The gut microbiota and liver cancer have a complex interaction. However, the role of gut microbiome in liver tumor initiation remains unknown. Herein, liver cancer was induced using hydrodynamic transfection of oncogenes to explore liver tumorigenesis in mice. Gut microbiota depletion promoted liver tumorigenesis but not progression. Elevated sterol regulatory element-binding protein 2 (SREBP2) was observed in mice with gut flora disequilibrium. Pharmacological inhibition of SREBP2 or Srebf2 RNA interference attenuated mouse liver cancer initiation under gut flora disequilibrium. Furthermore, gut microbiota depletion impaired gut tryptophan metabolism to activate aryl hydrocarbon receptor (AhR). AhR agonist Ficz inhibited SREBP2 posttranslationally and reversed the tumorigenesis in mice. And, AhR knockout mice recapitulated the accelerated liver tumorigenesis. Supplementation with Lactobacillus reuteri , which produces tryptophan metabolites, inhibited SREBP2 expression and tumorigenesis in mice with gut flora disequilibrium. Thus, gut flora disequilibrium promotes liver cancer initiation by modulating tryptophan metabolism and up-regulating SREBP2.

The comprehensive role of interleukin (IL) 18 during liver regeneration is barely studied. Our aim is to evaluate the role of IL18 in liver regeneration after partial hepatectomy (PH) in mice. The expression profile of IL18 in the liver and the gut after 70% PH was measured. Liver samples after 70% and 85% PH from IL18 knockout (IL18−/−) mice and wild type (WT) mice were collected for comparison of liver regeneration. The effect of recombinant IL18 on liver regeneration was tested in IL18−/− mice, and the utility of IL18 binding protein (BP) was also evaluated following 70% PH in WT mice. Expression levels of IL18 in the liver and the gut elevated after 70% PH. The liver weight/body weight ratios (LBWRs) after PH were significantly higher in IL18−/− mice than those in WT mice. Recombinant IL18 injection significantly decreased LBWR at 7 days after 70% PH in IL18−/− mice. The expression of cyclin D1, EdU labeling index, and Ki‐67 proliferation index were much higher in IL18−/− mice than those in WT mice after 70% PH. The expression level of glypican 3 (GPC3) in WT mice significantly elevated during liver regeneration. In contrast, the expression level of GPC3 in IL18−/− mice remained roughly unchanged during liver regeneration. IL18BP injection significantly increased the LBWR at 7 days after 70% PH in WT mice. In conclusion, endogenous IL18 inhibited liver regeneration after PH in mice, possibly through up‐regulating GPC3. IL18BP may be an effective agent to promote liver regeneration after PH.

Objective: To achieve radical resection of locally advanced pancreatic ductal adenocarcinoma (PDAC), and tested the safety and benefits of intestinal autotransplantation in pancreatic surgery. Background: PDAC has an extremely dismal prognosis. Radical resection was proved to improve the prognosis of patients with PDAC; however, the locally advanced disease had a very low resection rate currently. We explored and evaluated whether the combination of modern advances in systemic treatment and this macroinvasive surgery was feasible in clinical practice. Methods: Patients diagnosed as PDAC with superior mesenteric artery involvement and with or without celiac trunk involvement were included. Patients were treated with modified-FOLFIRINOX chemotherapy with or without anti-PD-1 antibodies and were applied to tumor resection combined with intestinal autotransplantation. Data on operative parameters, pathologic results, mortality, morbidity, and survival were analyzed. Results: A total of 36 consecutive cases were applied to this strategy and underwent radical resection combined with intestinal autotransplantation. Among these patients, 24 of them received the Whipple procedure, 11 patients received total pancreatectomy, and the other 1 patient received distal pancreatectomy. The median operation time was 539 minutes. Postoperative pathology showed an R0 resection rate of 94.4%, and tumor invasion of a superior mesenteric artery or superior mesenteric vein was confirmed in 32 patients. The median number of dissected lymph nodes was 43, and 25 patients were positive for lymph node metastasis. The median time of intensive care unit From the