Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma.

We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of ∼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal-like reprogramming of the tumor microenvironment. Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including re-emergence of fetal-associated endothelial cells (PLVAP/VEGFR2) and fetal-like (FOLR2) tumor-associated macrophages. In a cross-species comparative analysis, we discovered remarkable similarity between mouse embryonic, fetal-liver, and tumor macrophages. Spatial transcriptomics further revealed a shared onco-fetal ecosystem between fetal liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem in fetal liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease.

Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency.

Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals and tissues. It also provides a global, comprehensive, and detailed description of ILC heterogeneity in humans across patients and tissues.

Obstructive jaundice due to intraductal tumour thrombus in recurrent hepatocellular carcinoma: what is the optimal therapeutic approach?

Icteric Hepatocellular Carcinoma (HCC) is known to cause intraluminal biliary obstruction by one of three mechanisms: hemobilia from the tumour, migration of tumor debris, or continuous growth along the biliary tree. It is however a very rare presentation of HCC and an important differential diagnosis in the approach to obstructive jaundice. We report a case of a recurrent intraductal hepatocellular carcinoma. The patient initially underwent surgical resection of segment five HCC nine months ago with clear margins. The patient now presents with obstructive jaundice and imaging showed a right intraductal tumour involving the confluence, left and common hepatic ducts. He underwent a right hepatectomy and bile duct tumour thrombectomy despite the apparent absence of a parenchymal tumour. Histological examination showed a 2 mm focus of parenchymal tumour with extension of the tumour into the bile duct. In this case report, we reviewed the literature and describe the different surgical approaches to intraductal hepatocellular carcinomas and discuss the pathological aspects of these bile duct tumour thrombus. We report the favourable outcome of surgical resection for intraductal hepatocellular carcinoma and emphasize that intraductal HCC is not a late stage of disease and adequate surgical resection can still provide a reasonable disease free survival.

Renal artery stump to inferior vena cava fistula: unusual clinical presentation and transcatheter embolization with the Amplatzer vascular plug.

Fistulous communication between the renal artery stump and inferior vena cava following nephrectomy is rare. We describe the case of a 52-year-old man with a fistula detected on investigation for hemolytic anemia in the postoperative period. The patient had had a nephrectomy performed 2 weeks prior to presentation for blunt abdominal trauma. The fistula was successfully occluded percutaneously using an Amplatzer vascular plug. The patient recovered completely and was discharged 2 weeks later.