[A retrospective controlled study of TACE-HAIC-targeted-immune quadruple therapy for intermediate and advanced-stage hepatocellular carcinoma].

Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC)-targeted-immune quadruple therapy in patients with intermediate and advanced-stage hepatocellular carcinoma (HCC). Methods: 101 patients with intermediate and advanced stage HCC were enrolled according to the inclusion and exclusion criteria, and then they were divided into a combination group and a control group. Patients in the combination group was treated with TACE-HAIC-targeted-immune quadruple therapy, while the control group was only treated with TACE therapy. The overall survival (OS), progression-free survival (PFS), and treatment-related adverse reactions were statistically analyzed in the two groups of patients. Statistical analysis was carried out by t-test, χ2 test, rank sum test, Kaplan-Meier curve, log-rank test, Cox regression (or proportional hazards model) analysis according to different data. Results: The tumor objective response rate and disease control rate as evaluated by mRECIST 1.1 criteria in the combination group were 80% and 94%, respectively, which were significantly higher than those in the control group, 41.2% (P<0.001) and 74.5% (P=0.007). The OS and PFS of the combination group were 15.6 months [95%CI 11.3-NA ] and 8.8 months [95%CI 6.9-12.0], respectively, which were significantly better than the control group at 6.1 months [95%CI 5.3-6.6] (P<0.001) and 3.2 months [95%CI 3.0-3.6] (P<0.001). Gastric ulcer incidence was significantly higher in the combination group (9/50, 18%) than that in the control group (2/51, 3.9%) (P=0.023). Conclusion TACE-HAIC-targeted-immune quadruple therapy is a more effective treatment mode for intermediate and advanced-stage HCC than TACE alone, and attention should be paid to the monitoring of target immune-related adverse reactions.

[Safety and efficacy of TIPS combined with iodine-125 seed strands in the treatment of patients with hepatocellular carcinoma combined with portal vein tumor thrombosis].

Objective: To study the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with iodine-125 (125Ⅰ) seed strands implantation in patients with hepatocellular carcinoma combined with portal vein tumor thrombosis. Methods: 25 cases with diffuse intrahepatic tumor combined with tumor thrombus type Ⅲ/Ⅳ requiring TIPS were simultaneously implanted with 125Ⅰseed strand. Tumor thrombus was controlled with 125I seed implantation brachytherapy to keep the TIPS pathway unobstructed, reduce the portal vein pressure, and observe the changes in the cause of death of the patients. During the same period, 30 cases without TIPS and seed strand implantation were used as controls. Data between groups were compared using t-test, Chi-Squared test or Fisher's exact test. Results: TIPS combined with 125Ⅰ seed strand implantation was safe in patients with diffuse hepatocellular carcinoma combined with type III/IV portal vein tumor thrombus, and 92.0% (23/25) of the patients maintained unobstructed TIPS pathway. Compared with the control group, patients in the treatment group died of fewer lead-related complications, and most died from chronic liver failure (84.0% vs. 56.7%, χ2 = 4.771, P=0.029). The incidence of upper gastrointestinal bleeding was significantly decreased (12.0% vs. 46.7%, χ2 =7.674, P=0.006) and ascites severity was significantly improved (mild 40.0% vs. 16.7%, moderate 52.0% vs. 20.0%, severe 8.0% vs. 46.7%, χ2 =13.246 , P=0.001). Conclusions: TIPS combined with 125Ⅰ seed strand implantation is safe and feasible in patients with diffuse intrahepatic tumor combined with tumor thrombus type Ⅲ/Ⅳ. Moreover, it can effectively keep the shunt patency and reduce portal vein pressure, thereby reducing the incidence of upper gastrointestinal bleeding and improving the degree of ascites. TIPS combined with 125Ⅰ seed strand implantation may be used as a standard treatment modality for patients requiring TIPS therapy combined with tumor thrombus type Ⅲ/Ⅳ.

[Paclitaxel enhances the protective effect of myocardial ischemia preconditioning on ischemia/reperfusion injury in aged rat].

Objective: To investigate if paclitaxel can enhance the protective effect of myocardial ischemia preconditioning on ischemia/reperfusion injury in aged ratand explore related mechanism. Methods: Primary cardiomyocytes of Sprague-Dawley rats were isolated by trypsin and divided into 5 groups(n=6 each): control group, hypoxia injury group, hypoxia preconditioning group, paclitaxel group,and paclitaxel+hypoxia preconditioning group. The structure of microtubules and the expression of hypoxia-inducible factor-1α(HIF-1α) were analyzed by immunofluorescence staining. The Langendorff isolated heart perfusion model was applied in 4 groups: hypoxia reperfusion injury group, hypoxia preconditioning group, paclitaxel group, and paclitaxel+hypoxia preconditioning group. Each group was further divided into elderly subgroup and adult subgroup (n=6 each). Left ventricular developed pressure and maximum rate of rise in left ventricular pressure were analyzed. Results: (1) Primary cardiomyocyte experiments showed that the myocardial tubular microtubule structure in control group was intact and evenly stained; most of the microtubules in the hypoxia-injured group were absent and the tubular tissue was broken; the hypoxia-induced damage on microtubule structure was smaller in the hypoxic preconditioning group compared with the hypoxic injury group (microtubule staining was not uniform, and the lattice structure was broken, but not that obvious as in the hypoxia group); the tubular structure of the microtubules of the paclitaxel group was basically complete, and the staining was basically uniform.The integrity of tubular structure was maintained to some extent, similar to a normal microtubule structure in paclitaxel+hypoxia preconditioning group. The expression of HIF-1α in the cytoplasm and nucleus was very low in the control group, which was evidenced in both cytoplasm and nucleus in the hypoxic injury group.The expression was further increased in hypoxic preconditioning group, significant nuclear HIF-1 expression was found in the paclitaxel group, the expression was aggregated in the nucleus in the Paclitaxel+ hypoxia preconditioning group. (2)In Langendorff isolated heart perfusion model, left ventricular developed pressure was similar between the elderly subgroup and the adult subgroup at the end of the infusion,after precondition, 5 minutes of reperfusion, 30 minutes of reperfusion, and 60 minutes of reperfusion in the hypoxic injury group (all P> 0.05).In the hypoxic injury group, both the elderly subgroup and the adult subgroup had lower left ventricular developed pressure at 30 minutes of reperfusion when compared with the end of the infusion((15.63±4.88) mmHg (1 mmHg=0.133 kPa) vs. (95.63±22.14)mmHg and (17.31±2.75)mmHg vs. (91.00±9.58)mmHg, respectively,all P<0.05). In the hypoxic preconditioning group, the adult subgroup had higher left ventricular developed pressure at 5 and 30 minutes of reperfusion when compared with the elderly subgroup((7.13±1.02) mmHg vs. (3.75±1.06)mmHg and (43.94±3.21)mmHg vs.(16.31±1.54)mmHg, respectively,all P<0.01). In the paclitaxel group, the adult subgroup had higher left ventricular developed pressure at 30 and 60 minutes of reperfusion when compared with the elderly subgroup((44.31±7.59)mmHg vs. (5.44±1.21)mmHg, (51.56±6.03)mmHg vs. (22.19±5.14)mmHg, respectively, all P<0.01). In the paclitaxel+hypoxia preconditioning group, both the elderly subgroup and the adult subgroup had lower left ventricular developed pressure at 30 minutes of reperfusion when compared with the end of the infusion((18.63±4.30)mmHg vs. (99.94±8.23) mmHg, P<0.01; (49.69±5.34)mmHg vs. (95.31±5.26)mmHg, P<0.05). Meanwhile, the adult subgroup had higher left ventricular developed pressure at 30 minutes of reperfusion when compared with the elderly subgroup((49.69±5.34)mmHg vs. (18.63±4.33)mmHg, P<0.01).The adult subgroup had higher change rate of maximum rate of rise in left ventricular pressure at 60 minutes of reperfusion when compared with the elderly subgroup in hypoxia preconditioning group, paclitaxel group, and paclitaxel combined hypoxia preconditioning group((62.83±3.92)% vs. (33.33±3.20)%, (44.17±2.32)% vs. (36.67±2.88)%, (72.50±2.66)% vs. (53.17±2.56)%, respectively,all P<0.01). Conclusion: Paclitaxel can enhance the myocardial protective effect of myocardial ischemia preconditioning through stabilizing microtubules of cardiomyocytes and promoting HIF-1α localization in the nucleus.