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.

Protein kinases: The key contributors in pathogenesis and treatment of nonalcoholic fatty liver disease-derived hepatocellular carcinoma.

Protein kinases (PKs), one of the largest protein families, can be further divided into different groups based on their substrate or structure and function. PKs are important signaling messengers in numerous life activities, including cell metabolism, proliferation, division, differentiation, senescence, death, and disease. Among PK-related diseases, nonalcoholic fatty liver disease (NAFLD) has been recognized as a major contributor to hepatocellular carcinoma (HCC) and liver transplantation. Unfortunately, NAFLD-derived HCC (NAFLD-HCC) has poor prognosis because it is typically accompanied by older age, multiple metabolic syndromes, obstacles in early-stage diagnosis, and limited licensed drugs for treatment. Accumulating evidence suggests that PKs are implicated in the pathogenic process of NAFLD-HCC, via aberrant metabolism, hypoxia, autophagy, hypoxia, gut microbiota dysbiosis, and/or immune cell rearrangement. The present review aims to summarize the latest research advances and emphasize the feasibility and effectiveness of therapeutic strategies that regulate the expression and activities of PKs. This might yield clinically significant effects and lead to the design of novel PK-targeting therapies. Furthermore, we discuss emerging PK-based strategies for the treatment of other malignant diseases similar to NAFLD-HCC.

JAK2 inhibitor combined with DC-activated AFP-specific T-cells enhances antitumor function in a Fas/FasL signal-independent pathway.

OBJECTIVE: Combination therapy for cancer is more effective than using only standard chemo- or radiotherapy. Our previous results showed that dendritic cell-activated α-fetoprotein (AFP)-specific T-cells inhibit tumor in vitro and in vivo. In this study, we focused on antitumor function of CD8(+) T-cells combined with or without JAK2 inhibitor. METHODS: Proliferation and cell cycle were analyzed by CCK-8 and flow cytometry. Western blot was used to analyze the expression level of related protein and signaling pathway. RESULTS: We demonstrated reduced viability and induction of apoptosis of tumor cells with combination treatment. Intriguingly, cell cycle was blocked at the G1 phase by using AFP-specific CD8(+) T-cells combined with JAK2 inhibitor (AG490). Furthermore, an enhanced expression of BAX but no influence on Fas/FasL was detected from the tumor cells. CONCLUSION: These results indicate a Fas/FasL-independent pathway for cellular apoptosis in cancer therapies with the treatment of AFP-specific CD8(+) T-cells combined with JAK2 inhibitor.

Braun Enteroenterostomy Following Pancreaticoduodenectomy: A Systematic Review and Meta-Analysis.

Pancreaticoduodenectomy (PD) holds high postoperative morbidity. How to resolve this issue is challenged. An additional anastomosis (Braun enteroenterostomy) following PD may decrease the postoperative morbidity, but holds conflicting results. The objective of this study is to investigate the advantages and disadvantages of Braun enteroenterostomy in PD.Clinical studies compared perioperative outcomes between the Braun group and the non-Braun group following PD before December 21, 2014 were retrieved and filtered from PubMed, EMBASE, Web of Science, the Cochrane Library, and Chinese electronic databases (VIP database, WanFang database, and CNKI database). Relevant data were extracted according to predesigned sheets. Blood loss, operating time, and postoperative mortality and morbidity were evaluated using odds ratio (OR), weighted mean difference, or standard mean difference (SMD).Ten studies concerning 1614 patients were included. No significant differences between the Braun and the non-Braun group were identified in mortality (OR: 0.65, 95% confidence interval [CI]: 0.26-1.60), intraoperative blood loss (SMD: -0.035, 95% CI: -0.253 to 0.183), postoperative pancreatic fistula (POPF) (OR: 0.67, 95% CI: 0.35-1.67), bile leakage (OR: 0.537, 95% CI: 0.287-1.004), postoperative gastrointestinal hemorrhage (OR: 1.17, 95% CI: 0.578-2.385), intraabdominal abscesses (OR: 0.793, 95% CI: 0.444-1.419), wound complications (OR: 0.806, 95% CI: 0.490-1.325), and hospital stay (SMD: -0.098, 95% CI: -0.23 to 0.033). Braun enteroenterostomy extended operating time (SMD: 0.39, 95% CI: 0.02-0.78), but it was associated with lower reoperation rate (OR: 0.380, 95% CI: 0.149-0.968), lower morbidity rate (OR: 0.66, 95% CI: 0.49-0.91), lower clinically relevant delayed gastric emptying (Grades B and C) (OR: 0.375, 95% CI: 0.164-0.858), lower nasogastric tube reinsertion (OR: 0.436, 95% CI: 0.232-0.818), and less postoperative vomiting (OR: 0.444, 95% CI: 0.262-0.755).Braun enteroenterostomy can be safely performed during PD. It is beneficial for patients and could be recommended in PD from the current published data.PROSPERO registration number: CRD42015016198.

The SDF-1/CXCR4 axis regulates migration of transplanted bone marrow mesenchymal stem cells towards the pancreas in rats with acute pancreatitis.

Stromal cell-derived factor-1 (SDF-1) and its receptor, CXC chemokine receptor-4 (CXCR4), are important regulators in the migration of bone marrow mesenchymal stem cells (BMSCs). However, the mechanisms underlying this effect in acute pancreatitis (AP) have not been investigated. In this study, BMSCs were identified by specific cell surface markers and differentiation potentials, and labeled with chloromethylbenzamido-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (CM-Dil) for in vivo cell tracking. AP was induced by retrograde infusion of sodium taurocholate into the common bile duct in rats. The expression of SDF-1 in the injured pancreas was determined by immunohistochemistry and western blot analysis. BMSCs were incubated with or without anti-CXCR4 antibody and the contribution of SDF-1 to the migration of BMSCs was investigated. Our results demonstrated that the expression of SDF-1 was significantly increased in the injured pancreas, and that these levels peaked on days 5-7 and began to decrease on day 10. SDF-1 induced a dose-dependent migration of BMSCs in an in vitro transwell migration assay, which was almost completely blocked by AMD3100 (CXCR4-specific antagonist) or anti-CXCR4 antibody. In addition, by encouraging the migration of CM-Dil-labeled BMSCs, the SDF-1/CXCR4 axis facilitated the repair of the injured pancreas. This effect was inhibited by the anti-CXCR4 antibody. Taken together, these results indicate that the interaction of locally produced SDF-1 with CXCR4 on BMSCs, has an important regulatory role in the migration of BMSCs towards the injured pancreas in AP.