Ablation Of Hepatocellular Carcinoma Research Articles

Dendritic cell-cytokine killer combined with microwave ablation reduced recurrence for hepatocellular carcinoma compared to ablation alone.

Several international practice guidelines have recommended local ablation as the first-line treatment for early-stage hepatocellular carcinoma (HCC). This study aims to investigate the synergetic anti-tumor impact of dendritic cell-cytokine killer (DC-CIK) combined with microwave ablation (MWA) for HCC. This retrospective study included 1,141 patients from the American Joint Committee on Cancer stage I-II HCC, who were treated with therapeutic MWA. The immunotherapy group encompassing 40 patients received additional immunotherapy with DC-CIK, whereas the control group consisting of 1,101 patients was treated with MWA alone. Propensity score matching (PSM) with ratio of 1:3 was employed to balance selection bias. The oncological outcome and immune status were measured after combination therapy. The immunotherapy group patients exhibited significant longer disease-free survival (DFS, primary HCC: p= 0.036; recurrent HCC: p= 0.026). For patients with primary HCC, the recurrence frequency was reduced (p= 0.002), and recurrence interval (19 months vs. 9 months, p< 0.001) was prolonged in the immunotherapy group. Subgroup analysis revealed that patients ⩽ 60 years old, moderately-differentiated HCC, or co-infected with Hepatitis B Virus (HBV) had a significant benefit over DFS in the immunotherapy group. After combination therapy, the serum CD3+ (p= 0.049), CD8/CD28+ (p= 0.045) were elevated. Combination therapy with DC-CIK and MWA can significantly reduce the recurrence and prolong DFS, especially for patients ⩽ 60 years old or with moderately-differentiated HCC or co-infected with HBV.

Macrophage hitchhiking for systematic suppression in postablative multifocal hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), particularly the multifocal HCC, features aggressive invasion and dismal prognosis. Locoregional treatments were often refractory to eliminate tumor tissue, resulting in residual tumor cells persisting and subsequent progression. Owing to problematic delivery to the tumor tissue, systemic therapies, such as lenvatinib (LEN) therapy, show limited clinical benefit in preventing residual tumor progression. Therefore, more advanced strategies for postablative multifocal HCC are urgently needed. Motivated by the chemotaxis in tumor penetration of macrophages, we report a strategy named microinvasive ablation-guided macrophage hitchhiking (MAMH) for the targeted therapy toward HCC. In this study, the strategy leverages the natural inflammatory gradient induced by ablation to guide LEN-loaded macrophages toward tumor targeting, which increased by ~10-fold the delivery efficiency of LEN in postablative HCC in vivo. MAMH has demonstrated significant antitumor activity in various HCC models, including the hydrodynamic tail vein injection multifocal HCC mouse model and the orthotopic xenograft HCC rabbit model, systematically inhibiting residual tumor progression after ablation and prolonging the median survival of tumor-bearing mice. The potential antitumor mechanism was explored using techniques such as flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemistry. We found that the strategy significantly suppressed tumor cell proliferation and neovascularization, and such enhanced delivery of LEN stimulated systemic immune responses and induced durable immune memory. The macrophage hitchhiking strategy demonstrates exceptional therapeutic efficacy and biosafety across various species, offering promising prospects for clinical translation in controlling residual tumor progression and improving outcomes following HCC ablation.

Lusutrombopag Reduces the Risk of Hemoperitoneum Caused by Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma Compared with Platelet Transfusion.

Patients with liver cirrhosis develop thrombocytopenia and an increased risk of bleeding events after invasive procedures. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count. This study assessed whether lusutrombopag reduces the risk of hemoperitoneum following percutaneous radiofrequency ablation for hepatocellular carcinoma, compared with platelet transfusion. Participants in the present study comprised patients with severe thrombocytopenia (platelet count < 50,000/μL) enrolled between November 2012 and March 2020, excluding patients with idiopathic thrombocytopenia or anticoagulant use. Hemoperitoneum rate, hemostasis rate, hemoglobin reduction rate, rate of achieving a platelet count  50,000/μL, and increases in platelet count and factors contributing to hemoperitoneum were retrospectively analyzed. This study enrolled 41 patients, comprising 18 patients administered lusutrombopag and 23 patients who received platelet transfusion. The major hemoperitoneum rate after RFA was tend to lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%). All of the major hemoperitoneum was observed in the platelet transfusion group. Hemoglobin reduction rate was lower in the lusutrombopag group (-0.17%) than in the platelet transfusion group (6.79%, P = 0.013). Hemostasis rate was lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%, P = 0.045). The rate of achievement of a platelet counts  50,000/μL the day after RFA was higher in the lusutrombopag group (100%) than in the platelet transfusion group (60.9%, P = 0.005). Lusutrombopag may be able to perform RFA more safely with respect to the hemoperitoneum caused by percutaneous radiofrequency ablation compared with platelet transfusion.

Technique efficacy and complications after ablation as first surgical intervention for hepatocellular carcinoma: A nationwide database study

IntroductionDespite limited evidence, technique efficacy and complications may be important short-term outcomes after ablation for hepatocellular carcinoma (HCC). We aimed to report these outcomes after ablation as the first surgical intervention for HCC. MethodsThis nationwide cohort study was based on data from the Danish Liver and Biliary Duct Cancer Database and medical records. Variables associated with outcomes were investigated using logistic regression. ResultsFrom 2013 to 2023, 433 patients were included of which 79% were male, 73% had one tumor, and 90% had cirrhosis. Complete ablation was achieved after percutaneous, laparoscopic, and open approach in 84%, 100%, and 96% of the procedures, respectively. Most patients did not experience complications (76%). Open ablation compared with percutaneous was associated with higher risk of complications in multivariable adjusted analysis (Clavien-Dindo grade 2–5 (odds ratio 5.34, 95% confidence interval [2.36; 12.08]) and 3B-5 (5.70, [2.03; 16.01]), and lower risk of incomplete ablation (0.19 [0.05; 0.65]). Number of tumors ≥3 was associated with a higher risk of incomplete ablation (3.88, [1.45; 10.41]). Tumor diameter ≥3 cm was associated with increased risk of complications grade 2–5 (2.84, [1.29; 6.26]) and 3B-5 (4.44, [1.62; 12.13]). Performance status ≥2 was associated with risk of complications grade 3B-5 (5.98, [1.58; 22.69]). Tumor diameter was not associated with technique efficacy. ConclusionOpen ablation had a higher rate of complete ablation compared with percutaneous but was associated with a higher risk of complications. Tumor diameter ≥3 cm and performance status ≥2 were associated with a higher risk of complications.

Upfront multi-bipolar radiofrequency ablation for HCC in transplant-eligible cirrhotic patients with salvage transplantation in case of recurrence.

We aim to assess the long-term outcomes of percutaneous multi-bipolar radiofrequency (mbpRFA) as the first treatment for hepatocellular carcinoma (HCC) in transplant-eligible cirrhotic patients, followed by salvage transplantation for intrahepatic distant tumour recurrence or liver failure. We included transplant-eligible patients with cirrhosis and a first diagnosis of HCC within Milan criteria treated by upfront mbp RFA. Transplantability was defined by age <70 years, social support, absence of significant comorbidities, no active alcohol use and no recent extrahepatic cancer. Baseline variables were correlated with outcomes using the Kaplan-Meier and Cox models. Among 435 patients with HCC, 172 were considered as transplantable with HCCs >2 cm (53%), uninodular (87%) and AFP >100 ng/mL (13%). Median overall survival was 87 months, with 75% of patients alive at 3 years, 61% at 5 years and 43% at 10 years. Age (p = .003) and MELD>10 (p = .01) were associated with the risk of death. Recurrence occurred in 118 patients within Milan criteria in 81% of cases. Local recurrence was observed in 24.5% of cases at 10 years and distant recurrence rates were observed in 69% at 10 years. After local recurrence, 69% of patients were still alive at 10 years. At the first tumour recurrence, 75 patients (65%) were considered transplantable. Forty-one patients underwent transplantation, mainly for distant intrahepatic tumour recurrence. The overall 5-year survival post-transplantation was 72%, with a tumour recurrence of 2.4%. Upfront multi-bipolar RFA for a first diagnosis of early HCC on cirrhosis coupled with salvage liver transplantation had a favourable intention-to-treat long-term prognosis, allowing for spare grafts.

Transarterial chemoembolization combined with radiofrequency ablation for medium and large hepatocellular carcinoma: insufficient ablation is associated with intrahepatic distant metastasis and extrahepatic metastasis.

To compare the prognosis of complete and insufficient ablation of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treating medium and large hepatocellular carcinoma (HCC) and to explore the differences in recurrence patterns between the two groups. Patients´ medical records and imaging data of patients with confirmed HCC from January 2014 to January 2022 were collected. These patients were divided into 2 groups: complete ablation (n=172) and insufficient ablation (n=171). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier curve and the log-rank test was used to compared. Fisher's exact test was used to compare recurrence patterns between the two groups. The median OS time was 72.8 months (95%CI:69.5-76.1) and 62.0 months (95%CI: 55.3-68.7) in the complete and insufficient ablation groups, respectively. The median PFS time in the complete ablation group was 67.8 months (95% CI: 65.2-70.4) and 38.6 months (95%CI: 29.8-47.4) in the insufficient ablation group. The OS and PFS rates of the complete ablation group were significantly better than those of the insufficient ablation group (P<0.001). In the complete ablation group, 25(41%) patients experienced local tumor progression(LTP), 36(59%) experienced intrahepatic distant progression(IDP), and 0(0%) experienced extrahepatic progression (EP). In the insufficient ablation group, 51 (32.1%) patients experienced LTP, 96 (60.4%) experienced IDP, and 12 (7.5%) experienced EP. The progression patterns of the two groups were statistically significant (P=0.039). Insufficient ablation indicates a poor survival outcome of TACE combined with RFA for medium and large HCC and can promote intrahepatic distant and extrahepatic metastasis.

Radiofrequency ablation versus microwave ablation for hepatocellular carcinoma with cirrhosis: a propensity score analysis.

Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most frequently used percutaneous ablation techniques for the treatment of liver cancer. The aim of our study was to identify the ablation method that had a better long-term prognosis for patients with cirrhotic hepatocellular carcinoma (HCC). This retrospective study consisted of HCC patients with cirrhosis who underwent RFA and MWA between January 2014 to December 2021 at Beijing You'an Hospital. Patients were divided into two groups according to the therapeutic approaches: the RFA group and the MWA group. The prognosis was compared before and after 1:1 propensity score matching (PSM). A total of 800 HCC patients with cirrhosis who received interventional treatment from January 2014 to December 2021 were prospectively enrolled. After PSM, there were 268 patients in each of the RFA and MWA groups. The statistically significant differences in recurrence-free survival (RFS) and overall survival (OS) between RFA and MWA groups can be observed, both before and after PSM. Besides, 1-, 3-year RFS, and 5-year OS rates were higher in those the RFA group than in the MWA group. Age, tumor size, gamma glutamyl transferase (GGT), and hepatitis B surface antigen (HBsAg) were independent risk factors for RFS. Child-Pugh, lymphocyte (Lym), GGT, and treatment modality were independent risk factors for OS. For patients with HCC associated with cirrhosis, RFA can provide a better prognosis than MWA, with lower recurrence and mortality rate.

Current perspectives on radiotherapy in hepatocellular carcinoma management: a comprehensive review.

This review examines the transformative role of external beam radiotherapy (EBRT) in managing hepatocellular carcinoma (HCC), spotlighting the progression from traditional EBRT techniques to advanced modalities like intensity-modulated radiotherapy (RT), stereotactic body RT (SBRT), and innovative particle therapy, including proton beam therapy and carbon ion RT. These advancements have significantly improved the precision and efficacy of RT, marking a paradigm shift in the multimodal management of HCC, particularly in addressing complex cases and enhancing local tumor control. The review underscores the synergistic potential of integrating RT with other treatments like transarterial chemoembolization, systemic therapies such as sorafenib, and emerging immunotherapies, illustrating enhanced survival and disease control outcomes. The efficacy of RT is addressed for challenging conditions, including advanced HCC with macrovascular invasion, and RT modalities, like SBRT, are compared against traditional treatments like radiofrequency ablation for early-stage HCC. Additionally, the review accentuates the encouraging outcomes of particle therapy in enhancing local control and survival rates, minimizing treatment-related toxicity, and advocating for continued research and clinical trials. In conclusion, the integration of RT into multimodal HCC treatment strategies, coupled with the emergence of particle therapy, is crucial for advancing oncologic management, emphasizing the need for relentless innovation and personalized treatment approaches.

Hug sign in intraprocedural cone-beam-CT to predict short-term response to combined treatment of hepatocellular carcinoma

ObjectivesCombined treatment of ablation and chemoembolization for hepatocellular carcinoma represents a promising therapy to increase treatment efficacy and improve patient survival. The “hug sign” is a recently introduced radiological sign consisting in deposition of beads/contrast agent during transarterial chemoembolization in the hyperemic area surrounding the post-ablation volume, seen during intraprocedural unenhanced cone-beam CT, that may indicate intraprocedural success. Aim of our retrospective study was to analyze the usefulness of the “hug sign” at the intraprocedural unenhanced cone-beam CT as an early predictor of response to combined treatment, based on the hug sign angle.Materials and methodsBetween January 2017 and September 2021 all patients with hepatocellular carcinoma which underwent a combined treatment of thermal ablation followed by chemoembolization were enrolled. All treated patients underwent immediate post-procedural unenhanced cone-beam CT to evaluate the deposition of contrast agent, lipiodol or radiopaque beads and to assess the percentage of coverage of the ablated area with the contrast agent (hug sign angle). Patients with missing pre-procedural, intra-procedural and/or post-procedural data/imaging, or with poor-quality post-procedural cone-beam CT images were excluded.Results128 patients (mean age, 69.3 years ± 1.1 [standard deviation]; 87 men) were evaluated. Our study evidenced that 84.4% (81/85) of patients with a hug sign angle of 360° had no residual tumor at the first 1-/3-months follow-up examination. A hug sign angle of 360° also showed to be an independent protective factor against residual tumor at multivariate analysis.ConclusionUnenhanced cone-beam CT performed at the end of a combined treatment with ablation plus chemoembolization can effectively predict an early treatment response on radiological images, when a hug sign angle of 360° was detected.

Spatial distribution pattern of local tumor progression analysis after microwave ablation of hepatocellular carcinoma based on three-dimensional magnetic resonance imaging

Objective: To investigate the spatial distribution pattern of local tumor progression (LTP) for hepatocellular carcinoma (HCC) ≤5 cm after microwave ablation. Methods: A retrospective analysis was performed on 169 HCCs with matched MRI before and after ablation from December 2009 to December 2019. A tumor MRI was reconstructed using three-dimensional visualization technology. LTP was classified as contact or non-contact, early or late stage, according to whether LTP was in contact with the edge of the ablation zone and the occurrence time (24 months). The tumor-surrounded area was divided into eight quadrants by using the eight-quadrant map method. An analysis was conducted on the spatial correlation between the quadrant where the ablative margin (AM) safety boundary was located and the quadrant where different types of LTP occurred. The t-test, or rank-sum test, was used for the measurement data. 2-test for count data was used to compare the difference between the two groups. Results: The AM quadrant had a distribution of 54.4% LTP, 64.2% early LTP stage, and 69.1% contact LTP, suggesting this quadrant was much more concentrated than the other quadrants (P < 0.001). Additionally, the AM quadrant had only 15.2% of non-contact type LTP and 17.1% of late LTP, which was not significantly different from the average distribution probability of 12.5% (100/8%) among the eight quadrants (P = 0.667, 0.743). 46.6% of early contact type LTP was located at the ablation needle tip, 25.2% at the body, and 28.1% at the caudal, while the location distribution probabilities of non-early contact LTP were 34.8%, 31.8%, and 33.3%, respectively. Conclusion: LTP mostly occurs in areas where the ablation safety boundary is the shortest. However, non-contact LTP and late LTP stages exhibit the feature of uniform distribution. Thus, this type of LPT may result from an inadequate non-ablation safety boundary.

Radiofrequency ablation of hepatocellular carcinoma guided by real-time physics-based ablation simulation: a prospective study

Objectives To assess the safety and efficacy of radiofrequency ablation (RFA) guidance software that incorporated patient-specific physics-based simulation of each ablation volume. Materials and methods Patients referred for curative ablation of hepatocellular carcinoma (HCC) of 2–5 cm diameter were prospectively enrolled. RFA was performed under general anesthesia. Procedure planning and intraprocedural modifications were guided by computer simulation of each ablation. The segmented target (tumor with 5 mm margin) was registered to and superimposed on subsequent 3D multiplanar images. The applied RF energy was used to calculate a simulated ablation volume which was displayed relative to the electrode and segmented target, to depict any untreated target tissue. After each additional ablation, the software updated the accumulated simulated ablation volume in relation to the target. The primary endpoints were technical efficacy and rate of local tumor progression (LTP). Results Sixty-eight tumors were ablated during 57 procedures in 52 patients (68.3 ± 9.2 years old, 78.8% male); 15 (26.3%) had multiple lesions and 23 (39.1%) had prior HCC treatment. The mean tumor diameter was 2.73 (±0.64) cm. The intraprocedural simulation directed additional overlapping ablations in 75.9% of tumors. Technical success and efficacy were 100% at 3-month contrast enhanced CT or MRI follow-up after the single treatment session. Cumulative incidence function estimates for 1- and 2-year LTP were 3.9% and 20.2%, respectively. Conclusion This prospective study found computer-assisted guidance that simulated each ablation was both safe and efficacious. The low rate of LTP was similar to studies that employed stereotactic guidance and ablation confirmation, without requiring a second contrast enhanced study.

Microwave Ablation in the Thermal Treatment of Hepactocellular Carcinoma: Case Report

Hepatocellular carcinoma (HCC) stands as one of the most prevalent malignant tumors [1], and is the cause of over one million deaths annually worldwide [2]. While surgical resection remains the preferred treatment for early-stage hepatocellular carcinoma (HCC) in well-compensated cirrhosis patients, thermal ablation techniques offer a credible non-surgical option. Their minimal invasiveness, high tolerability, safety, established efficacy in local disease control, virtually unlimited repeatability, and cost-effectiveness render them valuable alternatives. Microwave ablation (MWA) of HCC appears to be a safe and effective treatment. Here we report a case of 53-year-old male, followed for hepatitis C complicated by compensated cirrhosis, During the follow up, Laboratory tests found liver function tests were eleveted, α-fetoprotein (AFP) was normal. Abdominal ultrasound showed a focal hepatic mass straddling segments VI and VIII, rounded, well-limited, with heterogeneous hyperechoic echostructure, and splenomegaly. Contrast-enhanced abdominal computed tomography showed a chronic liver desease with a focal lesion straddling segments VI and VIII, oval, tissue-like, hypodense in the center, measuring 50x41mm, with signs of early arterial enhancement consistent with HCC characteristics and signs of portal hypertension and a multicystic kidney. Hepatic MRI revealed a chronic liver disease straddling segments VII and VIII of a hepatic lesion measuring 23x 22mm classified as Li-RADS 4 with signs of portal hypertension and splenomegaly. Based on these results, the patient was diagnosed as HCC with well compensated cirrhosis, and in view of the fact that he had only a single lesion and was in functional grade A of Child-Pugh classification and staged as BCLC-A in the Barcelona Clinic Liver Cancer (BCLC) staging system, the patient benefited from microwave ablation for his HCC, with good clinical, biological and radiological evolution. Microwave Ablation (MWA) emerges ..........

Laparoscopic liver resection is superior to radiofrequency ablation for small hepatocellular carcinoma: a systematic review and meta-analysis of propensity score-matched studies.

The approach in small hepatocellular carcinoma (HCC) is controversial, no prospective randomized trials to compare ablative or surgical approaches. We compared the surgical and oncological outcomes after laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) in small HCC patients based on matched cohort studies that performed propensity score matching (PSM). We systemically searched the PubMed, Cochrane Library, Embase, Web of Science, and the Chinese BioMedical Literature (CBM) databases. All published propensity score-matched studies that compared LH and RFA for small HCC were included in this study. Eight studies with a total of 1273 small HCC cases were included. The results of the meta-analysis revealed that there was no significant difference in the 1- year overall survival (OS) rate between the two groups, whereas the LH group had significantly higher 3- year overall survival rate (RR = 1.14, 95% CI 1.08-1.20, p < 0.00001) as well as 1- and 3-year disease-free survival (DFS) rates (RR = 1.31, 95% CI 1.22-1.42, p < 0.00001; RR = 1.66, 95% CI 1.46-1.90, p < 0.00001) than the RFA group. Meanwhile, the local recurrence rate and intrahepatic distant recurrence rate were significantly lower in the LH group than in the RFA group (RR = 0.29, 95% CI 0.20-0.42, p < 0.00001; RR = 0.67, 95% CI 0.49-0.92, p = 0.01). In comparison with the LH group, the RFA group had a lower incidence of overall and major postoperative complications (RR = 1.81, 95% CI 1.47-2.24, p < 0.00001; RR = 2.76, 95% CI 1.48-5.12, p = 0.001), but there was no significant difference in postoperative mortality between the two groups. In addition, further comparison of single postoperative complications showed that the incidence of ascites was lower in the RFA group than in the LH group (RR = 3.62, 95% CI 1.64-7.96, p = 0.001), whereas there was no significant difference in the incidence of postoperative bleeding, abdominal infection and bile leakage between the two groups (RR = 3.50, 95% CI 0.74-16.61, p = 0.11; RR = 5.00, 95% CI 0.59-42.23, p = 0.14; RR = 4.00, 95% CI 0.45-35.23, p = 0.21). Besides, the hospital stay was shorter in the RFA group than in the LH group (MD = 4.29, 95% CI 2.06-6.53, p = 0.0002). Our meta-analysis demonstrated that in comparison with RFA in the treatment of small HCC, LH provided superior long-term OS and DFS together with lower rates of local and intrahepatic distant recurrence after surgery. However, RFA was associated with better short-term outcomes.

Long-term survival analysis of ultrasound-guided percutaneous microwave ablation for hepatocellular carcinoma conforming to the Milan criteria: primary versus recurrent HCC

Background This study compared long-term outcomes between patients with initial hepatocellular carcinoma (IHCC) and those with recurrent HCC (RHCC) treated with microwave ablation (MWA). Methods This retrospective study included 425 patients with HCCs (294 IHCCs and 131 RHCCs) within the Milan criteria who were treated with ultrasound-guided percutaneous MWA between January 2008 and November 2021. All patients with RHCC had previously undergone MWA for initial HCC. Overall survival (OS) and recurrence-free survival (RFS) rates were compared between the IHCC and RHCC groups before and after propensity score matching (PSM). Results Before matching, the 1-, 3-, 5-, and 10-year OS rates in the IHCC group were 95.9%, 78.5%, 60.2%, and 42.5%, respectively, which were significantly higher than those in the RHCC group (93.8%, 70.0%, 42.0%, and 6.6%, respectively). This difference remained significant after PSM. However, subgroup analyses suggested that there were no significant differences in OS rates between IHCC and RHCC in patients with solitary HCC ≤3.0 cm, AFP ≤200 ng/mL, ablative margins ≥0.5 cm, or Albumin-Bilirubin (ALBI) grade 1. RFS was significantly higher in IHCC than in RHCC before and after PSM, as well as in subgroup analyses. ALBI grade (hazard ratio (HR), 2.38; 95% CI: 1.46–3.86; p < 0.001), serum AFP level (HR, 2.07; 95% CI: 1.19–3.62; p = 0.010) and ablative margins (HR, 0.18; 95% CI: 0.06-0.59; p = 0.005) were independent prognostic factors for OS of RHCC. Serum AFP(HR, 1.29; 95% CI: 1.02–1.63, p = 0.036) level was the only factor associated with RFS in RHCC. Conclusions MWA yielded comparable OS in IHCC and RHCC patients with solitary HCC ≤3.0 cm, AFP ≤200 ng/mL, ablative margins ≥0.5 cm, or ALBI grade 1.

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.

Hepatitis C Virus-Related One-Year Hepatocellular Carcinoma Recurrence After Directly Acting Antivirals: A Randomized Controlled Trial.

Available data on hepatocellular carcinoma (HCC) recurrence after direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV) are conflicting. No randomized trials were done. This study aims to compare the 1-year HCC recurrence rates in patients who received DAAs after tumor ablation versus those who postponed HCV treatment for 1year. Included patients were randomized after complete HCC ablation into two groups: a postponed DAAs group for whom DAAs initiation was postponed for 12months and a DAAs group who were given sofosbuvir/velpatasvir. Patients were followed for 1year. Eighty-four HCV patients with a mean age of 56.35 ± 8.12years were included; 78.57% of them were males. The number of lesions per patient ranged from 1 to 3 lesions, and the size of the largest lesion ranged from 1.5 to 5cm. There were no statistically significant differences between both groups regarding baseline characteristics. In the DAAs group (43 patients), 11 patients had HCC recurrence, while 25 patients in the postponed DAAs group (41 patients) had HCC recurrence. Using Kaplan-Meier analysis, the 1-year recurrence-free survival (RFS) was significantly higher in the DAAs group (72.2% vs. 38%, P = 0.001). On multivariate analysis, both higher albumin levels (HR 0.147, 95% CI 0.066-0.329) and receiving DAAs (HR 0.358, 95% CI 0.176-0.730) 1year after ablation were associated with significantly lower recurrence. Direct-acting antiviral usage after complete hepatocellular carcinoma ablation significantly decreases the 1-year HCC recurrence rates, but the risk of recurrence is still not eliminated.The study registration number on clinicaltrials.gov : NCT04653818 (initial release on 28/11/2020).

Evaluation of the effectiveness of surgical resection and ablation for the treatment of early-stage hepatocellular carcinoma: A retrospective cohort study.

The optimal treatment strategy for early-stage hepatocellular carcinoma (HCC) remains controversial, specifically in regard to surgical resection (SR) and ablation. The aim of this study was to investigate the impact of SR and ablation on recurrence and prognosis in early-stage HCC patients, to optimize treatment strategies and improve long-term survival. A retrospective analysis was conducted on 801 patients diagnosed with Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC and treated with SR or ablation between January 2015 and December 2019. The effectiveness and complications of both treatments were analyzed, and patients were followed up to measure recurrence and survival. Propensity score matching (PSM) was employed to increase comparability between the two groups. The Kaplan-Meier method was used to analyze recurrence and survival, and a Cox risk proportional hazard model was used to identify risk factors that affect recurrence and surviva. Before PSM, the overall survival (OS) rates were similar in both groups, with recurrence-free survival (RFS) rates better in the SR group than in the ablation group. After PSM, there was no significant difference in OS between the two groups. However, the RFS rates were significantly better in the SR group than in the ablation group. The ablation group exhibited superior outcomes compared to the SR group, with shorter treatment times, reduced bleeding, shorter hospital stays, and lower hospital costs. Concerning the location of the HCC within the liver, comparable efficacy was observed between SR and ablation for disease located in the noncentral region or left lobe. However, for HCCs located in the central region or right lobe of the liver, SR was more effective than ablation. This study revealed no significant difference in OS between SR and ablation for early-stage HCC, with SR providing better RFS and ablation demonstrating better safety profiles and lower hospital costs. These findings offer valuable insights for clinicians in determining optimal treatment strategies for early-stage HCC patients, particularly in terms of balancing efficacy, safety, and cost considerations.

Can Machine Learning Predict Favorable Outcome After Radiofrequency Ablation of Hepatocellular Carcinoma?

The standard practice for limited-stage hepatocellular carcinoma (HCC) is the resection or the use of local ablative techniques, such as radiofrequency ablation (RFA). The outcome after RFA depends on a complex interaction between the patient's general condition, hepatic function, and disease stage. In this study, we aimed to explore using a machine learning model to predict the response. A retrospective study was conducted for patients with RFA for a localized HCC between 2018 and 2022. The collected clinical, radiologic, and laboratory data were explored using Python and XGBoost. They were split into a training set (70%) and a validation set (30%). The primary end point of this study was to predict the probability of achieving favorable outcomes 12 months after RFA. Favorable outcomes were defined as the patient was alive and HCC was controlled. One hundred and eleven patients were eligible for the study. Males were 78 (70.3%) with a median age of 57 (range of 43-81) years. Favorable outcome was seen in 62 (55.9%) of the patients. The 1-year survival rate and control rate were 94.6%, and 61.3%, respectively. The final model harbored an accuracy and an AUC of 90.6% and 0.95, respectively, for the training set, while they were 78.9% and 0.80, respectively, for the validation set. Machine learning can be a predictive tool for the outcome after RFA in patients with HCC. Further validation by a larger study is necessary.

Integrating Navigation-Assisted Ablation in the Locoregional Treatment of Hepatocellular Carcinoma

With the increasing prevalence of hepatocellular carcinoma (HCC), ablative therapy is a critical treatment option to achieve a cancer-free state. The anatomic location of the tumor can be a challenge, and select hepatic locations of a tumor require laparoscopic-assisted strategies to safely reach and treat the lesion. To assess the association of real-time ultrasonography-augmented navigation for HCC ablation with patient survival, operative time, and rate of incomplete ablations. This retrospective case-control study was conducted among a prospectively collected database of more than 750 patients with HCC who were treated with ablation therapy with and without the use of navigation at a single quaternary medical center from June 2011 to January 2021. Data were analyzed from October 2022 through June 2023. Real-time ultrasonography-augmented navigation. The primary outcome was rate of incomplete ablations in patients undergoing HCC ablation with vs without navigation. Secondary outcomes included overall survival (OS), progression-free survival (PFS), and operative time. The analytic cohort included 467 patients (mean [SD] age, 62.4 [7.8] years; 355 male [76.0%]; 21 Hispanic [4.5%], 67 non-Hispanic Black [14.5%], and 347 Non-Hispanic White [75.0%] among 463 patients with race and ethnicity data). The most common etiology of liver disease was hepatitis C infection (187 patients with etiology data [40.0%]), and 348 of 458 patients with TMN staging data (76.0%) had TNM stage 1 disease. There were 187 individuals treated with navigation and 280 individuals treated without navigation. Patients who underwent navigation-assisted ablation were more likely to have stage 2 disease based on TNM staging (62 of 183 patients [33.9%] vs 47 of 275 patients [17.1%] with TMN data; P < .002) and had a higher mean (SD) number of lesions (1.3 [0.5] vs 1.2 [0.5] lesions; P = .002) and a longer mean (SD) operation time (113.2 [29.4] vs 109.6 [32.3] minutes; P = .04). Patients who underwent navigation were also more likely to have tumors in segment 8 (59 patients [32.1%] vs 53 of 275 patients with segment data [19.3%] with segment data; P = .005) and less likely to have tumors in segment 4 (20 patients [10.9%] vs 54 patients with segment data [19.6%]; P = .005). Overall mean (SD) time to recurrence after treatment was 10.0 (12.5) months, with similar rates for patients with navigation vs no navigation. There were no differences in incomplete ablation rate (10 patients [9.2%] vs 10 patients [10.5%]; P = .32), OS, or PFS between patients undergoing ablation with and without navigation. In this study, use of navigation was associated with comparable outcomes to undergoing ablation without navigation, although patients with navigation had more locally advanced disease. These findings suggest that use of real-time navigation in laparoscopic-assisted ablation of liver cancer should be considered as a useful tool for treating challenging tumors.

Abstract No. 558 Radiation Segmentectomy vs Microwave Ablation for Small Hepatocellular Carcinomas

Abstract No. 558 Radiation Segmentectomy vs Microwave Ablation for Small Hepatocellular Carcinomas