Screening for gastric cancer using exhaled breath samples.

BACKGROUND: The aim was to derive a breath-based classifier for gastric cancer using a nanomaterial-based sensor array, and to validate it in a large screening population. METHODS: A new training algorithm for the diagnosis of gastric cancer was derived from previous breath samples from patients with gastric cancer and healthy controls in a clinical setting, and validated in a blinded manner in a screening population. RESULTS: The training algorithm was derived using breath samples from 99 patients with gastric cancer and 342 healthy controls, and validated in a population of 726 people. The calculated training set algorithm had 82 per cent sensitivity, 78 per cent specificity and 79 per cent accuracy. The algorithm correctly classified all three patients with gastric cancer and 570 of the 723 cancer-free controls in the screening population, yielding 100 per cent sensitivity, 79 per cent specificity and 79 per cent accuracy. Further analyses of lifestyle and confounding factors were not associated with the classifier. CONCLUSION: This first validation of a nanomaterial sensor array-based algorithm for gastric cancer detection from breath samples in a large screening population supports the potential of this technology for the early detection of gastric cancer.

A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions.

BACKGROUND: Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints. METHODS: Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry. RESULTS: Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and/or peptic ulcer, as compared with less severe gastric conditions. The concentrations both in the room air and in the breath samples were in the single p.p.b.v range, except in the case of isoprene. CONCLUSION: The preliminary results of this pilot study could open a new and promising avenue to diagnose GC and distinguish it from other gastric diseases. It should be noted that the applied methods are complementary and the potential marker compounds identified by gas-chromatography/mass spectrometry are not necessarily responsible for the differences in the sensor responses. Although this pilot study does not allow drawing far-reaching conclusions, the encouraging preliminary results presented here have initiated a large multicentre clinical trial to confirm the observed patterns for GC and benign gastric conditions.

Molecular characterisation and expression analysis of SEREX-defined antigen NUCB2 in gastric epithelium, gastritis and gastric cancer.

NUCB2 is an EF-hand Ca2+ binding protein that has been implicated in various physiological processes like calcium homeostasis, hypothalamic regulation of feeding and TNF receptor shedding. In our previous study we identified NUCB2 as a potential tumour antigen eliciting autoantibody responses in 5.4% of gastric cancer patients but not in the healthy individuals.The current study aimed to elucidate the molecular mechanism underlying NUCB2 immunogenicity and to gain an insight into the physiological functions of NUCB2 in the stomach. mRNA expression analysis demonstrated that NUCB2 is ubiquitously expressed in normal tissues, including lymphoid tissues, and downregulated in gastric tumours when compared with the adjacent relatively normal stomach tissues.The search for molecular alterations resulted in the identification of novel mRNA variants transcribed from an alternative promoter and expressed predominantly in gastric cancers. Western blot analysis demonstrated that the protein levels correspond to mRNA levels and revealed that NUCB2 is phosphorylated in gastric mucosa. Furthermore, a 55 kDa isoform,generated presumably by yet an unidentified post-translational modification was detected in gastric tumours and AGS gastric cancer cells but was absent in the relatively normal gastric mucosa and thereby might have served as a trigger for the immune response against NUCB2. Staining of stomach tissue microarray with anti-NUCB2 antibody revealed that it is expressed in the secretory granules of chief cells and in the cytoplasm of parietal cells in the functioning gastric glands which are lost in atrophic glands and tumour cells. Hence we propose that NUCB2 may be implicated in gastric secretion by establishing an agonist-releasable Ca2+ store in ER or Golgi apparatus, signalling via heterotrimeric Galpha proteins and/or mediating the exocytosis of the secretory granules.

Should we screen for Helicobacter pylori to prevent gastric cancer?

Although the strategy for Helicobacter pylori infection management is well defined and quite well followed in a number of situations, including peptic ulcer disease, the issue of H. pylori screening and eradication in the general population still remains. The following debate attempts to find the answer of whether or not H. pylori screening should be performed in the asymptomatic population for preventing gastric cancer. As yet, there is no final evidence-based consensus about the need to screen for H. pylori in order to decrease the incidence of gastric cancer.

High consumption of fatty fish from the Baltic Sea is associated with changes in human lymphocyte subset levels.

Fatty fish from the Baltic Sea accumulate immunotoxic persistent organochlorine compounds. In a previous study we found inverse correlations between such fish consumption and natural killer (NK) cell levels in a Swedish population. The present study concerns 68 Latvian subjects with high, low or intermediate fish consumption. High fish consumption correlated positively with B cell levels and CD4+/CD8+ ratios, but negatively with levels of cytotoxic (CD8+) T cells. Furthermore, NK cell levels correlated inversely with plasma selenium, one of several strong correlates with fish intake. A high fish diet includes a set of possible immunomodulating agents. It is presently not possible to pinpoint the cause for the observed subset deviations or to establish their possible biological importance.

Value of gastrin-17 in detecting antral atrophy.

PURPOSE: Decreased 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/METHODS: 241 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 <1 pmol/L at fast and <5 pmol/L after stimulation were considered indicative of atrophy. RESULTS: The 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). CONCLUSIONS: The 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.

Molecular characterisation and expression analysis of SEREX-defined antigen NUCB2 in gastric epithelium, gastritis and gastric cancer.

NUCB2 is an EF-hand Ca2+ binding protein that has been implicated in various physiological processes like calcium homeostasis, hypothalamic regulation of feeding and TNF receptor shedding. In our previous study we identified NUCB2 as a potential tumour antigen eliciting autoantibody responses in 5.4% of gastric cancer patients but not in the healthy individuals. The current study aimed to elucidate the molecular mechanism underlying NUCB2 immunogenicity and to gain an insight into the physiological functions of NUCB2 in the stomach. mRNA expression analysis demonstrated that NUCB2 is ubiquitously expressed in normal tissues, including lymphoid tissues, and downregulated in gastric tumours when compared with the adjacent relatively normal stomach tissues. The search for molecular alterations resulted in the identification of novel mRNA variants transcribed from an alternative promoter and expressed predominantly in gastric cancers. Western blot analysis demonstrated that the protein levels correspond to mRNA levels and revealed that NUCB2 is phosphorylated in gastric mucosa. Furthermore, a 55 kDa isoform, generated presumably by yet an unidentified post-translational modification was detected in gastric tumours and AGS gastric cancer cells but was absent in the relatively normal gastric mucosa and thereby might have served as a trigger for the immune response against NUCB2. Staining of stomach tissue microarray with anti-NUCB2 antibody revealed that it is expressed in the secretory granules of chief cells and in the cytoplasm of parietal cells in the functioning gastric glands which are lost in atrophic glands and tumour cells. Hence we propose that NUCB2 may be implicated in gastric secretion by establishing an agonist-releasable Ca2+ store in ER or Golgi apparatus, signalling via heterotrimeric Gα proteins and/or mediating the exocytosis of the secretory granules.

Surgical treatment of gastric cancer in Latvia: results of centralized experience.

BACKGROUND: Although the mortality for gastric cancer is decreasing in Western Europe and United States, it still remains high in Eastern Europe. This study was aimed at evaluating short- and long-term results of surgical treatment of gastric cancer performed in Latvia Oncology Center. METHODS: Retrospectively collected data from 461 patients who underwent gastrectomy with curative intent in Latvia Oncology Center from January 2001 to December 2005 were analyzed statistically. RESULTS: An average (range) of 92.2 (81-102) R0-R1 gastrectomies was performed each year. Post-operative complications occurred in 75 patients (16.3%); in-hospital mortality was 3.3%. The overall 5-year survival was 50.8%. In 444 cases (96.3%) there was histopathologic confirmation of R0-resection with a 5-year survival of 52.5% (P<0.001). Considering pT category, 5-year survival was 88.6% for pT1 patients, 65% for pT2, 42.3% for pT3 and 27% for pT4 (P<0.001). Considering pN category, 5-year survival was 67% for pN0 patients, 30% for pN1 and 29% for pN2-3 (P<0.001). CONCLUSIONS: Clinico-pathologic characteristics of patients who underwent resection with curative intent are comparable to other Western experiences. Short- as well as long-term results are also similar if not for pN+ patients where no difference between pN1 and pN2 cases was observed.

[Prevention of occupational and community health problems using Falisan Universal liquid caustic]. / Zur Klärung arbeits- und kommunalhygienischer Probleme beim Einsatz von Falisan-Universal-Flüssigbeize.

Based on tests with Falisan-Universal fluid caustic the authors report on measuring results of laboratory tests and analyses of utilization. The air pollution caused by the active agent phenyl mercury acetate and the formulation remedy dimethylformamide is assessed. Conclusions are made for the caustic's application and for its tests.

Prevalence of childhood asthma, rhinitis and eczema in Scandinavia and Eastern Europe.

There is evidence that the prevalence of allergies and asthma differs between populations in western and eastern Europe. This study investigated the prevalence of wheezing, rhinitis and eczema among schoolchildren in urban and rural areas of Scandinavia and the formerly socialist countries of Eastern Europe. A total of 79,000 children from two age groups (13-14 yrs and 6-7 yrs) in 18 study centres responded to a questionnaire within the International Study of Asthma and Allergy in Children (ISAAC). The 12 month period prevalence of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema was calculated. The prevalence of wheezing among the 13-14 yr old children was 11.2-19.7% in Finland and Sweden, 7.6-8.5% in Estonia, Latvia and Poland and 2.6-5.9% in Albania, Romania, Russia, Georgia and Uzbekistan (except Samarkand). The prevalence of itching eyes and flexural dermatitis varied in a similar manner between the three regions. The regional differences were less pronounced among the 6-7 yr old children in the seven participating centres. The highest prevalence of rhinitis was recorded in April-July in Scandinavia and during the winter months in the other countries. The prevalence of atopy-related disorders was higher in Scandinavia than in Estonia, Latvia and Poland, which in turn had a higher prevalence than five other countries of eastern Europe with a culture less similar to western Europe. This supports the hypothesis that "Western life style" is associated with a high prevalence of childhood allergy.