Thermal Ablation For Hepatocellular Carcinoma Research Articles

Multimodal Theranostic Nanoparticles for Necrosis Targeting, Fluorescence/SPECT Imaging, and Radiotherapy of Residual Tumors after Hepatocellular Carcinoma Ablation.

Thermal ablation has been commonly used as an effective treatment for hepatocellular carcinoma; however, peri-necrotic tumor residues after ablation play a significant role in tumor recurrence and poor prognosis. Therefore, developing agents that can effectively target and eliminate residual tumors is critically needed. Necrosis targeting strategies have potential implications for evaluating tumor necrosis areas and treating the surrounding residual tumors. To address this issue, we have developed a biodegradable nanoparticle with necrosis avidity that is compatible with fluorescence imaging, single photon emission computed tomography (SPECT) imaging, and necrosis targeted radiotherapy. The nanoparticles were synthesized using iodine-131-labeled hypericin (131I-Hyp) as the core and amphiphilic copolymer poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) as the shell. The developed nanoparticle, PNP@(131I-Hyp), has a uniform spherical morphology with a size of 33.07 ± 3.94 and 45.93 ± 0.58 nm determined by cryogenic transmission electron microscopy (cryo-TEM) and dynamic light-scattering analysis (polydispersity index = 0.19 ± 0.01), respectively, and having a good stability and blood compatibility in vitro. In mouse subcutaneous ablated-residual tumor models, fluorescence and SPECT imaging demonstrated that PNP@(131I-Hyp) prominently accumulated in the tumor and was retained for as long as 168 h following intravenous injection. Moreover, ex vivo analyses showed that PNP@(131I-Hyp) mainly gathered in the necrotic zones of subcutaneous tumors and inhibited residual tumors by radiotherapy. In addition, histological examination of harvested organs and hematological analysis demonstrated that intravenous injection of 5 mCi/kg nanoparticles caused no gross abnormalities. This multifunctional nanoparticle, therefore, has necrosis imaging and targeted therapeutic effects on residual tumors after thermal ablation of hepatocellular carcinoma, showing potential for clinical application.

Three-dimensional ultrasound fusion imaging in precise needle placement for thermal ablation of hepatocellular carcinoma

Purpose To investigate the value of three-dimensional ultrasound fusion imaging (3DUS FI) technique for guiding needle placement in hepatocellular carcinoma (HCC) thermal ablation. Methods A total of 57 patients with 60 HCCs with 3DUS FI-guided thermal ablation were retrospectively included in the study. 3DUS volume data of liver were acquired preoperatively by freehand scanning with the tumor and predetermined 5 mm ablative margin automatically segmented. Plan of needle placement was made through a predetermined simulated ablation zone to ensure a 5 mm ablative margin with the coverage rate toward tumor and ablative margin. With real-time ultrasound and 3DUS fusion imaging, ablation needles were placed according to the plan. After ablation, the ablative margin was immediately evaluated by contrast-enhanced ultrasound and 3DUS fusion imaging. The rate of adequate ablative margin, complete response (CR), local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) was evaluated. Results According to postoperative contrast-enhanced CT or MR imaging, the complete response rate was 100% (60/60), and 83% of tumors (30/36) achieved adequate ablative margin (>5 mm) three-dimensionally. During the follow-up period of 6.0-42.6 months, LTP occurred in 5 lesions, with 1- and 2-year LTP rates being 7.0% and 9.4%. The 1- and 2-year DFS rates were 76.1% and 65.6%, and 1- and 2-year OS rates were 98.1% and 94.0%. No major complications or ablation-related deaths were observed in any patients. Conclusions Three-dimensional ultrasound fusion imaging technique may improve the needle placement of thermal ablation for HCC and reduce the rate of LTP.

Thermal ablation of hepatocellular carcinoma.

Percutaneous treatment of hepatocellular carcinoma (HCC) by means of thermal ablation (TA) has been introduced in clinical guidelines as a potentially curative treatment for the early stages of the disease since the early 2000s. Due to its safety profile and cost-effectiveness, TA can be offered as a first-line treatment for patients with HCC smaller than 3 cm. Thermal ablative techniques are in fact widely available at many centres worldwide and include radiofrequency (RF) and microwave (MW) ablation, with the latter increasingly applied in clinical practice in the last decade. Pre-clinical studies highlighted, as potential advantages of MW-based ablation, the ability to achieve higher temperatures (>100°C) and larger ablation zones in shorter times, with less susceptibility to blood flow-induced heat sink effects. Despite these advantages, there is no evidence of superior overall survival in patients treated with MW as compared to those treated with RF ablation. Local control has been proven to be superior to MW ablation with a similar complication rate. It is expected that further improvement of TA results in the treatment of HCC will result from the refinement of guidance and monitoring tools and the careful assessment of ablation margins. Thermal ablative treatments may also be performed on nodules larger than 3 cm by applying multiple devices or combining percutaneous and intra-arterial approaches. The role of novel immunotherapy regimens in combination with ablation is also currently under evaluation in clinical trials, with several potential benefits. In this review, indications, technical principles, results, and future prospects of TA for the treatment of HCC will be examined.

Prognostic value of baseline MRI features in patients treated with thermal ablation for hepatocellular carcinoma

PurposeTo investigate prognostic value of baseline MRI features for time-to-recurrence (TTR) and local recurrence in patients with early hepatocellular carcinoma (HCC). MethodBaseline and follow-up images of 88 patients treated with thermal ablation followed by adjuvant sorafenib or matching placebo due to HCC within the phase II prospective randomized trial (SORAMIC) were included. Baseline MRI images were evaluated in terms of atypical enhancement (lack of wash-in or wash-out), lesion diameter, tumor capsule, peritumoral enhancement on arterial phase, intratumoral fat, irregular margin, satellite lesions, and peritumoral hypointensity on hepatobiliary phase. Prognostic value of these features for TTR and local recurrence were assessed with univariable and multivariable Cox proportional hazard models. ResultsRecurrence at any location was diagnosed during follow-up in 30 patients, and the median TTR was 16.4 (95% CI, 15 – NA) months. The presence of more than one lesion (p = 0.028) and peritumoral hypointensity on hepatobiliary phase images (p = 0.012) at baseline were significantly associated with shorter TTR in univariable analysis. AFP > 15 mg/dL (p = 0.084), and history of cirrhosis (p = 0.099) were marginally non-significant. Peritumoral hypointensity on hepatobiliary phase images was the only significant risk factor for recurrence in multivariable analysis (p = 0.003).Local recurrence (adjacent to thermal scar) was diagnosed in eleven (8.3%) out of 132 lesions that underwent thermal ablation. The only significant risk factor for local recurrence was a lesion diameter larger than 3 cm (22.2% vs. 4.5%, p = 0.007). ConclusionsPeritumoral hypointensity on hepatobiliary phase can serve as imaging biomarker to identify increased recurrence risk in patients undergoing thermal ablation for early-stage HCC.

Dynamic Changes of Cytokine Profiles and Their Correlation With Tumor Recurrence Following Thermal Ablation in Hepatocellular Carcinoma.

The 5-year recurrence rate of thermal ablation for hepatocellular carcinoma (HCC) is high, and whether this treatment strategy induces systemic immune response remains elusive. This study aimed to investigate the effects of thermal ablation on HCC patients' cytokine profiles and to explore the correlation of cytokine profiles with tumor recurrence after ablation. A total of 22 HCC patients were included in this prospective study. The levels of 27 cytokines in the peripheral blood of HCC patients were measured before ablation (baseline), week 1, and week 4 after ablation using a Bio-Plex Pro Human Cytokine 27-plex Assay kit. Cytokines showed different dynamic changing trends after ablation treatment. It was found that the level of IL-6 was significantly elevated at week 1 and returned to the baseline level at week 4 after ablation. The level of IL-10 was slightly reduced at week 1 and significantly decreased at week 4. The levels of MCP-1, macrophage inflammatory protein-1β (MIP-1β), and TNF-α were similarly reduced at week 1 and increased at week 4. The levels of IL-17, platelet-derived growth factor-BB (PDGF-BB), and regulated upon activation, normal T cell expressed and secreted (RANTES) showed little to no change at week 1 while an observable increase at week 4. Patients with a high IL-10 level (2.99 pg/ml) at baseline and low levels of TNF-α (20.4 pg/ml), PDGF-BB (107.78 pg/ml), and RANTES (2303.94 pg/ml) at week 4 were at risk of tumor recurrence during 1-year follow-up. The results suggested that thermal ablation activated systemic immune responses by changing the levels of cytokines. The results also demonstrated that measurement of IL-10 at baseline, TNF-α, PDGF-BB, and RANTES at week 4 after ablation might predict the risk of tumor recurrence.

Analysis of Infectious Complications after Thermal Ablation of Hepatocellular Carcinoma and the Impact on Long-Term Survival.

This study aims to complete a detailed record of the clinical characteristics and treatment of HCC patients with post-ablation infection and evaluate the infections on recurrence-free survival (RFS) and overall survival (OS) among patients receiving ultrasound-guided thermal ablation. 3117 patients with liver tumors receiving thermal ablation from January 2010 to December 2021 were analyzed. A total of 49 patients with infectious complications after thermal ablation were selected as the infection group. A total of 49 patients without postoperative infection were randomly selected among those who underwent ablation within three days before or after the treatment date of the infection group as the control group. The clinical characteristics of both groups were analyzed by an independent sample t-test and chi-square test. A log-rank test was performed to compare the RFS and OS data. A multivariate Cox regression model was employed to identify prognostic factors influencing RFS and OS. Subgroup analyses of mild and severe infections were conducted to explore the infection-related situation further. Between mild and severe infection groups, there were statistically significant differences in the infection position (p = 0.043), positive rate of body fluid culture (p = 0.002), proportion of catheter drainage (p = 0.017), use of advanced antibiotics (p = 0.006), and outcome (p = 0.00). The Kaplan-Meier survival analysis revealed that postoperative infection was significantly correlated with tumor recurrence (p = 0.028), and severe infection was significantly associated with overall survival (p = 0.049). The cox model showed that postoperative infection was an independent variable for RFS deterioration (HR = 1.724, 95% CI: 1.038-2.862, p = 0.035). Postoperative infection among patients receiving ultrasound-guided thermal ablation adversely affected tumor progression. In addition, empirical antibiotics and catheterization to reduce pressure inside the lesion should be utilized to minimize symptoms in patients with postoperative infection.

Complications after Thermal Ablation of Hepatocellular Carcinoma and Liver Metastases: Imaging Findings.

Tumour ablation is a strategy of treatment of hepatic tumours in patients with small hepatocellular carcinoma (HCC) (<3 cm) or in patients unfit for surgical resection. Moreover, tumor ablation can be used as an adjuvant therapy or may be used in association with resection in case of patients with poor functional liver disease. These types of treatment usually could be performed percutaneously under image guidance. The most clinically verified and used ablation modalities are Radiofrequency Ablation (RFA) and microwave ablation (MWA). However, despite both of them are considered minimally invasive techniques, they could be related to post-procedural complications. The International Working Group on Image-Guided Tumor and the Society of Interventional Radiology (SIR) identified major and minor post-ablative complications. Major complications, as vascular complications, occur in 2.2% to 3.1% of cases and include all the high risk pathological conditions which could increase the level of care or result in hospital admission or substantially prolonged hospital stay (SIR classifications C–E). Minor complications, as biliary complications, occur in 5% to 8.9% and include self-limiting conditions that are considered to be of low risk for the patient’s outcome. The purpose of this review is to summarise the main pathological ultrasound (US) and Computed Tomography (CT) findings, that may arise after ablative treatment. To simplify the analysis, the pathological pictures are divided according to the site of damage into vascular, biliary and extrahepatic complications.

MO-0222 Propensity score-based comparison of SBRT versus thermal ablation for hepatocellular carcinoma

MO-0222 Propensity score-based comparison of SBRT versus thermal ablation for hepatocellular carcinoma

Outcomes after primary and repeat thermal ablation of hepatocellular carcinoma with or without liver transplantation

ObjectivesThermal ablation (TA) is an established treatment for early HCC. There is a lack of data on the efficacy of repeated TA for recurrent HCC, resulting in uncertainty whether good oncologic outcomes can be obtained without performing orthotopic liver transplantation (OLTx). This study analyses outcomes after TA, with a special focus on repeat TA for recurrent HCC, either as a stand-alone therapy, or in relationship with OLTx.MethodsData from a prospectively registered database on interventions for HCC in a tertiary hepatobiliary centre was completed with follow-up until December 2020. Outcomes studied were rate of recurrence after primary TA and after its repeat interventions, the occurrence of untreatable recurrence, OS and DSS after primary and repeat TA, and complications after TA. In cohorts matched for confounders, OSS and DSS were compared after TA with and without the intention to perform OLTx.ResultsAfter TA, 100 patients (56·8%) developed recurrent HCC, of whom 76 (76·0%) underwent up to four repeat interventions. During follow-up, 76·7% of patients never developed a recurrence unamenable to repeat TA or OLTx. OS was comparable after primary TA and repeat TA. In matched cohorts, OS and DSS were comparable after TA with and without the intention to perform OLTx.ConclusionsWe found TA to be an effective and repeatable therapy for primary and recurrent HCC. Most recurrences can be treated with curative intent. There are patients who do well with TA alone without ever undergoing OLTx.Key Points• Recurrent HCC after primary TA can often be treated effectively with repeat TA. Survival after repeat TA is comparable to primary TA.• In matched cohorts, outcomes after TA with and without subsequent waitlisting for OLTx are comparable.• There are patients who do well for many years with primary and repeat TA alone; some despite multiple recurrences.

Combined transarterial iodized oil injection and computed tomography-guided thermal ablation for hepatocellular carcinoma: utility of the iodized oil retention pattern

PurposeTo investigate whether the iodized oil (Lipiodol, Guerbet Group, Villepinte, France) retention pattern influences the treatment efficacy of combined transarterial Lipiodol injection (TLI) and thermal ablation in patients with hepatocellular carcinoma (HCC).MethodsData of 198 patients (280 HCC lesions), who underwent TLI plus computed tomography (CT)-guided thermal ablation at three separate medical institutions between June 2014 and September 2020, were reviewed and analyzed. The Lipiodol retention pattern was classified as complete or incomplete based on non-enhanced CT at the time of ablation. The primary outcome was local recurrence-free survival (LRFS) for lesions; the secondary outcome was overall survival (OS) for patients. Propensity score matching (PSM) was performed using a caliper width of 0.1 between the two groups. Differences in LRFS and OS between the two groups were compared using the log-rank test.ResultsA total of 133 lesions exhibited a complete Lipiodol retention pattern, while 147 exhibited an incomplete pattern. After PSM analysis of baseline characteristics of the lesions, 121 pairs of lesions were matched. LRFS was significantly longer for lesions exhibiting complete retention than for those exhibiting incomplete retention (P = 0.030). After PSM analysis of patient baseline characteristics, 74 pairs of patients were matched. There was no significant difference in OS between the two groups (P = 0.456).ConclusionLipiodol retention patterns may influence the treatment efficacy of combined TLI and thermal ablation for HCC lesions. However, a survival benefit for the Lipiodol retention pattern among HCC patients was not observed and needs further confirmation.

Utility of Fusion Imaging for Percutaneous Thermal Ablation of Hepatocellular Carcinoma in the Caudate Lobe

The treatment outcomes of ultrasound-guided percutaneous thermal ablation of hepatocellular carcinoma in the caudate lobe with and without fusion imaging (FI) assistance were evaluated and compared. Twenty-six patients with 28 tumors in the FI group and 8 patients with 8 tumors in the non-FI group were included. Although a higher number of tumors measured >20 mm in the FI group, the technique efficacy and local tumor progression were similar between the 2 groups (P > .99 and P = .45, respectively). FI aided in the detection, guidance, and treatment monitoring of thermal ablation for caudate lobe hepatocellular carcinomas, especially for tumors measuring >20 mm.

A novel mono-modality fusion imaging method based on three-dimensional contrast-enhanced ultrasound for the evaluation of ablation margins after microwave ablation of hepatocellular carcinoma.

To investigate the feasibility and accuracy of using preoperative and postoperative three-dimensional contrast-enhanced ultrasound (3D CEUS) fusion imaging in the evaluation of safety margins after thermal ablation of hepatocellular carcinoma (HCC). A total of the 24 patients with HCC who underwent microwave ablation (MWA) between June 2020 and December 2020 were enrolled in this study. All patients received preoperative and postoperative 3D CEUS. The preoperative and postoperative 3D CEUS images were then fused. The success rate and evaluation time were recorded. The ablation margin and whether or not the safety margin was reached were calculated and recorded. If the ablation safety margin was not reached, the residual ablation volume needed to cover the safety margin was calculated automatically. The agreement between contrast-enhanced computed tomography(CECT) and 3D CEUS fusion imaging in the evaluation of ablation margins was explored using the kappa coefficient. The 3D CEUS fusion success rate was 95.8% (23/24), with a mean fusion time of (4.1±1.8) minutes. Twenty-three tumors were completely ablated, and the safety margin was achieved for 9 tumors. The ablation margin of 14 tumors was <5 mm. The mean uncovered safety margin volume was (2.27±2.11) mL, and the mean proportion of the uncovered safety margin to the whole safety margin was 16.8%. According to the results of preoperative and postoperative CECT fusion imaging, the ablation margin of 13 tumors was <5 mm, and the ablation margin of 10 tumors was >5 mm. The 2 methods showed excellent consistency, with a Kappa value of 0.911 (P=0.000012). This study has presented a novel mono-modality fusion imaging method based on CEUS. We demonstrated that 3D CEUS fusion has a short fusion time and a high success rate, as well as good consistency with enhanced CT fusion. Therefore, 3D CEUS fusion is a feasible and accurate tool for evaluating the immediate efficacy of thermal ablation of HCC.

Early Identification of Residual Tumors following Microwave Ablation Using Contrast-Enhanced Ultrasonography in a Rabbit VX2 Liver Cancer Model.

Objective It is difficult to evaluate the ablation effect immediately after thermal ablation of liver cancer by clinical imaging methods, due to the immediate formation of an annular inflammatory reaction band (IRB). This study is aimed at exploring the early identification indicators of the IRB and residual tumor postmicrowave ablation (MVA) using contrast-enhanced ultrasonography (CEUS). Methods MVA was used to inactivate part of the tumor nodules in rabbit VX2 liver cancer models, leading to the coexistence of the IRB with residual tumors. Quantitative analysis of the perfusion parameters of the tumor and ablation zone was performed using CEUS, followed by liver biopsy and VEGFR-2 immunohistochemical staining. Results All rabbits successfully tolerated VX2 tumor inoculation and MVA operation. No statistically significant difference existed between the IRB vs. residual tumors, the IRB vs. junctional areas, and residual tumors postablation vs. VX2 tumors before ablation in regional blood volume, blood velocity, and blood flow estimated by parameters A, k, and A∗k of CEUS quantitative analysis. There was a statistically significant difference between the IRB and normal liver parenchyma in regional blood velocity and blood flow (p = 0.005 and p = 0.023, respectively). Normal liver parenchyma showed nonspecific VEGFR-2 staining, while VX2 tumor before ablation and residual tumor after ablation both showed positive VEGFR-2 staining; the necrosis zone showed negative staining by VEGFR-2 immunohistochemical staining. Conclusion MVA had no significant effect on the residual tumor hemodynamics. The blood flow in the IRB increased significantly as compared to normal liver parenchyma, resembling tumor hemodynamic patterns. CEUS can detect residual tumors immediately postablation only when they protrude from the annular-shaped IRB. In addition, VEGFR-2 targeted CEUS may have a great potential for detecting residual tumor after thermal ablation of hepatocellular carcinoma.

Validation of the Liver Imaging Reporting and Data System Treatment Response Criteria After Thermal Ablation for Hepatocellular Carcinoma

Validation of the Liver Imaging Reporting and Data System Treatment Response Criteria After Thermal Ablation for Hepatocellular Carcinoma

Validation of the Liver Imaging Reporting and Data System Treatment Response Criteria After Thermal Ablation for Hepatocellular Carcinoma.

Single hepatocellular carcinoma (HCC) tumors can be successfully eradicated with thermal ablation (TA). We assessed the validity of the Liver Imaging Reporting and Data System Treatment Response (LR-TR) criteria with a retrospective analysis of a single-center database of patients with small HCC tumors (<3cm in diameter) who underwent both laparoscopic TA and liver transplantation (LT) from 2004 to 2018. Postablation MRIs were assigned LR-TR categories (nonviable, equivocal, and viable) for ablated lesions and Liver Imaging Reporting and Data System (LI-RADS) categories (probable or definite HCC) for untreated lesions. Interpretations were compared with the histopathology of the post-LT explanted liver. There were 45 patients with 81 tumors (59 ablated and 22 untreated; mean size, 2.2cm), and 23 (39%) of the ablated tumors had viable HCC on histopathology. The sensitivity/specificity of LR-TR categories (nonviable/equivocal versus viable) of ablated tumors was 30%/99%, with a positive predictive value (PPV)/negative predictive value (NPV) of 93%/69%. The sensitivity varied with residual tumor size. The sensitivity/specificity of LI-RADS 4 and 5 diagnostic criteria at detecting new HCC was 65%/94%, respectively, with a PPV/NPV of 85%/84%. The interrater reliability (IRR) was high for LR-TR categories (90% agreement, Cohen's ĸ=0.75) and for LI-RADS LR-4 and LR-5 diagnostic categories (91% agreement, Cohen's ĸ=0.80). In patients with HCC <3cm in diameter, LR-TR criteria after TA had high IRR but low sensitivity, suggesting that the LR-TR categories are precise but inaccurate. The low sensitivity may be secondary to TA's disruption in the local blood flow of the tissue, which could affect the arterial enhancement phase on MRI. Additional investigation and new technologies may be necessary to improve imaging after ablation.

Thermal ablation for hepatocellular carcinoma: what's new in 2019.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, but a major proportion of patients are not appropriate candidates for surgical resection or transplantation. For this reason, image-guided tumor ablation using thermal energy for early-stage HCC has become an accepted curative treatment option in all HCC treatment guidelines due to its minimal invasiveness and proven outcomes. In recent years, microwave ablation (MWA) has been gaining popularity worldwide over radiofrequency ablation (RFA) due to its better performance with high temperature heating and lack of heat sink effects. However, more high-level evidence of real survival gain is required before MWA will completely replace RFA. Although cryoablation and irreversible electroporation are promising for safe and effective ablation in the liver, clinical evidence for these remains limited. In addition to specific ablative modalities, therapeutic outcomes can be improved by current technological advances in fusion imaging, contrast-enhanced ultrasound, and post-ablation antiviral therapy. In fact, immuno-ablation has the great potential to maximize therapeutic outcomes after ablation. The purpose of this review is to briefly illustrate the current status of ablation in HCC treatment guidelines and update on recently introduced therapeutic outcomes and new advances in ablation-related techniques.

Intra-Procedural CT/MR-Ultrasound Fusion Imaging Helps to Improve Outcomes of Thermal Ablation for Hepatocellular Carcinoma: Resultsin 502 Nodules.

The aim was to assess the value of intra-procedural CT/MR-ultrasound (CT/MR-US) fusion imaging in the management of thermal ablation for hepatocellular carcinoma (HCC). This retrospective study was approved by the institutional review board. From May 2010 to October 2016, 543 HCC nodules in 440 patients (387 men and 53 women; age range: 25-84 years) that met the Milan Criteria were treated by percutaneous thermal ablation using intra-procedural CT/MR-US fusion imaging. The HCC nodules were divided into subgroups and compared (≤ 3 cm and > 3 cm, or high-risk and low-risk location, or inconspicuous and conspicuous, respectively). Technique efficacy and major complication were calculated. Cumulative local tumor progression (LTP), tumor-free and overall survival rates were estimated with the Kaplan-Meier method. CT/MR-US fusion imaging was successfully registered in 419 patients with 502 nodules. The technique efficacy rate of thermal ablation was 99.4 %. The major complication rate was 1.9 %. The cumulative LTP rates were 3.2 %, 5.6 % and 7.2 % at 1, 3, and 5 years, respectively. There were no significant differences for the comparisons of cumulative LTP rates between different subgroups (P = 0.541, 0.314, 0.329). The cumulative tumor-free survival rates were 74.8 %, 54.0 % and 37.5 % at 1, 3, and 5 years, respectively. The cumulative overall survival rates were 97.8 %, 87.1 % and 81.7 % at 1, 3, and 5years, respectively. Intra-procedural CT/MR-ultrasound fusion imaging is a useful technique for percutaneous liver thermal ablation. It could help to achieve satisfying survival outcomes for HCC patients who meet the Milan Criteria.

Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model.

BackgroundLocal recurrence following thermal ablation of hepatocellular carcinoma (HCC) larger than 2-3 cm remains a challenging clinical problem. Prior studies suggest that phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)-dependent protein kinase B (AKT) signaling mediates HCC cell survival caused by moderate heat stress in vitro, but these findings need in vivo validation.PurposeTo test the hypothesis that neoadjuvant inhibition of PI3K/mTOR/AKT signaling reduces HCC tumor growth in vivo after laser ablation and to evaluate the effects of moderate heat stress on molecular signaling and cellular function in HCC cells in vitro.Materials and MethodsHCC tumor-bearing mice were randomized to neoadjuvant PI3K/mTOR inhibitor (BEZ235) or control groups followed by an intentional partial laser ablation or sham ablation; there were at least nine mice per group. Postablation tumor growth was monitored up to 7 days. Tumor volumes were compared for drug or ablation groups by using two-way analysis of variance. N1S1 HCC cells pretreated with BEZ235 or control and subjected to moderate heat stress (45°C for 10 minutes) or control (37°C for 10 minutes) were analyzed by using mass spectrometry. Protein interaction networks were derived from protein expression analysis software, and cellular function activation state (Z-score) and fold-change in AKT phosphorylation were calculated.ResultsThere was a 37%-75% reduction in HCC tumor volume by day 7 after ablation in the BEZ235 plus ablation group (713 mm3 ± 417) compared with vehicle plus sham (1559 mm3 ± 552), vehicle plus ablation (1041 mm3 ± 591), and BEZ235 plus sham (1108 mm3 ± 523) groups (P < .001, P = .04, and P = .005, respectively). PI3K/mTOR inhibition prevented moderate heat stress-induced AKT signaling (Z-score, -0.2; P < .001) and isoform-specific AKT phosphorylation compared with the vehicle plus heat stress group. PI3K/mTOR inhibition prevented moderate heat stress-induced global effects on HCC molecular signaling and cellular function, including decreased cell survival, growth, and proliferation (Z-score, -0.3 to -3.2; P < .001) and increased apoptosis and cell death (Z-score, 0.4-1.1; P < .001).ConclusionModerate heat stress induces PI3K/mTOR/AKT-dependent global effects on hepatocellular carcinoma (HCC) cell survival, function, and death. Neoadjuvant PI3K/mTOR/AKT inhibition reduces postablation HCC tumor growth.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by White in this issue.

Intraprocedural computed tomography/magnetic resonance-contrast-enhanced ultrasound fusion imaging improved thermal ablation effect of hepatocellular carcinoma: Comparison with conventional ultrasound.

To retrospectively compare the treatment effect of intraprocedural computed tomography/magnetic resonance-contrast-enhanced ultrasound (CT/MR-CEUS) fusion imaging (FI) with that of conventional ultrasound (US) in the guidance and assessment of thermal ablation of hepatocellular carcinoma (HCC). The FI group (112 patients with 129 HCC) was treated between April 2010 and December 2012, whereas the US group (83 patients with 90 HCC) was treated between January 2008 and March 2010. Either CT/MR-CEUS FI or US was used to guide puncture, provide immediate assessment, and guide supplementary ablation. Technical efficacy, cumulative local tumor progression rate (LTP), recurrence-free survival (RFS), and overall survival (OS) were evaluated and compared during follow-up. Technical success rate of CT/MR-CEUS FI was also recorded. Technical efficacy was significantly higher in the FI group than in the US group (100% vs. 86.7%, P < 0.001). The 1-, 2-, 3-, 4-, 5-, and 6-year cumulative LTP rates in the FI group were significantly lower than in the US group (3.8%, 4.9%, 6.0%, 6.0%, 7.2%, and 7.2% vs. 16.9%, 20.1%, 25%, 25%, 25%, and 25%, respectively; P < 0.001); RFS and OS were significantly higher in the FI group than in the US group (P = 0.027 and P = 0.049, respectively). The technical success rate of FI was 85.3%. Intraprocedural CT/MR-CEUS FI improved the treatment effect of thermal ablation of HCC by immediately assessing treatment response and guiding supplementary ablation relative to those resulting from the use of conventional US.

Role of CD200/CD200R Signaling Pathway in Regulation of CD4+T Cell Subsets During Thermal Ablation of Hepatocellular Carcinoma.

BackgroundIn this study, we assessed the role of CD200 and CD200 receptor (CD200R) in regulating CD4+T cell subsets and assessed the therapeutic efficacy of thermal ablation for liver hepatocellular carcinoma (HCC) in rats.Material/MethodsSeventy-eight male C57BL/6 rats were randomly divided into 7 groups: a control group, a model group, a CD200FC group, an anti-CD200R1 mAb group, a thermal ablation group, a thermal ablation+CD200 FC group, and a thermal ablation+anti-CD200R1 mAb group. The levels of CD200, CD200R1, Th1, Th17, and Treg in peripheral blood were detected by flow cytometry. Immunohistochemistry was used to detect CD200, CD200R1, IFN-γ, IL-17, Foxp3 protein expression in tumor tissues.ResultsThe levels of CD200, CD200R1, Th17, and Treg were significantly increased after CD200FC treatment (p<0.05). After treatment with anti-CD200R1 mAb, the levels of CD200, CD200R1, Th17, and Treg decreased and Th1 increased. Compared with the control group, the expression of CD200, CD200R1, IL-17, and Foxp3 in the model group increased significantly, and the expression of IFN-γ decreased significantly (p<0.05). The expression of CD200, CD200R1, IL-17, and Foxp3 was significantly reduced by adding anti-CD200R1 mAb, and the expression of IFN-γ was increased (p<0.05). After the thermal ablation treatment, the proteins continued to decrease and the expression of IFN-γ continued to increase.ConclusionsThe CD200/CD200R pathway participates in HCC tumor growth and the expression of CD4+T cell subsets in cancer tissues. Furthermore, thermal ablation treatment inhibited cancer recurrence.