Flow diversion in the treatment of carotid injury and carotid-cavernous fistula after transsphenoidal surgery

We describe a case of iatrogenic carotid injury with secondary carotid-cavernous fistula (CCF) treated with a silk flow diverter stent placed within the injured internal carotid artery and coils placed within the cavernous sinus. Flow diverters may offer a simple and potentially safe vessel-sparing option in this rare complication of transsphenoidal surgery. The management options are discussed and the relevant literature is reviewed.     

A case of S‐100‐negative CD1a‐positive indeterminate cell histiocytosis

Histiocytoses are a group of rare disorders characterized by a proliferation of monocytes/macrophages and dendritic cells. We present a case of a 3‐year‐old girl with a diffuse papular eruption without systemic symptoms demonstrating a proliferation of strongly CD1a⁺ histiocytes, but negative for S‐100 and langerin on histopathology. Systemic work‐up including bone marrow biopsy was unremarkable, and the patient received a diagnosis of CD1a⁺ S^? 100‐indeterminate cell histiocytosis.     

LY3214996 relieves acquired resistance to sorafenib in hepatocellular carcinoma cells

Background: Sorafenib, an oral multi-kinase inhibitor of rapidly accelerated fibrosarcoma; vascular endothelial growth factor receptor-2/3, platelet-derived growth factor receptor, c-Kit, and Flt-3 signaling, is approved for treatment of advanced hepatocellular carcinoma (HCC). However, the benefit of sorafenib is often diminished because of acquired resistance through the reactivation of ERK signaling in sorafenib-resistant HCC cells. In this work, we investigated whether adding LY3214996, a selective ERK1/2 inhibitor, to sorafenib would increase the anti-tumor effectiveness of sorafenib to HCC cells.Methods: The Huh7 cell line was used as a cell model for treatment with sorafenib, LY3214996, and their combination. Phosphorylation of the key kinases in the Ras/Raf/MAPK and PI3K/Akt pathways, protein expression of the cell cycle, and apoptosis migration were assessed with western blot. MTT and colony-formation assays were used to evaluate cell proliferation. Wound-healing assay was used to assess cell migration. Cell cycle and apoptosis analyses were conducted with flow cytometry.Results: LY3214996 decreased phosphorylation of the Ras/Raf/MAPK and PI3K/Akt pathways, including p-c-Raf, p-P90RSK, p-S6K and p-eIF4EBP1 activated by sorafenib, despite increased p-ERK1/2 levels. LY3214996 increased the anti-proliferation, anti-migration, cell-cycle progression, and pro-apoptotic effects of sorafenib on Huh7^R cells.Conclusions: Reactivation of ERK1/2 appears to be a molecular mechanism of acquired resistance of HCC to sorafenib. LY3214996 combined with sorafenib enhanced the anti-tumor effects of sorafenib in HCC. These findings form a theoretical basis for trial of LY3214996 combined with sorafenib as second-line treatment of sorafenib-resistant in advanced HCC.