Pathophysiology of portal vein thrombosis (PVT) in cirrhosis is still not entirely understood. Elevated levels of lipopolysaccharides (LPS) in portal circulation are significantly associated with hypercoagulation, increased platelet activation and endothelial dysfunction. The aim of the study was to investigate if LPS was associated with reduced portal venous flow, the third component of Virchow\'s triad, and the underlying mechanism. Serum nitrite/nitrate, as a marker of nitric oxide (NO) generation, and LPS were measured in the portal and systemic circulation of 20 patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedure; portal venous flow velocity (PVV) was also measured in each patient and correlated with NO and LPS levels. Serum nitrite/nitrate and LPS were significantly higher in the portal compared to systemic circulation; a significant correlation was found between LPS and serum nitrite/nitrate (R = 0.421; p < 0.01). Median PVV before and after TIPS was 15 cm/s (6-40) and 31 cm/s (14-79), respectively. Correlation analysis of PVV with NO and LPS showed a statistically significant negative correlation of PVV with portal venous NO concentration (R = - 0.576; p = 0.020), but not with LPS. In vitro study with endothelial cells showed that LPS enhanced endothelial NO biosynthesis, which was inhibited by L-NAME, an inhibitor of NO synthase, or TAK-242, an inhibitor of TLR4, the LPS receptor; this effect was accomplished by up-regulation of eNOS and iNOS. The study shows that in cirrhosis, endotoxemia may be responsible for reduced portal venous flow via overgeneration of NO and, therefore, contribute to the development of PVT.

In physiological glucose homeostasis, the liver plays a crucial role in the extraction of glucose from the portal circulation and storage as glycogen to enable release through glycogenolysis upon fasting. In addition, insulin secreted by the pancreas is partly eliminated from the systemic circulation by hepatic first-pass. Therefore, patients with a congenital porto-systemic shunt present a unique combination of (a) postabsorptive hyperinsulinemic hypoglycaemia (HH) because of decreased insulin elimination and (b) fasting (ketotic) hypoglycaemia because of decreased glycogenolysis. Patients with porto-systemic shunts therefore provide important insight into the role of the portal circulation and hepatic function in different phases of glucose homeostasis.

Circulating tumor cells (CTC) enter the blood from many carcinomas and represent a likely source of metastatic dissemination. In contrast to the peripheral circulation, KRAS mutation- positive CTC thrive in the portal venous blood of patients with pancreatic ductal adenocarcinoma (PDAC). To analyze the essential interactions that contribute to carcinoma CTC growth and immune resistance, portal venous blood was collected during pancreatico-duodenectomy in 41 patients with peri-ampullary pathologies (PDAC = 11; ampullary adenocarcinoma (AA) = 15; distal cholangiocarcinoma (CC) = 6; IPMN = 7; non-malignant pancreatitis = 2). FACS-isolated cell populations from the portal circulation were reconstituted ex vivo using mixed cell reaction cultures (MCR). During the first 48hr, PDAC, AA, and CC patient CTC were all highly proliferative (mean 1.7 hr/cell cycle, 61.5% ± 20% growing cells) and resistant to apoptosis (mean 39% ±  25% apoptotic cells). PDAC CTC proliferation and resistance to T cell cytotoxicity were decreased among patients who received pre-operative chemotherapy (p = 0.0019, p = 0.0191, respectively). After 7 days in culture, CTC from PDAC, CC, and AA patients recruited multiple immune cell types, including CD105 + CD14 + myeloid fibroblasts, to organize into spheroid-like clusters. It was only in PDAC and CC-derived MCR that cluster formation promoted CTC survival, growth, and fibroblast differentiation. FACS depletion of CTC or myeloid fibroblast cells eliminated cluster network formation, and re-introduction of these cell populations reconstituted such ability. Our findings suggest that PDAC and CC CTC survival within the portal venous circulation is supported by their interactions with immune cells within multi-cell type clusters that could represent vectors of local recurrence and metastatic progression.

We performed brain magnetic resonance imaging in 40 patients after the Fontan procedure and 40 control subjects. Pituitary volumes in patients after Fontan were significantly larger than those in the control subjects (472 [425-527] vs 257 [182-311]; P < .0001), and were significantly related to central venous pressure.

The distinction between the medical and the surgical approach to disease has been a cornerstone of medical practice, and indeed with respect to the business and technology of medicine. It is common knowledge that diabetes is a medical disease-namely that drug therapy, whether it be via insulin or other medications, is the primary approach to therapy. This article argues that a reevaluation of the generalized (e.g., medication-based) approach to systemic blood sugar control may be in order. A consideration of the growing importance of interventional, device-based, or other surgical approaches to the primary management of diabetes has enormous implications for clinical practice as well as, of course, the business and technology of diabetes care.