Therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Immune checkpoint inhibitor therapy is the backbone of numerous combination regimens for improving the therapeutic response of patients with hepatocellular carcinoma (HCC). We aimed to investigate the therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable HCC. METHODS: Patients with unresectable HCC who received sorafenib and followed at Taipei Tzu Chi Hospital from January 2016 to May 2022 were selected for this study, and those treated with nivolumab plus sorafenib and those with sorafenib alone were propensity score matched. The primary outcome was overall survival (OS) presented as a hazard ratio calculated using Cox proportional hazards regression models. RESULTS: In the analysis, 36 patients receiving nivolumab plus sorafenib and 36 receiving sorafenib alone were propensity score matched. The median OS for those receiving nivolumab plus sorafenib and sorafenib alone were 3.6 years and 1.2 years, respectively (p = 0.031). The hazard ratio of OS for nivolumab plus sorafenib compared to sorafenib alone was 0.36 (95 %CI, 0.19-0.70; p = 0.003). Furthermore, patients receiving nivolumab plus sorafenib with a baseline α-fetoprotein(AFP) < 10 ng/mL and early reduction in AFP had a 100 % objective response rate and disease control rate. CONCLUSION: In patients with unresectable HCC, nivolumab plus sorafenib resulted in better OS outcomes than sorafenib.

Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression.

One of the signaling components involved in hepatocellular carcinoma (HCC) progression is the focal adhesion adaptor paxillin. Hydrogen peroxide inducible clone-5 (Hic-5), one of the paralogs of paxillin, exhibits many biological functions distinct from paxillin, but may cooperate with paxillin to trigger tumor progression. Screening of Hic-5 in 145 surgical HCCs demonstrated overexpression of Hic-5 correlated well with intra- and extra-hepatic metastasis. Hic-5 highly expressed in the patient derived HCCs with high motility such as HCC329 and HCC353 but not in the HCCs with low motility such as HCC340. Blockade of Hic-5 expression prevented constitutive migration of HCC329 and HCC353 and HGF-induced cell migration of HCC340. HCC329Hic-5(-), HCC353Hic-5(-), HCC372Hic-5(-), the HCCs stably depleted of Hic-5, exhibited reduced motility compared with each HCC expressing Scramble shRNA. Moreover, intra/extrahepatic metastasis of HCC329Hic-5(-) in SCID mice greatly decreased compared with HCC329Scramble. On the other hand, ectopic Hic-5 expression in HCC340 promoted its progression. Constitutive and HGF-induced Hic-5 expression in HCCs were suppressed by the reactive oxygen species (ROS) scavengers catalase and dithiotheritol and c-Jun N-terminal kinase (JNK) inhibitor SP600125. On the contrary, depletion of Hic-5 blocked constitutive and HGF-induced ROS generation and JNK phosphorylation in HCCs. Also, ectopic expression of Hic-5 enhanced ROS generation and JNK phosphorylation. These highlighted that Hic-5 plays a central role in the positive feedback ROS-JNK signal cascade. Finally, the Chinese herbal derived anti-HCC peptide LZ-8 suppressed constitutive Hic-5 expression and JNK phosphorylation. In conclusion, Hic-5 mediates ROS-JNK signaling and may serve as a therapeutic target for prevention of HCC progression.

Minilaparoscopic herniorrhaphy in pediatric inguinal hernia: a durable alternative treatment tostandard herniotomy.

BACKGROUND: The purpose of the article is to report our long-term results of minilaparoscopic inguinal hernia repair in children. METHODS: Between September 2003 and September 2008, 161 children with inguinal hernia were treated with minilaparoscopic herniorrhaphy. The asymptomatic contralateral internal ring was routinely explored and repaired if a patent processus vaginalis of not less than 2 cm was noted. Patients who were followed for less than 1 year and those who were lost to follow-up were excluded from the study. Intraoperative and postoperative complications and hernia recurrences were documented. RESULTS: In total, 146 patients were eligible for final analysis. A total of 196 minilaparoscopic herniorrhaphies were performed. The mean follow-up period was 3 years. There were 4 hernia recurrences (2%) in 3 boys. There were no procedure-related complications. None of the patients with a negative contralateral exploration or a contralateral patent processus vaginalis of less than 2 cm had a contralateral metachronous inguinal hernia. CONCLUSIONS: Our long-term results reveal that minilaparoscopic herniorrhaphy combined with hernia sac transection is a safe and effective alternative treatment to standard open herniotomy.