y These authors contributed equally.A nonspecific inflammatory and thrombotic reaction termed instant blood-mediated inflammatory reaction (IBMIR) has been reported when allogenic or xenogenic islets come into contact with blood. This reaction is known to cause significant loss of transplanted islets. We hypothesized that IBMIR occurs in patients undergoing total pancreatectomy followed by autologous islet transplantation (TP-AIT) and tested this hypothesis in 24 patients and in an in vitro model. Blood samples drawn during the peritransplant period showed a significant and rapid increase of thrombinanti-thrombin III complex (TAT) and C-peptide during islet infusion, which persisted for up to 3 h, along with a decreased platelet count. A concomitant increase in levels of inflammatory proteins IL-6, IL-8 and interferoninducible protein-10 was observed. An in vitro model composed of pure islets plus autologous blood also demonstrated significantly increased levels of TAT (p < 0.05), C-peptide (p < 0.05), tumor necrosis factoralpha (p < 0.05) and MCP-1 (p < 0.05), as well as strong tissue factor expression in islets. Islet viability decreased significantly but was rescued by the presence of low-molecular-weight dextran sulfate. In conclusion, AIT-induced elevation of TAT and destruction of islets suggests that IBMIR might occur during AIT. Modulating this process may help improve islet engraftment and the insulin independence rate in TP-AIT patients.
BackgroundThe M2 phenotype of tumor-associated macrophages (TAM) inhibits the anti-tumor inflammation, increases angiogenesis and promotes tumor progression. The transcription factor Nuclear Factor (erythroid-derived 2)-Like 2 (Nrf2) not only modulates the angiogenesis but also plays the anti-inflammatory role through inhibiting pro-inflammatory cytokines expression; however, the role of Nrf2 in the cancer cell and macrophages interaction is not clear.MethodsHepatocellular carcinoma cells (Hep G2 and Huh 7) and pancreatic cancer cells (SUIT2 and Panc-1) were co-cultured with monocytes cells (THP-1) or peripheral blood monocytes derived macrophages, then the phenotype changes of macrophages and epithelial-mesenchymal transition of cancer cells were detected. Also, the role of Nrf2 in cancer cells and macrophages interaction were investigated.ResultsIn this study, we found that cancer cells could induce an M2-like macrophage characterized by up-regulation of CD163 and Arg1, and down-regulation of IL-1b and IL-6 through Nrf2 activation. Also, Nrf2 activation of macrophages promoted VEGF expression. The Nrf2 activation of macrophages correlated with the reactive oxygen species induced by cancer cells derived lactate. Cancer cells educated macrophages could activate Nrf2 of the cancer cells, in turn, to increase cancer cells epithelial-mesenchymal transition (EMT) through paracrine VEGF. These findings suggested that Nrf2 played the important role in the cancer cells and macrophages interaction.ConclusionsMacrophage Nrf2 activation by cancer cell-derived lactate skews macrophages polarization towards an M2-like phenotype and educated macrophages activate Nrf2 of the cancer cells to promote EMT of cancer cells. This study provides a new understanding of the role of Nrf2 in the cancer cell and TAM interaction and suggests a potential therapeutic target.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0262-x) contains supplementary material, which is available to authorized users.
Objective: The aim of this study was to investigate the potential of an intraoperative 3D hologram, which was a computer graphics model liver, with mixed reality techniques in liver surgery. Summary Background Data: The merits for the application of a hologram for surgical support are: 1) no sterilized display monitor; 2) better spatial awareness; and 3) 3D images shared by all the surgeons. Methods: 3D polygon data using preoperative computed tomography data was installed into head mount displays, HoloLens (Microsoft Corporation, Redmond, WA). Results: In a Wi-Fi-enabled operative room, several surgeons wearing HoloLens succeeded in sharing the same hologram and moving that hologram from respective operators’ angles by means of easy gesture-handling without any monitors. The intraoperative hologram contributed to better imagination of tumor locations, and for determining the parenchymal dissection line in the hepatectomy for the patients with more than 20 multiple colo-rectal liver metastases. In another case, the hologram enabled a safe Gliisonean pedicle approach for hepato-cellular carcinoma with a hilar anatomical anomaly. Surgeons could easily compare the real patient's anatomy and that of the hologram just before the hepatic hilar procedure. Conclusions: This initial experience suggested that an intraoperative hologram with mixed reality techniques contributed to “last-minute simulation,” not for “navigation.” The intraoperative hologram might be a new next-generation operation-supportive tool in terms of spatial awareness, sharing, and simplicity.
CD133 expression tended to be related to higher incidences of intrahepatic metastasis and positive expression of hypoxia-inducible factor-1alpha; furthermore, it was independently related to worse prognosis. Therefore, the CD133 expression is a potential prognostic indicator in IHCC.
Hepatectomy for HCC was a feasible option even in super elderly patients aged 80 years or older with accurate selection.
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