Clinical Relevance of Transjugular Liver Biopsy in Comparison with Percutaneous and Laparoscopic Liver Biopsy

Background. Transjugular liver biopsy (TJLB) is frequently used to obtain liver specimens in high-risk patients. However, TJLB sample size possibly limits their clinical relevance. Methods. 102 patients that underwent TJLB were included. Clinical parameters and outcome of TJLB were analyzed. Control samples consisted of 112 minilaparoscopic liver biopsies (mLLBs) and 100 percutaneous liver biopsies (PLBs). Results. Fewer portal tracts were detected in TJLB (4.3 ± 0.3) in comparison with PLB (11.7 ± 0.5) and mLLB (11.0 ± 0.6). No difference regarding the specification of indeterminate liver disease and staging/grading of chronic hepatitis was observed. In acute liver failure (n = 32), a proportion of hepatocellular necrosis beyond 25% was associated with a higher rate of death or liver transplantation. Conclusions. Despite smaller biopsy samples the impact on the clinical decision process was found to be comparable to PLB and mLLB. TJLB represents a helpful tool to determine hepatocellular necrosis rates in patients with acute liver failure

Plasma bile acids are not associated with energy metabolism in humans

Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p &lt;0.05) and T2DM (-32%, p &lt;0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p &lt;0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18% compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither total nor individual plasma BA levels correlated with energy expenditure. In addition, energy expenditure was identical in patients with a cholestatic versus a non-cholestatic origin of liver disease while plasma total BA levels differed four-fold between the groups. In conclusion, in the various (patho) physiological conditions studied, plasma BA levels were not associated with changes in energy expenditure. Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism.</p

PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity

The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 &gt;20%) from 57 patients and in 22 samples we correlated it with TAIC density by assessing intratumoral infiltration of CD3+, CD8+, and CD68+ cells. Furthermore, the tumor microenvironment was evaluated according to the classification of Teng et al. We detected PD-L1 expression in 31.6% of NEN G3. Its expression usually was weak and more IC than TC expressed PD-L1. The proportion of tumors positive for PD-L1 was comparable in NEN from different sites of origin but varied depending on tumor differentiation and disease extension. No positive IHC staining was found in 3 well-differentiated neuroendocrine tumors (NETs) with a proliferation rate above 20% (NET G3). When analyzing TAIC, we rarely (18.2%) detected intratumoral CD8+ cells, whereas infiltration by CD3+ and CD68+ cells was more common (45.5 and 59.1%, respectively). By combining CD3+ cells and PD-L1 status, we identified the immune ignorant phenotype of tumor microenvironment as being the most common phenotype, supporting the concept of a preferably combined immunotherapeutic approach in neuroendocrine carcinoma (NEC)

Etiology, management, and outcome of the Budd-Chiari syndrome

Background: The Budd-Chiari syndrome (BCS) is hepatic venous outflow obstruction. What is known about the syndrome is based on small studies of prevalent cases. Objective: To characterize the causes and treatment of incident BCS. Design: Consecutive case series of patients with incident BCS, enrolled from October 2003 to October 2005 and followed until May 2006. Setting: Academic and nonacademic hospitals in France, Spain, Italy, Great Britain, Germany, Belgium, the Netherlands, Portugal, and Switzerland. Patients: Persons older than 16 years with definite hepatic outflow obstruction diagnosed by imaging. Persons with hepatic outflow obstruction due to heart failure, sinusoidal obstruction syndrome, cancer, or liver transplantation were excluded. Measurements: Signs and symptoms; laboratory and imaging findings; diagnosis; treatment; and overall, transplantation-free, and intervention-free survival. Results: 163 incident cases of BCS were identified. Median follow-up was 17 months (range, 0.1 to 31 months). Most patients (84%) had at least 1 thrombotic risk factor, and many (46%) had more than 1; the most common was myeloproliferative disorders (49% of 103 tested patients). Patients were mainly treated with anticoagulation (140 patients [86%]), transjugular intrahepatic portosystemic shunting (56 patients [34%]), or liver transplantation (20 patients [12%]), and 80 patients (49%) were managed noninvasively. Only 3 patients underwent surgical shunting. The survival rate was 87% (95% CI, 82% to 93%) at 1 year and 82% (CI, 75% to 88%) at 2 years. Limitation: Treatment was not standardized across all centers, and data on important clinical variables were missing for some patients. Conclusion: Most patients with BCS have at least 1 thrombotic risk factor, and many have more than 1; myeloproliferative disorders are most common. One- and 2-year survival rates are good with contemporary management, which includes noninvasive therapies (anticoagulation and diuretics) and invasive techniques. Transjugular intrahepatic portosystemic shunting seems to have replaced surgical shunting as the most common invasive therapeutic procedure. Primary Funding Source: Fifth Framework Programme of the European Commission

The ice-free topography of Svalbard

We present a first version of the Svalbard ice-free topography (SVIFT1.0) using a mass-conserving approach for mapping glacier ice thickness. SVIFT1.0 is informed by more than 900’000 point-measurements of glacier thickness, totalling almost 8’300 km of thickness profiles. It is publicly available for download. Our estimate for the total ice volume is 6’253km3, equivalent to 1.6cm sea-level rise. The thickness map suggests that 13% of the glacierised area is grounded below sea-level. Thickness values are provided together with a map of error estimates that comprise uncertainties in the thickness surveys as well as in other input variables. Aggregated error estimates are used to define a likely ice-volume range of 5’200-7’400km3. The ice-front thickness of marine-terminating glaciers is a key quantity for ice-loss attribution because it controls the potential ice discharge by iceberg calving into the ocean. We find a mean ice-front thickness of 133m for the archipelago

Assoziation neuroendokriner Kopf- und Halskarzinome mit HPV-Infektion und der Expression immunregulatorischer Zellen

Einleitung: Neuroendokrine Zellen finden sich in verschiedenen Geweben der Kopf-Hals-Region. Vereinzelt wurden neuroendokrine Karzinome (NEC) mit einer prognostisch relevanten HPV-Infektion assoziiert. HPV-positive Tumore scheinen stärker von regulatorischen T-Zellen sowie PD-1 positiven T-Zellen infiltriert zu sein. PD-1 positive Zellen wurden mit einem besseren Outcome für den Patienten assoziiert. PD-1 positive T-Lymphozyten sind beispielsweise Voraussetzung für einen Therapieerfolg mit PD-1 Antikörpern wie Prembrolizumab.Methodik: Retrospektive Bestimmung des HPV-Status (p16, HPV-PCR) an Paraffinmaterial histologisch gesicherter NEC des oberen Aerodigestivtrakts von 2006 bis 2016, sowie immunhistochemische Analyse (IHC) der Entzündungsmediatoren PD-L1 (überexprimiert vom Tumor), PD-1 (exprimiert von Lymphozyten), CD8 (zytotoxische T-Zellen), PD-L2 (exprimiert von Makrophagen zur Inhibition von CD8 über TH2 T-Zellen). Erfassung klinischer Patienten- und Verlaufsdaten. Ergebnisse: Fallserie von n=7 NEC (n=3 zervikales NEC-CUP, n=2 Larynx, n=1 NNH, n=1 Hypopharynx, n=5 männlich, n=2 weiblich, im Alter zwischen 44 und 72 Jahren) mit Ergebnissen der HPV-PCR Sequenzierung und IHC von Entzündungsmediatoren (PD-L1, PD-1, PD-L2, CD8). Nach Therapie (n=3 primäre Operation, n=2 primäre Radiochemotherapie, n=1 primäre Radiatio, n=1 palliative Chemotherapie) sind n=3 Patienten rezidivfrei, n=2 ohne Progress und n=2 verstorben. Diskussion: Während HNSCC eine bessere Prognose bei HPV-Assoziation zeigen, scheinen HPV-assoziierte NEC besonders aggressiv zu sein. Aufgrund der geringen Fallzahlen der NEC bedarf es einer Multicenter-Analyse im Hinblick auf ihren HPV-Status, um die Rolle von HPV in der Genese und im Verlauf dieser seltenen Tumore weiter zu eruieren.Der Erstautor gibt keinen Interessenkonflikt an

Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis

Patients with liver cirrhosis have a high incidence of insulin resistance and diabetes. This study was designed to determine circulating levels and hepatic production of retinol-binding protein 4 (RBP4) in relation to parameters of hepatic and systemic metabolism in patients with liver cirrhosis. Circulating RBP4 levels were measured in 19 patients with liver cirrhosis at different clinical stages of the disease and in 20 age-, sex- and body mass index (BMI)-matched controls. Hepatic production rates of RBP4 and glucose were assessed by measuring the arterial hepatic venous concentration difference together with hepatic blood flow. Insulin resistance was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI) and the homeostasis model assessment of insulin resistance (HOMA-IR), energy expenditure by indirect calorimetry and body composition by bioelectrical impedance analysis (BIA). Compared with controls, RBP4 levels in cirrhosis were decreased (8.1 +/- 1.8 vs. 22.6 +/- 2.4 mg/l, P <0.001) due to decreased hepatic production (P <0.05). RBP4 correlated with hepatic protein synthesis capacity (P <0.01), but not with insulin resistance, energy expenditure, BMI or body fat mass. Plasma RBP4 correlated with hepatic glucose production (P <0.05). These data demonstrate that RBP4 in cirrhosis (i) is decreased due to reduced hepatic production, (ii) is not associated with insulin resistance, and (iii) might have a beneficial role by decreasing hepatic glucose production and could thus also be regarded as a hepatokine