Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma (uHCC). HAIC-based treatment showed great potential for treating uHCC. However, large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking. AIM: To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors, programmed cell death of protein 1 (PD-1) and its ligand (PD-L1) blockers (triple therapy) under real-world conditions. METHODS: Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis. Study-level pooled analyses of hazard ratios (HRs) and odds ratios (ORs) were performed. This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades (AIPB) at Sun Yat-sen University Cancer Center from January 2018 to April 2023. Propensity score matching (PSM) was performed to balance the bias between the groups. The Kaplan-Meier method and cox regression were used to analyse the survival data, and the log-rank test was used to compare the suvival time between the groups. RESULTS: A total of 13 randomized controlled trials were included. HAIC alone and in combination with sorafenib were found to be effective treatments (P values for ORs: HAIC, 0.95; for HRs: HAIC + sorafenib, 0.04). After PSM, 176 HCC patients were included in the analysis. The triple therapy group (n = 88) had a longer median overall survival than the AIPB group (n = 88) (31.6 months vs 14.6 months, P < 0.001) and a greater incidence of adverse events (94.3% vs 75.4%, P < 0.001). CONCLUSION: This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC. Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Microwave ablation versus liver resection for primary intrahepatic cholangiocarcinoma within Milan criteria: a long-term multicenter cohort study.

Background: Ablation has been recommended by worldwide guidelines as first-line treatment for hepatocellular carcinoma (HCC), while evidence regarding its efficacy for primary intrahepatic cholangiocarcinoma (iCCA) is lacking. We aimed to study the efficacy of ablation in treating iCCA by comparing its prognosis with surgery. Methods: In this real-world multicenter cohort study from January 2009 to June 2022, 10,441 iCCA patients from ten tertiary hospitals were identified. Patients who underwent curative-intent microwave ablation (MWA) or liver resection (LR) for tumors within Milan criteria were included. One-to-many propensity score matching (PSM) at variable ratios (1:n ≤4) was used to balance baseline characteristics. Mediation analysis was applied to identify potential mediators of the survival difference. Findings: 944 patients were finally enrolled in this study, with 221 undergoing MWA and 723 undergoing LR. After PSM, 203 patients in the MWA group were matched with 588 patients in the LR group. The median follow-up time was 4.7 years. Compared with LR, MWA demonstrated similar overall survival (5-year 44.8% versus 40.4%; HR 0.96, 95% CI 0.71-1.29, P = .761). There was an improvement in the 5-year disease-free survival rate for MWA from 17.1% during the period of 2009-2016 to 37.3% during 2017-2022, becoming comparable to the 40.8% of LR (P = .129). The proportion of ablative margins ≥5 mm increased from 25% to 61% over the two periods, while this proportion of surgical margins was 62% and 77%, respectively. 34.5% of DFS disparity can be explained by the mediation effect of margins (P < .0001). Similar DFS was observed when both ablative and surgical margins exceeded 5 mm (HR 0.83, 95% CI 0.52-1.32, P = .41). Interpretation: MWA may be considered as a viable alternative to LR for iCCA within Milan criteria when an adequate margin can be obtained. Funding: National Natural Science Foundation of China.

Pseudo-capsulated Hepatocellular Carcinoma: Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization.

RATIONALE AND OBJECTIVES: The effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolization (TACE) for cases with single pseudo-capsuled hepatocellular carcinoma (pHCC), as well as their survival outcomes, were investigated. MATERIALS AND METHODS: A total of 196 cases with single pHCC (diameter >5 cm) receiving initial HAIC (n = 92) and TACE (n = 104) were enrolled. The propensity score match (PSM) approach based on Cox models was employed to tune any possible imbalance in treatment assignment. The overall survival (OS), objective response rate (ORR), progression-free survival (PFS), and partial response rate (PRR) of the subjects were investigated using the log-rank test. The independent risk factors for outcomes were investigated by univariate and multivariate analyses, and the results were analyzed using the Cox regression model. RESULTS: The median follow-up of the subjects was 22.3 months. After PSM, no significant difference was found in the OS of the HAIC and TACE groups (OS, 12.0 vs. 16.8 months; P = .267), while the median PFS of the TACE group was prolonged compared with the HAIC group (PFS, 5.7 vs. 2.8 months; P = .003). Moreover, PRR and ORR of the TACE group were prolonged compared with the HAIC group (PRR, 34.6% vs. 21.7%; P = .046; ORR, 35.6% vs. 21.7%; P = .033). The nomogram model showed high predictive accuracy and significant discrimination. CONCLUSION: TACE therapy could delay tumor progression compared with HAIC for cases with a single pHCC.

Camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and hepatic artery infusion chemotherapy for hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (TRIPLET): a phase II study.

Hepatic arterial infusion chemotherapy (HAIC) using a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promise for hepatocellular carcinoma (HCC) patients classified under Barcelona Clinic Liver Cancer (BCLC) stage C. In China, the combined therapy of camrelizumab and apatinib is now an approved first-line approach for inoperable HCC. This study (NCT04191889) evaluated the benefit of combining camrelizumab and apatinib with HAIC-FOLFOX for HCC patients in BCLC stage C. Eligible patients were given a maximum of six cycles of HAIC-FOLFOX, along with camrelizumab and apatinib, until either disease progression or intolerable toxicities emerged. The primary outcome measured was the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Thirty-five patients were enrolled. Based on RECIST v1.1 criteria, the confirmed ORR stood at 77.1% (95% CI: 59.9% to 89.6%), with a disease control rate of 97.1% (95% CI: 85.1% to 99.9%). The median progression-free survival was 10.38 months (95% CI: 7.79 to 12.45). Patient quality of life had a transient deterioration within four cycles of treatment, and generally recovered thereafter. The most frequent grade ≥3 or above treatment-related adverse events included reduced lymphocyte count (37.1%) and diminished neutrophil count (34.3%). The combination of camrelizumab, apatinib, and HAIC demonstrated encouraging results and manageable safety concerns for HCC at BCLC stage C.

A multitask deep learning radiomics model for predicting the macrotrabecular-massive subtype and prognosis of hepatocellular carcinoma after hepatic arterial infusion chemotherapy.

BACKGROUND: The macrotrabecular-massive (MTM) is a special subtype of hepatocellular carcinoma (HCC), which has commonly a dismal prognosis. This study aimed to develop a multitask deep learning radiomics (MDLR) model for predicting MTM and HCC patients' prognosis after hepatic arterial infusion chemotherapy (HAIC). METHODS: From June 2018 to March 2020, 158 eligible patients with HCC who underwent surgery were retrospectively enrolled in MTM related cohorts, and 752 HCC patients who underwent HAIC were included in HAIC related cohorts during the same period. DLR features were extracted from dual-phase (arterial phase and venous phase) contrast-enhanced computed tomography (CECT) of the entire liver region. Then, an MDLR model was used for the simultaneous prediction of the MTM subtype and patient prognosis after HAIC. The MDLR model for prognostic risk stratification incorporated DLR signatures, clinical variables and MTM subtype. FINDINGS: The predictive performance of the DLR model for the MTM subtype was 0.968 in the training cohort [TC], 0.912 in the internal test cohort [ITC] and 0.773 in the external test cohort [ETC], respectively. Multivariable analysis identified portal vein tumor thrombus (PVTT) (p = 0.012), HAIC response (p < 0.001), HAIC sessions (p < 0.001) and MTM subtype (p < 0.001) as indicators of poor prognosis. After incorporating DLR signatures, the MDLR model yielded the best performance among all models (AUC, 0.855 in the TC, 0.805 in the ITC and 0.792 in the ETC). With these variables, the MDLR model provided two risk strata for overall survival (OS) in the TC: low risk (5-year OS, 44.9%) and high risk (5-year OS, 4.9%). INTERPRETATION: A tool based on MDLR was developed to consider that the MTM is an important prognosis factor for HCC patients. MDLR showed outstanding performance for the prognostic risk stratification of HCC patients who underwent HAIC and may help physicians with therapeutic decision making and surveillance strategy selection in clinical practice.

Nanocompartment-confined polymerization in living systems.

Polymerization in living systems has become an effective strategy to regulate cell functions and behavior. However, the requirement of high concentrations of monomers, the existence of complicated intracorporal interferences, and the demand for extra external stimulations hinder their further biological applications. Herein, a nanocompartment-confined strategy that provides a confined and secluded environment for monomer enrichment and isolation is developed to achieve high polymerization efficiency, reduce the interference from external environment, and realize broad-spectrum polymerizations in living systems. For exogenous photopolymerization, the light-mediated free-radical polymerization of sodium 4-styrenesulfonate induces a 2.7-fold increase in the reaction rate with the protection of a confined environment. For endogenous hydrogen peroxide-responsive polymerization, p­aminodiphenylamine hydrochloride embedded in a nanocompartment not only performs a 6.4-fold higher reaction rate than that of free monomers, but also activates an effective second near-infrared photoacoustic imaging-guided photothermal immunotherapy at tumor sites. This nanocompartment-confined strategy breaks the shackles of conventional polymerization, providing a universal platform for in vivo synthesis of polymers with diverse structures and functions.

Development and validation of prognostic nomograms for large hepatocellular carcinoma after HAIC.

Background and aims: Hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen (oxaliplatin plus fluorouracil and leucovorin) is a promising option for large hepatocellular carcinoma (HCC). However, post-HAIC prognosis can vary in different patients due to tumor heterogeneity. Herein, we established two nomogram models to assess the survival prognosis of patients after HAIC combination therapy. Methods: A total of 1082 HCC patients who underwent initial HAIC were enrolled between February 2014 and December 2021. We built two nomogram models for survival prediction: the preoperative nomogram (pre-HAICN) using preoperative clinical data and the postoperative nomogram (post-HAICN) based on pre-HAICN and combination therapy. The two nomogram models were internally validated in one hospital and externally validated in four hospitals. A multivariate Cox proportional hazards model was used to identify risk factors for overall survival (OS). The performance outcomes of all models were compared by area under the receiver operating characteristic curve (AUC) analysis with the DeLong test. Results: Multivariable analysis identified larger tumor size, vascular invasion, metastasis, high albumin-bilirubin grade, and high alpha-fetoprotein as indicators for poor prognosis. With these variables, the pre-HAICN provided three risk strata for OS in the training cohort: low risk (5-year OS, 44.9%), middle risk (5-year OS, 20.6%), and high risk (5-year OS, 4.9%). The discrimination of the three strata was improved significantly in the post-HAICN, which included the above-mentioned factors and number of sessions, combination with immune checkpoint inhibitors, tyrosine kinase inhibitors, and local therapy (AUC, 0.802 versus 0.811, p < 0.001). Conclusions: The nomogram models are essential to identify patients with large HCC suitable for treatment with HAIC combination therapy and may potentially benefit personalized decision-making. Lay summary: Hepatic arterial infusion chemotherapy (HAIC) provides sustained higher concentrations of chemotherapy agents in large hepatocellular carcinoma (HCC) by hepatic intra-arterial, result in better objective response outperformed the intravenous administration. HAIC is significantly correlated with favorable survival outcome and obtains extensive support in the effective and safe treatment of intermediate advanced-stage HCC. In view of the high heterogeneity of HCC, there is no consensus regarding the optimal tool for risk stratification before HAIC alone or HAIC combined with tyrosine kinase inhibitors or immune checkpoint inhibitors treatment in HCC. In this large collaboration, we established two nomogram models to estimate the prognosis and evaluate the survival benefits with different HAIC combination therapy. It could help physicians in decision-making before HAIC and comprehensive treatment for large HCC patients in clinical practice and future trials.

Postprogression treatment of lenvatinib plus PD-1 inhibitor in advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.

PURPOSE: This study compares the efficacy and safety of lenvatinib and programmed cell death protein (PD)-1 versus lenvatinib alone for advanced hepatocellular carcinoma (Ad-HCC) refractory to hepatic arterial infusion chemotherapy (HAIC). METHODS: From April 2016 to September 2021, 145 patients with Ad-HCC refractory to HAIC based on modified Response Evaluation Criteria in Solid Tumors criteria were enrolled by two radiologists and classified into the HAIC-lenvatinib group (H-L, n = 87) and HAIC-lenvatinib-PD-1 group (H-L-P, n = 58). A propensity score-matching method was used to reduce selective bias. The overall survival (OS) and postprogression-free survival (PPS) rates were compared using the Kaplan-Meier method with log-rank test. Multivariable analyses of independent prognostic factors were evaluated by means of the forward stepwise Cox regression model. RESULTS: After propensity score matching 1:1, the median OS was 43.6 months in the H-L-P group and was significantly longer than that (18.9 months) of the H-L group (p = .009). The median PPS was 35.6 months in the H-L-P group and was significantly longer than that (9.4 months) of the H-L group (p = .009). Multivariate analyses showed that the factors that significantly affected the OS were α-fetoprotein (hazard ratio [HR], 2.14; 95% CI, 1.26-3.98; p = .006), early response to HAIC (HR, 0.44; 95% CI, 1.20-3.85; p = .009), and H-L treatment (HR, 0.52; 95% CI, 0.30-0.86; p = .012). Modified albumin-bilirubin grade (HR, 1.32; 95% CI, 1.03-1.70; p = .026), early response to HAIC (HR, 0.44; 95% CI, 0.25-0.77; p = .004), and H-L (HR, 0.47 ; 95% CI, 0.28-0.78; p = .003) significantly affected the PPS. CONCLUSIONS: This combination therapy of PD-1 inhibitors plus lenvatinib has promising survival benefits in the management of patients with Ad-HCC refractory to HAIC. PLAIN LANGUAGE SUMMARY: Lenvatinib plus programmed death 1 inhibitor is an effective and safe postprogression treatment and improved significantly overall survival and postprogression-free survival compared with lenvatinib alone in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.

Combining Preoperative Clinical and Imaging Characteristics to Predict MVI in Hepatitis B Virus-Related Combined Hepatocellular Carcinoma and Cholangiocarcinoma.

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) is a rare form of primary liver malignancy. Microvascular invasion (MVI) indicates poor postsurgical prognosis in cHCC-CCA. The objective of this study was to investigate preoperative predictors of MVI in hepatitis B virus (HBV) -related cHCC-CCA patients. METHODS: A total of 69 HBV-infected patients with pathologically confirmed cHCC-CCA who underwent hepatectomy were included. Univariate and multivariate analyses were conducted to determine independent risk factors that were then incorporated into the predictive model associated with MVI. Receiver operating characteristic analysis was used to assess the predictive performance of the new model. RESULTS: For the multivariate analysis, γ-glutamyl transpeptidase (OR, 3.69; p = 0.034), multiple nodules (OR, 4.41; p = 0.042) and peritumoral enhancement (OR, 6.16; p = 0.004) were independently associated with MVI. Active replication of HBV indicated by positive HBeAg showed no differences between MVI-positive and MVI-negative patients. The prediction score using the independent predictors achieved an area under the curve of 0.813 (95% CI 0.717-0.908). A significantly lower recurrence-free survival was observed in the high-risk group with a score of ≥1 (p < 0.001). CONCLUSION: γ-glutamyl transpeptidase, peritumoral enhancement and multiple nodules were independent preoperative predictors of MVI in HBV-related cHCC-CCA patients. The established prediction score demonstrated satisfactory performance in predicting MVI pre-operatively and may facilitate prognostic stratification.

Effect of percutaneous stenting strategy of unresectable malignant hilar biliary obstruction by three-dimensional reconstruction volumetry.

PURPOSE: To explore clinical outcomes of percutaneous stent implantation using volumetric criteria for unresectable malignant hilar biliary obstruction (MHBO). Additionally, aimed to identify the predictors of patients' survival. METHODS: Seventy-two patients who were initially diagnosed with MHBO between January 2013 to December 2019 in our center were retrospectively included. Patients were stratified according to the drainage achieved ≥50%, <50% of the total liver volume. Patients were divided into two groups: Group A (≥50% drainage), and Group B (<50% drainage). The main outcomes were evaluated in terms of relief of jaundice, effective drainage rate, and survival. Related factors that affect survival were analyzed. RESULTS: 62.5% of the included patients reached effective biliary drainage. The successful drainage rate was significantly higher in Group B than in Group A (p < 0.001). The median overall survival (mOS) of included patients was 6.4 months. Patients who received drainage ≥50% of hepatic volume achieved longer mOS than those who received drainage <50% of hepatic volume (7.6 months vs. 3.9 months, respectively, p = 0. 011). Patients who received effective biliary drainage had longer mOS than those who received ineffective biliary drainage (10.8 months vs. 4.4 months, respectively, p < 0.001). Patients who received anticancer treatment had longer mOS than those who only received palliative therapy (8.7 months vs. 4.6 months, respectively, p = 0.014). In the multivariate analysis, KPS Score ≥ 80 (p = 0.037), ≥50% drainage achieved (p = 0.038), and effective biliary drainage (p = 0.036) were protective prognostic factors that affected patients' survival. CONCLUSION: Drainage achieved ≥50% of the total liver volume by percutaneous transhepatic biliary stenting seemed to have a higher effective drainage rate in MHBO patients. Effective biliary drainage may create chances for these patients to receive anticancer therapies that seem to provide survival benefits.

TIPS plus sequential systemic therapy of advanced HCC patients with tumour thrombus-related symptomatic portal hypertension.

OBJECTIVES: Portal vein tumour thrombus (PVTT)-related symptomatic portal hypertension (SPH) leads to a poor prognosis in hepatocellular carcinoma (HCC) patients. A transjugular intrahepatic portosystemic shunt (TIPS) can effectively relieve SPH but its effect remains unclear in PVTT-related SPH. This study aimed to evaluate the clinical value of the TIPS procedure combined with sequential systemic therapy in advanced HCC patients with PVTT-related SPH. METHODS: After 1:1 propensity score matching (PSM), this retrospective study analysed 42 patients who underwent TIPS placement plus sequential systemic therapy (group A) and 42 patients who received only symptomatic and supportive treatment (group B). The evaluated outcomes were overall survival (OS) and SPH control rate. Cox proportional hazards regression analysis was used to compare OS in the two groups. RESULTS: In group A, the technical success rate of the TIPS procedure was 95.2%, and no severe complications occurred. The rebleeding rates in group A and group B were 5.0% and 73.7%, respectively (p < 0.001), and the ascites control rates were 92.0% and 28.0%, respectively (p < 0.001). The median OS of group A was significantly better than that of group B (9.6 [95% CI: 7.1, 12.0] vs. 4.9 [95% CI: 3.9, 5.8], months, p < 0.001). Multivariable analysis showed that TIPS plus sequential systemic therapy (hazard ratio [HR] = 5.799; 95% CI: 3.177, 10.585; p < 0.001) was an independent prognostic factor related to OS. Additionally, PVTT degree (I+II) (p = 0.008), AFP ≤ 400 ng/ml (p = 0.003), and Child-Pugh class A (p = 0.046) were significant predictors of OS. CONCLUSION: TIPS plus sequential systemic therapy is safe and feasible for treating advanced HCC with tumour thrombus-related SPH. KEY POINTS: • Portal vein tumour thrombus (PVTT) is common in advanced hepatocellular carcinoma (HCC) and transforms compensated portal hypertension into symptomatic portal hypertension (SPH). • HCC patients with PVTT-related SPH have a very poor prognosis, and there are no effective treatments recommended by the guidelines. • Therefore, a treatment strategy that utilises a transjugular intrahepatic portosystemic shunt (TIPS) to manage SPH combined with sequential systemic therapy in advanced HCC patients is explored in this study for its feasibility and clinical value. This research can fill the gap in current research data to provide clinically meaningful treatment options.

Single-Centre Retrospective Study Using Propensity Score Matching Comparing Left Versus Right Internal Jugular Vein Access for Transjugular Intrahepatic Portosystemic Shunt (TIPS) Creation.

PURPOSE: To compare the safety and efficacy of left versus right internal jugular vein access for portal vein puncture during transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with a small liver and short vertical puncture distance. MATERIALS AND METHODS: The vertical distance from the hepatic vein orifice to the puncture point of the portal vein was measured by CT and DSA. A distance ≤ 30 mm is defined as a short vertical puncture distance. After 1:1 propensity score matching (PSM), 29 patients of left internal jugular vein-TIPS (LIJ-TIPS) and 29 patients of right internal jugular vein-TIPS (RIJ-TIPS) were included. The number of needle punctures, fluoroscopy time, and radiation dose during the puncture process were statistically analyzed. RESULTS: There was no significant difference in the average vertical puncture distances on CT or DSA between LIJ-TIPS and RIJ-TIPS (19.10 ± 0.60 mm vs. 19.30 ± 0.60 mm, P = 0.840; 22.02 ± 0.69 mm vs. 22.23 ± 0.64 mm, P = 0.822, respectively). The average number of needle punctures, fluoroscopy time, and radiation dose in LIJ-TIPS were significantly lower than those in RIJ-TIPS (2.07 ± 0.20 vs. 4.10 ± 0.24, P < 0.001; 78.45 ± 12.80 s vs. 201.16 ± 23.71 s, P < 0.001; 31.55 ± 7.04 mGy vs. 136.69 ± 16.38 mGy, P < 0.001, respectively). Within three punctures, the technical success rate in LIJ-TIPS was significantly higher than that in RIJ-TIPS (86.2 vs. 27.6%, P < 0.001). The incidence of hemoperitoneum in LIJ-TIPS was significantly lower than that in RIJ-TIPS (0% vs. 13.8%, P = 0.038). CONCLUSION: The left internal jugular vein could be used as primary access for TIPS creation in patients with a small liver and short vertical puncture distance.

Four types of tumor progression after microwave ablation of single hepatocellular carcinoma of ≤5 cm: incidence, risk factors and clinical significance.

OBJECTIVES: To evaluate the incidence, risk factors and clinical significance of four types of tumor progression (TP) after microwave ablation (MWA) of single hepatocellular carcinoma (HCC) of <5 cm. METHODS: The data of 340 treatment-naïve, HCC patients with a single HCC of <5 cm underwent MWA between April 2012 and November 2017 were retrospectively reviewed. TPs including local tumor progression (LTP), intrahepatic distant recurrence (IDR), aggressive intrasegmental recurrence (AIR) and extrahepatic distant recurrence (EDR) were reviewed and compared between BCLC stage 0 and A. Univariate and multivariate analysis were performed on clinicopathological variables and different TPs to identify factors affecting long-term overall survival (OS). RESULTS: In a median follow-up period of 25.6 months (range, 3.1-61.4 months), the rate of LTP, IDR, AIR and EDR was 6.2% (21/340), 29.1% (98/340), 3.2% (11/340) and 7.9% (27/340). The four types of TP occurrence rates in BCLC stage 0 were comparable to those in BCLC stage A (p = 0.492, 0.971, 0.681 and 0.219). Univariate analysis showed that age (p < 0.001, hazard ratio [HR] = 2.783), comorbidities (p = 0.042, HR = 1.864), IDR, AIR and EDR (p = 0.027, HR = 1.719; p = 0.001, HR = 3.628; p = 0.009, HR = 2.638) were independently associated with OS. Multivariate analysis showed older age (p < 0.001, HR = 2.478), the occurrence of AIR (p < 0.001, HR = 2.648) and the occurrence of EDR (p = 0.002, HR = 2.222), were associated with poor OS. CONCLUSIONS: The occurrence rate of IDR is the highest of all TPs following MWA of a single HCC of <5cm. Old age, AIR and EDR had an adverse effect on long-term OS.

Consensus of Minimally Invasive and Multidisciplinary Comprehensive Treatment for Hepatocellular Carcinoma - 2020 Guangzhou Recommendations.

In China, the majority of patients with hepatocellular carcinoma (HCC) result from long-term infection of hepatitis B. Pathologically, HCC is characterized by rich blood supply, multicentric origins, early vascular invasion and intrahepatic metastasis. Therefore, HCC is not a local disease but a systemic disease at the beginning of its occurrence. For this reason, a comprehensive treatment strategy should be adopted in the management of HCC, including local treatments (such as surgical resection, radiofrequency ablation, microwave ablation, chemical ablation and cryoablation, etc.), organ-level treatments [such as transcatheter arterial infusion of chemotherapy and transcatheter arterial chemoembolization (TACE)], and systemic treatments (such as immunotherapy, antiviral therapy and molecular targeted therapy, etc.). This consensus sets forth the minimally-invasive and multidisciplinary comprehensive guideline of HCC, focusing on the following eight aspects (1) using hepaticarteriography, CT hepatic arteriography (CTHA), CT arterial portography (CTAP), lipiodol CT (Lp-CT), TACE-CT to find the intrahepatic lesion and make precise staging (2) TACE combined with ablation or ablation as the first choice of treatment for early stage or small HCC, while other therapies are considered only when ablation is not applicable (3) infiltrating HCC should be regarded as an independent subtype of HCC (4) minimally-invasive comprehensive treatment could be adopted in treating metastatic lymph nodes (5) multi-level subdivision of M-staging should be used for individualized treatment and predicting prognosis (6) HCC with severe hepatic decompensation is the only candidate criterion for liver transplantation (7) bio-immunotherapy, traditional Chinese medicine therapy, antiviral therapy, and psychosocial and psychopharmacological interventions should be advocated through the whole course of HCC treatment (8) implementation of multicenter randomized controlled trials of minimally-invasive therapy versus surgery for early and intermediate stage HCC is recommended.

Infiltrative Hepatocellular Carcinoma: Transcatheter Arterial Chemoembolization Versus Hepatic Arterial Infusion Chemotherapy.

AIMS: To compare the effectiveness, safety, and survival outcomes in patients with infiltrative hepatocellular carcinoma (HCC) who underwent hepatic arterial infusion chemotherapy (HAIC) and transarterial chemoembolization (TACE). METHODS: A total of 160 patients with infiltrative HCCs who underwent initial TACE (n = 68) and HAIC (n = 92) treatment from January 2016 to March 2020. We applied the propensity score matching (PSM) to adjust for potential imbalances. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were compared between two groups. Multivariate analysis was evaluated through the forward stepwise Cox regression model and ß coefficients was applied for the nomogram construction. RESULTS: The median follow-up duration for the study population was 20.8 months. After PSM, the median OS and PFS in the HAIC group were significantly higher than those in the TACE group (OS, 13.3 vs 10.8 months; p = 0.043; PFS, 7.8 vs 4.0 months; p = 0.035) and the ORR and DCR in the HAIC group were significantly higher than those in the TACE group (ORR, 34.8% vs 11.8%; p = 0.001; DCR, 54.3% vs 36.8%; p = 0.028). A nomogram model comprising albumin-bilirubin grade, treatment responses, sessions, and treatment modalities, showed good predictive accuracy and discrimination (training set, concordance index [C-index] of 0.789; validation set, C-index of 0.757), which outperformed other staging systems and conventional indices. CONCLUSION: HAIC improve significantly survival compared to TACE in patients with infiltrative HCC. A prospective randomized trial is ongoing to confirm this finding.

Development and validation of a clinicopathological-based nomogram to predict seeding risk after percutaneous thermal ablation of primary liver carcinoma.

OBJECTIVES: To develop a clinicopathological-based nomogram to improve the prediction of the seeding risk of after percutaneous thermal ablation (PTA) in primary liver carcinoma (PLC). METHODS: A total of 2030 patients with PLC who underwent PTA were included between April 2009 and December 2018. The patients were grouped into a training dataset (n = 1024) and an external validation dataset (n = 1006). Baseline characteristics were collected to identify the risk factors of seeding after PTA. The multivariate Cox proportional hazards model based on the risk factors was used to develop the nomogram, which was used for assessment for its predictive accuracy using mainly the Harrell's C-index and receiver operating characteristic curve (AUC). RESULTS: The median follow-up time was 30.3 months (range, 3.2-115.7 months). The seeding risk was 0.89% per tumor and 1.5% per patient in the training set. The nomogram was developed based on tumor size, subcapsular, α-fetoprotein (AFP), and international normalized ratio (INR). The 1-, 2-, and 3-year cumulative seeding rates were 0.1%, 0.7% and 1.2% in the low-risk group, and 1.7%, 6.3% and 6.3% in the high-risk group, respectively, showing significant statistical difference (P < .001). The nomogram had good calibration and discriminatory abilities in the training set, with C-indexes of 0.722 (95% confidence interval [CI]: 0.661, 0.883) and AUC of 0.850 (95% CI: 0.767, 0.934). External validation with 1000 bootstrapped sample sets showed a good C-index of 0.706 (95% CI: 0.546, 0.866) and AUC of 0.736 (95% CI: 0. 646, 0.827). CONCLUSIONS: The clinicopathological-based nomogram could be used to quantify the probability of seeding risk after PTA in PLC.

Assessment in the Survival Outcome After Transarterial Chemoembolization Combined with Cryoablation for Hepatocellular Carcinoma (Diameter > 4cm) Based on the Albumin-Bilirubin Grade and Platelet-Albumin-Bilirubin grade: A Preliminary Study.

OBJECTIVE: Based on the albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grade to assess the long-term outcomes of patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with cryoablation (TACE-CRA). MATERIALS AND METHODS: We studied 86 patients with HCC nodules (up to 3 HCCs with maximum diameters of 4.1-12.0 cm) who subsequently underwent TACE-CRA from July 2007 to August 2018. The overall survival (OS) was compared between groups classified by ALBI and PALBI grade. Baseline characteristics were collected to identify the risk factors for determination of poor OS after TACE-CRA. The prognostic performances of CTP class, ALBI and PALBI grade were compared. RESULTS: After a median follow-up time of 33.8 months, 41 patients had died. The cumulative1-, 3- and 5-year OS rates were 74.5%, 38.0% and 29.3%, respectively. Stratified according to ALBI grade, the cumulative 3- and 5-year OS rates were 41.2% and 41.2% in grade 1, respectively, and 20.9% and 9.8% in grades 2-3, respectively (P < 0.001). Stratified according to PALBI grade, the cumulative 3- and 5-year OS rates were 41.2% and 37.5% in grade 1, respectively, and 36.3% and 21.2% in grades 2-3, respectively (P = 0.002). Multivariate analysis results showed that older age, and ALBI grade 2-3 were associated with overall mortality. ALBI grade demonstrated significantly greater area under the curve values than CTP class and PALBI in predicting 1-, 3- and 5-year OS. CONCLUSION: ALBI grade offers accurate prediction of long-term outcome for patients with HCC (diameter > 4 cm) after TACE-CRA.

Bronchobiliary fistula after ablation of hepatocellular carcinoma adjacent to the diaphragm: Case report and literature review.

BACKGROUND: Bronchobiliary fistula is a rare, but life-threatening complication after ablation of hepatocellular carcinoma. Few cases of bronchobiliary fistula have been reported and the treatment is controversial. METHODS: From 2006 to 2019, a total of 11 patients were diagnosed with bronchobiliary fistula after ablation and received nonsurgical treatment. RESULTS: All 11 patients presented with cough and bilioptysis. There were only two patients in which MRI revealed an obvious fistulous tract connecting the pleural effusion and biliary lesions. Pleural effusion, liver abscess and hepatic biloma were found in other patients. Three patients died of uncontrolled bronchobiliary fistula. CONCLUSIONS: Bronchobiliary fistula is a rare post-ablation complication but should be taken into consideration in clinical decisions. Minimally invasive interventional treatment is a relatively effective means of dealing with bronchobiliary fistula, but as for the more severe cases, greater clinical experience is required.

Computed tomography-guided radiofrequency ablation combined with transarterial embolization assisted by a three-dimensional visualization ablation planning system for hepatocellular carcinoma in challenging locations: a preliminary study.

OBJECTIVE: To assess the clinical efficacy and safety of computed tomography-guided radiofrequency ablation(CT-RFA) combined with transarterial embolization(TAE) assisted by a three-dimensional visualization ablation planning system(3DVAPS) for hepatocellular carcinoma(HCC) in challenging locations. METHODS: Data from 62 treatment-naive patients with hepatocellular carcinoma(HCC), with 83 lesions in challenging locations, and who met the Milan criteria and underwent CT-RFA between June 2013 and June 2016 were reviewed. Patients were divided into one of two groups according to different treatment modalities: study group (TAE combined with RFA assisted by 3DVAPS [n = 32]); and control (RFA only [n = 30]). Oncological outcomes included ablation-related complications, local tumor progression (LTP), and overall survival (OS). Univariate and multivariate Cox proportional hazards regression analyses were performed to assess risk factors associated with LTP and OS. RESULTS: HCC lesions (mean size, 1.9 ± 1.0 mm in diameter) abutting the gastrointestinal tract (n = 25), heart and diaphragm (n = 21), major vessels (n = 13), and gallbladder (n = 3) were treated. A significant difference was detected in LTP between the two groups (P = 0.034), with no significant difference in OS between the two groups (P = 0.193). There were no severe complications related to ablation. Univariate analysis revealed that sex (P = 0.046) and child-turcotte-pugh (CTP) grade (P<0.001) were risk factors for OS, whereas CTP grade and treatment method (P<0.001) were risk factors for LTP. Multivariate analysis revealed that CTP grade B (P = 0.005) was independently associated with poor OS, and RFA alone (P<0.001) was independently associated with poor LTP. CONCLUSION: CT-RFA combined with TAE assisted by a 3DVAPS provided ideal clinical efficiency for HCC in challenging locations and was a highly safe treatment modality.