Gastritis staging: interobserver agreement by applying OLGA and OLGIM systems

Atrophic gastritis remains a difficult histopathological diagnosis with low interobserver agreement. The aim of our study was to compare gastritis staging and interobserver agreement between general and expert gastrointestinal (GI) pathologists using Operative Link for Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia (OLGIM). We enrolled 835 patients undergoing upper endoscopy in the study. Two general and two expert gastrointestinal pathologists graded biopsy specimens according to the Sydney classification, and the stage of gastritis was assessed by OLGA and OLGIM system. Using OLGA, 280 (33.4 %) patients had gastritis (stage I–IV), whereas with OLGIM this was 167 (19.9 %). OLGA stage III– IV gastritis was observed in 25 patients, whereas by OLGIM stage III–IV was found in 23 patients. Interobserver agreement between expert GI pathologists for atrophy in the antrum, incisura angularis, and corpus was moderate (kappa?=?0.53, 0.57 and 0.41, respectively, p?<?0.0001), but almost perfect for intestinal metaplasia (kappa?=?0.82, 0.80 and 0.81, respectively, p?<?0.0001). However, interobserver agreement between general pathologists was poor for atrophy, but moderate for intestinal metaplasia. OLGIM staging provided the highest interobserver agreement, but a substantial proportion of potentially high-risk individuals would be missed if only OLGIM staging is applied. Therefore, we recommend to use a combination of OLGA and OLGIM for staging of chronic gastritis.     

Traumatic dental injuries and Alpine skiing

Abstract – The purpose of this study was to determine the occurrence and type of traumatic dental injuries after maxillofacial injuries as a result of Alpine skiing. During an 8‐year period (from January 1991 to December 1998) 7600 patients with facial injuries were registered at the Department of Oral and Maxillofacial Surgery, University of Innsbruck, Austria. Of 784 patients with skiing‐related facial injuries (524 males, 260 females) 326 (41.6%) sustained injuries to 639 teeth. The age groups predominantly affected were between 7 and 32 years. Luxation injuries occurred in 338 (53%) teeth, fractures accounted for 270 tooth injuries (42%), and only 35 (5%) were lost at the place of the accident. Of skiers with traumatic dental injuries 58% had concomitant soft tissue injuries, while 23.3% had associated facial bone fractures. The most common causes of injury were falls in 42% (329 patients) and collisions with other persons in 24.1% (189 patients). Being hit by one's own sports equipment (11%) was the third most common cause. Collisions with obstacles accounted for 9% and lift accidents for 5.6% of injuries. The probability of suffering dentoalveolar trauma during skiing varied depending on the injury mechanism. There was a 2–fold risk for dentoalveolar trauma when colliding with objects, a 3.5‐fold risk when hit by one's own equipment and a 8.5‐fold risk during lift accidents. Dental injuries occurred in about 2% of all injured skiers. Dental health professionals should be aware of the high incidence and the distribution of dental trauma and facial injuries caused by skiing.     

Histone deacetylase inhibitors suppress the inducibility of nuclear factor-kappaB by tumor necrosis factor-alpha receptor-1 down-regulation

Recently, the inhibition of histone deacetylase (HDAC) enzymes has attracted attention in the oncologic community as a new therapeutic opportunity for hematologic and solid tumors including non-small cell lung cancer (NSCLC). In hematologic malignancies, such as diffuse large B-cell lymphoma, the HDAC inhibitor (HDI), suberoylanilide hydroxamic acid (SAHA), has recently entered phase II and III clinical trials. To further advance our understanding of their action on tumor cells, we investigated the possible effect of HDI treatment on the functionality of the nuclear factor-kappaB (NF-kappaB) pathway in NSCLC. We found that in the NSCLC cell lines, A549 and NCI-H460, the NF-kappaB pathway was strongly inducible, for example, by stimulation with tumor necrosis factor-alpha (TNF-alpha). Incubation of several NSCLC cell lines with HDIs resulted in greatly reduced gene expression of TNF-alpha receptor-1. HDI-treated A549 and NCI-H460 cells down-regulated TNF-alpha receptor-1 mRNA and protein levels as well as surface exposure, and consequently responded to TNF-alpha treatment with reduced IKK phosphorylation and activation, delayed IkappaB-alpha phosphorylation, and attenuated NF-kappaB nuclear translocation and DNA binding. Accordingly, stimulation of NF-kappaB target gene expression by TNF-alpha was strongly decreased. In addition, we observed that SAHA displayed antitumor efficacy in vivo against A549 xenografts grown on nude mice. HDIs, therefore, might beneficially contribute to tumor treatment, possibly by reducing the responsiveness of tumor cells to the TNF-alpha-mediated activation of the NF-kappaB pathway. These findings also hint at a possible use of HDIs in inflammatory diseases, which are associated with the overproduction of TNF-alpha, such as rheumatoid arthritis or Crohn's disease.     

The Validity of a Biomarker Method for Indirect Detection of Gastric Mucosal Atrophy Versus Standard Histopathology

Background  

Atrophy of the stomach mucosa is considered to be premalignant lesion for gastric cancer development; easy identification of this condition from a blood-sample would allow identifying the group of individuals at increased risk for cancer development.     

Development of a chiral HPLC method to evaluate in vivo enantiomeric inversion of an unstable, polar radiosensitizer in plasma

A chiral HPLC method to quantify in vivo enantiomeric inversion of prodrug CI-1010 (IR) or its drug IIR (PD 146923), a radiosensitizer, upon X-irradiation of dosed rats was developed. These polar enantiomers were separated only by using normal-phase chiral HPLC. A Chiralpak AS column provided the best separation. Isolation of analytes from plasma employed solid-phase extraction (SPE), and required conditions that were compatible with normal-phase HPLC. Options for SPE were restricted by the chemically reactive nature of both prodrug and drug, which produced analyte losses as high as 100%. Acceptable recoveries using SPE required evaluation of conditions for analyte chemical stability. The validated method gave a lower-limit of quantitation (LLOQ) of 200 ng/ml for each enantiomer extracted from 0.15 ml of plasma. The LLOQ of the inverted enantiomer could be detected in the presence of 10,000 ng/ml of the dosed enantiomer. Precision (RSD) ranged from 14.2 to 4.4%, and from 24.2 to 5.1% for IIS and IIR, respectively. Accuracy (RE) was +/- 13.1 and +/- 13.2%, respectively. Recoveries ranged from 44.3 to 71.4%, and from 40.7 to 67.9%, for IIS and IIR, respectively.     

Value of gastrin-17 in detecting antral atrophy

PurposeDecreased plasma gastrin-17 (G-17), particularly after protein stimulation, is indicative of atrophy in the antral stomach mucosa. Available data on the value of this biomarker is inconclusive. Our study was aimed to evaluate the performance of the G-17 test in Caucasian and Asian patients for antral atrophy evaluation either in fasting state or after protein stimulation.Material/Methods241 dyspeptic patients aged 55 and above from Latvia (125), Lithuania (76) and Taiwan (40) were enrolled. G-17 levels were detected in plasma samples obtained either during fasting or after a protein-rich test meal. Levels <1pmol/L at fast and <5 pmol/L after stimulation were considered indicative of atrophy.ResultsThe sensitivity of the test was 15.8%, its specificity 88.7%, and the overall accuracy 83% in the fasting state, and 36.8, 86.5, and 82.6%, respectively, after stimulation. In the Caucasian subgroup, the corresponding figures were 15.4, 91.5, and 86.6% in the fasting state and 30.8, 92.6, 88.6% after stimulation; but for the Asian subgroup the corresponding figures were 16.7, 73.5, and 65% (fasting) and 50, 52.9, and 52.5% (stimulated).ConclusionsThe performance of G-17 was better after protein stimulation. G-17 was highly specific in the Caucasian, but not in the Asian subgroups. Still the low test sensitivity either at fast or following protein stimulation does not allow us to recommend it for wide screening purpose to diagnose antral atrophy.