Lipiodol retention within hepatic cavernous hemangioma

Intraarterial injection of Lipiodol has been recommended to differentiate hepatocellular carcinoma from benign lesions such as cavernous hemangioma, because uptake and prolonged retention of the contrast medium is a characteristic of the malignant tumors. In two cases of cavernous hemangioma of the liver in which we injected Lipiodol, uptake and retention up to 3 months was demonstrated. We conclude that the intraarterial injection of Lipiodol may not be reliable in differentiating hepatocellular carcinoma from cavernous hemangioma of the liver.     

False-negative rate of abdominal sonography for detecting hepatocellular carcinoma in patients with hepatitis B and elevated serum alpha-fetoprotein levels

OBJECTIVE: Routine screening for hepatocellular carcinoma among chronic carriers of hepatitis B virus using a combination of abdominal sonography and serum alpha-fetoprotein levels is widely practiced. Negative results on an abdominal sonogram generally indicate the absence of hepatocellular carcinoma despite the elevation of alpha-fetoprotein levels, but the false-negative rate of abdominal sonography has not been established prospectively. SUBJECTS AND METHODS: In our screening program, we routinely investigated patients with Lipiodol (iodized oil) CT when they presented with alpha-fetoprotein levels above 20 ng/mL or a focal lesion as depicted on abdominal sonography. Lipiodol CT comprised a hepatic angiogram with injection of Lipiodol selectively in the hepatic arteries, followed by an unenhanced CT scan 10 days later. Positive findings on Lipiodol CT were confirmed histologically by biopsy or surgical resection. We defined false-negative as histologic diagnosis of hepatocellular carcinoma within 3 months of normal findings on screening abdominal sonography. RESULTS: One hundred three patients with elevated alpha-fetoprotein levels were investigated with Lipiodol CT within 2 months of abdominal sonography. Of these, three of 70 patients with negative abdominal sonography had histologically confirmed hepatocellular carcinoma. Thus, abdominal sonography has a false-negative rate of 4.3%. Lipiodol CT is associated with a significant false-positive rate of 43.7%. The sensitivity, specificity, and positive predictive value of abdominal sonography for early detection of hepatocellular carcinoma among hepatitis B virus carriers with elevated alpha-fetoprotein levels was 85.7%, 81.7%, and 54.5%, respectively. CONCLUSION: Negative results on a screening abdominal sonogram among hepatitis B virus carriers with elevated alpha-fetoprotein levels does not rule out the presence of small hepatocellular carcinoma. Routine use of Lipiodol CT as a supplementary screening tool is not recommended.     

Biloma following transcatheter oily chemoembolization.

Hepatic biloma (bile cyst) developed in a patient after transcatheter oily chemoembolization (TOCE) with Lipiodol for hepatocellular carcinoma. The patient was treated conservatively and underwent the next TOCE uneventfully. An inappropriately large dose of Lipiodol, anticancer agent, and Gelfoam can induce biloma; however, it is not reasonable to abstain from TOCE for hepatocellular carcinoma in fear of biloma.     

Metastatic nodules of hepatocellular carcinoma: detection with angiography, CT, and US

Accurate detection of intrahepatic metastases, or daughter nodules, of primary hepatocellular carcinoma is of crucial importance. Due to the introduction of infusion hepatic angiography, computed tomography (CT) after Lipiodol (iodized oil) infusion, and intraoperative ultrasound (US), tumors less than 10 mm in diameter are now frequently found. We compared the diagnostic accuracy of these three modalities in the detection of nodules in 45 patients who had hepatocellular carcinoma (confirmed by biopsy). CT with Lipiodol was superior to hepatic angiography in demonstrating nodules when they were overlapped by the primary tumor or very small in size. Intraoperative US demonstrated nodules in four avascular or hypovascular hepatocellular carcinomas, which both hepatic angiography and CT failed to demonstrate. In cases associated with severe liver cirrhosis, differentiation of small nodules from regenerating cirrhotic nodules was sometimes difficult with intraoperative US. The combined use of these three modalities is indispensable for the accurate detection of small nodules of metastatic hepatocellular carcinoma.     

Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion

Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has the unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014 .     

Interventional radiology for advanced hepatocellular carcinoma: comparison of hepatic artery infusion chemotherapy and transcatheter arterial lipiodol chemoembolization

OBJECTIVE: The prognosis of advanced hepatocellular carcinoma remains poor. The aim of this study was to compare the efficacy of hepatic artery infusion chemotherapy and transcatheter arterial Lipiodol chemoembolization for treatment of advanced tumor. SUBJECTS AND METHODS. Thirty-seven patients with hepatocellular carcinoma and unresectable tumors were enrolled. In the hepatic artery infusion chemotherapy group (n = 16), cisplatin (10 mg/person, on days 1-5) and subsequent 5-fluorouracil (250 mg/person, on days 1-5) were administered for four serial courses. In the transcatheter arterial Lipiodol chemoembolization group (n = 21), an emulsion of Epirubicin (20-30 mg/person) and Lipiodol was administered every 3-4 weeks. RESULTS: The tumor response rates (complete response plus partial response for all cases) of the hepatic artery infusion chemotherapy and transcatheter arterial Lipiodol chemoembolization groups were 56.3% and 23.8%, respectively, showing the significantly higher rate in the former than in the latter group. The cumulative survival rates between the two groups were not significantly different; whereas in those patients whose tumors were classified as TNM stage IV or as having the maximal tumor size of greater than 5 cm, patients tended to have higher survival rates in the hepatic artery infusion chemotherapy group than in the transcatheter arterial Lipiodol chemoembolization group. Univariate analysis identified the serum aspartate aminotransferase value as solely significant. Patients' adverse reactions were successfully managed by treatment of symptoms. Adverse events, such as obstructions of the catheter or hepatic artery or infection around the catheter, rarely occurred. CONCLUSION: Hepatic artery infusion chemotherapy had a better antitumor effect than transcatheter arterial Lipiodol chemoembolization and may be a useful therapeutic option for more advanced hepatocellular carcinoma.     

Computed tomography detection of small daughter nodules in hepatocellular carcinoma after iodized oil infusion into the hepatic artery

The detectability of small daughter nodules of hepatocellular carcinoma by computed tomography after hepatic arterial infusion of Lipiodol (iodized oil) and by infusion hepatic angiography was studied in 102 cases. The Lipiodol was selectively accumulated by the tumor. Tumors and small daughter nodules appeared as high-density areas on computed tomography. In 24 cases daughter nodules were identified only by computed tomography. In 50 cases computed tomography demonstrated superior ability to detect the daughter nodules when compared with infusion hepatic angiography. In 21 cases the daughter nodules were detected for the first time in areas other than the main site of the primary tumor. Lipiodol-computed tomography is very effective in the diagnosis of daughter nodules of hepatocellular carcinoma.     

Management of postsurgical recurrence of hepatocellular carcinoma with rhenium 188-HDD labeled iodized oil

Surgical resection with partial hepatectomy is the treatment of choice in patients with hepatocellular carcinoma (HCC). However, after recurrence, which is common, such patients have limited therapeutic options. In the present report, transarterial radionuclide therapy (TART) with rhenium 188 HDD-labeled Lipiodol was used to treat a patient with postsurgical recurrence of HCC. The patient tolerated therapy well and the lesions were completely ablated with a single dose of 188Re; the patient is free of disease for 14 months. TART with 188Re-HDD Lipiodol appears to be a promising new therapy in case of HCC recurrence after partial hepatectomy and requires further investigation.     

Intrahepatic microvascular changes after intrahepatic arterial injection of lipiodol in normal and cirrhotic rats]

Iodized oil (Lipiodol) has been used for the diagnosis and treatment of hepatic malignancies, especially that of hepatocellular carcinoma. However, few reports have appeared concerning intrahepatic microvascular changes following intrahepatic arterial injection of Lipiodol. In the present study, Lipiodol was injected into the hepatic arteries of normal and cirrhotic rats, the changes of intrahepatic microvascular structures were serially investigated by scanning electron microscopy of microvasculature casts. In normal rats following intrahepatic arterial injection of Lipiodol, impairments of capillary vessels in the peribiliary plexus (PBP) were noted. The degrees of PBP impairments were most severe 2 days after the injection of Lipiodol. However, 10 days after the injection of Lipiodol, these impairments had almost completely vanished. There was no changes of terminal arterial and portal branches. In cirrhotic rats, proliferations of the perinodular arterial plexus (PNAP) and dilatations of the PBP were noted. After intrahepatic arterial injection of Lipiodol, the impairments of the PBP were noted, as in the normal rats. However, the degrees of these impairments were milder than those in the normal rats. It was considered that the decrease of the PBP impairments caused by Lipiodol were influenced by proliferation of the PNAP and dilatations of the PBP in cirrhotic rats. After intrahepatic arterial injection of Lipiodol in normal and cirrhotic rats, there was no development of collateral vessels. It was believed, therefore, that this fact was an advantage in the treatment of hepatic carcinoma by Lipiodol.     

肝癌热疗的临床应用价值

肝癌热疗是通过全身加热或局部加热的方法进行的。局部加热与经导管动脉内化疗栓塞相结合，即介入性热化疗，它对提高治疗效果有广泛的应用价值。本文对肝癌热疗的理论依据、技术方法、研究现状和治疗效果进行了综述。     

Hypovascular hepatocellular carcinoma undetected at angiography and CT with iodized oil

Eighteen patients with 22 hepatocellular carcinoma (HCC) lesions less than 2 cm in diameter were examined with conventional angiography, digital subtraction angiography (DSA), and computed tomography (CT) after intraarterial injection of iodized oil (Lipiodol CT). Eight lesions detected at ultrasound examination of eight patients were not identified at conventional angiography, DSA, or Lipiodol CT. At histologic examination, all eight lesions were found to consist of well-differentiated carcinoma of grade I or II on the Edmondson-Steiner scale, and four had fatty change in cancer cells. Percutaneous tissue-core biopsy was indispensable in the diagnosis of well-differentiated HCC lesions that could not be diagnosed with conventional angiography, DSA, and Lipiodol CT.     

The magnetic resonance of small hepatocarcinoma. A comparison with echography, computed tomography, digital angiography and computed tomography with lipiodol]

Diagnostic techniques as a whole and periodic ultrasonography (US) in particular frequently allows tumors < 3 cm (small hepatocellular carcinomas) to be detected in patients suffering from liver cirrhosis. Multifocal diseases are a major limitation to surgery. Recently, MR imaging has shown its capabilities in the diagnosis of small hepatocellular carcinomas. In our study the diagnostic value of MR imaging was compared with that of US, of pre- and post-contrast CT, of digital angiography and of CT after lipiodol injection (Lipiodol CT). The morphologic and signal intensity MR features of small hepatocellular carcinomas were investigated. Fifteen cirrhotic patients with 31 nodules of hepatocellular carcinoma < 3 cm were examined. All patients were studied with US, MR imaging, angiography and Lipiodol CT; 12/15 patients underwent CT. Histologic confirmation was obtained in 12 nodules (2 at surgery and 10 by means of percutaneous biopsy); in the extant 19 cases the diagnosis was made by combining US, CT, MR, angiographic and lipiodol-CT findings; in 9 tumors < 1 cm Lipiodol retention one month after angiography was considered as diagnostic. MR imaging detected 21/31 nodules (63%), US 22/31 (66.6%), CT 12/24 (50%), angiography 24/31 (74%), lipiodol CT 29/31 (92.5%). Mc Nemar test showed no difference in sensitivity between MR imaging and CT, MR and angiography, MR and US, lipiodol CT and angiography; however, the differences between the detection rates of MR imaging and Lipiodol CT and CT and lipiodol CT and US were statistically significant (p < 0.05). The difference in sensitivity between the detection rates of lipiodol CT and US was just above the threshold value which is usually considered significant (p = 0.065). One false positive was observed on US and none with MR, CT, angiography and lipiodol CT. On Se T1-weighted images 18 nodules were hyperintense, 2 isointense and 2 hypointense; on proton-density images 14 nodules were hyperintense, 7 isointense and none hypointense. On SE T2-weighted images 18 nodules were hyperintense, 3 isointense and none hypointense. A pseudocapsule was seen in 10/17 nodules (58%), especially on T1-weighted images. Accuracy and limitations of each technique and morphologic and signal intensity MR findings of small hepatocellular carcinoma are discussed. We believe that US is still the best diagnostic technique for the screening of hepatocellular carcinomas in cirrhotic livers.(ABSTRACT TRUNCATED AT 400 WORDS)     

Transarterial Embolization with Sorafenib in Animal Livers: A Pharmacokinetics Study

PurposeTo assess the safety and feasibility of the targeted delivery of the antiangiogenic drug sorafenib to the liver using transarterial chemoembolization methodology as a novel approach to hepatocellular carcinoma (HCC) therapy.Materials and MethodsSeven healthy New Zealand white rabbits were used in the study. After placement of a catheter in the common hepatic artery, six rabbits were treated with chemoembolization of sorafenib in iodized oil (Lipiodol) (sorafenib dose 0.1 mg/kg), and one rabbit received Lipiodol only. Liquid chromatography tandem mass spectrometry was used to measure the concentration of sorafenib in the peripheral blood and liver tissue 24 hours and 72 hours after treatment. Histochemical staining of the liver sections and biochemical measurements were performed.ResultsThe administration of sorafenib in Lipiodol emulsions by transarterial chemoembolization resulted in sorafenib concentrations of 794 ng/g ± 240 and 64 ng/g ± 15 in the liver tissue 24 hours and 72 hours after treatment. The average liver-to-serum ratios 24 hours and 72 hours after treatment were approximately 14 and 22. The histochemical staining of the liver tissue sections and aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase and total bilirubin concentrations indicated no significant liver damage.ConclusionsTransarterial chemoembolization with sorafenib in Lipiodol is an effective methodology for the localized delivery of this drug to the liver and has possible practical implications in therapeutic interventions for the treatment of hepatocellular carcinoma.     

肝动脉化疗栓塞后碘油在肝癌内聚积、存留和消失的血管造影、CT与病理对照研究

用血管造影和ＣＴ对照分析肝动脉化疗栓塞后碘油在肝癌内的初期聚积特点，用ＣＴ动态观察碘油在肝癌内的存留和消失时间，同时与栓塞后切除标本行病理对照研究。结果表明：碘油能选择性聚积于多血供的肝癌内，且聚积量与肿瘤血供有关。少血供肝癌无或少有碘油聚积。碘油能选择性聚积并持续存留部是肿瘤栓后坏死区，一般存留２～６月甚至更长，伴肿瘤明显缩小；碘油虽能选择性聚积但逐渐消失部是肿瘤栓后存活区，一般１～２月消失，肿瘤缩小不明显或反增大。少量碘油在非癌肝实质一般２周消失。对碘油聚积、存留物消失问题的阐明，为肝癌的介入治疗提供了理论依据。     

Hepatocellular carcinoma with skeletal metastasis: management with intraarterial radioactive iodine

Two patients with skeletal metastasis from hepatocellular carcinoma (HCC) treated with internal radiation are presented. An oily contrast medium injected into the hepatic artery accumulates in the hepatic tumor tissue and remains there for long periods: therefore, an oily contrast tagged with radioactive iodine could intensify therapeutic effect on tumors. I-131 was tagged onto Lipiodol, an iodized oil, and injected into the arteries supplying the tumors of skeletal metastasis and hepatocellular carcinoma delivering high internal radiation to both primary and secondary lesions. At 6-month follow-up period, tumor has decreased in size and patients are alive and pain free.     

Computed tomography after Lipiodol chemoembolization in hepatocellular carcinoma

In order to ascertain the patterns of Lipiodol uptake and the diagnostic value of Lipiodol-CT in hepatocellular carcinoma (HCC), we present a retrospective analysis of CT and histological findings after Lipiodol chemoembolization. After chemoembolization 22 consecutive patients with H HCC wer studied with CT and pathological cor relat ion was available in all cases. Two patterns of Lipiodol uptake were defined: nodular (with complete or incomplete Lipiodol retention) and diffuse pattern. Lipiodol-CT demonstrated all principal tumors and 7 satellite CT lesions in 16 cases of nodular pattern, while 13 satellite lesions were not detected. Significant tumor necrosis (mean necrotic rate >90 %) was detected in 13cases of nodular pattern with complete Lipiodol retention. No significant necrosis was present in nodular pattern with incomplete retention, nor in diffuse pattern. Lipiodol-CT remain, an important diagnostic cool in presurgical evaluation of HCC, although some satellite lesions remain undetected. Nodular pattern correlates well with significant necrosis, but diffuse pattern does not.     

经导管肝动脉化疗栓塞术的技术细节与进展

经导管肝动脉化疗栓塞术（TACE）是治疗肝癌的最常用方法,但其技术细节存在较多争议,难以标准化。通过文献复习,笔者发现：超选择插管是TACE的基本要求;碘油以其可塑的栓塞作用成为不可或缺的栓塞材料;追加固体栓塞材料可延长生存期;化疗药物的作用值得质疑;"按需TACE"与"TACE抵抗"的理念逐渐被接受。本文就此进行了综述。     

肝动脉化疗栓塞治疗中碘油用量的现状与研究进展

肝动脉化疗栓塞治疗已成为不可切除性肝癌的重要治疗方法,而到目前为止,碘化油的应用剂量尚无客观标准,多依靠术者的经验而定。本文分析了常规TACE与超常规剂量TACE的优劣,并对碘油剂量术前量化的可行性展开综述。     

Chemoembolization of hepatocellular carcinoma in cases of isolated liver involvement]

Chemoembolization is an effective treatment for hepatocellular carcinoma, giving results equally as good as surgical therapy for T2 tumours. Survival can be prolonged and side-effects can be reduced by combining Lipiodol and Gelfoam for chemoembolization, employing a modified technique, with repeated procedures, and using appropriate follow-up treatment. The toxicity of the procedure is acceptable, but it requires supportive therapy necessitating an intense interdisciplinary co-operation.     

Accumulation of Iodized Oil Within the Non-Neoplastic Liver Adjacent to Hepatocellular Carcinoma via the Drainage Routes of the Tumor After Transcatheter Arterial Embolization

PURPOSE: After transcatheter arterial embolization (TAE) with iodized oil (Lipiodol), a relatively dense accumulation of Lipiodol is often seen in the nontumorous liver adjacent to a hypervascular hepatocellular carcinoma (HCC) nodule. We compared this phenomenon with the findings obtained with single-level dynamic CT during hepatic arteriography (SLDCTHA) and presumed its possible mechanism. METHODS: Fifty-six patients with HCC underwent hepatic angiography including SLDCTHA followed by segmental or subsegmental TAE with a mixture of an anticancer drug and Lipiodol. We compared the drainage area of the HCC depicted on SLDCTHA with the Lipiodol accumulation in the nontumorous liver adjacent to the HCC on CT after TAE (LpCT). RESULTS: In 26 of the 56 patients, a definite corona enhancement around the HCC, suggesting the drainage of blood from the tumor into the surrounding liver parenchyma, was seen on the late phase of SLDCTHA. In 17 of these 26 patients (65.4%), LpCT showed a more intense accumulation of Lipiodol in the nontumorous liver adjacent to the HCC that corresponded to the drainage area revealed on SLDCTHA. CONCLUSION: The drainage of blood from the HCC was considered to be a possible mechanism of the accumulation of Lipiodol in the nontumorous liver adjacent to the HCC.