HCC Nodules Research Articles

Achieving SVR in patients with hepatitis C-related HCC is associated with an improvement in overall survival: real word data

Aims: The optimal timing for DAA therapy initiation in patients with chronic hepatitis C (CHC) and HCC is still debated. The aim of our study was to provide real-world data on virological response and overall survival in patients with hepatitis C-related HCC. Methods: Retrospectively, we included patients with HCV-related HCC between 2015 and 2020. The primary outcome was to compare the SVR rate in the patients with active or historical HCC who were treated with DAA therapy. The secondary outcome was to measure the overall survival of those patients. Results: 98 patients were included, and the majority were cirrhotic with compensated liver disease. 71.4% received DAA therapy at the time of initial HCC diagnosis and 11.2% received HCV treatment at the time of HCC recurrence (Active HCC cohort). 17.3% had previously received HCC treatment, but there was no evidence of recurrence at the time of DAA (Historical HCC Cohort). The SVR rate was 81.6%, but decreased to 75.7% in patients with active HCC. The presence of active HCC and the number of HCC nodules were the only factors associated with not achieving SVR in the multivariate analysis. The median survival was higher in those who achieved SVR. Active HCC and failure to achieve SVR were the main factors associated with mortality. Conclusions: Treating hepatitis C in patients with HCC is feasible with significant rates of SVR, even if SVR rates decrease in patients with active HCC and these patients require more than one DAA therapy. Failure to achieve SVR is one of the main factors associated with mortality.

Nodule-in-nodule architecture of hepatocellular carcinomas: enhancement patterns in the hepatobiliary phase and pathological features.

This study aimed to evaluate the enhancement patterns in the hepatobiliary phase (HBP) and pathological features of nodule-in-nodule-type hepatocellular carcinoma (NIN-HCC) patients. In this single-institution retrospective study, 27 consecutive cirrhosis patients with 29 histologically confirmed NIN-HCCs who underwent preoperative examination via Gd-EOB-DTPA-enhanced MRI were enrolled from January 2016 to September 2023. Two blinded radiologists assessed the imaging features of both the inner and outer nodules in NIN-HCCs to reach a consensus on the Liver Imaging Reporting & Data System (LI-RADS) categories of the lesions. Based on the different enhancement patterns of the inner and outer nodules in the HBP, NIN-HCCs were classified into different groups and further divided into different types. Imaging features and LI-RADS categories were subsequently compared among the groups. Pathological findings for NIN-HCCs were also evaluated. Among 29 NIN-HCCs, all inner nodules showed hypervascularity, with a maximum diameter of 13.2 ± 5.5mm; 51.7% (15/29) showed "wash-in with washout" enhancement; and 48.3% (14/29) showed "wash-in without washout" enhancement. All outer nodules showed hypovascularity, with a maximum diameter of 25.6 ± 7.3mm, and 51.9% (14/29) showed a washout appearance on PVP. Among all the lesions, the maximum diameter was 27.5 ± 6.8mm; 12 (41.4%) lesions were LR-4, and 17 (58.6%) lesions were LR-5. NIN-HCCs were classified into hypointense (62.1%, 18/29) and isointense (37.9%, 11/29) groups based on the signal intensity of the outer nodules in the HBP. In the hypointense group, 2 (6.9%) of the inner nodules were hypointense (type A), 11 (37.9%) were isointense (type B), and 5 (17.2%) were hyperintense (type C) compared to the background hypointense outer nodules. In the isointense group, 9 (31.0%) of the inner nodules were hypointense (type D), 2 (6.9%) were isointense (type E), and no (0%) was hyperintense (type F) compared to the background isointense outer nodules. There were no significant differences in the diameter, dynamic enhancement patterns of the inner or outer nodules, or LI-RADS scores of the lesions between the hypointense group and the isointense group (all P > 0.05). Histologically, the inner nodules of NIN-HCCs were mainly composed of moderately differentiated HCC (75.9% 22/29), whereas the outer nodules consisted of either well-differentiated HCC or high-grade dysplastic nodules (HGDNs). NIN-HCCs exhibit specific MRI findings closely associated with their pathological features. The spectrum of HBP enhancement patterns provides valuable insights into the underlying cell biological mechanisms of these lesions. NIN-HCC subtypes may be used as a morphologic marker in the early stage of multistep hepatocarcinogenesis.

Curative effect of percutaneous microwave ablation therapy on hepatocellular carcinoma survival: a 15-year real-world study

Objective: To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma. Methods: 2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival. Results: A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P < 0.001, especially for liver cancer 3.1~5.0 cm (P < 0.001). Conclusion: Microwave ablation therapy is a safe and effective method for BCLC stage 0-B, with significantly enhanced technical efficacy and survival rate over time.

Two-dimensional perfusion angiography permits direct visualization of redistribution of flow in hepatocellular carcinoma during b-TACE

ObjectivesTo demonstrate in vivo redistribution of the blood flow towards HCC’s lesions by utilizing two-dimensional perfusion angiography in b-TACE procedures.Material and methodsIn total, 30 patients with 35 HCC nodules treated in the period between January 2019 and November 2021. For each patient, a post-processing software leading to a two-dimensional perfusion angiography was applied on each angiography performed via balloon microcatheter, before and after inflation. On the colour map obtained, reflecting the evolution of contrast intensity change over time, five regions of interests (ROIs) were assessed: one on the tumour (ROI-t), two in the immediate peritumoural healthy liver parenchyma (ROI-ihl) and two in the peripheral healthy liver parenchyma (ROI-phl). The results have been interpreted with a novel in silico model that simulates the hemodynamics of the hepatic arterial system.ResultsAmong the ROIs drawn inside the same segment of target lesion, the time-to-peak of the ROI-t and of the ROI-ihl have a significantly higher mean value when the balloon was inflated compared with the ROIs obtained with deflated balloon (10.33 ± 3.66 s vs 8.87 ± 2.60 s (p = 0.015) for ROI-t; 10.50 ± 3.65 s vs 9.23 ± 2.70 s (p = 0.047) for ROI-ihl). The in silico model prediction time-to-peak delays when balloon was inflated, match with those observed in vivo. The numerical flow analysis shows how time-to-peak delays are caused by the obstruction of the balloon-occluded artery and the opening of intra-hepatic collateral.ConclusionThe measurements identify predictively the flow redistribution in the hepatic arteries during b-TACE, supporting a proper positioning of the balloon microcatheter.

Time to surgery is not an oncological risk factor in HCC patients undergoing liver resection

PurposeGiven limitations of the health care systems in case of unforeseeable events, e.g., the COVID pandemic as well as trends in prehabilitation, time from diagnosis to surgery (time to surgery, (TTS)) has become a research issue in malignancies. Thus, we investigated whether TTS is associated with oncological outcome in HCC patients undergoing surgery.MethodsA monocentric cohort of 217 patients undergoing liver resection for HCC between 2009 and 2021 was analyzed. Individuals were grouped according to TTS and compared regarding clinical characteristics. Overall survival (OS) and recurrence-free survival (RFS) was compared using Kaplan-Meier analysis and investigated by univariate and multivariable Cox regressions.ResultsTTS was not associated with OS (p=0.126) or RFS (p=0.761) of the study cohort in univariate analysis. In multivariable analysis age (p=0.028), ASA (p=0.027), INR (0.016), number of HCC nodules (p=0.026), microvascular invasion (MVI; p<0.001), and postoperative complications (p<0.001) were associated with OS and INR (p=0.005), and number of HCC nodules (p<0.001) and MVI (p<0.001) were associated with RFS. A comparative analysis of TTS subgroups was conducted (group 1, ≤30 days, n=55; group 2, 31–60 days, n=79; group 3, 61–90 days, n=45; group 4, >90 days, n=38). Here, the median OS were 62, 41, 38, and 40 months (p=0.602 log rank) and median RFS were 21, 26, 26, and 25 months (p=0.994 log rank). No statistical difference regarding oncological risk factors were observed between these groups.ConclusionTTS is not associated with earlier tumor recurrence or reduced overall survival in surgically treated HCC patients.

Local tumor control of intermediate and advanced stage hepatocellular carcinoma after local ablative treatment with image-guided interstitial high-dose-rate brachytherapy: A subgroup analysis of 286 HCC nodules

Image-guided interstitial high-dose-rate brachytherapy (iBT) has been demonstrated to offer high local tumor control rates (LTC) of >90% after local ablation of intermediate and advanced hepatocellular carcinoma (HCC; BCLC B and C). The purpose of this study was to show the efficacy of iBT stratified by subgroups and to identify clinical characteristics associated with superior local tumor control (LTC) based on a highly heterogenous patient population METHODS AND MATERIALS: A cumulative number of 286 HCC nodules in 107 patients were retrospectively analyzed. Clinical and imaging follow-ups were conducted every 3 months after treatment. Analyzed clinical factors were: etiology, presence of liver cirrhosis, radiographic features, lesion size, pretreatment, administered dose, presence of portal hypertension, portal vein thrombosis, and level of alpha-fetoprotein (AFP). LTC rate was 88.8% for a median follow-up of 14.3 months (range 3-81 months; 95% CI: 85-92%). Median minimal enclosing tumor dose (D100) was 16.1 Gy (range 7.1-30.3 Gy; reference dose 15 Gy). Subgroup analysis showed significant fewer local recurrences for alcoholic liver disease (ALD)-related HCCs compared to those related to other causes of liver cirrhosis (nonalcoholic fatty liver disease, virus-related liver cirrhosis and other causes) (p = 0.015). LTC was significantly lower after prior surgical resection (p = 0.046). No significant variance was observed for the applied D100 in each group or for all other clinical factors tested. IBT achieves high LTC rates across treated subgroups. However, further studies should particularly address the possible impact of underlying etiology on local recurrence with emphasis on a possible higher radiosensitivity of ALD-related HCCs.

Budd-Chiari syndrome and its associated hepatocellular carcinoma: Clinical risk factors and potential immunotherapeutic benefit analysis.

Hepatocellular carcinoma (HCC) is a well-described complication of Budd-Chiari syndrome (BCS). However, the risk factors of BCS in developing HCC and clinical characteristics and imaging features of BCS-associated HCC is still to be determined. Data from 113 consecutive patients with primary BCS in Qilu hospital were retrospectively studied. The clinical features of 12 HCC patients associated with BCS were also analyzed. Chi-square analysis was performed to analyze the differences in clinical characteristics. The treatment regime and CT imaging features of BCS-associated HCC were also illustrated. 113 consecutive patients admitted to our hospital between January 2009 and June 2016 with a primary diagnosis of BCS were enrolled. 10.6% (12/113) was diagnosed with HCC. The BCS patients were mainly male gender with an average age of 49.2 years. Symptom duration longer than one year exhibited decreased serum ALT and AST and increased ascites ratio. BCS-associated HCC patients were presented with IVC block and stricture of the hepatic venous outflow tract. Patients with HCC were older and showed elevated serum AST and total bilirubin. Most nodules of HCC located in the right posterior lobe with heterogeneous enhancement during the arterial phase and washout during the delayed phase. The results indicate that BCS patients with IVC block and stricture of hepatic venous outflow tract seem to be associated with HCC. BCS associated HCC nodules exhibited irregular and heterogeneous enhancement in the arterial phase and washout on the delayed phase.

Clinical value of contrast-enhanced ultrasound in early diagnosis of small hepatocellular carcinoma (≤ 2 cm).

BACKGROUNDHepatocellular carcinoma (HCC) is the most common type of primary liver malignancy. Contrast-enhanced ultrasound (CEUS) uses contrast microbubbles during ultrasound, allowing the detection and characterization of malignant focal liver lesions with much higher diagnostic accuracy than conventional ultrasound; however, there are few reports focusing on the pattern of enhancement of CEUS for the diagnosis of HCC smaller than 2 cm.AIMTo investigate the clinical value of CEUS in the early detection of small HCC with high risk factors.METHODSA total of 395 patients with 632 nodules at high risk of HCC, who underwent regular follow-up at Xuhui Dahua Hospital from January 2007 to December 2021, were retrospectively examined. Conventional ultrasonography combined with CEUS was adopted to analyze the echo, size, location, and enhancement characteristics of benign and malignant nodules, as well as the enhancement methods for HCC with different diameters. RESULTSThe follow-up rate and duration were 92.15% (364/395) and 51.28 ± 45.09 mo, respectively. Conventional ultrasonography combined with CEUS revealed 65 (11.80%) nodules with a follow-up diagnosis of HCC, 19 (3.45%) dysplastic nodules, and 467 (84.75%) benign cirrhotic hyperplastic nodules. Among 65 cases of confirmed HCC, 40 (61.54%) were transformed from hypoechoic nodules, 9 (13.85%) from hyperechoic nodules, and the remaining 16 (24.62%) from isoechoic nodules. Significant differences in CEUS characteristics were found among cirrhotic nodules, dysplastic nodules, and HCC nodules at each phase. Significant differences in the enhancement mode were observed between nodules ≤ 1 cm and those 1–2 cm. The smaller the HCC nodule, the later the contrast agent began to flush and the longer the duration of contrast enhancement. CONCLUSIONConventional ultrasonography combined with CEUS could identify small HCC and help monitor patients with an early diagnosis of HCC. Significant differences in the enhancement mode are noted between nodules ≤ 1 cm and those 1–2 cm.

Alcohol use disorder identification test renamed Glu-Glu Test in an area of north-west of Italy: preliminary descriptive results.

The first two causes of liver cirrhosis and hepatocellular carcinoma are alcoholic and dysmetabolic. In the early stages alcohol related liver disease (ALD) is silent. For this reason, more efforts should be made to identify early individuals with hazardous/harmful alcohol consumption (AC). Alcohol use disorder identification test (AUDIT) is a validated test. ASL3 (Ligurian Local Health Company 3) has included the AUDIT renamed Glu-Glu Test on its institutional website dedicated to citizens. The renaming was carried out to bring citizens closer to the test with greater ease, especially younger citizens. At the end of the compilation of the test, the calculator provides the citizen with his score: in relation to his possible risk band, provides him with the appropriate advice. In case of a score higher than 7, ultrasonography and elastography (2D-SWE) are proposed. From December 15, 2021, to July 15, 2022, 270 asymptomatic subjects requested a medical examination autonomously, without the indication of a health worker. In 167 patients the score found hazardous AC, in 65 harmful AC and in 38 alcohol addiction. In case of hazardous AC, fibrosis grade 1-2 was evidenced in 16.7%, fibrosis grade 3 in 4.8% and fibrosis grade 4 in 3.6% of subjects. In case of harmful AC fibrosis grade 1-2 was evidenced in 37%, grade 3 in 9%, grade 4 in 6%. In this group an HCC nodule was diagnosed. In case of alcohol addiction, fibrosis grade 1-2 was evidenced in 73.6%, grade 3 in 10.5% and grade 4 in 10.5%. This preliminary experience clearly tells us that it is possible to make an early diagnosis of fibrosis and HCC starting from the AC reported autonomously by citizens.

A multicenter randomized controlled trial to evaluate the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma (SURF trial): Analysis of overall survival.

4093 Background: The initial report of the multicenter SURF trial (surgery vs. radiofrequency ablation [RFA] for small hepatocellular carcinoma [HCC]) showed that recurrence-free survival (RFS) did not differ significantly between patients undergoing surgery and RFA. The focus of the present report was to assess the effect on overall survival (OS). Methods: The SURF trial was a multicenter, open-label, randomized, controlled, phase 3 trial conducted in 49 institutions in Japan. Patients (aged between 29 and 79 years) with Child-Pugh scores ≤ 7, largest HCC diameter ≤ 3 cm, and ≤ 3 HCC nodules were considered eligible. Before enrollment, both liver surgeons and hepatologists who perform RFA confirm that all the patients can be treated using both surgery and RFA. Patients were then randomly assigned in a 1:1 ratio to undergo surgery or RFA, stratified by age, hepatitis-C virus infection, numbers of HCC, largest HCC diameter, and institution. The co-primary endpoints were RFS and OS. As per the protocol, RFS was reported previously at 3 years after the last accrual of patients. OS was planned at 5 years after the last accrual. This trial is registered in UMIN000001795. Results: During 2009–2015, 308 patients were enrolled. After excluding ineligible patients, the surgery and RFA groups included 150 and 152 patients, respectively. Baseline factors did not differ significantly between the groups. In both groups, 90% of patients had solitary HCC. The median largest HCC diameter was 1.8 cm (interquartile range, 1.5–2.2 cm) in the surgery group and 1.8 cm (interquartile range, 1.5–2.3 cm) in the RFA group. The median (range) follow-up period was 6.4 (0.4–10.8) years in the surgery group and 6.6 (0–10.7) years in the RFA group. OS did not differ significantly between the surgery and RFA groups as the 5-year OS (95% confidence interval [CI]) was 74.6% (66.5%–81.0%) in the surgery group and 70.4% (62.2%–77.3%) in the RFA group (hazard ratio (HR), 0.96; 95% CI, 0.64–1.43; P= 0.828). The analysis after long-term follow-up in the current report showed that RFS was not significantly different between the surgery and RFA groups: the 5-year RFS (95% CI), 54.7% (46.0%–62.5%) vs. 50.5% (42.1%–58.3%); HR 0.90; 95% CI 0.67–1.22; P= 0.498. Conclusions: SURF trial revealed that OS and RFS were not significantly different between patients undergoing surgery and RFA for small HCC (≤ 3 cm and 3 nodules). Clinical trial information: 000001795.

Quantitative assessment of HCC wash-out on CT is a predictor of early complete response to TACE

ObjectivesTo investigate the predictive value of four-phase contrast-enhanced CT (CECT) for early complete response (CR) to drug-eluting-bead transarterial chemoembolization (DEB-TACE), with a particular focus on the quantitatively assessed wash-in and wash-out.MethodsA retrospective analysis of preprocedural CECTs was performed for 129 HCC nodules consecutively subjected to DEB-TACE as first-line therapy. Lesion size, location, and margins were recorded. For the quantitative analysis, the following parameters were computed: contrast enhancement ratio (CER) and lesion-to-liver contrast ratio (LLC) as estimates of wash-in; absolute and relative wash-out (WOabs and WOrel) and delayed percentage attenuation ratio (DPAR) as estimates of wash-out. The early radiological response of each lesion was assessed by the mRECIST criteria and dichotomized in CR versus others (partial response, stable disease, and progressive disease).ResultsAll quantitatively assessed wash-out variables had significantly higher rates for CR lesions (WOabsp = 0.01, WOrelp = 0.01, and DPAR p = 0.00002). However, only DPAR demonstrated an acceptable discriminating ability, quantified by AUC = 0.80 (95% CI0.73–0.88). In particular, nodules with DPAR ≥ 120 showed an odds ratio of 3.3(1.5–7.2) for CR (p = 0.0026). When accompanied by smooth lesion margins, DPAR ≥ 120 lesions showed a 78% CR rate at first follow-up imaging. No significative association with CR was found for quantitative wash-in estimates (CER and LLC).ConclusionsBased on preprocedural CECT, the quantitative assessment of HCC wash-out is useful in predicting early CR after DEB-TACE. Among the different formulas for wash-out quantification, DPAR has the best discriminating ability. When associated, DPAR ≥ 120 and smooth lesion margins are related to relatively high CR rates.Key Points• A high wash-out rate, quantitatively assessed during preprocedural four-phase contrast-enhanced CT (CECT), is a favorable predictor for early radiological complete response of HCC to drug-eluting-bead chemoembolization (DEB-TACE).• The arterial phase of CECT shows great dispersion of attenuation values among different lesions, even when a standardized protocol is used, limiting its usefulness for quantitative analyses.• Among the different formulas used to quantify the wash-out rate (absolute wash-out, relative wash-out, and delayed percentage attenuation ratio), the latter (DPAR), based only on the delayed phase, is the most predictive (AUC = 0.80), showing a significant association with complete response for values above 120.

Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection.

Simple SummaryHepatocellular carcinoma (HCC) recurrence is still a major issue after liver resection. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which has not been completely understood, especially with respect to tumor recurrence. The aim of this study is to complement potentially predictive clinical factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. We confirmed that serum bilirubin level, number of HCC nodules and size of the larger nodule are linked to a higher risk of tumor recurrence. Loss of heterozygosity in the PTEN loci was found to be associated with a lower risk of HCC recurrence.Background: Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. Methods: 124 HCC patients, who underwent a primary hepatic resection from January 2016 to December 2019, were recruited for this study. Next-generation sequencing (NGS) analysis and allelic imbalance assessment in a case-control subgroup analysis were performed. A time-to-recurrence analysis was performed as well by means of Kaplan–Meier estimators. Results: Cumulative number of HCC recurrences were 26 (21%) and 32 (26%), respectively, one and two years after surgery. Kaplan–Meier estimates for the probability of recurrence amounted to 37% (95% C.I.: 24–47) and to 51% (95% C.I.: 35–62), after one and two years, respectively. Multivariable analysis identified as independent predictors of HCC recurrence: hepatitis C virus (HCV) infection (HR: 1.96, 95%C.I.: 0.91–4.24, p = 0.085), serum bilirubin levels (HR: 5.32, 95%C.I.: 2.07–13.69, p = 0.001), number of nodules (HR: 1.63, 95%C.I.: 1.12–2.38, p = 0.011) and size of the larger nodule (HR: 1.11, 95%C.I.: 1.03–1.18, p = 0.004). Time-to-recurrence analysis showed that loss of heterozygosity in the PTEN loci (involved in the PI3K/AKT/mTOR signaling pathway) was significantly associated with a lower risk of HCC recurrence (HR: 0.35, 95%C.I.: 0.13–0.93, p = 0.036). Conclusions: multiple alterations of cancer genes are associated with HCC progression. In particular, the evidence of a specific AI mutation presented in 20 patients seemed to have a protective effect on the risk of HCC recurrence.

Drug-eluting Bead-Transcatheter Arterial Chemoembolization for Advanced Hepatocellular Carcinoma Refractory to Conventional Lipiodol-based Transcatheter Arterial Chemoembolization.

PurposeTo evaluate the potential of drug-eluting bead (DEB)-transcatheter arterial chemoembolization (TACE) as a treatment option for patients with refractory to conventional lipiodol-based TACE (c-TACE) especially with decreased liver function.Patients and MethodsWe retrospectively evaluated the treatment results of DEB-TACE for 89 HCC nodules in 27 patients with c-TACE refractory according to liver function.ResultsAlthough overall survival was significantly better in Child–Pugh A patients than in Child–Pugh B patients (median survival time, MST: 561 vs 347 days, p=0.031), progression-free survival was almost similar in both patients between Child–Pugh A and B (MST: 79 vs 87 days, p=0.534). Regarding antitumor response, the objective response rate (ORR) and disease-control rate (DCR) were 5.3/12.5% and 52.7/87.5% in Child–Pugh A/B, respectively. In each 89 HCC nodules, ORR and DCR were almost similar between Child–Pugh A and B (ORR, 20.3 vs 13.3%; DCR, 77.0 vs 73.3%, respectively). Adverse events of DEB-TACE were well-tolerated, and liver function was reserved during DEB-TACE procedures.ConclusionDEB-TACE could be a therapeutic option for advanced HCC patients with c-TACE refractory and decreased liver function.

Microwave ablation versus radiofrequency ablation for perivascular hepatocellular carcinoma: a propensity score analysis

BackgroundTo compare the efficacy and safety of microwave ablation (MWA) and radiofrequency ablation (RFA) as first-line treatments for perivascular HCC. MethodsThis multicentre study enrolled 170 patients with perivascular HCC who underwent MWA or RFA. The ablation response, progression-free survival (PFS), overall survival (OS), and complications between the treatment groups for the total and propensity score-matched (PSM) cohorts were compared. ResultsThe disease control rates for MWA and RFA were similar in total (94% vs. 91%, p = 0.492) and PSM (93% vs. 93%, p = 1.00) cohorts. The PFS rates at 1, 3, and 5 years were 71%, 55% and 52% in MWA group and 61%, 33% and 28% in RFA group (p = 0.017). The OS rates were comparable between two groups in total (p = 0.249) and PSM cohorts (p = 0.345). In subgroup analyses, the PFS of patients with periportal HCC (45 vs. 36 months, p = 0.048) and a single HCC nodule (51 vs. 42 months, p = 0.014) were significantly better in MWA group than RFA. Major complications were more frequent in the MWA group than in RFA (27% vs. 7%, p < 0.001). ConclusionCompared with RFA, MWA provides better control of tumour progression especially in periportal HCC or single-nodule perivascular HCC patients.

A closer look to the new frontier of artificial intelligence in the percutaneous treatment of primary lesions of the liver.

The purpose of thermal ablation is induction of tumor death by means of localized hyperthermia resulting in irreversible cellular damage. Ablative therapies are well-recognized treatment modalities for HCC lesions and are considered standard of care for HCC nodules < 3cm in diameter in patients not suitable for surgery. Effective lesion treatment rely on complete target volume ablation. Technical limitations are represented by large (> 3cm) or multicentric nodules as well as complex nodule location and poor lesion conspicuity. Artificial Intelligence (AI) is a general term referred to computational algorithms that can analyze data and perform complex tasks otherwise prerogative of Human Intelligence. AI has a variety of application in percutaneous ablation procedures such as Navigational software, Fusion Imaging, and robot-assisted ablation tools. Those instruments represent relative innovations in the field of Interventional Oncology and promising strategies to overcome actual limitations of ablative therapy in order to increase feasibility and technical results. This work aims to review the principal application of Artificial Intelligence in the percutaneous ablation of primary lesions of the liver with special focus on how AI can impact in the treatment of HCC especially on potential advantages on the drawbacks of the conventional technique.

Characterization of Early Hepatocellular Carcinoma and High-Grade Dysplastic Nodules on Contrast-Enhanced Ultrasound: Correlation With Histopathologic Findings.

To explore the enhancement features of early hepatocellular carcinoma (HCC, including well-differentiated HCC and high-grade dysplastic nodules with a focus of HCC) and high-grade dysplastic nodules (HGDNs) on contrast-enhanced ultrasound (CEUS), correlated with the histopathologic findings. This retrospective study enrolled 81 patients with 85 pathologically confirmed hepatic lesions (69 early HCCs and 16 HGDNs). All of the hepatic lesions were examined by CEUS with SonoVue (Bracco SpA, Milan, Italy) before surgery or biopsy. The enhancement features of early HCCs and HGDNs were evaluated and compared with histopathologic findings. Thirty-eight (55.1%) early HCCs showed arterial-phase hyperenhancement (APHE). The major enhancement pattern of early HCCs was APHE without portal venous/late-phase wash-out (20 of 69 [29.0%]). Eight (11.6%) early HCCs manifested APHE. Wash-out was observed in 30 (43.5%) early HCCs. Sixteen (23.2%) early HCCs showed very-late wash-out (>120 seconds). Wash-out was not observed in all HGDNs. Of the 16 HGDNs, arterial-phase isoenhancement without portal venous/late-phase wash-out was the major enhancement pattern (n = 7 [43.8%]). The degree of CD34 expression of sinusoidal endothelial cells was more diffuse in early HCCs than in HGDNs (56.5% versus 12.5%; P = .001). Arterial-phase enhancement patterns of early HCCs on CEUS were correlated with the degree of CD34 expression (P = .039). Enhancement patterns were significantly different between early HCCs and HGDNs on CEUS. Diffuse CD34 expression of sinusoidal endothelial cells in early HCC was correlated with APHE on CEUS.

Laparoscopic ablation therapies for hepatocellular carcinoma: could specific indications for the laparoscopic approach influence the effectiveness?

Percutaneous thermo-ablation (TA) may be unfeasible for the tumor location: laparoscopic ablation therapies (LATs) are an alternative option. The aim of this study is to assess the efficacy of LATs in the treatment of HCC not eligible for percutaneous TA or surgical resection. LAT was offered to 503 patients fulfilling at least one of the following criteria: (a) patients with a single nodule or up to three nodules smaller than 3cm not suitable for surgery; (b) patients not suitable for percutaneous TA; (c) short-term recurrence of HCC (< 3months). Technical success was achieved with one session in 467 patients (93%). One-month mortality and severe morbidity rates were 0.4% and 2.19%, respectively. During a median follow-up of 38.4months in the remaining 501 patients, 361 (67%) developed intrahepatic recurrence: it appeared as a local tumor progression (LTP) in 74 cases (15%). Subcapsular lesions showed lower LTP rates (p = 0.008), as well as HCC nodules contiguous to viscera (p = 0.012). In the treatment of HCC, LAT has proved to be a safe and effective technique that enables to treat lesions not eligible for percutaneous approach, with a low morbidity rate.

Diagnostic Test of PIVKA-II as A Tumor Marker for Hepatocellular Carcinoma

Alpha-Fetoprotein (AFP) is a tumor marker that has been widely used for HCC, but there has been no increased AFP in35-45% patients with HCC. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is abnormal prothrombinsecreted in HCC and is expected to be used as a diagnostic marker of HCC. The objective of this study was to compare serumPIVKA-II levels in the patients with HCC, cirrhosis, and healthy control and determine the diagnostic value of PIVKA-II forhepatocellular carcinoma. This was a cross-sectional, analytical observational study to identify the diagnostic value ofPIVKA-II for HCC diagnosis. The diagnosis of 20 cirrhotic patients and 15 patients with HCC was established by using medicalhistory, physical examination, and additional tests according to the diagnosis criteria. A group of 12 individuals with normalliver function was used as healthy control subjects. Serum PIVKA-II levels were analyzed with the immunoassay method. Forthe comparison study, the independent-samples Kruskal Wallis test was used. Also, to determine sensitivity, specificity,positive and negative predictive value (PPV and NPV), ROC curve analysis, and 2x2 contingency table was used. The serumPIVKA-II levels in the patients with HCC were significantly higher than in cirrhotic patients (p=0.000) and healthy control(p=0.000). Sensitivity, specificity, PPV, and NPV of PIVKA-II for diagnosis of HCC in cirrhotic patients at a cut-off value of140.85 mAU/mL were 93.33%, 75%, 73.68%, and 93.75%, respectively (AUC=0.87).PIVKA-II had a high diagnostic value forHCC diagnosis. Diagnostic tests that compare serum PIVKA-II levels in any size of HCC nodules might be needed in thefuture.

Fusion Navigation Technique for Management of Difficult to Access Hepatocellular Carcinoma: A Single Center Experience

Introduction: Sonography is the most universally used imaging technique for planning and performing thermal ablation in Hepatocellular carcinoma patients due to its efficiency and safety. However, the presence of HCC nodules that are hardly visible on traditional sonography is a major drawback to its use during thermal ablation. Real-time image fusion (fusion imaging) or real-time virtual sonography is a new technology that has been developed. Aim: To determine the value of fusion/navigation guided percutaneous thermal ablation in the management of hepatocellular carcinoma that has poor conspicuity at conventional sonography. Subjects and Methods: This study included 70 HCC patients (BCLC A and B). Percutaneous radiofrequency ablation was done via real-time image fusion for 14 patients with poorly visible HCC nodules (study group), while Percutaneous radiofrequency ablation was done via traditional sonography for 56 patients with HCC nodules (control group). Results: The median time to reach the tumor was significantly shorter by using fusion navigation technique (P = 0.034). By using fusion navigation technique 92% of the lesions were completely ablated while 55% only were completely ablated by using ultrasonography (P = 0.014). One year after the procedure , by using fusion navigation technique 92% of the patients had complete response and only 55% of the patients had complete response by using conventional ultrasonography (P = 0.011). The survival distributions for both interventions were statistically significantly different, χ2 = 10.12, P = 0.001. Conclusion: Fusion imaging-guided percutaneous RFA is a reasonable and efficient treatment of patients with HCC undetectable by traditional ultrasonography.

Thermal ablation with fusion imaging guidance of hepatocellular carcinoma without conspicuity on conventional or contrast-enhanced US: surrounding anatomical landmarks matter.

Evaluating clinical and technical factors affecting thermal ablation of B-Mode/CEUS inconspicuous HCC nodules, relying only on fusion imaging (FI) performed under conscious sedation and using previously acquired CT or MR. Among 367 HCC nodules treated in the study period, data of 37 B-mode/CEUS undetectable HCC nodules treated with FI-guided ablation were extracted from our prospectively collected institutional database. Analyzed variables included patients' sex, age, cirrhosis etiology, Child-Pugh status, size of the lesion, liver segment, subcapsular or central liver site, type of imaging used for fusion (MR/CT), and the presence of surrounding anatomical landmarks (SAL) < 3cm from the index lesion. The primary efficacy was 59.4% (22/37 nodules); nine lesions (24.3%) were partially ablated (PA), six lesions (16.7%) were mistargeted (MA). Eight nodules were retreated with a CA obtained in all cases (100% CA, secondary efficacy in 30/37-81.1%). LTP was observed in 2/30 cases (6.7%). Two minor complications were registered (Clavien-Dindo, Grade1, CIRSE Classification Grade 2). SAL were related to a better ablation outcome (37.5% vs 84.6% p = 0.01). No differences were observed between CA group and PA-MA group in terms of lesion size (15.4mm vs 14.9mm p = 0.63), liver segment (p = 0.58), subcapsular or central liver site (8/22 36% vs 4/15 26.7% p = 0.84), and imaging (MR vs CT, p = 0.72). Even in the presence of potentially critical conditions (completely B-Mode/CEUS inconspicuous nodules, spontaneous breathing, and previously acquired CT or MRI), FI-only guidance is safe and allows having good primary, secondary efficacy and LTP rates. The outcome of the procedure is heavily affected by the presence of SAL.