Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Stomach Neoplasms

Atrophy

Gastritis, Atrophic

Metaplasia

Precancerous Conditions

Gastritis

Gastrointestinal Diseases

Stomach Diseases

Gastroenteritis

Stomach Cancer

This will include patients with:

* existing diagnosis of proximal GIM undergoing endoscopic surveillance
* a new diagnosis of proximal GIM requiring repeat endoscopy
* a historical diagnosis of GIM retrieved from the pathology records through retrospective analysis and lost in follow up
* gastric adenocarcinoma from upper GI multidisciplinary meeting.

Controls will be patients with no known premalignant conditions of the upper GI tract and fit to undergo an upper endoscopy. They will be recruited via standard referral routes for upper GI endoscopy due to upper GI symptoms via standard referral routes. Individuals must be able to provide informed consent.

Cytosponge is a less invasive procedure than endoscopy and consists of an expandable, spherical mesh, which is attached to a string and contained within a soluble capsule. Five minutes after swallowing (once the capsule has dissolved), the spherical mesh, which measures around 3cm in diameter can be retrieved by pulling on the string. Upon retrieval the Cytosponge scrapes against the surface of the top of the stomach and oesophagus and collect epithelial cells. The Cytosponge sample is then placed into a preservative fluid and the specimen is processed for molecular tests. Trefoil Factor 3 (TFF3) is a protein that is expressed in intestinal type epithelia of the gastrointestinal tract. TFF3 is the best biomarker, which can be coupled to the Cytosponge to diagnose intestinal metaplasia.

Cytosponge-TFF3

Massimiliano di Pietro, MD

Andreas Hadjinicolaou, MD PhD

Tara Evans

Andreas Hadjinicolaou, MD

Andreas Hadjicinolaou, MD PhD

Gastric cancer has a very poor prognosis. The disease is often diagnosed at a late stage, when curative treatment options are limited or ineffective. There is a condition that predisposes to gastric cancer, known in medical terms as Gastric intestinal metaplasia (GIM). This pre-cancerous condition can be diagnosed with an endoscopic camera test, but it often very subtle and can be missed at routine endoscopy. There is evidence that about 7% of gastric cancers are missed at previous endoscopy.

The Cytosponge-trefoil factor 3 (TFF-3) is a pill on a string combined to a molecular biomarker which could help early diagnosis of gastric cancer and GIM. Cytosponge-TFF3 has been showed in previous research to be useful to diagnose Barrett's oesophagus, a condition of the food pipe similar to GIM.

The aim of this study is to investigate the utility of the Cytosponge in combination with molecular biomakers to diagnose GIM

This is a case-control study whose goal is to compare the non-endoscopic test (Cytosponge-TFF3) to standard endoscopy to diagnose gastric intestinal metaplasia (GIM), a precursor lesion for gastric cancer. The main objective of the study is to determine the sensitivity and specificity of the Cytosponge-TFF3 to detect gastric intestinal metaplasia (GIM) affecting the proximal stomach.

In parallel to this clinical study, a experimental study will be carried out aimed at evaluating the utility of molecular biomarkers to refine/improve the diagnostic accuracy of the Cytosponge test. The hypothesis is that the non-invasive Cytosponge, in combination with molecular biomarkers, can accurately detect GIM to the same extent as conventional, but more invasive, endoscopic procedures.

Patients will be invited to participate in the study if they are due their surveillance endoscopy, because they have the disease of interest (GIM or GC; cases) or have been referred for an upper endoscopy for abdominal complaint (controls). On the day of the endoscopy the patient will swallow the Cytosponge under supervision of a trained research nurse prior to the endoscopic procedure. The participant will also provide information on demographics, clinical exposures (alcohol, tobacco, drugs), have measurements of weight and height taken and they will also complete a validated gastrointestinal symptoms questionnaire. A blood sample will be taken from the cannula used for the sedatives or through venepuncture. The patients will then undergo their planned endoscopy with additional sampling of gastric juice (suctioned through the endoscope) and some additional research biopsies in addition to a standardized clinical protocol to diagnose GIM. The above research procedures will be performed prior and during the endoscopy. No further research procedures will follow afterwards beyond the day of the endoscopy.

The aim is to develop a non-invasive test which can be used to screen patients at risk for GIM to allow early detection and treatment of pre-cancerous gastric lesions and ultimately reduce the number of patients dying of gastric cancer.

Human tissue obtained in this study will include:

1. Upper gastrointestinal tract tissue from endoscopic biopsy samples for the purpose of tissue diagnosis and for discovery validation of molecular biomarkers
2. Blood
3. Gastric juice (via Cytosponge \[as supernatant\] or via endoscopic aspiration)
4. Gastric cytology (via Cytosponge)

Nucleic acids (DNA/RNA) will be extracted from tissue biopsies, gastric juice vesicles and blood.

Cytosponge for Gastric Intestinal Metaplasia

An Investigation on Cytosponge and Molecular Biomarkers to Identify Patients With Gastric Intestinal Metaplasia (GIM)

Patient details will be pseudo-anonymised, with no identifiable information to be shared outside the clinical research team. Electronic transfers of pseudo-anonymised data will meet industry and NHS-mandated standards including encryption to at least Advanced Encryption Standard (AES) 256. Data will be stored on study database for 10 yrs after study completion, in a linked anonymised manner. Participants will be aware that their PID might be accessed by external regulatory bodies for the purposes of assessing legal compliance and meeting relevant regulatory obligations. Anonymised clinical and lifestyle information may be transferred and stored in international repositories for access by international researchers in line with patient consent.

Temporary access to PID might occur in the event of pathology review by central pathology panel, but PID will not be stored outside local research institution.

Proportion of GIM cases extending to the proximal stomach diagnosed based on gold standard endoscopy with biopsies correclty classified by Cytosponge-TFF3 testing

A panel of clinical and molecular biomakers on biopsies, Cytosponge and blood, will be used to construct a model to predict the histopathological stage of disease (OLGA/OLGIM + grade of neoplasia)

Adverse events realted to Cytosponge will be recorded immediate after administration and at 2 weeks after study visit

University College London Hospitals

Nottingham University Hospitals NHS Trust

University of Cambridge

Senior Clinical Investigator Scientist

Infections

Communicable Diseases

Adenoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Pathological Conditions, Anatomical

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Subjects without Helicobacter pylori infection and without atrophy

Subjects with Helicobacter pylori infection and without atrophy

Subjects with Helicobacter pylori infection and with atrophy

Subjects without Helicobacter pylori infection and with atrophy

Sun-Young Lee, MD

Serum pepsinogen (PG) levels are considered reliable markers for progression of atrophic gastritis with a stepwise reduction in the serum PG I level or PG I/II ratio. A combination of serum PG levels and Helicobacter pylori serology are used as a biomarker strategy for detection of individuals at increased risk of gastric neoplasm based on Correa's hypothesis. The investigators aimed to uncover whether this combination method could predict the risk of gastric neoplasms and the progression of chronic atrophic gastritis after 3 years. All the participants will be followed for an expected average of 3 years.

According to the Correa's hypothesis, the combination method using serum pepsinogen levels and serum Helicobacter pylori antibody would predict the risk and cell type of gastric neoplasm. However, in endemic regions of H. pylori infection such as in East Asian countries (Korea, Japan, and China), most of the aged population are have current or had past H. pylori infection. Therefore, in this study, we are going to uncover whether the risk of gastric neoplasm is significantly higher in the atrophy(+)/H. pylori(-) group followed by atrophy(+)/H. pylori(+), atrophy(-)/H. pylori(+), and atrophy(-)/H. pylori(-) groups. In addition, we are going to investigate whether those slow-growing gastric neoplasms such as differentiated gastric cancers with Lauren's intestinal type and gastric adenoma are more commonly developed in atrophy group following the Correa's hypothesis, whereas rapid-growing gastric neoplasms such as poorly-cohesive carcinoma or undifferentiated gastric cancers with Lauren's diffuse type are more commonly developed in the subjects without atrophy. Taken as a whole, our study result will provide an evidence whether this biomarker strategy are useful for the detection of individuals at increased risk of gastric neoplasm.

Serum for Helicobacter pylori antibody and pepsinogen levels Gastric biopsy for the diagnosis of intestinal metaplasia, atrophy, inflammatory cells, Helicobacter pylori, and the presence of gastric neoplasm if any.

Long-term Follow-up Prognosis of Atrophic Gastritis After 3 Years

Significance of Helicobacter Pylori Infection and Pepsinogen Levels on the Prognosis of Atrophic Gastritis - Observational Study

Presence of Helicobacter pylori infection

Degree of gastric atrophy measured by serum pepsinogen I and II levels

Konkuk University Medical Center

Associate professor

Patients with clinical or histological diagnosis of stomach cancer

M. Constanza Camargo, Ph.D.

Alejandro Corvalan, M.D.

Background:

Gastric cancer is a leading cause of cancer deaths around the world. This disease is a serious problem in places like East Asia, Central and South America, and Eastern Europe. Researchers want to study the causes of gastric cancer and its precursors. They want to reduce the number of people with stomach cancer.

Objectives:

To learn more about bacteria factors and other causes of gastric cancer. To study potential markers associated with precancerous gastric lesions (intestinal metaplasia).

Eligibility:

Adults ages 40-70 years at certain hospitals in Chile who:

Are going to have upper gastrointestinal endoscopies

OR have stomach cancer and need surgery

Design:

Participants will give gastric tissue samples.

Some participants will donate a portion of the stomach tissue that is removed as part of their clinical care.

Participants will give access to reports of their stomach exam. They will allow researchers to photograph the microscope slides of their tissue samples.

Participants will answer questions. The topics of the questions include:

Age, height, weight

Education

Habits including tobacco and alcohol

Personal and family history of disease

Reproductive history

Diet

Some participants will give blood, urine, saliva, and stool samples. Study staff will collect the blood. They will tell the participants how to collect the other samples themselves.

The burden of gastric adenocarcinoma is unevenly distributed, with several Asian and Latin American countries having particularly high incidence rates. Although chronic infection with Helicobacter pylori is the primary cause of this cancer, environmental and host cofactors modify the course of infection and determine whether infected individuals develop cancer. Due to the lack of adequate screening strategies and consequent late diagnosis, trends in mortality are similar to incidence, making this neoplasia the third leading cause of cancer death worldwide. The International Agency for Research on Cancer predicts that there will be no reduction in gastric cancer cases until at least 2030 due to population growth and aging. H. pylori-related gastric carcinogenesis is a multi-step process and mucosal lesions of intestinal metaplasia (IM) and dysplasia confer increased risk of progression. Therefore, case-control studies of these premalignant lesions may provide insights into cancer etiology and inform risk stratification. In addition, biomarkers to identify high-risk individuals are needed for early detection and curative treatment. Accordingly, we propose a 3-year study of Chilean adults undergoing upper gastrointestinal endoscopy for clinical purposes to identify 600 subjects with advanced premalignant lesions (i.e., incomplete-type IM, complete-type IM with extension to gastric corpus and dysplasia) for informative comparisons with 600 controls with non-atrophic gastritis, a benign histologic change apparent in most H. pylori infected individuals. As an additional case group, 100 individuals with newly diagnosed gastric cancer will be recruited from the same clinics. This multidisciplinary project will simultaneously evaluate bacterial, host and environmental factors towards a better understanding of gastric cancer etiology that may guide future efforts for prevention and control. We will explore risk factors that have been insufficiently studied, such as various hormones, H. pylori genomics, non- H. pylori gastric microbiota, and other parasitic infections. We will also evaluate potential noninvasive screening markers, including pepsinogens, hormones, miRNAs and DNA methylation. Results from this study may lead to improved management recommendations for individuals with advanced IM. Additionally, the resulting biobank of gastric tissue, blood, urine, saliva and stool will enable state-of-the-art molecular assays and serve as a resource for future research in this area.

gastric tissue, serum, plasma, buffy coat, saliva, urine, and stool.

Gastric Cancer Precursor Lesions (GCPL) Study

National Cancer Institute (NCI)

Adenocarcinoma

Disease Progression

Carcinoma

Participants with presence of atrophic gastritis, intestinal metaplasia, and dysplasia and risk of the progression of these lesions

The questionnaire on clinical, environmental, lifestyle, and dietary risk factors will be administered

Questionnaire

Monika Laszkowska, MD

Xiang Shu, PhD

Monika Laszkowska, PhD

The purpose of this study is to create a registry of participants with precursor lesions for gastric cancer, including gastric atrophy, intestinal metaplasia, and dysplasia. Normal controls and individuals with gastric cancer for comparison of baseline characteristics will also be enrolled.

A Study Collecting Health Information to Understand and Prevent Gastric Cancer

Gastric Cancer Prevention: Understanding Precursor Lesions and Risk Factors for Progression to Cancer

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The primary objective of this study is to create a registry of individuals with precursor lesions for gastric cancer, including gastric atrophy, intestinal metaplasia, and dysplasia. Normal controls and individuals with gastric cancer for comparison of baseline characteristics will also be enrolled.

Memorial Sloan Kettering Cancer Center

Helicobacter Infections

Disease Attributes

Bacterial Infections

Gram-Negative Bacterial Infections

Mycoses

Bacterial Infections and Mycoses

All Drugs and Chemicals

Anti-Infective Agents

Antibodies

Anti-Bacterial Agents

Immunoglobulins

Immunoglobulin G

Screening for H. pylori infection is planned in 5121 citizens living in different administrative districts of Moscow. The cohort will be formed based on age and sex structure of the Moscow population. The presence of H. pylori will be analyzed using 2 non-invasive methods - 13C-urease breath test and serological test (detection of IgG antibodies to H. pylori). An epidemiological questionnaire will be filled out for each respondent which will display basic information on the patient (gender, age, eating habits, bad habits, family history of cancer, etc.), as well as characterize the main symptoms, if any.

Based on pepsinogen (PG) I levels and PG II (serological markers of atrophy of the gastric mucosa), patients with a high risk of atrophic gastritis and precancerous lesions in the gastric mucosa will be identified and the age and sex structure of atrophic gastritis prevalence in Moscow will be constructed.

From 5121 respondents, 500 patients with confirmed H. pylori infection and serological markers of atrophic gastritis and a control group of infected with H. pylori without serological markers of gastric mucosa atrophy will be selected. They will undergo esophagogastroduodenoscopy with two gastric mucosa biopsies. The first will be conducted according to the OLGA system with a pathology assessment of the stage and degree of gastritis, while the second will be taken to determine the antimicrobial susceptibility of H. (polymerase chain reaction and culture). Correlations between serological and patholgy data on atrophy will be assessed in order to determine the reliability of serological screening for atrophy in the Moscow population.

Upper endoscopy will be performed by endoscopists using modern endoscopes (Fujinon EG-590WR, Olimpus GIF-H190 and others) while patient is sedated. Using sterile biopsy forceps, biopsy specimens will be taken from five areas of the stomach (two biopsy specimens - greater and lesser curvature of the antrum of the stomach; two biopsy specimens - lesser and greater curvature (or anterior and posterior wall) of the body of the stomach and one from the corner of the stomach) for pathology assessment. Pathology assessment of the gastritis stage and degree will be conducted according to the OLGA system developed by the international group of gastroenterologists and pathologists (Atrophy Club).

OLGA and H.pylori culture

Dmitry S. Bordin, MD, PhD

Mariia Kiriukova, MD

Dmitry Bordin, MD,PHD

H. pylori is transmitted from individual to individual and causes chronic active gastritis in all infected people. H. pylori infection can result in gastroduodenal ulcers, atrophic gastritis (AG), gastric carcinoma, and gastric MALT lymphoma.

More than 90% of gastric carcinomas are linked to H. pylori infection that causes chronic AG. A long course of the disease leads to the loss of gastric glands (chronic AG) followed by gastric intestinal metaplasia (GIM), dysplasia, and cancer. This defines two cancer prevention strategies: primary that consists of detection and eradication of H. pylori and secondary that focuses on endoscopic screening for pre-neoplastic lesions and follow-up.

Primary prevention planning requires reliable information on the H. pylori prevalence in the population. To design secondary prevention measures, an understanding of the age-sex structure of precancerous changes in the gastric mucosa (the prevalence of atrophic gastritis) is necessary.

H. pylori eradication is the basis of primary prevention of gastric cancer (GC). Approximately 36,000 new cases of GC are registered in the Russian Federation each year, and more than 34,000 patients die from the disease. Men get sick 1.3 times more often than women, the peak incidence occurs at the age of over 50 years. The poor outcomes reflect the late stage of diagnosis of this potentially preventable and treatable cancer. The lack of up-to-date data on the H. pylori prevalence in Moscow hinders developing of measures for the detection and timely treatment of this infection as well as the reduction of GC morbidity and mortality.

Aim: to analyze the prevalence of H. pylori infection and pre-neoplastic lesions in the gastric mucosa in the Moscow population to develop a strategy for gastric cancer and early detection.

Main goals:

1. To determine the prevalence of H. pylori in the Moscow population according to the non-invasive diagnostic method - 13C-urea breath test.
2. To determine the prevalence of H. pylori in the Moscow population according to the serological method - level of IgG antibodies to H.pylori.
3. To assess the prevalence of the gastric mucosa atrophy using serological markers (pepsinogen-I, pepsinogen-II and Gastrin-17) in the different age groups of the Moscow population.
4. To assess the state of the gastric mucosa according to endoscopic and morphological studies using the OLGA system, and their correlation with serological markers of atrophy (pepsinogen I level less than 30 µg/l and/or pepsinogen I/pepsinogen II ratio less than 3).
5. Develop recommendations for GC prevention and early detection strategy.

The planned study will contain two sample cohorts:

Cohort 1 Screening for H. pylori infection is planned in 5121 citizens living in different administrative districts of Moscow. The cohort will be formed based on age and sex structure of the Moscow population. The presence of H. pylori will be analyzed using 2 non-invasive methods - 13C-urease breath test and serological test (detection of IgG antibodies to H. pylori). An epidemiological questionnaire will be filled out for each respondent which will display basic information on the patient (gender, age, eating habits, bad habits, family history of cancer, etc.), as well as characterize the main symptoms, if any.

Based on pepsinogen (PG) I levels and PG II (serological markers of atrophy of the gastric mucosa), patients with a high risk of atrophic gastritis and precancerous lesions in the gastric mucosa will be identified and the age and sex structure of atrophic gastritis prevalence in Moscow will be constructed.

Cohort 2 From 5121 respondents, 500 patients with confirmed H. pylori infection and serological markers of atrophic gastritis and a control group of infected with H. pylori without serological markers of gastric mucosa atrophy will be selected. They will undergo esophagogastroduodenoscopy with two gastric mucosa biopsies. The first will be conducted according to the OLGA system with a pathology assessment of the stage and degree of gastritis, while the second will be taken to determine the antimicrobial susceptibility of H. (polymerase chain reaction and culture). Correlations between serological and patholgy data on atrophy will be assessed in order to determine the reliability of serological screening for atrophy in the Moscow population.

Research methods Diagnostics of H. pylori will be carried out using a modern, non-invasive and accurate method - 13C-urea breath test (13C-UBT).

13C-UBT is recognized as the "gold standard" in the non-invasive diagnosis of H. pylori infection, has a high sensitivity and specificity, above 95%. The test is easy to perform, convenient for patients, and has no side effects.

The main reagent in this test is a solution of urea labeled with the carbon isotope C13. The test is based on the hydrolysis of urea by urease produced by H. pylori that forms ammonia and CO2. After an individual takes a test solution with 13C-labeled urea, 13C-labeled urea, and then 13C carbon dioxide, are absorbed into the bloodstream, enter the lungs and are excreted with exhaled air. Initially, before taking the test solution, the patient's exhaled air is collected in a special sealed bag No. 1. The patient then drinks the test solution. After 30 minutes, a second air sample is exhaled into bag No. 2 that is also hermetically sealed. Then the air samples are analyzed on an infrared spectrometer IR-force 200 that determines the isotope ratio 13С/12С. The increase in labeled CO2 is expressed as delta over baseline (DOB). A DOB greater than 2.0‰ is used as a diagnostic criterion for H. pylori infection.

The infrared (IR) spectrometers of IR-force generation consist of 13C and 12C isotope high selectivity detectors. The specific absorption of CO2 in infrared light with a wavelength of 2-8 microns is used. The spectrometer uses specific optical and mathematical principles to reduce the mutual influence of 13CO2 and 12CO2, which increases the accuracy of the instrument and guarantees the reliability of the entire system. The IR analyzer determines the excess of the 13C/12C ratio over the baseline, i.e. level before taking 13C-urea. In addition, a thermostat is used to maintain a constant temperature and exclude the influence of the external environment.

This test will be conducted in Moscow Clinical Research Center named after A.S. Loginov that is equipped with an IR-force infrared spectrometer and trained specialists.

The second diagnostic test for the presence of H. pylori infection is a serological method - the detection of IgG antibodies to H. pylori. This method is recommended for epidemiological studies but is inferior to the 13C-urease breath test in terms of sensitivity, which is 76% to 84% while the specificity of the method is quite high - 90%. The serological method is based on the detection of specific circulating antibodies to H. pylori in the blood with enzyme immunoassay. The serological analysis will be carried out in Moscow Clinical Research Center named after A.S. Loginov.

Pepsinogens analyses will allow identifying chronic atrophic gastritis and can be used in large-cohorts screening to identify groups of individuals with a high risk of GC, which would require further follow-up with basic endoscopy and pathology investigations. The analysis of PG I provides information on the state of the glands in gastric fundus, PG II - of all parts of the stomach, and their ratio (PG I / PG II) reflects the functional status of the gastric mucosa and closely correlates with the progression of atrophic changes in the gastric mucosa. Normal test results indicate a good condition of the mucous membrane; PG I - 30-165 µg/l, Pepsinogen II - 4 to 22 µg/l, PG I / PG II ratio \> 3. Patients with a low concentration of pepsinogen I (\<30 ng/ml) and a low PG I / PG II ratio (\<3) are likely to have atrophic gastritis of the body of the stomach, precancerous lesions (metaplasia, diplasia), as well as adenocarcinoma that will have to be confirmed by endoscopic and pathology examination. One of the diagnostic sets that assess the serum levels of PG I, PG II, and their ratio (PG I / PG II), as well as determine the concentration of gastrin-17 and the presence of IgG antibodies to H. pylori, is "GastroPanel". The analysis will be carried out in one of the labs of Moscow Clinical Research Center named after A.S. Loginov using enzyme immunoassay.

Upper endoscopy will be performed by endoscopists using modern endoscopes (Fujinon EG-590WR, Olimpus GIF-H190 and others) while patient is sedated. Using sterile biopsy forceps, biopsy specimens will be taken from five areas of the stomach (two biopsy specimens - greater and lesser curvature of the antrum of the stomach; two biopsy specimens - lesser and greater curvature (or anterior and posterior wall) of the body of the stomach and one from the corner of the stomach) for pathology assessment. Pathology assessment of the gastritis stage and degree will be conducted according to the OLGA system developed by the international group of gastroenterologists and pathologists (Atrophy Club).

The stage of atrophy will be assessed on a 4-point scale from 0 to 3, depending on the percentage of atrophied glands. No atrophy (0%) - 0 points, mild atrophy (1-30%) - 1 point, moderate atrophy (31-60%) - 2 points and 3 points - severe atrophy (more than 60%). The obtained data in points will be compared with the developed tables and determine the stage of gastritis from 0 to IV. The degree of gastritis reflects the severity of inflammation, is assessed in the same biopsy specimens by the lymphoplasmacytic and leukocytic infiltration dense in accordance with the visual analog scale, and is expressed in accordance with its assessment table in gradations from 0 to IV.

Number of respondents: 5121 citizens.

Inclusion Criteria:

* Age 18 to 80 years;
* Signed informed consent form.

Criteria for non-inclusion:

* history of taking antibiotics, bismuth-containing drugs within 30 days before the visit and proton pump inhibitors within 14 days before the visit;
* The presence of clinically significant neurological, cardiovascular, gastrointestinal (total of partial gastrectomy), hepatic, renal, immune and other diseases in medical history;
* Patients with diagnosed cancers of any kind who require specialized treatment and/or are currently undergoing anticancer treatment;
* Psychiatric illnesses, including in the past, which, in the opinion of the investigator, make the patient's participation in the study unacceptable;
* Pregnancy;
* Patients who tend to refuse to participate in the study and comply with doctor's recommendations;
* Inability or unwillingness to give informed consent to participate in the study or to fulfill the requirements of the study;

Criteria for exclusion of patients from the study

1. Refusal of further use of the drug;
2. Deterioration of objective indicators of the patient's condition;

Study design The total duration of participation of each patient in the study will be about 2-6 weeks.

Visit 1 (5121 respondents) - day 0: inclusion in the study, informed consent signing, filling out the questionnaire, conducting a 13C-urease breath test, taking a blood test for Gastropanel.

Visit 2 - 500 respondents with serological signs of atrophy (pepsinogen I \< 30 ng/ml and/or PGI/PGII \< 3 µg/l) and from the control group (14±7 days): EGDS + biopsy according to OLGA.

Expected results

* Large-scale screening of persons for H. pylori infection will allow estimating the actual prevalence of infection among residents of Moscow, which is necessary for planning measures for the primary prevention of gastric cancer.
* Determination of serological markers of atrophy and their correlation with the data of morphological studies will allow assessing the sex and age structure of pre-neoplastic changes in the gastric mucosa, which is necessary to develop an algorithm for secondary prevention of gastric cancer.
* The results of the study will allow developing a comprehensive program for the prevention and early detection of gastric cancer based on an evidence-based combination of primary and secondary prevention strategies.

gastric mucosa biopsy for OLGA-assessment and culture (H.p. atimicrobal susceptibility)

Epidemiology of Helicobacter Pylori Infection in Moscow

(pepsinogen-I, pepsinogen-II and Gastrin-17)

OLGA assessment of biopsy samples (pepsinogen I level less than 30 µg/l and/or pepsinogen I/pepsinogen II ratio less than 3).

Moscow Clinical Scientific Center

Esophageal Neoplasms

Duodenal Neoplasms

Polyps

Barrett Esophagus

Head and Neck Neoplasms

Esophageal Diseases

Intestinal Neoplasms

Duodenal Diseases

Intestinal Diseases

Esophageal Cancer

Patients referred for clinically indicated EGD, without known precancerous condition. Patients will receive endoscopy with standardised biopsy and photodocumentation protocol

Massimiliano Di Pietro, MD

Bincy Alias

Ines Modolell, MD

Andreas V Hadjinicolaou

Cancers of the upper gastro-intestinal tract, including esophagus (gullet), stomach and small bowel, are amongst the deadliest malignancies. The main reason for their high mortality rate is that they are usually diagnosed late when curative treatments are no longer effective. However, these types of cancer generally arise from well-described pre-cancerous diseases, such as Barrett's esophagus and gastric intestinal metaplasia. This provides an opportunity for clinicians to detect these pre-cancerous conditions early and offer adequate cure or clinical monitoring before they progress to cancer. A camera test (gastroscopy) is the gold-standard test to detect pre-cancerous diseases in these organs.

There has been limited research to set the standards for performance of a gastroscopy, especially with regards to diagnosis of pre-cancerous conditions, which require knowledge and skills by the physician performing the test (endoscopist). Therefore, the hypothesis behind this study is that the aforementioned pre-cancerous diseases are understudied and often go undetected. This study aims to understand how often endoscopists should diagnose these pre-cancerous diseases on routine gastroscopy and help define the standards to measure performance. The investigators will assess the following rates: i. how often endoscopists diagnose these pre-cancerous lesions during endoscopy; ii. How often these conditions are diagnosed on biopsies taken according to a standardized protocol; iii. How often these condition should have been diagnosed by the endoscopists based on the review of pictures by expert endoscopists. The investigators will also compare the rates of correct diagnosis by endoscopists with different levels of experience and based on the times spent to complete the diagnostic test.

Investigating these aspects will enhance the understanding of the medical community with regards to the diagnosis of these pre-cancerous lesions and set endoscopy standards to improve their early detection and treatment before they progress to cancer. This will translate to improved cancer prevention and benefit for patients.

BACKGROUND Esophagogastroduodenoscopy (EGD) is the gold-standard test for investigating upper gastrointestinal (GI) tract pathology. The learning curve for EGD is generally steep and it is often performed by trainees at the mid stages of core training as well as nurse endoscopists. Currently the Joint Advisory Group for GI endoscopy (JAG) recommends a minimum number of 200 procedures to acquire the skills and perform endoscopy independently. However, there has been very little research done to set the standard required to measure EGD performance. The only validated quality indicators in EGD include the successful J-manoeuvre rate and D2 intubation rate, which reflect very basic skills and do not measure diagnostic ability. This contrasts with key performance indicators (KPI) for colonoscopy, for which extensive research has led to development of formal quality performance indicators. In colonoscopy formal quality indicators include (i) cecal intubation rate, (ii) adenoma detection rate, (iii) rectal retroversion rate, (iv) colonoscopy withdrawal time, (v) polyp retrieval rate, (vi) post-colonoscopy colorectal cancer rate and (vii) perforation rate. This has allowed researchers to demonstrate that poor quality colonoscopy leads to an increase in the incidence of interval cancers.

Similar benchmarks have not been set for the upper GI tract. A recent UK study revealed that 7.7% cases of upper GI cancers were missed on previous EGD and that there was a correlation between missed cancer and high number of procedures per lists and hence, arguably, those performed under user time pressure. This is in line with studies on other Western populations indicating that between 5.3% and 13.9% of patients with upper GI cancers have had normal EGD reported within the previous 3 years. Given that gastroscopy is the most commonly performed procedure in endoscopy units in the UK and its demand is increasing, there is an urge to identify diagnostic KPI to measure diagnostic skills, to improve quality of the endoscopies and to reduce the rate of missed diagnoses. Furthermore, such minimum quality standards are extremely important to counteract the potential negative effects on the performance of the pressure faced by endoscopy departments to deliver diagnostic and therapeutic procedures in a timely fashion. The importance of adequate procedure time for diagnostic accuracy has been demonstrated both in the detection of oesophageal and gastric neoplastic lesions. For detection of upper GI neoplasia, it has been demonstrated that a minimum of 7 minutes per procedure should be spent in order to ensure adequate visualisation and allow detection of high-risk lesion . In a Korean study, that compared faster with slower endoscopists, all of whom had adequate training and experience, the slower endoscopists (withdrawal time from duodenum \>3min) had a significantly higher detection rate of upper GI neoplasia. Finally, in the context of Barrett's oesophagus (BO), longer inspection times during EGD correlated with increase detection rate.

Pre-malignant lesions in the upper GI tract are generally understudied when compared to those in the lower GI tract. Furthermore, their epidemiology seems to vary with geography, and this has not been inadequately investigated in the UK. Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma. The population prevalence is difficult to estimate given that the condition can be asymptomatic, and the diagnosis is only made by endoscopy and biopsy. It is estimated that the prevalence in the general population in Western Countries is 1-2% with significant geographic variation, but increases in patients undergoing endoscopic procedures (4.0% in Dutch population, 5.6% USA). However, the majority of studies looking at BE prevalence are confounded by the fact that most procedures were performed for GERD symptoms generating selection bias. In studies performed in patients referred for colonoscopy (n=1500 approximately) the prevalence of BE varied between 6.8% and 16.7%.

Similar to oesophageal cancer, gastric cancer has its own pre-malignant precursors including gastric intestinal metaplasia (GIM) and gastric atrophy (GA) . The endoscopic diagnosis of GA and GIM however is not straightforward as the colorimetric shift from normal to pathological mucosa is subtle and additional endoscopic signs such as disappearance of gastric folds can be affected by the degree of air insufflation. The prevalence of GA can reach up to 33.3% in Western Europeans and is higher in East Asia. For GIM, the reported population prevalence in Western Countries ranges from 7 to 28.6%. These rates are however probably affected by selection bias, such as enrichment of individuals affected by H. pylori infection. In a Dutch study on patient referred for colonoscopy 0.8% had GA, 7.1% had both GA and GIM and 1.4% had gastric dysplasia.

For esophageal squamous dysplasia, the precursor lesion of oesophageal squamous cell carcinoma, prevalence estimates are between 3 and 38%. This reflects the variation in endoscopic methods, histopathological scoring and the studied populations from high-risk geographic regions such has Korea. The prevalence of squamous dysplasia in Western Countries in not well known, since it is generally very difficult to diagnose on white light endoscopy. It can be argued that squamous dysplasia is vastly underdiagnosed in clinical practice as the ratio between oesophageal adenocarcinoma and squamous cell carcinoma in the UK is just over 2:1, however squamous dysplasia is rarely diagnosed.

Duodenal adenoma is another understudied pre-malignant lesion that can in fact undergo malignant transformation in 30-85% of cases and as such, needs to be recognised and treated early and definitively . These occur very often in the context of familial adenomatous polyposis (FAP) syndrome, whereas sporadic duodenal adenomas are much rarer with a prevalence of 0.03-0.4% (32, 33).

The majority of studies looking at prevalence of pre-malignant upper GI conditions in the general population referred for EGD are limited by the lack of standardised endoscopy and biopsy protocols. In addition, none of the studies looked at variation of prevalence based on experience. Furthermore, no expert review of endoscopic images has been performed to ensure quality of the diagnosis. Although quality standards in upper GI endoscopy have been proposed by the British Society of Gastroenterology and European Society of Gastrointestinal Endoscopy, the majority of the statements in these guidelines have a low level of evidence and weak to moderate strength of the recommendation. Most importantly, none of the statements refer to diagnostic KPI, given that the expected detection rate of the upper GI pre-neoplastic and early neoplastic lesions at endoscopy is unknown. This represents a gap that our study aims to tackle.

HYPOTHESIS The hypothesis is that the prevalence of upper Gi pre-malignant condition is underestimated based on available literature data and that the detection rate of pre-cancerous upper GI lesions improves with a more rigorous and systematic approach to performing EGD. In the future, using diagnostic KPI to monitor performance of upper GI endoscopists will result in improved outcomes of oesophago-gastric cancer.

STUDY OBJECTIVES The aim of this study is to assess endoscopic and pathological outcomes during routine EGD using standard photo-documentation and biopsy protocol.

The primary objective is to define the prevalence of pre-malignant or early malignant upper GI tract lesions as measured by a standardised endoscopy and biopsy protocol. This is further broken down into categories of pre-malignant pathology, namely: 1) Barrett's esophagus with and without dysplasia; 2) squamous dysplasia;, 3) gastric atrophy/gastric intestinal metaplasia; , 4) gastric adenoma; and 5) duodenal adenoma.

The secondary objectives are:

1. Missed rate of endoscopic diagnosis compared to pathological diagnosis
2. Missed rate of endoscopic diagnosis compared to expert review of endoscopic photos
3. Correlation between duration of the endoscopy and detection of pre-neoplastic and neoplastic lesions
4. Quality of the endoscopic pictures taken in routine endoscopy
5. Correlation between endoscopist experience and rate of detection
6. Correlation between use of image enhanced endoscopy and rate of detection
7. Interobserver agreement among expert and not expert endoscopists
8. Correlation between life-style factors and pathological outcomes

STUDY DESIGN This will be a multicenter population study. Recruiting centers will be a range of Teaching and District General Hospitals in England. 1000 patients referred for urgent or routine endoscopy to evaluate upper GI symptoms will be recruited. The detection rates of upper GI tract pre-malignant lesions in our study procedures will be compared to standard historical data from each participating institution. An equivalent population from the year prior to the start of recruitment, matched for age, sex, indication for endoscopy and referral pathway, will be retrieved from the archives of each participating NHS Trust and directly contrasted to this study population to evaluate whether the detection rate of pre-malignant upper GI tract lesions improves with a more rigorous and systematic approach to performing EGD using a standardized photo documentation and biopsy protocol. In this way, the investigators can evaluate the immediate impact of our study and the utility of the proposed diagnostic KPI. As an example, the investigators already have date to show that in 2019 over 8,500 EGD were performed in Cambridge alone, of which 53% had biopsies taken. Based on matched pathology record, only 29 new diagnoses of GA or GIM were made during the same time period, suggesting the possibility of large under-detection of premalignant stomach. The endoscopic pictures will be evaluated by two expert endoscopists with interest in detection and treatment of upper GI pre-malignant and early malignant conditions. The quality of the pictures will be scored on a visual analogue scale based on two parameters: optical quality and representation of the intended section of the upper GI tract. The endoscopists will note the presence of premalignant conditions. In case of disagreement, a third investigator will review the picture to achieve a gold standard endoscopic diagnosis.

Clinical samples from biopsies taken during endoscopic procedures for the purpose of tissue diagnosis

Diagnostic Performance Indicators in Upper GI Endoscopy:PROSPERO Study

PROspective Multicentre Study to Identify Diagnostic Key PERfOrmance Indicators in Upper GI Endoscopy (PROSPERO)

The primary outcome is calculating the proportion of patients diagnosed with pre-malignant pathology in the upper GI tract. This is further broken down into categories of pre-malignant pathology, namely; 1) duodenal adenoma, 2) gastric atrophy/gastric intestinal metaplasia (IM), 3) gastric adenoma, 4) Barrett's oesophagus and 5) squamous dysplasia.

The detection rates of upper GI tract pre-malignant lesions in our study procedures will be compared to standard historical data currently available to update and guide future practice guidelines.

(defined as any pathological diagnosis that was not suspected by the endoscopist on visualisation alone)

(defined as endoscopic lesions identified by expert review and not reported by primary endoscopist)

Assessment of whether duration of the endoscopy associates with diagnosis of pre-neoplastic lesions

defined as quantitative assessment of photo on a Visual Analogue Scale by expert endoscopists

Assessment of whether year of endoscopy practice correlate with the rate of detection of pre-malignant lesions

Assessment of whether use of dye or electronic chromoendoscopy improves detection of lesions

Agreement will be assess with Cohen kappa values

Assessment of utility of life-style information to predict diagnosis

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cytosponge for Gastric Intestinal Metaplasia	NCT05657080	Gastric Cancer Gastric Intesti... Gastric Atrophy	Cytosponge-TFF3	18 Years -	University of Cambridge
Long-term Follow-up Prognosis of Atrophic Gastritis After 3 Years	NCT01824953	Gastric Neoplas... Gastric Cancer Gastric Adenoma Gastric Atrophy Intestinal Meta...		18 Years - 90 Years	Konkuk University Medical Center
Gastric Cancer Precursor Lesions (GCPL) Study	NCT03188406	Intestinal Meta... Gastric Cancer		40 Years - 70 Years	National Cancer Institute (NCI)
Cytosponge for Gastric Intestinal Metaplasia	NCT05657080	Gastric Cancer Gastric Intesti... Gastric Atrophy	Cytosponge-TFF3	18 Years -	University of Cambridge
Cytosponge for Gastric Intestinal Metaplasia	NCT05657080	Gastric Cancer Gastric Intesti... Gastric Atrophy	Cytosponge-TFF3	18 Years -	University of Cambridge
A Study Collecting Health Information to Understand and Prevent Gastric Cancer	NCT06370143	Gastric Atrophy Gastric Intesti... Dysplasia Gastric Adenoca... Gastric Cancer	Questionnaire	18 Years -	Memorial Sloan Kettering Cancer Center
Gastric Cancer Precursor Lesions (GCPL) Study	NCT03188406	Intestinal Meta... Gastric Cancer		40 Years - 70 Years	National Cancer Institute (NCI)
Epidemiology of Helicobacter Pylori Infection in Moscow	NCT05775120	Gastric Atrophy Gastric Cancer Helicobacter Py...	OLGA and H.pylo...	18 Years - 99 Years	Moscow Clinical Scientific Center
A Study Collecting Health Information to Understand and Prevent Gastric Cancer	NCT06370143	Gastric Atrophy Gastric Intesti... Dysplasia Gastric Adenoca... Gastric Cancer	Questionnaire	18 Years -	Memorial Sloan Kettering Cancer Center
Diagnostic Performance Indicators in Upper GI Endoscopy:PROSPERO Study	NCT04843397	Esophageal Canc... Gastric Cancer Barrett Esophag... Gastric Atrophy Gastric Intesti... Duodenal Adenom... Esophageal Dysp... Duodenum Cancer Gastric Polyp Barretts Esopha...		18 Years -	University of Cambridge

Spots Global Cancer Trial Database for gastric atrophy