal Syrinx Due to Lipiodol-Induced Arachnoiditis.

We present a case of a progressive symptomatic intramedullary cyst, diagnosed decades after Lipiodol injection. Lipiodol was originally administered intrathecally for the radiologic diagnosis of spinal masses. A link between the lesion and the history of Lipiodol injection was never suspected. Surgical exploration revealed a membrane above the lesion, separating the intradural space in a cranial and caudal compartment. On the level of the cyst, we identified glassy pearls containing a fatty liquid, compatible with Lipiodol deposits. We hypothesize that the syrinx is secondary to the impact of cerebrospinal fluid pulsations on the reactive membrane and that this membrane originated from an arachnoiditis caused by Lipiodol deposits. Lipiodol was indeed abandoned after it was found to cause arachnoiditis and neurologic sequelae. Despite the cessation of its usage, the causal role of Lipiodol in arachnoiditis and spinal cyst formation should still be considered, as symptoms may arise many years after Lipiodol administration.

Conventional versus drug-eluting beads chemoembolization for infiltrative hepatocellular carcinoma: a comparison of efficacy and safety.

BACKGROUND: To compare the efficacy and safety between conventional transarterial chemoembolization (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with infiltrative hepatocellular carcinoma (iHCC). METHODS: A total of 89 iHCC patients who were treated with either cTACE (n = 33) or DEB-TACE (n = 56) between April 2013 and September 2017 were included in this retrospective study. Patients with the situations that might have a poor outcome were defined as advanced disease including Child-Pugh class B, bilobar lesions, tumor size greater than 10 cm, ECOG 1-2, tumor burden of 50-70%, and the presence of ascites, arterioportal shunt (APS), and portal venous tumor thrombus (PVTT). The tumor response was measured 1-month and 3-month after the procedure. Progression-free survival (PFS) was calculated. Toxicity was graded by Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The differences in tumor response, PFS, and toxicity were compared between the DEB-TACE group and cTACE group. RESULTS: At 1-month and 3-month after the procedure, the objective response rate (ORR) in the overall study population was similar in DEB-TACE group and cTACE group. The disease control rate (DCR), at 1-month after the procedure, was significantly higher in the patients treated with DEB-TACE relative to those treated with cTACE (P = 0.034), while after 3 months, the difference did not differ between two groups. DEB-TACE showed a higher DCR than cTACE in patients with tumor size greater than 10 cm (P = 0.036) or associated with APS (P = 0.030) at 1-month after the procedure, while after 3 months, the difference was only noted in patients with APS (P = 0.036). The median PFS in DEB-TACE group was 96 days, while in cTACE group was 94 days, and there was no difference in PFS between two groups (P = 0.831). In the side effect analysis, abdominal pain (P = 0.034) and fever (P = 0.009) were more frequently present in the cTACE group than DEB-TACE group, but there was no difference in high grade liver toxicity between the two groups. CONCLUSIONS: Compared to cTACE, DEB-TACE offers slightly better DCR and tolerability for iHCC patients, particularly in patients associated with APS and large tumor size. However, DEB-TACE does not provide higher PFS than cTACE.

Pancreas lipiodol embolism induced acute necrotizing pancreatitis following transcatheter arterial chemoembolization for hepatocellular carcinoma: A case report and literature review.

RATIONALE: Transcatheter arterial chemoembolization (TACE) is recognized as one of the most commonly used modalities for non-surgical treatment for advanced hepatocellular carcinoma (HCC). Ectopic lipiodol embolism is an extremely rare complication of TACE. PATIENT CONCERNS: A 61-year-old man who had a 10-year history of cirrhosis caused by hepatitis B infection was diagnosed with ascites and HCC. Subsequently, the patient underwent TACE. However, he experienced persistent left upper abdominal pain, poor appetite, nausea, moderate fever and accompanied by elevation of serum and urine amylase on the 2nd and 3nd day after treatment. DIAGNOSES: The patient was diagnosed as having acute hemorrhagic necrotizing pancreatitis based on biochemical and inflammatory markers and CT findings. We deduced that the acute necrotizing pancreatitis was caused by a small branch of the left hepatic artery feeding the pancreas tail and embolizing the drug and lipiodol shunting to the tail of the pancreas. INTERVENTIONS: The patient was treated for 5 days according to the comprehensive treatment of acute necrotizing pancreatitis, by the inhibition of the secretion of pancreatic juice, relieving pain, and total parenteral nutrition and forbidding diet. The symptoms of the patient were observed to improve, and SAMS and urinary amylase (UAMS) level decreased to 143 IU/L and 254 IU/L, respectively and oral diet was permitted. OUTCOME: After a period of 2 weeks, the contrast abdominal CT showed slightly decreased fluid collection of the peri-pancreatic space. Moreover, it also showed flocculous and linear high-density shadow in the pancreatic tail, suggesting lipiodol deposition in the pancreatic tail. Subsequently, the symptoms were observed to abate, and the patient left the hospital. On the 21st day after TACE, the patient had a follow up in our outpatient department; the biochemical characteristics and inflammatory markers were observed to be normal CONCLUSION:: AP is still a rare complication after TACE. Etiology is still attributed to the occurrence of shunting and embolization drug reflux. Strategies strengthening the catheter tip that is placed as close to the distal branches of the hepatic artery for the possible careful injection of embolic materials is still the key to avoid post-TACE AP.

Intra-arterial EmboCept S® and DC Bead® effectively inhibit tumor growth of colorectal rat liver metastases.

BACKGROUND: Intra-arterial therapy with embolics is established for the treatment of malignancies of the liver. However, there are no studies comparing the different effects of various embolics used in clinical practice. Herein, we analyzed the effect of 3 different embolics on tumor growth in a rat model of colorectal liver metastases. METHODS: Eight days after subcapsular implantation of 5 × 105 colorectal cancer cells (CC531) in the left liver lobe of WAG/Rij rats were randomized into 4 groups (n = 8) and underwent intra-arterial hepatic therapy. Animals received either EmboCept S®, DC Bead® or Lipiodol® Ultra-Fluid. Animals of the control group received a comparable amount of saline. Tumor growth was measured on day 8 and 11 using a three-dimensional 40 MHz ultrasound device. On day 11 tumor and liver tissue were removed for histological and immunohistochemical analyses. RESULTS: On day 11 animals of the control group showed a tumor growth of ~ 60% compared to day 8. Application of Lipiodol Ultra-Fluid® did not significantly influence tumor growth (~ 40%). In contrast, treatment with EmboCept S® or DC Bead® completely inhibited tumor growth. Of interest, application of EmboCept S® did not only completely inhibit tumor growth but even decreased tumor size. Immunohistochemical analysis showed a significant increase of necrotic areas within the tumors after application of EmboCept S® and DC Bead® compared to Lipiodol® Ultra-Fluid. CONCLUSION: The present study demonstrates that an intra-arterial therapy with EmboCept S® and DC Bead®, but not Lipiodol® Ultra-Fluid, results in a complete inhibition of rat colorectal liver metastatic growth.

Ethiodized poppyseed oil versus ioversol for image quality and adverse events in hysterosalpingography: a prospective cohort study.

BACKGROUND: This study aimed to investigate the image quality and adverse events (AEs) of ethiodized poppyseed oil (EPO) compared with ioversol as contrast agents in hysterosalpingography (HSG). METHODS: Two hundred twenty-eight patients underwent HSG were consecutively recruited in this prospective cohort study, and were accordingly divided into EPO group (N = 165) and ioversol group (N = 63). The quality of image was assessed according to the European Guidelines on quality criteria for diagnostic radiographic images. AEs during, within 2 h and at 1-month post-HSG were recorded. RESULTS: EPO displayed elevated image quality compared with ioversol including the total image quality score (P < 0.001), the cervical canal display score (P < 0.001), shape and outline of uterus score (P < 0.01), cervical mucosa or folds score (P < 0.001), oviduct isthmus score (P < 0.001), ampulla and fimbriae of oviduct score (P < 0.001) and celiac diffuse image score (P < 0.001). Multivariate linear regression displayed that EPO (P < 0.001) was an independent predictive factor for increased total image quality score. AEs were similar between EPO group and ioversol group during and within 2 h post-HSG (all P > 0.05). However, at 1-month post-HSG, the number of patients had unchanged and faded menstrual blood color decreased but the proportion of patients with deepened menstrual color increased in EPO group compared with ioversol group (P = 0.007). In addition, the number of patients had iodine residue in uterine cavity was elevated in EPO group compared with ioversol group (P < 0.001). CONCLUSION: EPO is more efficient in image quality and equally tolerant compared to ioversol as contrast agents in HSG.

Combined Therapy with Transarterial Chemoembolization and Radiofrequency Ablation for Hepatocellular Carcinoma: Does the Degree of Ethiodized Oil Accumulation within the Tumor Affect the Therapeutic Efficacy?

PURPOSE: To evaluate the effects of the degree of ethiodized oil accumulation achieved by transarterial chemoembolization followed by radiofrequency (RF) ablation on the treatment efficacy for a single intermediate-sized hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 153 consecutive patients who underwent chemoembolization and RF ablation for a single intermediate-sized HCC (2-5 cm) were included. On the basis of the degree of ethiodized oil accumulation in HCC on cone-beam CT images, patients who underwent chemoembolization and RF ablation were classified into 2 groups: compact accumulation (≥ 75%) and noncompact accumulation (< 75%). The rates of cumulative local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) were compared between groups. RESULTS: Of the 153 patients, 89 were classified into the compact ethiodized oil accumulation group and 64 in the noncompact ethiodized oil accumulation group. There were no significant differences in patient demographic or HCC characteristics between groups except for the incidence of liver cirrhosis (P = .038) and the tumor margin morphology (P = .008). The cumulative LTP rate was significantly lower in the compact accumulation group than in the noncompact accumulation group (P = .013). There were no significant differences in the incidences of complications, DFS rates (P = .055), or OS rates (P = .184). CONCLUSIONS: The degree of ethiodized oil accumulation does not play a role in decreasing the OS or DFS rate after chemoembolization and RF ablation for intermediate-sized HCC; however, it may contribute to reducing the rate of LTP.

Percutaneous Portal Vein Embolization Using a Simplified Sheathless 18-Gauge Trocar Needle Approach: Review of Efficacy and Safety.

PURPOSE: Portal vein (PV) embolization (PVE) is traditionally performed via a PV sheath with selective embolization of PV branches. Here, the efficacy and safety of PVE with the use of only an 18-gauge needle is reported. MATERIALS AND METHODS: Consecutive patients who underwent PVE from 2009 through 2017 were retrospectively reviewed. Forty-five patients (mean age, 60 y ± 7.6; 38 men) underwent 45 PVE procedures. Hepatocellular carcinoma, cholangiocarcinoma, and metastases accounted for 26 (58%), 13 (29%), and 6 (13%) patients, respectively. PVE was performed by puncturing a branch of right PV with an 18-gauge needle under US guidance. Via the same needle, direct portography was performed, followed by PVE with an N-butyl cyanoacrylate/Lipiodol mixture. Percentage increase of future liver remnant (FLR) volume and increase in ratio of FLR to total liver volume were estimated as measures of efficacy. Complications were reported according to Society of Interventional Radiology classification. Fluoroscopy time, procedure time, and dose-area product (DAP) were recorded. RESULTS: Technical success rate was 100%. The median DAP, fluoroscopy time, and procedure time were 74,387 mGy·cm2 (IQR, 90,349 mGy·cm2), 3.5 min (IQR, 2.10 min), and 24 min (IQR, 10.5 min). Among the 23 patients with complete CT volumetry data, mean increase in the ratio of FLR to total liver volume and percentage increase of FLR volume were 12.5% ± 7.7 and 50% ± 33, respectively. There were 3 minor complications (asymptomatic nonocclusive emboli in FLR) and 3 major complications (1 hepatic vein emboli, 1 subphrenic collection, and 1 hepatic infarct). CONCLUSIONS: PVE via a sheathless 18-gauge needle approach is feasible, with satisfactory FLR hypertrophy.

The Utility of Indigo Carmine and Lipiodol Mixture for Preoperative Pulmonary Nodule Localization before Video-Assisted Thoracic Surgery.

PURPOSE: To evaluate the safety and efficacy of a mixture of indigo carmine and lipiodol (MIL) as a marker of pulmonary nodule before video-assisted thoracic surgery (VATS). MATERIALS AND METHODS: One hundred sixty-eight sessions of pulmonary marking were performed using MIL before VATS for 184 nodules (mean size, 1.2 ± 0.6 cm; range, 0.3-3.6 cm) on 157 patients (83 men and 74 women; median age, 66 years). The mean distance between the lung surface and the nodule was 0.8 ± 0.7 cm (range, 0-3.9 cm). MIL was injected near the nodule using a 23-gauge needle. Mean number of 1.2 ± 0.4 (range, 1-3) punctures were performed in a session for the target nodules, with mean number of 1.1 ± 0.3 (range, 1-3). Successful targeting, localization, and VATS were defined as achievement of lipiodol accumulation at the target site on computed tomography, detection of the nodule in the operative field by fluoroscopy or visualization of dye pigmentation, and complete resection of the target nodule with sufficient margin, respectively. RESULTS: The successful targeting rate was 100%, and the successful localization rate was 99.5%, with dye pigmentation for 160 nodules (87.0%) and intraoperative fluoroscopy for 23 nodules (12.5%). Successful VATS was achieved for 181 nodules (98.4%). Two nodules (1.1%) were not resectable, and surgical margin was positive in 1 nodule (0.5%). Complications requiring interventions occurred in 5 sessions (3.0%) and included pneumothorax with chest tube placement (n = 3) and aspiration (n = 2). No complication related to the injected MIL occurred. CONCLUSIONS: MIL was safe and useful for preoperative pulmonary nodule marking.

Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial.

PURPOSE: To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 812 patients with inoperable HCC were randomized (stable emulsion, n = 402; unstable emulsion, n = 410). The 2 emulsions were prepared by using the same protocol except that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C. The solvent in the stable emulsion arm was contrast medium and distilled water, and the solvent in the unstable emulsion arm was distilled water. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), tumor response, adverse events (AEs), and plasma epirubicin concentrations. RESULTS: In vitro, stable emulsions did not occur until 1 day, and unstable emulsions, with a lower peak plasma concentration (P = .001) in vivo, exhibited rapid separation of the oil and aqueous phases after 10 minutes. Median OS times in the stable and unstable emulsion arms were 17.7 and 19.2 months, respectively (P = .81). No differences were found in TTP, tumor response, and AEs except for myelosuppression (anemia, 3.5% vs 7.6%; thrombocytopenia, 11.5% vs 17.7%), which was significantly more severe and frequent in the unstable emulsion arm (P = .013). CONCLUSIONS: Chemoembolization is equally effective with the use of stable and unstable emulsions, but the use of a stable emulsion has the advantage of less myelosuppression and a favorable pharmacokinetic profile.

Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver (RETNET): study protocol for a randomized controlled trial.

BACKGROUND: Neuroendocrine tumors (NETs) are the second most common gastrointestinal malignancy after colon cancer. Up to 90% of patients with NETs develop liver metastases, which are a major determinant of symptoms and survival. Current guidelines recommend embolotherapy for progressive or symptomatic NET liver metastases, but the optimal technique among bland embolization, lipiodol chemoembolization, and drug-eluting bead chemoembolization remains unknown and controversial. METHODS/DESIGN: A prospective, open-label, multicenter randomized controlled trial will be conducted in patients with progressive or symptomatic unresectable NET liver metastases. Patients will be randomized to treatment with bland embolization, lipiodol chemoembolization, or drug-eluting microsphere chemoembolization, with 60 enrollees per arm. The primary endpoint will be hepatic progression-free survival (HPFS) following initial embolotherapy by RECIST criteria. The sample size is powered to detect an HR of 1.78 for HPFS following chemoembolization compared with bland embolization, which was estimated on the basis of existing retrospective studies. Secondary endpoints include overall progression-free survival, duration of symptom control, quality of life, rate of adverse events, and interval between embolotherapy cycles. Interim safety analyses will be performed at 10 and 30 patients per arm. DISCUSSION: The RETNET trial is a prospective, multicenter randomized controlled trial designed to determine the optimal embolotherapy technique for NET liver metastases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02724540 . Registered on March 31, 2016.

Transarterial chemoembolization for unresectable hepatocellular carcinoma: A comparison of the efficacy and safety of 2 embolic agents.

The aim of this study was to compare the efficacy and safety of 2 different embolic agents, namely gelatin sponge particle (GSP) and Lipiodol, for transarterial chemoembolization (TACE) of unresectable hepatocellular carcinoma (HCC).We retrospectively reviewed 87 consecutive patients with unresectable HCC who underwent Lipiodol TACE with lobaplatin and 87 consecutive patients with unresectable HCC who underwent GSP TACE with lobaplatin between January 2013 and June 2017 in our institution as the initial treatment. Both groups were compared considering the clinical and laboratory outcomes and imaging findings before and after TACE. Tumor response and adverse events were also evaluated.There was significant difference in the rate of complete and overall response between the groups (P = .029 and .001, respectively), specifically when the tumor size was >5 cm (P = .001). The disease control rate was significantly better in the GSP group than in the Lipiodol group (94.3% vs. 86.4%, P = .011). The response differences in higher stages were significant between the 2 groups (P = .035 and .007, respectively). The grades of adverse events were also significantly different between the groups (P = .000).GSP-as an embolic agent in TACE for HCC-could significantly increase the rate of tumor response 1 month after treatment, especially in large tumors, without any significant increase in severe adverse events, when compared to Lipiodol.

Feasibility and Safety of Repeated Transarterial Chemoembolization Using Miriplatin-Lipiodol Suspension for Hepatocellular Carcinoma.

AIM: To retrospectively evaluate the feasibility and safety of repeated transarterial chemoembolization (TACE) three or more times using miriplatin-lipiodol (M-LPD) suspension (repeated M-LPD TACE) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Sixteen patients who underwent repeated M-LPD TACE were examined. Total dose of miriplatin, lipiodol and porous gelatin sponge particles and adverse events of the first and last M-LPD TACE were evaluated. RESULTS: The mean±standard deviation (SD) of the total number of M-LPD TACE per patient was 3.7±1.1. The mean±SD dose of total miriplatin, lipiodol and porous gelatin sponge particles per patient was 303±103 mg, 21±7.3 ml and 84±57 mg, respectively. There were no significant differences in any adverse events between the first and last M-LPD TACE. CONCLUSION: Repeated M-LPD TACE for HCC is feasible and safe in selected patients.