Sodium Cholate Bile Acid-Stabilized Ferumoxytol-Doxorubicin-Lipiodol Emulsion for Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma

PurposeTo develop bile acid-stabilized multimodal magnetic resonance (MR) imaging and computed tomography (CT)-visible doxorubicin eluting lipiodol emulsion for transarterial chemoembolization of hepatocellular carcinoma (HCC).Materials and MethodsFerumoxytol, a US Food and Drug Administration-approved iron oxide nanoparticle visible under MR imaging was electrostatically complexed with doxorubicin (DOX). An amphiphilic bile acid, sodium cholate (SC), was used to form a stable dispersion of ferumoxytol-DOX complex in lipiodol emulsion. Properties of the fabricated emulsion were characterized in various component ratios. Release kinetics of DOX were evaluated for the chemoembolization applications. Finally, in vivo multimodal MR imaging/CT imaging properties and potential therapeutic effects upon intra-arterial (IA) infusion bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion were evaluated in orthotopic McA-Rh7777 HCC rat models.ResultsDOX complexed with ferumoxytol through electrostatic interaction. Amphiphilic SC bile acid at the interface between the aqueous ferumoxytol-DOX complexes and lipiodol enabled a sustained DOX release (17.2 ± 1.6% at 24 hours) at an optimized component ratio. In McA Rh7777 rat HCC model, IA-infused emulsion showed a significant contrast around tumor in both T2-weighted MR imaging and CT images (P = .044). Hematoxylin and eosin and Prussian blue staining confirmed the local deposition of IA-infused SC bile acid-stabilized emulsion in the tumor. The deposited emulsion induced significant increases in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) stain-positive cancer cell apoptosis compared to those in a group treated with the nonstabilized emulsion.ConclusionsSC bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion demonstrated sustained drug release and multimodal MR imaging/CT imaging capabilities. The new lipiodol-based formulation may enhance the therapeutic efficacy of chemoembolization in HCC.     

Use of a Glass Membrane Pumping Emulsification Device Improves Systemic and Tumor Pharmacokinetics in Rabbit VX2 Liver Tumor in Transarterial Chemoembolization

PurposeTo evaluate the phamacokinetics of epirubicin in conventional transarterial chemoembolization using a developed pumping emulsification device with a microporous glass membrane in VX2 rabbits.Materials and MethodsEpirubicin solution (10 mg/mL) was mixed with ethiodized oil (1:2 ratio) using the device or 3-way stopcock. Forty-eight rabbits with VX2 liver tumor implanted 2 weeks prior to transarterial chemoembolization were divided into 2 groups: a device group (n = 24) and a 3-way-stopcock group (n = 24). Next, 0.5 mL of emulsion was injected into the hepatic artery, followed by embolization using 100–300-μm microspheres. The serum epirubicin concentrations (immediately after, 5 minutes after, and 10 minutes after) and the tumor epirubicin concentrations (20 minutes after and 48 hours after) were measured after transarterial chemoembolization. Histopathologic evaluation was performed with a fluorescence microscope.ResultsThe area under the curve and maximum concentrations of epirubicin in plasma were 0.45 ± 0.18 μg min/mL and 0.13 ± 0.06 μg/mL, respectively, in the device group and 0.71 ± 0.45 μg min/mL and 0.22 ± 0.17 μg/mL, respectively, in the 3-way-stopcock group (P = .013 and P = .021, respectively). The mean epirubicin concentrations in VX2 tumors at 48 hours in the device group and the 3-way-stopcock group were 13.7 ± 6.71 and 7.72 ± 3.26 μg/g tissue, respectively (P = .013). The tumor necrosis ratios at 48 hours were 62 ± 11% in the device group and 51 ± 13% in the 3-way-stopcock group (P = .039).ConclusionsConventional transarterial chemoembolization using the pumping emulsification device significantly improved the pharmacokinetics of epirubicin compared to the current standard technique using a 3-way stopcock.     

Serum MicroRNA-210 as a Predictive Biomarker for Treatment Response and Prognosis in Patients with Hepatocellular Carcinoma undergoing Transarterial Chemoembolization

PurposeTo investigate whether serum microRNA-210 (miR-210) level can serve as an indicator of prognosis and a predictor of efficacy of transarterial chemoembolization in patients with hepatocellular carcinoma (HCC).Materials and MethodsSerum miR-210 level was measured in 113 patients with HCC before transarterial chemoembolization (t1), 3 days after transarterial chemoembolization (t2), and 4 weeks after transarterial chemoembolization (t3) and compared with 39 healthy control subjects. The correlations between miR-210 levels and clinicopathologic factors, tumor responsiveness, and prognosis were analyzed. The modified Response Evaluation Criteria in Solid Tumors assessment was conducted at t3.ResultsA higher mean baseline miR-210 level was observed in patients with HCC compared with control subjects (3.69 ± 2.04 vs 1.08 ± 0.45, P < .001). A positive correlation between baseline miR-210 level and tumor size (P < .001), vascular invasion (P = .005), tumor differentiation (P = .037), and Barcelona Clinic Liver Cancer stage (P < .001) was observed. Elevated baseline miR-210 level also served as an independent prognostic factor predicting poor overall survival (risk ratio, 2.082; P = .003). Patients who did not respond to transarterial chemoembolization had higher baseline miR-210 levels than patients who did respond to treatment (4.34 ± 1.67 vs 3.28 ± 2.15, P < .001). In addition, miR-210 levels increased significantly 4 weeks after transarterial chemoembolization in nonresponders (5.79 ± 2.06 at t3 vs 4.34 ± 1.67 at t1, P < .001), whereas no significant change was observed in responders (3.53 ± 2.20 at t3 vs 3.28 ± 2.15 at t1, P = .116). Lastly, an inverse correlation was identified between miR-210 change t1–t3 with the time to radiologic progression (P < .001).ConclusionsSerum miR-210 may represent a novel biomarker for predicting efficacy of transarterial chemoembolization and overall survival for patients with HCC.     

Inhibition of Growth in a Rabbit VX2 Thigh Tumor Model with Intraarterial Infusion of Carbon Dioxide–Saturated Solution

PurposeTo evaluate the efficacy of intraarterial infusion of CO₂-saturated solution in rabbit VX2 thigh tumors.Materials and MethodsFourteen Japanese white rabbits had VX2 tumors implanted in the right femoral muscle 3 weeks before intraarterial infusion. Rabbits were divided into control and CO₂ groups (n = 7 each). Fifty milliliters of solution (saline solution and CO₂-saturated solution for the control and CO₂ groups, respectively) was administered via a 24-gauge catheter in the ipsilateral iliac artery close to the feeding artery of the VX2 tumor. All rabbits were killed for tumor harvest on day 3 after the procedure. Tumor volume was evaluated with in vivo direct caliper measurement and contrast-enhanced computed tomography (CT). Tumor apoptotic changes were examined by DNA fragmentation assay and immunoblot analysis. The tumor growth ratio and apoptotic cell rate were analyzed.ResultsBody weight was equally increased in both groups, but the mean tumor growth ratio was significantly decreased in the CO₂ group compared with the control group (−9.5% ± 7.9 vs 27.2% ± 6.6 and 4.1% ± 4.4 vs 35.7% ± 4.5 measured by calipers and contrast-enhanced CT, respectively; P < .01). Apoptotic activity in the CO₂ group was higher than in the control group (number of apoptotic cells per area, 215.0 ± 58.7 vs 21.8 ± 5.4; adjusted relative density of cleaved caspase-3, 0.23 ± 0.07 vs 0.04 ± 0.01; P < .01).ConclusionsIntraarterial infusion of CO₂-saturated solution inhibits rabbit VX2 thigh tumor growth by activation of apoptotic cell death through cleaved caspase-3 upregulation.     

Transarterial Chemoembolization Using 100-μm Drug-Eluting Microspheres in Patients with Hepatocellular Carcinoma: A Prospective Study and Midterm Follow-up

PurposeThe purpose of this study was to assess the safety and efficacy of drug-eluting embolic (DEE) transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients who are ineligible for curative treatment, using doxorubicin-loaded Tandem (Varian Medical) microspheres.Materials and MethodsBetween October 2015 and December 2017, 98 patients with unresectable HCC (69 males, 29 females; mean age, 60.5 ± 10.0 years of age; and American Joint Committee on Cancer [AJCC] stage ≦T3a) treated with DEE transarterial chemoembolization using 100-μm doxorubicin-loaded microspheres were enrolled prospectively. All studies were reviewed and approved by the Institutional Review Board of Chang Gung Memorial Hospital. Dynamic contrast-enhanced computed tomography or magnetic resonance imaging 1 month after treatment was used for tumor response assessment according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Outcomes included overall survival (OS), progression-free survival (PFS), and downstaging profile.ResultsMedian follow-up was 21.2 months. At follow-up examinations at 0.5-, 1-, 1.5- and 2.5-year follow-up, OS rates were 93.8%, 89.5%, 79.4%, and 77.0%, respectively. Complete response (CR), partial response, stable disease, and progressive disease were noted in 50 (51.0%), 23 (23.5%), 18 (18.4%), and 7 (7.1%) patients, respectively, with 93.9% disease control rate and 74.5% objective response rate. Mean OS was 28.7 months, and mean PFS was 19.6 months. Number of nodules >3, bilobar disease, larger tumor, and higher AJCC stage correlated with worse CR. No serious adverse events occurred after DEE transarterial chemoembolization. Successful downstage rate was 73.3% (22 of 30) and number of nodules predicting successful downstaging was 7 nodules (cutoff).ConclusionsTandem DEE transarterial chemoembolization provides safe and effective treatment for HCC and a bridge or downstage therapy for liver transplantation.     

Combination Therapies: Quantifying the Effects of Transarterial Embolization on Microwave Ablation Zones

Purpose

To quantify the effect of transarterial embolization on microwave (MW) ablations in an in vivo porcine liver model.

Quantitative Automated Segmentation of Lipiodol Deposits on Cone-Beam CT Imaging Acquired during Transarterial Chemoembolization for Liver Tumors: A Deep Learning Approach

PurposeTo show that a deep learning (DL)–based, automated model for Lipiodol (Guerbet Pharmaceuticals, Paris, France) segmentation on cone-beam computed tomography (CT) after conventional transarterial chemoembolization performs closer to the “ground truth segmentation” than a conventional thresholding-based model.Materials and MethodsThis post hoc analysis included 36 patients with a diagnosis of hepatocellular carcinoma or other solid liver tumors who underwent conventional transarterial chemoembolization with an intraprocedural cone-beam CT. Semiautomatic segmentation of Lipiodol was obtained. Subsequently, a convolutional U-net model was used to output a binary mask that predicted Lipiodol deposition. A threshold value of signal intensity on cone-beam CT was used to obtain a Lipiodol mask for comparison. The dice similarity coefficient (DSC), mean squared error (MSE), center of mass (CM), and fractional volume ratios for both masks were obtained by comparing them to the ground truth (radiologist-segmented Lipiodol deposits) to obtain accuracy metrics for the 2 masks. These results were used to compare the model versus the threshold technique.ResultsFor all metrics, the U-net outperformed the threshold technique: DSC (0.65 ± 0.17 vs 0.45 ± 0.22, P < .001) and MSE (125.53 ± 107.36 vs 185.98 ± 93.82, P = .005). The difference between the CM predicted and the actual CM was 15.31 mm ± 14.63 versus 31.34 mm ± 30.24 (P < .001), with lesser distance indicating higher accuracy. The fraction of volume present ([predicted Lipiodol volume]/[ground truth Lipiodol volume]) was 1.22 ± 0.84 versus 2.58 ± 3.52 (P = .048) for the current model’s prediction and threshold technique, respectively.ConclusionsThis study showed that a DL framework could detect Lipiodol in cone-beam CT imaging and was capable of outperforming the conventionally used thresholding technique over several metrics. Further optimization will allow for more accurate, quantitative predictions of Lipiodol depositions intraprocedurally.     

Safety and Feasibility of Same-day Discharge of Patients with Unresectable Hepatocellular Carcinoma Treated with Doxorubicin Drug-eluting Bead Transcatheter Chemoembolization

PurposeThe aim of this study was to investigate the safety and feasibility of same-day discharge of patients with unresectable hepatocellular carcinoma (HCC) after doxorubicin drug-eluting bead (DEB) transarterial chemoembolization and to elucidate the factors predisposing to overnight admission.Materials and MethodsConsecutive patients with unresectable HCC who underwent superselective 100–300 μm DEB transarterial chemoembolization were included. The parameters of same-day therapy (group A) were compared with those of patients admitted overnight (group B). A χ2 test and a t test were used to compare categorical and continuous variables accordingly.ResultsSeventy-six patients (mean, 61 y) received 110 DEB transarterial chemoembolization treatments over an 8-month study period. In 84.5% (93/110) of DEB transarterial chemoembolization procedures, the patients were discharged on the same day (group A). The causes of hospitalization included the worsening of comorbidities in 41.1% (7/17), pain control in 29.4% (5/17), and groin and closure device–related complications in 29.4% (5/17) of patients. The mean Charlson comorbidity scores in groups A and B were 6.96 (standard deviation [SD] ± 1.98) and 8.47 (SD ± 2.18) (P = .0005), respectively. All of the patients in group B had Barcelona Clinic Liver Cancer (BCLC) stages C and D HCC (P = .024). There were no Common Terminology Criteria for Adverse Events (CTCAE) grade III or worse adverse events (AEs). There was no mortality or emergency visits within 30 days of discharge.ConclusionsSame-day discharge after superselective DEB transarterial chemoembolization for unresectable HCC is safe and feasible. BCLC C or D stage of disease, a higher Charlson comorbidity score, and groin or closure device complications are correlated with a greater likelihood for overnight admission.     

Imaging targeted at tumor with 188Re-labeled VEGF189 exon 6-encoded peptide and effects of the transfecting truncated KDR gene in tumor-bearing nude mice

IntroductionPlanar imaging of ¹⁸⁸Re-labeled vascular endothelial growth factor (VEGF)₁₈₉ exon 6-encoded peptide (QKRKRKKSRYKS) with single photon emission computed tomography (SPECT) in tumor-bearing nude mice and effects of the transfecting truncated KDR gene on its imaging were investigated, so as to provide a basis for further applying the peptide to tumor-targeted radionuclide treatment.MethodsQKRKRKKSRYKS, coupling with mercaptoacetyltriglycine (MAG₃) chelator was labeled with ¹⁸⁸Re; then in vivo distribution, planar imaging with SPECT and blocking experiment in tumor-bearing nude mice were analyzed. Recombinant adenovirus vectors carrying the truncated KDR gene were constructed to transfect tumor tissues to evaluate the effects of truncated KDR on the in vivo distribution and tumor planar imaging of ¹⁸⁸Re-MAG₃–QKRKRKKSRYKS in tumor-bearing nude mice.ResultsThe labeled peptide exhibited a sound receptor binding activity. Planar imaging with SPECT demonstrated significant radioactivity accumulation in tumor 1 h after injection of the labeled peptide and disappearance of radioactivity 3 h later. Significant radioactivity accumulation was also observed in the liver, intestines and kidneys but was not obvious in other tissues. An hour after injection of the labeled peptide, the percentage of the injected radioactive dose per gram (%ID/g) of tumor and tumor/contralateral muscle tissues ratio were 1.98±0.38 and 2.53±0.33, respectively, and increased to 3.08±0.84 and 3.61±0.59 in the group transfected with the truncated KDR gene, respectively, and radioactivity accumulation in tumor with planar imaging also increased significantly in the transfection group.Conclusion¹⁸⁸Re-MAG₃–QKRKRKKSRYKS can accumulate in tumor tissues, which could be increased by the transfection of truncated KDR gene. This study provides a basis for further applying the peptide to tumor targeted radionuclide imaging and treatment.     

Dynamic Contrast-Enhanced MR Imaging Evaluation of Perfusional Changes and Ablation Zone Size after Combination Embolization and Ablation Therapy

PurposeThe objectives of this study were to assess the utility of dynamic contrast-enhanced magnetic resonance (MR) imaging in quantifying parenchymal perfusional changes after embolization and to characterize the association between pharmacokinetic (PK) parameters and final microwave ablation volume.Materials and MethodsPK parameters from dynamic contrast-enhanced MR imaging were used to quantify perfusional changes in the liver after transarterial embolization of the right or left lobe in a swine liver model (n = 5). Each animal subject subsequently underwent microwave ablation (60 W for 5 minutes) of the embolized and nonembolized liver lobes. Changes in PK parameters from dynamic contrast-enhanced MR imaging were correlated with their respective final microwave ablation volumes in each liver lobe.ResultsMicrowave ablation volumes of embolized liver lobes were significantly larger than those of nonembolized liver lobes (28.0 mL ± 6.2 vs 15.1 mL ± 5.2, P < .001). PK perfusion parameters were significantly lower in embolized liver lobes than in nonembolized liver lobes (K^trans = 0.69 min^?1 ± 0.15 vs 1.52 min^?1 ± 0.37, P < .001; k_ep = 0.69 min^?1 ± 0.19 vs 1.54 min^?1 ± 0.42, P < .001). There was a moderate but significant correlation between normalized k_ep and ablation volume, with each unit increase in normalized k_ep corresponding to a 9.8-mL decrease in ablation volume (P = .035).ConclusionsPK-derived parameters from dynamic contrast-enhanced MR imaging can be used to quantify perfusional changes after transarterial embolization and are directly inversely correlated with final ablation volume.     

Hepatic Artery Infusion Chemotherapy Using Fluorouracil,Leucovorin, and Oxaliplatin versus Transarterial Chemoembolization as Initial Treatment for Locally Advanced Hepatocellular Carcinoma: A Propensity Score–Matching Analysis

PurposeTo compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with a modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) regimen with that of transarterial chemoembolization as a locoregional treatment for patients with locally advanced hepatocellular carcinoma (HCC).MethodsThis retrospective study included adult patients with locally advanced HCC who received first-line treatment with either HAIC-mFOLFOX or conventional transarterial chemoembolization monotherapy from January 2015 to December 2016. The outcomes, including tumor response rates, evaluated via imaging assessment using the modified response evaluation criteria in solid tumors; overall survival; progression-free survival; and safety, were compared. The propensity score–matching methodology was used to reduce the influence of confounding factors on the outcomes.ResultsThe study included 131 patients with locally advanced HCC who underwent transarterial chemoembolization and 101 who received HAIC-mFOLFOX as initial treatment. After propensity score matching (n = 67 in each group), patients who received HAIC-mFOLFOX had a higher objective response rate (43.3% vs 13.4%, P = .001), longer median overall survival (13.9 vs 6.0 months, P < .001), and longer median progression-free survival (6.4 vs 2.8 months, P = .001) than those who underwent transarterial chemoembolization. The survival benefit with HAIC-mFOLFOX was strengthened in patients with HCC with vascular invasion (hazard ratio: 0.379; 95% confidence interval: 0.237–0.607). HAIC-mFOLFOX was associated with lower incidences of severe adverse events (8.9% vs 22.9%) and liver toxicity than transarterial chemoembolization.ConclusionsCompared with transarterial chemoembolization, HAIC-mFOLFOX is a potentially safer and more effective locoregional therapy for patients with locally advanced HCC.     

Transarterial Chemoembolization Using Gelatin Sponges or Microspheres Plus Lipiodol-Doxorubicin versus Doxorubicin-Loaded Beads for the Treatment of Hepatocellular Carcinoma

ObjectiveTo retrospectively compare treatment of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) using gelatin sponges or microspheres plus lipiodol-doxorubicin vs. doxorubicin-loaded drug-eluting beads (DEB).ResultsNo significant difference was found at baseline among the three groups. The doxorubicin dosage in group C was significantly (p < 0.001) higher compared to the dose used in groups A or B (median, 50 mg vs. 31 mg or 25 mg). Significantly (p < 0.001) more patients in group C achieved complete response compared to those in groups A or B (32.1% vs. 6.3% or 2.4%). Significantly (p < 0.001) less patients in group C had progressive disease compared to those in groups A or B (34.0% vs. 57.8% or 68.3%). Minor AEs were more common in groups A and B compared to group C, with rates of 54.7%, 34.1%, and 5.7%, respectively.ConclusionIn patients with HCC, TACE with DEB offers better safety and efficacy profiles compared to either TACE with gelatin sponges or TACE with microspheres.     

Quantitative Assessment of Lipiodol Deposition after Chemoembolization: Comparison between Cone-Beam CT and Multidetector CT

PurposeTo evaluate the ability of cone-beam computed tomography (CBCT) performed directly after transarterial chemoembolization to assess ethiodized oil (Lipiodol) deposition in hepatocellular carcinoma (HCC) and compare it with unenhanced multidetector computed tomography (CT).Materials and MethodsConventional transarterial chemoembolization was used to treat 15 patients with HCC, and CBCT was performed to assess Lipiodol deposition directly after transarterial chemoembolization. Unenhanced multidetector CT was performed 24 hours after transarterial chemoembolization. Four patients were excluded because the margin of tumor or area of Lipiodol deposition was unclear. The image enhancement density of the entire tumor and liver parenchyma was measured by ImageJ software, and tumor-to-liver contrast (TLC) was calculated. In addition, volumetric measurement of tumor and Lipiodol was performed by semiautomatic three-dimensional volume segmentation and compared using linear regression to evaluate consistency between the two imaging modalities.ResultsThe mean value of TLC on CBCT was not significantly different from TLC on multidetector CT (337.7 HU ± 233.5 vs 283.0 HU ± 152.1, P = .103).The average volume of the whole tumor and of only the regions with Lipiodol deposition and the calculated average percentage of Lipiodol retention on CBCT were not significantly different compared with multidetector CT (tumor volume, 9.6 cm³ ± 11.8 vs 10.8 cm³ ± 14.2, P = .142; Lipiodol volume, 6.3 cm³ ± 7.7 vs 7.0 cm³ ± 8.1, P = .214; percentage of Lipiodol retention, 68.9% ± 24.0% vs 72.2% ± 23.1%, P = .578). Additionally, there was a high correlation in the volume of tumor and Lipiodol between CBCT and multidetector CT (R² = 0.919 and 0.903).ConclusionsThe quantitative image enhancement and volume analyses demonstrate that CBCT is similar to multidetector CT in assessing Lipiodol deposition in HCC after transarterial chemoembolization.     

Combined Transarterial Embolization and Percutaneous Sclerotherapy as Treatment for Refractory and Nonresectable Aneurysmal Bone Cysts

PurposeTo evaluate the safety and effectiveness of combined transarterial embolization and percutaneous sclerotherapy in the treatment of refractory and nonresectable aneurysmal bone cysts (ABCs) as assessed by imaging and clinical outcomes.Materials and MethodsThis retrospective, single-center study included 16 consecutive patients (9 women and 7 men; median age, 17 years [range, 6–25 years]) who underwent combined transarterial embolization (using ethylene vinyl alcohol) and percutaneous sclerotherapy (using ethanol gel and polidocanol) for refractory and nonresectable ABCs. The median follow-up was 27.3 months (range, 6.7–47.5 months). Grade of mineralization (5-point Likert scale), grade of fluid-fluid levels (FFLs; 4-point Likert scale), and contrast-enhancing lesion volume were evaluated before and after treatment. The quality of life was determined before and after treatment using the Musculoskeletal Tumor Society (MSTS) score and the 36-Item Short Form Survey (SF-36) health questionnaire.ResultsA mean of 1.6 ± 0.7 transarterial embolizations and 3.2 ± 1.7 percutaneous sclerotherapies were performed. No adverse events were observed. All patients showed either partial or complete response; no patient showed ABC recurrence. The grade of mineralization (3.7 ± 0.7 after therapy vs 1.4 ± 0.5 at baseline; P < .0001) and grade of FFL (3.5 ± 0.8 after therapy vs 1.9 ± 0.6 at baseline; P < .0001) significantly improved after therapy compared with baseline. The mean contrast-enhancing lesion volume significantly decreased after treatment compared with baseline (45.9 mm³ ± 96.1 vs 156.0 mm³ ± 115.3, respectively; P = .0003). The MSTS scores (28.8 ± 1.8 after treatment vs 14.1 ± 8.6 at baseline; P < .0001) and SF-36 findings revealed a significant improvement in the quality of life after treatment compared with baseline, leaving most patients without relevant constraints.ConclusionsCombined transarterial embolization and percutaneous sclerotherapy is a minimally invasive, safe, and effective treatment option for refractory and nonresectable ABCs. Treatment fostered bone mineralization and significantly improved patients’ quality of life.     

Transarterial Chemoembolization Followed by Radiofrequency Ablation for Hepatocellular Carcinoma: Impact of the Time Interval between the Two Treatments on Outcome

PurposeTo compare the efficacy of radiofrequency (RF) ablation after transarterial chemoembolization within or beyond 30 days for medium-large or multiple recurrent hepatocellular carcinomas (HCCs).Materials and MethodsIn this single-center retrospective study conducted from 2007 through 2015, 135 patients with a single recurrent HCC (>3 cm) or multiple (2–5 tumors) recurrent HCCs underwent transarterial chemoembolization plus RF ablation. A total of 62 patients underwent RF ablation after transarterial chemoembolization within 30 days (sequential group) and 73 patients underwent RF ablation after transarterial chemoembolization beyond 30 days (delayed group). Outcomes of interests included overall survival (OS), progression-free survival (PFS), and complete response (CR) rate.ResultsThe median OS and PFS were 49.8 and 38.0 months for sequential group, and 31.0 and 11.6 months for the delayed group. The sequential group experienced significantly better OS (hazard ratio [HR]: 0.517; P = .002) and PFS (HR, 0.621; P = .021). Among patients with multiple tumors or a single tumor >5 cm, the sequential group still had significantly longer OS (P = .022; P = .018, respectively) and PFS (P = 0.042; P = .036, respectively) than the delayed group, although no significant differences were observed among patients with solitary 3- to 5-cm tumors (P = .138; P = .803, respectively). The sequential group had a significantly better CR rate than the delayed group (85.4% vs. 68.5%, respectively; P = .035). Significant predictors of OS and PFS included maximum tumor size, number of tumors, and time interval between transarterial chemoembolization and RF ablation.ConclusionsTransarterial chemoembolization plus sequential RF ablation within 30 days was more effective for recurrent HCCs than transarterial chemoembolization plus delayed RF ablation. The time interval within 30 days is required for treating large or multiple HCCs but may not be necessary for solitary medium-sized HCC.     

Yttrium-90 Radiation Segmentectomy of Hepatocellular Carcinoma: A Comparative Study of the Effectiveness,Safety, and Dosimetry of Glass-Based versus Resin-Based Microspheres

PurposeTo evaluate the differences in safety, effectiveness, and dosimetry between glass-based and resin-based ablative yttrium-90 (⁹⁰Y) transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC).Materials and MethodsUsing the modified Response Evaluation Criteria in Solid Tumors and Common Terminology Criteria for Adverse Events, both tumor response and adverse events (AEs) were assessed at 3 months after ⁹⁰Y-TARE. Post procedure ⁹⁰Y-bremsstrahlung single-photon emission computed tomography/computed tomography voxel-based dosimetry analysis was used to create tumor dose (TD) and normal tissue dose (NTD) volume histograms, and to calculate tumor particle loading and specific activity. The TD and NTD receiver operating characteristic curves evaluated the dose threshold able to predict objective (partial or complete) and complete tumor responses in addition to any-grade and grade ≥3 AE incidences. The chi-square test and Student t-test were used to assess variable differences where appropriate.ResultsBetween 2019 and 2020, 81 patients with HCC (20 in the resin-based cohort and 61 in the glass-based cohort) underwent ablative ⁹⁰Y-TARE. The resin-based cohort had more males (89% vs 65%, P = .03), lower tumor-to-normal ratio (1.81 ± 0.39 vs 2.22 ± 0.94, P = .03), higher tumor particle loading (40,172 particles/mL ± 28,039 vs 17,081 particles/mL ± 12,555, P = .0001), lower specific activity (158 Bq/particle ± 3 vs 1,058 Bq/particle ± 331, P = .001), and lower mean TD (308 Gy ± 210 vs 794 Gy ± 523, P = .0002) than the glass-based cohort. No significant differences in baseline characteristics or posttreatment AEs were noted. The overall objective and complete response rates were 85% (95% resin-based vs 82% glass-based; P = .1) and 65% (95% resin-based vs 56% glass-based; P = .003), respectively. The mean TD thresholds able to predict the objective and complete responses were 176 Gy and 247 Gy for resin-based radioembolization and 290 Gy and 481 Gy for glass-based radioembolization, respectively. A maximum NTD of 999 Gy predicted any-grade AEs in glass-based ablative ⁹⁰Y-TARE.ConclusionsCompared with glass-based ablative ⁹⁰Y-TARE, resin-based ablative ⁹⁰Y-TARE can offer comparable safety and effectiveness profiles for patients with HCC. The impact of the significantly different tumor particle loading, particle specific activities, and delivered TDs on tumor response outcomes merits further investigation.     

Multi-detector CT enterography in active inflammatory bowel disease: Image quality and diagnostic efficacy of a low-radiation high contrast protocol

PurposeTo prospectively evaluate image quality and diagnostic efficacy of a low radiation-high contrast (LR-HC) CT Enterography (CTE) in active Inflammatory Bowel Disease (IBD).Materials and methodsEighty-five (36M; 49F; 17–75 yrs) patients with active IBD underwent contrast-enhanced CTE and were stratified in two groups according to age (< or ≥45 yrs): Group A (N = 45; 32 ± 9 yrs; 58 ± 10 kg) and Group B (N = 40; 58 ± 10 yrs; 61 ± 13 kg). Each group received a different amount of radiation (Noise Index, NI) and non-ionic iodinated contrast media (LOCM) as follows: Group A (NI = 15; 2.5 ml/kg) and Group B (NI = 12.5; 2 ml/kg). Thyroid functional tests were performed in all patients of group A at 4–6 wks. Signal- and contrast-to-noise ratios were calculated for liver (L) and abdominal aorta (A). Statistical analysis was performed by Student's t- or Chi-square test for continuous and categorical data, respectively.ResultsNo patient of Group A developed signs of thyrotoxicosis. SNR_L, CNR_L and diagnostic accuracy of CTE were 8.4 ± 1.7 vs 8.9 ± 2.1 (p = 0.256), 5.4 ± 1.5 vs 5.6 ± 1.7 (p = 0.486) and 91.1 vs 92.5% (p = 0.764) whereas the effective dose and the LOCM administered were 6.7 ± 2.2 vs 13.9 ± 6.0 mSv (p < 0.001) and 144 ± 25 vs 122 ± 25 ml (p < 0.001) for Group A and B, respectively.ConclusionLR-HC CTE is a dose-effective protocol in the evaluation of active IBD in young patients.     

Outpatient Transarterial Chemoembolization of Hepatocellular Carcinoma: Review of a Same-Day Discharge Strategy

Purpose

To test the hypothesis that same-day discharge of selected transarterial chemoembolization patients would not increase 30-day readmission rate compared with overnight observation.

Clinical Significance of the Initial and Best Responses after Chemoembolization in the Treatment of Intermediate-Stage Hepatocellular Carcinoma with Preserved Liver Function

PurposeTo evaluate the clinical implications of initial and best responses during repeated transarterial chemoembolization procedures for hepatocellular carcinoma (HCC).Materials and MethodsThis study included 726 patients who received a diagnosis of intermediate-stage HCC with Child-Pugh class A liver function between 2007 and 2016, and who were treated with transarterial chemoembolization as the first-line treatment. Evaluation of treatment response was based on the modified response evaluation criteria in solid tumors. Overall survival (OS) was compared between response categories after implementation of landmark analysis.ResultsOf the 726 patients, an objective response (complete response [CR] or partial response [PR]) was observed as the initial response in 78.1% of patients. Regarding the best response during the transarterial chemoembolization series, 87.2% of patients were overall responders. The median OS of initial responders (n = 483) was not significantly different from that of subsequent responders at the 1-year landmark (stable disease [SD] after first transarterial chemoembolization but CR or PR after repeated transarterial chemoembolization; n = 61; 46.2 vs 40.1 months, respectively; P = .145). Likewise, the median OS of initial CR patients (n = 326) was not significantly different from that of the subsequent CR group (n = 126) at the 1-year landmark (PR or SD after first transarterial chemoembolization but CR after repeated transarterial chemoembolization; 53.4 vs 46.3 months, respectively; P = .455). Multivariate Cox analyses showed that the objective responses, the initial responses (hazard ratio [HR], 0.638; P = .001), and the best responses (HR, 0.304; P < .001) had the significant prognostic significance for OS.ConclusionsBoth the initial and best responses during repeated transarterial chemoembolization were significantly associated with OS in patients with intermediate-stage HCC and preserved liver function.     

Comparison of the Efficacy of Dexmedetomidine plus Fentanyl Patient-controlled Analgesia with Fentanyl Patient-controlled Analgesia for Pain Control in Uterine Artery Embolization for Symptomatic Fibroid Tumors or Adenomyosis: A Prospective,Randomized Study

PurposeTo investigate whether dexmedetomidine infusion could reduce opioid consumption and opioid-related side effects after uterine artery embolization (UAE).Materials and MethodsFifty patients undergoing UAE for symptomatic leiomyomas or adenomyosis were randomized into two groups. In 25 patients, dexmedetomidine infusion was started at 0.2 μg/kg/h at 30 minutes before the procedure, followed by 0.4 μg/kg/h for 6 hours after the procedure. In another 25 patients (control group), volume-matched normal saline solution was administered. Both groups received fentanyl-based intravenous patient-controlled analgesia (PCA; fentanyl 10 μg/h with a bolus dose of 20 μg) during the 24 hours after the procedure. Nonspherical polyvinyl alcohol particles were used. Pain scores, fentanyl consumption, need for additional analgesics, and side effects were assessed for 24 hours after UAE.ResultsCompared with the control group, patients in the dexmedetomidine group required 28% less PCA fentanyl during the 24 hours after UAE (P = .006). Numeric rating scale scores for pain (5.0±2.4 vs 7.0±2.2; P = .026) and the need for additional analgesics (two of 25 vs 17 of 25; P<.001) were lower in the dexmedetomidine group than in the control group during the first 1 hour after UAE. The incidence and severity of nausea and vomiting during the 24 hours after UAE were lower in the dexmedetomidine group than in the control group (P < .05).ConclusionsThe addition of dexmedetomidine infusion to fentanyl PCA provides better analgesia, fentanyl-sparing effect, and less nausea and vomiting, without significant hemodynamic instability.