Gastropanel for Gastric Atrophy and Cancer Risk Assessment
Gastropanel for Gastric Atrophy and Cancer Risk Assessment
Background: Atrophic gastritis (AG) is the single most important precursor condition for
 gastric cancer (GC) known so far. H. pylori infection is the most important causative agent
 of gastritis, and subsequent AG. The GastroPanel test (Biohit HealthCare, Helsinki, Finland),
 a blood test evaluating the four biomarkers specific for the gastric mucosa pepsinogen I
 (P-PGI), pepsinogen II (P-PGII), gastrin-17 (P-G-17) and H. pylori antibody (P-HpAb), is the
 first non-invasive diagnostic tool providing possibilities for detecting the patients at risk
 for GC and peptic ulcer as well as malabsorption of vitamin B12, iron, magnesium, calcium and
 some drugs. A well designed clinical study is warranted to fully assess the performance of
 GastroPanel examination in detecting the gastric lesions which can lead to GC. The
 investigators aim to perform a clinical study in an adult population in United Kingdom in
 order to determine the diagnostic accuracy of the GastroPanel test in evaluating AG and other
 specific gastric conditions associated with an increased risk for GC. Methods: Two hundred
 and fifty patients (45 years and older, both genders) will be enrolled among the patients
 with dyspepsia referred for gastroscopy at Homerton University Hospital (London, United
 Kingdom). During the same visit, all patients are subjected to gastroscopy examination, with
 directed biopsies from the antrum and corpus, following the protocol of the operative link on
 gastritis assessment (OLGA) classification for chronic gastritis and Sydney Classification.
 Biopsies are examined at the Pathology laboratory of Homerton University Hospital and
 interpreted using the OLGA staging system as well as the Sydney system for classification of
 gastritis. Specific aims: The principal goal of this clinical trial is to establish the
 performance of the GastroPanel examination in detecting AG and other specific gastric
 conditions associated with an increased risk for GC. In particular, the investigators will
 evaluate AG in the antrum, AG in the corpus, AG in both antrum and corpus (=atrophic
 pangastritis), biopsy-confirmed dysplasia (intestinal metaplasia) of the gastric mucosa. For
 all these conditions, the investigators will calculate the diagnostic accuracy of the
 GastroPanel test.
At present, the diagnosis of most gastric and oesophageal diseases, requires an endoscopic
 examination which is an invasive, time-consuming and expensive procedure. At present, there
 are few non-invasive methods (e.g. tests for Helicobacter pylori) available for the diagnosis
 of the upper gastrointestinal tract diseases. Any of these tests do not, however, give
 possibilities for a comprehensive diagnosis of the different phenotypes of gastritis, i.e.,
 whether superficial or atrophic, and located in the antrum or corpus. Importantly, these
 tests do not give any clues about the severity (grade) of these lesions, as defined by the
 Sydney and OLGA classification .

 To obviate the excessive use of this invasive and expensive procedure (endoscopy), there is
 an urgent need to develop non-invasive diagnostic tools capable of accurately detecting the
 patients at high risk for GC, i.e. the different phenotypes of gastritis as well as their
 related H. pylori infections . After ELISA-testing for P-PG I, p-PG II, P-G-17 and P-Hp-Ab in
 a plasma sample, an endoscopic examination can be preserved only for those patients whose
 GastroPanel test results suggest AG, whereas an endoscopic examination can be avoided in
 subjects with negative GastroPanel result, or in whom the test biomarkers indicate a
 non-atrophic gastritis or a healthy stomach (18). Gastroscopy is also recommended if the
 GastroPanel examination reveals high acid output (P-G-17 below 1,0 pmol/l) or chronic H.
 pylori infection with symptoms.

 This clinical trial is conducted as collaboration between Biohit HealthCare (Helsinki,
 Finland) and Homerton University Hospital (London, UK) (hereafter called "the Partners"). The
 study is performed in Homerton Hospital, supervised by a steering committee consisting of
 members from both research Partners.

 Enrolment of the patients in the study will take place at Homerton Hospital including
 consecutive patients over 45 years of age, referred for gastroscopy at the Outpatient
 Department of Endoscopy. The estimated cohort to be screened is at least 250 subjects (both
 genders), to reach a cohort of 100 patents enriched with equal numbers (n=25) of all
 conditions (see: Section 2, above) classified as study endpoints.

 Patient enrolment is taking place in a single step. In brief, the potentially eligible
 patients are identified among the gastroscopy-referral outpatients by the members of the
 research team. At this stage, every patient will be asked to consent the study and sign a
 written consent to participate. Because all patients are enrolled among the subjects
 attending the 11 Endoscopy clinic due to an appointment to gastroscopy, their preparation
 will be compliant with the preparatory steps needed for the GastroPanel examination (details
 below).

 Eligible patients are all adult females and males, with dyspeptic symptoms (epigastric pain,
 bloating and epigastric discomfort). However, the following patients should be considered
 non-eligible: 1) the patients whose treatment requires surgery, or immediate follow-up
 treatment for major symptoms, as well as 2) those that refuse to participate.

 In this study, all patients examined with the GastroPanel test will be subjected to
 gastroscopy, providing the histological confirmation to be used as the gold standard in
 calculating the performance indicators for the test.

 All patients participating in this study shall undergo a routine gastroscopy examination,
 which will be complemented by biopsy sampling from the antrum and corpus, according to the
 principles of the Sydney and OLGA classification sampling. In endoscopy, all observed
 abnormal mucosal lesions are noted and photographed, and if necessary (e.g. suspicion of
 malignancy) subjected to additional biopsy.

 All statistical analyses will be performed using the SPSS 21.0.0 for Windows (IBM, NY, USA)
 and STATA/SE 13.0 software (STATA Corp., Texas, USA). The descriptive statistics will be done
 according to routine procedures. Performance indicators (sensitivity, specificity, positive
 predictive value, PPV, negative predictive value, NPV and their 95%CI) of individual markers
 and whole GastroPanel test will be calculated separately for each study endpoint, using the
 STATA/SE software and the diagti algorithm introduced by Seed et al. (2001). This algorithm
 also calculates the area under ROC (Receiver Operating Characteristics) called AUC, for each
 biomarker at each endpoint. Because GastroPanel is a quantitative ELISA test, these ROC
 curves can be used to identify the optimal sensitivity/specificity balance that gives each
 biomarker an optimal threshold for detection of each study endpoint. Significance of the
 difference between AUC values can be estimated using STATA's roccomb test with 95%CI.
Inclusion Criteria:

 -  Adult females and males over 45 years of age with dyspeptic symptoms (epigastric pain,
 bloating and epigastric discomfort)

 Exclusion Criteria:

 -  Patients who require surgery or immediate follow-up treatment for major symptoms,
 including hematemesis, melena, acute epigastric pain

 -  Patients who previously underwent upper gastrointestinal surgery

 -  Patients with diabetes

 -  Pregnant women

 -  Subjects who refuse to participate or are unable to give consent