Since its introduction in 1977, transarterial chemoembolization (TACE) has widely been accepted treatment for unresectable intermediate stage hepatocellular carcinoma (HCC). Conventional TACE (c-TACE) uses an emulsion of chemotherapeutic agent and ethiodized oil with subsequent embolization of the feeding artery using gelatin sponge. Drug eluting beads (DEB) were introduced in clinical practice in the 2000s and have since been used as an alternative to c-TACE with better outcomes, especially in larger tumors. Considering the widespread use of TACE in HCC, it is important to revisit the current knowledge and the advances that have developed for better safety and efficacy. This article aims to emphasize on the current knowledge and importance of TACE, touch upon the technical aspects including post-TACE care, response assessment, and discontinuation strategies and highlight the recent advances in the technology, catheters, and embolization particles. Thus, despite a rapid change in treatment algorithms and availability of newer drugs for HCC, TACE will remain an integral part of HCC treatment alone or in combination with other therapies.

This retrospective multicenter study is aimed at evaluating the diagnostic accuracy and influence factors of serum des-gamma-carboxy prothrombin (DCP) as a diagnostic biomarker of hepatocellular carcinoma (HCC).

Clinical data were collected from 4555 subjects with DCP tests, composed of primary liver cancer (PLC), metastatic liver cancer (MLC), chronic hepatitis (CH), liver cirrhosis (LC), benign liver diseases (BLD), biliary tract diseases (BTD), non-liver cancers (NLC), and non-liver benign diseases (NLBD). The clinical data collected included medical history, treatment records, various serum tests, and imaging examination.

Serum DCP was measured with Abbott agents in each center. In HCC, serum DCP concentration was at 9086.00 ± 366.10 mAU/mL, higher than that in other diseases (p < 0.05). At 40.00 mAU/mL recommended by instruction, positive rates of serum DCP were at 85.11% in HCC, 30.12% in intrahepatic cholangiocellular carcinoma (ICC), 31.65% in MLC, 13.95% in BLD, 18.14% in CH, 27.87% in LC, 15.75% in BTD, 35.29% in NLC, and 20.00% in NLBD. In this study, the diagnostic specificity of serum DCP in HCC was affected by liver function. In HCC, serum AFP concentrations also increased compared to non-HCC diseases (p < 0.05), but specificity varied with agents from different providers. Serum DCP decreased after the surgical removal of HCC, but remained elusive in systemic treatment.

Serum DCP may serve as an optimal biomarker for the diagnosis of HCC, but its accuracy appears influenced by liver function; attention needs to be paid to the liver function of patients for false positivity.

Achieving complete response (CR) is a desirable goal in early-to-intermediate-stage hepatocellular carcinoma (HCC). While systemic and locoregional therapies show promise, optimal drug discontinuation criteria remain unclear. This study aims to investigate drug-off criteria for atezolizumab plus bevacizumab as a proof-of-concept study.

This retrospective multicenter study included child-pugh class A patients with unresectable HCC without extrahepatic spread or macrovascular invasion who received atezolizumab plus bevacizumab as first-line therapy. Modified clinical CR (mCCR) was defined as CR per mRECIST with sustained normal alpha-fetoprotein (AFP) levels (< 10.0 ng/dl). Recurrence-free survival (RFS) and overall survival (OS) were analyzed based on the "drug-off" criteria defined by following: (1) mRECIST CR with locoregional therapies, (2) sustained normalization of AFP/AFP-L3/ des-gamma-carboxy prothrombin (DCP) for 12-24 weeks, and (3) complete tumor vascularity disappearance by contrast-enhanced ultrasonography (CEUS) or pathological curative resection.

The median follow-up was 16.5 months (95% CI 15.2-17.8). Among 51 patients achieving mCCR, 11 underwent surgery, with pathological CR in three cases. In contrast, viable lesions were observed in 7 of 40 cases assessed using CEUS. All patients meeting the drug-off criteria (n = 9) showed no recurrence and none of them experienced mortality, while 45.2% (19/42) of those not meeting the criteria experienced recurrence (median RFS: 12.8 months, p = 0.007). The median OS was not reached in dug-off criteria met patients (n = 9), 37.7 months (95% CI: NA) in non-criteria met patients (n = 42), and 27.1 months (95% CI 16.7-37.6) in non-mCCR patients (n = 184) (p < 0.001).

In patients with unresectable and TACE-unsuitable early-to-intermediate-stage HCC who met the drug-off criteria, significantly improved RFS and OS were observed compared those who did not meet the criteria. However, further validation studies are required to confirm the utility of the criteria.

Portal and hepatic vein tumor thrombosis is associated with inferior outcomes in patients with hepatocellular carcinoma (HCC), and systemic treatment alone is often insufficient. This phase II trial evaluated the efficacy and safety of combining sorafenib with radiotherapy in advanced HCC with thrombosis.

Registered at ClinicalTrials.gov (NCT03535259), this phase II single-arm prospective trial targeted patients with HCC with portal or hepatic vein tumor thrombosis, liver minus gross tumor volume >700 ml, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1. Participants underwent 40-66 Gy radiotherapy for the hepatic primary tumor and vein tumor thrombosis, with concurrent oral sorafenib (400 mg twice daily) until disease progression or unacceptable adverse events. The primary endpoint was median overall survival (mOS) and the secondary endpoints included overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST), median progression-free survival (mPFS), time to tumor progression (TTP), tumor thrombosis control, and grade ≥3 adverse events.

Between May 2018 and January 2020, 86 patients were enrolled with a median radiotherapy dose of 54 Gy (40-65 Gy). At a median follow-up of 17.2 months, mOS, mPFS, and TTP stood at 16.5, 6.1, and 6.8 months, respectively. ORR reached 47.7% and 52.3% per RECIST and mRECIST, respectively. For the tumor thrombosis, 2-year control rates per mRECIST were 93.1%. No grade 5 adverse events were noted, whereas thrombocytopenia (22.1%) and leukopenia (14.0%) were the main grade 3 adverse events.

Concurrent sorafenib and radiotherapy is an effective and well-tolerated treatment for patients with HCC with portal or hepatic vein tumor thrombosis.

Treatment options for patients with hepatocellular carcinoma (HCC) and vascular tumor thrombus are limited. The efficacy and safety of concurrent sorafenib and radiation for HCC with portal or hepatic vein tumor thrombosis has not been elucidated. This phase II trial shows that concurrent sorafenib and radiotherapy is effective and well-tolerated in the treatment of advanced HCC with portal vein or hepatic vein tumor thrombosis.

This study is registered at ClinicalTrials.gov (NCT03535259).

Transarterial chemoembolization (TACE) is a significant intervention in hepatocellular carcinoma (HCC) management, but controversies persist regarding its application in advanced cases with vascular invasion or extrahepatic metastasis. This systematic review aims to explore TACE's efficacy and safety in these cases.

A literature search was conducted on TACE in HCC patients with vascular invasion or extrahepatic metastasis. The study compared TACE with surgical resection/chemotherapeutic drugs or with no group as well. Safety was assessed for adverse outcomes and efficacy, including overall survival, mean survival, and progression-free survival (PFS). Data extraction included study characteristics, patient demographics, intervention details, outcomes, and adverse events.

A study of 28 studies involving 3740 patients found that TACE showed diverse safety and efficacy outcomes. Safety evaluations focused on liver function tests, while patient-reported symptoms included fever, pain, vomiting, and gastrointestinal issues. Overall survival was under 10 months in 9 studies, with PFS lower in the TACE group compared to conservative treatments. Survival rates ranged from 93.4% at 3 months to 13% at 24 months across studies. The study identified potential subsets where TACE exhibited efficacy, especially in cases with favorable liver function or specific tumor classifications.

Our findings suggest a potential role for TACE in certain subsets of advanced HCC patients. Tailored treatment algorithms, informed by rigorous clinical trials and considering various prognostic factors, hold the potential to enhance the management and outcomes for this complex patient population.

This study was developed to compare the efficacy of combined D-TACE-HAIC + lenvatinib + PD-1 inhibitor treatment to that of TACE + sorafenib treatment for patients with intermediate and advanced HCC.

Here, a retrospective analysis of patients with unresectable HCC who underwent transarterial chemoembolization (TACE) from March 2018 to March 2022 at the our hospital was conducted. In total, 60 patients underwent treatment with drug-eluting beads-TACE-hepatic arterial infusion chemotherapy (D-TACE-HAIC) combined with lenvatinib and PD-1 inhibitors (Group A), while 21 underwent combined TACE and sorafenib treatment (Group B).

In this study cohort, the rate of surgical conversion in Group A was significantly higher than that in Group B (33.3% vs 9.5%). As per the Revised Evaluation Criteria for Clinical Efficacy in Solid Tumors (mRECIST) criteria, the objective remission rate in Group A was significantly higher than that in Group B (86.6% vs 33.4%). Group A also exhibited significantly higher rates of overall adverse events including hypertension, abdominal pain, leukopenia, thrombocytopenia, and hypoproteinemia as compared to Group B, although the incidence of hand-foot syndrome in Group A was significantly reduced as compared to Group B (13.3% vs 42.8%). The median progression-free and overall survival (PFS and OS) of patients in Group A were 13.2 and 28.8 months, with both being significantly higher than the corresponding intervals in Group B (5.7 and 10.8 months, respectively). Cox multivariate analyses identified combination D-TACE-HAIC + lenvatinib+ PD-1 inhibitor treatment as being independently associated with patient PFS and OS.

In summary, D-TACE-HAIC + lenvatinib + PD-1 inhibitor treatment exhibits a favorable safety profile, outperforming TACE + sorafenib treatment for unresectable HCC patients while improving overall rates of translational efficacy, increasing rates of surgical conversion, prolonging patient survival, and conferring long-term survival benefits.

Embolic and ablative locoregional therapies (LRTs) for hepatocellular carcinoma are widely used to cure, bridge, or downstage patients for more definitive therapies. Common ablative therapies include microwave ablation and radiofrequency ablation, while embolic options include transarterial chemoembolization and 90Y transarterial radioembolization. While these therapies can be highly effective for the appropriate stage of disease, LRTs can suffer from a high rate of posttreatment recurrences. Considerations for administration of specific therapies include disease burden and underlying liver function. Recent data on concomitant or adjuvant systemic therapy, with LRT, have the potential to improve disease control and improve outcomes in this high-risk patient population.

The Barcelona Clinic Liver Cancer staging system classifies hepatocellular carcinoma on the basis of tumor characteristics, liver function, and Eastern Cooperative Oncology Group performance status. Hepatocellular carcinoma is divided into five stages, and the treatment options for intermediate-stage hepatocellular carcinoma have evolved in recent years. Transcatheter arterial chemoembolization remains the standard treatment for intermediate-stage (stage B) hepatocellular carcinoma. However, the concepts of transcatheter-arterial-chemoembolization-unsuitable and transcatheter-arterial-chemoembolization-refractory tumors have emerged. The authors herein describe three Japanese patients with hepatocellular carcinoma who were treated with atezolizumab and bevacizumab followed by transcatheter arterial embolization or transcatheter arterial chemoembolization. Cases 1 and 2 were transcatheter-arterial-chemoembolization-unsuitable, and Case 3 was transcatheter-arterial-chemoembolization-refractory. All patients achieved a complete response, assessed according to the modified Response Evaluation Criteria in Solid Tumors guidelines.

The first patient was a 65-year-old Japanese man with a primary 11 cm hepatocellular carcinoma. He started treatment with atezolizumab and bevacizumab but developed grade 3 liver injury after two courses, leading to the discontinuation of these drugs and subsequent bland transcatheter arterial embolization. The second patient was an 82-year-old Japanese woman with multiple primary hepatocellular carcinomas. After one course of atezolizumab and bevacizumab, the treatment was interrupted because of grade 3 proteinuria. Bland transcatheter arterial embolization was performed after completing one course of atezolizumab and bevacizumab and one course of atezolizumab alone. The third patient was an 83-year-old Japanese man with recurrent multiple hepatocellular carcinomas. Despite 12 courses of atezolizumab and bevacizumab, the tumor in segment 4 of the liver increased in size and showed arterial-phase enhancement. Transcatheter arterial chemoembolization was performed to treat this tumor. All three patients achieved a complete response based on the modified Response Evaluation Criteria in Solid Tumors guidelines.

Atezolizumab and bevacizumab followed by transcatheter arterial embolization may be an effective treatment strategy for patients with intermediate-stage hepatocellular carcinoma that is transcatheter-arterial-chemoembolization-refractory or transcatheter-arterial-chemoembolization-unsuitable.

Hepatocellular carcinoma (HCC) is the most common primary carcinoma arising from the liver. Although HCC can arise de novo, the vast majority of cases develop in the setting of chronic liver disease. Hepatocarcinogenesis follows a well-studied process during which chronic inflammation and cellular damage precipitate cellular and genetic aberrations, with subsequent propagation of precancerous and cancerous lesions. Surveillance of individuals at high risk of HCC, early diagnosis, and individualized treatment are keys to reducing the mortality associated with this disease. Radiological imaging plays a critical role in the diagnosis and management of these patients. HCC is a unique cancer in that it can be diagnosed with confidence by imaging that meets all radiologic criteria, obviating the risks associated with tissue sampling. This article discusses conventional and emerging imaging techniques for the evaluation of HCC.

Switching to systemic therapy after transarterial chemoembolization (TACE) refractoriness is more inclined to preserve liver function and decrease disease progression. Hence, we conducted a comparison between the advantages of sorafenib therapy and the continuation of TACE in patients with intermediate-stage hepatocellular carcinoma (HCC) who developed TACE refractoriness.

This retrospective cohort work involved 1,200 patients with HCC who received TACE therapy at our institution between January 2018 and December 2022. Out of these, a total of 436 participants were determined to be resistant to TACE treatment throughout their clinical progression. Out of them, 271 were finally included and categorized into two groups: (1) patients who shifted from TACE to sorafenib, and (2) patients who maintained TACE treatment. The study assessed the overall survival (OS) and time to disease progression (TTDP) of patients who were resistant to TACE, comparing both groups based on when they achieved Child-Pugh C or acquired advanced-stage HCC.

Following confirmation of refractoriness to TACE therapy, 163 opted to continue with TACE (TACE group), whereas 108 shifted to sorafenib treatment (sorafenib group). The median TTDP was 23.36 months, while the median OS was 25.3 months, in the sorafenib group, and 11.6 and 14.2 months, correspondingly, in the TACE group (p = 0.0001).

Switching to sorafenib treatment significantly improved OS and TTDP in patients with intermediate-stage HCC who were refractory to TACE. These finding highlights sorafenib's potential as an effective alternative for managing disease progression in patients unresponsive to TACE, offering a valuable treatment option in this challenging clinical scenario.

Circulating tumor cells are a promising biomarker in many malignancies. CTC dissemination during the operative procedure can lead to disease recurrence. The effect of preoperative transarterial embolization on the release of CTCs and miRNA panels and oncological outcomes in large hepatocellular carcinomas has been evaluated.

The study included non-metastatic HCC >5 cm in size, that were completely resected after TAE (n = 10). Blood was collected pre-TAE, post-TAE, postoperative (day 2,30 and 180) and analyzed for the presence of CTC and miRNA (miR-885-5p, miR-22-3p, miR-642b-5p). The samples were subjected to CTC enrichment, isolation and staining using the markers CD45, EpCAM, and cytokeratin (CK). The data was analyzed using Gene Expression Suite software.

The CTC enumeration resulted in three groups: Group 1- CTC present at both pre-TAE and postoperative day 30 (n = 4), Group 2- CTC present at pre-TAE and clearing at postoperative day 30 (n = 2), Group 3- No CTC detected at any stages (n = 3). Group 2 patients had better survival compared with the other groups. Downregulation of miRNA 22-3p also had favorable prognostic implications.

Although preoperative TAE does not seem to impact CTC shedding, CTC clearance may prove to be a valuable biomarker in prognosticating HCC. A larger study to evaluate the significance of CTCs as a prognostic marker is warranted to further evaluate these findings.

Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) is an essential therapeutic and prognostic factor. E-cadherin plays a crucial role in adhesive properties and intercellular interaction in various cancer tissues, including HCC, but the expression profile and functional contribution of E-cadherin in PVTT remain unknown. This study aimed to analyze the expression of E-cadherin in the main tumor tissue and PVTT tissue of HCC, and evaluate the functional roles of E-cadherin in PVTT formation.

A retrospective analysis was performed using the medical records of patients who underwent liver resection for HCC with PVTT, analyzing tissue specimens from 1995 to 2016. E-cadherin expression is evaluated using immunohistochemistry and western blot. The study also uses a c-Met inhibitor to explore its impact on E-cadherin expression in vitro and in vivo using cell lines and a tumor xenograft mouse model.

The results revealed a reduced E-cadherin expression in PVTT tissue than in the main tumor tissue. The inhibition of c-Met activation, frequently detected in HCC, upregulated E-cadherin expression in HCC cell lines. Furthermore, treatment with c-Met inhibitors induced changes in epithelial morphology, and inhibited migration and invasion of HCC cell lines.

This study demonstrates the downregulation of E-cadherin in PVTT, and underscores the potential of c-Met inhibition in upregulating E-cadherin and inhibiting metastatic behavior. Understanding the significance of E-cadherin and c-Met in HCC progression provides a foundation for future clinical investigations into the therapeutic effects of c-Met inhibitors on PVTT in HCC patients.

With ultrasound sensitivity limited in hepatocellular carcinoma (HCC) surveillance and few prospective studies on non-contrast abbreviated MRI (NC-AMRI), this study aimed to assess its diagnostic performance in detecting HCC.

This prospective study involved cirrhotic patients with contrast-enhanced MRI (CE-MRI) Liver Imaging Reporting and Data System (LI-RADS) LR-3 and LR-4 observations detected during HCC surveillance. Patients underwent average 3 complete CE-MRI rounds at 3-6 months interval, with approximately 12-month follow-up. NC-AMRI included diffusion-weighted (DWI), T2-weighted imaging (T2WI), and T1-weighted imaging (T1WI). NC-AMRI protocol images were analysed for diagnostic performance, with subgroup analyses. CE-MRI and NC-AMRI images were independently reviewed by 2 experienced radiologists, with inter-reader agreement assessed with Kappa coefficient. The reference standard was the American Association for the Study of Liver Diseases-defined presence of arterial hypervascularity and washout during the portal-venous or delayed phases on CE-MRI.

In 166 CE-MRI follow-ups of 63 patients (median age: 63 years; 60.3% male, 39.7% female), 12 patients developed HCC, with average size of 19.6 mm. The NC-AMRI (DWI + T2WI + T1WI) showed 91.7% sensitivity (95%CI, 61.5-99.8) and 91.6% specificity (95%CI, 86.0-95.4), area under receiver operating characteristic 0.92 (95%CI, 0.83-1.00). Across different Body Mass Index categories, lesion size, Child-Turcotte-Pugh classes, Albumin-Bilirubin (ALBI) grades, and Model for End-Stage Liver Disease classes, sensitivity remained consistent. However, specificity differed significantly between ALBI grade 1 and 2 (86.7% vs. 98.4%, P = .010), and between viral and non-viral cirrhosis (93.8% vs. 80.8%, P = .010).

NC-AMRI proved clinically feasible, and exhibits high diagnostic performance in HCC detection.

This study highlights efficacy of NC-AMRI in detecting HCC among cirrhotic patients with LR-3 and LR-4 observations, representing significant progress in HCC surveillance.

Some patients undergoing liver resection for hepatocellular carcinoma (HCC) have poor outcomes. Therefore, we aimed to propose a new resectability classification for patients with HCC.

We classified patients into three categories: resectable (R), borderline resectable (BR), and unresectable (UR). Patients (n = 409) who underwent hepatectomy for HCC were assigned to the non-UR (R and BR classes combined; n = 285) and UR-HCC classes (n = 68; training cohort). Patient characteristics in the BR-HCC and R-HCC groups were compared. The new criteria were tested in a validation cohort (n = 295).

Of the 285 patients, 229 and 56 were classified into the R- and BR-HCC classes, respectively, using macrovascular invasion, tumor size, and future liver remnant/modified albumin-bilirubin scores. Patients with BR-HCC demonstrated significantly worse progression-free and overall survival (p < 0.0001 and p < 0.0001, respectively) than patients with R-HCC in the training cohort. Similar results were observed in the validation cohort. Multivariate analysis of the non-UR-HCC group in the training cohort revealed that the tumor number and BR-HCC were independent predictive factors for poor overall survival.

This classification can help select patients with BR-HCC for preoperative treatment before considering surgery.

Transarterial chemoembolization (TACE) is an established therapeutic strategy for intermediate stage Barcelona Clinic Liver Cancer (BCLC) hepatocellular carcinoma (HCC). However, patients who are early refractory to TACE may not benefit from repeated TACE treatment. Our primary objective was to assess the diagnostic value of inflammatory markers in identifying early TACE refractory for patients with early (BCLC 0 and A) or intermediate (BCLC B) stage HCC. We retrospectively reviewed the HCC patients who underwent TACE as the initial treatment in two hospitals. Patients with early TACE refractoriness had significantly poorer median overall survival (OS) (16 vs 40 months, P<0.001) and progression-free survival (PFS) (7 vs 23 months, P<0.001) compared to TACE non-refractory patients. In the multivariate regression analysis, tumor size (P<0.001), bilobular invasion (P=0.007), high aspartate aminotransferase-to-platelet ratio index (APRI) (P=0.007), and high alpha fetoprotein (AFP) level (P=0.035) were independent risk factors for early TACE refractoriness. The predictive model showcasing these factors exhibited high ability proficiency, with an area under curve (AUC) of 0.833 (95%CI=0.774-0.892) in the training cohort, 0.750 (95%CI: 0.640-0.861) in the internal-validation cohort, and 0.733 (95%CI: 0.594-0.872) in the external-validation cohort. Calibration curve analysis revealed good agreement between the actual and predicted probabilities of early TACE refractoriness. Our preliminary study estimated the potential value of inflammatory markers in predicting early TACE refractoriness and provides a predictive model to assist in identifying patients who may not benefit from repeat TACE treatment.

To investigate whether protein induced by vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors.

A multi-center prospective observational study was performed at nine regional institutions around China. Children with hepatic mass (Group T) were divided into hepatoblastoma group (Group THB) and hemangioendothelioma group (Group THE), children with extrahepatic abdominal mass (Group C). Peripheral blood was collected from each patient prior to surgery or chemotherapy. The area under the curve (AUROC) was used to evaluate the diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP.

The mean levels of PIVKA-II and AFP were both significantly higher in Group T than Group C (p = 0.001, p < 0.001), in Group THB than Group THE (p = 0.018, p = 0.013) and in advanced HB than non-advanced HB (p = 0.001, p = 0.021). For the diagnosis of childhood hepatic tumors, AUROC of PIVKA-II (cut-off value 32.6 mAU/mL) and AFP (cut-off value 120 ng/mL) was 0.867 and 0.857. The differential diagnostic value of PIVKA-II and AFP in hepatoblastoma from hemangioendothelioma was further assessed, AUROC of PIVKA-II (cut-off value 47.1mAU/mL) and AFP (cut-off value 560 ng/mL) was 0.876 and 0.743. The combined markers showed higher AUROC (0.891, 0.895 respectively) than PIVKA-II or AFP alone.

The serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. The combination of PIVKA-II with AFP further increased the diagnostic performance.

Clinical Trials, NCT03645655. Registered 20 August 2018, https://www.

gov/ct2/show/NCT03645655 .

Vascular invasion of hepatocellular carcinoma involves tumor plugs in the main trunk of the portal vein, bile ducts, and veins, and it indicates poor prognosis. It is often associated with portal hypertension, which requires evaluation and management. Treatment includes hepatic resection, systemic pharmacotherapy, hepatic arterial infusion chemotherapy, and radiation therapy. Recurrence rates post-hepatic resection are high, and systemic drug therapy often has limited therapeutic potential in patients with a poor hepatic reserve. Single therapies are generally inadequate, necessitating combining multiple therapies with adjuvant and systemic pharmacotherapy before and after hepatectomy. This narrative review will provide an overview of the treatment of hepatocellular carcinoma with vascular invasion.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Most patients are diagnosed at an advanced stage, limiting their treatment options. The traditional assessment of liver function using the Child-Pugh score has limitations due to its subjectivity. The albumin-bilirubin (ALBI) grade delivers a more precise evaluation of liver function. This study examines overall survival (OS) in advanced HCC patients treated with first-line systemic therapy and the impact of ALBI grading on these outcomes.

A total of 104 patients with advanced HCC treated between January 2017 and December 2023 with one of the three first-line therapy options: Sorafenib, lenvatinib or atezolizumab/bevacizumab were retrospectively analyzed. The Kaplan-Meier method was utilized to examine the survival results, and the log-rank test was employed to evaluate the variations in survival among ALBI grades and therapy types. Cox proportional hazards regression examined the impact of ALBI grading and other covariates on OS, with a significance threshold of p < 0.05 for the multivariable model.

The median age of HCC patients was 58.5 years, with 70% males, and a primary etiology of hepatitis C (43%). The median OS and time to progression (TTP) in this cohort were 9 months and 3.25 months. In ALBI grade I patients, the OS was 21 months, while in grade II or III patients, it was just 5 months. Treatment-related side effects necessitated dose reductions in over 84% of patients. Albumin-bilirubin grade, Child-Pugh class, and treatment modifications due to adverse effects were significant predictors of survival.

Lenvatinib appears to have better survival outcomes compared to other options. The albumin-bilirubin grading is a useful method for evaluating liver function and forecasting survival rates for individuals with HCC.

Our findings support the use of ALBI grading in clinical decision-making for advanced HCC.

Naviwala MSS, Tariq M, Ahmed F, et al. Overall Survival and the Impact of Albumin-bilirubin Grade in Patients with Advanced Hepatocellular Carcinoma: Data from a Tertiary Care Hospital in a Lower-middle-income Country. Euroasian J Hepato-Gastroenterol 2024;14(2):251-257.

To observe and assess the efficacy and safety of donafenib combined with transarterial chemoembolization (TACE) to treat unresectable hepatocellular carcinoma (HCC).

This prospective, single-arm, single-center, phase II clinical study enrolled 36 patients with initial unresectable HCC who had not undergone any systemic treatment. The patients received donafenib plus TACE (n = 26) or donafenib plus TACE plus programmed death receptor 1 inhibitors (n = 10). The primary endpoint was short-term efficacy, with secondary endpoints including progression-free survival (PFS), time to response (TTR), disease control rate (DCR), and adverse events. The tumor feeding artery diameter was also measured.

Efficacy evaluation of all 36 patients revealed 6 cases of complete response, 19 of partial response, 8 of stable disease, and 3 of progressive disease. Six (16.7%) patients successfully underwent conversion surgery, all achieving R0 resection, and 2 (5.6%) achieved a complete pathological response. The objective response rate (ORR) was 69.4% and the DCR was 91.7%. The median PFS was 10.7 months, the median overall survival was not reached, and the median TTR was 1.4 months. The median survival rates at 6, 12, and 18 months were 85.0%, 77.6%, and 71.3%, respectively. The median PFS rates at 6, 12, and 18 months were 65.3%, 45.6%, and 34.2%, respectively. Treatment-related adverse events (TRAEs) occurred in all 25 subjects, including 4 (11.3%) grade 3 TRAEs. No grade 4 or 5 TRAEs occurred. The tumor feeding artery diameter was significantly decreased following treatment (P = 0.036). Multivariable analysis revealed the sum of baseline target lesion diameters, best tumor response, and combined immunotherapy as independent predictors of PFS.

TACE plus donafenib reduced the tumor feeding artery diameter in patients with unresectable HCC. The safety profile was good, and a high ORR was achieved.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although alpha-fetoprotein (AFP) has been used for 60+ years as an HCC diagnostic serum marker, its accuracy is debated. Notably, the role of interleukin 10 (IL-10) in cancer development and metastasis is elevated in various tumor types, including HCC and chronic HCV infection. Our study aimed to investigate the diagnostic performance of IL-10 and AFP as biomarkers for HCV-induced HCC in an Egyptian population.

Eighty participants were recruited and categorized into three groups: HCV-related HCC (n=40), HCV-related cirrhosis (n=40), and control (n=20).The collected blood samples were analyzed to evaluate liver function, AFP levels, and IL-10 levels.

Our analysis showed that AFP demonstrated low sensitivity (40% false-negative) and low specificity (33% false-positive).IL-10 levels were significantly higher (P < 0.001) in patients with HCC than in the cirrhosis and control groups. The serum AFP and IL-10 combination revealed significantly increased sensitivity (97.5%), diagnostic accuracy (71.1%), AUC (0.798), PPV (73.3%), and NPV ( 69.5%) when compared with either of them alone.

the reliability of AFP as a major HCC marker was poor. However, IL-10 levels are a novel biomarker for the degree of HCC inflammation, considering IL-10's potential role in HCV-HCC development. We suggest combining AFP with IL-10 to improve the diagnostic and prognostic value of HCC considerably. Future research on these biomarkers should prioritize their clinical validity, prognostic usefulness, and compatibility with other therapeutic approaches as immunotherapy.

The prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI.

From July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0.

Thirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed.

Hepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

Hepatic arterial infusion chemotherapy (HAIC) has demonstrated remarkable local therapeutic efficacy in treating patients with large unresectable hepatocellular carcinoma (HCC). Additionally, the combination of lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has demonstrated promising antitumor effects in unresectable HCC. Therefore, we conducted a retrospective analysis to evaluate the efficacy and safety of combining HAIC with lenvatinib and PD-1 inhibitors as a first-line therapeutic approach in high-burden HCC patients.

We conducted a retrospective analysis on patients diagnosed with high-burden HCC who had major portal vein tumor thrombosis (Vp3 and Vp4) or tumor occupancy exceeding 50% of the liver. These patients received a first-line treatment consisting of HAIC with a combination of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), along with lenvatinib and PD-1 inhibitors between November 2020 and June 2023. The primary endpoints of this study included progression-free survival (PFS) and overall survival (OS), while the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs).

Ninety-one patients were enrolled in this study, with a median PFS of 8.8 months (95% confidence interval [CI]: 5.75-11.78) and a median OS of 14.3 months (95% CI: 11.23-17.31). According to RECIST 1.1 criteria, the ORR was 52.7%, and DCR was 95.6%. According to the mRECIST criteria, the ORR was 72.5%, and the DCR was 96.5%. Among all patients, 86 (94.5%) experienced TRAEs, and there were no instances of treatment-related deaths.

The combination of HAIC-FOLFOX with lenvatinib and PD-1 inhibitors as a first-line therapy has exhibited notable therapeutic efficacy and well-tolerated adverse events among patients with high-burden HCC.

Purpose To investigate the association of tumor arterial burden (TAB) on preoperative MRI with transarterial chemoembolization refractoriness (TACER) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). Materials and Methods This retrospective study included patients with HCC who underwent repeated transarterial chemoembolization (TACE) treatments between January 2013 and December 2020. HCC was confirmed with pathology or imaging, and patients with other tumors, lost follow-up, or with a combination of other treatments were excluded. TACER was defined as viable lesions of more than 50% or increase in tumor number after two or more consecutive TACE treatments, continuous elevation of tumor markers, extrahepatic spread, or vascular invasion. TAB assessed with preoperative MRI was divided into high and low groups according to the median. A Cox proportional hazards model was used to determine the predictors of TACER and PFS. Results A total of 355 patients (median age, 61 years [IQR, 54-67]; 306 [86.2%] men, 49 [13.8%] women) were included. During a median follow-up of 32.7 months, the high TAB group had significantly faster TACER and decreased PFS than the low TAB group (all log-rank P < .001). High TAB was the strongest independent predictor of TACER and PFS in multivariable Cox regression analyses (hazard ratio [HR], 2.23 [95% CI: 1.51, 3.29]; HR, 2.30 [95% CI: 1.61, 3.27], respectively), especially in patients with Barcelona Clinic Liver Cancer stage A or a single tumor. The restricted cubic spline plot demonstrated that the HR of TACER and PFS continuously increased with increasing TAB. Conclusion High preoperative TAB at MRI was a risk factor for faster refractoriness and progression in patients with HCC treated with TACE. Keywords: Interventional-Vascular, MR Angiography, Hepatocellular Carcinoma, Transarterial Chemoembolization, Progression-free Survival, MRI Supplemental material is available for this article. © RSNA, 2024.

This study aimed to evaluate the long-term outcomes of fully laparoscopic ultrasound-guided radiofrequency ablation (LURFA) in malignant hepatic tumors that are difficult to curatively treat with the percutaneous approach or laparoscopic liver resection (LLR).

Between 2011 and 2021, 62 patients with malignant hepatic tumors (37 hepatocellular carcinomas [HCCs] and 25 metastatic colorectal cancers [mCRCs]), who were not feasible to be curatively treated by percutaneous radiofrequency ablation or LLR, were enrolled and treated only by LURFA. Patients who underwent concurrent surgical resection were excluded. The cumulative incidence rates of local recurrence (LR) and survival were analyzed.

All 93 tumors with a median diameter of 22.0 mm (IQR, 8.0-50.0) and a median number of 1.5 tumors (IQR, 1.0-6.0) in 62 patients were successfully treated. According to the IWATE criteria for LLR, 33 of 62 patients (53.2%) had tumors in difficult locations (segments I, VII, VIII, and IVa). Over a median follow-up period of 92.4 months (IQR, 60.0-128.0), the 1-, 2-, 3-, 5-, 8-, and 10-year cumulative incidence rates of LR were 6.9%, 13.8%, 17.2%, 17.2%, 20.9%, and 20.9%, respectively. In patients with HCC, 1-, 3-, 5-, and 8-year survival rates were 97.2%, 80.6%, 55.6%, and 40.1%, respectively. In patients with mCRC, 1-, 3-, 5-, and 8-year survival rates were 100.0%, 36.4%, 27.3%, and 16.4%, respectively. Adverse events of grade 3 occurred in only 3 of 62 patients (4.8%).

Full LURFA is a safe and effective treatment for malignant hepatic tumors, even in difficult percutaneous ablation or LLR areas.

To investigate the imaging features indicating portal vein invasion (PVI) of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI and to create more accurate diagnostic criteria than the presence of portal vein tumor thrombosis (PVTT) on MRI.

This retrospective study included patients with surgically resected HCC larger than 5 cm, and the presence of PVI was investigated. On MRI, we evaluated the image findings of portal vein occlusion, the parenchymal signal change caused by hemodynamic alterations of the portal vein, and their combination showing the highest odds ratio (OR) to define the diagnostic criteria for radiological PVI detection (rPVI criteria). The diagnostic performance and recurrence-free survival were compared between the rPVI criteria and the presence of PVTT using McNemar's test and Kaplan-Meier method, respectively. Interobserver agreement was evaluated using Cohen's weighted ĸ statistics.

Of 189 enrolled patients, 25 (13.2%) had PVI on histology. To diagnose PVI on MRI, either peripheral wedge-shaped arterial peritumoral hyperemia with an abrupt cut-off of a portal vein or the presence of PVTT had the highest OR (41.67, p < 0.001). The sensitivity of PVI was significantly increased under this diagnostic criterion (64.0% to 88.0%; p = 0.031) with comparable accuracy (95.2% vs. 94.7%; p > 0.999). In terms of recurrence-free survival, the patient group with rPVI was significantly worse (p = 0.017) compared with the patients without rPVI. Interobserver agreement of radiologic findings was substantial (ĸ = 0.64).

Diagnostic criteria for radiologically PVI detection increase the sensitivity more than the only presence of PVTT.

Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC), but recurrence after TACE is common. The present phase 2, prospective, multicenter, single-arm trial, the TACTICS-L trial, investigated the efficacy and safety of TACE plus lenvatinib (LEN), a drug that more strongly promotes vascular normalization and has a better objective response rate (ORR) than sorafenib (jRCTs031180074).

Participants were patients with HCC who had not previously received systemic therapy, hepatic arterial infusion chemotherapy, or immunotherapy and who were ineligible for resection or percutaneous ablation therapy. LEN was to be administered 14-21 days before the first TACE, stopped 2 days before TACE, and resumed 3 days after TACE. Key inclusion criteria were unresectable HCC, Child-Pugh A liver function, 0-2 prior TACE sessions, tumor size ≤10 cm, number of tumors ≤10, and ECOG performance status 0-1. Key exclusion criteria were vascular invasion and extrahepatic spread. The primary endpoint was progression-free survival (PFS) by RECICL, and secondary endpoints were time to untreatable progression, ORR, overall survival (OS), and safety.

A total of 62 HCC patients were enrolled in this trial. The median age was 72 years, 77.4% of patients were men, and 95.2% had PS 0. The primary endpoint of median PFS was 28.0 months (90% confidence interval [CI] 25.1-31.0) after a minimum 24 months of follow-up. The secondary endpoint of median OS was not reached (90% CI 35.5 months-NR). LEN-TACE achieved a high response rate and high complete response (CR) rate (4 weeks after the first TACE: ORR 79.0%, CR rate 53.2%; best response: ORR 88.7%, CR rate 67.7%) by RECICL. Exploratory subgroup analyses showed that the characteristics of responders/nonresponders (ORR and CR rate) were similar and that LEN-TACE would be effective in all subgroups, including the population in whom TACE alone would be less likely to be curative (e.g., patients with the non-simple nodular type or a high tumor burden). The relative dose intensity of LEN before the first TACE was important for achieving higher CR rate/ORR by LEN-TACE. No new safety concerns were observed.

The results of this trial provide encouraging evidence, supporting the efficacy and favorable safety profile of LEN-TACE in patients who are ineligible for locoregional therapy.

For patients with primary and secondary liver tumors that are functionally or technically nonresectable, liver transplantation remains the sole curative treatment option. Over the years the benefits of transplantation have also been validated for conditions other than hepatocellular carcinoma. Currently, amidst a period of organ shortage the broadening of transplantation indications is a topic of ongoing debate. Although recent studies have confirmed the long-term success of transplantation within multimodal treatment regimens, this approach has yet to become the standard treatment for many conditions.

This article explores the potential of liver transplantation in individualized multimodal oncological treatment strategies.

Liver transplantation has become an integral component of the treatment regimen for hepatocellular carcinoma. In Germany there is a prioritized organ allocation facilitated by the granting of a standard exception for cases with a smaller tumor burden. Over the years numerous studies have demonstrated comparable long-term results using different listing criteria. Both intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma can be curatively treated with transplantation in Germany, although this is typically within the context of clinical studies. The neoadjuvant therapy and patient selection, based on tumor burden and the response to preliminary treatment, play a crucial role in influencing long-term survival and recurrence rates. The success of transplantation for liver metastases from neuroendocrine malignancies or colorectal carcinomas, which cannot be removed by partial resection, also significantly hinges on the patient selection. The role of living donor liver transplantation is becoming increasingly more pivotal in this context.

Transarterial chemoembolization (TACE) represents a significant therapeutic modality for hepatocellular carcinoma (HCC). We aimed to develop a gene signature to accurately predict patient TACE response and explore the underlying mechanisms.

Three independent datasets were utilized, including GSE104580, GSE14520 and external validation from the Cancer Hospital Chinese Academy of Medical Sciences. GSE104580 was randomly partitioned into a training set and a validation set, whereas GSE14520 was categorized into a resection group and a TACE group. Logistic regression was used to develop a TACE effectiveness model. Immunohistochemistry is utilized to confirm the protein expression trends of the signature genes. Immune infiltration and functional enrichment analyses were conducted to investigate the potential underlying mechanisms.

A 2-gene signature consisting of glycine N-methyltransferase (GNMT) and matrix metalloproteinase-12 (MMP12) was constructed, and based on this, all the patients were assigned TACE effectiveness scores and categorized into high effectiveness (HE) and low effectiveness (LE) groups. The HE group exhibited a better prognosis than the LE group in the various cohorts (p < 0.05). In the external validation set, immunohistochemistry confirmed the expression of the signature genes exhibiting an upregulated trend of GNMT in the HE group and MMP12 in the LE group, the LE group also exhibited a poorer prognosis [for overall survival (OS), HE group: 881 days vs LE group: 273 days (p < 0.05), and for progression-free survival (PFS), HE group: 458 days vs LE group: 136 days (p < 0.05)]. Multivariate analysis in all the datasets identified LE status as an independent risk factor for OS, disease-free survival (DFS) and PFS. The infiltration level of M0 macrophages and activated mast cells in the LE group was significantly higher than in the HE group. The hypoxia signaling pathway and glycolysis pathway were significantly enriched in the LE group.

The loss of GNMT and the overexpression of MMP12 may be critical factors influencing TACE efficacy.

The purpose of this study was to investigate the added value of color parameter imaging (CPI) in the differential diagnosis of focal liver lesions (FLLs) with "homogeneous hyperenhancement but not wash out" on contrast-enhanced ultrasound (CEUS).

A total of 101 patients with 108 FLLs were enrolled in this study. All the FLLs received US and CEUS examinations. The stored CEUS clips of target lesions were postprocessed with CPI analysis by radiologists. The receiver operator characteristic (ROC) curve was used to evaluate the added value of CPI. The McNamara test was used to compare the diagnostic sensitivity, specificity, and accuracy between CEUS and CPI patterns. Univariate and multivariate logistic regression analyses were used to develop a CPI nomogram. The C index and calibration curve were used to evaluate the predictive ability of the nomogram. The intraclass correlation coefficient was used to test the reproducibility and reliability of CPI. Decision curve analysis (DCA) was used to evaluate the added value of applying CPI.

The following CPI features were more frequently observed in malignant FLLs: eccentric perfusion (malignant: 70.0% vs. benign: 29.2%, p < 0.001), feeding artery (51.7% vs. 4.2%, p < 0.001), mosaic (63.3% vs. 6.3%, p < 0.001), red ingredients >1/3 (90.0% vs. 14.6%, p < 0.001). In addition, centripetal (43.8% vs. 18.3%, p = 0.004), peripheral nodular (54.2% vs. 1.7%, p < 0.001), subcapsular vessel (12.5% vs. 0.0%, p = 0.004), spoke-wheel vessels (25.0% vs. 5.0%, p = 0.003), branched vessels (22.9% vs. 5.0%, p = 0.006), blue and pink ingredients >2/3 (85.4% vs. 10.0%, p < 0.001) were more observed in benign FLLs. A nomogram incorporating peripheral nodular, spoke-wheel vessels, and red ingredients >1/3 was constructed. The model had satisfactory discrimination (AUC = 0.937), and the optimal diagnostic threshold value was 0.740 (0.983, 0.850). By the DCA, the model offered a net benefit over the treat-all-patients scheme or the treat-none scheme at a threshold probability 5%-93%.

Using CPI can detect and render subtle information of the main features of FLLs on CEUS; it is conducive to the radiologist for imaging interpretation, and a combining read of the CEUS and CPI of the FLLs with features of "homogenous hyperenhancement and no washout" can improve significantly the diagnostic performance of CEUS for FLLs.

The synergistic effect of locoregional therapy in combination with systemic therapy as a conversion therapy for unresectable hepatocellular carcinoma (uHCC) is unclear. The purpose of this study was to evaluate the efficacy and safety of transcatheter arterial chemoembolisation (TACE) combined with lenvatinib and camrelizumab (TACE + LEN + CAM) as conversion therapy for uHCC.

This single-arm, multicentre, prospective study was conducted at nine hospitals in China. Patients (aged 18-75 years) diagnosed with uHCC, an Eastern Cooperative Oncology Group performance score (ECOG-PS) of 0-1 and Child-Pugh class A received camrelizumab (200 mg, every 3 weeks) and lenvatinib (bodyweight ≥60 kg: 12 mg/day; <60 kg: 8 mg/day) after TACE treatment. Surgery was performed after tumour was assessed as meeting the criteria for resection. Patients who did not meet the criteria for surgery continued to receive triple therapy until disease progression or intolerable toxicity. Primary endpoints were objective response rate (ORR) according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and safety. Secondary endpoints included the surgical conversion rate, radical (R0) resection rate, and disease control rate (DCR). This study was registered with Chinese Clinical Trial Registry (ChiCTR2100050410).

Between Oct 25, 2021, and July 20, 2022, 55 patients were enrolled. As of the data cutoff on June 1, 2023, the median follow-up was 13.3 months (IQR 10.6-15.9 months). The best tumour response to triple therapy was complete response (CR) in 9 (16.4%) patients, partial response (PR) in 33 (60.0%) patients, stable disease (SD) in 5 (9.1%) patients, or progressive disease (PD) in 7 (12.7%) patients. The ORR was 76.4% (42/55, 95% CI, 65.2-87.6%), and the DCR was 85.5% (47/55, 95% CI, 76.2-94.8%) per mRECIST. Twenty-four (43.6%) of the 55 patients suffered from grade 3-4 treatment-related adverse events (TRAEs). No grade 5 TRAEs occurred. A total of 30 (30/55, 54.5%) patients were converted to resectable HCC and 29 (29/55, 52.7%) patients underwent resection. The R0 resection rate was 96.6% (28/29). The major pathologic response (MPR) and pathologic complete response (pCR) rates in the surgery population were 65.5% (19/29) and 20.7% (6/29), respectively. Only one patient developed a Clavien-Dindo IIIa complication (abdominal infection). No Clavien-Dindo IIIb-V complications occurred. The median OS and median PFS were not reached.

The triple therapy (TACE + LEN + CAM) is promising active for uHCC with a manageable safety. Moreover, triple therapy has good conversion efficiency and the surgery after conversion therapy is feasible and safe. To elucidate whether patients with uHCC accepting surgical treatment after the triple therapy can achieve better survival benefits than those who receive triple therapy only, well-designed randomised controlled trials are needed.

This study was funded by the Natural Science Foundation of Fujian Province, China (2022J01691) and the Youth Foundation of Fujian Province Health Science and Technology Project, China (2022QNA035).

Intermediate-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI) is associated with high recurrence rates and poor survival outcomes after surgery. This study aimed to evaluate the efficacy of postoperative transarterial chemoembolization (TACE) on prognosis of intermediate-stage HCC patients with MVI after curative liver resection (LR).

Patients who had intermediate-stage HCC with MVI and underwent curative LR between January 2013 and December 2019 at three institutions in China were identified for further analysis. Overall survival (OS) and recurrence-free survival (RFS) were compared between patients treated with and without postoperative TACE by propensity score-matching.

A total of 246 intermediate-stage HCC patients with MVI were enrolled, 137 entered into the LR group and 109 entered into the LR+TACE group. The 1-year, 3-year, and 5-year RFS rates were 42.0, 27.2, and 17.8% in LR+TACE group, and 31.8, 18.2, and 8.7% in LR group. The 1-year, 3-year, and 5-year OS rates were 81.7, 47.2, and 26.1% in the LR+TACE group, and 67.3, 35.6, and 18.5% in the LR group. Compared with LR alone, LR+TACE was associated with significantly better RFS [hazard ratio (HR), 1.443; 95% CI: 1.089-1.914; P =0.009] and OS (HR, 1.438; 95% CI: 1.049-1.972; P =0.023). No difference was observed with RFS and OS in single TACE and multiple TACE in the matched cohort.

Postoperative adjuvant TACE could be beneficial for intermediate-stage HCC patients with MVI.

Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core "S-D-A-D-S" NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application.

To investigate the efficacy and safety of tyrosine kinase inhibitors (TKIs: sorafenib and lenvatinib) plus PD-1 inhibitor (camrelizumab) versus TKIs alone in transarterial chemoembolization-refractory (TACE-refractory) hepatocellular carcinoma (HCC).

Data of TACE-refractory HCC patients treated with TACE+TKIs+PD-1 inhibitor (TACE+TKIs+PD-1group) (n=57) or TACE+TKIs (TACE+TKIs group) (n=50) from January 2019 to January 2022 were retrospectively collected and analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were evaluated by univariate and multivariate analyses.

Compared with the TKIs group, both PFS and OS were prolonged in the TACE+TKIs+PD-1 group (median PFS: 7 months vs. 5 months, P=0.007; median OS: 17 months vs. 11 months, P=0.002). In multivariate analysis, tumor size and treatment were independent prognostic factors for PFS and OS. The incidence and severity of AEs related to the treatment between the two groups showed no significant difference.

The treatment of TACE combined with TKIs plus camrelizumab demonstrated promising efficacy and safety in TACE-refractory HCC.