Evaluation of models to predict prognosis in patients with advanced hepatocellular carcinoma treated with TACE combined with apatinib.

BACKGROUND: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. METHODS: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. RESULTS: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. CONCLUSION: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

Assessment of disease control rate and safety of sorafenib in targeted therapy for advanced liver cancer.

OBJECTIVE: The clinical efficacy and safety of sorafenib in patients with advanced liver cancer (ALC) were evaluated based on transarterial chemoembolization (TACE). METHODS: 92 patients with ALC admitted to our hospital from May 2020 to August 2022 were randomly rolled into a control (Ctrl) group and an observation (Obs) group, with 46 patients in each. Patients in the Ctrl group received TACE treatment, while those in the Obs group received sorafenib molecular targeted therapy (SMTT) on the basis of the treatment strategy in the Ctrl group (400 mg/dose, twice daily, followed by a 4-week follow-up observation). Clinical efficacy, disease control rate (DCR), survival time (ST), immune indicators (CD3+, CD4+, CD4+/CD8+), and adverse reactions (ARs) (including mild fatigue, liver pain, hand-foot syndrome (HFS), diarrhea, and fever) were compared for patients in different groups after different treatments. RESULTS: the DCR in the Obs group (90%) was greatly higher to that in the Ctrl group (78%), showing an obvious difference (P < 0.05). The median ST in the Obs group was obviously longer and the median disease progression time (DPT) was shorter, exhibiting great differences with those in the Ctrl group (P < 0.05). Moreover, no great difference was observed in laboratory indicators between patients in various groups (P > 0.05). After treatment, the Obs group exhibited better levels in all indicators. Furthermore, the incidence of ARs in the Obs group was lower and exhibited a sharp difference with that in the Ctrl group (P < 0.05). CONCLUSION: SMTT had demonstrated good efficacy in patients with ALC, improving the DCR, enhancing the immune response of the body, and reducing the incidence of ARs, thereby promoting the disease outcome. Therefore, it was a treatment method worthy of promotion and application.

Microwave coagulation for liver metastases.

BACKGROUND: Liver metastases (i.e. secondary hepatic malignancies) are significantly more common than primary liver cancer. Long-term survival after radical surgical treatment is approximately 50%. For people in whom resection for cure is not feasible, other treatments must be considered. One treatment option is microwave coagulation utilising electromagnetic waves. It involves placing an electrode into a lesion under ultrasound or computed tomography guidance. OBJECTIVES: To evaluate the beneficial and harmful effects of microwave coagulation versus no intervention, other ablation methods, or systemic treatments in people with liver metastases regardless of the location of the primary tumour. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest date of search was 14 April 2023. SELECTION CRITERIA: Randomised clinical trials assessing beneficial or harmful effects of microwave coagulation and its comparators in people with liver metastases, irrespective of the location of the primary tumour. We included trials no matter the outcomes reported. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodological procedures. Our primary outcomes were: all-cause mortality at the last follow-up and time to mortality; health-related quality of life (HRQoL); and any adverse events or complications. Our secondary outcomes were: cancer mortality; disease-free survival; failure to clear liver metastases; recurrence of liver metastases; time to progression of liver metastases; and tumour response measures. We used risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) to present the results. Two review authors independently extracted data and assessed the risk of bias using the Cochrane RoB 1 tool. We used GRADE methodology to assess the certainty of the evidence. MAIN RESULTS: Three randomised clinical trials fulfilled the inclusion criteria. The control interventions differed in the three trials; therefore, meta-analyses were not possible. The trials were at high risk of bias. The certainty of evidence of the assessed outcomes in the three comparisons was very low. Data on our prespecified outcomes were either missing or not reported. Microwave coagulation plus conventional transarterial chemoembolisation (TACE) versus conventional TACE alone One trial, conducted in China, randomised 50 participants (mean age 60 years, 76% males) with liver metastases from various primary sites. Authors reported that the follow-up period was at least one month. The trial reported adverse events or complications in the experimental group only and for tumour response measures. There were no dropouts in the trial. The trial did not report on any other outcomes. Microwave ablation versus conventional surgery One trial, conducted in Japan, randomised 40 participants (mean age 61 years, 53% males) with multiple liver metastases of colorectal cancer. Ten participants were excluded after randomisation (six from the experimental and four from the control group); thus, the trial analyses included 30 participants. Follow-up was three years. The reported number of deaths from all causes was 9/14 included participants in the microwave group versus 12/16 included participants in the conventional surgery group. The mean overall survival was 27 months in the microwave ablation and 25 months in the conventional surgery group. The three-year overall survival was 14% with microwave ablation and 23% with conventional surgery, resulting in an HR of 0.91 (95% CI 0.39 to 2.15). The reported frequency of adverse events or complications was comparable between the two groups, except for the required blood transfusion, which was more common in the conventional surgery group. There was no intervention-related mortality. Disease-free survival was 11.3 months in the microwave ablationgroup and 13.3 months in the conventional surgery group. The trial did not report on HRQoL. Microwave ablation versus radiofrequency ablation One trial, conducted in Germany, randomised 50 participants (mean age 62.8 years, 46% males) who were followed for 24 months. Two-year mortality showed an RR of 0.62 (95% CI 0.26 to 1.47). The trial reported that, by two years, 76.9% of participants in the microwave ablationgroup and 62.5% of participants in the radiofrequency ablation group survived (HR 0.63, 95% CI 0.23 to 1.73). The trial reported no deaths or major complications during the procedures in either group. There were two minor complications only in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial reported technical efficacy in 100% of procedures in both groups. Distant recurrence was reported for 10 participants in the microwave ablation group and nine participants in the radiofrequency ablation group (RR 1.03, 95% CI 0.50 to 2.08). No participant in the microwave ablation group demonstrated local progression at 12 months, while that occurred in two participants in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial did not report on HRQoL. One trial reported partial support by Medicor (MMS Medicor Medical Supplies GmbH, Kerpen, Germany) for statistical analysis. The remaining two trials did not provide information on funding. We identified four ongoing trials. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect of microwave ablation in addition to conventional TACE compared with conventional TACE alone on adverse events or complications. We do not know if microwave ablation compared with conventional surgery may have little to no effect on all-cause mortality. We do not know the effect of microwave ablation compared with radiofrequency ablation on all-cause mortality and adverse events or complications either. Data on all-cause mortality and time to mortality, HRQoL, adverse events or complications, cancer mortality, disease-free survival, failure to clear liver metastases, recurrence of liver metastases, time to progression of liver metastases, and tumour response measures were either insufficient or were lacking. In light of the current inconclusive evidence and the substantial gaps in data, the pursuit of additional good-quality, large randomised clinical trials is not only justified but also essential to elucidate the efficacy and comparative benefits of microwave ablation in relation to various interventions for liver metastases. The current version of the review, in comparison to the previous one, incorporates two new trials in two additional microwave ablation comparisons: 1. in addition to conventional TACE versus conventional TACE alone and 2. versus radiofrequency ablation.

Comparing Safety and Efficacy of TACE + Apatinib in Combination with a PD-1 Inhibitor versus a Non-triple Therapy for Treating Advanced Primary Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: This meta-analysis was performed to compare the efficacy and safety of a triple therapy, involving transcatheter arterial chemoembolization (TACE) + apatinib combined with a programmed-cell death protein-1 (PD-1) inhibitor versus TACE + apatinib, a dual therapy with apatinib and PD-1 inhibitor, and TACE alone for the treatment of advanced primary hepatocellular carcinoma (HCC). METHODS: A computerized systematic search of databases, such as PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, and VIP e-Journals was performed to retrieve studies comparing TACE + apatinib combined with a PD-1 inhibitor versus a non-triple therapy for the treatment of advanced primary HCC. The literature search, quality assessment, and data extraction were performed independently by two researchers. Stata 16.0 software was employed to analyze the data. Heterogeneity was assessed utilizing the I2 statistic and p-value, followed by conducting sensitivity analysis. RESULTS: A total of 2,352 patients were enrolled from 8 studies, including 900 patients in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor, 877 patients in the TACE + apatinib group, 52 patients in the apatinib + a PD-1 inhibitor group, and 112 patients in the TACE group. The results revealed that the objective response rate (ORR) was significantly higher in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor than that in the non-triple therapy group [odds ratio (OR)=2.47, 95% confidence interval (95%CI): 1.61-3.78]. Besides, disease control rate (DCR) was greater in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor than that in the non-triple therapy group (OR=1.87, 95%CI: 1.44-2.44). Patients in the triple therapy group experienced a significant extension of overall survival (OS) (HR=0.42, 95%CI: 0.36-0.49). In addition, there was no significant difference in the overall rate of adverse events (AEs) between the two groups (OR=1.05, 95%CI: 0.89-1.22). CONCLUSIONS: Compared with the non-triple therapy group, the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor outperformed in terms of tumor response and long-term survival with manageable AEs.

Molecular mechanisms of TACE refractoriness: Directions for improvement of the TACE procedure.

Transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma and selected patients with advanced hepatocellular carcinoma. However, TACE does not achieve a satisfactory objective response rate, and the concept of TACE refractoriness has been proposed to identify patients who do not fully benefit from TACE. Moreover, repeated TACE is necessary to obtain an optimal and sustained anti-tumour response, which may damage the patient's liver function. Therefore, studies have recently been performed to improve the effectiveness of TACE. In this review, we summarise the detailed molecular mechanisms associated with TACE responsiveness and relapse after this treatment to provide more effective targets for adjuvant therapy while helping to improve TACE regimens.

Treatment of localized hepatocellular carcinoma: resection vs. ablation vs. radiation.

Hepatocellular carcinoma (HCC) is a common malignancy with many patients presenting with local disease. As of date, the use of radiation is not included in the commonly utilized Barcelona Clinic Liver Cancer (BCLC) classification but is in the National Comprehensive Cancer Network guidelines. Radiation can volumetrically cover the entire tumor and with novel technologic advances can be administered non-invasively with excellent clinical outcomes with few adverse events. The gold standard for localized early HCC (such as BCLC-A) is resection or transplantation. In patients who are not candidates for surgical treatment, locoregional therapy should be considered as an optimal therapy for these patients. Tumor ablation techniques such as microwave ablation (MWA) and radiofrequency ablation (RFA) are excellent tools to control local disease or bridge to transplantation. Should these not be possible though then ablation with external beam radiation is also capable of yielding comparable local control and serve as a bridge to transplant without worse rates of adverse events. For tumors that meet Milan criteria for transplantation, in comparison to transarterial chemoembolization (TACE), there is considerable randomized evidence demonstrating better local control, less adverse events, better progression-free survival (PFS), and less costly. It can be utilized as a bridge in Barcelona liver class B. For larger localized tumors though (extrahepatic disease or vascular invasion like BCLC-C), stereotactic body radiation therapy (SBRT) is shown via a randomized clinical trial to have a survival benefit, local control benefit, and no worse adverse events compared to systemic therapy. In this setting, it should be considered the local consolidation standard of care.

Systemic chemotherapy plus transarterial chemoembolization versus systemic chemotherapy alone for unresectable intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study.

PURPOSE: Systemic chemotherapy (SYS) is the first-line treatment of unresectable intrahepatic cholangiocarcinoma (ICC). However, the survival benefit of SYS is still limited. This study compared the efficacy and safety of patients with unresectable ICC treated with transarterial chemoembolization (TACE) plus SYS to SYS alone. MATERIAL AND METHODS: The multicenter retrospective cohort study included patients aged ≥ 18 years old with pathologically diagnosed ICC. Patients with unmeasurable lesions, not receiving SYS treatment, Child-Pugh grade C, Eastern Cooperative Oncology Group performance status score of 3 or higher, prior liver resection, incomplete medical information, or discontinuation of the first SYS treatment were excluded. Data collection was mainly from the hospital system, and the survival outcome of patients was obtained through follow-up. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Propensity score matching at a 1:1 ratio using the nearest neighbor matching algorithm was performed to reduce selection bias between the TACE plus SYS and SYS alone groups. The Cox proportional hazards model was used to identify prognostic factors associated with OS and to estimate their hazard ratios. Modified Response Evaluation Criteria in Solid Tumors criteria were utilized to evaluate the response of tumors to therapy. RESULTS: Between June 2016 and February 2023, 118 unresectable ICC patients from three hospitals were included in this study. Of them, 37 were in the TACE plus SYS group and 81 were in the SYS alone group. The median OS in the combination group was 11.3 months, longer than the 6.4 months in the SYS alone group (P = 0.011). A greater objective response rate (ORR) and disease control rate (DCR) were observed in the combination group than in the SYS alone group (ORR, 48.65 vs. 6.17%, P < 0.001; DCR, 89.19 vs. 62.96%, P = 0.004). There were 16 patients in each group after matching, and the matched results remained consistent regarding OS and tumor response. Adverse events (AEs) were similar in the two groups after matching. CONCLUSION: Compared to SYS alone, the combination treatment of TACE plus SYS was more effective than SYS alone in improving OS, ORR, and DCR without any significant increase in AEs. TACE plus SYS may be a viable treatment option for patients with unresectable ICC.

Child-Pugh grade deterioration stratified by the etiology after transcatheter arterial chemoembolization as initial treatment for hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, TACE can cause deterioration of liver functions. We aimed to identify the factors that influence deterioration of liver function after TACE. We retrospectively analyzed 262 patients who underwent TACE as initial treatment for HCC with Child-Pugh grade A. We divided them into three groups stratified by the etiology of underlying liver disease. Patients were classified into hepatitis B virus (HBV) group, hepatitis C virus (HCV) group, and non-HBV / non-HCV (NBNC) group. Liver functions at one month after TACE and time to Child-Pugh grade B or C were compared between the three groups. The HBV, HCV and NBNC groups contained 23, 123 and 116 patients, respectively. The decline in albumin level after TACE was significantly higher in NBNC group than other groups (p = 0.02). NBNC group showed a shorter time to Child-Pugh grade deterioration compared with HBV group and HCV group (p < 0.001). Multivariate Cox regression analysis showed that NBNC group was a significant factor for Child-Pugh grade deterioration (Hazard ratio 3.74, 95% confidence interval 1.89-7.40, p < 0.001). These results revealed that liver functions worsened most remarkably in NBNC group after TACE.

An interpretable machine learning model based on contrast-enhanced CT parameters for predicting treatment response to conventional transarterial chemoembolization in patients with hepatocellular carcinoma.

OBJECTIVE: To explore the potential of pre-therapy computed tomography (CT) parameters in predicting the treatment response to initial conventional TACE (cTACE) in intermediate-stage hepatocellular carcinoma (HCC) and develop an interpretable machine learning model. METHODS: This retrospective study included 367 patients with intermediate-stage HCC who received cTACE as first-line therapy from three centers. We measured the mean attenuation values of target lesions on multi-phase contrast-enhanced CT and further calculated three CT parameters, including arterial (AER), portal venous (PER), and arterial portal venous (APR) enhancement ratios. We used logistic regression analysis to select discriminative features and trained three machine learning models via 5-fold cross-validation. The performance in predicting treatment response was evaluated in terms of discrimination, calibration, and clinical utility. Afterward, a Shapley additive explanation (SHAP) algorithm was leveraged to interpret the outputs of the best-performing model. RESULTS: The mean diameter, ECOG performance status, and cirrhosis were the important clinical predictors of cTACE treatment response, by multiple logistic regression. Adding the CT parameters to clinical variables showed significant improvement in performance (net reclassification index, 0.318, P < 0.001). The Random Forest model (hereafter, RF-combined model) integrating CT parameters and clinical variables demonstrated the highest performance on external validation dataset (AUC of 0.800). The decision curve analysis illustrated the optimal clinical benefits of RF-combined model. This model could successfully stratify patients into responders and non-responders with distinct survival (P = 0.001). CONCLUSION: The RF-combined model can serve as a robust and interpretable tool to identify the appropriate crowd for cTACE sessions, sparing patients from receiving ineffective and unnecessary treatments.

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial).

PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.

The impact of preoperative interview and prospective nursing on perioperative psychological stress and postoperative complications in patients undergoing TACE intervention for hepatocellular carcinoma.

TACE has become one of the main methods for the treatment of liver cancer. The study aimed to investigate the effects of preoperative interview and prospective nursing in patients with hepatic carcinoma undergoing transcatheter chemoembolization (TACE). Eighty-six patients with hepatocellular carcinoma who underwent TACE intervention treatment at our hospital between 2020 and 2023 were selected and randomly assigned to 2 groups using computerized randomization. The control group (n = 43) received routine nursing care, while the study group (n = 43) received preoperative interviews in combination with prospective nursing during the procedure. The patients' heart rate, mean arterial pressure, and blood pressure variations were recorded, along with their mood changes after intervention. The postoperative pain and satisfaction levels were compared between the 2 groups of patients, and the incidence of postoperative complications was observed. The heart rate, systolic blood pressure, and diastolic blood pressure of the 2 groups of patients were compared 1 day before the operation (P > .05). Compared to 1 day before the operation, there was no significant change for the study group at 10 minutes after entering the room. However, the control group showed an increase. Both groups showed an increase in heart rate, systolic blood pressure, and diastolic blood pressure after the operation, with the study group having lower values than the control group (P < .05). The levels of tension, fatigue, anxiety, energy, anger, depression, self-esteem, and POMS index were compared between the 2 groups before intervention (P > .05). After intervention, there were significant differences between the 2 groups(P < .05). Immediately after the operation, the NRS scores of the 2 groups of patients were compared (P > .05). Compared to the control group, the study group showed a decrease in NRS scores at 12, 24, and 48 hours after the operation (P < .05). The nursing satisfaction rate of the study group patients was 97.67% (42/43), which was higher than the nursing satisfaction rate of the control group of 76.74% (33/43) (P < .05). Compared to routine nursing, preoperative visits and prospective nursing interventions can effectively alleviate patients' psychological stress reactions, relieve pain, reduce the incidence of complications, and improve patients' satisfaction with nursing care.

Development of an immunosuppressed orthotopic hepatocellular carcinoma rat model for the evaluation of chemo- and radioembolization therapies.

Hepatocellular carcinoma (HCC) is widely known to be chemo-resistant and presents with significant liver disease resulting in low tolerability to systemic chemotherapy. As a counter measure, more targeted therapies such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been developed. To further optimize these therapies, animal models are critical in elucidating the molecular events in disease progression and test new treatment options. The present study focuses on the development of a hepatoma bearing rat model. N1S1 rat hepatoma cells were transfected by a lentiviral method and injected into the liver of Sprague Dawley (SD) and Rowett Nude (RNU) rats. Longitudinal tumor growth was observed by bioluminescence imaging (BLI) and liver/tumor histology. In both models, tumors were visible within 4 days post cell inoculation. Tumor take rates were 52 % and 73 % for male and female SD rats, respectively, and 100 % for male RNU rats. By day 12 and 15 post inoculation, we recorded complete tumor regression in male and female SD rats. Liver histology showed advanced fibrosis in the tumor regressed SD rats, whilst RNU rats exhibited the characteristic sheet pattern of Novikoff tumor with mild liver fibrosis. Increased CD3 and TUNEL staining observed in SD rat livers may be key factors for tumor regression. Our data reveal that the immunocompetent SD rats are not recommended as a model for therapeutic investigations. The immunosuppressed RNU rats, however, are characterized by consistent and reliable tumor growth and thus a desirable model for future therapeutic investigations.

Impact of Hyperglycemia on Complication and Mortality after Transarterial Chemoembolization for Hepatocellular Carcinoma.

BACKGRUOUND: Current guidelines regarding periprocedural glycemic control to prevent complications after nonsurgical invasive procedures are insufficient. Transarterial chemoembolization (TACE) is a widely used treatment for unresectable hepatocellular carcinoma. We aimed to investigate the association between diabetes mellitus (DM) per se and the degree of hyperglycemia with postprocedural complications after TACE. METHODS: A total of 22,159 TACE procedures performed at Seoul National University Hospital from 2005 to 2018 were retrospectively analyzed. The associations between DM, preprocedural glycosylated hemoglobin (HbA1c), and periprocedural average glucose with postprocedural adverse outcomes were evaluated. The primary outcome was occurrence of postprocedural bacteremia. Secondary outcomes were acute kidney injury (AKI), delayed discharge and death within 14 days. Periprocedural glucose was averaged over 3 days: the day of, before, and after the TACE procedures. Propensity score matching was applied for procedures between patients with or without DM. RESULTS: Periprocedural average glucose was significantly associated with bacteremia (adjusted odds ratio per 50 mg/dL of glucose, 1.233; 95% confidence interval, 1.071 to 1.420; P=0.004), AKI, delayed discharge, and death within 14 days. DM per se was only associated with bacteremia and AKI. Preprocedural HbA1c was associated with delayed discharge. Average glucose levels above 202 and 181 mg/dL were associated with a significantly higher risk of bacteremia and AKI, respectively, than glucose levels of 126 mg/dL or lower. CONCLUSION: Periprocedural average glucose, but not HbA1c, was associated with adverse outcomes after TACE, which is a nonsurgical invasive procedure. This suggests the importance of periprocedural glycemic control to reduce postprocedural complications.

The long-term efficacy and safety of apatinib are inferior to sorafenib in the first-line treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Apatinib, a novel tyrosine kinase inhibitor independently developed by China, has been widely used in the treatment of advanced hepatocellular carcinoma (HCC) in recent years. For more than a decade, sorafenib has been the classic first-line treatment option for patients with advanced HCC. However, the results of clinical studies comparing the efficacy and safety of these 2 drugs are still controversial. Therefore, the aim of this meta-analysis is to evaluate the efficacy and safety of apatinib versus sorafenib as first-line treatment for advanced HCC. METHODS: Up to August 14, 2023, the databases of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang were searched, and clinical studies of experimental group (apatinib or apatinib plus transarterial chemoembolization [TACE]) versus control group (sorafenib or sorafenib plus TACE) in the first-line treatment of advanced HCC were included. Two researchers evaluated the quality of the included studies and extracted the data. Revman 5.4 software was used for meta-analysis. RESULTS: A total of 12 studies involving 1150 patients were included. Five studies are apatinib alone versus sorafenib alone, and the other 7 studies are apatinib plus TACE versus sorafenib plus TACE. The results of the meta-analysis showed that compared with sorafenib alone, apatinib could improve (OR = 3.06, 95%CI: 1.76-5.31), had no advantage in improving DCR (OR = 1.52, 95%CI: 0.86-2.68) and prolonging PFS (HR = 1.35, 95%CI: 0.94-1.96), and was significantly worse in prolonging OS (HR = 1.43, 95%CI: 1.08-1.88). Similarly, apatinib plus TACE was inferior to sorafenib plus TACE in prolonging OS (HR = 1.15, 95%CI: 1.03-1.28), although it improved ORR (OR = 1.49, 95%CI: 1.03-2.16). In terms of adverse drug events, the overall incidence of adverse events, and the incidence of drug reduction and discontinuation in the experimental group were significantly higher than those in the control group (P < .05). The incidence of hypertension, proteinuria, and oral mucositis in the experimental group was significantly higher than that in the control group (P < .05). CONCLUSION: In the setting of first-line treatment of advanced HCC, apatinib has improved short-term efficacy (ORR) compared with sorafenib, but the safety and long-term efficacy of apatinib are inferior to sorafenib.

Non-cirrhotic hyperammonaemic encephalopathy secondary to metastatic pancreatic neuroendocrine tumour treated with peptide receptor radio nucleotide therapy and transarterial chemoembolisation.

Neuroendocrine tumours (NETs) are rare cancers which often carry significant morbidity and mortality, frequently related to burden of liver metastases. Hyperammonaemia and subsequent hepatic encephalopathy carries a poor prognosis and has been described in these patients. We discuss a case of a woman in her 50s with hyperammonaemic encephalopathy and a new diagnosis of pancreatic NET with hepatic metastases. She presented with a reduced conscious state a few days post commencing chemotherapy. This was considered to have a multifactorial pathophysiology: the primary driver being large volume hepatic metastases and contributed by portosystemic microshunting, sepsis, severe weight loss and malnutrition. We describe how each of these exacerbating factors was addressed and highlight the effective multimodal treatment approach consisting of sequential transarterial chemoembolisation followed by peptide receptor radio nucleotide therapy, resulting in the resolution of hyperammonaemic encephalopathy and radiological partial metabolic response.

Plasma metabolomic analysis of human hepatocellular carcinoma before and after transcatheter arterial chemoembolization.

Introduction: Hepatocellular carcinoma (HCC) is the fourth most prevalent cancer in China. Transcatheter arterial chemoembolization (TACE) is a common interventional therapy for HCC. In this study, we aimed to explore specific metabolites that can accurately predict prognosis after TACE in patients with HCC. Methods: Patients with HCC and healthy volunteers (n = 20 each) were recruited to our study; plasma samples were collected from patients before and after TACE and from healthy volunteers. Plasma samples were subjected to untargeted ultra-high performance liquid chromatography-high resolution mass spectrometry metabolomics analysis, to identify metabolites significantly associated with the prognosis of patients with HCC after TACE. Results: Orthogonal filtered partial least squares discriminant analysis confirmed significant separation of the pre-TACE, post-TACE, and healthy groups, and 34 differential metabolites were identified between the pre-TACE and post-TACE groups. KEGG analysis revealed that phenylalanine, tyrosine, and tryptophan biosynthesis pathways and the phenylalanine metabolism pathway were potentially altered in HCC genesis and during TACE. Phenylalanine and tyrosine are involved in both pathways and were increased in the pre-TACE group relative to controls, with phenylalanine further increased in the post-TACE group. Receiver operating characteristic (ROC) curve analysis indicated that PC 36:4|PC 18:2_18:2 (area under the ROC curve (AUC) = 0.798) is a potential marker for assessment of prognosis in patients with HCC after TACE. Moreover, ROC curve analysis indicated that palmitoylcarnitine (AUC = 1) is a marker with potential value for HCC diagnosis. Conclusions: Limited studies had been conducted on the detection of metabolites in the plasma of HCC patients before and after TACE. PC 36:4|PC 18:2_18:2 is a potential marker for evaluation of the therapeutic effects of TACE. This finding may be beneficial for the treatment of patients with HCC after TACE.

Immune Effects of Intra-Arterial Liver-Directed Therapies.

Image-guided intra-arterial locoregional therapies (LRTs) such as transarterial embolization, transarterial chemoembolization, and transarterial radioembolization exhibit effects on the immune system. Understanding the humoral (cytokine, chemokine, and growth factor) and cellular (T cell, neutrophil, dendritic cell, and macrophage) mechanisms underlying the immune effects of LRT is crucial to designing rational and effective combinations of immunotherapy and interventional radiology procedures. This article aims to review the immune effects of intra-arterial LRTs and provide insight into strategies to combine LRTs with systemic immunotherapy.

5-FU promotes HBV replication through oxidative stress-induced autophagy dysfunction.

BACKGROUND & AIMS: Hepatitis B virus (HBV) reactivation is a major problem that must be overcome during chemotherapy for HBV-related hepatocellular carcinoma (HCC). However, the mechanism underlying chemotherapy-associated HBV reactivation is still not fully understood, hindering the development of improved HBV-related HCC treatments. METHODS: A meta-analysis was performed to assess the HBV reactivation risk during transcatheter arterial chemoembolization (TACE). To investigate the regulatory effects and mechanisms of 5-FU on HBV replication, an HBV mouse model was established by pAAV-HBV1.2 hydrodynamic injection followed by intraperitoneal 5-FU injection, and different in vitro models (HepG2.2.15 or Huh7 cells) were established. Realtime RT‒qPCR, western blotting, luciferase assays, and immunofluorescence were used to determine viral parameters. We also explored the underlying mechanisms by RNA-seq, oxidative stress evaluation and autophagy assessment. RESULTS: The pooled estimated rate of HBV reactivation in patients receiving TACE was 30.3 % (95 % CI, 23.1%-37.4 %). 5-FU, which is a chemotherapeutic agent commonly used in TACE, promoted HBV replication in vitro and in vivo. Mechanistically, 5-FU treatment obviously increased autophagosome formation, as shown by increased LC3-II levels. Additionally, 5-FU impaired autophagic degradation, as shown by marked p62 and mCherry-GFP-LC3 upregulation, ultimately promoting HBV replication and secretion. Autophagy inhibition by 3-methyladenine or chloroquine significantly altered 5-FU-induced HBV replication. Furthermore, 5-FU-induced autophagy and HBV replication were markedly attenuated with a reactive oxygen species (ROS) scavenger. CONCLUSIONS: Together, our results indicate that ROS-induced autophagosome formation and autophagic degradation play a critical role in 5-FU-induced HBV reactivation.

Automated Feeder-Detection Software for Renal Cell Carcinoma Embolization: A Retrospective Evaluation of Detection Rate Using Transarterial Time-Resolved Computed Tomography Angiography.

PURPOSE: To evaluate the detection rate of feeding arteries in renal cell carcinoma with automated feeder-detection software and determine the optimal imaging phase for accurate feeder detection with transarterial time-resolved computed tomography angiography. MATERIALS AND METHODS: The performance of automated feeder-detection software was retrospectively evaluated using transarterial renal time-resolved computed tomography angiography images of 15 renal cell carcinomas (mean size, 22.1 mm); the images were obtained via the renal artery using a hybrid angio-CT system with 320-row computed tomography, across nine phases with 0.5-s intervals over a contrast delay time of 1.0-5.0 s. Automated feeder-detection software was applied to each phase in all tumors (135 image series in total). The feeder-detection rate (i.e., sensitivity) in each phase was evaluated, and the number of false feeders demonstrated by the software was counted for each tumor. RESULTS: A total of 22 feeders were identified. The feeder-detection rate was the highest (95.5% [21/22]) at delay times of 1.5 s and 2.0 s and lower in later phases. At delay times of 1.0 s and 1.5 s, the software demonstrated no or only a few (≤ 3) false feeders in 93.3% (14/15) of the tumors. In later phases, however, many (≥ 4) false feeders were observed in > 50% of tumors. CONCLUSION: The automated feeder-detection software showed a favorable feeder-detection rate and may be useful in transarterial embolization for renal cell carcinoma. The optimal delay time to avoid the demonstration of false feeders and achieve a high detection accuracy was 1.5 s. LEVEL OF EVIDENCE IV: Case Series.

Reappraisal of Portal Vein Tumor Thrombosis as a Prognostic Factor for Patients with Hepatocellular Carcinoma.

Background/Aims: : This study aimed to assess whether hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) could have favorable prognoses with proper treatment under selective conditions. Methods: : This retrospective, single-center study involved 1,168 patients diagnosed with HCC between January 2005 and December 2006, before the introduction of sorafenib. Overall survival (OS) was estimated using the Kaplan-Meier method, and the Cox proportional hazards model was used to identify and adjust the variables associated with OS. Results: : In nodular-type HCC, the OS differed significantly according to the presence of PVTT (log-rank p<0.001), and the level of PVTT, not only its presence, was a major independent factor affecting OS. PVTT at the Vp1-3 branch was associated with significantly longer OS than was PVTT at the Vp4 level (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.04 to 3.21). In multivariate analysis, the OS was further stratified according to the PVTT level and tumor type, representing that nodular HCC without PVTT exhibited the best OS, whereas nodular HCC with Vp4 PVTT (adjusted HR, 2.59; 95% CI, 1.57 to 4.28) showed a poor prognosis similar to that of infiltrative HCC. The PVTT level was consistently correlated with OS in patients treated with transarterial chemoembolization. Nodular HCC without PVTT showed the best prognosis, while nodular HCC with Vp1-3 PVTT also exhibited a favorable OS, although inferior to that without PVTT (adjusted HR, 1.47, 95% CI, 0.92 to 2.36). Conclusions: : Active treatment such as transarterial chemoembolization can be considered for selected PVTT cases. The level of PVTT and type of HCC were independent prognostic factors.