Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

The formation of Ca^(2+) gradients at the cleavage furrows during cytokinesis of Zebrafish embryos

In dividing embryos,a localized elevation in intracellular Ca^(2+)([Ca^(2+)]i)at the cleavage furrow has been shown to be essential for cytokinesis.However,the underlying mechanisms for generating and maintaining these[Ca^(2+)]_(i) gradients throughout cytokinesis are not fully understood.In the present study,we analyzed the role of inositol 1,4,5-trisphosphate receptors(IP3Rs)and endoplasmic reticulum(ER)distribution in determining the intracellular Ca^(2+) gradients in early zebrafish blastomeres.Application of the injected Ca^(2+) indicator,Indo-1,showed that during the first cell division a standing Ca^(2+) gradient was formed~35 min after fertilization,with the[Ca^(2+)]_(i) spatially decaying from 500–600 nmol/L at the cleavage furrow to 100–200 nmol/L around the nucleus.While the IP3R immunohistochemical fluorescence was relatively concentrated in the peri-furrow region,ER labeling was relatively enriched in both peri-furrow and peri-nuclear regions.Numeric simulation suggested that a divergence in the spatial distribution of IP3R and the locations of Ca^(2+) uptake within the ER was essential for the formation of a standing Ca^(2+) gradient,and the Ca^(2+) gradient could only be well-established under an optimal stoichiometry of Ca^(2+) uptake and release.Indeed,while inhibition of IP3R Ca^(2+) release blocked the generation of the Ca^(2+)gradient at a lower[Ca^(2+)]_(i) level,both Ca^(2+) release stimulation by inositol 1,4,5-trisphosphate(IP3)injection and ER Ca^(2+) pump inhibition by cyclopiazonic acid also eliminated the Ca^(2+) gradients at higher[Ca^(2+)]_(i) levels.Our results suggest a dynamic relationship between ER-mediated Ca^(2+) release and uptake that underlies the maintenance of the perifurrow Ca^(2+) gradient and is essential for cytokinesis of zebrafish embryos.