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.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

[Therapeutic effect of recombinant human growth hormone on children with growth hormone deficiency and different pituitary developmental conditions: a prospective study]. / é‡ç»„äººç”Ÿé•¿æ¿€ç´ æ²»ç–—ä¸åŒåž‚ä½“å‘è‚²çŠ¶å†µç”Ÿé•¿æ¿€ç´ ç¼ºä¹ç—‡æ‚£å„¿ç–—æ•ˆçš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS: In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.

Regulator of G-protein signaling 14 protects the liver from ischemia-reperfusion injury by suppressing TGF-ß-activated kinase 1 activation.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion injury (IRI) is a common complication of hepatectomy and liver transplantation. However, the mechanisms underlying hepatic IRI have not been fully elucidated. Regulator of G-protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates the G-protein and mitogen-activated protein kinase (MAPK) signaling pathways. However, the role of RGS14 in hepatic IRI remains unclear. APPROACH AND RESULTS: We found that RGS14 expression increased in mice subjected to hepatic ischemia-reperfusion (IR) surgery and during hypoxia reoxygenation in hepatocytes. We constructed global RGS14 knockout (RGS14-KO) and hepatocyte-specific RGS14 transgenic (RGS14-TG) mice to establish 70% hepatic IRI models. Histological hematoxylin and eosin staining, levels of alanine aminotransferase and aspartate aminotransferase, expression of inflammatory factors, and apoptosis were used to assess liver damage and function in these models. We found that RGS14 deficiency significantly aggravated IR-induced liver injury and activated hepatic inflammatory responses and apoptosis in vivo and in vitro. Conversely, RGS14 overexpression exerted the opposite effect of the RGS14-deficient models. Phosphorylation of TGF-ß-activated kinase 1 (TAK1) and its downstream effectors c-Jun N-terminal kinase (JNK) and p38 increased in the liver tissues of RGS14-KO mice but was repressed in those of RGS14-TG mice. Furthermore, inhibition of TAK1 phosphorylation rescued the effect of RGS14 deficiency on JNK and p38 activation, thus blocking the inflammatory responses and apoptosis. CONCLUSIONS: RGS14 plays a protective role in hepatic IR by inhibiting activation of the TAK1-JNK/p38 signaling pathway. This may be a potential therapeutic strategy for reducing incidences of hepatic IRI in the future.

Combined iodine-125 seed strand, portal vein stent, transarterial chemoembolization, lenvatinib and anti-PD-1 antibodies therapy for hepatocellular carcinoma and Vp4 portal vein tumor thrombus: A propensity-score analysis.

Objective: To evaluate the safety and efficacy of interventional therapy (iodine-125[125I] seed strand and portal vein stent [PVS] implantation plus transarterial chemoembolization [TACE]) combined with systemic therapy (lenvatinib plus anti-PD-1 antibody) as first-line treatment for hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT). Patients and methods: From December 2018 to October 2021, 87 HCC patients with Vp4 PVTT were included in this single-center retrospective study. Forty-seven patients underwent interventional therapy combined with lenvatinib and anti-PD-1 antibody (group A), while 40 cases underwent interventional therapy combined with lenvatinib only (group B). Overall response rate (ORR), stent occlusion rates (SOR), median overall survival (OS), median progression-free survival (PFS) and median stent patency time (SPT) were compared between the 2 groups. Results: The mean intended dose (r = 10 mm; z = 0; 240 days) was 64.9 ± 1.0 Gy and 64.5 ± 1.1 Gy in group A and B, respectively (p = 0.133). ORR and SOR were significantly different between group A and B (ORR, 55.3% vs 17.5%, p < 0.001; SOR, 12.8% vs 35.0%, p = 0.014). In the propensity-score matching (PSM) cohort, the median OS, median PFS and median SPT were significantly longer in group A compared with group B (32 PSM pairs; OS, 17.7 ± 1.7 vs 12.0 ± 0.8 months, p = 0.010; PFS, 17.0 ± 4.3 vs 8.0 ± 0.7 months, p < 0.001; SPT, not-reached vs 12.5 ± 1.1 months, p = 0.028). Conclusion: This interventional therapy combined with lenvatinib and anti-PD-1 antibody is safe and effective for HCC patients with Vp4 PVTT.

Corrigendum: Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Outcomes in Patients With Unresectable Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Plus Sorafenib.

[This corrects the article DOI: 10.3389/fmolb.2021.624366.].

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Outcomes in Patients With Unresectable Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Plus Sorafenib.

Objectives: To investigate the predictive value of inflammatory biomarkers in patients with unresectable hepatocellular carcinoma (HCC) for outcomes following the combination treatment of transarterial chemoembolization (TACE) plus sorafenib. Materials and Methods: A total of 314 (270 male and 44 female) treatment-naïve patients with unresectable HCC treated by TACE plus sorafenib between January 2011 and December 2018 were enrolled in the retrospective study. The primary outcome was overall survival (OS). The secondary outcome was progression-free survival (PFS). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were obtained within 3-7 days before the initial TACE and the median value of the NLR and PLR was considered as the cut-off value. Results: The median value of NLR and PLR was 2.42 and 100, respectively. The median OS and PFS of the entire cohort were 18.7 months (95% CI: 16.8-20.6) and 9.1 months (95% CI: 8.5-9.8), respectively. The low NLR and PLR group showed improved OS and PFS compared with the high NLR and PLR group [21.8 months (95% CI: 15.2-28.5) vs. 15.4 months (95% CI: 12.4-18.3), p < 0.0001; 21.6 months (95% CI: 15.8-27.5) vs. 14.9 months (95% CI: 11.9-17.8), p = 0.00027, respectively]. In addition, the low NLR and PLR group also provided a longer PFS than the high NLR and PLR group [10.4 months (95% CI: 8.9-12.0) vs. 8.1 months (95% CI: 7.1-9.2), p = 0.00022; 10.3 months (95% CI: 8.6-11.9) vs. 8.2 months (95% CI: 7.2-9.2), p < 0.0001, respectively]. High NLR and PLR at baseline were predictive factors of poor OS (p = 0.02 and p = 0.004) and PFS (p = 0.045 and p = 0.005). Conclusion: This study showed the prognostic value of quantitative inflammatory biomarkers in correlation with OS and PFS in unresectable HCC patients undergoing TACE plus sorafenib treatment.

Random Survival Forests to Predict Disease Control for Hepatocellular Carcinoma Treated With Transarterial Chemoembolization Combined With Sorafenib.

Objectives: To use baseline variables to predict one-year disease control for patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) combined with sorafenib as initial treatment by applying a machine learning approach based on the random survival forest (RF) model. Materials and Methods: The multicenter retrospective study included 496 patients with HCC treated with TACE combined with sorafenib between January 2014 and December 2018. The independent risk factors associated with one-year disease control (complete response, partial response, stable disease) were identified using the RF model, and their predictive importance was determined using the Gini index. Tumor response was assessed according to modified Response Evaluation Criteria in Solid Tumors. Results: The median overall survival was 15.5 months. A total of 186 (37.5%) patients achieved positive one-year disease control. The Barcelona Clinic Liver Cancer (BCLC) stage (Gini index: 20.0), tumor size (≤7 cm, >7 cm; Gini index: 9.0), number of lobes involved (unilobar, bilobar; Gini index: 6.4), alpha-fetoprotein level (≤200 ng/dl, >200 ng/dl; Gini index: 6.1), albumin-bilirubin grade (Gini index: 5.7), and number of lesions (1, >1; Gini index: 5.3) were identified as independent risk factors, with the BCLC stage as the most important variable. The RF model achieved a higher concordance index of 0.724 compared to that for the logistic regression model (0.709). Conclusions: The RF model is a simple and accurate approach for prediction of one-year disease control for patients with HCC treated with TACE combined with sorafenib.

Embolization of the Transhepatic Tract after Percutaneous Portal Vein Interventions: Single-Centre Retrospective Study Comparing n-butyl Cyanoacrylate Versus Coils.

PURPOSE: The aim of this study was to compare the safety and efficacy of transhepatic puncture tract embolization with n-butyl cyanoacrylate (n-BCA) versus coils after percutaneous transhepatic portal vein interventions in patients with hepatocellular carcinoma (HCC). It was also the aim of the study to evaluate the extent of artifacts in CT exams during FU. METHODS: Single-center retrospective study from 2017-2019 in 190 patients who underwent percutaneous transhepatic portal vein interventions. The transhepatic puncture tracts were embolized with n-BCA in 88 patients (Group A) and with coils in 102 patients (Group B). Procedure-related complications and image noise around coils and n-BCA were compared between the groups. No significant differences were noted at baseline between both groups (platelets, coagulation, liver disease, types of procedures, liver function, liver tumors). RESULTS: All patients underwent transhepatic puncture tract embolization. Procedure-related complications were only observed in patients from Group B: subcapsular hemorrhage (n = 2; 1.96%), hepatic artery hemorrhage (n = 1; 0.98%), and pseudoaneurysms combined with hemobilia occurred (n = 1; 0.98%). In Group A, the distal part of the punctured portal vein branch was embolized with n-BCA in 1 patient (1.14%). Four major complications in Group B Vs 0 in Group A were observed, respectively (p < 0.0001). The image noise around n-BCA was significantly lower than that around coils (10.7 ± 1.7 HU vs. 54.3 ± 15.0 HU, p < .001). CONCLUSIONS: n-BCA tract embolization is more effective than using coils, with fewer bleeding events, at the cost of a higher potential for unintended embolization of portal vein branches.

Prognosis Nomogram for Hepatocellular Carcinoma Patients with Portal Vein Invasion Undergoing Transarterial Chemoembolization Plus Sorafenib Treatment: A Retrospective Multicentre Study.

OBJECTIVES: To explore the outcomes of combined transarterial chemoembolization (TACE) with sorafenib in hepatocellular carcinoma (HCC) patients with portal vein tumour thrombus (PVTT) and to establish a prognostic prediction nomogram to differentiate target patients and stratify risk. MATERIALS AND METHODS: This multicentre, retrospective study consisted of 185 consecutive treatment-naïve patients with HCC and PVTT treated with TACE plus sorafenib from three institutions between January 1st, 2012 and December 31st, 2017. The primary outcome measurement of the study was overall survival (OS). The type of PVTT was classified by the Liver Cancer Study Group of Japan. The prognostic nomogram was established based on the predictors and was performed with interval validation. RESULTS: The median OS of the Vp1-3 and Vp4 groups was 12.4 months (11.7-18.9) and 8.5 months (7.6-11.2) (P = 0.00098), respectively, and there was a significant difference in the median OS between the Vp1-2 and Vp3 subgroups (16.4 months (12.2-27.9) vs. 10.9 months (8.4-18.1), P = 0.041). The multivariate Cox regression analysis suggested that tumour size, albumin-bilirubin grade, and PVTT type were independent prognostic factors. The C-index value of the nomogram based on these predictors in the entire cohort was 0.731 (0.628-0.833). CONCLUSIONS: After the combined therapy of TACE and sorafenib, advanced HCC patients with segmental or subsegmental PVTT showed better survival than those with main PVTT. The nomogram can be applied to identify advanced HCC patients with PVTT who may benefit most from the combination treatment and be helpful for making decision in clinical practice.