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Participants with Active Tuberculosis Disease Intervention: Diagnostic Test: VOC detection in breath and in skin headspace Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Diagnostic Test: Breath sampling Intervention: Headspace analysis for biological material

Participants Without Active Tuberculosis Disease Intervention: Diagnostic Test: VOC detection in breath and in skin headspace Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Diagnostic Test: Breath sampling Intervention: Headspace analysis for biological material

Patients with histologically confirmed gastric cancer Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Upper endoscopy with biopsies Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Diagnostic Test: Feacal sampling Intervention: Headspace analysis for biological material Intervention: Procedure/Surgery: Histological examination of surgical speciment

Patients without gastric adenocarcinoma but with histologically confirmed dysplasia (either high- or low-grade) of the stomach Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Upper endoscopy with biopsies Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Headspace analysis for biological material Intervention: Diagnostic Test: Fecal sampling Intervention: Procedure/Surgery: Histological examination of surgical specimen

Patients graded Stage III-IV according to OLGIM (Operative Link of Gastric Intestinal Metaplasia Assessment) staging system, Stage III-IV according to OLGA (Operative Link for Gastric Atrophy Assessment), and those with incomplete type of intestinal metaplasia, but excluding those with dysplasia Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Upper endoscopy with biopsies Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Diagnostic Test: Fecal sampling Intervention: Procedure/Surgery: Histological examination of surgical specimen Intervention: Headspace analysis for biological material

Staged 0-III according to OLGIM. Dysplasia should be excluded Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Upper endoscopy with biopsies Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Diagnostic Test: Fecal sampling Intervention: Headspace analysis for biological material

Patients with histologically confirmed colorectal cancer (adenocarcinoma) Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Colonoscopy with biopsies Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Diagnostic Test: Fecal sampling Intervention: Headspace analysis for biological material Intervention: Procedure/Surgery: Histological examination of surgical specimen

Patients without colorectal adenocarcinoma, but carrying high-risk adenomatous polyps being described by one of the following: 1) size≥1 cm; 2) high-grade dysplasia; 3) villous component. Prior to removal of the lesions Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Colonoscopy with biopsies Intervention: Headspace analysis for biological material Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Diagnostic Test: Fecal sampling Intervention: Procedure/Surgery: Histological examination of surgical specimen

Patients without colorectal adenocarcinoma and without colorectal high-risk lesions Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Colonoscopy with biopsies Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Diagnostic Test: Fecal sampling Intervention: Headspace analysis for biological material

Patients having undergone colonoscopy without an evidence for colorectal lesions Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Colonoscopy with biopsies Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Diagnostic Test: Fecal sampling Intervention: Headspace analysis for biological material Intervention: Procedure/Surgery: Histological examination of surgical specimen

Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Diagnostic Test: Fecal sampling Intervention: Headspace analysis for biological material

Patients with histologically confirmed pancreatic cancer Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Headspace analysis for biological material

Patients with clinically and/or histologically and/or radiologically confirmed chronic pancreatitis Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Headspace analysis for biological material

Patients with histologically confirmed primary liver cancer Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Headspace analysis for biological material

Patients with histologically confirmed liver cirrhosis of viral or other ethiology Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Headspace analysis for biological material

Patients with serologically confirmed infectious disease or individuals of high risk (e.g. population in season of flu epidemy). This group does not include tuberculosis Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Headspace analysis for biological material

Patients with histologically confirmed oncological diseases, excluding gastric, colorectal, pancreatic and primary liver cancer Intervention: Diagnostic Test: Breath sampling Intervention: Procedure/Surgery: Whole blood/ Plasma / serum sampling Intervention: Headspace analysis for biological material

VOC will be detected in breath with off-line and on-line testing and in skin headspace with off-line testing

VOC detection in breath and in skin headspace

Breath sampling for VOCs detections will be carried out using nano-sensor based devices (electronic nose)

Breath sampling

Upper endoscopy with proper biopsy work-up will be used for identification and stratification of gastric lesions as well as acquisition of biopsies for microbiota testing

Upper endoscopy with biopsies

Colonoscopy with proper biopsy or polypectomy material work-up will be used for identification and stratification of colorectal lesions as well as acquisition of biopsies for microbiota testing

Colonoscopy with biopsies

Whole blood/Plasma/serum sampling will be used to obtain information for group stratification

Whole blood/ Plasma / serum sampling

Facal samples will be obtained for faecal occult blood testing as well as microbiota analysis

Faecal sampling

Routine histological exam for patients undergoing curative or palliative surgery. Indication for surgery are set based on underlying condition. Study does not interfere with decision making for surgical treatment

Histological examination of surgical specimen

VOC analysis from headspace of surgical specimen, biopsy materials, blood/plasma, microbiota etc.

Headspace analysis for biological material

Mārcis Leja, PhD, MD

Lelde Lauka, MD

Andra Cīrule, MD

Detection of Volatile Organic Compounds (VOC) directly from tissue by headspace analysis (skin, surgery material, other tissue) and exhaled breath is feasible using affordable user-friendly novel nano-chemo sensors that can accurately be used for screening and monitoring purpose

Study propose to explore a novel approach for the diagnosis and monitoring of diseases. The approach is based on the detection of volatile organic compounds (VOCs) that are emitted from the cells and detected directly from tissue, such as skin, surgery material, blood as well as from exhaled breath.

In the literature there are several reports on VOCs which can be detected by Gas Chromatography - Mass Spectrometry (GC-MS) means directly from: (i) the headspace of TB cells (i.e., the mixture of volatile biomarkers trapped above the TB cells in a sealed vessel); (ii) the exhaled breath or (iii) from urine. Excellent results in detection of the tuberculosis disease by using nanosensor array were shown by Nakhleh et al achieved 90% sensitivity, 93% specificity and 92% accuracy in discrimination between healthy and diseased patients using electronic nose devices with a single sensor. None of the reported studies identified the tentative recognition of the tuberculosis-related VOCs and quantified the concentration differences between samples from ill and healthy controls. Further investigation of the exhaled breath tuberculosis-related VOC by GC-MS means will improve the knowledge and simultaneously will help to improve the nanosensor array design.

Several studies have shown that disease-rated VOC patterns can be transmitted through the skin, and, therefore, skin can be used as a source for disease detection and identification. The principle of this detection approach is that disease-related changes are reflected in measurable changes in the skin through exchange via the blood. In addition, several studies have suggested that the VOC levels are elevated even in early stages of the disease, because they reflect a change in the human's body chemistry (as a result of the development of disease condition), rather than the amount of infected cells. Complementary studies have shown that VOCs can be emitted to the skin within minutes after they have emerged in the infected part of the human's body. What is particularly significant about this approach is that each type of (infectious) disease has its own unique pattern of VOCs, and, therefore, the presence of one (infectious) disease would not screen other disease types. Nevertheless, to the best of our knowledge, the detection of tuberculosis VOCs through skin has not been examined yet. Additionally, all studies targeting skin VOCs have been carried out by means of spectrometry and spectroscopy techniques. In few cases, electronic nose devices were used. These techniques are powerful tools for detecting VOCs. However, to date, the use of these techniques has been impeded by the need for moderately to highly expensive equipment's, the high levels of expertise required to operate such instruments, the speed required for sampling and analysis, and the need for preconcentration techniques. For VOC skin testing and breath testing of tuberculosis to become widely used in clinical practice, several advances in the knowledge of tuberculosis specific VOCs and sensor development need to occur. Nanoparticles containing flexible sensors, based on organic films, are more likely to become a clinical diagnostic tool, because they are significantly smaller, easier-to-use, and significantly less expensive.

In recent years comprehensive studies have shown excellent data for using VOCs from exhaled breath as tool for diagnosing gastric cancer. In one of the biggest studies carried out by Chinese and Latvian centers, malignancy could be identified with 89% sensitivity and 90% specificity after cross-validation, irrespective of important confounding factors in gastric patients such as tobacco or alcohol consumption and H. pylori infection. A breath test for GC staging could also be demonstrated by distinguishing stage I\&II cancers from stage III\&IV cancers with 89% sensitivity and 94% specificity. These studies used both - mass spectometry and nano-sensors technologies. Most recent study published in ASC Nano journal in January 2017 reported on more extended use of nanoarry sensors in breath analysis, blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined (chronic kidney failure, idiopathic Parkinson's disease, atypical Parkinsonism , multiple sclerosis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, pulmonary arterial hypertension, pre-eclampsia in pregnant women, head and neck cancer, lung cancer, colorectal cancer, bladder cancer, kidney cancer, prostate cancer, gastric cancer, and ovarian cancer. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others.

Therefore, this study is aimed to test VOCs detecting technologies as diagnostic and monitoring tools for digestive tract and infectious diseases.

Surgery and biopsy material as well as blood samples will contain himan DNA

Volatiles in Breath and Headspace Analysis - Diagnostic Markers

Volatile Organic Compounds in Breath and Headspace Analysis - Diagnostic and Monitoring Markers for Diseases

Tuberculosis specific VOC detected in breath and in skin headspace

Sensitivity, specificity, overall accuracy of nanoarray sensor testing for VOCs to detect the target lesions in the blinded analysis

List of VOCs assayed by GC-MS with statistical difference between the study groups

VOC pattern changes after specific required treatment (medical eradication of bacteria/viruses, surgery/endoscopic removal for cancers or high risk lesion)

VOC pattern changes at the time of surveillance in case of relapse (malignant diseases).

List of gastrointestinal microbiota groups (phylum/genus level) with positive correlation to particular VOCs

Technion, Israel Institute of Technology

Riga East University Hospital

JLM Innovation GmbH

University of Latvia

Colonic Polyps

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Colonic Diseases

Rectal Diseases

Patients with histologically proven Colorectal cancer detected during the colonoscopy

Patients with no sign of any colorectal disease who are submitted to colonoscopy

The alveolar fraction of Colorectal cancer patients and Healthy controls will be sampled using a breath sampler able to fix the volatile organic compound on absorbable tubes

Donato Altomare, Prof

Arcangelo Picciariello, MD

Donato F Altomare, Prof

Donato Altomare, MD

Volatile organic compounds (VOCs) are low molecular weight (\<1 kDa) compounds which represent the final products of cell metabolism. Their composition can be affected by several factors including diet, hormones, environment and the presence of diseases, in particular, cancer.

Colorectal cancer (CRC) is one of the commonest tumours and is an important cause of cancer-related mortality.

The expression of VOCs in breath that are linked to a patient's disease state could offers a powerful, non-invasive approach to identifying CRC patients.

Volatile organic compounds (VOCs) are low molecular weight (\<1 kDa) compounds which represent the final products of cell metabolism. Their composition can be affected by several factors including diet, hormones, environment and the presence of diseases, in particular, cancer.

Endogenous breath VOCs can originate anywhere in the body, reversed in the venous blood stream and than to the lung alveoli where some of them are exhaled .

Alteration in VOC production in patients with cancer has been postulated to relate to (per)oxygenation of cell membrane-based polyunsaturated fatty acids resulting from genetic and/or protein mutations within tumour cells and the increased relative prevalence of reactive oxygen species within cancer cells. VOCs consist largely of benzene, alkanes and aldehydes (or their derivatives), and several studies have demonstrated that various cancers, including lung and breast cancer,melanoma, mesothelioma and hepatocellular carcinoma, are associated with specific VOC profiles that differ from normal.

Volatile organic compounds are present in various excreted biological materials (urine, blood, faeces an breath) and their analysis offers a possibility for cancer screening.

Colorectal cancer (CRC) is one of the commonest tumours and is an important cause of cancer-related mortality. It is the second leading cause of cancer-related death in Europe and the third in the USA.

Colonoscopy is the gold standard for the diagnosis of CRC, although its cost prevents its use for mass screening. Furthermore colonoscopy is not well accepted by patients since it is an invasive exam. Faecal immunochemical blood testing (FIT) is the most widely used noninvasive screening tool, showing fairly good specificity but a high variation in sensitivity (61-91%) and adherence to screening programmes rarely reaches 50-70% of the target population.

The expression of VOCs in breath that are linked to a patient's disease state could offers a powerful, non-invasive approach to identifying CRC patients.

Volatile Organic Compounds (VOCs) Profile in Colorectal Cancer Patients and Healthy Controls.

Volatile Organic Compounds (VOCs) Could Discriminate Patients With Colorectal Cancer From Healthy Controls.

A specificity of 80% and a sensitivity of 90% will be considered reliable

Societa Italiana di Chirurgia ColoRettale

Herbal and Botanical

Cola

The breath of all patients with positive FIT (fecal immunochemical test) but negative colonoscopy will be sampled using a breath sampler

The breath of all patients with positive FIT (fecal immunochemical test) and a colorectal cancer detected by colonoscopy will be sampled using a breath sampler

The breath of all patients with positive FIT (fecal immunochemical test) and a colonic polyp detected by colonoscopy will be sampled using a breath sampler

The breath of all subjects included will be sampled using a device able to capture the alveolar air and to fix it on carbon tubes, Then the tubes will be desorbed and analysed using gas chromatography

Donato F Altomare, MD

Elisabetta Martinelli, MD

Endogenous breath VOCs (Volatile Organic Compounds) are present in various excreted biological materials (urine, blood, faeces an breath) and their analysis offers a possibility for cancer screening. Some of these VOCs are reversed in the venous blood stream and reach the lung alveoli where some of them are exhaled.

Colorectal cancer (CRC) is one of the commonest tumours and is an important cause of cancer-related mortality. Colonoscopy is the gold standard for the diagnosis of CRC.

Screening with fecal immunochemical test (FIT) is associated with a 13-18% CRC-mortality reduction.

Aim of the study To compare the reliability of this breath analysis with Immunochemically-based Fecal Occult Blood Test.

Volatile organic compounds (VOCs) are low molecular weight (\<1 kDa) compounds which represent the final products of cell metabolism. Their composition can be affected by several factors including diet, hormones, environment and the presence of diseases, in particular, cancer.

Endogenous breath VOCs are present in various excreted biological materials (urine, blood, faeces an breath) and their analysis offers a possibility for cancer screening. Some of these VOCs are reversed in the venous blood stream and reach the lung alveoli where some of them are exhaled.

Colorectal cancer (CRC) is one of the commonest tumours and is an important cause of cancer-related mortality. Colonoscopy is the gold standard for the diagnosis of CRC, although its cost prevents its use for mass screening. Furthermore colonoscopy is not well accepted by patients since it is an invasive exam. Screening with fecal immunochemical test (FIT) is associated with a 13-18% CRC-mortality reduction in major randomized studies and is the most widely used non-invasive screening tool, showing fairly good specificity but a high variation in sensitivity (61-91%) and adherence to screening programmes rarely reaches 50-70% of the target population.

Recently the breath analysis has been demonstrated to be a new well accepted and non-invasive tool to detect colorectal cancer.

The purpose of this trial is to compare the reliability of this breath analysis with Immunochemically-based Fecal Occult Blood Test, which is the routinely employed tool for mass screening. A group of subjects adherent to the regional screening program for colorectal cancer prevention, who resulted positive to the FIT, will be enrolled in this study, and will have a breath sampling before undergoing colonoscopy. The predictive ability of the Breath test will be tested in a blind fashion in this selected group of high-risk subjects.

VOCs vs FIT for Colorectal Cancer Screening

The Effectiveness of Breath Analysis Versus FIT for Colorectal Cancer Screening

Evaluate the sensitivity of fecal immunochemical test to detect Colorectal cancer patients

Evaluate the sensitivity Breath analysis to detect colorectal cancer patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Volatiles in Breath and Headspace Analysis - Diagnostic Markers	NCT03228095	Tuberculosis Gastric Cancer Peptic Ulcer Atrophic Gastri... Intestinal Meta... Gastric Dysplas... Colorectal Canc... Colorectal Poly... Colorectal Aden... Pancreatic Canc... Pancreatitis, C... Liver Cancer Liver Cirrhosis Flu, Human Other Infectiou... Inflammatory Bo...	VOC detection i... Breath sampling Upper endoscopy... Colonoscopy wit... Whole blood/ Pl... Faecal sampling Histological ex... Headspace analy...	18 Years -	University of Latvia
Volatile Organic Compounds (VOCs) Profile in Colorectal Cancer Patients and Healthy Controls.	NCT04217083	Colorectal Canc... Colon Polyp	Breath sampling	18 Years - 95 Years	Societa Italiana di Chirurgia ColoRettale
VOCs vs FIT for Colorectal Cancer Screening	NCT04407416	Colorectal Canc... Colorectal Poly...	Breath sampling	35 Years - 85 Years	Societa Italiana di Chirurgia ColoRettale
Volatiles in Breath and Headspace Analysis - Diagnostic Markers	NCT03228095	Tuberculosis Gastric Cancer Peptic Ulcer Atrophic Gastri... Intestinal Meta... Gastric Dysplas... Colorectal Canc... Colorectal Poly... Colorectal Aden... Pancreatic Canc... Pancreatitis, C... Liver Cancer Liver Cirrhosis Flu, Human Other Infectiou... Inflammatory Bo...	VOC detection i... Breath sampling Upper endoscopy... Colonoscopy wit... Whole blood/ Pl... Faecal sampling Histological ex... Headspace analy...	18 Years -	University of Latvia
Volatile Organic Compounds (VOCs) Profile in Colorectal Cancer Patients and Healthy Controls.	NCT04217083	Colorectal Canc... Colon Polyp	Breath sampling	18 Years - 95 Years	Societa Italiana di Chirurgia ColoRettale
VOCs vs FIT for Colorectal Cancer Screening	NCT04407416	Colorectal Canc... Colorectal Poly...	Breath sampling	35 Years - 85 Years	Societa Italiana di Chirurgia ColoRettale

Spots Global Cancer Trial Database for breath sampling