Small Hepatocellular Carcinoma Research Articles

Long-term outcome and eligibility of radiofrequency ablation for hepatocellular carcinoma over 3.0 cm in diameter

Percutaneous radiofrequency ablation (RFA) is effective for the treatment of small hepatocellular carcinoma (HCC) with a diameter ≤ 3.0 cm. The present study aimed to elucidate the prognostic factors and clarify the indication of treatment for RFA outcomes in patients with HCC with a diameter > 3.0 cm. Among 2188 patients with HCC who underwent RFA, 100 patients with HCC with a diameter > 3.0 cm were enrolled in this study between August, 2000 and August, 2021. We analyzed local therapeutic efficacy, long-term outcomes, and prognostic factors in patients with HCC with a diameter > 3.0 cm. Among all patients, 77 patients achieved complete ablation in one session. There were no treatment-related deaths or major complications. Local tumor recurrence occurred in 48% (n = 48) of the patients, and distant tumor recurrence occurred in 82% (n = 82) of the patients during the study period. The survival rates at 1-, 3-, 5-, 10-, and 15- years were 93.0%, 66.0%, 40.0%, 15.5%, and 10.2%, respectively. Cox proportional hazards regression analysis confirmed that distant tumor recurrence, Child–Pugh class B, and pre-ablation des-γ-carboxy prothrombin (DCP) levels ≥ 200 mAU/mL were independent unfavorable prognostic factors with a hazard ratio of 3.34 (95% CI, 1.57–7.11; P = 0.002), 2.43 (95% CI, 1.35–4.37; P = 0.003), and 1.83 (95% CI, 1.14–2.93; P = 0.012), respectively. In conclusion, patients with HCC with a diameter > 3.0 cm with Child–Pugh class A and DCP levels < 200 mAU/mL might be eligible for RFA treatment.

Diagnostic performance of gadoxetic acid-enhanced abbreviated magnetic resonance imaging protocol in small hepatocellular carcinoma (≤2 cm) in high-risk patients.

Biannual Ultrasound showed insufficient sensitivity in detecting small or early-stage hepatocellular carcinoma (HCC). Abbreviated magnetic resonance imaging (A-MRI) protocols with fewer sequences demonstrated higher HCC detection sensitivity than ultrasound with acceptable cost and examination time. To compare the diagnostic performance of gadoxetic acid-enhanced A-MRI with a full sequence MRI (F-MRI) protocol for small HCC (≤2 cm) in cirrhotic or hepatitis B virus-infected high-risk patients. Two hundred and four consecutive patients with 166 pathologically confirmed small HCC who underwent preoperative gadoxetic acid-enhanced MRI were retrospectively included. A-MRI set comprised T1-weighted hepatobiliary phase imaging, T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient mapping. Two independent radiologists blinded to clinical data assessed the A-MRI set and F-MRI set. Per-patient HCC and per-lesion HCC diagnostic performance were compared. Per-patient HCC detection sensitivity of A-MRI set was 93.8% and 91.2% for observer 1 and observer 2, and, for the F-MRI set, the per-patient HCC detection sensitivity was 96.6% and 95.2%, respectively. There was no significant difference in per-patient sensitivity, specificity and per-lesion HCC detection sensitivity between the two imaging sets for both readers. (P = 0.06-0.25) The A-MRI set showed higher sensitivity on HCC without arterial phase hyperenhancement, and the F-MRI set demonstrated with higher sensitivity on HCC with arterial phase hyperenhancement (P < 0.05). A-MRI using diagnostic criteria including hypointensity on hepatobiliary phase plus mild to moderate hyperintensity on T2-weighted imaging or restricted diffusion demonstrated comparable sensitivity and specificity for small HCC compared to the F-MRI protocol in high-risk patients.

Radiofrequency ablation of subcapsular versus nonsubcapsular hepatocellular carcinomas ≤ 3cm: analysis of long-term outcomes from two large-volume liver centers.

To compare the safety and efficacy of RFA for single HCCs ≤ 3cm in subcapsular versus nonsubcapsular locations using a propensity score matched analysis. This retrospective study included patients with solitary HCCs ≤ 3cm in size who underwent percutaneous RFA from 2005 to 2015 as initial treatment at two large-volume liver centers. Patients were divided into two groups, consisting of those with subcapsular and nonsubcapsular tumor locations. Complications, local tumor progression (LTP), and overall survival (OS) were compared in these two groups before and after propensity score matching (PSM). The study population consisted of 964 patients (712 men [74%]) of mean age 58.3years. Of these 964 patients, 561 (58%) had nonsubcapsular and 403 (42%) had subcapsular HCCs. PSM generated 402 pairs of patients. Major complication rate was low, but significantly higher in the subcapscular group (p = 0.047). Rates of technical effectiveness in these two groups were 99% and 98%, respectively (p = 0.315). However, during follow-up, cumulative 1-, 3-, 5-, and 10-year LTP and OS rates did significantly differ in both entire and PSM cohorts, resulting in the latter 8%, 15%, 20%, and 26% in the nonsubcapsular group vs. 13%, 24%, 30%, and 31% in the subcapsular group (p = 0.015), and 99%, 91%, 80%, and 59% vs. 98%, 85%, 73%, and 50% in the two groups (p = 0.004), respectively. Rates of major complications, LTP, and OS differed significantly following first-line RFA treatment of single HCCs ≤ 3cm in favor of the nonsubcapsular locations. This large-scale study provides evidence that radiofrequency ablation for small (≤ 3cm) hepatocellular carcinomas is safer and more effective in nonsubcapsular location than in subcapsular location. • There exist conflicting outcomes on the effectiveness of RFA for early HCC depending on tumor location. • Rate of local tumor progression was significantly higher in the subcapsular hepatocellular carcinomas. • Overall survival rate was significantly poorer in the subcapsular hepatocellular carcinomas.

Correlation Between Serum ESPL1 and Hepatitis B Virus-related Hepatocellular Carcinoma Histological Grade: A Chinese Single-center Case-control Study.

Serum markers to determine the histological grade of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) are still limited. This study aimed to investigate if serum extra spindle pole bodies-like 1 (ESPL1) protein could reflect the histological grade of HBV-related HCC. A total of 154 patients with HBV-related HCC were enrolled in the experimental group and 41 non-HBV-related patients in the control. Enzyme-linked immunosorbent assay was used to detect serum ESPL1 levels. The differences in serological ESPL1, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) were compared between the two groups. HCC tumor diameter was measured, and pathological examination was performed to compare the relationship between ESPL1, AFP, and DCP and tumor size and histological grade. Serum AFP and DCP levels showed no significant difference between experimental group and control group, and increased when the tumor diameter increased but were not related to HCC histological grade. Serological ESPL1 levels were higher in the experimental group than those in the control group, and positively correlated with the histological grade. In the experimental group, tumor size and histological grade were almost independent (Kappa=0.000); patients with medium size tumors had the highest serum ESPL1 levels and the highest proportion of poorly differentiated carcinomas, whereas 75.6% of patients with small size tumors had moderately differentiated carcinomas and only 20% well differentiated carcinomas. Serum ESPL1 can reflect the malignant degree of HBV-related HCC and is helpful in identifying small size HCC tumors.

Chemoembolization versus Radiotherapy for Single Hepatocellular Carcinomas of ≤3 cm Unsuitable for Image-Guided Tumor Ablation.

Local ablation therapy (LAT) is primarily recommended for solitary inoperable hepatocellular carcinomas (HCCs) of ≤3 cm in diameter. However, only two-thirds of uninodular small HCCs are suitable for LAT, and the second-best treatment option for managing these nodules is unclear. We aimed to compare the therapeutic outcomes of chemoembolization and radiotherapy in small HCCs unsuitable for LAT. The study included 651 patients from a tertiary referral center who underwent planning sonography for LAT. These patients had 801 solitary HCCs of ≤3 cm in diameter and were treated with LAT, chemoembolization, or radiotherapy. Local tumor progression (LTP)-free survival and overall survival (OS) were measured according to the type of treatment of the index nodule. LAT, chemoembolization, and radiotherapy were used to treat 561, 185, and 55 nodules in 467, 148, and 36 patients, respectively. LTP-free survival was significantly shorter in patients treated with chemoembolization than for those treated with LAT (multivariate hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.61 to 3.47) but not for those treated with radiotherapy (HR, 0.83; 95% CI, 0.38 to 1.83). However, OS was not affected by treatment modality. Matching and weighting analyses confirmed that radiotherapy gave comparable results to chemoembolization in terms of OS despite better LTP-free survival (HR, 2.91; 95% CI, 1.13 to 7.47 and HR, 3.07; 95% CI, 1.11 to 8.48, respectively). Our data suggest that chemoembolization and radiotherapy are equally effective options for single small HCCs found to be unsuitable for LAT after sonographic planning. Betterfit indications for each procedure should be established by specifically designed studies.

Anatomical ablation for small hepatocellular carcinomas using multiple applicators: a preliminary study

BackgroundAnatomical ablation, defined as thermal ablation of tumor-bearing small portal territories, may provide excellent local tumor control in peripherally-located small hepatocellular carcinomas (HCC), which has been a major concern with percutaneous ablation alone.PurposeTo evaluate the technical feasibility and therapeutic outcomes of anatomical ablation using multiple radiofrequency (RF) applicators for the ablation of tumor-bearing small portal territories of peripherally-located small (≤ 4 cm) HCCs.Materials and methodsPatients with peripherally-located single HCCs (≤ 4 cm) to be treated with anatomical ablation using multiple RF applicators between January 2020 and March 2022 were enrolled in this prospective study. Anatomical ablation was performed for the index tumor under real-time US-CT/MR fusion imaging guidance, with one or two clustered electrode needles placed across the tumor-bearing portal vein branches. Technical success and complications of anatomical ablations were assessed. Cumulative incidence of local tumor progression (LTP) and recurrence-free survival were estimated using the Kaplan–Meier method.ResultsFifty-five HCCs (mean size, 1.77 ± 0.59 cm) in 55 participants (mean age, 66.4 ± 7.7 years; 39 men, 16 women) were treated with anatomical ablation; 98.2% (54/55) technical success was achieved. No major complications were noted. Among the 55 participants, LTP occurred in only one patient who had experienced technical failure of anatomical ablation. Estimated 1- and 2-year cumulative incidences of LTP were 0% and 3.7%, respectively. Five patients developed intrahepatic remote recurrence during the median follow-up period of 19.2 months (range, 3.7–28.8 months); therefore, estimated 1- and 2-year recurrence-free survival was 91.7% and 85.0%, respectively.ConclusionAnatomical ablation using multiple RF applicators provided the excellent results of local tumor control in patients with peripherally-located small (≤ 4 cm) HCCs.Trial registrationclinicaltrial.gov identifier: NCT05397860.

Feeding artery: a valuable feature for differentiation of regenerative nodule, dysplastic nodules and small hepatocellular carcinoma in CEUS LI-RADS.

To investigate whether the feeding artery (FA) feature can aid in discriminating small hepatocellular carcinoma (HCC) using the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) from precancerous lesions. Between June 2017 and May 2021, a total of 347 patients with 351 precancerous liver lesions or small HCCs who underwent CEUS were enrolled. Two independent radiologists assigned LI-RADS categories to all lesions and assessed the presence of the FA feature, which was used as an ancillary feature to either upgrade or downgrade the LI-RADS category. The diagnostic performance of CEUS LI-RADS, both with and without the FA feature, was evaluated based on accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. The FA feature was found to be more prevalent in HCC (85.54%, p < 0.001) than in regenerative nodules (RNs, 29.73%), low-grade dysplastic nodules (LGDNs, 33.33%), and high-grade dysplastic nodules (HGDNs, 55.26%). Furthermore, the presence of arterial phase hyperenhancement (APHE), washout (WO), and FA in liver nodules was associated with a higher expression of GPC-3 and Ki-67 compared to the group without these features (p < 0.001). After adjusting, the sensitivity and accuracy of LR-5 for HCC improved from 68.67% (95%CI: 62.46%, 74.30%) to 77.51% (95%CI: 71.72%, 82.44%) and from 69.23% (95%CI: 64.11%, 74.02%) to 73.79% (95%CI: 68.86%, 78.31%), respectively. The FA feature is a valuable feature for distinguishing small HCC and precancerous lesions and could be added as a possible ancillary feature in CEUS LI-RADS which was backed up by biomarkers. The presence of a feeding artery is a valuable imaging feature in the differentiation of HCC and precancerous lesions. Incorporating this characteristic in the CEUS LI-RADS can enhance the diagnostic ability. • Feeding artery is more frequent in HCC than in regenerative nodules, low-grade dysplastic nodules, and high-grade dysplastic nodules. • Feeding artery feature is a valuable ancillary feature for CEUS LI-RADS to differentiate regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, and HCC. • The existence of feeding artery, arterial phase hyperenhancement, and washout is associated with more GPC-3 positive expression and higher Ki-67 expression than the group without these features.

Application of a preoperative scoring system for small liver lesions in predicting small hepatocellular carcinoma

Application of a preoperative scoring system for small liver lesions in predicting small hepatocellular carcinoma

LI-RADS category is associated with treatment outcomes of small single HCC: surgical resection vs. radiofrequency ablation.

To assess whether the Liver Imaging Reporting and Data System (LI-RADS) category is associated with the treatment outcomes of small single hepatocellular carcinoma (HCC) after surgical resection (SR) and radiofrequency ablation (RFA). This retrospective study included 357 patients who underwent SR (n =209) or RFA (n =148) for a single HCC of ≤ 3 cm between 2014 and 2016. LI-RADS categories were assigned. Overall survival (OS), recurrence-free survival (RFS), and local tumor progression (LTP) rates after treatment were compared according to the LI-RADS category (LR-4/5 vs. LR-M) before and after propensity score matching (PSM). Prognostic factors for treatment outcomes were assessed. In total, 357 patients (mean age, 59 years; men, 272) with 357 HCCs (294 LR-4/5 and 63 LR-M) were included. After PSM (n =78 in each treatment group), there were 10 and 11 LR-M HCCs in the SR and RFA group, respectively. There were no significant differences in OS or RFS. However, SR provided a lower 5-year LTP rate than RFA (1.4% vs. 14.9%, p = 0.001). SR provided a lower 5-year LTP rate than RFA for LR-M HCCs (0% vs. 34.4%, p = 0.062) and LR-4/5 HCCs (1.5% vs. 12.0%, p = 0.008). The LI-RADS category was the sole risk factor associated with poor OS (hazard ratio [HR] 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032). LI-RADS classification is associated with the treatment outcome of HCC, supporting favorable outcomes of SR over RFA for LTP, especially for HCCs categorized as LR-M. Liver Imaging Reporting and Data System category has a potential prognostic role, supporting favorable outcomes of surgical resection over radiofrequency ablation for local tumor progression, especially for hepatocellular carcinoma categorized as LR-M. • SR provided a lower 5-year LTP rate than RFA for HCCs categorized as LR-M (0% vs. 34.4%, p = 0.062) and HCCs categorized as LR-4/5 (1.5% vs. 12.0%, p = 0.008). • There is a steeply increased risk of LTP within 1 year after RFA for LR-M HCCs, compared to SR. • The LI-RADS category was the sole risk factor associated with poor OS (HR 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032) in patients with HCC of ≤ 3 cm treated with SR or RFA.

Fusion imaging versus ultrasound-guided percutaneous thermal ablation of liver cancer: a meta-analysis.

Ultrasound-guided percutaneous thermal ablation has become an alternative treatment for small hepatocellular carcinoma (HCC). Recent evidence suggests that fusion imaging (FI) may improve the feasibility and efficacy of thermal ablation for HCC, while the clinical evidence remains limited. To compare FI versus ultrasound-guided thermal ablation for HCC. Relevant cohort or randomized controlled trials were found by searching Medline, Web of Science, Cochrane Library, and Embase. The pooling of results was performed using a random-effects model incorporating heterogeneity. In this meta-analysis, 15 studies involving 1472 patients (1831 tumors) for FI-guided ablation and 1380 patients (1864 tumors) for ultrasound-guided ablation were included. Pooled results showed that compared to conventional HCC ablation guided by ultrasound, the FI-guided procedure showed a similar technique efficacy rate (risk ratio [RR] = 1.01, 95% confidence interval [CI] = 1.00-1.02, P = 0.25; I2 = 30%). However, FI-guided tumor ablation was associated with a lower incidence of overall complications (RR = 0.70, 95% CI = 0.50-0.97, P = 0.03; I2 = 0%). Moreover, patients receiving FI-guided tumor ablation had a lower risk of local tumor progression during follow-up than those with ultrasound-guided ablation (RR = 0.61, 95% CI = 0.47-0.78, P < 0.001; I2 = 13%). Subgroup analysis according to FI strategy, imaging techniques in controls, and tumor diameter showed consistent results (p for subgroup difference all >0.05). FI-guided thermal ablation may be more effective and safer than ultrasound-guided ablation for patients with HCC.

The combination of non-contrast abbreviated MRI and alpha foetoprotein has high performance for hepatocellular carcinoma screening

ObjectivesThis study aimed to compare two abbreviated MRI (AMRI) protocols to complete MRI for HCC detection: non-contrast (NC)-AMRI without/with alpha foetoprotein (AFP) and dynamic contrast-enhanced (Dyn)-AMRI.MethodsThis retrospective single-center study included 351 patients (M/F: 264/87, mean age: 57y) with chronic liver disease, who underwent MRI for HCC surveillance between 2014 and 2020. Two reconstructed AMRI sets were obtained based on complete MRI: NC-AMRI (T2-weighted imaging (WI) + diffusion-WI) and Dyn-AMRI (T2-WI + dynamic T1-WI) and were assessed by 2 radiologists who reported all suspicious lesions, using LI-RADS/adapted LI-RADS classification. The reference standard was based on all available patient data. Inter-reader agreement was assessed and MRI diagnostic performance was compared to the reference standard.ResultsThe reference standard demonstrated 83/351 HCC-positive patients (prevalence: 23.6%, median size: 22 mm, and positive MRIs: 83/631). Inter-reader agreement was substantial for all sets. Sensitivities of Dyn-AMRI and complete MRI (both 92.8%) were similar, higher than NC-AMRI (72.3%, p < 0.001). Specificities were not different between sets. NC-AMRI + AFP (92.8%) had similar sensitivity to Dyn-AMRI and complete MRI. In patients with small size HCCs (≤ 2 cm), sensitivities of Dyn-AMRI (85.3%) and complete MRI (88.2%) remained similar (p = 0.564), also outperforming NC-AMRI (52.9%, p < 0.05). NC-AMRI + AFP had similar sensitivity (88.2%) to Dyn-AMRI and complete MRI (p = 0.706 and p = 1, respectively).ConclusionsDyn-AMRI has similar diagnostic performance to complete MRI for HCC detection, while both outperform NC-AMRI, especially for small size HCCs. NC-AMRI + AFP demonstrates similar sensitivity to Dyn-AMRI and complete MRI.Clinical relevance statementDue to the low sensitivity of ultrasound for hepatocellular screening, new screening methods are needed. Abbreviated MRI (AMRI) is a candidate, especially non-contrast AMRI with serum alpha foetoprotein as the acquisition time is low, without the need for contrast medium injection.Key Points• Dynamic contrast-enhanced abbreviated MRI using extracellular gadolinium-based contrast agent and complete MRI have similar diagnostic performance for hepatocellular carcinoma detection in an at-risk population.• Non-contrast abbreviated MRI with alpha foetoprotein has similar diagnostic performance to dynamic contrast-enhanced abbreviated MRI and complete MRI, including when considering small size hepatocellular carcinoma ≤ 2 cm.• Non-contrast abbreviated MRI and dynamic contrast-enhanced abbreviated MRI can be performed in 7 and 10 min, excluding patient setup time.

Beyond Survival: Adverse Events and Care Delivery Outcomes after Early Liver Cancer Treatment in a Nationally Representative Cohort

PurposeTo compare secondary outcomes after ablation (AB), surgical resection (SR), and liver transplant (LT) for small hepatocellular carcinomas (HCCs), including resource utilization and adverse event (AE) rates. Materials and MethodsUsing Surveillance, Epidemiology, and End Results Program (SEER)–Medicare, HCCs <5 cm that were treated with AB, SR, or LT in 2009–2016 (n = 1,067) were identified using Healthcare Common Procedure Coding System codes through Medicare claims. Index procedure length of stay, need for intensive care unit (ICU) level care, readmission rates, and AE rates at 30 and 90 days were compared using chi-square tests or Fisher exact tests. Examined AEs included hemorrhage, abscess formation, biliary injury, pneumonia, sepsis, liver disease–related AEs, liver failure, and anesthesia-related AEs, identified by International Classification of Diseases, Ninth/10th Revision, codes. ResultsThe median length of stay for initial treatment was 1 day, 6 days, and 7 days for AB, SR, and LT, respectively (P < .001). During initial hospital stay, 5.0%, 40.8%, and 63.4% of AB, SR, and LT cohorts, respectively, received ICU-level care (P < .001). By 30 and 90 days, there were significant differences among the AB, SR, and LT cohorts in the rate of postprocedural hemorrhage, abscess formation, biliary injury, pneumonia, sepsis, liver disease–related AEs, and anesthesia-related AEs (P < .05). By 90 days, the readmission rates after AB, SR, and LT were 18.6%, 28.2%, and 40.6% (P < .001), respectively. ConclusionsAB results in significantly less healthcare utilization during the initial 90 days after procedure compared with that after SR and LT due to shorter length of stay, lower intensity care, fewer readmissions, and fewer AEs.

Clinical feasibility of radiofrequency ablation using novel adjustable separable electrodes with a multipurpose needle for treating small hepatocellular carcinomas: a prospective single center study

Background The novel separable clustered electrode system with two adjustable active tips (ICAEs) and a fine multipurpose needle (MPN) for in situ temperature monitoring and adjuvant agent injection was developed and validated in an animal study. The purpose of this study was to evaluate the technical efficacy and complication of the novel electrode system for patients who have small HCC. Methods In this prospective, single-center clinical trial, ten participants with 14 small (≤ 2 cm, BCLC 0-A) HCCs referred for RFA were enrolled. A novel electrode system consisting of two ICAEs and one MPN with a thermometer and side holes was used for RFA. The RF energy was delivered using a multichannel RF system combining bipolar and switching monopolar modes. Technical success, efficacy, and complications were evaluated on immediate and one-month follow-up CT. Results Technical success was achieved in 92.9% (13/14) of tumors. One participant withdrew consent after RFA, and technical efficacy was achieved in 91.7% (11/12) of tumors. None showed thermal injury to nontarget organs. All patients were discharged the day after RFA without major complications. The active electrode lengths were adjusted in 60% (6/10) of patients during the procedure to tailor the ablation zone (83.3%, n = 5) or treat two tumors with different sizes (16.7%, n = 1). MPN was capable of continuous temperature monitoring during all ablations (100%, 14/14). Conclusions RFA using a novel electrode system showed acceptable technical efficacy and safety in patients with small HCCs. Further comparative studies are needed for the investigation of the system’s potential benefits compared to conventional electrodes.

Therapeutic Outcome of Stereotactic Body Radiotherapy for Small Hepatocellular Carcinoma Lesions – A Systematic Review and Network Meta-analysis

Surgical resection, stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) have seldom been compared for small hepatocellular carcinoma (HCC). We explored the treatment outcomes of SBRT for small HCC by conducting a network meta-analysis (NMA). We compared the efficacy and safety of surgical resection, RFA and SBRT for liver-confined small HCC (three or fewer lesions with a diameter ≤5 cm). The study endpoint included the odds ratios of the 1-, 3- and 5-year progression/recurrence/disease-free survival (disease progression-free survival; DPFS) and overall survival rates, as well as severe complications. Forty-five studies included 21 468 patients. In the NMA with comparable data, SBRT had comparable 1-, 3- and 5-year DPFS but significantly worse pooled long-term overall survival (3- and 5-year overall survival) than surgical resection (odds ratio 1.39, 95% confidential interval 1.3–1.89; odds ratio 1.33, 95% confidence interval 1.06–1.69, respectively). SBRT was associated with significantly better pooled 1-year DPFS compared with RFA (odds ratio 0.39, 95% confidence interval 0.15–0.97), with the remaining outcomes being comparable. SBRT had significantly less incidence of severe complications compared with surgical resection (odds ratio 0.62, 95% confidence interval 0.42–0.88) and RFA (odds ratio 0.2, 95% confidence interval 0.03–0.94). In conclusion, for small HCCs (≤5 cm) with one to three nodules, SBRT may be favourable to reduce the risks of severe complications. In terms of DPFS, SBRT may be recommended as an alternative first-line therapy for RFA and surgical resection. The results regarding overall survival should be interpreted with caution, considering the potentially uneliminated bias. There is a clear need for well-designed randomised trials to conclusively identify real differences in efficacy between these treatments, especially SBRT and surgical resection.

TACE sequential MWA guided by cone-beam computed tomography in the treatment of small hepatocellular carcinoma under the hepatic dome

PurposeAn assessment is being conducted to determine the safety and effectiveness of using Cone-beam computed tomography (CBCT)-guided transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) sequentially to treat small hepatocellular carcinomas (HCCs) located in the hepatic dome.Materials and methodsFifty-three patients with small HCCs in the hepatic dome who underwent TACE combined with simultaneous CBCT-guided MWA were studied. Inclusion criteria were a single HCCs ≤ 5.0 cm or a maximum of three. The safety and interventional-related complications were monitored, and local tumor progression (LTP), overall survival (OS), and prognostic factors for LTP/OS were evaluated.ResultsThe procedures were successfully accomplished in all patients. According to Common Terminology Criteria for Adverse Events (CTCAE), adverse reactions and complications are mainly Grade 1 or 2 (mild symptoms, no or local/noninvasive intervention indicated). Liver and kidney function and alpha-fetoprotein (AFP) levels remained within a reasonable range after 4 weeks of treatment (both p < 0.001). The mean LTP was 44.406 months (95% CI: 39.429, 49.383) and the mean OS rate was 55.157 months (95% CI: 52.559, 57.754). The combination treatment achieved 1-, 3-, and 5-year LTP rates of 92.5%, 69.6%, and 34.5%, respectively; and 1-, 3-, and 5-year OS rates of 100.0%, 88.4%, and 70.2%, respectively. Results from both univariate and multivariate Cox regression analyses showed that the tumor diameter (< 3 cm) and the distance to the hepatic dome (≥ 5 mm, < 10 mm) had a significant impact on the patient’s LTP and OS, and were related to better survival.ConclusionCBCT-guided TACE combined with simultaneous MWA was a safe and successful treatment of HCCs located under the hepatic dome.

Quantitative image features of gadoxetic acid-enhanced MRI for predicting glypican-3 expression of small hepatocellular carcinoma ≤3 cm

To explore the value of quantitative image features of gadoxetic acid-enhanced magnetic resonance imaging (MRI) for predicting Gglypican-3 (GPC3) expression of single hepatocellular carcinoma (HCC) ≤3 cm. One hundred and forty-nine patients with histopathologically confirmed HCC were included retrospectively. Quantitative image features and clinicopathological parameters were analysed. The significant predictors for GPC3 expression were identified using multivariate logistic regression analyses. Nomograms were constructed from the prediction model and the progression-free survival (PFS) rate was evaluated by the Kaplan-Meier method. The tumour-to-liver signal intensity (SI) ratio on the hepatobiliary phase (HBP; odds ratio [OR]=0.004; p=0.001), serum alpha-fetoprotein (AFP)>20 ng/ml (OR=6.175; p<0.001), and non-smooth tumour margin (OR=4.866; p=0.002) were independent significant factors for GPC3 expression. When the three factors were combined, the diagnostic specificity was 97.7% (42/43). The nomogram based on the predictive model performed satisfactorily (C-index: 0.852). Kaplan-Meier curves showed that patients with GPC3-positive HCCs have lower PFS rates than patients with GPC3-negative HCCs (Log-rank test, p=0.006). The tumour-to-liver SI ratio on the HBP combined with serum AFP >20 ng/ml and non-smooth tumour margin are potential predictive factors for GPC3 expression of small HCC ≤3cm. GPC3 expression is correlated with a poor prognosis in HCC patients.

Efficacy of laparoscopic liver resection for small hepatocellular carcinoma located in the posterosuperior segments: A multi-institutional study using propensity score matching by the Kyushu Study Group of Liver Surgery.

Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3cm located in PS. In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. The original cohort of patients with HCC ≤3cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287ml, p<0.001), postoperative complications (0.71 vs. 8.57%, p=0.003), and postoperative hospital stay (median, 9 vs. 14days, p<0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3cm located in PS.

Comparative long-term outcomes of laparoscopic left lateral sectionectomy and radiofrequency ablation for single small hepatocellular carcinoma located in left lateral segments of the liver

Comparative long-term outcomes of laparoscopic left lateral sectionectomy and radiofrequency ablation for single small hepatocellular carcinoma located in left lateral segments of the liver

A gadoxetic-acid enhancement flux analysis of small liver nodules (≤2 cm) in patients at high risk of hepatocellular carcinoma

PurposeTo discriminate between benignities and hepatocellular carcinomas (HCCs) in patients at high risk of HCC using a novel enhancement flux analysis for gadoxetic-acid enhanced MRI. MethodThis study retrospectively collected 181 liver nodules in 156 patients at high risk of HCC who underwent gadoxetic acid-enhanced MRI examinations with following surgical resection from 1st August 2017 to 31st December 2021 as the training set; another 42 liver nodules in 36 patients were prospectively collected from 1st January 2022 to 1st October 2022 as the test set. The time-intensity curves (TICs) of liver nodules were formed with consecutive time points: 0 s, 20 s, 1 min, 2 min, 5 min, 10 min, 15 min, and 20 min since contrast injection. A novel enhancement flux analysis was applied by using a biexponential function fitting to distinguish benignities and HCC. Besides, previously published models including maximum enhancement ratio (ERmax), percentage signal ratio (PSR), and ERmax+PSR were compared. The areas under the receiver operating characteristic curves (AUCs) were compared among these methods. ResultsThe novel enhancement flux analysis showed the highest AUCs in the training set (0.897, 95%CI: 0.833–0.960) and the test set (0.859, 95%CI: 0.747–0.970) among all models. The AUCs of PSR, ERmax and ERmax+PSR were 0.801 (95%CI: 0.710–0.891), 0.620 (95%CI: 0.510–0.729), and 0.799 (95%CI: 0.709–0.889) in the training set, and were 0.701 (95%CI: 0.539–0.863), 0.529 (95%CI: 0.342–0.717), and 0.708 (95%CI: 0.549–0.867) in the test set. ConclusionsThe biexponential flux analysis for gadoxetic-acid enhanced MRI presents a better potential in accurate diagnosis of small HCC nodules.

Comparative Study of Long-Term Outcomes of Laparoscopic Liver Resection versus Radiofrequency Ablation for Single Small Hepatocellular Carcinoma Located in Left Lateral Segments of the Liver.

Background and Objectives: Laparoscopic liver resection (LLR) is now widely recognized as the primary surgical option for hepatocellular carcinomas (HCC) smaller than 3 cm located in the left lateral segment of the liver. Nevertheless, there is a scarcity of studies comparing laparoscopic liver resection with radiofrequency ablation (RFA) in these cases. Materials and Methods: We retrospectively compared the short- and long-term outcomes of Child-Pugh class A patients who underwent LLR (n = 36) or RFA (n = 40) for a newly diagnosed single small (≤3 cm) HCC located in the left lateral segment of the liver. Results: Overall survival (OS) was not significantly different between the LLR and RFA groups (94.4% vs. 80.0%, p = 0.075). However, disease-free survival (DFS) was better in the LLR group than in the RFA group (p < 0.001), with 1-, 3-, and 5-year DFS rates of 100%, 84.5%, and 74.4%, respectively, in the LLR group vs. 86.9%, 40.2%, and 33.4%, respectively, in the RFA group. The hospital stay was significantly shorter in the RFA group than in the LLR (2.4 vs. 4.9 days, p < 0.001). The overall complication rate was higher in the RFA group than in the LLR group (15% vs. 5.6%). In patients with an α-fetoprotein level of ≥20 ng/mL, the 5-year OS (93.8% vs. 50.0%, p = 0.031) and DFS (68.8% vs. 20.0%, p = 0.002) rates were greater in the LLR group. Conclusions: LLR showed superior OS and DFS compared to RFA in patients with a single small HCC situated in the left lateral segment of the liver. LLR can be considered for patients with an α-fetoprotein level of ≥20 ng/mL.