Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma.

Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.

Plasma Cell-Free Adenomatous Polyposis Coli Gene Promoter Methylation as a Prognostic Biomarker for Hepatocellular Carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Lack of biomarkers for follow-up after treatment is a clinical challenge. DNA methylation has been proposed to be a potential biomarker in HCC. However, there is still a lack of evidence of its clinical use. This study aimed to evaluate the value of using plasma Adenomatous Polyposis Coli promoter methylation level (APC-MET) as a potential biomarker in HCC treatment. METHOD: A total of 96 patients with HCC at BCLC stage B who underwent local tumor ablation treatment were prospectively included in this study. APC-MET was examined in the plasma of each patient before and 1 month after treatment. The prediction value of APC-MET for survival outcome and disease status after treatment was analyzed and adjusted with alpha-fetoprotein and protein induced by vitamin K absence-II using Cox regression analysis. RESULTS: Univariate Cox regression analysis showed preoperative APC-MET >0 (HR, 2.9, 95% CI: 1.05-8.05, p = 0.041) and postoperative APC-MET >0 (HR, 3.47, 95% CI: 1.16-10.4, p = 0.026) were both predictors of death, and preoperative APC-MET >0 was a predictor of disease progression after treatment (HR, 2.04, 95% CI: 1.21-3.44, p = 0.007). In multivariate models, preoperative APC-MET >0 was a significant predictor of disease progression after adjusting with the other two traditional biomarkers (HR, 1.82, 95% CI: 1.05-3.17, p = 0.034). CONCLUSIONS: Hypermethylation of APC promoter appears to be a potential biomarker that could predict patient survival and disease progression outcomes in patients with intermediate-stage HCC after local ablation treatment.

[Clinical efficacy and prognostic risk factors of salvage liver transplantation, rehepatectomy, and local ablation in the treatment of postoperative recurrence of hepatocellular carcinoma].

Objective: To investigate and analyze the clinical efficacy of salvage liver transplantation (SLT), rehepatectomy (RH), local ablation (LA), and prognostic risk factors in patients with postoperative recurrence of hepatocellular carcinoma. Methods: Clinical data of 145 patients with recurrent liver cancer in the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army from January 2005 to June 2018 were retrospectively collected. SLT group, RH group, and LA group included 25, 44, and 76 cases, respectively. Follow-up and statistics were recorded on the overall survival rate, relapse-free survival rate, and complications of the three groups of patients at 1, 2, and 3 years after surgery. Univariate and multivariate COX analyses were used to analyze the prognostic risk factors in patients with recurrent HCC. Results: The overall survival rates of 1, 2, and 3 years following surgery in the SLT, RH, and LA groups were 100.0%, 84.0%, 72.0%, 95.5%, 77.3%, 65.9%, 90.8%, 76.3%, and 63.2%, respectively, when the recurrence of liver cancer met the Milan criteria. The overall survival rate did not differ statistically between SLT and RH (P = 0.303) or between RH and LA (P = 0.152). There were statistically significant differences in recurrence-free survival between SLT and RH or RH and LA (P = 0.046). There was no statistically significant difference in the incidence of complications between SLT and RH or RH and LA (P > 0.017). Age > 65 years was an independent risk factor affecting the overall survival rate in patients with recurrent HCC. Age > 65 years and recurrence time < 24 months were independent risk factors affecting the recurrence-free survival rate in patients with recurrent HCC. Conclusion: SLT is the best treatment option when the recurrence of HCC meets Milan's criteria. RH and LA are the appropriate treatment plans for recurrent HCC when the liver source is limited.

Chances, challenges and outcomes of patients with complex bilobar colorectal liver metastases approached by a combined multimodal therapy with liver resection and local ablative therapy.

BACKGROUND AND OBJECTIVES: In treatment of colorectal liver metastases (CRC-LM), liver surgery combined with systemic therapies and local ablation (LAT) allows improved survival. This study aims at the outcomes of patients with complex bilobar CRC-LM who were intended to undergo multimodal therapy with liver resection and LAT. METHODS: Forty-three CRC-LM patients with recommendation for multimodal treament were extracted from 5878 tumor board decisions between 2014 and 2017. Outcome variables included patient survival, as well as completion of hepatic clearance. Prognostic factors were identified by correlation and a Cox proportional hazards model. RESULTS: Out of 43 patients only 23 achieved complete clearance of CRC-LM. One- and 3-year overall survival of patients with cleared liver disease was 100% and 91.7%, respectively, as compared to 83.8% and 12.1%. Incomplete hepatic clearance was the strongest independent risk factor for overall survival (hazards ratio [HR], 5.86; p = .009). Risk factors for incomplete clearance were higher age (r = .34; p = .026), comorbidities (r = .40; p = .008), major complications (r = .34; p = .024), and prolonged intensive care unit stay (r = .41; p = .017). CONCLUSION: Completion of hepatic clearance is crucial to achieve long-term survival in patients with complex bilobar CRC-LM. Careful patient selection and treatment planning should avoid treatment failure before completing the intended therapy plan when multimodal treatments are planned.

Multidisciplinary management and outcome in pancreatic cancer patients treated with high-intensity focused ultrasound.

Introduction: High-intensity focused ultrasound (HIFU) for pancreatic cancer is a growing therapeutic field which has been proven to reduce cancer pain and provide a local tumor control additionally to standard palliative care. However, less is known about the multidisciplinary and especially anesthesiological management of HIFU treatment although an interdisciplinary approach is crucial for treatment success.Material and methods: Anesthesiological and radiological records of 71 HIFU-treated pancreatic cancer patients were analyzed with regard to the following items: intervention time, sonication time, total energy, anesthesia time, peri-interventional medication, body temperature maximum and minimum, pain scores before and 1 day, 6 weeks and 3 months after intervention, peri-interventional complications. Effects on pain scores were estimated with a mixed panel data model. Bivariate associations between interventional variables were examined with the Spearman's correlation.Results: HIFU treatment was performed without major adverse events. Peri-procedural hyperthermia >37.5 °C occurred in 2 patients, hypothermia <35 °C in 8 cases. Interventional variables did not correlate significantly with pain scores, opioid dose, nor body temperature. 85.5% of patients experienced significant early pain relief within the first week after intervention. Post-interventional pain relief is associated with morphine equivalent opioid dose (p = 0.025) and treatment time (p = 0.040).Conclusion: While HIFU can be considered safe and effective treatment option, procedure-associated pain and temperature management represent challenges for the interdisciplinary HIFU intervention team. Especially short-term pain relief depends on the combined effort of the radiologist and anesthesiologist.

Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors : A systematic analysis of 102 cases.

OBJECTIVE: Image-guided high-dose-rate interstitial brachytherapy (iBT) with iridium-192 is an effective treatment option for patients with liver malignancies. Little is known about long-term radiation effects on the bile duct system when central hepatic structures are exposed to iBT. This retrospective analysis investigates the occurrence of posthepatic cholestasis (PHC) and associated complications in patients undergoing iBT. MATERIALS AND METHODS: We identified patients who underwent iBT of hepatic malignancies and had point doses of ≥1 Gy to central bile duct structures. Patients with known bile duct-related diseases or prior bile duct manipulation were excluded. RESULTS: 102 patients were retrospectively included. Twenty-two patients (22%) developed morphologic PHC after a median of 17 (3-54) months; 18 of them were treated using percutaneous transhepatic cholangiopancreatography drainage or endoscopic retrograde cholangiopancreatography. The median point dose was 24.8 (4.4-80) Gy in patients with PHC versus 14.2 (1.8-61.7) Gy in those without PHC (p = 0.028). A dose of 20.8 Gy (biological effective dose, BED3/10 = 165/64.1 Gy) was identified to be the optimal cutoff dose (p = 0.028; 59% sensitivity, 24% specificity). Abscess/cholangitis was more common in patients with PHC compared to those without (4 of 22 vs. 2 of 80; p = 0.029). Median survival did not differ between patients with and without PHC (43 vs. 36 months; p = 0.571). CONCLUSION: iBT of liver malignancies located near the hilum can cause PHC when the central bile ducts are exposed to high point doses. Given the long latency and absence of impact of iBT-induced PHC on median survival, the rate of cholestasis and complications seen in our patients appears to be acceptable.

Local Ablation Does Not Worsen Perioperative Outcomes After Liver Transplant for Hepatocellular Carcinoma.

OBJECTIVE. Local ablation of hepatocellular carcinoma (HCC) before liver transplant has important advantages, such as preventing disease progression, tumor downstaging, and offering a test of time. However, it might render liver transplant more technically demanding. Thus far, its potential effect on liver transplant outcomes is still unknown, and, therefore, the current study was performed. MATERIALS AND METHODS. Patients who underwent liver transplant for HCC at a single tertiary referral center between 2008 and 2016 were included and retrospectively analyzed. Patients who underwent liver resection and local ablation before liver transplant were excluded. Patients treated with local ablation before liver transplant were compared with those not treated with local ablation, both before and after propensity score matching. In addition, the local ablation group was compared with patients who underwent primary resection before liver transplant. Posttreatment mortality and morbidity were determined, and overall and disease-free survival rates were calculated. RESULTS. In total, 182 patients were included. Twenty-six patients underwent resection but not local ablation before liver transplant. Of the remaining 156 patients, 66 (42%) underwent local ablation before liver transplant and 90 (58%) did not. Perioperative mortality and morbidity were similar in both groups before and after propensity score matching (8% and 74% in the local ablation group vs 10% and 83% in the non-local ablation group, p = 0.60 and 0.17, respectively). In addition, no significant differences in long-term outcomes were observed between the groups before and after propensity score matching. Also, no differences were observed in outcomes in the local ablation group versus the liver resection group. CONCLUSION. Local ablation before liver transplant does not have a negative effect on outcomes after liver transplant for HCC.

Improved survival following splenectomy combined with curative treatments for hepatocellular carcinoma in Child B patients: A propensity score matching study.

AIMS: To explore the benefits of curative treatments (liver resection or local ablation) combined with splenectomy for patients with hepatocellular carcinoma (HCC) and Child grade B liver function. METHODS: We reviewed 245 patients with Child grade B liver function who underwent treatment with curative intent for HCC. Among these patients, 116 patients underwent curative treatment combined with splenectomy (the splenectomy group); the other 129 patients only underwent curative treatment (the non-splenectomy group). A one-to-one matching produced 95 paired patients, perioperative and oncological outcomes were compared, and liver function changes were reassessed 1 year later. RESULTS: The perioperative liver failure rates were 7.4% and 6.3% (P = 1.000) and the 90-day mortality was 4.2% and 6.3% (P = 0.747) in the splenectomy group and non-splenectomy group, respectively. The 1-, 3-, and 5-year overall survival rates were remarkably greater in the splenectomy group than in the non-splenectomy group (92.6% vs. 79.8%, 53.4% vs. 34.7%, and 19.9% vs. 11.0%, respectively; P = 0.004). In the univariate and multivariate analyses, splenectomy was identified as a protective factor for long-term survival. The proportion of patients whose liver function improved to Child A 1 year after surgery was also higher in the splenectomy group than in the non-splenectomy group (95.4% vs. 83.3%; P = 0.048). CONCLUSIONS: Compared with non-splenectomy, curative treatments combined with splenectomy for patients with HCC and Child B grade liver function showed no different perioperative outcomes but achieved significant survival benefit. Splenectomy is a beneficial factor for patients with HCC and Child B liver function; liver function improved significantly 1 year after splenectomy.

Radioablation of liver malignancies with interstitial high-dose-rate brachytherapy : Complications and risk factors.

BACKGROUND: To evaluate complications and identify risk factors for adverse events in patients undergoing high-dose-rate interstitial brachytherapy (iBT). MATERIAL AND METHODS: Data from 192 patients treated in 343 CT- or MRI-guided interventions from 2006-2009 at our institution were analyzed. In 41 %, the largest tumor treated was ≥ 5 cm, 6 % of the patients had tumors ≥ 10 cm. Prior to iBT, 60 % of the patients had chemotherapy, 22 % liver resection, 19 % thermoablation or transarterial chemoembolization (TACE). Safety was the primary endpoint; survival data were obtained as the secondary endpoints. During follow-up, MRI or CT imaging was performed and clinical and laboratory parameters were obtained. RESULTS: The rate of major complications was below 5 %. Five major bleedings (1.5 %) occurred. The frequency of severe bleeding was significantly higher in patients with advanced liver cirrhosis. One patient developed signs of a nonclassic radiation-induced liver disease. In 3 patients, symptomatic gastrointestinal (GI) ulcers were detected. A dose exposure to the GI wall above 14 Gy/ml was a reliable threshold to predict ulcer formation. A combination of C-reactive protein ≥ 165 mg/l and/or leukocyte count ≥ 12.7 Gpt/l on the second day after the intervention predicted infection (sensitivity 90.0 %; specificity 92.8 %.) Two patients (0.6 %) died within 30 days. Median overall survival after the first liver treatment was 20.1 months for all patients and the local recurrence-free surviving proportion was 89 % after 12 months. CONCLUSIONS: Image-guided iBT yields a low rate of major complications and is effective.

Treatment of hepatocellular carcinoma: beyond international guidelines.

Treatment of hepatocellular carcinoma (HCC) is guided by the tumour stage. The Barcelona clinical liver cancer (BCLC) score endorsed by the European Society of the Liver EASL divides patients into five prognostic categories, each with a distinct treatment indication. Hepatic resection, orthotopic liver transplantation and percutaneous local ablation are strongly indicated in accurately selected patients with very early (BCLC 0) and early stage (BCLC A) tumours providing a survival rate of between 50 and 75% at year five. In patients with a large tumour burden such as those with intermediate stage BCLC B, repeated treatments with transarterial chemoembolization (TACE) are advocated with clinical benefits (from 16 to 22 months). Survival may also improve in patients who are in poor condition or who do not respond to TACE and those with an advanced HCC (BCLC C), following oral therapy with the multikinase inhibitor, sorafenib. However, most recommendations are based on uncontrolled studies and expert opinions rather than well-designed controlled trials, and up to one-third of patients do not fit recommendations because of advanced age, the presence of significant comorbidities or a strategic location of the nodule. For these patients, treatment of HCC beyond guidelines is often advocated.

Treatment of hepatocellular carcinoma: beyond international guidelines.

The management of hepatocellular carcinoma (HCC) is decided according to evidence-based recommendations generated by international societies: according to these recommendations, the tumour stage, as determined by the Barcelona clinical liver cancer (BCLC) score, divides patients into five prognostic categories, each with a distinct treatment indication. Radical therapies such as hepatic resection, orthotopic liver transplantation and percutaneous local ablation are strongly indicated in patients with very early and early stage tumours (BCLC O and A), a choice which mainly depends on a combination of tumour volume, status of underlying liver disease, the presence of comorbidities and the patient's age. Although radical therapies provide a survival rate of between 50% and 75% at year five in well selected patients, tumour recurrence is frequent following resection and ablation compared to transplantation (70% vs. 10% respectively), which has the additional advantage of preventing morbidity and mortality from portal hypertension. Generally, while radical therapies are contraindicated in patients with a large tumour burden, such as those with intermediate stage BCLC B, survival in the subset of these patients with well compensated cirrhosis may improve from 16 to 20 months, on average, following repeated treatments with transarterial chemoembolization (TACE). Survival may also improve in patients who are in poor condition or who do not respond to TACE and in those with an advanced HCC (BCLC C) following oral therapy with the multikinase inhibitor sorafenib. However, because most recommendations are based on uncontrolled studies and expert opinions rather than well designed, high powered randomized controlled trials, treatment criteria need to be adapted to special groups because real life cohorts do not match the selection criteria suggested by the guidelines. Indeed, up to one-third of patients with early stage tumours who are unfit for radical therapy because of advanced age, the presence of significant comorbidities or a strategic location of the nodule, are forced to receive palliative care. BCLC A patients with moderate portal hypertension and certain BCLC B patients could still be eligible for hepatic resection if a chance for 50% survival at 5 years is still perceived as being cost-effective by both the patient and caregivers.

Salvage treatment for local recurrence of hepatocellular carcinoma after local ablation therapy.

AIM: Local recurrence of hepatocellular carcinoma (HCC) after local ablation therapy (LAT) is a serious problem; however, the optimal treatment strategy remains unclear. METHODS: A retrospective analysis was conducted of 50 patients with local recurrence of HCC after LAT that underwent either salvage hepatectomy (n = 23) or radiofrequency ablation (RFA; n = 27). Their background characteristics, intraoperative data, and postoperative short- and long-term outcome were analyzed. RESULTS: The RFA group was found to be significantly associated with an impaired liver functional reserve, smaller number and size of tumors. The hepatectomy group showed a significantly longer operation time, greater intraoperative blood loss and more frequent red blood cell transfusion. In-hospital stay mortality and morbidity rate did not significantly differ. The disease-free and overall survival showed no significant difference between the groups. Although local recurrence after salvage treatment was found in zero (0%) for hepatectomy and in seven (25.9%) for RFA, that did not affect the overall survival. The tumor size at the prior LAT was identified as an independent prognostic factor for disease-free survival and serum albumin for overall survival. CONCLUSION: Whereas salvage hepatectomy for local recurrent HCC is recommended for selected patients in terms of its good local control effect, salvage RFA is also acceptable because it is less invasive and also has a reasonable long-term outcome.

Usefulness of Body Position Change during Local Ablation Therapies for the High-Risk Location Hepatocellular Carcinoma.

Local ablation therapies are important treatment options for early-stage hepatocellular carcinoma (HCC). Various techniques have been used to perform these therapies efficiently and safely. However, few reports have discussed the usefulness of body position change (BPC). This study aimed to investigate the usefulness of BPC during local ablation therapies in patients with HCC. We evaluated 283 HCC nodules that underwent local ablation therapy. These nodules were categorized into high- or low-risk locations on the basis of their proximity to large vessels, adjacent extrahepatic organs, or poor visibility under ultrasound (US) guidance. The technical success rates, procedure time, and prognosis were evaluated. In this study, 176 (62%) nodules were classified in the high-risk location group. The high-risk location group was treated with techniques such as BPC, artificial pleural fluid, artificial ascites, fusion imaging, and contrast-enhanced US more frequently than the low-risk location group. The technical success rates were 96% and 95% for the high- and low-risk location groups, respectively. Within the high-risk location group, those without BPC had a lower success rate than those with BPC (91% vs. 99%, p = 0.015). Notably, BPC emerged as the sole contributing factor to the technical success rate in the high-risk location group (OR = 10, 95% CI 1.2-86, p = 0.034). In contrast, no differences were found in the procedure time, local tumor progression rates, intrahepatic distant recurrence rates, and overall survival between the groups with and without BPC in the high-risk location group. In conclusion, BPC during local ablation therapy in patients with HCC in high-risk locations was safe and efficient. The body position should be adjusted for HCC in high-risk locations to maintain good US visibility and ensure a safe puncture route in patients undergoing local ablation therapies.

Local Ablation for Hepatocellular Carcinoma: 2024 Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association.

Local ablation for hepatocellular carcinoma, a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the first-line treatment for early-stage hepatocellular carcinoma. The lack of organized evidence and expert opinions regarding patient selection, preprocedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-Guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.

GALAD score as a prognostic model for recurrence of hepatocellular carcinoma after local ablation.

BACKGROUND: Currently, the high recurrence rate still forms severe challenges in hepatocellular carcinoma (HCC) treatment. The GALAD score, including age, gender, alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) was developed as a diagnostic model. However, evidence is still lacking to confirm the capability of the GALAD score to predict the recurrence of HCC. METHODS: This study included 390 HCC patients after local ablation at Beijing You'an Hospital from January 1, 2018, to December 31, 2022. Firstly, the area under the receiver operating characteristic (ROC) curve (AUC) was calculated to assess the predictive capability of the GALAD score. Then, the Kaplan-Meier (KM) curve and log-rank test were used to compare the prognosis between two groups classified by GALAD score. Finally, a nomogram for high-risk patients was established by Lasso-Cox regression. It was assessed by ROC curves, calibration curves, and decision curve analysis (DCA). RESULTS: The ROC curve (AUC: 0.749) and KM curve showed the GALAD score had good predictive ability and could clearly stratify patients into two groups through the risk of recurrence. Prognostic factors selected by Lasso-Cox regression contained tumor number, tumor size, and globulin. The nomogram for high-risk patients showed reliable discrimination, calibration, and clinical utility. CONCLUSION: This research displayed that the GALAD score is an effective model for predicting the recurrence of HCC. Meanwhile, we found the poor prognosis of the high-risk group and created a nomogram for these patients.

Ultrasound-guided percutaneous high-frequency irreversible electroporation in porcine livers using four electrode needles: A feasibility and safety study.

BACKGROUND: Malignant liver tumors seriously endanger human health. Among different therapeutic approaches, high-frequency irreversible electroporation (H-FIRE) is a recently emerging tumor ablation technique. The objective of this study was to evaluate the feasibility and safety of ultrasound-guided percutaneous H-FIRE using four electrode needles in porcine livers. METHODS: Twelve experimental pigs underwent percutaneous H-FIRE ablation using a compound steep-pulse therapeutic device. Liver tissues adjacent to the gallbladder, blood vessels, and bile ducts were selected as the ablation targets. Pigs were randomly divided into three groups: (1) immediately after ablation (N = 4), (2) 2 days after ablation (N = 4), and (3) 7 days after ablation (N = 4). Blood routine, liver and kidney function, and myocardial enzyme levels were measured before and after ablation. Ultrasound, contrast-enhanced ultrasound (CEUS), contrast-enhanced magnetic resonance imaging (MRI), and hematoxylin-eosin staining were performed to evaluate the ablation performance. RESULTS: Ultrasound-guided percutaneous H-FIRE ablations using four electrode needles were successfully performed in all 12 experimental pigs. The general conditions of the pigs, including postoperative activities and feeding behaviors, were normal, with no significant changes compared with the preoperative conditions. The imaging features of ultrasound, CEUS, and MRI demonstrated no significant changes in the gallbladder walls, bile ducts, or blood vessels close to the ablation areas. Laboratory tests showed that liver function indices and myocardial enzymes increased temporarily after H-FIRE ablation, but decreased to normal levels at 7 days after ablation. Histopathological examinations of porcine liver specimens showed that this technique could effectively ablate the target areas without damaging the surrounding or internal vascular systems and gallbladder. CONCLUSIONS: This study demonstrated the feasibility and safety of ultrasound-guided percutaneous H-FIRE ablation in porcine livers in vivo, and proposed a four-needle method to optimize its clinical application.

High-risk Patients With Colorectal Liver Metastases Assessed by the Beppu Score Can Have Excellent Survival Through Multidisciplinary Treatment Including Local Ablation.

BACKGROUND/AIM: The Beppu score assessed by the Japanese Society of Hepato-Biliary-Pancreatic Surgery nomogram helps predict postoperative disease-free survival for patients with resectable colorectal liver metastases (CRLM). Using the Beppu score, patients with resectable CRLM were divided into three groups according to recurrence risk: low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). Hepatectomy following preoperative chemotherapy is recommended for high-risk patients. The surgical outcome, local recurrence rates, and long-term survival were assessed, focusing on local ablation. PATIENTS AND METHODS: Twenty high-risk and unresectable CRLM patients were enrolled between April 2016 and April 2022. Hepatectomy with or without local ablation was performed after induction chemotherapy. Local ablation was permissive for patients with effective chemotherapy (partial response and stable disease) with CRLM ≤2 cm and ≥5 mm distant from major vessels. RESULTS: The median diameters and numbers of CRLM were 26 (10-150) mm and 9 (1-46). All 18 patients who received preoperative chemotherapy were disease controls. Local ablation was performed simultaneously on hepatectomy in 14 patients. The median diameters and numbers of the ablated nodules were 12 (5-17) mm and 3 (1-21). Local recurrence was 8.5% per 82 ablative nodules. Three-year disease-free and five-year overall survival was 57.4% and 56.2%, respectively. There was no significant difference in patients with or without local ablation. CONCLUSION: Our treatment strategy for high-risk CRLM patients is feasible and can provide an excellent long-term prognosis regardless of adding local ablation to hepatectomy.

Machine Learning Model Based on Prognostic Nutritional Index for Predicting Long-Term Outcomes in Patients With HCC Undergoing Ablation.

AIMS: To develop multiple machine learning (ML) models based on the prognostic nutritional index (PNI) and determine the optimal model for predicting long-term survival outcomes in hepatocellular carcinoma (HCC) patients after local ablation. METHODS: From January 2009 to December 2019, we analyzed data from 848 primary HCC patients who underwent local ablation. ML models were constructed and evaluated using the concordance index (C-index), concordance-discordance area under curve (C/D AUC), and Brier scores. The optimal ML model was interpreted using the partial dependence plot (PDP) and SHapley Additive exPlanations (SHAP) framework. Additionally, the prognostic performance of our model was compared with other models. RESULTS: Alkaline phosphatase, preoperation alpha-fetoprotein level, PNI, tumor number, and tumor size were identified as independent prognostic factors for ML model construction. Among the 19 ML algorithms tested, the Aorsf model showed superior performance in both the training cohort (C/D AUC: 0.733; C-index: 0.736; Brier score: 0.133) and validation cohort (C/D AUC: 0.713; C-index: 0.793; Brier score: 0.117). The time-dependent AUC of the Aorsf model for predicting overall survival was as follows: 1-, 3-, 5-, 7-, and 9-year were 0.828, 0.765, 0.781, 0.817, and 0.812 in the training cohort, 0.846, 0.859, 0.824, 0.845, and 0.874 in the validation cohort, respectively. The PDP and SHAP algorithms were employed for visual interpretation. Furthermore, time-AUC and decision curve analysis demonstrated that the Aorsf model provided superior clinical benefits compared to other models. CONCLUSION: The PNI-based Aorsf model effectively predicts long-term survival outcomes after ablation therapy, making a significant contribution to HCC research by improving surveillance, prevention, and treatment strategies.

Local ablation for hepatocellular carcinoma: 2024 expert consensus-based practical recommendation of the Korean Liver Cancer Association.

Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the firstline treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and posttreatment management of patients.

Development and Validation of a Prognostic Nomogram for Patients with AFP and DCP Double-Negative Hepatocellular Carcinoma After Local Ablation.

Purpose: Although alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) have a certain predictive ability for the prognosis of hepatocellular carcinoma (HCC), there are still some cases of aggressive recurrence among patients with AFP and DCP double-negative HCC (DNHC) after local ablation. However, prediction models to forecast the prognosis of DNHC patients are still lacking. Thus, this retrospective study aims to explore the prognostic factors in DNHC patients and develop a nomogram to predict recurrence. Patients and methods: 493 DNHC patients who underwent the local ablation at Beijing You'an Hospital between January 1, 2014, and December 31, 2022, were enrolled. A part that was admitted from January 1, 2014, to December 31, 2018, was designated to the training cohort (n = 307); others from January 1, 2019, to December 31, 2022, were allocated to the validation cohort (n = 186). Lasso regression and Cox regression were employed with the aim of screening risk factors and developing the nomogram. The nomogram outcome was assessed by discrimination, calibration, and decision curve analysis (DCA). Results: Independent prognostic factors selected by Lasso-Cox analysis included age, tumor size, tumor number, and gamma-glutamyl transferase. The area under the receiver operating characteristic (ROC) curves (AUCs) of the training and validation groups (0.738, 0.742, 0.836, and 0.758, 0.821) exhibited the excellent predicted outcome of the nomogram. Calibration plots and DCA plots suggest desirable calibration performance and clinical utility. Patients were stratified into three risk groups by means of the nomogram: low-risk, intermediate-risk, and high-risk, respectively. There exists an obvious distinction in recurrence-free survival (RFS) among three groups (p<0.0001). Conclusion: In conclusion, we established and validated a nomogram for DNHC patients who received local ablation. The nomogram showed excellent predictive power for the recurrence of HCC and could contribute to guiding clinical decisions.