Konrads Funka

Ultrasensitive Silicon Nanowire for Real-World Gas Sensing: Noninvasive Diagnosis of Cancer from Breath Volatolome

We report on an ultrasensitive, molecularly modified silicon nanowire field effect transistor that brings together the lock-and-key and cross-reactive sensing worlds for the diagnosis of (gastric) cancer from exhaled volatolome. The sensor is able to selectively detect volatile organic compounds (VOCs) that are linked with gastric cancer conditions in exhaled breath and to discriminate them from environmental VOCs that exist in exhaled breath samples but do not relate to the gastric cancer per se. Using breath samples collected from actual patients with gastric cancer and from volunteers who do not have cancer, blind analysis validated the ability of the reported sensor to discriminate between gastric cancer and control conditions with >85% accuracy, irrespective of important confounding factors such as tobacco consumption and gender. The reported sensing approach paves the way to use the power of silicon nanowires for simple, inexpensive, portable, and noninvasive diagnosis of cancer and other disease conditions.

Detection of precancerous gastric lesions and gastric cancer through exhaled breath

Objectives Timely detection of gastric cancer (GC) and the related precancerous lesions could provide a tool for decreasing both cancer mortality and incidence. Design 968 breath samples were collected from 484 patients (including 99 with GC) for two different analyses. The first sample was analysed by gas chromatography linked to mass spectrometry (GCMS) while applying t test with multiple corrections (p value<0.017); the second by cross-reactive nanoarrays combined with pattern recognition. For the latter, 70% of the samples were randomly selected and used in the training set while the remaining 30% constituted the validation set. The operative link on gastric intestinal metaplasia (OLGIM) assessment staging system was used to stratify the presence/absence and risk level of precancerous lesions. Patients with OLGIM stages III–IV were considered to be at high risk. Results According to the GCMS results, patients with cancer as well as those at high risk had distinctive breath-print compositions. Eight significant volatile organic compounds (p value<0.017) were detected in exhaled breath in the different comparisons. The nanoarray analysis made it possible to discriminate between the patients with GC and the control group (OLGIM 0–IV) with 73% sensitivity, 98% specificity and 92% accuracy. The classification sensitivity, specificity, and accuracy between the subgroups was as follows: GC versus OLGIM 0–II—97%, 84% and 87%; GC versus OLGIM III–IV—93%, 80% and 90%; but OLGIM I–II versus OLGIM III–IV and dysplasia combined—83%, 60% and 61%, respectively. Conclusions Nanoarray analysis could provide the missing non-invasive screening tool for GC and related precancerous lesions as well as for surveillance of the latter. Trial registration number Clinical Trials.gov number, NCT01420588 (3/11/2013).

Breath testing as potential colorectal cancer screening tool

Although colorectal cancer (CRC) screening is included in organized programs of many countries worldwide, there is still a place for better screening tools. In this study, 418 breath samples were collected from 65 patients with CRC, 22 with advanced or nonadvanced adenomas, and 122 control cases. All patients, including the controls, had undergone colonoscopy. The samples were analysed with two different techniques. The first technique relied on gas chromatography coupled with mass spectrometry (GC‐MS) for identification and quantification of volatile organic compounds (VOCs). The T‐test was used to identify significant VOCs (p values < 0.017). The second technique relied on sensor analysis with a pattern recognition method for building a breath pattern to identify different groups. Blind analysis or leave‐one‐out cross validation was conducted for validation. The GC‐MS analysis revealed four significant VOCs that identified the tested groups; these were acetone and ethyl acetate (higher in CRC), ethanol and 4‐methyl octane (lower in CRC). The sensor‐analysis distinguished CRC from the control group with 85% sensitivity, 94% specificity and 91% accuracy. The performance of the sensors in identifying the advanced adenoma group from the non‐advanced adenomas was 88% sensitivity, 100% specificity, and 94% accuracy. The performance of the sensors in identifying the advanced adenoma group was distinguished from the control group was 100% sensitivity, 88% specificity, and 94% accuracy. For summary, volatile marker testing by using sensor analysis is a promising noninvasive approach for CRC screening.

Breath Testing as Potential Colorectal Cancer Screening Tool

Although colorectal cancer (CRC) screening is included in organized programs of many countries worldwide, there is still a place for better screening tools. In this study, 418 breath samples were collected from 65 patients with CRC, 22 with advanced or nonadvanced adenomas, and 122 control cases. All patients, including the controls, had undergone colonoscopy. The samples were analysed with two different techniques. The first technique relied on gas chromatography coupled with mass spectrometry (GC‐MS) for identification and quantification of volatile organic compounds (VOCs). The T‐test was used to identify significant VOCs (p values < 0.017). The second technique relied on sensor analysis with a pattern recognition method for building a breath pattern to identify different groups. Blind analysis or leave‐one‐out cross validation was conducted for validation. The GC‐MS analysis revealed four significant VOCs that identified the tested groups; these were acetone and ethyl acetate (higher in CRC), ethanol and 4‐methyl octane (lower in CRC). The sensor‐analysis distinguished CRC from the control group with 85% sensitivity, 94% specificity and 91% accuracy. The performance of the sensors in identifying the advanced adenoma group from the non‐advanced adenomas was 88% sensitivity, 100% specificity, and 94% accuracy. The performance of the sensors in identifying the advanced adenoma group was distinguished from the control group was 100% sensitivity, 88% specificity, and 94% accuracy. For summary, volatile marker testing by using sensor analysis is a promising noninvasive approach for CRC screening.

Interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms are not associated with premalignant gastric conditions: a combined haplotype analysis.

Objective Contradictory results have been reported about the role of interleukin-1B (IL1B) and IL1 receptor antagonist (IL1RN) alleles in gastric carcinogenesis. Here, IL1B and IL1RN polymorphisms were analyzed as genotypes and haplotypes in relation to the presence of atrophic gastritis (AG) and intestinal metaplasia in the stomach. Methods Two hundred and seventy-eight patients (212 Caucasians and 66 Asians) aged 50 years and above, referred for upper endoscopy because of dyspeptic symptoms, were included in the study. Gastric biopsies were histologically assessed according to the updated Sydney classification. Genomic DNA was typed for polymorphisms at position -3737, -1464, -511, -31 for the IL1B gene and the allele 2 of IL1RN using restriction fragment length polymorphism of amplified PCR fragments and intron-spanning PCR analysis, respectively. Results IL1B-1464-C/C genotype was associated with higher presence of AG in antrum of the stomach in Caucasians [odds ratio: 4.8 (95% confidence interval=1.7–14.3); P=0.028]. IL1B-1464-G/C genotype was associated with lower incidence of AG in corpus of the stomach in Asians [odds ratio: 0.7 (95% confidence interval=0.5–0.8); P=0.02]. IL1RN*2 allele was not linked with AG or intestinal metaplasia in all parts of the stomach both among Asians and Caucasians. Overall, data show that none of the major four IL1B polymorphisms (IL1B-3737C>T, -1464G>C, -511C>T, -31T>C) and the IL1RN*2 is individually, or in its haplotype configuration, linked to the presence of premalignant lesions in Caucasians. Conclusion The determination of these IL1-related loci does not have any predictive value for stratification of subgroups with respect to gastric cancer risk.

Gastric plasma biomarkers and Operative Link for Gastritis Assessment gastritis stage.

Introduction The Operative Link for Gastritis Assessment (OLGA) staging system has been proposed as a histopathological reporting system of gastric atrophy. Noninvasive methods for indirect evaluation of gastric mucosal atrophy by biomarkers are also being introduced. Objectives To analyze gastric mucosal atrophy by biomarkers, pepsinogen I (PgI), pepsinogen II (PgII), PgI/PgII ratio, fasting gastrin-17 (G-17), stimulated gastrin-17 (sG-17), in relation to OLGA gastritis stage. Patients and methods Gastric biopsies were taken from 269 prospective patients referred for upper endoscopy because of dyspeptic problems and evaluated by two expert pathologists (D.J. and P.S.). Atrophy was assessed according to the OLGA staging system. Pg I, PgII, Pg I/II, G-17, sG-17 were determined in a plasma sample. Results The mean levels of PgI and PgI/PgII decreased significantly from 90.8 &mgr;g/l and 7.6 in stage 0 gastritis to 64.3 &mgr;g/l and 4.3 in high-stage gastritis. The mean values of G-17 and sG-17 were significantly higher among patients with stage II gastritis compared with stage 0 and high-stage gastritis. The proportion of patients with normal mucosa and nonatrophic gastritis according to biomarkers decreased from 78% in stage 0 to 22% in high-stage (III–IV) gastritis. Among the latter no case with normal mucosa, according to biomarkers, was observed. Conclusions A significant inverse correlation between the mean levels of PgI, PgI/II ratio and the OLGA stage was observed. Percentage of dyspeptic patients with normal mucosa, by blood biomarkers, decreased with increasing OLGA gastritis stages. OLGA staging system provides a good frame for scientific analysis of gastric mucosal atrophy.

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.

The effect of incisura angularis biopsy sampling on the assessment of gastritis stage.

Objectives It is important to stratify patients according to the magnitude of risk for gastric cancer development; the OLGA (Operative Link for Gastritis Assessment) and OLGIM (Operative Link on Gastric Intestinal Metaplasia) staging systems of lesions in the stomach mucosa have been proposed for this purpose. There are some discrepancies in the current guidelines regarding the value of incisura angularis biopsies. The aim of our study was to assess the value of incisura angularis biopsy in staging gastritis according to the OLGA and OLGIM systems by examining the atrophic, metaplastic and inflammatory changes in the antrum, incisura angularis and corpus. Patients and methods We enrolled 835 patients undergoing upper endoscopy. Three expert gastrointestinal pathologists graded biopsy specimens according to the Sydney classification and the stage of gastritis was assessed by the OLGA and OLGIM systems. Results The results demonstrated that severe atrophic, metaplastic and chronic inflammatory changes were more frequently observed in the incisura angularis mucosa than in the antrum or corpus mucosae (P<0.05). There was a general downgrading of stage by 18.0% for OLGA and by 4.0% for OLGIM when the incisura angularis was excluded from the staging. Furthermore, there was a 30–35% downgrading for high-risk OLGA/OLGIM stages. Conclusion The incisura angularis undergoes more severe atrophic, metaplastic and chronic inflammatory changes than the antrum and corpus. Incisura angularis biopsies should be routinely included in the biopsy sampling protocol.

Interobserver variation in assessment of gastric premalignant lesions: higher agreement for intestinal metaplasia than for atrophy.

Background Either atrophy or intestinal metaplasia of the gastric mucosa are considered premalignant lesions. The new operative link for gastritis assessment staging system is based on the detection of atrophy, and the operative link for assessment of intestinal metaplasia staging system is based on the detection of intestinal metaplasia. Good interobserver agreement is necessary for identification of any premalignant condition. Aims The aim of this study was to compare the agreement between findings of gastric atrophy and intestinal metaplasia by expert and general pathologists and to analyze the possible reasons behind any possible disagreement. Methods Patients with dyspeptic symptoms, aged 55 years and above, without previous Helicobacter pylori eradication were enrolled and analyzed according to the updated Sydney Classification by two expert pathologists and an experienced general pathologist; the results were compared with the consensus driven by the two experts. Results Gastric biopsy specimens from 121 patients (91 women) were included in the analysis; the mean age of the patients was 67.4 years. H. pylori infection was present in 61.2% of patients. The level of agreement between the general pathologist and the two experts (&kgr;-value) was 0.12, 0.46, and 0.87, respectively, for detecting atrophy in the corpus; 0.77, 0.77, and 0.65, respectively, for detecting intestinal metaplasia in the corpus; 0.06, 0.51, and 0.54, respectively, for detecting atrophy in the antrum; and 0.69, 0.85, and 0.79, respectively, for detecting metaplasia in the antrum. Conclusion The agreement was substantially higher for intestinal metaplasia than for atrophy. This could result in discrepancies when the operative link for gastritis assessment and operative link for assessment of intestinal metaplasia staging systems are applied and can be caused by differences in the criteria used to define atrophy.

Sa1896 Nanomaterial-Based Sensor Technology Can Detect Gastric Cancer and Peptic Ulcer Disease With a High Accuracy From an Exhaled Air Sample

BACKGROUND. Early and non-invasive detection of gastric cancer (GC) is remaining a challenge in many high-risk areas. OBJECTIVES. To investigate the feasibility of gastric cancer and peptic ulcer disease detection by measuring volatile organic compounds (VOCs) in the exhaled breath by a nanomaterial-based sensor technology. METHODS. Alveolar exhaled breath samples were collected from 99 GC patients, 53 peptic ulcer disease (PUD) patients and 342 controls in Latvia (Caucasian population) having been investigated by upper endoscopy. Nanomaterial-based sensors Gold nano particles (GNP) and single-wall carbon nanotube (SWCNT) were used to discriminate the GC and the PUD groups from the healthy controls by loading discriminant factor analysis (DFA) pattern recognition. Classification success was calculated by (i) building an algorithm for 70% of the samples as a training set and (ii) randomly blinding 30% of the samples as a validation set. RESULTS. The blind DFA models showed: (i) An excellent discrimination between the GC patients and controls (91% accuracy); (ii) An excellent discrimination between the GC patients and PUD patients (86% accuracy); (iii) Good discrimination between the PUD patients and controls (80% accuracy). CONCLUSIONS: The obtained results are demonstrating the good potential of VOC detection in exhaled breath by nanomaterial-based sensor technology in diagnosing GC and PUD. Performance characteristics of nanomaterial-based sensor technology to detect gastric cancer and peptic ulcer disease