Small Hepatocellular Carcinoma Research Articles

[Short-term and long-term results after minimally invasive liver resection for solitary small hepatocellular carcinoma : Analysis of 714 patients from the Italian group of minimally invasive liver surgery (IGoMILS) register].

[Short-term and long-term results after minimally invasive liver resection for solitary small hepatocellular carcinoma : Analysis of 714 patients from the Italian group of minimally invasive liver surgery (IGoMILS) register].

Clinical outcomes of transarterial chemoembolization in Child-Turcotte Pugh class A patients with a single small (≤3cm) hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics. This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy. One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8months, P=0.001). Median RFS was 19.1months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2cm) were poor prognostic factors of OS. The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3cm) HCC in CTP class A patients.

Small graft size and hepatocellular carcinoma outcomes in living donor liver transplantation: a retrospective multicentric cohort study.

This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and HCC outcomes. Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014-2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR<0.7% vs. GRWR≥0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. The eligible cohort consisted of 2005 LDLT recipients (GRWR<0.7 [n=59] vs. GRWR≥0.7 [n=1946]). In the entire cohort, 5-year RFS was significantly lower in the GRWR<0.7 than in the GRWR≥0.7 group (66.7% vs. 76.7%, P =0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P =0.234). This trend was similar in the matched cohort ( P =0.014 for RFS and P =0.096 for HCC recurrence). In multivariable analyses, GRWR<0.7 was an independent risk factor for RFS (adjusted HR [aHR] 1.89, P =0.012), but the result was marginal for HCC recurrence (aHR 1.61, P =0.066). In the pretransplant tumor burden subgroup analysis, GRWR<0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P <0.001 for RFS; aHR 2.92, P =0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P <0.001 for RFS; aHR 2.61, P =0.019 for HCC recurrence). A GRWR<0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high.

Laparoscopic liver resection versus radiofrequency ablation for small hepatocellular carcinoma: randomized clinical trial.

The aim of this study was to compare the efficacy of laparoscopic liver resection versus radiofrequency ablation for treatment of small hepatocellular carcinoma. This single-centre RCT was conducted at a tertiary referral centre in China. Patients with small hepatocellular carcinoma who had a single nodule no larger than 5 cm, or up to three nodules of 3 cm or smaller, were eligible. Patients were assigned randomly in a 1 : 1 ratio to either laparoscopic liver resection or radiofrequency ablation. Blinding was not attempted. Sample size calculations led to 75 patients per group. The primary outcome was overall survival, and the secondary outcome was recurrence-free survival. Seventy-five patients were included in each group. Overall survival (HR 1.26, 95% c.i. 0.69 to 2.30; P = 0.451) and recurrence-free survival (HR 1.34, 0.86 to 2.08; P = 0.189) did not differ between the resection and ablation groups. The 1-, 3- and 5-year overall survival rates were 94.7, 80.0, and 74.7% respectively after laparoscopic liver resection versus 93.3, 78.7, and 67.9% after radiofrequency ablation. Corresponding recurrence-free survival rates were 78.7, 61.3, and 51.6%, and 69.3, 53.3, and 41.0%, respectively. For small hepatocellular carcinoma, percutaneous radiofrequency ablation provides therapeutic effects similar to those of laparoscopic liver resection. NCT02243384 (http://www.clinicaltrials.gov).

Predicting microvascular invasion in small (≤ 5 cm) hepatocellular carcinomas using radiomics-based peritumoral analysis

ObjectiveWe assessed the predictive capacity of computed tomography (CT)-enhanced radiomics models in determining microvascular invasion (MVI) for isolated hepatocellular carcinoma (HCC) ≤ 5 cm within peritumoral margins of 5 and 10 mm.MethodsRadiomics software was used for feature extraction. We used the least absolute shrinkage and selection operator (LASSO) algorithm to establish an effective model to predict patients’ preoperative MVI status.ResultsThe area under the curve (AUC) values in the validation sets for the 5- and 10-mm radiomics models concerning arterial tumors were 0.759 and 0.637, respectively. In the portal vein phase, they were 0.626 and 0.693, respectively. Additionally, the combined radiomics model for arterial tumors and the peritumoral 5-mm margin had an AUC value of 0.820. The decision curve showed that the combined tumor and peritumoral radiomics model exhibited a somewhat superior benefit compared to the traditional model, while the fusion model demonstrated an even greater advantage, indicating its significant potential in clinical application.ConclusionThe 5-mm peritumoral arterial model had superior accuracy and sensitivity in predicting MVI. Moreover, the combined tumor and peritumoral radiomics model outperformed both the individual tumor and peritumoral radiomics models. The most effective combination was the arterial phase tumor and peritumor 5-mm margin combination. Using a fusion model that integrates tumor and peritumoral radiomics and clinical data can aid in the preoperative diagnosis of the MVI of isolated HCC ≤ 5 cm, indicating considerable practical value.Critical relevance statementThe radiomics model including a 5-mm peritumoral expansion is a promising noninvasive biomarker for preoperatively predicting microvascular invasion in patients diagnosed with a solitary HCC ≤ 5 cm.Key points• Radiomics features extracted at a 5-mm distance from the tumor could better predict hepatocellular carcinoma microvascular invasion.• Peritumoral radiomics can be used to capture tumor heterogeneity and predict microvascular invasion.• This radiomics model stands as a promising noninvasive biomarker for preoperatively predicting MVI in individuals.Graphical

Recommended Ten Years' Follow-Up Strategy for Small Hepatocellular Carcinoma after Radiofrequency Ablation: A Cost-Effectiveness Evaluation.

An optimal follow-up schedule for small (≤3 cm) hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) remains unclear in clinical guidelines. We aimed to assess the cost-effectiveness of follow-up strategies in patients with small HCC after RFA. In total, 11,243 patients were collected from global institutions to calculate recurrence rates. Subsequently, a Markov model covering a 10-year period was developed to compare 25 surveillance strategies involving different surveillance techniques (computed tomography [CT], magnetic resonance imaging or ultrasonography [US] and alpha-fetoprotein [AFP]) and intervals (3 or 6 months). The study endpoint was incremental cost-effectiveness ratio (ICER), which represented additional cost per incremental quality-adjusted life-year (QALY). Sensitivity analysis was conducted by varying the values of input parameters to observe the ICER. In a base case analysis, the dominant strategy was CT every three months during an initial two years, followed by semi-annual CT, and then switch to biannual the combination of US screening and AFP testing after five years (m3_CT-m6_CT-m6_USAFP), with an ICER of $68,570.92 compared to the "not followed" strategy. One-way sensitivity analysis showed the ICER consistently remained below the willingness-to-pay (WTP) threshold of $100,000.00. In a probabilistic sensitivity analysis, m3_CT-m6_CT-m6_USAFP was the most cost-effective approach in 95.6% of simulated scenarios at a WTP threshold. For small HCC after RFA, the recommended follow-up strategy is CT, with scans scheduled every three months for the first two years, every six months thereafter, and transition to biannual the combination of US screening and AFP testing after five years.

Multiscale Structured Trimetal Oxide Heterojunctions for Urinary Metabolic Phenotype-Dependent Screening of Early and Small Hepatocellular Carcinoma.

Developing a standardized screening tool for the detection of early and small hepatocellular carcinoma (HCC) through urinary metabolic analysis poses a challenging yet intriguing research endeavor. In this study, a range of intricately interlaced 2D rough nanosheets featuring well-defined sharp edges is fabricated, with the aim of constructing diverse trimetal oxide heterojunctions exhibiting multiscale structures. By carefully engineering synergistic effects in composition and structure, including improved adsorption, diffusion, and other surface-driven processes, the optimized heterojunctions demonstrate a substantial enhancement in signal intensity compared to monometallic or bimetallic oxides, as well as fragmented trimetallic oxides. Additionally, optimal heterojunctions enable the extraction of high-quality urinary metabolic fingerprints using high-throughput mass spectrometry. Leveraging machine learning, discrimination of HCC patients from high-risk and healthy populations achieves impressive performance, with area under the curve values of 0.940 and 0.916 for receiver operating characteristic and precision-recall curves, respectively. Six crucial metabolites are identified, enabling accurate detection of early, small-tumor, alpha-fetoprotein-negative HCC (93.3%-97.3%). A comprehensive screening strategy tailored to clinical reality yields precision metrics (accuracy, precision, recall, and F1 score) exceeding 95.0%. This study advances the application of cutting-edge matrices-based metabolic phenotyping in practical clinical diagnostics.

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.

Comparison of laparoscopic hepatectomy and percutaneous radiofrequency ablation for the treatment of small hepatocellular carcinoma: a meta-analysis

AimThe purpose of this study was to compare the long-term outcomes of laparoscopic hepatectomy (LH) and percutaneous radiofrequency ablation (PRFA) for the treatment of small hepatocellular carcinoma.MethodsWe systematically searched PubMed, Embase, Web of Science, and Medline from January 2000 to May 2022 for literature comparing the efficacy of LH and PRFA in the treatment of small hepatocellular carcinoma (largest tumour diameter ≤ 3 cm, number of intrahepatic tumours ≤3, or diameter of a single intrahepatic lesion ≤5 cm.). We assessed overall survival (OS), recurrence-free survival (RFS), local recurrence and complication rates.ResultsA total of 1886 patients with small HCC were included in the 8 studies included in this study, of which 839 underwent LH and 1047 underwent PRAF. The results of the meta-analysis showed that the two groups had the same 3-year (HR: 0.99, 95% CI: 0.67 to 1.47) and 5-year (HR: 1.30, 95% CI: 0.90 to 1.87) OS rates, and the LH group had better 3-year (HR: 0.58, 95% CI: 0.49 to 0.68) and 5-year (HR: 0.56, 95% CI: 0.37 to 0.85) RFS rates. The LH group had a lower local recurrence rate (OR: 0.19, 95% CI: 0.12 to 0.32), but the PRFA group had a lower complication rate (OR: 2.49, 95% CI: 1.76 to 3.54).ConclusionThere was no difference in OS between LH and PRFA in the treatment of small HCC. LH had a higher RFS rate and a lower local recurrence rate, but PRFA had a lower complication rate. In general, the long-term efficacy of LH in the treatment of small HCC is better than that of PRFA. Considering the advantages of less trauma and a low complication rate of PRFA, a large number of RCT studies are needed for further verification in the future.

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

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

Chemoembolization versus radiofrequency ablation for single small (≤ 3 cm) hepatocellular carcinoma: a propensity score matching analysis.

To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A). The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS). The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group. RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function. This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas. •The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear. •Overall survival rate was significantly higher in the RFA group. •The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.

Biomimetic Responsive Nanoconverters with Immune Checkpoint Blockade Plus Antiangiogenesis for Advanced Hepatocellular Carcinoma Treatment.

The first-line treatment for advanced hepatocellular carcinoma (HCC) combines immune checkpoint inhibitors and antiangiogenesis agents to prolong patient survival. Nonetheless, this approach has several limitations, including stringent inclusion criteria and suboptimal response rates that stem from the severe off-tumor side effects and the unfavorable pharmacodynamics and pharmacokinetics of different drugs delivered systemically. Herein, we propose a single-agent smart nanomedicine-based approach that mimics the therapeutic schedule in a targeted and biocompatible manner to elicit robust antitumor immunity in advanced HCC. Our strategy employed pH-responsive carriers, poly(ethylene glycol)-poly(β-amino esters) amphiphilic block copolymer (PEG-PAEs), for delivering apatinib (an angiogenesis inhibitor), that were surface-coated with plasma membrane derived from engineered cells overexpressing PD-1 proteins (an immune checkpoint inhibitor to block PD-L1). In an advanced HCC mouse model with metastasis, these biomimetic responsive nanoconverters induced significant tumor regression (5/9), liver function recovery, and complete suppression of lung metastasis. Examination of the tumor microenvironment revealed an increased infiltration of immune effector cells (CD8+ and CD4+ T cells) and reduced immunosuppressive cells (myeloid-derived suppressor cells and T regulatory cells) in treated tumors. Importantly, our nanomedicine selectively accumulated in both small and large HCC occupying >50% of the liver volume to exert therapeutic effects with minimal systemic side effects. Overall, these findings highlight the potential of such multifunctional nanoconverters to effectively reshape the tumor microenvironment for advanced HCC treatment.

Liver resection versus microwave ablation for solitary and small (≤ 3 cm) HCC with early recurrence in different stages of liver cirrhosis: A propensity score matching study

BackgroundThis study aimed to compare the effectiveness of liver resection (LR) and microwave ablation (MWA) in hepatocellular carcinoma (HCC) patients with early recurrence and varying stages of cirrhosis. MethodThis study analyzed patients with HCC who underwent hepatectomy and experienced early tumor recurrence (≤3 cm) between December 2002 and December 2020 at the Tongji Hospital. Treatment effectiveness was assessed using a propensity score matching (PSM) analysis. ResultsThis study included 295 patients (106, LR; 189, MWA), 86 patients in each of the 2 groups were chosen for further comparison, after PSM. After PSM, both LR and MWA demonstrated similar recurrence-free survival (RFS) and overall survival (OS) rates (p = 0.060 and p = 0.118, respectively). However, the LR group had more treatment-related complications. In patients with moderate or severe cirrhosis, no significant differences in RFS or OS rates were found between the LR and MWA groups (p = 0.779 and p = 0.772, respectively). In patients without cirrhosis or with mild cirrhosis, LR showed better RFS and OS rates than MWA (p = 0.024 and p = 0.047, respectively). Multivariate analysis after PSM identified moderate or severe cirrhosis and recurrence intervals ≤12 months as independent predictors of poor RFS and OS in patients with early recurrence of HCC. ConclusionLR is more effective than MWA for early recurrence of HCC in patients without cirrhosis or with mild cirrhosis, showing improved RFS and OS rates. In patients with moderate or severe cirrhosis, the OS and RFS were statistically equal between the two therapies. However, MWA may be preferred owing to its low complication rate.

Mean ADC values and arterial phase hyperintensity discriminate small (≤ 3cm) well-differentiated hepatocellular carcinoma from dysplastic nodule.

This research endeavor sought to distinguish small (≤ 3cm) well-differentiated hepatocellular carcinoma (WD-HCC) from dysplastic nodules (DN) by employing traditional imaging features and mean apparent diffusion coefficient (mADC) values derived from diffusion-weighted imaging (DWI). In this retrospective analysis, we assessed a cohort of ninety patients with confirmed dysplastic nodules (DNs) (n = 71) or well-differentiated hepatocellular carcinoma (WD-HCC) (n = 41) who had undergone dynamic contrast-enhanced magnetic resonance imaging between March 2018 and June 2021. Multivariable logistic regression analyses were executed to pinpoint characteristics that can effectively differentiate histologic grades. A region-of-interest (ROI) encompassing all lesion voxels was delineated on each slice containing the mass in the ADC map. Subsequently, the whole-lesion mean ADC (mADC) were computed from these delineations. A receiver operating characteristic (ROC) curve was generated to assess the discriminatory efficacy of the mADC values in distinguishing between WD-HCC and DN. Among the histopathological types from benign to malignant, mADC showed a significant decrease (P < 0.001). The mADCs were effective in distinguishing WD-HCC from DN [AUC, 0.903 (95% CI 0.849-0.958)]. The best cutoffs for theYoudenindexwere 0.0012mm2/s for mADC, with moderate sensitivity (70.7%) and high specificity (94.4%). MRI features including hyperintensity at arterial phase (odds ratio, 21.2; P = 0.009), mADC < 0.0012mm2/s (odds ratio, 52.2; P < 0.001) were independent predictors for WD-HCC at multivariable analysis. The AUC value of hyperintensity at arterial phase was 0.857 (95% CI 0.786-0.928). The composite diagnostic criterion of arterial hyperintensity + mADC < 0.0012mm2/s showed good performance [AUC, 0.926 (95% CI 0.878-0.975)], displaying increased sensitivity compared to individual assessments involving arterial hyperintensity (P = 0.013), mADC < 0.0012mm2/s (P = 0.004), or LR-5 (P < 0.001), with similar specificity compared to LR-5 (P = 0.193). DN and WD-HCC displayed contrasting diffusion characteristics, attainable to distinguish with satisfactory accuracy. The utilization of arterial phase hyperintensity and mADC < 0.0012 on MRI facilitated the differentiation of WD-HCC from DN.

Perfluorobutane application value in microwave ablation of Small Hepatocellular Carcinoma (

No studies have been retrieved comparing perfluorobutane with sulfur hexafluoride for microwave ablation (MWA) in small hepatocellular carcinoma(sHCC). To retrospective investigate the value of perfluorobutane ultrasonography contrast agent in ultrasonography (US)-guided MWA of sHCC. We conducted a retrospective clinical controlled study about US-guided percutaneous MWA in patients with sHCC, and in patients undergoing intra-operative treatment with perfluorobutane or sulfur hexafluoride. In both groups, a contrast agent was injected to clear the tumor and then a needle was inserted. A 5-point needle prick difficulty score was developed to compare needle prick difficulty in the two groups of cases. A total of 67 patients were included: 25 patients in group perfluorobutane, aged 41-82 (60.64±9.46), tumor size 1.1-2.8 (1.78±0.45) cm. 42 patients in group sulfur hexafluoride, aged 38-78 (62.26±9.27), with tumor size of 1.1-3.0 (1.89±0.49) cm. There was no significant difference in age or tumor size in both groups (P >  0.05). Puncture difficulty score (5-point): 2.0-2.7 (2.28±0.29) in group perfluorobutane, and 2.0-4.7 (2.95±0.85) in group sulfur hexafluoride, and the difference between the two groups was statistically significant (P <  0.05). Enhanced imaging results within 3 months after surgery: complete ablation rate was 100% (25/25) in the group perfluorobutane, 95.2% (40/42 in the group sulfur hexafluoride), with no significant difference between the two groups (P >  0.05). Perfluorobutane kupffer phase can make the operator accurately deploy the ablation needle and reduce the difficulty of operation.

Radiofrequency Ablation versus Surgical Resection in Elderly Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Although the disease burden of elderly cancer patients is rapidly increasing, reliable scientific information, value and preference information of domestic patients, and standardized guidelines for determining the treatment of elderly cancer patients are lacking. The aim of this study is to compare the therapeutic effects of radiofrequency ablation (RFA) and surgery in hepatocellular carcinoma (HCC) patients aged 65 years or older. For the meta-analysis, the databases including PubMed (MEDLINE), EMBASE, OVID Medline, and the Cochrane Library were systematically searched. After the abstract-based review by two investigators, selected manuscripts were read in detail. The surgery group showed higher overall survival (OS) (HR 1.44, 95% CI 1.22-1.70) and disease-free survival (DFS) (HR 1.40, 95% CI 1.00-1.97) than the RFA group. This was also shown in small HCC of less than 3 cm (OS, HR 1.42, 95% CI 1.00-2.03; DFS, HR 1.32, 95% CI 0.91-1.91). This might be related to the high local recurrence in the RFA group (OR 4.90, 95% 2.16-11.08). On the other hand, adverse events were significantly lower in the RFA group (OR 0.22, 95% CI 0.14-0.36), which led to a decrease in the duration of hospital stay (mean difference -14.88 days, 95% CI -22.44--7.32). In elderly HCC patients, survival in the surgery group was significantly higher than in the RFA group, but various complications tended to increase; so, appropriate patient selection is required.

Ablative and non-surgical therapies for early and very early hepatocellular carcinoma: a systematic review and network meta-analysis.

A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function. To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm). Systematic review and network meta-analysis. Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews. Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research. Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified (n ≥ 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included (n = 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials. Many studies were small and of poor quality. No comparative studies were found for some therapies. The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection. PROSPERO CRD42020221357. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in Health Technology Assessment; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.

Aberrantly expressed HIF-1α enhances HCC stem cell-like traits via Wnt/β-catenin signaling activation after insufficient radiofrequency ablation.

Radiofrequency ablation has become a favorable treatment modality for small hepatocellular carcinoma (HCC) recently; however, insufficient radiofrequency ablation (RFA) was shown to lead to enhanced invasiveness and metastasis of HCC in our previous study, while the underlying molecular mechanism has not been understood. In order to explore the influence of the hypoxic microenvironment on residual cancer and cancer stem cell (CSC)-like characteristics of HCC cells in this process, an in vitro hypoxic model and an insufficient RFA mouse model were established with HCC cancer cell lines. Immunochemistry staining and western blot were used to examine the expression of hypoxia-inducible factor (HIF)-1α and liver CSC markers. The 3D colon formation assay, tumor cell invasion assay, and gene transfection assays were applied to test the change in liver CSC stemness and HCC cell invasion. After insufficient RFA treatment, the upregulated HIF-1α expression was associated with an increase in the CSC-like population in residual cancer. In vitro, hypoxic tumor cells showed aggressive CSC-like properties and phenotypes. Wnt/β-catenin signaling activation was shown to be necessary for the acquisition of liver CSC-like characteristics under hypoxic conditions. Overall, the aberrantly enhanced HIF-1α expression enhanced the liver CSC-like traits via abnormal Wnt/β-catenin signaling activation after insufficient RFA, and the overexpressed HIF-1α would be a vital factor and useful biomarker during the HCC recurrence and metastasis.

Ablation versus Radiation Segmentectomy for Small Liver Tumors

AbstractHepatocellular carcinoma (HCC) is a liver malignancy that affects more than a million people worldwide with a complex multifactorial etiology. After the diagnosis of HCC is made, physicians establish management using the Barcelona Clinic Liver Cancer (BCLC) guidelines revolving around tumor stage, liver function, performance status, and patient preferences. According to recent updates to these guidelines, thermal ablation is the second-best curative option apart from surgical resection for small HCC (&lt; 2 cm). While thermal ablation is standard of care, recent studies have suggested that radiation segmentectomy (RS) has similar outcomes, limited hepatotoxicity, and ultimately a cost-efficient approach. Although there is limited literature on RS, this article compares ablation techniques against radiation segmentectomy for small HCC tumors.

Liver-tumor mimics as a potential translational framework for planning and testing irreversible electroporation with multiple electrodes.

Irreversible electroporation (IRE) has emerged as an appealing non-ionizing, non-thermal ablation therapy, independent of antineoplastic drugs. Limited but successful outcomes in IRE conducted in vivo, in small focal hepatocellular carcinomas (HCC), have been reported. Nonetheless, the electric parameters of IRE are usually delivered in an unplanned manner. This work investigates the integration of computational modeling to hydrogels mimicking the HCC microenvironment, as a powerful framework to: circumvent ethical concerns of in vivo experimentation; safely tune the electric parameters reaching the IRE electric field threshold; and propel the translation of IRE as a routine clinical alternative to the treatment of HCC. Therefore, a parametric study served to evaluate the effects of the pulse amplitude, the number of pulses and electrodes, the treatment time, the hydrogel-tumor size, and the cell type. The ablation extent was surveyed by confocal microscopy and magnetic resonance imaging (MRI) in cylindrical and realistic tumor-shaped hydrogels, respectively. A large ablation (70%-100%) was verified in all constructs.