Ablative Chemoembolization for Hepatocellular Carcinoma: A Prospective Phase I Case-Control Comparison with Conventional Chemoembolization.

Purpose To evaluate the feasibility, safety, and treatment effectiveness of ablative chemoembolization (ACE) in the treatment of hepatocellular carcinoma (HCC) and compare with a similar patient cohort who underwent conventional transarterial chemoembolization (cTACE). Materials and Methods This was a prospective phase I nonrandomized study conducted between March 2013 and October 2016 in accordance to the Declaration of Helsinki and Declaration Good Clinical Practice with written informed consent. There were 36 men and eight women (median age, 64 years [interquartile range, 58-74] and 74.5 years [interquartile range, 70-80], respectively). The primary end points were treatment safety and tumor response. The secondary end points were time to progression, progression-free survival, conversion to partial hepatectomy, and viable HCC within the tumor specimen. The end points of the study group (n = 22) were compared with those of a case-matched control group (n = 22) of patients who underwent conventional cTACE during the same period by using a Pearson χ2 test. Results Treatment with ACE was successfully completed in all patients without adverse effects. The complete response (CR) rates by patient or by tumor were both 100%. The median time to progression and median progression-free survival were significantly longer in the study group than in the control group (both were 28 months vs 10 months, respectively; P < .001). The number of patient conversions to hepatectomy was seven for ACE and three for cTACE. In the tumor specimens, viable tumor was found in two of eight specimens that underwent ACE and three of three that underwent cTACE. Conclusion ACE is a feasible, safe, and well-tolerated treatment for patients with HCC; it is highly effective and may be more effective than cTACE in achieving CR. © RSNA, 2017 Online supplemental material is available for this article.

Transarterial Ethanol Ablation for Unresectable Hepatocellular Carcinoma: Analysis of Clinical and Tumor Outcomes.

PURPOSE: To evaluate survival, tumor response, and treatment toxicity of transarterial ethanol ablation (TEA) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective study involved 186 patients (146 men and 40 women; median age, 65 y [interquartile range, 57-72.3 y]). Of 186 patients, 146 (78.5%) were hepatitis B virus carriers, 18 (9.7%) were hepatitis C virus carriers, 82 (44.1%) had tumors ≥ 5 cm, and 43 (23.1%) had multifocal tumors. Overall survival (OS), complete response (CR) by European Association for the Study of the Liver criteria, time to progression (TTP), progression-free survival (PFS), and treatment toxicities were evaluated. Univariate and multivariate analyses for prognostic factors of OS were performed. RESULTS: Median OS was 25.7 months (95% confidence interval [CI], 20.9-30.5) and varied significantly between Child-Pugh A and B (28.7 mo vs 13.4 mo, P < .001), and Barcelona Clinic Liver Cancer A and B or C (37.1 mo vs 17.7 mo, P = .001). Prognostic factors for longer OS were solitary tumor, tumor size < 5 cm, > 1 treatments, and CR of all tumors at 6 months. TTP was 9.1 months (95% CI, 6.9-11.3). PFS was 8.4 months (95% CI, 7.1-9.7). CR occurred in 69.1% (159/230) of lesions and 48.9% (88/180) of patients at 6 months. Any one symptom of the postembolization syndrome of grade 2 severity occurred in < 22% (41/186) of patients. No treatment-related hepatitis or death occurred within 30 days. Transient respiratory decompensation occurred in three patients (1.6% [3/186]), and alcoholic intoxication occurred in one patient (0.5% [1/186]). CONCLUSIONS: TEA appears to be safe and effective for local control of HCC.

Irreversible Electroporation of the Femoral Neurovascular Bundle: Imaging and Histologic Evaluation in a Swine Model.

PURPOSE: To evaluate imaging, histologic changes, and safety of irreversible electroporation (IRE) on the femoral neurovascular bundle in a swine model. MATERIALS AND METHODS: The study was approved by the institutional animal ethics committee. IRE was performed on the right femoral neurovascular bundle of 9 swine, which were subsequently sacrificed at 24 hours (n = 4, acute group), 7 days (n = 4, subacute group), or 21 days (n = 1, delayed group). Clinical observation, computed tomography (CT), and pathologic examination were carried out. RESULTS: After the procedure, 7 of 9 subjects were able to stand and walk, and the remaining 2 subjects could eventually do so within 1 week. The femoral vessels were patent on CT and gross examination. There was microscopic evidence of venous thrombosis in 75% of the subacute group. Except for mild perineural inflammation observed in 1 subject in the subacute group, the femoral nerves were intact on gross and histologic examination. Significant damage to the surrounding muscle and soft tissue was identified on CT and histology, manifesting as necrosis, hematoma, and inflammation. CONCLUSIONS: The ablative effect of IRE on muscle and soft tissue manifested as necrosis, hemorrhage, and inflammation. Histologic changes were observed in the perineural tissue and veins in a few subjects. The clinical implication of such changes and safety of clinical use of IRE for lesions encasing the neurovascular bundle in humans are yet to be determined.

Evaluation of carotid angioplasty and stenting for radiation-induced carotid stenosis.

BACKGROUND AND PURPOSE: We aimed to evaluate the procedural safety, clinical, and angiographic outcome of carotid angioplasty and stenting for high-grade (≥70%) radiation-induced carotid stenosis (RIS) using atherosclerotic stenosis (AS) as a control. METHODS: In this 6-year prospective nonrandomized study, we compared the carotid angioplasty and stenting outcome of 65 consecutive patients (84 vessels) with RIS with that of a control group of 129 consecutive patients (150 vessels) with AS. Study end points were 30-day periprocedural stroke or death, ipsilateral ischemic stroke, technical success, procedural characteristics, instent restenosis (ISR; ≥50%) and symptomatic ISR. RESULTS: The median follow-up was 47.3 months (95% confidence interval, 26.9-61.6). Imaging assessment was available in 74 vessels (RIS) and 120 vessels (AS) in 2 years. Comparing RIS group with AS group, the rates of periprocedural stroke or death were 1.5% (1/65) versus 1.6% (2/129; P=1); ipsilateral ischemic stroke rates were 4.6% (3/65) versus 4.7% (6/129; P=1); the annual risks of ipsilateral ischemic stroke were 1.2% (3 patient/254.7 patient year) versus 1.2% (6 patient/494.2 patient year; P=0.89); technical success rates were both 100%. Stenting of common carotid artery and the use of multiple stents was more common in the RIS group (P=0 in both cases); ISR rates were 25.7% (19/74) versus 4.2% (5/120; P<0.001); symptomatic ISR rates were 6.8% (5/74) versus 0.8% (1/120; P=0.031). CONCLUSIONS: The safety, effectiveness, and technical difficulty of carotid angioplasty and stenting for RIS are comparable with that for AS although it is associated with a higher rate of ISR. CLINICAL TRIAL REGISTRATION: This trial was not registered as enrollment started in 2006.

Unresectable hepatocellular carcinoma: randomized controlled trial of transarterial ethanol ablation versus transcatheter arterial chemoembolization.

PURPOSE: To compare effectiveness of transarterial ethanol ablation (TEA) and transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma and determine whether TEA leads to better overall survival and tumor response than TACE. MATERIALS AND METHODS: In this institutional review board-approved preregistered randomized controlled trial (n = 200), informed consent was obtained. Primary outcome was overall survival; secondary outcomes were time to progression (TTP), progression-free survival (PFS), tumor response at computed tomography, and treatment-related toxicity. Eligible patients were randomized at a 1:1 ratio. Treatment included transcatheter delivery of ethiodized oil-ethanol mixture (2:1 ratio by volume up to 60 mL) for TEA and cisplatin-ethiodized oil emulsion (0.5 mg cisplatin per milliliter up to 30 mg), followed by 1-mm gelatin-sponge pellets, for TACE. Study was terminated after interim analysis (n = 98); 90 patients were available for analysis. Overall survival, TTP, and PFS were analyzed with Kaplan-Meier method; differences were compared with log-rank test. RESULTS: Study was terminated prematurely after interim analysis, which showed no difference in overall survival; this was unlikely to change with further patient accrual. Median overall survival in TEA and TACE was 24.3 months (95% confidence interval [CI]: 12.8, 32.7) and 20.1 months (95% CI: 9.3, 31.2), respectively (P = .358). Median TTP and PFS for intralesional progression were longer with TEA than TACE (TTP, 34.6 months [95% CI: 28.2, 41] vs 26.05 months [95% CI: 18.7, 33.3]; PFS, 14.8 months [95% CI: 10.2, 19.5] vs 9.3 months [95% CI: 7.1, 11.5]) (P = .028 and 0.029, respectively). Complete response rate on a tumor basis was persistently and significantly higher with TEA at 3 months (62 of 88 [70%] vs 39 of 76 [51%], P = .012), 6 months (64 of 88 [73%] vs 41 of 76 [54%], P = .012), and 12 months (66 of 88 [75%] vs 45 of 76 [59%], P = .031). CONCLUSION: Although there was no significant difference in overall survival, TEA demonstrated better complete tumor response, longer time to intralesional progression, and longer PFS.

Ketamine-related cholangiopathy: a retrospective study on clinical and imaging findings.

PURPOSE: Ketamine is a commonly abused recreational drug in Southeast Asia. There are emerging reports on ketamine abuse causing liver injury and biliary dilatation. This retrospective study aims to investigate the clinical and radiological features of this condition. METHODS: A retrospective search in the database of our institute was performed from January 2008 to February 2014 for patients who were ketamine abusers, with deranged liver function and/or epigastric pain, and had computed tomography of the abdomen or magnetic resonance cholangiopancreatography. Patient demographics, clinical data, and radiological findings were reviewed. RESULTS: Twenty-six patients (11 male and 15 female) were included in this study. Eighteen (69 %) patients had fusiform dilatation of the common bile ducts (CBDs) without evidence of intrinsic or extrinsic obstruction, and non-dilated intrahepatic ducts. The degree of CBD dilatation correlated with duration of abuse. In five patients who achieved abstinence, the CBD dilatation showed improvement. CONCLUSIONS: Ketamine-related cholangiopathy manifested as fusiform dilatation of the CBD without evidence of obstructive lesions. Severity of CBD dilatation appears to be correlated with the duration of ketamine, and the condition is potentially reversible in abstinent patients.

Intracranial aneurysms: midterm outcome of pipeline embolization device--a prospective study in 143 patients with 178 aneurysms.

PURPOSE: To evaluate the midterm clinical and angiographic outcomes after pipeline embolization device (PED) placement for treatment of intracranial aneurysms. MATERIALS AND METHODS: This prospective nonrandomized multicenter study was approved by the review boards of all involved centers; informed consent was obtained. Patients (143 patients, 178 aneurysms) with unruptured saccular or fusiform aneurysms or recurrent aneurysms after previous treatment were included and observed angiographically for up to 18 months and clinically for up to 3 years. Study endpoints included complete aneurysm occlusion; neurologic complications within 30 days and up to 3 years; clinical outcome of cranial nerve palsy after PED placement; angiographic evidence of occlusion or stenosis of parent artery and that of occlusion of covered side branches at 6, 12, and 18 months; and clinical and computed tomographic evidence of perforator infarction. RESULTS: There were five (3.5%) cases of periprocedural death or major stroke (modified Rankin Scale [mRS] > 3) (95% confidence interval [CI]: 1.3%, 8.4%), including two posttreatment delayed ruptures, two intracerebral hemorrhages, and one thromboembolism. Five (3.5%) patients had minor neurologic complications within 30 days (mRS = 1) (95% CI: 1.3%, 8.4%), including transient ischemic attack (n = 2), small cerebral infarction (n = 2), and cranial nerve palsy (n = 1). Beyond 30 days, there was one fatal intracerebral hemorrhage and one transient ischemic attack. Ten of 13 patients (95% CI: 46%, 93.8%) completely recovered from symptoms of cranial nerve palsy within a median of 3.5 months. Angiographic results at 18 months revealed a complete aneurysm occlusion rate of 84% (49 of 58; 95% CI: 72.1%, 92.2%), with no cases of parent artery occlusion, parent artery stenosis (<50%) in three patients, and occlusion of a covered side branch in two cases (posterior communicating arteries). Perforator infarction did not occur. CONCLUSION: PED placement is a reasonably safe and effective treatment for intracranial aneurysms. The treatment is promising for aneurysms of unfavorable morphologic features, such as wide neck, large size, fusiform morphology, incorporation of side branches, and posttreatment recanalization, and should be considered a first choice for treating unruptured aneurysms and recurrent aneurysms after previous treatments. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120422/-/DC1.

Comparison of Survival Outcomes in Transarterial Ethanol Ablation and Liver Resection for Solitary Hepatocellular Carcinoma ≤ 5 cm in Patients Stratified by Liver Function.

PURPOSE: To compare the survival outcomes of patients treated with transarterial ethanol ablation (TEA) with those treated with liver resection (LR) for solitary HCC less than 5 cm in diameter, in patients stratified according to liver function using ALBI grade. MATERIALS AND METHODS: This retrospective study approved by the Institutional Committee included all treatment-naïve patients with solitary HCC (≤ 5 cm) and Child-Pugh score 5, and who had received TEA (33 patients) or LR (192 patients) between 2004 and 2012. Treatment outcomes were compared between patients treated with TEA and LR after a period of at least 7 years of follow-up. Comparison was repeated for those patients with ALBI grade 2 or 3. RESULTS: Both overall survival (OS, months) and recurrence-free survival (RFS months) were significantly longer in the LR group (OS: LR 129.7[119.5, 140], TEA 69.1[55.9, 82.3], P < 0.0001; RFS: LR 91.3[43.5, 139.1], TEA 13.8 [11, 16.5], P < 0.0001). In patients with ALBI grade 2 or 3, there was no significant difference between the groups in OS or RFS (OS: LR 43.1[0, 91.2], TEA 55.4 [43.7, 67.2], P = 0.65; RFS: LR 17.8 [11.4, 24.2], TEA 11.9 [6.7, 17.1], P = 0.132). Transient epigastric discomfort and low-grade fever without consequence occurred in 8 patients (8/33 or 24.2%) in the TEA group. CONCLUSION: The overall survival after LR for HCCs ≤ 5 cm was superior to that after TEA but similar when compared in patients with ALBI grade 2 or 3, the ALBI grade is useful for patient selection for TEA or LR for HCCs ≤ 5 cm.

Comparison of Chemoembolization, Radioembolization, and Transarterial Ethanol Ablation for Huge Hepatocellular Carcinoma (≥ 10 cm) in Tumour Response and Long-Term Survival Outcome.

PURPOSE: To compare transarterial chemoembolization (TACE), transarterial radioembolization using Yttrium-90 (TARE), and transarterial ethanol ablation (TEA) for huge hepatocellular carcinoma (HCC) in treatment responses and long-term survival outcomes. MATERIALS AND METHODS: In this retrospective study approved by institutional committee, inclusion criteria were tumour ≥ 10 cm, newly diagnosed, treatment naïve, Child A, Performance Score 0 or 1, no venous invasion or extrahepatic disease on contrast-enhanced CT or MRI. There were 107 patients (Supportive Care [SC] 17, TACE 54, TARE 17, TEA 19). Survival outcomes of SC and TACE were compared (TACE selected as benchmark for transarterial treatments). Tumour response and overall survival (OS) of the three groups were compared. RESULTS: OS of TACE (vs. SC) was significantly longer (9.9 [5.9, 24.1] months versus 2.8 [1.5, 10.2], p = 0.001). Complete response of TEA was significantly better (TEA 10/19 [52.6%] versus TARE 2/17 [12.5%], p = 0.013, versus TACE 9/54 [16.7%], p = 0.002). OS of TEA (vs. TACE) was significantly longer (21.6 [12, 41] months versus 9.9 [5.9, 24.1], p = 0.014, hazard ratio 0.6 (0.3, 1). OS of TEA (vs. TARE) was longer (21.6 [12, 41] months versus 11.9 [7, 28.7], p = 0.082, hazard ratio 0.6 (0.3, 1.3) in favour of TEA). CONCLUSION: In patients with huge HCC, transarterial treatment as represented by TACE had a survival benefit over supportive care. In this retrospective analysis, TEA was associated with better tumour response and survival outcome as compared to TACE or TARE; therefore, transarterial treatment could be useful for prolonging patient survival, and TEA could be a preferred option.

Transarterial Ethanol Ablation for Small Hepatocellular Carcinoma (≤ 3 cm): A Comparative Study Versus Radiofrequency Ablation.

PURPOSE: The objective was to evaluate the local treatment efficacy of transarterial ethanol ablation (TEA) as compared to radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This was a retrospective study between January 2005 and April 2017, in which the treatment outcomes of all patients who received either percutaneous TEA or RFA for HCC tumors of size ≤ 3 cm, of Child-Pugh grade A or B, received no prior treatment other than surgical resection, were compared. For TEA, a mixture of absolute ethanol and ethiodized oil at a proportion of 1:2 by volume was administered superselectively into the tumor via a microcatheter placed at the feeding arteries. The TEA group and the RFA group consisted of 68 consecutive patients (88 treated target tumors) and 129 consecutive patients (129 tumors), respectively. RESULTS: Technical success was achieved in all the target tumors in both groups. Grade 3 complication (CIRSE Classification) of prolonged fever occurred in 3 cases with multi-focal and large tumors in the TEA group. There was no statistically significant difference in complete response rate between the TEA group (84/88 or 95.5%) and the RFA group (188/195 or 96.4%) (p = 0.7). Time to progression in the TEA group [median 11.9 months, interquartile range (IQR) 5.6-18 months] was not statistically different from that in the RFA group (median 9.5 months, IQR 3.5-18.7 months) (p = 0.773). CONCLUSION: TEA could be an effective alternative of RFA for the local treatment of small HCC; it is especially valuable for tumors of unfavorable location.

Long-term outcomes of microwave versus radiofrequency ablation for hepatocellular carcinoma by surgical approach: A retrospective comparative study.

BACKGROUND: Both microwave ablation (MWA) and radiofrequency ablation (RFA) are commonly employed local ablation techniques for malignant liver tumors. However, comparative data on long-term results between these two techniques is scarce in the literature. METHODS: This is a retrospective comparative study between MWA and RFA for hepatocellular carcinoma (HCC) using surgical approach. RESULTS: The MWA group consisted of 26 patients while the RFA group consisted of 47 case-matched patients. The two groups were comparable, except patients were older and their platelet count was lower in the MWA group. The median follow-up period was 47.5 months in MWA group and 52.9 months in RFA group (p = 0.322). There was no difference in 5-year overall survival (MWA 73.1%, RFA 46.3%, p = 0.082) and 5-year disease free survival (MWA 13.8%, RFA 14.6%, p = 0.736). When a subgroup analysis of tumors ≥ 3.5 cm was performed, there were 16 patients in the MWA group and 21 patients in the RFA group, the 5-year overall and disease-free survival were MWA 75.0%, RFA 28.6% (p = 0.022) and MWA 25.0%, RFA 4.8% (p = 0.207), respectively. CONCLUSION: MWA is comparable to RFA for HCC in terms of long-term outcomes. For tumors ≥ 3.5 cm, MWA is associated with a better overall 5-year survival.

Mechanism and Natural Course of Tumor Involution in Hepatocellular Carcinoma Following Transarterial Ethanol Ablation.

PURPOSE: To evaluate the microvascular distribution of lipiodol-ethanol, the histological change of the tumor lesion, and the status of tumor involution over time in hepatocellular carcinoma (HCC) following transarterial ethanol ablation (TEA), in lesions that showed CT evidence of complete tumor response. MATERIALS AND METHODS: Patients with unresectable HCC were treated (183 patients, 242 lesions) with TEA using lipiodol-ethanol mixture (LEM) mixed in 2:1 ratio by volume and followed with CT at 3-month intervals for a median of 14.1 months. Liver tumors (n = 131) that showed CT evidence of complete tumor response, defined as the absence of any enhancing tumor throughout the follow-up period, were included. The surgical specimens of five patients who subsequently received partial hepatectomy were available for histological assessment. The microvascular distribution of LEM and the degree of tumor necrosis were analyzed. Tumor involution over time was assessed with CT in lesions that showed complete response. RESULTS: Lipid stain revealed lipiodol infiltration throughout arterioles, intratumoral sinusoidal spaces, tumor capsule, and peritumoral portal venules. Complete tumor necrosis (100 %) occurred in all 5 surgical specimens. The median (IQR) percentage tumor volume compared to baseline volumes at 12, 36, and 60 months was 32 % (23.5-52.5 %), 22 % (8-31 %), and 13.5 % (6-21.5 %), respectively. CONCLUSION: Intrahepatic HCC lesion that showed CT evidence of complete tumor response following TEA is associated with histological evidence of LEM infiltration throughout the intratumoral and peritumoral vasculature and complete tumor necrosis, as well as sustained reduction in tumor volume over time.