Update on cholangiocarcinoma: potential impact of genomic studies on clinical management.

The term cholangiocarcinoma (CCA) comprises neoplasms of the intrahepatic, perihilar, and distal bile duct. Five-year survival rates of patients with CCA are below 20 %, and no targeted therapy could prove a benefit in comparison to the standard treatment of cisplatinum and gemcitabine. In recent years, next generation sequencing studies revealed a profound genomic heterogeneity of CCA subtypes potentially affecting the design of future therapy trials.

CT-Guided Drainage of Pericardial Effusion after Open Cardiac Surgery.

Purpose: This study was designed to evaluate the safety and efficacy of CT-guided drainage of the pericardial effusion in patients after cardiac surgery.

Materials And Methods: The study included 128 consecutive patients (82 males, 46 females; mean age 66.6 years, SD: 4.

Removal of a giant left ventricular thrombus after myocardial infarction due to dissection of left anterior descending artery.

Left ventricular thrombus is a frequent complication after myocardial infarction and is associated with high risk for arterial embolic complications. In addition to oral anticoagulation, surgical thrombectomy may be a promising treatment for large and mobile thrombus. We report the rare case of a 27-year-old patient who presented with a giant left ventricular thrombus after expanded and silent myocardial infarction caused by spontaneous dissection of the left anterior descending coronary artery.

Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis.

Background & Aims: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC.

Methods: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia.

Guideline Compliance in Surgery for Thyroid Nodules - A Retrospective Study.

Diagnostic guidelines for thyroid nodules focus on malignancy risk assessment to avoid unnecessary diagnostic operations. These guidelines recommend a combination of tests in form of a diagnostic algorithm. The present study analyzed the recommended algorithm and its implementation by different medical professionals.

Eosinophilic cholangitis is a potentially underdiagnosed etiology in indeterminate biliary stricture.

Aim: To investigate presence and extent of eosinophilic cholangitis (EC) as well as IgG4-related disease in patients with indeterminate biliary stricture (IBS).

Methods: All patients with diagnosis of sclerosing cholangitis (SC) and histopathological samples such as biopsies or surgical specimens at University Hospital Frankfurt from 2005-2015 were included. Histopathological diagnoses as well as further clinical course were reviewed.

The MEK1 inhibitors UO126 and PD98059 block PDGF-AB induced phosphorylation of threonine 292 in porcine smooth muscle cells.

PDGF-AB and FGF-2 (GFs) induce smooth muscle cell (SMC) proliferation which is indispensible for arteriogenesis. While there is common agreement that GFs stimulate SMC proliferation through phosphorylation (P-) of MEK1/2 at Ser218/222, we previously demonstrated that the MEK inhibitors PD98059 and UO126 did not inhibit P-Ser218/222 as originally proposed but caused strong hyperphosphorylation. Here, we demonstrate that GFs increased phosphorylation of MEK1 at Thr292 while UO126 and PD98059 blocked this phosphorylation.

Intratumoral heterogeneity of intrahepatic cholangiocarcinoma.

No personalized therapy regimens could demonstrate a benefit in survival of intrahepatic cholangiocarcinoma (iCCA). Since genetic heterogeneity might influence single biopsy based targeted therapy or the outcome of clinical trials, aim of the present study was to investigate intratumoral heterogeneity of iCCA by whole exome sequencing. Therefore, samples from tumor center and tumor periphery of large iCCA lesions as well as a control from healthy liver tissue were obtained from four patients and whole exome sequencing was performed.

Prothrombin polymorphism A19911G, factor V HR2 haplotype A4070G, and plasminogen activator-inhibitor-1 polymorphism 4G/5G and the risk of retinal vein occlusion.

Background: Thus far, no data has become available to evaluate systematically the prevalences of prothrombin polymorphism A19911G (PT A19911G), factor V HR2 haplotype A4070G (FV A4070G), or plasminogen activator-inhibitor-1 polymorphism 4G/5G (PAI-1 4G/5G) in patients who develop retinal vein occlusion (RVO) without cardiovascular risk factors.

Materials And Methods: We retrospectively evaluated comprehensive thrombophilia data from 42 preselected RVO patients without cardiovascular risk factors. The prevalences of different gene mutations and polymorphisms including factor V Leiden mutation G1691A (FVL), FV A4070G, prothrombin mutation G20210A, PT A19911G, and PAI-1 4G/5G were compared with 241 healthy controls matched for age and sex.

In Silico Knockout Studies of Xenophagic Capturing of Salmonella.

The degradation of cytosol-invading pathogens by autophagy, a process known as xenophagy, is an important mechanism of the innate immune system. Inside the host, Salmonella Typhimurium invades epithelial cells and resides within a specialized intracellular compartment, the Salmonella-containing vacuole. A fraction of these bacteria does not persist inside the vacuole and enters the host cytosol.

Immediate Rule-Out of Acute Myocardial Infarction Using Electrocardiogram and Baseline High-Sensitivity Troponin I.

Aims: Serial measurements of high-sensitivity troponin are used to rule out acute myocardial infarction (AMI) with an assay specific cutoff at the 99th percentile. Here, we evaluated the performance of a single admission troponin with a lower cutoff combined with a low risk electrocardiogram (ECG) to rule out AMI.

Methods: Troponin I measured with a high-sensitivity assay (hs-TnI) was determined at admission in 1040 patients presenting with suspected AMI (BACC study).

Microwave Ablation of Symptomatic Benign Thyroid Nodules: Energy Requirement per ml Volume Reduction.

Microwave ablation (MWA) represents a novel thermal ablative treatment of benign thyroid nodules. The aim was to determine the energy required per ml volume reduction in order to match the required energy to the volume-of-interest (VOI). 25 patients with 25 nodules (6 solid, 13 complex and 6 cystic) were treated by microwave ablation (MWA).

The novel HLA-C*15:103 is characterised by an amino acid substitution in the alpha 2 domain.

HLA-C*15:103 allele is characterised by one amino acid substitution in the alpha 2 domain.

Thermal Ablation of Colorectal Lung Metastases: Retrospective Comparison Among Laser-Induced Thermotherapy, Radiofrequency Ablation, and Microwave Ablation.

Objective: The purpose of this study is to retrospectively evaluate local tumor control, time to tumor progression, and survival rates among patients with lung metastatic colorectal cancer who have undergone ablation therapy performed using laser-induced thermotherapy (LITT), radiofrequency ablation (RFA), or microwave ablation (MWA).

Materials And Methods: Data for this retrospective study were collected from 231 CT-guided ablation sessions performed for 109 patients (71 men and 38 women; mean [± SD] age, 68.6 ± 11.

Pilot study to test the feasibility of a trial design and complex intervention on PRIoritising MUltimedication in Multimorbidity in general practices (PRIMUMpilot).

Objective: To improve medication appropriateness and adherence in elderly patients with multimorbidity, we developed a complex intervention involving general practitioners (GPs) and their healthcare assistants (HCA). In accordance with the Medical Research Council guidance on developing and evaluating complex interventions, we prepared for the main study by testing the feasibility of the intervention and study design in a cluster randomised pilot study.

Setting: 20 general practices in Hesse, Germany.

Role of CD15 expression in dysplastic and neoplastic tissue of the bile duct - a potential novel tool for differential diagnosis of indeterminate biliary stricture.

Background And Aims: CD15 is expressed by various cancer types; among these are intrahepatic and perihilar cholangiocarcinoma (CCA). The aim of this study was to elucidate CD15 expression in distal CCA as well as in dysplastic biliary tissue and to determine its prognostic significance.

Methods And Results: Tissue samples from patients with intrahepatic (iCCA, n = 22), perihilar (pCCA, n = 7) and distal CCA (dCCA, n = 15), who underwent surgical resection in the period from 2010 to 2015 were evaluated for CD15 expression.

An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1).

Background: Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12) and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12.

Aneurysm Location as a Prognostic Outcome Factor After Subarachnoid Hemorrhage From Internal Carotid Artery Aneurysms and Potential Impact for Further Experimental Subarachnoid Hemorrhage Models.

Objective: Prognostic factors of favorable and unfavorable clinical outcome after aneurysmal subarachnoid hemorrhage (SAH) are still not completely known. We retrospectively analyzed the aneurysm location as a factor for patients' outcome after aneurysmal SAH.

Methods: We retrospectively selected patients from our prospectively collected database with aneurysm at the carotid bifurcation artery (n = 23) and posterior communicating artery (n = 170).

Cutaneous involvement as a rare first sign of systemic mantle cell lymphoma: A case report and review of the literature.

Mantle cell lymphoma (MCL) is a unique type of B-cell non-Hodgkin's lymphoma, which very rarely exhibits skin involvement. We herein describe the case of a 55-year-old woman, who initially presented with a nodular mass of the right infraorbital region. On histological analysis of the subcutaneous tissue, a diffuse neoplastic cell infiltration was identified, composed of medium-sized lymphoid cells with irregular nuclei, which was diagnosed as MCL.

High-Throughput RNAi Screening Identifies a Role for the Osteopontin Pathway in Proliferation and Migration of Human Aortic Smooth Muscle Cells.

Purpose: Understanding of the mechanisms of vascular smooth muscle cells (VSMCs) phenotypic regulation is critically important to identify novel candidates for future therapeutic intervention. While HTS approaches have recently been used to identify novel regulators in many cell lines, such as cancer cells and hematopoietic stem cells, no studies have so far systematically investigated the effect of gene inactivation on VSMCs with respect to cell survival and growth response.

Methods And Results: 257 out of 2000 genes tested resulted in an inhibition of cell proliferation in HaoSMCs.

Inhibition of let-7 augments the recruitment of epicardial cells and improves cardiac function after myocardial infarction.

Heart failure due to myocardial infarction is a major cause of mortality. The microRNA (miR) family let-7 is expressed during embryonic development and is up-regulated in differentiated cells. The aim of this study was to study the role of let-7 after acute myocardial infarction (AMI).

Intraductal biopsies in indeterminate biliary stricture: Evaluation of histopathological criteria in fluoroscopy- vs. cholangioscopy guided technique.

Background: Differentiating malignancy from benign disease in indeterminate biliary stricture by imaging modalities is limited. Definite diagnosis relies on histopathological diagnosis.

Aims: To assess accuracy of histopathological diagnosis of fluoroscopy-guided vs.