Minimally invasive technique for gastric GIST at challenging locations: single incision surgical gastroscopy.

Organ sparing resection of gastrointestinal stromal tumors (GISTs) located in the proximal stomach or esophagogastric junction can be challenging, resulting in proximal or total gastrectomy to facilitate a radical resection without tumor spill. We developed and evaluated a single incision surgical gastroscopy (SISG) procedure to provide a technically feasible alternative for the removal of gastric GISTs at these challenging locations. We developed an endoluminal resection of gastric GISTs through a small single abdominal incision and longitudinal ventral gastrotomy.

Molecular profiles of response to neoadjuvant chemoradiotherapy in oesophageal cancers to develop personalized treatment strategies.

Identification of molecular predictive markers of response to neoadjuvant chemoradiation could aid clinical decision-making in patients with localized oesophageal cancer. Therefore, we subjected pretreatment biopsies of 75 adenocarcinoma (OAC) and 16 squamous cell carcinoma (OSCC) patients to targeted next-generation DNA sequencing, as well as biopsies of 85 OAC and 20 OSCC patients to promoter methylation analysis of eight GI-specific genes, and subsequently searched for associations with histopathological response and disease-free (DFS) and overall survival (OS). Thereby, we found that in OAC, CSMD1 deletion (8%) and ETV4 amplification (5%) were associated with a favourable histopathological response, whereas SMURF1 amplification (5%) and SMARCA4 mutation (7%) were associated with an unfavourable histopathological response.

Biobanking of fresh-frozen endoscopic biopsy specimens from esophageal adenocarcinoma.

The process of preparing endoscopic esophageal adenocarcinoma samples for next-generation DNA/RNA sequencing is poorly described. Therefore, we assessed the feasibility and pitfalls of preparing esophageal adenocarcinoma endoscopic biopsies toward DNA/RNA samples suitable for next-generation sequencing. In this prospective study, four tumor biopsy samples were collected from consecutive esophageal cancer patients during esophagogastroduodenoscopy and fresh-frozen in liquid nitrogen.

Recent trends and predictors of multimodality treatment for oesophageal, oesophagogastric junction, and gastric cancer: A Dutch cohort-study.

Background: In recent years, evidence supporting multimodality treatment for oesophageal, oesophagogastric junction (OGJ), and gastric cancer has accumulated. This population-based cohort-study investigates trends and predictors of utilisation of multimodality treatment for oesophagogastric cancer in the Netherlands.

Patients And Methods: Data were obtained from the Netherlands Cancer Registry regarding patients with oesophageal (n = 5450), OGJ (n = 2168) and gastric cancer (n = 6683) without distant metastases who had undergone R0 or R1 surgery diagnosed between 2000 and 2012.

Does adjuvant chemoradiotherapy improve the prognosis of gastric cancer after an r1 resection? Results from a dutch cohort study.

Objective: The aim of this study was to investigate the impact of adjuvant chemoradiotherapy (CRT) on survival of non-metastatic gastric cancer patients who had undergone an R1 resection.

Methods: We compared the survival of patients after an R1 gastric cancer resection from the population-based Netherlands Cancer Registry who did not receive adjuvant CRT (no-CRT group) with the survival of resected patients who had been treated with adjuvant CRT (CRT group) at our institute. Patients who had a resection between 2002 and 2011 were included.

Detecting interval metastases and response assessment using 18F-FDG PET/CT after neoadjuvant chemoradiotherapy for esophageal cancer.

Aim: The aim of this study is to evaluate the potential of FDG PET/CT for the detection of interval distant metastases after neoadjuvant chemoradiotherapy (CRT) and the prediction of the pathologic response to CRT in esophageal cancer patients.

Patients And Methods: In this retrospective study, all esophageal cancer patients for whom CRT followed by surgery was planned between January 2008 and April 2013 and in whom an FDG PET/CT was performed before and after CRT were included. For the response analyses, both FDG PET/CT scans had to be made on a similar scanner.

The prognostic significance of an R1 resection in gastric cancer patients treated with adjuvant chemoradiotherapy.

Background: A microscopically irradical (R1) resection is a well-known adverse prognostic factor after gastric cancer surgery. However, the prognostic significance of an R1 resection in gastric cancer patients who are treated with chemoradiotherapy (CRT) after the operation has been poorly studied. Therefore, the aim of this study was to evaluate the effect of an R1 resection on (recurrence-free) survival in gastric cancer patients who were treated with CRT after surgery.

Surgical Treatment of Gastrointestinal Stromal Tumors Located in the Stomach in the Imatinib Era.

Background: Imatinib has changed the treatment of gastrointestinal stromal tumors (GISTs). Preoperative imatinib treatment can be administered to patients with locally advanced disease to reduce the risk of incomplete resection, tumor spill, and lessen the extent of resection. In metastatic GIST, surgery follows imatinib in responding patients with resectable disease.

Surgical treatment results of intestinal and diffuse type gastric cancer. Implications for a differentiated therapeutic approach?

Aim: To study the outcome of patients who were surgically treated for primary gastric cancer with specific attention to differences in treatment results for intestinal and diffuse type tumours.

Methods: All patients who underwent a potentially curative gastric resection between 1995 and 2011 in our institute were included. Patient, tumour and treatment characteristics were obtained retrospectively.

Quality of care indicators for the surgical treatment of gastric cancer: a systematic review.

Background: Quality assurance is increasingly acknowledged as a crucial factor for the (surgical) treatment of gastric cancer. The purpose of the current study was to define a minimum set of evidence-based quality of care indicators for the surgical treatment of locally advanced gastric cancer.

Methods: A systematic review of the literature published between January 1990 and May 2011 was performed, using search terms on gastric cancer, treatment, and quality of care.

Prognostication and prediction using gene expression profiling in oesophageal cancer.

Aim: To evaluate current literature on gene expression profiling in oesophageal cancer.

Methods: We performed a review of the literature (2000-2010) on prognostication and prediction using gene expression analysis in oesophageal cancer.

Results: Seventeen papers comprising 638 patients were included.

Factor Xa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation.

Coagulation proteases have been suggested to play a role in the pathogenesis of tissue remodeling and fibrosis. We therefore assessed the proinflammatory and fibroproliferative effects of coagulation protease factor (F)Xa. We show that FXa elicits a signaling response in C2C12 and NIH3T3 fibroblasts.

Adherence to HAART therapy measured by electronic monitoring in newly diagnosed HIV patients in Botswana.

Aims: This pilot study was designed to evaluate the feasibility and benefits of electronic adherence monitoring of antiretroviral medications in HIV patients who recently started Highly Active Anti Retroviral Therapy (HAART) in Francistown, Botswana and to compare this with self-reporting.

Methods: Dosing histories were compiled electronically using Micro Electro Mechanical Systems (MEMS) monitors to evaluate adherence to prescribed therapies. Thirty patients enrolled in the antiretroviral treatment program were monitored over 6 weeks.

A cross-over comparison of the anti-clotting effects of three low molecular weight heparins and glycosaminoglycuronan.

1. The anti-clotting effects after intravenous administration of three low molecular weight (LMW) heparins, Fragmin (KABI 2165), Fraxiparine (CY 216), Clexane (PK 10169) and the LMW mixture of glycosaminoglycuronans Orgaran (Org 10172) were compared in a randomized cross-over study in 12 healthy male volunteers. 2.

Influence of heparin and a low molecular weight heparinoid on specific endogenous and exogenous fibrinolytic factors during rest and exercise.

The effects of heparin (5,000 IU i.v.) and the low molecular weight heparinoid Org 10172 (Orgaran) (3,250 anti-Xa units i.

Pharmacokinetic considerations on Orgaran (Org 10172) therapy.

Pharmacokinetic investigations on Orgaran (Org 10172) have been conducted by monitoring the following biological effects: plasma anti-Xa, anti-IIa and IIa-generation-inhibiting (IIaGI) activities. In addition, a limited number of studies were conducted on the basis of concentrations of the No-affinity glycosaminoglyc(uron)an (NoA-GAG) fraction as determined by a competitive binding assay. In humans, widely different pharmacokinetic profiles for various biological effects were observed, with relatively short elimination half-lives for the anti-IIa and IIaGI activities of 4.

Studies of interaction of a low-molecular-weight heparinoid (Org 10172) with cloxacillin and ticarcillin in healthy male volunteers.

Pharmacokinetic and pharmacodynamic interactions between Org 10172 (intravenous bolus injection of 3,250 anti-Xa units), which is a low-molecular-weight heparinoid, cloxacillin (500 mg orally four times daily for 3 days), and ticarcillin (4,000 mg intravenously four times daily for 2 days) were evaluated in two separate studies with healthy male volunteers (n = 18). Both cloxacillin and ticarcillin caused a significant increase in elimination half-life of anti-Xa activity, i.e.

Partial in vivo neutralisation of plasma anticoagulant effects of Lomoparan (Org 10172) by protamine chloride.

In a cross-over study increasing doses of protamine hydrochloride (20-100 mg) or placebo were administered to six groups of four healthy male volunteers each, following a single intravenous dose of 3200 anti-Xa units of Org 10172. No neutralising effects were observed on the Org 10172 induced changes in the bleeding time, prothrombin time and thrombin time. A small and statistically not significant temporary decrease in anti-Xa activity was observed after doses of 80 and 100 mg protamine chloride.

Influence of chlorthalidone on the pharmacokinetics and pharmacodynamics of Org 10172 (Lomoparan), a low molecular weight heparinoid, in healthy volunteers.

The influence of chlorthalidone (100 mg PO) on the pharmacokinetics and pharmacodynamics of Org 10172 (IV bolus injection of 3250 anti-Xa units), a low molecular weight heparinoid, was studied in six healthy male volunteers using an open randomized two-way crossover design. Chlorthalidone produced a slight decrease in clearance of anti-Xa activity from 7.1 +/- 1.

The influence of Org 10172, a low molecular weight heparinoid, on antipyrine metabolism and the effect of enzyme induction on the response to Org 10172.

1. We have investigated the effect of repeated s.c.

Interaction of ORG 10172, a low molecular weight heparinoid, and digoxin in healthy volunteers.

Potential pharmacokinetic and pharmacodynamic interactions between a new low molecular weight heparinoid Org 10172 (bolus injection of 3250 anti-Xa units) and digoxin (0.25 mg once daily for 8 days) were studied in 6 healthy male volunteers using an open, randomised three-way cross-over design. Digoxin produced a slight increase in clearance of anti-Xa activity from 4.

A new low molecular weight heparinoid Org 10172 as anticoagulant in hemodialysis.

A low molecular weight heparinoid (Org 10172) was compared with unfractionated heparin in 36 patients on chronic hemodialysis in an open randomized cross-over study with three anti-coagulant treatment regimens for a single hemodialysis session. The anti-coagulant regimens were: a) standard heparin (3250-4750 I.U.

Interaction of the combined medication with the new low-molecular-weight heparinoid Lomoparan (Org 10172) and acenocoumarol.

A high intravenous dose of the low-molecular-weight heparinoid Lomoparan (Org 10172) was administered to 6 healthy males in a steady state of anticoagulation (Thrombotest) by acenocoumarol. Prothrombin time, activated partial thromboplastin time and Stypven time were prolonged to a degree which was greater than that expected on the base of the summation of the effects by each drug alone. This effect was observed for a period of up to 1 h.

Safety and pharmacokinetics of the low molecular weight heparinoid Org 10172 administered to healthy elderly volunteers.

1. In a cross-over study a new low molecular weight heparinoid Org 10172 was administered to 12 elderly male and female volunteers. It was well tolerated and no adverse effects occurred.