Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

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.

Novel beagle model of gastric local fibrotic target lesions for the evaluation and training of endoscopic techniques.

BACKGROUND: Novel endoscopic techniques used in the treatment of gastric lesions with local submucosal fibrosis need preclinical evaluation and training due to safety limitations. Therefore, the purpose of our study was to establish an animal model of gastric local fibrotic target lesions and assess its feasibility in the evaluation and training of endoscopic techniques. METHODS: In six experimental beagles, a 50% glucose solution was injected into three submucosal areas of the fundus, body, and antrum of the stomach to create gastric local fibrotic target lesions (experimental group). On post-injection day (PID) 7, the injection sites were assessed endoscopically to confirm the presence of submucosal fibrosis formation, and the dental floss clip traction assisted endoscopic submucosal dissection (DFC-ESD) procedure was performed on the gastric local fibrotic target lesions to confirm its feasibility after endoscopic observation. The normal gastric mucosa of six control beagles underwent the same procedure (control group). All the resected specimens were evaluated by histological examination. RESULTS: All 12 beagles survived without postoperative adverse events. On PID 7, 16 ulcer changes were observed at the injection sites (16/18) under the endoscope, and endoscopic ultrasonography confirmed the local submucosal fibrosis formation in all ulcer lesions. The subsequent DFC-ESD was successfully performed on the 32 gastric target lesions, and the mean submucosal dissection time in the ulcer lesions was greater than that in the normal gastric mucosa (15.3 ± 5.6 vs. 6.8 ± 0.8 min; P < 0.001). There was no difference in rates of en bloc resection, severe hemorrhage, or perforation between the two groups. Histological analysis of the ulcer lesions showed the absence of epithelial or muscularis mucosae and extensive submucosal fibrous tissue proliferations compared with normal gastric mucosa. Overall, endoscopists had high satisfaction with the realism and feasibility of the animal model. CONCLUSION: We developed a novel animal model of gastric local fibrotic target lesions to simulate difficult clinical situations, which strongly appeared to be suitable for the preclinical evaluation and learning of advanced endoscopic techniques.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

The efficacy and safety of Saccharomyces boulardii in addition to antofloxacin-based bismuth quadruple therapy for Helicobacter pylori eradication: a single-center, prospective randomized-control study.

Background: We previously reported that antofloxacin-based bismuth quadruple therapy was safe and effective for Helicobacter pylori (H. pylori) eradication. It is not clear whether the addition of Saccharomyces boulardii (S. boulardii) to antofloxacin-based quadruple therapy can improve the eradication rate of H. pylori and reduce adverse events. Objective: To investigate the effect of adding S. boulardii to antofloxacin-based quadruple therapy on the eradication rate of H. pylori and the adverse events. Design: Single-center, prospective randomized controlled study. Methods: A total of 172 patients with H. pylori infection were randomly assigned to the test and control groups. Patients in the control group (n = 86) received antofloxacin-based bismuth quadruple therapy for 14 days. On this basis, cases in the test group (n = 86) received S. boulardii 500 mg b.i.d. The eradication rate of H. pylori and adverse events were observed 4 weeks after the treatment. Results: There were no statistically significant differences in the eradication rates of H. pylori and frequency of diarrhea between the test group and control group (p > 0.05). The duration of diarrhea in the test group was significantly shorter than in the control group (p < 0.001). In addition, the two groups exhibited similar adverse event rates for epigastric pain, abdominal distention, dizzy, vomiting, and rash (p > 0.05). The severity of adverse reactions was similar between the two groups (p > 0.05), and most of them had mild adverse events. Conclusion: Although the addition of S. boulardii to antofloxacin-based quadruple therapy could not improve the eradication rate of H. pylori, it could shorten the time of antibiotic-associated diarrhea and reduce the incidence of diarrhea. Trial registration number: ChiCTR2200056931.

Efficacy and safety of computed tomography-guided microwave ablation with fine needle-assisted puncture positioning technique for hepatocellular carcinoma.

BACKGROUND: In microwave ablation (MWA), although computed tomography (CT) scanning can overcome gas interference, it cannot achieve real-time localization. Therefore, the puncture technique is more important in CT-guided ablation. AIM: To compare the fine needle-assisted puncture (FNP) positioning technique and the conventional puncture (CP) technique for the safety and efficacy of CT-guided MWA in treating hepatocellular carcinoma (HCC). METHODS: This retrospective study included 124 patients with 166 tumor nodules from February 2018 and June 2021. Seventy patients received CT-guided MWA under the FNP technique (FNP group), and 54 patients received MWA under the CP technique (CP group). Intergroup comparisons were made regarding local tumor progression (LTP), recurrence-free survival (RFS), overall survival (OS), and complications. The influencing variables of LTP and RFS were analyzed through univariate and multivariate regressions. RESULTS: The 1-, 2-, and 3-year cumulative incidences of LTP in the FNP group were significantly lower than those in the CP group (7.4%, 12.7%, 21.3% vs 13.7%, 32.9%, 36.4%; P = 0.038). The 1-, 2-, and 3-year RFS rates in the FNP group were significantly higher than those in the CP group (80.6%, 73.3%, 64.0% vs 83.3%, 39.4%, and 32.5%, respectively; P = 0.008). The FNP technique independently predicted LTP and RFS. Minor complications in the FNP group were lower than those in the CP group (P < 0.001). The difference in median OS was insignificant between the FNP and CP groups (P = 0.229). CONCLUSION: The FNP technique used in CT-guided MWA may improve outcomes in terms of LTP, RFS, and procedure-related complications for HCC.

Safety and efficacy of transcatheter arterial chemoembolization with embospheres in treatment of hepatocellular carcinoma.

OBJECTIVE: To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE) with embospheres for the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: Patients with unresectable HCC who were treated with TACE followed by embosphere treatment (Embo-TACE) or conventional TACE (cTACE) between May 2010 and March 2014 were retrospectively included in this study. The Embo-TACE group received lipiodol and chemotherapeutic agent emulsion, followed by embospheres. The cTACE group received lipiodol and chemotherapeutic agent emulsion, followed by gelatin sponge pellets. Time to progression (TTP), overall survival (OS), overall response rate (ORR), and safety were compared between the two groups. Univariate and multivariate regression analyses of the factors affecting survival were conducted. RESULTS: The median TTP and OS in the Embo-TACE group were significantly longer than those in the cTACE group (TPP: 7.0 months vs 5.4 months, P = 0.035; OS: 15 months vs 12 months, P = 0.032). Seven days after the first TACE treatment, alanine aminotransferase level was higher in the cTACE group than in the Embo-TACE group (P = 0.015). The ORR did not significantly differ between the two groups (P = 0.827). Additional therapy and local responses one month after the first TACE treatment were associated with OS. CONCLUSIONS: Embo-TACE resulted in a significant improvement in TTP and OS for patients with unresectable HCC, compared with cTACE. Furthermore, Embo-TACE was better tolerated. Additional therapy and local responses one month after the first TACE were independent prognostic factors for OS.

[Determination of Bi in Soils and Sediments by Atomic Fluorescence Spectrometry].

A method for determination of the contents of Bi in soils and sediments by atomic fluorescence spectrophotometry (AFS) was established by using aqua regia as the dissolved medium. In this paper, the instrument parameters, load flow and reducing agent concentration were optimized. Compared with microwave digestion and electric heating plate digestion, water bath digestion demonstrated the better digestion efficiency and was most commonly used. Under the optimal experimental conditions, the detection limit (LOD) was 0.01 mg·kg-1 (sample quantity 0.500 0 g, sample volume 50 mL), and the limit of quantitation (LOQ) was 0.04 mg·kg-1. The results were in good agreement with the centified value, and the relative error was -4.7%~-2.0%. For determination of soil and sediment actual samples, the relative standard deviation (RSD) were 2.5%~3.4% and 3.1%~3.4%, respectively, and the recoveries of the method respectively ranged from 97.6%~102% and 99.5%~104%.

Determination of Beryllium in Soil and Sediment by Graphite Furnace Atomic Absorption with a Microwave-Acid Digestion Method.

A method for determination of beryllium in soils and sediments by microwave-acid digestion/graphite furnace atomic absorption (GFAA) is described. In this paper, the working conditions of the instrument are optimized, the drawing of calibration curve is expounded, the pretreatment process of soil and sediments (including microwave heating process and the selection of digestion system) is discussed, and the interference of coexisting elements is examined. The sample was pretreated by microwave digestion parameters using HNO3/ HCl/HF mixed acid system. The method is fast and simple without matrix modifier, and has no interference by coexisting ions, and has high repeatability and reproducibility. Under the optimal experimental conditions, the limit of detection (LOD) is 0.004 9 mg · kg⁻¹ (sample quantity 0.200 0 g, sample volume 25 mL), and the limits of quantitation (LOQ) is 0.20 mg · kg⁻¹. This method is used to measure the standard samples and actual samples, whether in the laboratory, or between laboratories, has good accuracy and precision.

Efficacy of transcatheter arterial chemoembolization combined with cytokine-induced killer cell therapy on hepatocellular carcinoma: a comparative study.

BACKGROUND AND OBJECTIVE: Cytokine-induced killer (CIK) cells have high anti-tumor activity for hepatocellular carcinoma (HCC). Whether CIK cell therapy can eradicate residual cancer cells and prevent or postpone tumor relapse after transcatheter arterial chemoembolization (TACE) should be testified. This study was to evaluate the efficacy of CIK cell therapy combined with TACE on HCC. METHODS: A total of 146 consecutive patients with unresectable HCC were divided into combination group (72 patients treated with CIK cell therapy combined with TACE) and TACE group (74 patients treated only with TACE). The progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: The 6-month, 1-year, and 2-year PFS rates were 72.2%, 40.4%, 25.3% in combination group, and 34.8%, 7.7%, 2.6% in TACE group. The median time to progression was 11 months [95% confidence interval (CI), 8-14 months] in combination group and 5 months (95% CI, 4-7 months) in TACE group. The estimated 6-month, 1-year, and 2-year OS rates were 90.3%, 71.9%, 62.4% in combination group, and 74.6%, 42.8%, 18.8% in TACE group. The median OS was 31 months (95% CI, 27-35 months) in combination group and 10 months (95% CI, 7-13 months) in TACE group. The times of TACE, ECOG performance status, and CIK cell therapy were independent prognostic factors for PFS and OS. CONCLUSION: Adjuvant immunotherapy with CIK cells could greatly improve the efficacy of TACE on HCC, and plays an important role in prolonging the PFS and OS of HCC patients after TACE.

[Efficacy of transcatheter arterial chemoembolization combined thalidomide on hepatocellular carcinoma: a controlled randomized trial].

BACKGROUND & OBJECTIVE: Transcatheter arterial chemoembolization (TACE) is an important therapy for hepatocellular carcinoma (HCC), but the recurrence rate is still high and the long-term survival is unsatisfactory. This study was to evaluate the efficacy of TACE combined thalidomide on HCC. METHODS: From Aug. 2004 to Aug. 2006, 108 patients with unresectable primary HCC were randomized into combination (TACE plus thalidomide) group and TACE group. Combination group received oral administration of thalidomide (200 mg/d) for 1-6 months. Both groups were treated with 0.4-1.6 g gemcitabine, 100-200 mg oxaliplatin, and 0.5-1.0 g floxuridine as chemotherapeutic drugs, ethanol, glutin, and iodolipol as ambolic agent in TACE. The side effects of thalidomide and survival of the patients were observed. RESULTS: The median survival period was 18 months [95% confidence interval (CI), 12-24 months] in combination group and 13 months (95% CI, 10-16 months) in TACE group. The 6-month, 1-year, and 2-year survival rates were 92.9%, 82.7%, and 58.4% respectively in combination group, and 85.6%, 57.2%, and 32.3% respectively in TACE group. The median time to progression was significantly longer in combination group than in TACE group [181 days (95% CI, 91-271 days) vs. 97 days (95% CI, 33-161 days), P<0.05]. Excluding the patients who took thalidomide for less than 1 month, the median survival period was significantly longer in combination group than in TACE group [18 months (95% CI, 12-24 months) vs. 13 months (95% CI, 10-16 months), P<0.05]û the 6-month, 1-year, and 2-year survival rates were 96.6%, 70.8%, and 44.3% respectively in combination group, and 84.7%, 54.4%, and 14.9% respectively in TACE group. The occurrence rate of serious rashes was 11.1% and that of serious somnolency was 6.7%. Multivariate Cox analysis showed that the times of TACE was an independent prognostic factor of HCC. CONCLUSIONS: Compared with TACE alone, the combination of TACE and thalidomide can obviously postpone disease progression and prolong survival of HCC patients. The times of TACE is a prognostic factor of HCC after TACE.