Pyloric or Pseudopyloric Metaplasia of the Corpus Mucosa in Autoimmune Gastritis (PM_in_AIG)

To Validate That Pyloric or Pseudopyloric Metaplasia of the Corpus Mucosa is a Specific Pathological Feature of Autoimmune Gastritis

The study is aimed to investigate the different rates of pyloric/ pseudopyloric metaplasia or spasmolytic polypeptide-expressing metaplasia (SPEM) of corpus between autoimmune gastritis and H. pylori-infected non-ulcer dyspepsia.

Study Overview

• Status: Enrolling by invitation
• Conditions: Autoimmune Diseases; Metaplasia; Gastritis, Atrophic; Helicobacter Pylori Gastritis; Anemia, Pernicious
• Intervention / Treatment: Diagnostic test: Assess pyloric or pseudopyloric metaplasia of corpus by H&E stains; Diagnostic test: Assess pyloric or pseudopyloric metaplasia of corpus by TFF2 immunohistochemistry stains; Diagnostic test: The assessment of corpus-predominant gastritis index (CGI), Operative Link for Gastritis Assessment (OLGA), and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM)

Detailed Description

Autoimmune gastritis is not an uncommon disease among northern European ancestry, but its prevalence rates are unclear in other populations, including Taiwanese. A study showed that near 2% of persons more than 60 years old have undiagnosed pernicious anemia, one of the complications of autoimmune gastritis. Believed to be undiagnosed, patients are at risk of gastric malignancy and vitamin B12 deficiency-related complications until the end stage. Therefore, use of available diagnostic tools to diagnose patients with autoimmune gastritis has been important. However, autoimmune gastritis has a silent course and is not easy to be early recognized. Early recognition is important because in the late stage, vitamin B12 replacement treatment may correct pernicious anemia only but not neurologic disorders. Fundus and corpus atrophy with parietal cells loss presented 2 to 3 decades before anemia develops in autoimmune gastritis. It is no doubt that autoimmune gastritis could be diagnosed if vitamin B12 deficiency with megaloblastosis and anemia developed; however, it could be diagnosed earlier if the gastric pathological finding was noticed to be a diagnostic clue. Nevertheless, fundus and corpus atrophy is presented not only in autoimmune gastritis but also in H. pylori-related gastropathy. Therefore, we need a pathologic feature which could help physicians differentiate autoimmune gastritis from H. pylori-infected gastropathy. Here, we propose that pyloric or pseudopyloric metaplasia of corpus is distinct from H. pylori-infected gastropathy. We believe that this specific pathologic feature will be helpful to diagnose patients with autoimmune gastritis.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704302
    • National Cheng Kung University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The patients at the outpatient department or at the inpatient wards of National Cheng Kung University Hospital and Tainan hospital in Tainan, Taiwan, will be selected.

Description

Inclusion Criteria:

• Patients who present with relevant symptoms or signs of upper gastrointestinal diseases, including, but not limited to the following: impaired gastric emptying, epigastric discomfort, postprandial bloating, early satiety, epigastric pain, acid regurgitation, dyspepsia, anemia, or vitamin B12 deficiency, or iron deficiency, are candidates to be enrolled to receive gastroscopy.

Exclusion Criteria:

• The exclusion criteria are as follows including use of aspirin, non-steroidal anti-inflammatory drugs, or cyclooxygenase-2 selective inhibitors for more than 3 months, or diagnosis with upper gastrointestinal cancer including esophagus, stomach, duodenum, mucosa-associated lymphoid tissue lymphoma, other gastric lymphoma, or pancreas.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
The autoimmune gastritis group; Autoimmune gastritis is diagnosed if the anti-parietal cell antibody titer is positive and higher than 1:10 (ImmuGloTM COMVI mouse kidney/stomach IFA kit, Immco Diagnostics, Inc. Buffalo NY, USA).	Diagnostic test: Assess pyloric or pseudopyloric metaplasia of corpus by H&E stains; The pathologists assess pyloric or pseudopyloric metaplasia. Pyloric or pseudopyloric metaplasia of corpus is defined as the presence of torturous deep glands in a "pseudo-pylori" pattern with focal or complete loss of parietal cells. The score of pyloric or pseudopyloric metaplasia of the corpus mucosa is ranging from 0 to 3. Score 0 is no loss of parietal cells with normal fundus gland patterns. Score 1 presents focal loss of parietal cells and scattered patterns of pyloric or pseudopyloric metaplasia with few forming pylorus-like glands. Score 2 presents focal loss of parietal cells and scattered patterns of pyloric or pseudopyloric metaplasia mixed with >= 4 pylorus-like glands. Score 3 was clusters of pylorus-like glands; the metaplasia involves > 60% of mucosa and extends to the lower third of mucosa.; Other Names: H&E stains; Diagnostic test: Assess pyloric or pseudopyloric metaplasia of corpus by TFF2 immunohistochemistry stains; Mouse anti-human TFF2 monoclonal antibody (R&D Systems) is used to stain gastric corpus tissues to assess the presence and degree of SPEM. The score of TFF2 staining of the corpus mucosa is ranging from 0 to 3. Score 0 is not stained. Score 1 is a "scattered" pattern of TFF staining between parietal cells; the staining is limited in the middle third of the mucosa. Score 2 is TFF2-expressing cells distributed over both the middle and lower third of the glands. Score 3 is torturous gastric oxyntic glands with a diffuse expression of TFF2 into the whole glands over both the middle and lower third of the glands of the mucosa.; Other Names: TFF2 immunohistochemistry stains; Diagnostic test: The assessment of corpus-predominant gastritis index (CGI), Operative Link for Gastritis Assessment (OLGA), and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM); We take five gastric mucosal biopsies in each patient under gastroscopy, including two from the antrum (at the lesser and greater curvature, 2 cm within the pylorus, respectively), two from the corpus (at the lesser curvature of the lower corpus and the greater curvature of the middle corpus, respectively), and one from the lesser curvature of the high corpus. The pathologists assess the gastric pathology according to the updated Sydney system. Accordingly, the histological findings are translated into CGI, the Operative Link for Gastritis Assessment (OLGA), and the Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stages.; Other Names: updated Sydney system
The controls; The patients who are enrolled to validate pathogenesis after H. pylori infection. H. pylori infection is diagnosed by histological assessment. The matched controls are needed to be confirmed to have negative anti-parietal cell antibody.	Diagnostic test: Assess pyloric or pseudopyloric metaplasia of corpus by H&E stains; The pathologists assess pyloric or pseudopyloric metaplasia. Pyloric or pseudopyloric metaplasia of corpus is defined as the presence of torturous deep glands in a "pseudo-pylori" pattern with focal or complete loss of parietal cells. The score of pyloric or pseudopyloric metaplasia of the corpus mucosa is ranging from 0 to 3. Score 0 is no loss of parietal cells with normal fundus gland patterns. Score 1 presents focal loss of parietal cells and scattered patterns of pyloric or pseudopyloric metaplasia with few forming pylorus-like glands. Score 2 presents focal loss of parietal cells and scattered patterns of pyloric or pseudopyloric metaplasia mixed with >= 4 pylorus-like glands. Score 3 was clusters of pylorus-like glands; the metaplasia involves > 60% of mucosa and extends to the lower third of mucosa.; Other Names: H&E stains; Diagnostic test: Assess pyloric or pseudopyloric metaplasia of corpus by TFF2 immunohistochemistry stains; Mouse anti-human TFF2 monoclonal antibody (R&D Systems) is used to stain gastric corpus tissues to assess the presence and degree of SPEM. The score of TFF2 staining of the corpus mucosa is ranging from 0 to 3. Score 0 is not stained. Score 1 is a "scattered" pattern of TFF staining between parietal cells; the staining is limited in the middle third of the mucosa. Score 2 is TFF2-expressing cells distributed over both the middle and lower third of the glands. Score 3 is torturous gastric oxyntic glands with a diffuse expression of TFF2 into the whole glands over both the middle and lower third of the glands of the mucosa.; Other Names: TFF2 immunohistochemistry stains; Diagnostic test: The assessment of corpus-predominant gastritis index (CGI), Operative Link for Gastritis Assessment (OLGA), and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM); We take five gastric mucosal biopsies in each patient under gastroscopy, including two from the antrum (at the lesser and greater curvature, 2 cm within the pylorus, respectively), two from the corpus (at the lesser curvature of the lower corpus and the greater curvature of the middle corpus, respectively), and one from the lesser curvature of the high corpus. The pathologists assess the gastric pathology according to the updated Sydney system. Accordingly, the histological findings are translated into CGI, the Operative Link for Gastritis Assessment (OLGA), and the Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stages.; Other Names: updated Sydney system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pyloric or pseudopyloric metaplasia of corpus by positive TFF2 staining	The rates of pyloric or pseudopyloric metaplasia of corpus defined by positive TFF2 staining are compared between the two groups	1 to 3 months after gastric biopsy
The pyloric or pseudopyloric metaplasia of corpus by H&E staining	The rates of pyloric or pseudopyloric metaplasia of corpus defined by H&E staining are compared between the two groups.	7 days after gastric biopsy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The positive corpus-predominant gastritis index	The rates of positive corpus-predominant gastritis index defined by updated Sydney system are compared between the two groups.	7 days after gastric biopsy
The stages of the Operative Link for Gastritis Assessment (OLGA)	The stages of the Operative Link for Gastritis Assessment (OLGA) defined by updated Sydney are compared between the two groups.	7 days after gastric biopsy
The stages of the Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM)	The stages of the Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) defined by updated Sydney are compared between the two groups.	7 days after gastric biopsy

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital
• Collaborators: Tainan Hospital, Ministry of Health and Welfare
• Investigators: Principal Investigator: Hsiu-Chi Cheng, MD, PhD, National Cheng-Kung University Hospital

Publications and helpful links

General Publications

• Wada Y, Nakajima S, Kushima R, Takemura S, Mori N, Hasegawa H, Nakayama T, Mukaisho KI, Yoshida A, Umano S, Yamamoto K, Sugihara H, Murakami K. Pyloric, pseudopyloric, and spasmolytic polypeptide-expressing metaplasias in autoimmune gastritis: a case series of 22 Japanese patients. Virchows Arch. 2021 Jul;479(1):169-178. doi: 10.1007/s00428-021-03033-5. Epub 2021 Jan 30.
• Tsai YC, Hsiao WH, Yang HB, Cheng HC, Chang WL, Lu CC, Sheu BS. The corpus-predominant gastritis index may serve as an early marker of Helicobacter pylori-infected patients at risk of gastric cancer. Aliment Pharmacol Ther. 2013 May;37(10):969-78. doi: 10.1111/apt.12291. Epub 2013 Apr 2.
• Cheng HC, Tsai YC, Yang HB, Yeh YC, Chang WL, Kuo HY, Lu CC, Sheu BS. The corpus-predominant gastritis index can be an early and reversible marker to identify the gastric cancer risk of Helicobacter pylori-infected nonulcer dyspepsia. Helicobacter. 2017 Aug;22(4). doi: 10.1111/hel.12385. Epub 2017 Mar 22.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 3, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 14, 2022

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 1, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Autoimmune Diseases; Anemia, Pernicious; Helicobacter Pylori Gastritis; Metaplasia Intestinal; Metaplasia
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Immune System Diseases; Hematologic Diseases; Gastrointestinal Diseases; Stomach Diseases; Nutrition Disorders; Gastroenteritis; Anemia; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Anemia, Megaloblastic; Anemia, Macrocytic; Vitamin B 12 Deficiency; Gastritis; Autoimmune Diseases; Metaplasia; Gastritis, Atrophic; Anemia, Pernicious
• Other Study ID Numbers: B-ER-110-440

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No