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Purpose: To provide detailed reports on radiation doses during transarterial chemoembolization (TACE) in the cone-beam computed tomography (CBCT) era and to identify the associated factors., Methods: This retrospective study included 385 consecutive patients who underwent initial conventional TACE for hepatocellular carcinoma (HCC) between January 2016 and December 2017. In most cases, CBCT was performed at the common hepatic artery or celiac axis to confirm the location of the tumor and the three-dimensional hepatic artery anatomy. Superselective TACE was performed for all technically feasible cases. Information on total dose area product (DAP), total cumulative air kerma (CAK), fluoroscopy time, and DAP and CAK of each digital subtraction angiography (DSA) and CBCT scan was recorded. Multiple linear regression analysis was performed to identify the factors associated with increased DAP during TACE., Results: The mean values of total DAP and CAK were 165.2 ± 81.2 (Gy·cm²) and 837.1 ± 571.0 (mGy), respectively. The mean fluoroscopy time was 19.1 ± 10.3 min. The mean DAP caused by fluoroscopy, DSA, and CBCT was 51.8 ± 43.9, 28.0 ± 24.1, and 83.9 ± 42.1 Gy·cm², respectively. Male sex, a high body mass index, largest tumor size > 3 cm, presence of aberrant right and left hepatic arteries, and superselective TACE were identified as independent predictors of increased total DAP during TACE., Conclusion: We were able to provide detailed reports on radiation doses during TACE and associated factors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) according to the size of the beads for the treatment of small hepatocellular carcinoma (HCC)., Materials and Methods: This retrospective study included 212 patients with a single HCC ≤5 cm from five tertiary institutions. One hundred and nine patients were treated with 70-150-µm doxorubicin DEBs (group A), and 103 patients received 100-300-µm doxorubicin DEBs (group B). The initial tumor response (assessed between 3 weeks and 2 months after DEB-TACE), time to local tumor progression (TTLTP), restricted mean duration of complete response (RMDCR), rate of complications, incidence of post-embolization syndrome, and length of hospital stay were compared between the two groups. Logistic regression was used to analyze prognostic factors for initial tumor response., Results: The initial objective response rates were 91.7% (100/109) and 84.5% (87/103) for groups A and B, respectively ( P = 0.101). In the subgroup analysis of tumors ≤3 cm, the initial objective response rates were 94.6% (53/56) and 78.0% (39/50) for groups A and B, respectively ( P = 0.012). There was no significant difference in the TTLTP (median, 23.7 months for group A vs. 19.0 months for group B; P = 0.278 [log-rank], 0.190 [multivariable Cox regression]) or RMDCR at 24 months (11.4 months vs. 8.5 months, respectively; P = 0.088). In the subgroup analysis of tumors >3-cm, the RMDCR at 24 months was significantly longer in group A than in group B (11.8 months vs. 5.7 months, P = 0.024). The incidence of mild bile duct dilatation after DEB-TACE was significantly higher in group B than in group A (5.5% [6/109] vs. 18.4% [19/103], P = 0.003)., Conclusion: DEB-TACE using 70-150-µm microspheres demonstrated a higher initial objective response rate in ≤3-cm HCCs and a longer RMDCR at 24 months in 3.1-5-cm HCCs compared to larger DEBs (100-300-µm)., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Purpose: This study aims to test the hypothesis that idarubicin-based transarterial chemoembolization (IDA-TACE), using one of the most potent chemotherapeutic agents, could yield oncologic outcomes equivalent to or marginally improved over doxorubicin-based TACE (DOX-TACE)., Materials and Methods: This single-center, prospective, phase II, randomized controlled, non-inferiority, double-blind trial will enroll 128 treatment-naïve patients with HCC (≤ 5 tumors, 1-5 cm in diameter) for conventional TACE. Participants will be randomly assigned (1:1) to either IDA-TACE or DOX-TACE, with stratification by Child-Pugh class. Superselective conventional TACE will be performed using cone-beam CT and small-bore microcatheters. Patient evaluations, including dynamic imaging and blood tests, will occur at 1, 3, and 6 months post-initial treatment. The primary outcome measure is the objective response rate (ORR) according to mRECIST at 6 months. Secondary outcomes include 3-month and 6-month tumor responses, time-to-progression, the incidence of treatment-related serious adverse events within 30 days, and the incidence and severity of any adverse events., Statistics: Non-inferiority will be claimed if the upper limit of a one-sided 97.5% confidence interval for the proportion difference (i.e., "6-month ORR of DOX-TACE" - "6-month ORR of IDA-TACE") falls below 0.15 in both intention-to-treat and per-protocol analyses. The proportion difference and its confidence interval will be calculated by the Cochran-Mantel-Haenszel method to obtain a weighted average of stratum-specific proportion differences., Expected Gain of Knowledge: If IDA-TACE demonstrates outcomes comparable to DOX-TACE, this study could provide compelling evidence that various cytotoxic agents yield similar contributions in TACE, considering the minor role of chemotherapeutic agents in TACE., Trial Registration: ClinicalTrials.gov ( https://clinicaltrials.gov/ ). Identifier: NCT06114082. World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) ( https://trialsearch.who.int/Default.aspx ). Identifier: KCT0008166., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background/aims: : This study aimed to assess whether hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) could have favorable prognoses with proper treatment under selective conditions., Methods: : This retrospective, single-center study involved 1,168 patients diagnosed with HCC between January 2005 and December 2006, before the introduction of sorafenib. Overall survival (OS) was estimated using the Kaplan-Meier method, and the Cox proportional hazards model was used to identify and adjust the variables associated with OS., Results: : In nodular-type HCC, the OS differed significantly according to the presence of PVTT (log-rank p<0.001), and the level of PVTT, not only its presence, was a major independent factor affecting OS. PVTT at the Vp1-3 branch was associated with significantly longer OS than was PVTT at the Vp4 level (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.04 to 3.21). In multivariate analysis, the OS was further stratified according to the PVTT level and tumor type, representing that nodular HCC without PVTT exhibited the best OS, whereas nodular HCC with Vp4 PVTT (adjusted HR, 2.59; 95% CI, 1.57 to 4.28) showed a poor prognosis similar to that of infiltrative HCC. The PVTT level was consistently correlated with OS in patients treated with transarterial chemoembolization. Nodular HCC without PVTT showed the best prognosis, while nodular HCC with Vp1-3 PVTT also exhibited a favorable OS, although inferior to that without PVTT (adjusted HR, 1.47, 95% CI, 0.92 to 2.36)., Conclusions: : Active treatment such as transarterial chemoembolization can be considered for selected PVTT cases. The level of PVTT and type of HCC were independent prognostic factors.

Objective: The aim of this study was to evaluate the potential implications of fusion imaging with C-arm computed tomography (CACT) scans for repetitive conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma., Materials and Methods: Fifty-six cTACE sessions were performed using fusion CACT images from September 2020 to June 2021 in a tertiary referral center, and the data were retrospectively analyzed. Fusion of unenhanced and enhanced CACT images was considered when previously accumulated iodized oil hampered the identification of local tumor progression or intrahepatic distant metastasis (indication A), when a tumor was supplied by multiple arteries with different origins from the aorta and missing tumor enhancement was suspected (indication B), or when iodized oil distribution on immediate post-cTACE CACT images needed to be precisely compared with the pre-cTACE images (indication C). Fusion image quality, initial tumor response, time to local progression (TTLP) of index tumors, and time to progression (TTP) were evaluated., Results: The fusion quality was satisfactory with a mean misregistration distance of 1.4 mm. For the 40 patients with indication A, the initial tumor responses at 3 months were nonviable, equivocal, and viable in 27 (67.5%), 4 (10.0%), and 9 (22.5%) index tumors, respectively. The median TTLP and TTP were 14.8 months and 4.5 months, respectively. For 10 patients with indication B, the median TTLP and TTP were 8.3 months and 2.6 months, respectively. Among the 6 patients with indication C, 2 patients were additionally treated at the same cTACE session after confirming incomplete iodized oil uptake on fusion imaging., Conclusions: Fusion CACT images are useful in patients with hepatocellular carcinoma undergoing repetitive cTACE., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Intra-arterial treatment has been identified as one of the mainstays in the management of unresectable hepatocellular carcinoma. A thorough knowledge of tumor arterial supply enables selective therapy, which improves both safety and efficacy. The inferior phrenic artery (IPA) is the most common extrahepatic collateral artery that feeds hepatocellular carcinoma. The bilateral IPAs are known to have a specific vascular anatomy. A systemic-to-pulmonary shunt and a gastric branch from the IPAs may be present and should not be confused with tumor blush. The supraceliac aorta and celiac trunk are the common origin sites of the IPAs, and their orifice may be compressed by the diaphragm. Various techniques and catheters are used for catheterization of the IPAs, depending on their origin sites. Because the IPA is normally connected with the intercostal, internal mammary, retroperitoneal, and hepatic arteries, its hemodynamics may be altered when its orifice is occluded. In general, superselective chemoembolization via the target branch of the IPA is safe and effective. When a systemic-to-pulmonary shunt from the IPA is adequately embolized with coils or particles, radioembolization through the IPA can be performed safely in most cases. The cystic artery branches into deep and superficial cystic arteries; deep cystic arteries often supply tumors near the gallbladder. Chemoembolization through the cystic artery is relatively safe, with transient embolic materials. Radioembolization through the cystic artery has been recently tried, with acceptable efficacy and toxicity results, but it requires further investigation. © RSNA, 2022.

In this study, we elucidated for the first time the role of anti-cancer drugs in transarterial chemoembolization (TACE) via direct visualization of the spatial distribution of drugs with respect to blood vessels in intact transparent hepatocellular carcinoma (HCC) tissues. To date, precise estimation of drug penetration into tumors using thin 3D tissue sections has been challenging. This study utilized the tissue optical clearing technique to resolve the lack of tissue clarity, thereby enabling deep tissue imaging for the quantitative assessment of drug delivery following TACE. We compared the drug delivery effect, time-dependent embolic effect, and immunogenic response following conventional TACE (cTACE), drug-eluting embolic TACE (DEE-TACE), and transarterial embolization (TAE) in a rat model of HCC. After each treatment, three-dimensional drug delivery was quantitatively evaluated via the transparent liver tumor imaging, and time-dependent tumor necrosis was analyzed by serial tumor harvesting and histological staining. The results showed that chemotherapeutic agents travel only short distances after cTACE (∼80µm) and DEE-TACE (∼110µm), whereas necrosis occurs extensively within 24 h of treatment (85.3-97.2% of tumor cells). In addition, the percentages of CD4 and IL-17+ CD4 T cells increased significantly following treatment; however, drug-loading did not appear to affect the immune response following TACE. In conclusion, transarterially delivered chemotherapeutic agents appeared to exert a limited role, owing to the rapid and overwhelming effect of embolization. STATEMENT OF SIGNIFICANCE: TACE has been widely used for the treatment of HCC, especially for unresectable intermediate and advanced HCCs. Drug use in TACE is expected to provide patients with synergistic therapeutic benefits with the effect of embolic agents; however, the role of chemotherapeutic agents in TACE remains controversial. This study quantitatively verified that chemotherapeutic agents travel only short distances after TACE, while necrosis occurs extensively within 24h, and drug loading does not significantly affect immune responses following TACE. Three-dimensional imaging of intact transparent HCC can contribute to a better understanding of drug delivery mechanisms associated with TACE and also reveal that drug use in TACE may need to be reconsidered and limited to situations when embolization is expected to be insufficient., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the effect of a motion artifact correction algorithm (MACA) on cone-beam computed tomography (CT) during transarterial chemoembolization for hepatic malignancies., Materials and Methods: From June 2020 to March 2021, 42 patients with mild-to-severe motion artifacts detected using single cone-beam CT scans were evaluated retrospectively. The image quality of native and motion-corrected data was compared. The maximum intensity, sharpness, and full width at half maximum (FWHM) of 5 segmental hepatic arteries were quantitatively measured. The overall quality of maximum intensity projection (MIP) images, conspicuity of tumor-supplying arteries, and need for selective angiography to ascertain the vascular anatomy were qualitatively evaluated by multiple readers. Paired t and Wilcoxon signed rank tests were used to compare the parameters., Results: The mean maximum intensity and sharpness increased from 2,792.01 HU ± 451.36 to 3,148.40 HU ± 594.46 and from 0.31 ± 0.02/mm to 0.34 ± 0.02/mm, respectively, using the MACA (both P < .001). The MACA decreased the mean FWHM from 2.02 mm ± 0.27 to 1.78 mm ± 0.26 (P < .001). The overall quality of the MIP images and the conspicuity of the tumor-supplying artery were enhanced from 2.5 to 3.0 points and from 3.0 to 4.0 points, respectively (both P < .001). Selective angiography was expected to be omitted in 7 cases (16.7%, 7/42) after using the MACA., Conclusions: The MACA significantly improved both quantitative and qualitative image quality of cone-beam CT in selected patients with motion artifacts during transarterial chemoembolization for hepatic malignancies., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Several publications show that superselective conventional TransArterial ChemoEmbolization (cTACE), meaning cTACE performed selectively with a microcatheter positioned as close as possible to the tumor, improves outcomes, maximizing the anti-tumoral effect and minimizing the collateral damages of the surrounding liver parenchyma. Recent recommendations coming from the European Association for the Study of the Liver (EASL) and European Society of Medical Oncology (ESMO) highlighted that TACE must be used in Hepatocellular Carcinoma (HCC) "selectively targetable" and "accessible to supraselective catheterization." The goal of the manuscript is to better define such population and to standardize superselective cTACE (ss-cTACE) technique. An expert panel with extensive clinical-procedural experience in TACE, have come together in a virtual meeting to generate recommendations and express their consensus. Experts recommend that anytime cTACE is proposed, it should be ss-cTACE, preferably with a 1.5-2.0 Fr microcatheter. Ideally, ss-cTACE should be proposed to patients with less than five lesions and a maximum number of two segments involved, with largest tumor smaller than 5 cm. Angio Cone-Beam Computed Tomography (CBCT) should be used to detect enhancing tumors, tumor feeders and guide tumor targeting. Whole tumor volume should be covered to obtain the best response. Adding peritumoral margins is encouraged but not mandatory. The treatment should involve a water-in-oil emulsion, whose quality is assessable with the "drop test." Additional particulate embolization should be systematically performed, as per definition of cTACE procedure. Non-contrast CBCT or Multi-Detector Computed Tomography (MDCT) combined with angiography has been considered the gold standard for imaging during TACE, and should be used to assess tumor coverage during the procedure. Experts convene that superselectivity decreases incidence of adverse effects and improves tolerance. Experts recommend contrast-enhanced Computed Tomography (CT) as initial imaging on first follow-up after ss-cTACE, and Magnetic Resonance Imaging (MRI) if remaining tumor viability cannot be confidently assessed on CT. If no response is obtained after two ss-cTACE sessions within six months, patient must be considered unsuitable for TACE and proposed for alternative therapy. Patients are best served by multidisciplinary decision-making, and Interventional Radiologists should take an active role in patient selection, treatment allocation, and post-procedural care., (© 2022. The Author(s).)

Aim: To clarify the clinical and radiological features of isolated tumor thrombi in the inferior vena cava (IVC)/right atrium in patients with hepatocellular carcinoma (HCC) without hepatic vein invasion., Patients and Methods: In this retrospective study, from January 2007 to December 2019, a total of 35,163 chemoembolization sessions were performed in 7,704 patients with HCC. Among them, 10 (0.13%) patients had tumor thrombi in the IVC/right atrium without definitive hepatic vein invasion. Computed tomographic (CT) scans, digital subtraction angiograms, and cone-beam CT images were retrospectively reviewed and interpreted., Results: The tumor thrombi were supplied by the right inferior phrenic artery (n=8) or the right internal mammary artery (n=2). Follow-up CT scans in eight patients showed linear accumulation of iodized oil along the diaphragm, which was presumed to be a thrombosis of the phrenic vein. Retrospective review of formal radiological reports of pre-procedural CT scans revealed that a correct diagnosis of tumor thrombi of the IVC/right atrium was made in only three cases., Conclusion: HCC invading the phrenic vein may have tumor thrombi in the IVC/right atrium without hepatic vein invasion., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC)., Materials and Methods: This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and per-lesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed., Results: The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score ( p = 0.019) was an independent predictor of OS, and tumor multiplicity ( p < 0.001), tumor size ( p = 0.020), and Child-Pugh score ( p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score ( p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%)., Conclusion: DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary or secondary liver cancer. However, conventional TACE formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. Methods: To overcome these limitations, a doxorubicin-loaded albumin nanoparticle-conjugated microbubble complex in an iodized oil emulsion (DOX-NPs-MB complex in Lipiodol) has been developed as a new ultrasound-triggered TACE formulation. Results: (1) Microbubbles enhanced therapeutic efficacy by effectively delivering doxorubicin- loaded nanoparticles into liver tumors via sonoporation under ultrasound irradiation (US+). (2) Microbubbles constituting the complex retained their function as an ultrasound contrast agent in Lipiodol. In a rabbit VX2 liver cancer model, the in vivo study of DOX-NPs-MB complex in Lipiodol (US+) decreased the viability of tumor more than the conventional TACE formulation, and in particular, effectively killed cancer cells in the tumor periphery. Conclusion: Incorporation of doxorubicin-loaded microbubble in the TACE formulation facilitated drug delivery to the tumor with real-time monitoring and enhanced the therapeutic efficacy of TACE. Thus, the enhanced TACE formulation may represent a new treatment strategy against liver cancer., Competing Interests: Competing Interests: Hyungwon Moon and Hak Jong Lee are part of the IMGT Company that is behind the new concept of TACE formulation reported in this study. Hyuncheol Kim and JinWook Chung are shareholders of IMGT Company. The remaining authors have no competing interests to declare., (© The author(s).)

Purpose: To quantify iodized oil retention in tumors after transarterial chemoembolization using spectral computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC) and evaluate its performance in predicting 12-month tumor responses., Materials and Methods: From September 2017 to December 2018, 111 patients with HCC underwent initial conventional transarterial chemoembolization. Immediately after the procedure, unenhanced CT was performed using a spectral CT scanner, and the iodized oil densities in index tumors were measured. In tumor-level analyses, a threshold level of iodized oil density in the tumors was calculated using clustered receiver operating characteristic curve analyses to predict the 12-month tumor responses. In patient-level analyses, significant factors associated with a 12-month complete response, including the presence of tumors below the threshold value (ie, suspected residual tumors), were evaluated by logistic regression., Results: Forty-eight HCCs in 39 patients were included in the analyses. The lower 10th percentile of the iodine density was identified as the threshold for determining the 12-month nonviable responses. The area under the curve of the iodine density measurements in predicting the 12-month nonviable responses was 0.893 (95% confidence interval, 0.797-0.989). The threshold value of the iodine density of 10.68 mg/mL yielded a sensitivity of 82.76% and specificity of 94.74% (P < .001). In the patient-level analysis, the 12-month complete response was significantly associated with the presence of a suspected residual tumor, with an odds ratio of 72.0 (95% confidence interval, 7.273-712.770)., Conclusions: Spectral CT imaging using quantitative analysis of the iodized oil retention in target HCCs can predict tumor responses after a conventional transarterial chemoembolization procedure., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Background/aims: The role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival., Methods: Using prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017., Results: The median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients., Conclusion: The serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.

Background: The decision of transarterial chemoembolization (TACE) initiation and/or repetition remains challenging in patients with unresectable hepatocellular carcinoma (HCC). The aim was to develop a prognostic scoring system to guide TACE initiation/repetition., Methods: A total of 597 consecutive patients who underwent TACE as their initial treatment for unresectable HCC were included. We derived a prediction model using independent risk factors for overall survival (OS), which was externally validated in an independent cohort (n = 739)., Results: Independent risk factors of OS included Albumin-bilirubin (ALBI) grade, maximal tumor size, alpha-fetoprotein, and tumor response to initial TACE, which were used to develop a scoring system ("ASAR"). C-index values for OS were 0.733 (95% confidence interval [CI] = 0.570-0.871) in the derivation, 0.700 (95% CI = 0.445-0.905) in the internal validation, and 0.680 (95% CI = 0.652-0.707) in the external validation, respectively. Patients with ASAR< 4 showed significantly longer OS than patients with ASAR≥4 in all three datasets (all P < 0.001). Among Child-Pugh class B patients, a modified model without TACE response, i.e., "ASA(R)", discriminated OS with a c-index of 0.788 (95% CI, 0.703-0.876) in the derivation, and 0.745 (95% CI, 0.646-0.862) in the internal validation, and 0.670 (95% CI, 0.605-0.725) in the external validation, respectively. Child-Pugh B patients with ASA(R) < 4 showed significantly longer OS than patients with ASA(R) ≥ 4 in all three datasets (all P < 0.001)., Conclusions: ASAR provides refined prognostication for repetition of TACE in patients with unresectable HCC. For Child-Pugh class B patients, a modified model with baseline factors might guide TACE initiation.

Purpose: To evaluate accuracy of iodine quantification using spectral CT and the potential of quantitative iodized oil analysis as an imaging biomarker of chemoembolization., Materials and Methods: A phantom of an artificial liver with 6 artificial tumors containing different amounts of iodized oil (0-8 vol%) was scanned by spectral CT, and iodized oil density (mg/mL) and Hounsfield unit (HU) values were measured. In addition, VX2 hepatoma was induced in 23 rabbits. After chemoembolization using iodized oil chemoemulsion, the rabbits were scanned by spectral CT. The accumulation of iodized oil in the tumor was quantified in terms of iodized oil density and HUs, and the performances in predicting a pathologic complete response (CR) were evaluated by receiver operating characteristic curve analyses., Results: The mean difference between true iodine densities and spectral image-based measurements was 0.5 mg/mL. Mean HU values were highly correlated with mean iodine density (r 2  = 1.000, P < .001). In the animal study, a pathologic CR was observed in 17 of 23 rabbits (73.9%). The range of area under the curve values of iodine and HU measurements was 0.863-0.882. A tumoral iodine density of 3.57 mg/mL, which corresponds to 0.7 vol% iodized oil in the tumor, predicted a pathologic CR with a sensitivity of 70.6% and a specificity of 100.0%., Conclusions: Spectral CT imaging has a potential to predict tumor responses after chemoembolization by quantitatively assessing iodized oil in targets., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the performance of C-arm computed tomography (CT)-guided chemoembolization in patients with hepatocellular carcinoma (HCC) with serum α-fetoprotein (AFP) level > 20 ng/mL but with no overt tumor on CT and/or magnetic resonance imaging., Materials and Methods: From May 2010 to May 2017, 34 patients with HCC (25 men and 9 women; mean age, 59.7 y) who had elevated serum AFP levels (> 20 ng/mL) but no overt tumor on 6-mo imaging studies and had shown complete response (CR) after previous chemoembolization underwent C-arm CT-guided conventional chemoembolization. Three radiologists retrospectively reviewed the imaging studies (preprocedural images, C-arm CT scans, and follow-up images) in consensus, and clinical data including AFP levels were retrospectively obtained. Tumor detection by C-arm CT and treatment response after chemoembolization were assessed., Results: HCC was imaged at the time of chemoembolization in 24 of 34 patients (70.6%). C-arm CT detected tumors in 25 patients (73.5%); 23 detections were true positives, 2 were false positives, and 1 was a false negative (diaphragm metastasis). Among the 23 patients with true-positive results, the first follow-up enhanced imaging studies showed CR (n = 17), partial response (n = 1), progressive disease (n = 4), and indeterminate status (n = 1; treated by percutaneous ethanol injection)., Conclusions: C-arm CT-guided chemoembolization may help to detect and treat recurrent tumors in patients who have shown CR after previous chemoembolization but subsequently, during follow-up surveillance, had serum AFP levels > 20 ng/mL without an overt tumor evident on imaging studies., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Transarterial chemoembolization is the most common treatment for unresectable hepatocellular carcinomas (HCCs). However, when an HCC is located in the caudate lobe, many interventional radiologists are reluctant to perform chemoembolization and percutaneous ablation owing to the tumor's complex vascular supply and deep location. With the advent of C-arm CT, rendering the three-dimensional display of the hepatic artery and detecting the tumor-feeding vessels are possible and can help guide interventional radiologists to the tumor. The common origins of the caudate artery include the right hepatic artery, left hepatic artery, right anterior hepatic artery, and right posterior hepatic artery. The origins of the tumor-feeding arteries of a caudate lobe HCC can vary depending on the tumor's subsegmental location. Caudate lobe HCCs are commonly fed by multiple caudate arteries that are connected. In addition, extrahepatic collateral arteries frequently supply recurrent tumors in the caudate lobe. The caudate artery can supply portal vein thrombi or biliary tumor thrombi in patients with HCC. Several techniques such as preshaping the microcatheter or using the shepherd's hook technique are needed to catheterize the caudate artery in complex cases. Although uncommon, bile duct stricture is a serious complication following selective chemoembolization through the caudate artery. Identification and catheterization of the caudate artery have become possible in most patients by using C-arm CT and a fine microcatheter system, respectively. The authors review the anatomy of the caudate artery with C-arm CT and describe basic technical considerations in selective chemoembolization for caudate lobe HCCs. Unusual circumstances that require catheterization and techniques used for catheterizing the caudate artery are also described. Online supplemental material is available for this article. © RSNA, 2019.

Purpose: To assess feasibility and efficacy of CKD-516, a vascular disrupting agent, in transarterial chemoembolization in a liver tumor model., Materials and Methods: A VX2 carcinoma strain was implanted in rabbit liver (n = 40) and incubated for 2 weeks. After confirmation of tumor growth using computed tomography, transarterial chemoembolization was performed. CKD-516 was dissolved in ethiodized oil, and animals were allocated to 4 treatment groups (n = 10 in each): group A, ethiodized oil; group B, ethiodized oil/CKD-516; group C, ethiodized oil + doxorubicin; group D, ethiodized oil/CKD-516 + doxorubicin. To assess hepatic damage, serum aspartate transaminase and alanine transaminase levels were measured on day 1, 3, and 7 after delivery. To assess tumor necrosis, animals were euthanized on day 7, and explanted tumors were stained with hematoxylin and eosin and a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay. Percentage areas of viable tumors were calculated using digitalized histopathologic specimen images., Results: Tumor viability rates were 47.1% ± 11.4%, 27.5% ± 13.6%, 14.4% ± 12.5%, and 0.7% ± 1.0% in groups A, B, C, and D (P < .001). Liver enzyme levels were elevated after drug delivery but recovered during follow-up. Significant between-group differences were observed on days 1, 3, and 7 (aspartate transaminase and alanine transaminase: P = .0135 and P = .0134, P = .0390 and P = .0084, and P = .8260 and P = .0440)., Conclusions: Treatment with a combination of CKD-516 and conventional transarterial chemoembolization showed therapeutic benefit in a liver tumor model., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine whether clinically relevant portal hypertension (CRPH) influences outcome and whether it may serve as a prognostic marker in patients treated with transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC)., Methods: One hundred and forty-seven patients underwent conventional TACE as a first-line treatment for a single HCC. CRPH was graded as 0, 1, or 2. The influence of CRPH, together with other factors, on local tumour progression (LTP) and overall survival (OS) were analysed using Cox proportional hazards regression., Results: A higher CRPH grade (grade 1, p = 0.005, hazard ratio [HR] = 3.282; grade 2, p < 0.001, HR = 7.144) and less selective catheterization (p = 0.009, HR = 1.951) were significantly associated with early LTP. Regarding OS, older age, (p < 0.001, HR = 1.050), CRPH grade 2 (p = 0.024, HR = 2.058), and a larger tumour (p < 0.001, HR = 1.454) were significantly associated with early death., Conclusions: Portal hypertension was significantly associated with poor outcome after TACE, and non-invasive CRPH grading may be a useful prognostic marker of TACE., Key Points: • Portal hypertension was significantly associated with poor outcome after TACE. • Grading portal hypertension non-invasively can help predict TACE outcome in HCC patients. • CRPH grading can aid in selecting optimal candidates for TACE.

Purpose: To determine the necessity of preprocedural biliary drainage prior to chemoembolisation for hepatocellular carcinoma (HCC) with bile duct invasion., Materials and Methods: The study included 52 patients who received chemoembolisation for unresectable HCC invading bile duct and causing hyperbilirubinemia (>3 mg/dL). Patients were divided into three groups according to biliary drainage and its effect: effective drainage (n=21), ineffective drainage (n=17), and non-drainage (n=14). Thirty-day mortality, length of hospitalisation, adverse events recorded using Common Terminology Criteria for Adverse Events (CTCAE), survival, and tumour response was compared among three groups., Results: Thirty-day mortality rates were 14.3% (n=3), 17.6% (n=3), and 7.1% (n=1) for effective, ineffective, and non-drainage groups, respectively, and did not differ significantly among groups (p=0.780). The mean length of hospitalisation was shorter in non-drainage group compared to ineffective drainage group (12.1±11.4 vs 34.1±29.6 days, p=0.012). Mean differences in CTCAE grade for laboratory parameters before and after chemoembolisation were not significantly different among three groups. Survival among three groups was not significantly different (p=0.239-0.825). The tumour response was also not significantly different among three groups (p=0.679)., Conclusion: Biliary drainage may not be mandatory prior to chemoembolisation in patients with HCC invading the bile duct., Key Points: • Chemoembolisation without biliary drainage can be performed for icteric HCC. • Chemoembolisation without biliary drainage is not accompanied by increased adverse events. • Preprocedural biliary drainage may not be mandatory for chemoembolisation for icteric HCC.

Purpose: To evaluate the effectiveness and safety of cone-beam computed tomography (CT)-guided chemoembolization for probable hepatocellular carcinomas (HCCs) smaller than 1 cm in patients at high risk for HCC., Materials and Methods: From December 2009 to May 2014, 57 patients (43 male and 14 female; mean age, 61.1 y) at high risk for HCC underwent cone-beam CT-guided conventional chemoembolization for 79 treatment-naive probable HCCs < 1 cm. Probable HCCs were diagnosed when hepatic nodules showed arterial enhancement and washout on dynamic CT or magnetic resonance images. The Kaplan-Meier method and Cox proportional-hazards regression were used to evaluate the time to local progression (TTLP), time to progression (TTP), and overall survival (OS)., Results: Initial follow-up images obtained 2-3 months after chemoembolization showed complete response in all 79 tumors. The 1-, 2-, and 3-year local progression rates were 10.4%, 21.7%, and 35.7%, respectively. Subsegmental catheterization (P < .001; hazard ratio [HR] = .041) and segmental catheterization (P = .001; HR = .049) were significantly associated with longer TTLP. The 1-, 2-, and 3-year progression rates were 40.5%, 66.7%, and 78.6%, respectively. Tumor multiplicity (P = .004; HR = 2.612) was a significant risk factor for shorter TTP. The 1-, 2-, and 3-year OS rates were 100%, 98.2%, and 88.5%, respectively. Child-Turcotte-Pugh class B disease (P = .029; HR = 5.989) was significantly associated with shorter OS. No complications occurred after chemoembolization., Conclusions: Cone-beam CT-guided chemoembolization can be a useful and safe option for probable HCCs < 1 cm in patients at high risk for HCC., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

Sorafenib (SOF; an angiogenesis inhibitor) and 2,3,5-triiodobenzoic acid (TIBA; a contrast agent for computed tomography imaging)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were fabricated. Embolization, drug delivery, and tracing the distribution of MSs for liver cancer therapy were accomplished with the developed MSs after their intra-arterial (IA) administration. SOF/TIBA/PLGA MSs with 24.8-28.5 µm mean diameters were prepared, and the sustained release of SOF from MSs was observed. Lower systemic exposure (represented as the area under the curve [AUC]) and maximum drug concentration in plasma (C max ) values of the SOF/TIBA/PLGA MSs group (IA administration, 1 mg/kg) in the results of the pharmacokinetic study imply alleviated unwanted systemic effects (e.g., hand and foot syndrome), compared to the SOF solution group (oral administration, 10 mg/kg). In a rat hepatoma model, the increase of microvessel density (MVD) following arterial embolization (i.e., reactive angiogenesis) was partially limited by SOF/TIBA/PLGA MSs. This resulted in the SOF/TIBA/PLGA MSs group (IA administration, single dosing, 1 mg/kg) showing a smaller tumor size increase and viable tumor portion compared to the TIBA/PLGA MSs group. These findings suggest that a developed SOF/TIBA/PLGA MS can be a promising therapeutic system for liver cancer using a transarterial embolization strategy.

Purpose: To assess the efficacy and safety of transcatheter arterial chemoembolization with drug-eluting embolic (DEE) agents for nodular hepatocellular carcinoma (HCC)., Materials and Methods: The study design was a prospective multicenter registry-based, single-arm clinical trial that included 152 patients. One hundred three (67.8%) had a Child-Pugh class/score of A5, 114 (75.0%) had a performance status of 0, and 77 (50.7%) had Barcelona Clinic Liver Cancer (BCLC) stage A disease. The DEE chemoembolization procedures were performed with DC Bead particles loaded with doxorubicin solution. The primary endpoint of the study was 6-month tumor response assessed per modified Response Evaluation Criteria In Solid Tumors. Secondary endpoints were treatment safety and overall survival., Results: At 1-month posttreatment assessment, complete response (CR) and objective response (OR; ie, CR or partial response) rates were 40.1% and 91.4%, respectively. At 6-month assessment, 121 patients remained for analysis, and CR and OR rates were 43.0% and 55.4%, respectively. The cumulative progression-free survival (PFS) rate at 6 months was 65.0%. Child-Pugh score, tumor multiplicity, and tumor size were independent predictors of PFS (P = .020, P = .029, and P = .001, respectively). There was no 30-day mortality. The overall 6-month survival rate was 97.4%. There were no grade 4 adverse events or laboratory changes. Serious adverse events were reported in 7.2% of patients, and persistent deterioration of liver function was observed in 3.9%. Prominent biliary injury was demonstrated in 19.7% of patients. No liver abscess was observed., Conclusions: DEE chemoembolization for nodular HCC had an acceptable safety profile and acceptable 6-month tumor response and survival rates., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the clinical outcome and safety of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with segmental or subsegmental portal vein tumour thrombus (sPVTT) in patients with preserved hepatic function, and to address the efficacy of additional chemoinfusion after TACE (TACE+CI)., Methods: From January 2003 to December 2012, TACE was conducted on 81 patients with Child-Pugh score ≤7 who had HCC with sPVTT. Thirty-one of them underwent TACE+CI. The overall survival (OS) and serious adverse events (SAEs) were evaluated. The efficacy of TACE+CI was appraised after adjustment with inverse probability of treatment weighting (IPTW)., Results: The OS after TACE (median, 15.5 months) was significantly related with aspartate aminotransferase (hazard ratio [HR], 1.011), modified Barcelona Clinic Liver Cancer (BCLC) stage D (HR, 2.841), extrahepatic spread (HR, 4.862), and TACE+CI (HR, .367). The SAE incidence was significantly associated with modified BCLC stages (HR, 10.174 [proper-C] and 24.000 [D]). After IPTW adjustment, TACE+CI significantly improved OS (p = .028; HR, .511), but the SAE incidence was not significantly altered (p = .737; HR, .819)., Conclusions: TACE can be an effective and safe treatment option for HCC with sPVTT in patients with preserved hepatic function. Furthermore, additional chemoinfusion can enhance the therapeutic efficacy while maintaining the safety., Key Points: • TACE is effective and safe for treating HCC with sPVTT. • Modified BCLC stages can stratify the risk and benefit of TACE. • Additional chemoinfusion can enhance the therapeutic efficacy while maintaining the safety.

Objectives: The aim of this prospective study was to reveal the efficacy and safety of Yttrium-90 (Y) radioembolization in Korean patients with hepatocellular carcinoma (HCC)., Methods: A total of 40 HCC patients were prospectively recruited from 7 centers. The response to treatment was assessed on the basis of the modified Response Evaluation Criteria in Solid Tumors criteria. The time to progression and overall survival were also evaluated, and the assessment of safety was done according to National Cancer Institute Common Terminology Criteria, Version 3.0., Results: Forty-two treatments of Y radioembolization were carried out. Median follow-up was 29 months. At 3 months, the complete response, partial response (PR), and stable disease were seen in 4 (10.0%), 19 (47.5%), and 15 (37.5%) patients, respectively. The response rate was 57.5% (23/40), and disease control rate was 95% (38/40) at 3 months. The response rate at 6 months was 63.9% (23/36), and disease control rate was 83.3% (30/36). The median time to progression was 18 months. During follow-up, 10 HCC-related deaths occurred and the 3-year survival rate was 75%. In 19 patients with Barcelona Clinic Liver Cancer-B stage, the 3-year survival rate was 50%. The tumor number (>5) was the only significant predictor associated with survival. The most common adverse event was abdominal pain of mild to moderate degree, and all the complications were manageable. Twenty-six (65%) patients underwent other treatments such as transarterial chemoembolization because of local progression or remnant viable lesion., Conclusions: Y radioembolization might be a safe and effective treatment modality in intermediate-stage to advanced-stage HCC.

Purpose: This study was designed to analyze retrospectively the performance of cone-beam computed tomography (CBCT) hepatic arteriography in depicting tumors and their feeders and to investigate the related determining factors in chemoembolization for hepatocellular carcinoma (HCC)., Methods: Eighty-six patients with 142 tumors satisfying the imaging diagnosis criteria of HCC were included in this study. The performance of CBCT hepatic arteriography for chemoembolization per tumor and per patient was evaluated using maximum intensity projection images alone (MIP analysis) or MIP combined with multiplanar reformation images (MIP + MPR analysis) regarding the following three aspects: tumor depiction, confidence of tumor feeder detection, and trackability of tumor feeders. Tumor size, tumor enhancement, tumor location, number of feeders, diaphragmatic motion, portal vein enhancement, and hepatic artery to parenchyma enhancement ratio were regarded as potential determining factors., Results: Tumors were depicted in 125 (88.0 %) and 142 tumors (100 %) on MIP and MIP + MPR analysis, respectively. Imaging performances on MIP and MIP + MPR analysis were good enough to perform subsegmental chemoembolization without additional angiographic investigation in 88 (62.0 %) and 128 tumors (90.1 %) on per-tumor basis and in 43 (50 %) and 73 (84.9 %) on per-patient basis, respectively. Significant determining factors for performance in MIP + MPR analysis on per tumor basis were tumor size (p = 0.030), tumor enhancement (0.005), tumor location (p = 0.001), and diaphragmatic motion (p < 0.001)., Conclusions: CBCT hepatic arteriography provided sufficient information for subsegmental chemoembolization by depicting tumors and their feeders in the vast majority of patients. Combined analysis of MIP and MPR images was essential to enhance the performance of CBCT hepatic arteriography.

Purpose: To assess the safety and effectiveness of transarterial chemoembolization (TACE) of patients who have hepatocellular carcinomas (HCCs) with central bile duct invasion., Materials and Methods: The institutional review board approved this retrospective study and waived informed consent. Fifty-three patients, initially treated with TACE for HCCs with central bile duct invasion from January 1999 to September 2012, were included. Clinical, laboratory, and survival data were reviewed. Complications and hospitalization length were evaluated using the χ(2) test, Fisher's exact test, and logistic regression analysis. Survival was analyzed using the Kaplan-Meier method with log-rank test and Cox proportional hazard model., Results: Seven patients experienced TACE-related major complications (severe post-embolization syndrome in 3, non-fatal sepsis in 3, and secondary bacterial peritonitis in 1). The overall major complication rate was 13.2%, but there were no permanent adverse sequelae or deaths within 30 days. Serum total bilirubin ≥ 3.0 mg/dL was the only significant risk factor for long hospitalization [hazard ratio (HR) = 4.341, p = .022]. The median survival was 12.2 months. Extrahepatic metastasis (HR = 6.145, p < .001), international normalized ratio (PT-INR) ≥ 1.20 (HR = 4.564, p < .001), vascular invasion (HR = 3.484, p = .001), and intermediate tumor enhancement (HR = 2.417, p = .019) were significantly associated with shorter survival., Conclusion: TACE can be a safe and effective treatment for patients who have HCCs with central bile duct invasion. In particular, long-term survival can be expected if patients have strongly enhancing tumors without poor prognostic factors such as extrahepatic metastasis, PT-INR prolongation, and vascular invasion.

Purpose: To compare long-term survival after hepatic resection and transarterial chemoembolization of large solitary hepatocellular carcinomas (HCCs)., Materials and Methods: Analysis of 91 and 68 consecutive patients with large (≥ 5 cm) solitary HCCs who underwent hepatic resection and transarterial chemoembolization, respectively, was performed. Overall survival and time to progression (TTP) were estimated using the Kaplan-Meier method and compared using the Cox proportional hazards model. To control for treatment-selection bias, matched groups of patients were selected using a propensity score matching method, and survival analysis was repeated., Results: During the follow-up period (median, 60.7 mo; range, 0.5-122.2 mo), 42 (46%) patients in the hepatic resection group and 35 (51%) patients in the transarterial chemoembolization group died. The 1-year, 3-year, and 5-year overall survival rates of the hepatic resection and transarterial chemoembolization groups were 91.1%, 80.0%, and 66.4% (hepatic resection group) and 89.8%, 72.8%, and 49.6% (transarterial chemoembolization group) (P = .023). TTP was significantly longer in patients who underwent hepatic resection (P < .001). Hepatitis B surface antigen positivity and the absence of portal hypertension were independent predictors for favorable overall survival. For patients with platelet counts ≤ 100,000/mm(3), Child-Pugh score of 6, smaller HCCs (≤ 7 cm), or portal hypertension, hepatic resection and transarterial chemoembolization yielded similar overall survival rates. After propensity score matching, transarterial chemoembolization was comparable to hepatic resection in overall survival (P = .293), whereas TTP remained longer in patients who underwent hepatic resection (P = .001)., Conclusions: Transarterial chemoembolization can lead to results comparable to hepatic resection in the treatment of large solitary HCCs, particularly in patients with clinically presumed portal hypertension., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was designed to evaluate the efficacy and safety in performing chemoembolization of extrahepatic collateral arteries (EHC) for hepatocellular carcinoma (HCC) located in the caudate lobe., Methods: Between January 2006 and November 2013, chemoembolization via EHC was performed in 35 patients with 35 caudate HCCs. Preprocedural and follow-up CT or MR scans, angiographic images, and medical records were reviewed retrospectively in consensus. Chi-square analysis was used to evaluate the relationship between tumor characteristics and type of EHC and that between tumor response and the characteristics of the tumor and chemoembolization., Results: In 31 (88.6 %) patients, EHCs supplying the caudate HCC originated from the right inferior phrenic artery (RIPA). The remaining four HCCs were supplied by the gastroduodenal artery, dorsal pancreatic artery, and right and left gastric arteries. Superselective catheterization of tumor-feeding vessels from the EHC was achieved in 27 patients (77.1 %). There were no major complications. Individual tumor response supplied by the EHC at follow-up contrast-enhanced CT were as follows: complete response (n = 18), partial response (n = 9), stable disease (n = 3), and progressive disease (n = 3). Non-RIPA EHCs were significantly more common in patients who had previously received chemoembolization via the RIPA (50 %) than those who had not (6.5 %; P = 0.01). There was no significant predictive factor associated with tumor response., Conclusions: HCC in the caudate lobe can be supplied by several EHCs. Chemoembolization via these arteries can be performed safely and effectively.

Aim: To evaluate the characteristics of a 13762-MAT-B-III model in the rat liver and to assess the adequacy of the model for transarterial embolization (TAE) study., Materials and Methods: One hundred thousand 13762-MAT-B-III rat breast cancer cells were inoculated into the livers of 11 Fisher 344 rats. Natural course via magnetic resonance imaging (MRI) follow-up, histological characteristics and tumor response after TAE were evaluated., Results: The tumor induction rate of the 13762-MAT-B-III hepatoma model was 100%. Except for one tumor that started to regress after 14 days, the 13762-MAT-B-III hepatomas showed rapid growth, up to 13.1±1.4 mm, at 21 days. Peritoneal seeding was observed in all rats. TAE was conducted successfully in three rats on day 11. The TAE-treated hepatomas were significantly smaller on day 21 (p=0.040) and had a significantly greater apoptosis ratio (p=0.046)., Conclusion: The 13762-MAT-B-III hepatoma model can be useful in many interventional oncology studies by providing consistent and rapidly growing tumors., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: To describe the radiologic findings and imaging response of hepatocellular carcinoma (HCC) supplied by the lumbar artery., Methods: Between April 2004 and December 2012, we encountered HCC supplied by a lumbar artery in 21 patients. Two investigators retrospectively reviewed clinical and radiological findings of HCC supplied by the lumbar artery using computed tomography (CT) scans and digital subtraction angiograms., Results: Patients had received 1-27 sessions of previous chemoembolization procedures (mean 7.7 sessions, median 4 sessions). Mean tumor size was 5.3 cm. The locations of HCC supplied by lumbar artery were the bare area (n = 14, 67 %) and segment VI (n = 7, 33 %). Tumor-feeding arteries arose from the main lumbar artery (n = 7), proximal anterior division (n = 4), and distal anterior division (n = 14). In 20 patients, selective chemoembolization through the tumor-feeding arteries of the lumbar artery was achieved. In 1 patient, nonselective embolization at the main lumbar artery was performed. There was no complication such as skin necrosis or paralysis. On the first follow-up enhanced CT scan, target tumors fed by the lumbar artery showed complete response (n = 6), partial response (n = 4), stable disease (n = 3), and progressive disease (n = 8), but overall tumor response was partial response (n = 1) and progressive disease (n = 20)., Conclusion: When HCC is located in the inferior tip or bare area of the liver, a lumbar artery may supply the tumor. Although selective chemoembolization via the tumor-feeding vessel of the lumbar artery can be achieved in most cases, overall tumor response is commonly unfavorable.

In many studies for chemoembolization of hepatocellular carcinoma, the Lipiodol emulsion preparation protocols, especially the mixing steps, were unclear or even unrevealed at all. However, doxorubicin (DOX) release may depend on the composition and volume ratio (Lipiodol to DOX solution) of a Lipiodol emulsion. Therefore, we conducted a preclinical study to compare in-vitro drug release and in-vivo pharmacokinetics of DOX from diverse Lipiodol emulsions and drug-eluting beads (DEBs) and to compare the tumor response in a rabbit VX2 carcinoma model. DOX release profiles of four types of Lipiodol emulsions with different media (normal saline or Pamiray as an iodinated contrast medium), volume ratio (Lipiodol to DOX solution), and DEBs were investigated in-vitro. For the in-vivo study, 15 rabbits bearing VX2 carcinoma in the liver were treated with 4∶1 volume ratio Lipiodol emulsion (group A), 1∶1 volume ratio Lipiodol emulsion (group B), and DEBs (group C) chemoembolization. Blood and tissue sampling was conducted to evaluate DOX concentration in plasma and tissues, histological changes, and liver toxicity. The most stable emulsion was formed with Pamiray (including DOX) at a 4∶1 volume ratio. The AUC value of group A was significantly lower than that of group B (p = 0.003) but comparable to that of group C (p = 0.071). The Cmax value of group A was significantly different compared with those of group B (p = 0.004) and C (p = 0.015). The tissue drug concentration in group A was comparable to that in group C (p = 0.251). No viable tumor was detected in rabbits of group A and B. In group C, viable tumor less than 10% was seen in two of the five rabbits. There were no significant differences in liver enzyme levels after the procedure. In conclusion, DOX release and pharmacokinetics of presented emulsion systems depend substantially on their composition. Therefore, Lipiodol emulsion type should be considered when interpreting data and designing new studies dealing with chemoembolization.

Purpose: We aimed to elucidate the treatment outcomes of transcatheter arterial chemoembolization (TACE) and survival-associated factors in hepatocellular carcinoma (HCC) patients with hepatic vein (HV) and/or inferior vena cava (IVC) invasion., Methods: The subjects were consecutively enrolled, newly diagnosed HCC patients with HV/IVC invasion who underwent TACE (n = 62) at the Seoul National University Bundang Hospital from May 2003 to October 2012. Clinical characteristics, treatment responses, overall survival, and survival-related factors were analyzed., Results: The mean subject age was 56.6 years, 82.3% were hepatitis B surface antigen-positive, and 76.2% were classified as Child-Pugh class A. The tumor volume was ≥50% of the liver in 64.5% of patients, and 79, 41.9, and 9.7% of patients had accompanying portal vein, IVC, and right atrial invasion, respectively. TACE response rates for primary tumors and tumor thrombi in HV or IVC were 55.6 and 13%, respectively. Median overall survival was 10.9 months (range 0.1-23.0 months). Multivariate analysis showed that Child-Pugh class A (hazard ratio [HR] = 0.31; 95% confidence interval [CI] 0.14-0.72; p = 0.007), tumor volume <50% of liver (HR = 0.31; 95% CI 0.11-0.83; p = 0.019), alpha-fetoprotein (AFP) response (HR = 0.28; 95% CI 0.11-0.69; p = 0.006), and tumor thrombi treatment response (HR = 0.09; 95% CI 0.01-0.77; p = 0.027) were independent survival-related factors., Conclusions: TACE seems effective for HCC with HV/IVC invasion, especially in patients with preserved hepatic function, a treatment response for tumor thrombi, and an AFP response.

Purpose: To evaluate the postprocedural imaging findings and safety of repeated intra-arterial therapy via the cystic artery in patients with hepatocellular carcinoma (HCC)., Methods: This retrospective study was approved by our institutional review board. From February 2002 to January 2012, we performed repeated (two or more) chemotherapeutic infusion or chemoembolization via the cystic artery using iodized oil in 132 patients with HCCs. Computed tomographic (CT) scans, digital subtraction angiograms, and medical records were retrospectively reviewed by consensus., Results: A total of 340 sessions of intra-arterial therapy (160 sessions of chemotherapeutic infusion and 180 sessions of chemoembolization) via the cystic artery were undertaken in 132 patients. Fifty-five of 132 patients received both chemotherapeutic infusion and chemoembolization. The incidence of gallbladder wall thickening on follow-up contrast-enhanced CT was significantly higher in chemoembolization (48 of 180, 26.7 %) than in chemotherapeutic infusion (27 of 160, 16.9 %) (P = 0.035). Persistent gallbladder wall thickening was more frequently observed in chemoembolization (48 of 107, 44.9 %) than in chemotherapeutic infusion (27 of 90, 30 %) (P = 0.039). The major complication rate was 15 of 340 sessions (4.4 %) with 11 of 132 patients (8.3 %). Acute cholecystitis, which was related to intra-arterial therapy via the cystic artery, developed in two patients and was managed by conservative treatment., Conclusion: HCC supplied by the cystic artery can be safely treated by repeated intra-arterial chemotherapeutic infusion or chemoembolization using iodized oil through the cystic artery.

Purpose: To present radiologic findings that show favorable tumor response after chemoembolization via the left internal mammary artery (LIMA)., Materials and Methods: Between October 2002 and April 2013, 57 patients with hepatocellular carcinoma (HCC) underwent 69 sessions of chemoembolization via the LIMA. Imaging findings including tumor size, location, and visibility of tumor-feeding artery on cross-sectional images were retrospectively reviewed in consensus by two radiologists. Tumor response after chemoembolization via the LIMA was assessed by the modified Response Evaluation Criteria in Solid Tumors on follow-up multidetector computed tomography in consensus., Results: The mean tumor size supplied by the LIMA was 6.8 cm (range, 1.0-21.0 cm). HCCs supplied by the LIMA tended to be located in the subcapsular area including exophytic features (57 of 57; 100%) and were more likely to be located in the left lobe of the liver (56 of 57; 98%). HCCs supplied by the LIMA were more likely to be multiple or infiltrative (52 of 57; 91%) and marginally recurred (43 of 57; 75%). Feeding arteries of the LIMA were identified in a high percentage of cases (49 of 66; 74%) on cross-sectional images obtained before embolization. Regarding tumor response, tumors that were newly developed or exclusively supplied by the LIMA showed better target tumor response (P = .011 and P < .0001, respectively). On multivariate analysis, tumors exclusively supplied by the LIMA showed significantly better target tumor response with odds ratio of 16.32., Conclusions: Chemoembolization via the LIMA has a favorable target tumor response when HCCs are exclusively supplied by the LIMA., (Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze image quality and the factors that determine it for cone-beam computed tomography (CT) hepatic arteriography in chemoembolization for hepatocellular carcinoma (HCC)., Materials and Methods: From September 2009-December 2010, 399 consecutive patients referred for chemoembolization of HCC were scheduled for cone-beam CT scan. There were 12 patients (3%) excluded because of difficulty with breath-hold. Of the 387 patients who underwent cone-beam CT hepatic arteriography, 100 patients were ultimately included in the study according to inclusion criteria. Maximum intensity projection images were scored for image quality of each segmental hepatic artery. Potential determining factors for image quality were diaphragmatic motion, portal vein enhancement, and hepatic artery-to-parenchyma enhancement ratio. The flow rate of contrast media, x-ray delay, and location of the catheter tip were also evaluated., Results: It was possible to trace at least subsegmental hepatic arteries in 625 of 700 segments (89.3%) on cone-beam CT hepatic arteriography. Diaphragmatic motion, prominent portal vein enhancement, and low hepatic artery-to-parenchyma enhancement ratio worsened image quality (P < .001, P = .022, and P = .017). Owing to cardiac motion artifacts, image quality of the left lateral segments (S2 and S3) was poorer compared with the remaining hepatic segments (S4-S8)., Conclusions: In most cases, the quality of cone-beam CT hepatic arteriography images was good enough to trace subsegmental hepatic arteries at a minimum. Respiratory and cardiac motion, portal vein enhancement, and hepatic artery-to-parenchyma enhancement ratio significantly affected the image quality of cone-beam CT hepatic arteriography., (Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was designed to evaluate the safety of chemotherapeutic infusion or chemoembolization by way of the cystic artery in patients with hepatocellular carcinoma (HCC) supplied exclusively by the cystic artery., Methods: Between Jan 2002 and Dec 2011, we performed chemotherapeutic infusion or chemoembolization using iodized oil for the treatment of 27 patients with HCC supplied exclusively by the cystic artery. Computed tomography (CT) scans, digital subtraction angiograms, and medical records were retrospectively reviewed by consensus., Results: The cystic artery originated from the main right hepatic artery in 24 (89 %) patients, from the right anterior hepatic artery in 2 (7 %) patients, and from the left hepatic artery in 1 (4 %) patient. Selective catheterization of the cystic artery was achieved in all patients. Superselection of tumor-feeding vessels from the cystic artery was achieved in 7 patients (26 %). Chemotherapeutic infusion was performed in 18 patients (67 %), and chemoembolization was performed in 9 patients (33 %). There were no major complications and only 2 minor complications, including vasovagal syncope and nausea with vomiting. Individual tumor response supplied exclusively by the cystic artery at the follow-up enhanced CT scan were complete response (n = 16), partial response (n = 3), and stable disease (n = 8)., Conclusion: HCC supplied exclusively by the cystic artery can be safely treated without severe complications by chemotherapeutic infusion or chemoembolization using iodized oil through the cystic artery.

Background: Nonsurgical biliary drainage is considered as a priority for obstructive jaundice associated with unresectable hepatocellular carcinoma (HCC). Successful drainage allows the patient to receive antitumor therapy, such as transarterial chemoembolization (TACE). However, only limited data are available on clinical outcomes in patients who treated biliary drainage with subsequent TACE., Objective: This study evaluated the clinical outcome of biliary drainage with subsequent TACE in unresectable HCC patients with obstructive jaundice., Design: This was a retrospective study., Setting/subjects: A total of 60 patients received endoscopic biliary drainage (ERBD) or percutaneous transhepatic biliary drainage (PTBD) in two tertiary care referral centers., Measurements: Successful drainage and survival were measured., Results: Successful drainage was achieved in 39 (65%) patients. The median survival of 39 patients in whom successful drainage was achieved, regardless of which procedure was performed, was much longer than that of 21 patients without successful drainage (147 days versus 38 days, respectively, P<.001). In particular, the median survival was longer in 17 patients who underwent TACE after achieving successful drainage than in 22 patients who were treated conservatively after achieving successful drainage (410 days versus 77 days, respectively, P<.001). Multivariable analysis in 39 patients in the successful drainage group showed that TACE (hazard ratio 0.15; 95% confidence interval 0.05-0.45, P=.001) was an independent predictive factor of a favorable outcome., Conclusions: Effective palliation by successful biliary drainage with subsequent TACE might prolong the survival in patients with obstructive jaundice caused by unresectable HCC.

Objective: The objective of our study was to investigate the diagnostic performance of C-arm CT and its value to predict response of hepatocellular carcinoma (HCC) to trans-catheter arterial chemoembolization (TACE) compared with gadoxetic acid-enhanced MRI., Materials and Methods: Sixty-eight patients with HCCs (n=167; 145>1 cm, 22≤1 cm) underwent both C-arm CT immediately before TACE and gadoxetic acid-enhanced MRI within 2 weeks before TACE. Two radiologists rated the possibility of HCC using a 5-point confidence scale focused on the degree of arterial enhancement and the shape of the lesion seen on C-arm CT. They also graded the possibility of HCC on MRI based on the signal intensities on T1- and T2-weighted images, arterial enhancement, and hypointensity on both the late phase and the hepatobiliary phase. We also measured the apparent diffusion coefficient value. The diagnostic accuracy was evaluated using the alternative free-response receiver operating characteristic curve method. A multivariate logistic regression analysis was performed between the good-response and nonresponse HCCs for TACE., Results: The diagnostic accuracy of MRI was greater than that of C-arm CT (0.890 vs 0.681, respectively; p<0.001). However, in small HCCs (≤1 cm), C-arm CT showed a higher sensitivity than MRI (90.9% vs 70.5%, respectively; p=0.023) and a lower positive predictive value than MRI (40.8% vs 57.4%, p=0.073). Well-defined strong arterial enhancement on C-arm CT (odds ratio=8.08, p=0.05) was statistically significant for predicting therapeutic response of HCC to TACE., Conclusion: C-arm CT showed greater sensitivity than gadoxetic acid-enhanced MRI in depicting small HCCs (≤1 cm). Furthermore, well-defined strong arterial enhancement on C-arm CT can be used to predict therapeutic response of HCC to TACE.

Purpose: To report survival outcomes in patients with neuroendocrine tumor (NET) with hepatic metastasis who were treated by transcatheter arterial chemoembolization and determine prognostic factors that affect clinical outcome., Materials and Methods: Patients with NET with hepatic metastasis who underwent chemoembolization between April 2002 and July 2011 were included in this single-center, retrospective study. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. The influence of possible prognostic factors on survival was analyzed by log-rank method and multivariate Cox proportional-hazards method., Results: Forty-six patients with hepatic metastasis from nonpancreatic NETs (npNETs; n = 24) or pancreatic NETs (pNETs; n = 22) were included. The median PFS and OS times for the entire group were 16.2 and 38.6 months, respectively, and response rate was 58.1%. Patients with npNET had a similar PFS (17.4 mo vs 15.3 mo) and longer OS (55.0 mo vs 27.6 mo) compared with those with pNET, but there were no significant differences in PFS and OS between groups (P = .398 and P = .375, respectively). By univariate analysis, enterobiliary communication, hepatic tumor burden, and extrahepatic metastasis before the first chemoembolization were significant prognostic factors for poor OS (P = .001, P = .010, and P<.0001, respectively). By multivariate analysis, the same prognostic factors were significant and had relative risks of 4.63, 2.71, and 5.09, respectively., Conclusions: Transcatheter arterial chemoembolization is an effective treatment modality for hepatic metastasis from NETs, with a median OS of 38.6 months and response rate of 58%. Enterobiliary communication, large hepatic tumor burden, and extrahepatic metastasis were significant risk factors for poor survival outcome., (Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to clarify the frequency of and risk factors for liver abscess formation after transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma or metastatic hepatic tumors after undergoing bilioenteric anastomosis., Materials and Methods: From January 1996 to June 2012, 25 patients (21 men, four women; age range, 34-74 years) with hepatocellular carcinoma (n = 12) or metastatic hepatic tumors (n = 13) with an underlying bilioenteric anastomosis underwent 65 TACE procedures. The incidence of liver abscess, predisposing factors (diabetes, Child-Pugh class, leukopenia, tumor number, tumor size, tumor burden, tumor type, portal vein thrombus, lipiodol dose, particulate embolization, embolization selectivity, oily portogram, antibiotic prophylaxis, and occurrence of liver abscess at initial TACE), and clinical outcome were evaluated. Statistical analysis for relations between liver abscess and predisposing factors was performed by Fisher exact test and linear-by-linear association., Results: Liver abscess developed after 17 of 65 (26.2%) TACE procedures performed on 12 of 25 (48%) patients. Two patients died of progression of liver abscess into sepsis. Univariate and multivariate analyses showed that leukopenia (p = 0.029), occurrence of liver abscess at initial TACE (p = 0.082), and particulate embolization or oily portogram (grade 2) (p = 0.001) were associated with a higher incidence of liver abscess., Conclusion: The incidence of liver abscess was high among patients with bilioenteric anastomoses who underwent TACE. Leukopenia, occurrence of liver abscess at initial session of TACE, and particulate embolization or oily portogram (grade 2) were associated with the development of liver abscess.

Aim: To evaluate the feasibility of carbogen-challenge blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) for assessing the early response of liver tumors to chemoembolization in a rat hepatoma model., Materials and Methods: In a 9.4-Tesla scanner, a multiple gradient-recalled echo sequence was utilized for R2* measurement at 11 and 13 days after tumor implantation, first during room air breathing and then with carbogen gas (95% O2/5% CO2) breathing, to calculate the percentage changes of R2* values [ΔR2*(%)]. Transarterial chemoembolization was conducted 12 days after tumor implantation., Results: The ΔR2* value of the tumors was 10.61 ± 8.94% on pre-chemoembolization images and -0.16 ± 1.85% on post-chemoembolization images. There was a significant difference in the ΔR2* value of the tumors between pre-chemoembolization and post-chemoembolization BOLD MRI (p=0.013)., Conclusion: Carbogen-challenge BOLD MRI can be a non-invasive and useful method for the evaluation of early response of liver tumors to chemoembolization.

Purpose: Transarterial chemoembolization (TACE) is highly effective and safe therapeutic modality for unresectable hepatocellular carcinoma (HCC). However, the role of TACE for infiltrative HCC has never been elucidated owing to the concern about hepatic failure and subsequent mortality after the procedure. In this study, we aimed to document whether patients with infiltrative HCC would benefit from TACE., Methods: Child-Pugh class A/B patients who were newly diagnosed as infiltrative HCC and treated with curative-intent TACE were enrolled. All radiological images were reviewed by a radiologist with more than 20 years of experience in TACE., Results: Among 1,184 patients newly diagnosed as HCC, 233 (19.7 %) had infiltrative-type tumors and 128 (54.9 %) underwent curative-intent TACE. Although the median overall survival was 5.4 months (IQR 3.1-13.9 months) and 16 (12.5 %) patients had experienced significant complications, 19 (15.9 %) patients survived more than 2 years after the first diagnosis. In multivariable analysis, age >60 years old (HR 0.54, 95 % CI 0.31-0.92), Child-Pugh class A (HR 0.48, 95 % CI 0.30-0.76), and a major PVT without parasitic supply (HR 0.66, 95 % CI 0.44-0.99) were independent favorable prognostic factors. Development of significant complication after TACE was a significant hazard factor of survival (HR 1.99, 95 % CI 1.09-3.62)., Conclusions: In carefully selected patients with preserved hepatic function and good performance, TACE may achieve long-term survival of infiltrative HCC patients with major PVT without parasitic supply. However, the risk of morbidity and immediate mortality after TACE should be considered to select subjects for the procedure.

Aim: To evaluate the feasibility of the McA-RH7777 tumor model in Sprague-Dawley (SD) rats, for study of hepatoma and transarterial chemoembolization., Materials and Methods: McA-RH7777 rat hepatoma cells (1×10(7)) were inoculated into the left hepatic lobe of SD rats (n=38). Chemoembolization with left common carotid artery access was performed using an emulsion of iodized oil and doxorubicin, and polyvinyl alcohol particles. Tumor induction rate and response to chemoembolization were assessed by magnetic resonance imaging and histology., Results: Tumor induction rate of McA-RH7777 in SD rat livers was 73.3% (11/15). Hematoxylin-and-eosin staining revealed hypercellular tumor with a trabecular pattern that mimics human hepatocellular carcinoma. Chemoembolization was successfully conducted in all rats. There was a significant difference in tumor growth rates between the chemoembolization-treated and control groups (p<0.0001)., Conclusion: A rat tumor model of McA-RH7777 cells in SD rats is feasible and has the potential to be a good model for hepatoma and chemoembolization studies.

Purpose: The purpose of this study was to describe imaging appearances of hepatocellular carcinoma (HCC) supplied exclusively by the hepatic falciform artery (HFA) and safety of chemoembolization via the HFA., Methods: During the past 6 years, we have performed chemoembolization for the treatment of 12 patients with HCCs supplied exclusively by the HFA. Computed tomography (CT) scans, digital subtraction angiograms, and medical records were retrospectively reviewed by consensus., Results: Tumors were located in Couinaud segments IV (n = 7) and III (n = 5) and in subcapsular areas around the falciform ligaments. Tumor size ranged from 1.0 to 1.8 cm (mean, 1.3 cm; median, 1.3 cm). HFAs originated from A4 (n = 7), A3 (n = 4), and the left hepatic artery near the umbilical point (n = 1). All tumors were supplied exclusively by the HFA. Prophylactic embolization of the distal HFA before chemoembolization was performed using gelatin sponge particles in only one patient, and selective chemoembolization via the HFA was achieved in all patients. One patient suffered from a skin rash after chemoembolization and recovered after conservative management. Individual responses of tumors supplied exclusively by the HFA were complete response (n = 8), partial response (n = 1), and stable disease (n = 2) at the first follow-up enhanced CT scan., Conclusions: The HFA can supply HCC located in subcapsular areas around the falciform ligament, and the tumors can be safely chemoembolized without significant complications.