Transarterial Embolization Therapy Research Articles

Intravascular Casting Radiopaque Hydrogel Systems for Transarterial Chemo/Cascade Catalytic/Embolization Therapy of Hepatocellular Carcinoma.

This paper introduces catheter-directed intravascular casting hydrogels for transarterial chemo/starvation/chemodynamic embolization (TACSCE) therapy of hepatocellular carcinoma (HCC). Comprising Mn ion-crosslinked hyaluronic acid-dopamine (HD) with glucose oxidase (for glucose decomposition to H2O2 in starvation therapy), doxorubicin (for chemotherapy), and iopamidol (for X-ray imaging), these hydrogels are fabricated for transarterial embolization therapy guided by X-ray fluoroscopy. Mn4+ (from MnO2) demonstrates strong coordination with the catechol group of HD, providing hypoxia relief through O2 generation and cellular glutathione (GSH) consumption, compared to the OH radical generation potential of Mn2+. The gelation time-controlled, catheter-injectable, and rheologically tuned multitherapeutic/embolic gel system effectively reaches distal arterioles, ensuring complete intravascular casting with fewer complications related to organic solvents. Glucose deprivation, cascade reactive oxygen species (ROS) generation, GSH depletion, and sustained release profiles of multiple drug cargos from the hydrogel system are also achieved. The combined chemo/starvation/chemodynamic efficacies of these designed hydrogel systems are confirmed in HCC cell cultures and HCC-bearing animal models. The developed radiopaque/injectable/embolic/sol-to-gel transformable systems for TACSCE therapy may offer enhanced therapeutic efficacies compared to typical transarterial embolization and transarterial chemoembolization procedures for HCC.

Locoregional Therapy for Intrahepatic Cholangiocarcinoma: The Role of Intra-Arterial Therapies.

Intrahepatic cholangiocarcinoma (ICC) is a rare disease with a rising incidence. While surgical resection is the only curative option, the disease process is often identified in advanced stages, as this malignancy often remains clinically silent in early development. Only one-third of patients are eligible for resection at the time of diagnosis. For patients who cannot undergo resection, intra-arterial therapies are reasonable palliative treatment options; in rare occasions, these may be bridging therapies, as well. The premise of bland embolization and most chemoembolization intra-arterial therapies is that the arterial supply of the tumor is occluded to induce tumor necrosis, while radioembolization utilizes the arterial flow of the tumor to deliver radiation therapy. In this review, we discuss the use of transarterial embolization, transarterial chemoembolization, and selective internal radiation therapy for the treatment of ICC. Phase III randomized controlled clinical trials are difficult to tailor to this extremely rare and aggressive disease, but ultimately, further investigation should be pursued to define the patient population that will derive the greatest benefit from each modality.

Safety and Efficacy of Transarterial Embolization Therapy in Patients with Uncontrolled Epistaxis: A Single-Center Retrospective Observational Study

Aim: 
 This study aimed to present technical details and outcomes of endovascular treatment of patients who underwent endovascular embolization due to resistant and recurrent epistaxis in our center.
 Methods: 
 In this study, between January 2014 and January 2020, the patients who underwent endovascular treatment due to epistaxis in the interventional radiology unit at our hospital were evaluated retrospectively.
 Results:
 In this study, 4 (25%) female and 12 (75%) male patients were included in 16 patients. The mean age of the patients was 56.6 ± 17.8 years. The etiologies of epistaxis of the patients were as follows; 4 (25%) patients had nasal angiofibroma, 1 (6.2%) patient had larynx carcinoma, 1 (6.2%) patient had nasopharynx carcinoma, 1 (6.2%) patient had aneurysm rupture, 1 (6.2%) patient had epistaxis due to anticoagulant use, 8 (50%) patients had idiopathic epistaxis. In total, endovascular embolization was performed in all 18 procedures performed. In all 16 patients who underwent embolization, 100% technical success was achieved during the procedure, and no complications developed in the follow-up. However, in 2 (12.5%) procedures, embolization therapy was performed for the second time due to recurrent epistaxis after embolization.
 Conclusions: 
 In resistance and recurrent epistaxis cases, endovascular embolization is an alternative to surgical methods, a treatment method with a low risk of complications and a high success rate.

Life expectancy of patients with hepatocellular carcinoma according to the upfront treatment: A nationwide analysis.

The purpose of this study was to update the life expectancy of patients with hepatocellular carcinoma (HCC) in an exhaustive nationwide population according to the upfront treatment performed. From the French Program for the Medicalization of Information System database, all patients older than 18 years diagnosed with a de novo HCC from January 2011 to December 2018 were retrospectively selected. Five-year survival rates (95% confidence intervals [CI]) were computed according to the first surgical or interventional radiology procedures performed. A total of 63,996 patients (80% men) with a median age of 68 years (Q1, Q3: 61, 77) were selected, including 24,007 patients who underwent at least one procedure (5-year survival of 45.5%; (95% CI: 44.8-46.2), and 39,989 with none (5-year survival, 9.6%; (95% CI: 9.3-10.0). Only 20.5% (13,101/63,996) of patients could undergo an upfront curative procedure. Liver transplantation achieved the best outcome, whether performed upfront (n=791; 5-year survival, 79.0% [95% CI: 76.1-82.1]) or during subsequent steps (n=2217; 5-year survival 80.9% [95% CI: 79.2-82.7]). Tumor ablation (n=5306), open resection (n=5171), and minimally-invasive resection (n=1833) achieved 5-year survival rates of 53.8% (95% CI: 52.3-55.4), 54.1% (95% CI: 52.6-55.6), and 66.2% (95% CI: 63.7-68.7), respectively, with more patients with cirrhosis and subsequent procedures in the tumor ablation group. Patients with upfront transarterial (chemo)embolization (n=10,247) and selective internal radiation therapy (n=659) had 5-year survival rates of 31.3% (95% CI: 30.3-32.4) and 18.5% (95% CI: 15.2-22.5). While HCC remains mostly diagnosed at an advanced stage associated with a poor prognosis, all the curative options provide 5-year survival rates above 50%.

Abstract No. 298 Intravascular pressure changes during transarterial embolization therapy in a benchtop hepatic vascular model

Abstract No. 298 Intravascular pressure changes during transarterial embolization therapy in a benchtop hepatic vascular model

In situ Thermal-Responsive Magnetic Hydrogel for Multidisciplinary Therapy of Hepatocellular Carcinoma.

Current surgical single modality treatments for hepatocellular carcinoma (HCC) were restricted by recurrence, blood loss, significant trauma, and poor prognostic. Although multidisciplinary strategies for HCC treatment have been highly recommended by the clinical guidelines, there was limited choice of materials and treatments. Herein, we reported an in situ formed magnetic hydrogel with promising bioapplicable thermal-responsiveness, strong adhesion in wet conditions, high magnetic hyperthermia, and biocompatibility, leading to efficient HCC multidisciplinary treatment including postoperative treatment and transarterial embolization therapy. In vivo results indicated that this hydrogel could reduce the postoperative recurrence rate. The hemostatic ability of the thermal-responsive hydrogel was further demonstrated in both the liver scratch model and liver tumor resection. Computed tomography imaging suggested that the hydrogel could completely embolize the arterial vessels of rabbit liver tumor by vascular intervention operation, which could serve as multidisciplinary responsive materials to external magnetic field and body temperature for HCC treatment.

Nanoscale CaH2 materials for synergistic hydrogen-immune cancer therapy

<h2>Summary</h2> Herein, we prepared CaH₂ nanoparticles through liquid-phase exfoliation and first applied them as an antitumor therapeutic agent. Being dispersed in low-molecular-weight polyethylene glycol (PEG) and injected into the tumor, nano-CaH₂ would react with water to generate abundant hydrogen gas (H₂), calcium ions (Ca²⁺), and hydroxyl ions (OH⁻), enabling hydrogen therapy, tumor calcification, and neutralization of acidic tumor microenvironment (TME), respectively. The injectable nano-CaH₂ dispersion could lead to significant tumor growth inhibition. In addition, the local nano-CaH₂-induced tumor cell apoptosis and TME modulation would activate the immune system and promote tumor infiltration of immune cells, which, working together with immune checkpoint blockade, could elicit robust immune responses to inhibit abscopal distant tumors without direct nano-CaH₂ injection. Furthermore, nano-CaH₂ could be dispersed in lipiodol to obtain CaH₂-lipiodol dispersion for interventional transarterial embolization (TAE) therapy, and they showed obviously improved TAE therapeutic outcome on orthotopic rabbit liver cancer model compared with lipiodol alone.

Role of Imaging in Renal Cell Carcinoma: A Multidisciplinary Perspective.

With the expansion in cross-sectional imaging over the past few decades, there has been an increase in the number of incidentally detected renal masses and an increase in the incidence of renal cell carcinomas (RCCs). The complete characterization of an indeterminate renal mass on CT or MR images is challenging, and the authors provide a critical review of the best imaging methods and essential, important, and optional reporting elements used to describe the indeterminate renal mass. While surgical staging remains the standard of care for RCC, the role of renal mass CT or MRI in staging RCC is reviewed, specifically with reference to areas that may be overlooked at imaging such as detection of invasion through the renal capsule or perirenal (Gerota) fascia. Treatment options for localized RCC are expanding, and a multidisciplinary group of experts presents an overview of the role of advanced medical imaging in surgery, percutaneous ablation, transarterial embolization, active surveillance, and stereotactic body radiation therapy. Finally, the arsenal of treatments for advanced renal cancer continues to grow to improve response to therapy while limiting treatment side effects. Imaging findings are important in deciding the best treatment options and to monitor response to therapy. However, evaluating response has increased in complexity. The unique imaging findings associated with antiangiogenic targeted therapy and immunotherapy are discussed. An invited commentary by Remer is available online. Online supplemental material is available for this article. ©RSNA, 2021.

Abstract 422: Sequential targeted therapy and immunotherapy of a BRAF positive metastatic melanoma patient with BRAF inhibitor vemurafenib, MEK inhibitor cobimetnib and a novel PD-1 antibody Sintilimab

Abstract Targeted therapy has dramatically improved the outcome of BRAF mutated melanoma patients. However, its response is usually brisk and lacks the durability of immunotherapy. Decisions about targeted therapy alone, immunotherapy alone, targeted therapy/immunotherapy combination or immunotherapy after targeted therapy require an oncologist to comprehensively evaluate multiple clinical factors. Here we report the sequential treatment of a BRAF positive metastatic melanoma patient with non-standard regimes due to practical reasons. A 75-year old male patient presented a black cauliflower-like mass on back and bilateral axillary lymph nodes enlargement. Postoperative pathologic examination confirmed a nodular malignant melanoma of 1.6 cm in diameter and 0.7 cm thick. NGS sequencing of the tumor revealed the canonical BRAF V600E mutation. As vemurafenib was the only approved melanoma targeted therapy drug in China at the time of diagnosis, it was administered (960 mg bid) as first-line therapy since September 2019 and the patient's response was confirmed by the significant reduction and softening of the left axillary node. One month later the node rapidly enlarged to 15 cm, and the blood scab fell off followed by pulsatile massive hemorrhage (~1000 mL). We performed an emergent angiograph and a transarterial embolization (TAE), aimed at selectively occluding the tumor artery by using gelatin sponge particle and coils. The hemorrhage was significantly reduced after TAE therapy and a left axillary residual cavity was formed. When the patient presented a progression of lymph node metastases, BRAF/MEK inhibitor combination was selected as the second-line therapy from December 2019. He received vemurafenib at a dose of 480 mg bid combined with cobimetinib 60mg qd (3 consecutive weeks every 28 days), the treatment was ongoing till disease progression in April 2020. Immunohistochemical analysis of the biopsy specimen demonstrated PD-L1 expression in 4% of tumor cells and immunotherapy was chosen as the third-line therapy. Sintilimab, a PD-1 antibody approved in China for the treatment of classical Hodgkin lymphoma, is undergoing clincial trials for multiple solid tumors including melanoma. Given the high cost of immunotherapy and the fact that Sintilimab is the only PD-1 inhibitor included in China's National Reimbursement Drug List, the patient started off-label use of Sintilimab and achieved partial response. In summary, our patient had an unconventional timeline of multiple therapies including surgery, TAE, targeted therapy and immunotherapy. His case demonstrated that meaningful clinical responses can be achieved with sequential targeted therapy/immunotherapy in BRAF-mutated metastatic melanoma and the novel PD-1 antibody Sintilimab is worth further investigation for its efficacy in metastatic melanoma. Citation Format: Yu Zhang, Xiaomo Li, Tonghui Ma, Baoshan Cao. Sequential targeted therapy and immunotherapy of a BRAF positive metastatic melanoma patient with BRAF inhibitor vemurafenib, MEK inhibitor cobimetnib and a novel PD-1 antibody Sintilimab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 422.

Transarterial and Transvenous Coil Embolization of Direct Carotid-Cavernous Fistulas.

Transvenous embolization (TVE) is typically used in combination with the residual shunt of transarterial embolization (TAE) for the treatment of direct carotid-cavernous fistulas (direct CCFs). This report is about our additional embolization method using combination therapy. Five consecutive cases of direct CCF were presented; two were caused by aneurysms and three by head injuries. The treatment for each was started with TAE, with the addition of TVE if a shunt remained. At the time of TVE, a microcatheter positioned in the internal carotid artery passing from the cavernous sinus through the aneurysm neck or fistula was pulled back (pull-back method). It was then placed in the coil mass with TAE, and additional coils were filled. In two cases, the shunt disappeared by using only TAE, whereas it disappeared after being additionally embolized by the pull-back method in the remaining cases. All patients recovered with no postoperative complications. The TAE and TVE combination therapy with the pull-back method could efficiently embolize the residual shunt after TAE.

The Role of Interventional Radiology for the Treatment of Hepatic Metastases from Neuroendocrine Tumor: An Updated Review.

Interventional radiology plays an important role in the management of patients with neuroendocrine tumor liver metastasis (NELM). Transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) are intra-arterial therapies available for these patients in order to improve symptoms and overall survival. These treatment options are proposed in patients with NELM not responding to systemic therapies and without extrahepatic progression. Currently, available data suggest that TAE should be preferred to TACE in patients with NELM from extrapancreatic origin because of similar efficacy and better patient tolerance. TACE is more effective in patients with pancreatic NELM and SIRT has shown promising results along with good tolerance. However, large randomized controlled trials are still lacking in this setting. Available literature mainly consists in small sample size and retrospective studies with important technical heterogeneity. The purpose of this review is to provide an updated overview of the currently reported endovascular interventional radiology procedures that are used for the treatment of NELM.

Sarcopenia as a predictor of survival in patients undergoing bland transarterial embolization for unresectable hepatocellular carcinoma.

Sarcopenia has been associated with lower overall survival in patients with cirrhosis and hepatocellular carcinoma (HCC) undergoing surgical resection, TACE, TARE, or transplantation. This monocentric study evaluated the prognostic significance of sarcopenia in patients affected by HCC who received bland transarterial embolization (TAE) therapy, by analyzing its impact on survival and treatment-related complications. All consecutive patients who underwent the 1st TAE between March 1st 2011 and July 1st 2019 in our Institution were retrospectively studied. To evaluate sarcopenia, the skeletal muscle index (SMI) was calculated by normalizing the cross-sectional muscle area at the level of L3 on an abdominal CT scan prior to embolization (cm2) by patient height (m2). SMI cut-off values for sarcopenia were considered ≤ 39 cm2/m2 for women and ≤55 cm2/m2 for men. Data about age, gender, body mass index (BMI), underlying liver disease, liver function, MELD score, Child-Pugh score, multifocal disease, performance status, previous interventions, length of stay (LOS), complications after the procedure, readmission rate within 30 days, survival time from TAE and total number and type of TAE received following the first procedure were collected. From 2011 to 2019, 142 consecutive patients underwent 305 TAEs. Observation time ranged from 1.4 to 100.5 months (median 20.1 SD = 22). Sarcopenia at baseline was present in 121 (85%) patients. Overall 87 (61.2%) patients died during follow-up with survival rates at 1-, 2-, 3-, 4-, and 5-year of 71%, 41%, 22%, 16% and 11% respectively. After multivariate analysis sarcopenia (HR = 2.22, p = 0.046), previous ablation/resection (HR = 0.51, p = 0.005) and multifocal disease (HR = 1.84, p = 0.02) were associated with reduced survival. Sarcopenia did not influence the safety of TAE in terms of LOS (2 days vs 1.5 days, p = 0.2), early complications rate (8% vs 5%, p = 0.5) and readmission rate within 30 days (7% vs 5%, p = 0.74). Sarcopenia, estimated by the L3SMI method, is an emerging prognostic factor in patients with HCC undergoing bland TAE therapy as it is associated with increased mortality, without impairing the safety of the locoregional treatment. Measures to ameliorate the SMI, such as nutritional support and physical exercise, should be evaluated in clinical trials for HCC patients receiving liver embolization to determine their impact on overall survival.

An Arteriovenous Malformation of the Corpus Callosum Presenting Intraventricular Hemorrhages and Treated with Transarterial Embolization and Gamma Knife Therapy

An Arteriovenous Malformation of the Corpus Callosum Presenting Intraventricular Hemorrhages and Treated with Transarterial Embolization and Gamma Knife Therapy

Rethinking the Role of Radiation Therapy in the Treatment of Unresectable Hepatocellular Carcinoma: A Data Driven Treatment Algorithm for Optimizing Outcomes.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, with a majority of HCC patients not suitable for curative therapies. Approximately 70% of initially diagnosed patients cannot undergo surgical resection or transplantation due to locally advanced disease, poor liver function/underlying cirrhosis, or additional comorbidities. Local therapeutic options for patients with unresectable HCC, who are not suitable for thermal ablation, include transarterial embolization (bland, chemoembolization, radioembolization) and/or external beam radiation therapy (EBRT). Regarding EBRT specifically, technological advancements provide a means for safe and effective radiotherapy delivery in a wide spectrum of HCC patients. In multiple prospective studies, EBRT delivery in a variety of different fractionation schemes or in combination with transcatheter arterial chemoembolization (TACE) demonstrate improved outcomes, particularly with combination therapy. The Barcelona Clinic Liver Cancer classification provides a framework for treatment selection; however, given the growing complexity of treatment strategies, this classification system tends to simplify decision-making. In this review, we discuss the current literature regarding unresectable HCC and propose a modified treatment algorithm that emphasizes the role of radiation therapy for Child-Pugh score A or B patients with ≤3 nodules measuring >3 cm, multinodular disease or portal venous thrombosis.

Mammalian target of rapamycin inhibitor and transarterial embolization for treatment of tuberous sclerosis complex patients with renal angiomyolipoma

Objective: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease that results in multiorgan hamartomas. Patients with TSC also frequently have renal angiomyolipomas, which are rare but benign renal tumors. However, the main causes of mortality in these patients are angiomyolipoma-related chronic kidney disease and acute tumor hemorrhage. Angiomyolipomas are mostly treated in our hospital using mammalian target of rapamycin (mTOR) inhibitor therapy or transarterial embolization (TAE). This study was undertaken to evaluate and compare the short-term outcomes of a combined therapy of mTOR inhibitor and TAE in patients with TSC-associated angiomyolipoma. Materials and Methods: This was a retrospective observational study based on collected data obtained from chart reviews. The single-center data set covered patients diagnosed, treated, and followed up from September 10, 2008, to March 17, 2016, at a specialist center. Patients with TSC-associated angiomyolipoma treated with monotherapy or combined treatment of mTOR inhibitor and TAE were included in this study. We compared the tumor size with image studies in the baseline and follow-up periods in both groups. Results: In total, 15 patients (3 males and 12 females) were included; 8 patients underwent mTOR inhibitor monotherapy and 7 received the combined mTOR inhibitor and TAE therapy. The mean patient age was 37.7 (17–72) years. The maximal diameters of renal angiomyolipomas ranged from 2 to 20.9 (10.2 ± 5.4) cm for all patients at the time of treatment intervention. During an average follow-up duration of 22 (2–56) months, the mean size of the angiomyolipomas decreased from 9.3 ± 5.6 to 8.5 ± 5.3 cm in the monotherapy group and 11.5 ± 5.4–10.0 ± 5.8 cm in the patients in the combined therapy (P = 0.014). Conclusions: In comparison with m-TOR inhibitor monotherapy, TAE combined with mTOR inhibitor therapy allows management of tumor bleeding with acceptable complications, and it also statistically reduces the tumor size in patients with TSC-associated renal angiomyolipomas.

Liver transarterial embolizations in metastatic neuroendocrine tumors.

The management of patients with well-differentiated neuroendocrine tumors (NET) and non-resectable liver metastases is challenging. Liver-directed transarterial embolization (TAE), transarterial chemo-embolization (TACE) and selective internal radiation therapy (SIRT) have a place of choice among other treatment modalities. However, their utilization relies on a low level of proof, due to the lack of prospective data, the absence of comparative studies and considerable heterogeneity between local practices. TAE and TACE generally achieve average symptomatic, biological and radiological responses of 75%, 56% and 50%, with progression-free survival of 12-18months, with acceptable tolerance. Although not clearly demonstrated, TACE may be more effective than TAE in pancreatic NET, but not in small-intestine NET. SIRT has been developed more recently and may achieve similar results, with improved tolerance, but decreased cost-effectiveness, although no prospective comparison has been published to date. There is currently no strong argument to choose between TAE, TACE and SIRT, and they have not been compared to other treatment modalities. The evaluation of their efficacy has mostly relied on criteria based on size variations, which do not take into account tumor viability and metabolism, and thus may not be relevant. These techniques may be especially effective when performed as first-line therapies, in patients with non-major liver involvement (<75%) and with hypervascular metastases. Finally, studies exploring their combination with systemic therapies are ongoing.

In situ forming biodegradable poly(ε-caprolactone) microsphere systems: a challenge for transarterial embolization therapy. In vitro and preliminary ex vivo studies

ABSTRACTBackground: In situ forming biodegradable poly(ε-caprolactone) (PCL) microspheres (PCL-ISM) system was developed as a novel embolic agent for transarterial embolization (TAE) therapy of hepatocellular carcinoma (HCC). Ibuprofen sodium (Ibu-Na) was loaded on this platform to evaluate its potential for the treatment of post embolization syndrome.Methods: The influence of formulation parameters on the size/shape, encapsulation efficiency and drug release was investigated using mixture experimental design. Regression models were derived and used to optimize the formulation for particle size, encapsulation efficiency and drug release profile for TAE therapy. An ex vivo model using isolated rat livers was established to assess the in situ formation of microspheres.Results: All PCL-ISM components affected the studied properties and fitting indices of the regression models were high (Radj2 = 0.810 for size, 0.964 encapsulation efficiency, and 0.993 or 0.971 for drug release at 30 min or 48 h). The optimized composition was: PCL = 4%, NMP = 43.1%, oil = 48.9%, surfactant = 2% and drug = 2%. Ex vivo studies revealed that PCL-ISM was able to form microspheres in the hepatic arterial bed.Conclusions: PCL-ISM system provides a novel tool for the treatment of HCC and post-embolization syndrome. It is capable of forming microspheres with desirable size and Ibu-Na release profile after injection into blood vessels.

Radiological and Clinical Features of Vein of Galen Aneurysmal Malformation in Newborn Infants and, the Results of Endovascular Interventional Treatment: 10-Years Experience

Aim: To assess the clinical features, diagnosis, treatment and prognosis of newborn infants with a diagnosis of Vein of Galen Malformation (VGAM)during a 10-year period. Method: Eight patients with a diagnosis of VGAM in the neonatal period were assessed retrospectively in terms of clinical signs, diagnosis, treatment strategies and follow-up. Three of four patients who survived had neurological assessment whereas one was lost to follow-up because of moving to another city. Results: Seven of 8 patients had an antenatal diagnosis. In all cases, severe heart failure and pulmonary hypertension were present from the first day of life and hypotension, multiorgan failure, hydrocephaly and seizures developed in the following days. VGAM and its feeder arteries were mapped by cranial magnetic resonance imaging and magnetic resonance angiography. Transarterial embolization therapy was performed on 7 patients, of whom four babies survived and three babies died, while one patient died before any intervention. Conclusion: The mortality and morbidity rates of VGAM is high because of its mixed anatomy, pathophysiology and characteristic features leading to severe neurological sequelae in the survivors. Prognosis in high risk neonates can be improved with aggressive medical support and early endovascular embolization therapy.

Cinnamic Acid Derivatives Enhance the Efficacy of Transarterial Embolization in a Rat Model of Hepatocellular Carcinoma.

We hypothesize that the combination of transarterial embolization (TAE) plus inhibition of lactate export will limit anaerobic metabolism and reduce tumor survival compared to TAE alone. The purpose of this study was to test this hypothesis in a rat model of hepatocellular carcinoma (HCC). Rat N1-S1 hepatoma cells were assayed in vitro using the Seahorse XF analyzer to measure extracellular acidification (lactate excretion) comparing effects of the addition of caffeic acid (CA) or ferulic acid (FA) or UK-5099 with control. Monocarboxylate transporter Slc16a3 was knocked down by RNAi. N1S1 tumors were orthotopically implanted in rats and 4 groups evaluated: (1) Control, (2) TAE-only, (3) TAE plus CA, and (4) TAE plus FA. Tumor size was determined by ultrasound and analyzed by repeated measures statistics. Tumors harvested at 4weeks were examined by microscopy. Seahorse assays showed that CA and FA caused a significant reduction by >90% in lactate efflux by N1S1 tumor cells (p<0.01). Knockdown of Slc16a3 prevented inhibition by CA. In vivo tumors grew 30-fold in volume over 4weeks in untreated controls. By comparison, TAE resulted in near cessation of growth (10% in 4-week time period). However, both TAE+CA and TAE+FA caused a significant reduction of tumor volumes (87 and 72%, respectively) compared to control and TAE (p<0.05). Pathologic evaluation revealed residual tumor in the TAE group but no residual viable tumor cells in the TAE+CA and TAE+FA groups. Addition of CA or FA enhances the effectiveness of TAE therapy for HCC in part by blocking lactate efflux.

Intravoxel incoherent motion model-based analysis of diffusion-weighted magnetic resonance imaging with 3 b-values for response assessment in locoregional therapy of hepatocellular carcinoma.

PurposeThe aim of this study was to evaluate an intravoxel incoherent motion (IVIM) model–based analysis of diffusion-weighted imaging (DWI) for assessing the response of hepatocellular carcinoma (HCC) to locoregional therapy.Patients and methodsRespiratory-gated DWI (b=0, 50, and 800 s/mm2) was retrospectively analyzed in 25 patients who underwent magnetic resonance imaging at 1.5 T before and 6 weeks following the first cycle of transarterial chemoembolization therapy, transarterial ethanol-lipiodol embolization therapy, and transarterial radioembolization therapy. In addition to the determination of apparent diffusion coefficient, ADC(0,800), an estimation of the diffusion coefficient, D′, and the perfusion fraction, f′, was performed by using a simplified IVIM approach. Parameters were analyzed voxel-wise. Tumor response was assessed in a central slice by using a region of interest (ROI) covering the whole tumor. HCCs were categorized into two groups, responders and nonresponders, according to tumor size changes on first and second follow ups (if available) and changes of contrast-enhanced region on the first follow up.ResultsIn total, 31 HCCs were analyzed: 17 lesions were assigned to responders and 14 were to nonresponders. In responders, ADC(0,800) and D′ were increased after therapy by ~30% (P=0.00004) and ~42% (P=0.00001), respectively, whereas f′ was decreased by ~37% (P=0.00094). No significant changes were found in nonresponders. Responders and nonresponders were better differentiated by changes in D′ than by changes in ADC(0,800) (area under the curve =0.878 vs 0.819 or 0.714, respectively).ConclusionIn patients with HCCs undergoing embolization therapy, diffusion changes were better reflected by D′ than by conventional ADC(0,800), which is influenced by counteracting perfusion changes as assessed by f′.