Breath Fingerprint of Colorectal Cancer Patients Based on the Gas Chromatography-Mass Spectrometry Analysis.

The human body emits a multitude of volatile organic compounds (VOCs) via tissues and various bodily fluids or exhaled breath. These compounds collectively create a distinctive chemical profile, which can potentially be employed to identify changes in human metabolism associated with colorectal cancer (CRC) and, consequently, facilitate the diagnosis of this disease. The main goal of this study was to investigate and characterize the VOCs' chemical patterns associated with the breath of CRC patients and controls and identify potential expiratory markers of this disease. For this purpose, gas chromatography-mass spectrometry was applied. Collectively, 1656 distinct compounds were identified in the breath samples provided by 152 subjects. Twenty-two statistically significant VOCs (p-xylene; hexanal; 2-methyl-1,3-dioxolane; 2,2,4-trimethyl-1,3-pentanediol diisobutyrate; hexadecane; nonane; ethylbenzene; cyclohexanone; diethyl phthalate; 6-methyl-5-hepten-2-one; tetrahydro-2H-pyran-2-one; 2-butanone; benzaldehyde; dodecanal; benzothiazole; tetradecane; 1-dodecanol; 1-benzene; 3-methylcyclopentyl acetate; 1-nonene; toluene) were observed at higher concentrations in the exhaled breath of the CRC group. The elevated levels of these VOCs in CRC patients' breath suggest the potential for these compounds to serve as biomarkers for CRC.

Identification of Volatile Markers of Colorectal Cancer from Tumor Tissues Using Volatilomic Approach.

The human body releases numerous volatile organic compounds (VOCs) through tissues and various body fluids, including breath. These compounds form a specific chemical profile that may be used to detect the colorectal cancer CRC-related changes in human metabolism and thereby diagnose this type of cancer. The main goal of this study was to investigate the volatile signatures formed by VOCs released from the CRC tissue. For this purpose, headspace solid-phase microextraction gas chromatography-mass spectrometry was applied. In total, 163 compounds were detected. Both cancerous and non-cancerous tissues emitted 138 common VOCs. Ten volatiles (2-butanone; dodecane; benzaldehyde; pyridine; octane; 2-pentanone; toluene; p-xylene; n-pentane; 2-methyl-2-propanol) occurred in at least 90% of both types of samples; 1-propanol in cancer tissue (86% in normal one), acetone in normal tissue (82% in cancer one). Four compounds (1-propanol, pyridine, isoprene, methyl thiolacetate) were found to have increased emissions from cancer tissue, whereas eleven showed reduced release from this type of tissue (2-butanone; 2-pentanone; 2-methyl-2-propanol; ethyl acetate; 3-methyl-1-butanol; d-limonene; tetradecane; dodecanal; tridecane; 2-ethyl-1-hexanol; cyclohexanone). The outcomes of this study provide evidence that the VOCs signature of the CRC tissue is altered by the CRC. The volatile constituents of this distinct signature can be emitted through exhalation and serve as potential biomarkers for identifying the presence of CRC. Reliable identification of the VOCs associated with CRC is essential to guide and tune the development of advanced sensor technologies that can effectively and sensitively detect and quantify these markers.

Volatile Markers for Cancer in Exhaled Breath-Could They Be the Signature of the Gut Microbiota?

It has been shown that the gut microbiota plays a central role in human health and disease. A wide range of volatile metabolites present in exhaled breath have been linked with gut microbiota and proposed as a non-invasive marker for monitoring pathological conditions. The aim of this study was to examine the possible correlation between volatile organic compounds (VOCs) in exhaled breath and the fecal microbiome by multivariate statistical analysis in gastric cancer patients (n = 16) and healthy controls (n = 33). Shotgun metagenomic sequencing was used to characterize the fecal microbiota. Breath-VOC profiles in the same participants were identified by an untargeted gas chromatography-mass spectrometry (GC-MS) technique. A multivariate statistical approach involving a canonical correlation analysis (CCA) and sparse principal component analysis identified the significant relationship between the breath VOCs and fecal microbiota. This relation was found to differ between gastric cancer patients and healthy controls. In 16 cancer cases, 14 distinct metabolites identified from the breath belonging to hydrocarbons, alcohols, aromatics, ketones, ethers, and organosulfur compounds were highly correlated with 33 fecal bacterial taxa (correlation of 0.891, p-value 0.045), whereas in 33 healthy controls, 7 volatile metabolites belonging to alcohols, aldehydes, esters, phenols, and benzamide derivatives correlated with 17 bacterial taxa (correlation of 0.871, p-value 0.0007). This study suggested that the correlation between fecal microbiota and breath VOCs was effective in identifying exhaled volatile metabolites and the functional effects of microbiome, thus helping to understand cancer-related changes and improving the survival and life expectancy in gastric cancer patients.

Age-Based Comparative Analysis of Colorectal Cancer Colonoscopy Screening Findings.

Background and Objectives: Colorectal cancer (CRC) incidence is rapidly emerging among individuals <50 years, termed as early-onset colorectal cancer (EOCRC). This study aimed to probe variations in tumorigenic pathology and relevant manifestations (polyp and adenoma incidence) between suspected cases of EOCRC and late-onset CRC (LOCRC; ≥50 years of age). Materials and Methods: Between September 2022 and February 2023, colonoscopy-based screening data from 1653 patients were included in this study. All eligible participants were divided into two groups, depending upon patient age, where Group 1 consisted of 1021 patients aged <50 years while Group 2 consisted of 632 patients aged ≥ 50 years. Polyp samples were collected when identified peri-procedurally and characterized according to World Health Organization criteria. Results: Polyp detection rate was 42% for the <50-year age group, while this was 76% for the ≥50-year age group. Additionally, the <50-year age group predominated in hyperplastic polyp manifestation, particularly within the rectum and sigmoid colon. In addition, the ≥50-year age group had increased prevalence of serrated polyps and differing adenoma manifestations. Conclusions: This investigation served to highlight the importance of age stratification for CRC colonoscopy-based screening effectiveness, with particular reference to evaluations that are based on polyp localization within differing colon regions.

Sensing gastric cancer via point-of-care sensor breath analyzer.

BACKGROUND: Detection of disease by means of volatile organic compounds from breath samples using sensors is an attractive approach to fast, noninvasive and inexpensive diagnostics. However, these techniques are still limited to applications within the laboratory settings. Here, we report on the development and use of a fast, portable, and IoT-connected point-of-care device (so-called, SniffPhone) to detect and classify gastric cancer to potentially provide new qualitative solutions for cancer screening. METHODS: A validation study of patients with gastric cancer, patients with high-risk precancerous gastric lesions, and controls was conducted with 2 SniffPhone devices. Linear discriminant analysis (LDA) was used as a classifying model of the sensing signals obatined from the examined groups. For the testing step, an additional device was added. The study group included 274 patients: 94 with gastric cancer, 67 who were in the high-risk group, and 113 controls. RESULTS: The results of the test set showed a clear discrimination between patients with gastric cancer and controls using the 2-device LDA model (area under the curve, 93.8%; sensitivity, 100%; specificity, 87.5%; overall accuracy, 91.1%), and acceptable results were also achieved for patients with high-risk lesions (the corresponding values for dysplasia were 84.9%, 45.2%, 87.5%, and 65.9%, respectively). The test-phase analysis showed lower accuracies, though still clinically useful. CONCLUSION: Our results demonstrate that a portable breath sensor device could be useful in point-of-care settings. It shows a promise for detection of gastric cancer as well as for other types of disease. LAY SUMMARY: A portable sensor-based breath analyzer for detection of gastric cancer can be used in point-of-care settings. The results are transferrable between devices via advanced IoT technology. Both the hardware and software of the reported breath analyzer could be easily modified to enable detection and monitirng of other disease states.

Modular Breath Analyzer (MBA): Introduction of a Breath Analyzer Platform Based on an Innovative and Unique, Modular eNose Concept for Breath Diagnostics and Utilization of Calibration Transfer Methods in Breath Analysis Studies.

Exhaled breath analysis for early disease detection may provide a convenient method for painless and non-invasive diagnosis. In this work, a novel, compact and easy-to-use breath analyzer platform with a modular sensing chamber and direct breath sampling unit is presented. The developed analyzer system comprises a compact, low volume, temperature-controlled sensing chamber in three modules that can host any type of resistive gas sensor arrays. Furthermore, in this study three modular breath analyzers are explicitly tested for reproducibility in a real-life breath analysis experiment with several calibration transfer (CT) techniques using transfer samples from the experiment. The experiment consists of classifying breath samples from 15 subjects before and after eating a specific meal using three instruments. We investigate the possibility to transfer calibration models across instruments using transfer samples from the experiment under study, since representative samples of human breath at some conditions are difficult to simulate in a laboratory. For example, exhaled breath from subjects suffering from a disease for which the biomarkers are mostly unknown. Results show that many transfer samples of all the classes under study (in our case meal/no meal) are needed, although some CT methods present reasonably good results with only one class.

The Riga East University Hospital Stroke Registry-An Analysis of 4915 Consecutive Patients with Acute Stroke.

Background and Objectives: A hospital-based stroke registry is a useful tool for systematic analyses of the epidemiology, clinical characteristics, and natural course of stroke. Analyses of stroke registry data can provide information that can be used by health services to improve the quality of care for patients with this disease. Materials and Methods: Data were collected from the Riga East University Hospital (REUH) Stroke Registry in order to evaluate the etiology, risk factors, clinical manifestations, treatment, functional outcomes, and other relevant data for acute stroke during the period 2016-2020. Results: During a five-year period, 4915 patients (3039 females and 1876 males) with acute stroke were registered in the REUH Stroke Registry. The causative factors of stroke were cardioembolism (45.7%), atherosclerosis (29.9%), lacunar stroke (5.3%), stroke of undetermined etiology (1.2%), and stroke of other determined causes (1.2%). The most frequent localizations of intracerebral hemorrhage were subcortical (40.0%), lobar (18.9%), and brainstem (9.3%). The most prevalent risk factors for stroke were hypertension (88.8%), congestive heart failure (71.2%), dyslipidemia (46.7%), and atrial fibrillation (44.2%). In addition, 1018 (20.7%) patients were receiving antiplatelet drugs, 574 (11.7%) were taking statins, and 382 (7.7%) were taking anticoagulants. At discharge, 35.5% of the patients were completely independent (mRS (modified Rankin Scale) score: 0-2), while 49.5% required some form of assistance (mRS score: 3-5). The intrahospital mortality rate was 13.7%, although it was higher in the hemorrhage group (30.9%). Conclusions: Our stroke registry data are comparable to those of other major registries. Analysis of stroke registry data is important for improving stroke care and obtaining additional information for stroke studies.

Detection of gastric atrophy by circulating pepsinogens: A comparison of three assays.

BACKGROUND: Circulating levels of pepsinogens have been used in high gastric cancer-risk Asian and European populations to triage endoscopic evaluation for more severe pathology. There are different analytic methods with uncertain correlations. We therefore compared diagnostic performance of three commonly used pepsinogen assays to detect histologically confirmed gastric atrophy. METHODS: We tested plasma samples from adult patients with (n=50) and without (n=755) moderate or severe gastric corpus atrophy, as determined histologically by consensus of three expert pathologists. A single laboratory measured pepsinogens I (PgI) and II (PgII) using commercially available assays: two ELISA assays produced by Biohit (Finland) and Vector Best (Russia), and a latex agglutination assay from Eiken (Japan). Quantitative correlations were assessed by Spearman statistics. Receiver operating characteristic (ROC) curves vs histological diagnosis were calculated using both the manufacturers' and optimized cutoffs. RESULTS: Pepsinogen levels were highly correlated among the assays (pairwise Rhos: PgI≥0.84, PgII≥0.87; all P-values<.01). Based on manufacturers' cutoffs, sensitivities, specificities and areas under the ROC curve for detecting moderate to severe histological corpus atrophy by PgI/PgII were 44%/91%/0.70, 56%/84%/0.76, and 52%/90%/0.77 for Biohit, Vector Best and Eiken, respectively. Cutoffs optimized by ROC or data mining analyses did not substantially improve test performance. CONCLUSIONS: Commercial assays for pepsinogen have good relative agreement but are imperfect tests for clinical diagnosis of gastric atrophy. IMPACT: Pepsinogen testing alone does not provide sufficient information for gastric cancer risk stratification. Future investigations should focus on other potential markers, in combination with pepsinogens.

Pepsinogen testing for evaluation of the success of Helicobacter pylori eradication at 4 weeks after completion of therapy.

BACKGROUND AND OBJECTIVE: Pepsinogen levels in plasma are increased by inflammation in the gastric mucosa, including inflammation resulting from Helicobacter pylori infection. A decrease in pepsinogen II level has been suggested as a reliable marker to confirm the successful eradication of infection. The aim of our study was to evaluate the potential role of pepsinogens I and II, gastrin-17 and H. pylori antibodies in confirming successful eradication. MATERIAL AND METHODS: Altogether 42 patients (25 women, 17 men), mean age 45 years (range 23-74), were enrolled. Pepsinogens I and II, gastrin-17 and H. pylori IgG antibodies were measured in plasma samples using an ELISA test (Biohit, Oyj., Finland) before the eradication and 4 weeks after completing the treatment. The success of eradication was determined by a urea breath test. RESULTS: Eradication was successful in 31 patients (74%) and unsuccessful in 11 patients (26%). Pepsinogen II decreased significantly in both the successful (P=0.029) and unsuccessful (P=0.042) eradication groups. Pepsinogen I decreased significantly in the successful (P=0.025) but not the unsuccessful (P=0.29) eradication group. The pepsinogen I/II ratio increased in the successful eradication group (P=0.0018) but not in the group in which treatment failed (P=0.12). There were no differences in gastrin-17 or H. pylori antibody values. CONCLUSIONS: A decrease in pepsinogen II levels cannot be used as a reliable marker for the successful eradication of H. pylori 4 weeks after the completion of treatment. The increase in pepsinogen I/II ratio reflects differences in pepsinogen production following the eradication irrespective of improvement in atrophy.

Randomised clinical trial: efficacy and safety of H. pylori eradication treatment with and without Saccharomyces boulardii supplementation.

BACKGROUND: Standard triple therapy is commonly prescribed Helicobacter pylori eradication regimen in Europe. However, the world is witnessing declines in eradication success. It is crucial to find better treatment options. AIMS: To evaluate efficacy, compliance and side effects of H. pylori eradication treatment by adding Saccharomyces boulardii . METHODS: We conducted a randomized clinical trial within the GISTAR cohort, consisting of healthy individuals aged 40-64 years. Participants were administered clarithromycin-containing triple therapy (clarithromycin 500 mg, amoxicillin 1000 mg, esomeprazole 40 mg) twice daily. Randomization was applied based on two factors: 1)addition of Saccharomyces boulardii CNCM I-745 500 mg BID or not; 2)treatment duration of 10 or 14 days. Treatment completion and adverse events were assessed via telephone interview 21-28 days after medication delivery. The efficacy was evaluated using a 13C-urea breath test (UBT) six months after treatment. RESULTS: Altogether 404 participants were enrolled; data on adverse events were available from 391. Overall, 286 participants received follow-up UBT. Intention-to-treat analysis revealed higher eradication rates for 10-day probiotic treatment (70.8% vs. 54.6%, P  = 0.022), but not for 14-day. Probiotic subgroups combined showed non-significantly higher efficacy in per-protocol analysis (90.6% vs. 85.0%, P  = 0.183). S. boulardii reduced the frequency of adverse events ( P  = 0.033) in 14-day regimen, particularly treatment-associated diarrhea ( P  = 0.032). However, after the adjustment to control Type I error, results lost their significance. CONCLUSION: Addition of S. boulardii to 14-day clarithromycin-containing triple regimen non-significantly lowers the likelihood of diarrhea and does not increase the eradication rate.

Autoimmune gastritis serological biomarkers in gastric cancer patients.

The role of autoimmunity in the pathogenesis of gastric cancer remains controversial. We studied antiparietal cell antibody (anti-PCA) and anti-intrinsic factor antibody (anti-IFA) levels and their associations with pepsinogen I/pepsinogen II levels in patients with gastric adenocarcinoma compared to a control group with mild or no atrophy of the stomach mucosa. Plasma levels of anti-PCA and anti-IFA were measured by ELISA (Inova Diagnostics Inc, San Diego, California, USA). The cutoff value for anti-PCA and anti-IFA positivity was ≥25 units. Altogether 214 patients (126 men, 88 women, median age 64.46, range: 35-86) with confirmed gastric adenocarcinoma and 214 control cases paired for age and sex were included in the study. Positive anti-PCA was present in 22 (10.3%) gastric cancer patients and controls (P ≥ 0.999); positive anti-IFA in 6 (2.8%) and 4 (1.9.%), P < 0.232, respectively. We did not find significant differences in anti-PCA and anti-IFA positivity between gastric cancer patients and the control group; further investigation is required to better understand the potential involvement of autoimmune gastritis in the development of gastric cancer.

Role of pre-existing incomplete intestinal metaplasia in gastric adenocarcinoma: A retrospective case series analysis.

BACKGROUND: Risk stratification for patients with gastric precancerous lesions for endoscopic surveillance remains controversial. AIM: To analysis of patients having developed gastric adenocarcinoma during the period of follow-up. METHODS: We conducted a retrospective study on patients having undergone upper endoscopy prior to the development of gastric adenocarcinoma. The presence and stage of precancerous lesions as well as subtype of intestinal metaplasia at the baseline endoscopy got evaluated. Literature mini-review was performed. RESULTS: Out of 1681 subjects in the Biobank, gastric adenocarcinoma was detected in five cases in whom previous endoscopy data with biopsies either from the corpus or antral part were available. All of the patients had incomplete intestinal metaplasia during the baseline endoscopy; all three subjects in whom intestinal metaplasia subtyping was performed according to Filipe et al, had Type III intestinal metaplasia. Two of the five cases had low Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Intestinal Metaplasia Assessment (OLGIM) stages (I-II) at the baseline. CONCLUSION: The presence of incomplete intestinal metaplasia, in particular, that of Type III is a better predictor for gastric adenocarcinoma development than OLGA/OLGIM staging system. Subtyping of intestinal metaplasia have an important role in the risk stratification for surveillance decisions.

The Role of an Artificial Intelligence Method of Improving the Diagnosis of Neoplasms by Colonoscopy.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Colonoscopy is the gold standard examination that reduces the morbidity and mortality of CRC. Artificial intelligence (AI) could be useful in reducing the errors of the specialist and in drawing attention to the suspicious area. METHODS: A prospective single-center randomized controlled study was conducted in an outpatient endoscopy unit with the aim of evaluating the usefulness of AI-assisted colonoscopy in PDR and ADR during the day time. It is important to understand how already available CADe systems improve the detection of polyps and adenomas in order to make a decision about their routine use in practice. In the period from October 2021 to February 2022, 400 examinations (patients) were included in the study. One hundred and ninety-four patients were examined using the ENDO-AID CADe artificial intelligence device (study group), and 206 patients were examined without the artificial intelligence (control group). RESULTS: None of the analyzed indicators (PDR and ADR during morning and afternoon colonoscopies) showed differences between the study and control groups. There was an increase in PDR during afternoon colonoscopies, as well as ADR during morning and afternoon colonoscopies. CONCLUSIONS: Based on our results, the use of AI systems in colonoscopies is recommended, especially in circumstances of an increase of examinations. Additional studies with larger groups of patients at night are needed to confirm the already available data.

Assessing the utility of pepsinogens and gastrin-17 in gastric cancer detection.

OBJECTIVES: The aim of the study was to determine the proportion of gastric cancer patients with decreased levels of pepsinogen and gastrin-17 in plasma, with the goal of providing indirect evidence of the sensitivity of these biomarkers when applied in a cancer screening setting. METHODS: The levels of pepsinogens I and II, gastrin-17, and Helicobacter pylori immunoglobulin antibodies in plasma samples of gastric cancer patients were evaluated using the GastroPanel test system (Biohit Oyj, Helsinki, Finland). A decreased level of the pepsinogen I/II ratio was defined as less than three, while a decrease in gastrin-17 was defined as less than 1 pmol/L. Univariate analysis using non-parametric tests was used to investigate differences between normal and low concentrations of biomarkers. RESULTS: In total, 481 plasma samples from patients (59.9% male) with a median age of 64 years (ranging from 27 to 88 years) were analyzed. Out of the 400 cases of gastric cancer (83.2% of the total), 182 were categorized as the intestinal type, 141 as the diffuse type, 60 as the mixed type, and 17 as indeterminate according to the Lauren classification system. The H. pylori immunoglobulin test was positive in 74.0% of the patients. Pepsinogen I/II ratio was decreased in 32.4% (36.8% of the intestinal type); gastrin-17 in 12.3% (10.1% of the antral region) of all cases. CONCLUSION: The majority of gastric cancer patients had normal levels of pepsinogen and gastrin-17, suggesting that these biomarkers have limited application as screening tools in the Caucasian population.

The Association of Circulating L-Carnitine, γ-Butyrobetaine and Trimethylamine N-Oxide Levels with Gastric Cancer.

Our study aimed to evaluate the association between gastric cancer (GC) and higher concentrations of the metabolites L-carnitine, γ-butyrobetaine (GBB) and gut microbiota-mediated trimethylamine N-oxide (TMAO) in the circulation. There is evidence suggesting that higher levels of TMAO and its precursors in blood can be indicative of either a higher risk of malignancy or indeed its presence; however, GC has not been studied in this regard until now. Our study included 83 controls without high-risk stomach lesions and 105 GC cases. Blood serum L-carnitine, GBB and TMAO levels were measured by ultra-high-performance liquid chromatography-mass spectrometry (UPLC/MS/MS). Although there were no significant differences between female control and GC groups, we found a significant difference in circulating levels of metabolites between the male control group and the male GC group, with median levels of L-carnitine reaching 30.22 (25.78-37.57) nmol/mL vs. 37.38 (32.73-42.61) nmol/mL (p < 0.001), GBB-0.79 (0.73-0.97) nmol/mL vs. 0.97 (0.78-1.16) nmol/mL (p < 0.05) and TMAO-2.49 (2.00-2.97) nmol/mL vs. 3.12 (2.08-5.83) nmol/mL (p < 0.05). Thus, our study demonstrated the association between higher blood levels of L-carnitine, GBB, TMAO and GC in males, but not in females. Furthermore, correlations of any two investigated metabolites were stronger in the GC groups of both genders in comparison to the control groups. Our findings reveal the potential role of L-carnitine, GBB and TMAO in GC and suggest metabolic differences between genders. In addition, the logistic regression analysis revealed that the only significant factor in terms of predicting whether the patient belonged to the control or to the GC group was the blood level of L-carnitine in males only. Hence, carnitine might be important as a biomarker or a risk factor for GC, especially in males.

The Detection of Colorectal Cancer through Machine Learning-Based Breath Sensor Analysis.

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related deaths worldwide. While CRC screening is already part of organized programs in many countries, there remains a need for improved screening tools. In recent years, a potential approach for cancer diagnosis has emerged via the analysis of volatile organic compounds (VOCs) using sensor technologies. The main goal of this study was to demonstrate and evaluate the diagnostic potential of a table-top breath analyzer for detecting CRC. Breath sampling was conducted and CRC vs. non-cancer groups (105 patients with CRC, 186 non-cancer subjects) were included in analysis. The obtained data were analyzed using supervised machine learning methods (i.e., Random Forest, C4.5, Artificial Neural Network, and Naïve Bayes). Superior accuracy was achieved using Random Forest and Evolutionary Search for Features (79.3%, sensitivity 53.3%, specificity 93.0%, AUC ROC 0.734), and Artificial Neural Networks and Greedy Search for Features (78.2%, sensitivity 43.3%, specificity 96.5%, AUC ROC 0.735). Our results confirm the potential of the developed breath analyzer as a promising tool for identifying and categorizing CRC within a point-of-care clinical context. The combination of MOX sensors provided promising results in distinguishing healthy vs. diseased breath samples. Its capacity for rapid, non-invasive, and targeted CRC detection suggests encouraging prospects for future clinical screening applications.

Breath Volatile Organic Compounds in Surveillance of Gastric Cancer Patients following Radical Surgical Management.

As of today, there is a lack of a perfect non-invasive test for the surveillance of patients for potential relapse following curative treatment. Breath volatile organic compounds (VOCs) have been demonstrated to be an accurate diagnostic tool for gastric cancer (GC) detection; here, we aimed to prove the yield of the markers in surveillance, i.e., following curative surgical management. Patients were sampled in regular intervals before and within 3 years following curative surgery for GC; gas chromatography-mass spectrometry (GC-MS) and nanosensor technologies were used for the VOC assessment. GC-MS measurements revealed a single VOC (14b-Pregnane) that significantly decreased at 12 months, and three VOCs (Isochiapin B, Dotriacontane, Threitol, 2-O-octyl-) that decreased at 18 months following surgery. The nanomaterial-based sensors S9 and S14 revealed changes in the breath VOC content 9 months after surgery. Our study results confirm the cancer origin of the particular VOCs, as well as suggest the value of breath VOC testing for cancer patient surveillance, either during the treatment phase or thereafter, for potential relapse.

Randomised clinical trial: comparison of efficacy and adverse effects of a standard triple clarithromycin-containing regimen with high-dose amoxicillin and bismuth therapy in Helicobacter pylori eradication.

BACKGROUND: The clarithromycin-based triple therapy is the most prescribed Helicobacter pylori eradication regimen in Europe; it causes adverse effects in a significant proportion of subjects, leading to discontinuation. Alternative therapies are required because of increasing clarithromycin resistance or to decrease the adverse effects. AIMS: We compared the efficacy and spectrum of adverse effects of clarithromycin-based triple therapy with the high-dose amoxicillin/bismuth regimen. METHODS: A randomised clinical trial enrolled healthy individuals aged 40-64 years. H. pylori was assessed with a 13C-urea breath test. In total 579 H. pylori-positive subjects were randomly allocated in two groups: group 1: clarithromycin 500 mg, amoxicillin 1000 mg, esomeprazole 40 mg, all twice daily; group 2: bismuth subcitrate 240 mg twice daily, amoxicillin 1000 mg three times daily, esomeprazole 40 mg twice daily. Regimens were administered for 14 days.Information on treatment completion and adverse effects were collected via a telephone interview at 21-28 days after medication delivery. The efficacy was assessed by UBT 6 months after the treatment. RESULTS: We analysed 483 subjects for adverse effects (248 vs. 235 respectively). Furthermore, 316 subjects were analysed for efficacy. In per-protocol analysis, a higher efficacy was seen in group 1 (88.4 vs. 77.0%; P < 0.001); no difference was observed in compliance (90.3 and 91.2%). Therapy-related adverse effects were more common in group 1 (56.9 vs. 40.0%; P < 0.01). In intention-to-treat analysis no statistical difference in efficacy was revealed. CONCLUSIONS: Bismuth-based high-dose amoxicillin therapy showed a lower efficacy but was less frequently associated with adverse effects. Further research is required to examine the high-dose amoxicillin and bismuth-containing regimens in various populations to maximise eradication efficacy.

Factors Associated with False Negative Results in Serum Pepsinogen Testing for Precancerous Gastric Lesions in a European Population in the GISTAR Study.

The accuracy of plasma pepsinogen (Pg) as a marker for precancerous gastric lesions (PGL) has shown variable results. We aimed to identify factors associated with false negative (FN) cases in Pg testing and to adjust cut-off values for these factors in order to improve Pg yield. Plasma Pg was measured and upper endoscopy with biopsy was performed within the "Multicentric randomized study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study". A multivariable logistic model was built for FN and multiple factors. Values of Pg were compared and sensitivity and specificity were calculated using pre-existing Pg cut-offs for factors showing strong associations with FN. New cut-offs were calculated for factors that showed substantially lower sensitivity. Of 1210 participants, 364 (30.1%) had histologically confirmed PGL, of which 160 (44.0%) were FN. Current smokers, men, and H. pylori positives were more likely FN. Smoking in H. pylori negatives was associated with a higher Pg I/II ratio and substantially lower sensitivity of Pg testing than in other groups. Adjusting Pg cut-offs for current smokers by H. pylori presence improved sensitivity for detecting PGL in this group. Our study suggests that adjusting Pg cut-offs for current smokers by H. pylori status could improve Pg test performance.