Pathology background of targeted therapy; quality control in pathology

The administration of targeted therapy of gastric carcinoma is a very important recent improvement of its treatment and prognosis. The basis of the successful treatment is the excellent quality of pathology, now including HER2 testing: the use of validated methods and strict criteria. This is especially important if we consider that many gastric cancers are diagnosed in small biopsy material, in which HER2 testing is challenging. This requires standardized, validated methods and experienced pathologists. Being of diagnostic and predictive significance, high quality of both the technique and the interpretation of the test is mandatory. In order to achieve general high quality in this field, technical and interpretation external quality control of HER2 testing is necessary. Hungarian pathologists with the help of Roche Hungary Ltd. completed an external quality control round which showed that most of the participating laboratories are able. Kulka J, Szirtes I, Szász AM, Kupcsulik P, Kenessey I, Lotz G, Tímár J. Pathology background of targeted therapy; quality control in pathology.     

Pathological characteristics of esophago-respiratory fistulas of esophageal tumor origin

Esophago-respiratory fistulas, evolving as a result of esophageal tumors, are serious and lethal complications on account of the constant respiratory contamination and the inability to swallow. They can develop either as the complication of the end stage disease or sometimes even in the first stage of the malignancy. The objective was to reveal the characteristics of the disease. In a prospective single-center study in the period between 1984 and 2004, 243 fistulas were diagnosed. Their data were analyzed using multivariate analysis. The mean age of patients with fistula was 56.9 years, the male-to-female ratio was 4.3:1. The average time of the complaints was 5.2 months, while the time of manifestation of the fistula was 7.5 months. Dysphagia was diagnosed in 97.5% of the patients, fever in 36.9%, and cachexia in 59.5%, respectively. The average loss of weight was 10.4 kg and the average size of the tumor was 7.7 cm. Endoscopic intubation was performed in 176 cases. The average survival was 3.4 months. Patients with fistula were divided into two groups, where the characteristics of the disease were significantly different. Only in 66.3% was the fistula a late complication. In the other 33.7% of the cases the fistula was diagnosed in younger patients at the early stage of the disease, with a more aggressive, less differentiated histology. In these patients the weight loss, the grade of dysphagia and the size of the tumor were smaller, the possibilities of treatment were fewer, and survival were shorter.     

Ascorbate-mediated electron transfer in protein thiol oxidation in the endoplasmic reticulum

Addition of, or gulonolactone oxidase-dependent in situ generation of, ascorbate provoked the oxidation of protein thiols, which was accompanied by ascorbate consumption in liver microsomal vesicles. The maximal rate of protein thiol oxidation was similar upon gulonolactone, ascorbate or dehydroascorbate addition. Cytochrome P450 inhibitors (econazole, proadifen, quercetin) decreased ascorbate consumption and the gulonolactone or ascorbate-stimulated thiol oxidation. The results demonstrate that the ascorbate/dehydroascorbate redox couple plays an important role in electron transfer from protein thiols to oxygen in the hepatic endoplasmic reticulum, even in gulonolactone oxidase deficient species.     

1,3-Propanediol oxidoreductase production with Klebsiella pneumoniae DSM2026

We report a Klebsiella pneumoniae DSM2026 fermentation procedure for the efficient production of a key enzyme of 1,3-propanediol formation: 1,3-propanediol oxidoreductase (E.C. 1.1.1.202). The fermentation process is composed of an aerobic batch phase on glucose and glycerol and an anaerobic phase on glycerol. The role of the aerobic phase is to produce sufficiently high cell mass (12.9–14.6 g/l dry weight) and to activate the aerobic branch of the Klebsiella glycerol pathway, whereas in the anaerobic phase there is a rapid initiation of 1,3-propanediol oxidoreductase formation. A fast change from an aerobic to an anaerobic environment led to a redox imbalance, which resulted in the abrupt activation of the anaerobic branch of glycerol utilization, with the occurrence of a high 1,3-propanediol-oxidoreductase activity. A mathematical model with substrate inhibition showed that the adequate glycerol concentration for enzyme production was 14–16 g/l. The combination of the optimal substrate concentration together with the subsequent use of glucose and glycerol resulted in 90.6 ± 11.6 U enzyme activity referred to 1 l of fermentation broth and 10.3 ± 0.9 U/(1 h) productivity.     

Helicobacter pylori Infection in Congestive Gastropathy

Background. This study determines the prevalence and significance of Helicobacter pylori infection in portal hypertensive patients.
Materials and Methods. Patients numbered 118 and consisted of 90 patients with portal hypertension (66 men; 24 women; mean age, 49.1 ± 2.1 years) and 28 noncirrhotic patients with nonucler dyspepsia, (12 men; 16 women; mean age, 47.6 ± 2.8 years), who made up the control group. In all patients, diagnostic upper endoscopy was performed, and gastric biopsies were taken for histological examination and diagnosis of H. pylori.
Results. Of the portal hypertensive patients, 42 (47%) had congestive gastropathy, 11 (26%) of whom were positive for H. pylori. and 48 (53%) did not have gastropathy, 12 (25%) of whom were positive for H. pylori. In the control group, 15 of 28 (54%) were positive for H. pylori. H. Pylori was found less frequently in congestive gastropathy patients than in the control group. We found also that the presence and severity of congestive gastropathy is independent of H. pylori status.
Conclusions. We conclude that the role of H. pylori in the pathogenesis of congestive gastropathy is unlikely, and we suggest that there is no need for its routine eradication in cirrhotic patients.