ORIGINAL ARTICLE
Characteristics of the Gastric Mucosa in Patients With Intestinal Metaplasia Robert M. Genta, MD*w and Amnon Sonnenberg, MD, MSz
Abstract: Gastric intestinal metaplasia (IM) occurs in response to different injuries, some of which involve increased risk for gastric cancer, whereas others may not. The background in which IM arises has not been systematically investigated. This study was designed to determine the relative prevalence of the histopathologic conditions of the gastric mucosa associated with IM in a large cohort. We extracted from a database patients who had undergone esophagogastroduodenoscopy with gastric biopsies between January 2008 and December 2013 in endoscopy centers throughout the United States. For each subject we recorded demographic, clinical, and histopathologic information. We stratified patients according to the presence of IM and compared the prevalence of Helicobacter pylori infection, reactive gastropathy, minimal inflammatory and gastropathy changes, mucosal atrophy, gastric polyps, cancer, and lymphoma in the 2 groups. IM, present in 8.4% of the 810,821 unique patients, increased with age and was more common in male than in female individuals. Compared with other Americans, East Asian ancestry was associated with a 5-fold risk for IM. Helicobacter gastritis and its sequelae were present in 42.2% of patients with IM, and reactive gastropathy in 17.3%. In >50% of patients under the age of 30 and in 26% of older adults, foci of IM occurred in an almost normal gastric mucosa. Thus, approximately half of the patients with IM had no histopathologic evidence of current or previous Helicobacter gastritis, whereas almost one fifth had a background of reactive gastropathy. Longitudinal studies are needed to determine the relative risk for gastric cancer in patients with IM associated and not with Helicobacter infection. Key Words: gastric intestinal metaplasia, preneoplastic lesions, Helicobacter, H. pylori, gastritis, reactive gastropathy, gastric cancer (Am J Surg Pathol 2015;39:700–704)
From the *Miraca Life Sciences Research Institute, Irving, TX; wDepartments of Pathology and Medicine (Gastroenterology), VA Medical Center, University of Southwestern Medical Center, Dallas, TX; and zDepartment of Medicine (Gastroenterology), VA Medical Center, Oregon Health & Science University, Portland, OR. Conflicts of Interest and Source of Funding: R.M.G. is an employee of Miraca Life Sciences, Irving, TX. For the remaining author none were declared. Correspondence: Robert M. Genta, MD, Miraca Life Sciences, 6655 North MacArthur Blvd, Irving, TX 75039 (e-mail: robert.genta@ utsouthwestern.edu). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
700 | www.ajsp.com
I
ntestinal metaplasia (IM) of the gastric mucosa is considered a preneoplastic lesion, even if the risk of developing gastric cancer in an individual with IM is extremely low and is related to the condition that induced the metaplastic change, its extent and histologic subtype, the patient’s ethnicity, diet, and Helicobacter status.1 As no major national gastroenterology society has issued specific guidelines on how to interpret a diagnosis of IM or how to follow up a patient with this finding,2 gastroenterologists must rely exclusively on their clinical judgment. Questions regarding the need for and the frequency of follow-up are often asked of the pathologist, who is equally unequipped to provide evidence-based management advice. Because of this anarchic approach, a histopathologic diagnosis of gastric IM is met with a wide range of responses, from indifference to unnecessary surveillance. Yet, some details about the extension of the metaplastic changes and the background in which they occur could help make more informed management decisions. In addition to H. pylori infection, which is generally viewed as the most important cause of IM,3 other etiologies frequently invoked but rarely proved have been suggested, including high salt intake,4 consumption of smoked and canned foods,5 tobacco smoking,6 alcohol consumption,7 and chronic bile reflux.8 Although smoking may cause a small increase in the risk for gastric cancer, particularly in H. pylori-infected subjects, there is no direct evidence that it causes or significantly worsens non-Helicobacter gastritis.9 Bile reflux is a cause of reactive gastropathy, but this histopathologic finding is now so common that it is unlikely that all or even most cases can be related to the chronic exposure of the gastric mucosa to bile.10 Thus, with the exception of Helicobacter gastritis, we do not know what causes IM of the stomach. The question is relevant to management, as an association with either active Helicobacter gastritis or chronic gastritis (most often a sequela of previous Helicobacter infection)11–13 could have a more ominous significance than a small focus of metaplasia arising in either reactive or almost normal gastric epithelium. Yet, no study has attempted to determine the relative prevalence of the most common conditions of the gastric mucosa that accompany IM. This study, which includes >800,000 patients who had gastric biopsies diagnosed by the same group of pathologists, was designed to fill this gap. This information may be useful in making management decisions; it may also serve as an initial step in the quest to determine causes and relevance of IM not associated with H. pylori gastritis. Am J Surg Pathol
Volume 39, Number 5, May 2015
Am J Surg Pathol
Volume 39, Number 5, May 2015
PATIENTS AND METHODS Study Setting and Data Source We used a large national pathology database of subjects who underwent esophagogastroduodenoscopy (EGD) with gastric biopsies between January 2008 and December 2013 in endoscopy centers distributed throughout the United States and whose mucosal biopsy specimens were evaluated and reported by a single group of histopathologists. The database includes demographic, clinical, and endoscopic data (extracted from an abridged version of the electronic medical records that are transmitted with the biopsy specimens) and all histopathologic diagnoses and comments. The group consists of 35 pathologists with subspecialty training in gastrointestinal pathology who practice in the same environment. Consensus is maintained and updated through daily multiheaded microscope conferences, frequent didactic conferences, a journal club, a terminology/criteria review committee, and ongoing comprehensive quality assurance review. The Miraca Life Sciences internal review board determined that this study would be entirely performed by collecting existing data, documents, and reports and that the information would be recorded in such a manner that subjects cannot be identified. Therefore, pursuant to 45 CFR 46, section 101 b(4), the study was exempt from 45 CFR 46 regulations, and no informed consent was necessary.
Gastric Mucosa With Intestinal Metaplasia
peremia of the lamina propria, erosions, and smooth muscle proliferation.17 Biopsy sites (corpus or antrum) were assessed according to the endoscopist definition, as previously detailed; thus, a specimen designated as antrum was assigned to the site “antrum” even if the pathologist determined it to consist of oxyntic (corpus) mucosa.18
Data Analysis and Statistics The statistical analyses focused on the comparison of cases (patients with IM) and controls (patients without IM). The mean ages and their standard deviations among case and control groups were compared using a t test. The varying distributions of clinical and histopathologic findings among case and control groups were described in terms of odds ratios (OR) and their 95% confidence intervals (CI).
RESULTS Demographics There were 810,821 individual eligible patients (median age 57 y, 37.1% female). Gastric IM was present in 68,204 patients (8.4%), with a median age of 64 years, 40,314 of whom were male (59.1%). Thus, patients with IM were older than those without metaplasia and were slightly more likely to be male (OR 1.04; 95% CI, 1.021.05). Figure 1 shows the prevalence of IM in patients stratified by age group.
Study Design
Ethnicity
All unique patients who had gastric biopsies during the designated study period were extracted from the database using codes, natural language, and Boolean queries; patients’ demographic, clinical, and histopathologic data were recorded. If a patient had multiple EGDs, only data from the chronologically first procedure were included. Patients with a history of upper gastrointestinal surgery were excluded.
Ninety-one percent of the patients in the database were Americans of either European or African ancestry; 5.9% were Hispanics (persons of Mexican, Central American, or South American origin), and 2.5% were of East Asian ancestry (China, Korea, Japan, and Southeast Asian countries). As depicted in Table 1, East Asians were overrepresented among patients with IM, accounting for >9% of subjects with this finding.
Histopathologic Criteria
Gastric Mucosal Background
More than 90% of gastric biopsies in this laboratory are routinely stained with a specific anti-Helicobacter monoclonal immunochemical stain (Cell Marque, CA); the remainder are stained with a modified Giemsa stain (HP Blue, Anatech, Ltd., Battle Creek, MI); all specimens are also stained with Alcian blue–periodic acid-Schiff to enhance the detection of IM. Gastric biopsy specimens are diagnosed following the guidelines of the Updated Sydney System14 and the 2002 International Atrophy Consensus.15 OLGA scores are not routinely used, but the OLGA guidelines for the evaluation of atrophy and metaplasia are followed.16 Briefly, Helicobacter infection was diagnosed when the characteristic curved organisms were visualized in a gastric biopsy specimen. IM was diagnosed in the presence of goblet cells in the gastric mucosa. Chronic inactive gastritis was diagnosed when the lamina propria contained dense populations of lymphocytes and plasma cells.14 The diagnosis of reactive gastropathy was based on the 2006 guidelines, which include various combinations of foveolar hyperplasia, regenerative changes in the surface epithelium, edema or hy-
Table 2 shows the prevalence of H. pylori gastritis, Helicobacter-negative chronic active gastritis, chronic inactive gastritis, reactive gastropathy, atrophy, and mild or minimal inflammatory or reactive changes in patients with
Copyright
r
2015 Wolters Kluwer Health, Inc. All rights reserved.
FIGURE 1. Prevalence of IM in patients stratified by age group. www.ajsp.com |
701
Genta and Sonnenberg
Am J Surg Pathol
Volume 39, Number 5, May 2015
TABLE 1. Ethnic Distribution of Patients With IM Ethnicity
Total (n = 810,821) (n [%])
Other American Hispanic East Asian Other/Unknown
737,822 47,701 20,600 4698
Patients With IM (n = 68,204) (n [%])
(91.0) (5.9) (2.5) (0.6)
55,924 5777 6172 432
(82.0) (8.3) (9.1) (0.6)
OR (95% CI) 1 1.65 (1.60-1.70) 5.21 (5.05-5.38) 1.10 (0.99-1.21)
Other Americans were persons of either European or African ancestry; East Asians were overrepresented among patients with IM, accounting for >9% of subjects with this finding even as they constituted only 2.5% of the study population.
and without IM stratified by age group. In Figure 2, we have depicted the proportion of patients in each age group with one of the main categories of mucosal background. In this depiction, the category H. pylori-related includes both active infection and chronic inactive gastritis, a condition due to past H. pylori infection in the vast majority of cases.11–13
Associated Lesions Table 3 shows the prevalence of the most common gastric growths (benign polyps, adenocarcinoma, and lymphoma) in patients with and without concurrent IM. Fundic gland polyps were almost 3 times more common in patients without than in patients with IM, confirming the propensity of these polyps to arise in healthy gastric mucosa.19–21 All other polyps, as well as lymphoma and adenocarcinoma, were more frequently found in the presence of IM. Gastric ulcers were unrelated to IM (OR 1.06; 95% CI, 0.98-1.16).
Prevalence of IM by Location Of the 810,821 patients, 614,093 (75.7%) had biopsies from the antrum; among these, 56,494 had IM (9.2%); 337,817 (41.7%) had biopsies from the corpus, with 26,586 cases of IM (7.9%). Among those who had biopsies exclusively from the corpus (80,424 patients, or 9.9%), only 3912 (4.9%) had IM. These latter patients were 5.5% East Asians, who represented only 2.5% of the study population; of the 1375 East Asians who had cor-
pus biopsies only, 215 (15.6%) had IM, in contrast to 3697 (4.7%) of the 79,049 non-East Asians who had corpus biopsies only (OR 3.81; 95% CI, 3.28-4.43).
Clinical Presentation To determine whether patients with IM were more or less likely to present with certain clinical manifestations, and whether the background on which the metaplasia occurred was associated with certain presentation, we analyzed the frequency of the most common complaints stated as the reason for the EGD. Compared with patients without IM, those with IM were more likely to present with dyspepsia (9.6% vs. 7.8%; OR 1.26; 95% CI, 1.23-1.30; P < 0.001) and with anemia (9.9% vs. 7.4%; OR 1.37; 95% CI, 1.34-1.41; P < 0.001). In contrast, both vomiting (10.3% vs. 8.3%; OR 0.79; 95% CI, 0.77-0.82; P < 0.001) and gastroesophageal reflux (47.0% vs. 43.7%; OR 0.88; 95% CI, 0.86-0.89) were more common in subjects without metaplasia. Epigastric pain was reported equally in the 2 groups. Among patients with IM, anemia was present in 21.8% of patients who had concurrent extensive atrophy, likely reflecting the presence of autoimmune gastritis but in only 8.0% to 11.8% of patients with other histopathologic associations. These patients also had the lowest reported rates of gastroesophageal reflux (32.7%) compared with an average of 43.7% for the entire group.
TABLE 2. Relative Prevalence of H. pylori Gastritis (H. pylori+), Helicobacter-negative Chronic Active Gastritis (Hp-Neg-CAG), Chronic Inactive Gastritis With No H. pylori (CIG), Reactive Gastropathy (RG), Atrophy, and Mild or Minimal Inflammatory or Reactive Changes in Patients With (Top) and Without (Bottom) IM Stratified By Age Group Age Group IM (+) < 18 18-30 31-45 46-60 61-75 >75 IM () < 18 18-30 31-45 46-60 61-75 >75
Total
H. pylori (+) (%)
Hp-Neg-CAG (%)
CIG (%)
RG (%)
Atrophy (%)
Mild Changes (%)
184 1674 6588 19,582 26,448 13,728
1.7 10.9 20.0 23.4 21.0 18.0
3.3 2.5 2.3 2.2 2.4 2.9
13.3 14.9 15.2 14.8 17.5 20.6
12.7 17.9 17.5 17.1 17.0 18.1
0.55 1.13 2.41 3.02 5.23 6.61
53.0 38.0 30.0 27.4 26.0 23.6
9202 58,870 131,979 242,160 220,752 79,654
3.6 8.4 11.7 10.6 8.9 8.5
2.2 1.7 1.5 1.4 1.4 1.8
5.0 5.7 5.3 4.4 4.5 5.7
5.1 11.7 14.0 16.8 20.4 22.0
0.01 0.03 0.08 0.13 0.30 0.58
39.2 22.5 17.0 15.4 15.5 15.2
In each group, we have depicted the percentage of patients with each condition.
702 | www.ajsp.com
Copyright
r
2015 Wolters Kluwer Health, Inc. All rights reserved.
Am J Surg Pathol
Volume 39, Number 5, May 2015
FIGURE 2. Proportion of patients in each age group with one of the main categories of mucosal background phenotype. In this depiction, the category “H. pylori-related” includes both active infection and chronic inactive gastritis, a condition believed to be related to past H. pylori infection in the vast majority of cases.
DISCUSSION In this study of >800,000 subjects who had gastric biopsies in endoscopy practices throughout the United States, 8.4% had IM. As expected, the prevalence of IM increased with age, from
Characteristics of the Gastric Mucosa in Patients With Intestinal Metaplasia Robert M. Genta, MD*w and Amnon Sonnenberg, MD, MSz
Abstract: Gastric intestinal metaplasia (IM) occurs in response to different injuries, some of which involve increased risk for gastric cancer, whereas others may not. The background in which IM arises has not been systematically investigated. This study was designed to determine the relative prevalence of the histopathologic conditions of the gastric mucosa associated with IM in a large cohort. We extracted from a database patients who had undergone esophagogastroduodenoscopy with gastric biopsies between January 2008 and December 2013 in endoscopy centers throughout the United States. For each subject we recorded demographic, clinical, and histopathologic information. We stratified patients according to the presence of IM and compared the prevalence of Helicobacter pylori infection, reactive gastropathy, minimal inflammatory and gastropathy changes, mucosal atrophy, gastric polyps, cancer, and lymphoma in the 2 groups. IM, present in 8.4% of the 810,821 unique patients, increased with age and was more common in male than in female individuals. Compared with other Americans, East Asian ancestry was associated with a 5-fold risk for IM. Helicobacter gastritis and its sequelae were present in 42.2% of patients with IM, and reactive gastropathy in 17.3%. In >50% of patients under the age of 30 and in 26% of older adults, foci of IM occurred in an almost normal gastric mucosa. Thus, approximately half of the patients with IM had no histopathologic evidence of current or previous Helicobacter gastritis, whereas almost one fifth had a background of reactive gastropathy. Longitudinal studies are needed to determine the relative risk for gastric cancer in patients with IM associated and not with Helicobacter infection. Key Words: gastric intestinal metaplasia, preneoplastic lesions, Helicobacter, H. pylori, gastritis, reactive gastropathy, gastric cancer (Am J Surg Pathol 2015;39:700–704)
From the *Miraca Life Sciences Research Institute, Irving, TX; wDepartments of Pathology and Medicine (Gastroenterology), VA Medical Center, University of Southwestern Medical Center, Dallas, TX; and zDepartment of Medicine (Gastroenterology), VA Medical Center, Oregon Health & Science University, Portland, OR. Conflicts of Interest and Source of Funding: R.M.G. is an employee of Miraca Life Sciences, Irving, TX. For the remaining author none were declared. Correspondence: Robert M. Genta, MD, Miraca Life Sciences, 6655 North MacArthur Blvd, Irving, TX 75039 (e-mail: robert.genta@ utsouthwestern.edu). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
700 | www.ajsp.com
I
ntestinal metaplasia (IM) of the gastric mucosa is considered a preneoplastic lesion, even if the risk of developing gastric cancer in an individual with IM is extremely low and is related to the condition that induced the metaplastic change, its extent and histologic subtype, the patient’s ethnicity, diet, and Helicobacter status.1 As no major national gastroenterology society has issued specific guidelines on how to interpret a diagnosis of IM or how to follow up a patient with this finding,2 gastroenterologists must rely exclusively on their clinical judgment. Questions regarding the need for and the frequency of follow-up are often asked of the pathologist, who is equally unequipped to provide evidence-based management advice. Because of this anarchic approach, a histopathologic diagnosis of gastric IM is met with a wide range of responses, from indifference to unnecessary surveillance. Yet, some details about the extension of the metaplastic changes and the background in which they occur could help make more informed management decisions. In addition to H. pylori infection, which is generally viewed as the most important cause of IM,3 other etiologies frequently invoked but rarely proved have been suggested, including high salt intake,4 consumption of smoked and canned foods,5 tobacco smoking,6 alcohol consumption,7 and chronic bile reflux.8 Although smoking may cause a small increase in the risk for gastric cancer, particularly in H. pylori-infected subjects, there is no direct evidence that it causes or significantly worsens non-Helicobacter gastritis.9 Bile reflux is a cause of reactive gastropathy, but this histopathologic finding is now so common that it is unlikely that all or even most cases can be related to the chronic exposure of the gastric mucosa to bile.10 Thus, with the exception of Helicobacter gastritis, we do not know what causes IM of the stomach. The question is relevant to management, as an association with either active Helicobacter gastritis or chronic gastritis (most often a sequela of previous Helicobacter infection)11–13 could have a more ominous significance than a small focus of metaplasia arising in either reactive or almost normal gastric epithelium. Yet, no study has attempted to determine the relative prevalence of the most common conditions of the gastric mucosa that accompany IM. This study, which includes >800,000 patients who had gastric biopsies diagnosed by the same group of pathologists, was designed to fill this gap. This information may be useful in making management decisions; it may also serve as an initial step in the quest to determine causes and relevance of IM not associated with H. pylori gastritis. Am J Surg Pathol
Volume 39, Number 5, May 2015
Am J Surg Pathol
Volume 39, Number 5, May 2015
PATIENTS AND METHODS Study Setting and Data Source We used a large national pathology database of subjects who underwent esophagogastroduodenoscopy (EGD) with gastric biopsies between January 2008 and December 2013 in endoscopy centers distributed throughout the United States and whose mucosal biopsy specimens were evaluated and reported by a single group of histopathologists. The database includes demographic, clinical, and endoscopic data (extracted from an abridged version of the electronic medical records that are transmitted with the biopsy specimens) and all histopathologic diagnoses and comments. The group consists of 35 pathologists with subspecialty training in gastrointestinal pathology who practice in the same environment. Consensus is maintained and updated through daily multiheaded microscope conferences, frequent didactic conferences, a journal club, a terminology/criteria review committee, and ongoing comprehensive quality assurance review. The Miraca Life Sciences internal review board determined that this study would be entirely performed by collecting existing data, documents, and reports and that the information would be recorded in such a manner that subjects cannot be identified. Therefore, pursuant to 45 CFR 46, section 101 b(4), the study was exempt from 45 CFR 46 regulations, and no informed consent was necessary.
Gastric Mucosa With Intestinal Metaplasia
peremia of the lamina propria, erosions, and smooth muscle proliferation.17 Biopsy sites (corpus or antrum) were assessed according to the endoscopist definition, as previously detailed; thus, a specimen designated as antrum was assigned to the site “antrum” even if the pathologist determined it to consist of oxyntic (corpus) mucosa.18
Data Analysis and Statistics The statistical analyses focused on the comparison of cases (patients with IM) and controls (patients without IM). The mean ages and their standard deviations among case and control groups were compared using a t test. The varying distributions of clinical and histopathologic findings among case and control groups were described in terms of odds ratios (OR) and their 95% confidence intervals (CI).
RESULTS Demographics There were 810,821 individual eligible patients (median age 57 y, 37.1% female). Gastric IM was present in 68,204 patients (8.4%), with a median age of 64 years, 40,314 of whom were male (59.1%). Thus, patients with IM were older than those without metaplasia and were slightly more likely to be male (OR 1.04; 95% CI, 1.021.05). Figure 1 shows the prevalence of IM in patients stratified by age group.
Study Design
Ethnicity
All unique patients who had gastric biopsies during the designated study period were extracted from the database using codes, natural language, and Boolean queries; patients’ demographic, clinical, and histopathologic data were recorded. If a patient had multiple EGDs, only data from the chronologically first procedure were included. Patients with a history of upper gastrointestinal surgery were excluded.
Ninety-one percent of the patients in the database were Americans of either European or African ancestry; 5.9% were Hispanics (persons of Mexican, Central American, or South American origin), and 2.5% were of East Asian ancestry (China, Korea, Japan, and Southeast Asian countries). As depicted in Table 1, East Asians were overrepresented among patients with IM, accounting for >9% of subjects with this finding.
Histopathologic Criteria
Gastric Mucosal Background
More than 90% of gastric biopsies in this laboratory are routinely stained with a specific anti-Helicobacter monoclonal immunochemical stain (Cell Marque, CA); the remainder are stained with a modified Giemsa stain (HP Blue, Anatech, Ltd., Battle Creek, MI); all specimens are also stained with Alcian blue–periodic acid-Schiff to enhance the detection of IM. Gastric biopsy specimens are diagnosed following the guidelines of the Updated Sydney System14 and the 2002 International Atrophy Consensus.15 OLGA scores are not routinely used, but the OLGA guidelines for the evaluation of atrophy and metaplasia are followed.16 Briefly, Helicobacter infection was diagnosed when the characteristic curved organisms were visualized in a gastric biopsy specimen. IM was diagnosed in the presence of goblet cells in the gastric mucosa. Chronic inactive gastritis was diagnosed when the lamina propria contained dense populations of lymphocytes and plasma cells.14 The diagnosis of reactive gastropathy was based on the 2006 guidelines, which include various combinations of foveolar hyperplasia, regenerative changes in the surface epithelium, edema or hy-
Table 2 shows the prevalence of H. pylori gastritis, Helicobacter-negative chronic active gastritis, chronic inactive gastritis, reactive gastropathy, atrophy, and mild or minimal inflammatory or reactive changes in patients with
Copyright
r
2015 Wolters Kluwer Health, Inc. All rights reserved.
FIGURE 1. Prevalence of IM in patients stratified by age group. www.ajsp.com |
701
Genta and Sonnenberg
Am J Surg Pathol
Volume 39, Number 5, May 2015
TABLE 1. Ethnic Distribution of Patients With IM Ethnicity
Total (n = 810,821) (n [%])
Other American Hispanic East Asian Other/Unknown
737,822 47,701 20,600 4698
Patients With IM (n = 68,204) (n [%])
(91.0) (5.9) (2.5) (0.6)
55,924 5777 6172 432
(82.0) (8.3) (9.1) (0.6)
OR (95% CI) 1 1.65 (1.60-1.70) 5.21 (5.05-5.38) 1.10 (0.99-1.21)
Other Americans were persons of either European or African ancestry; East Asians were overrepresented among patients with IM, accounting for >9% of subjects with this finding even as they constituted only 2.5% of the study population.
and without IM stratified by age group. In Figure 2, we have depicted the proportion of patients in each age group with one of the main categories of mucosal background. In this depiction, the category H. pylori-related includes both active infection and chronic inactive gastritis, a condition due to past H. pylori infection in the vast majority of cases.11–13
Associated Lesions Table 3 shows the prevalence of the most common gastric growths (benign polyps, adenocarcinoma, and lymphoma) in patients with and without concurrent IM. Fundic gland polyps were almost 3 times more common in patients without than in patients with IM, confirming the propensity of these polyps to arise in healthy gastric mucosa.19–21 All other polyps, as well as lymphoma and adenocarcinoma, were more frequently found in the presence of IM. Gastric ulcers were unrelated to IM (OR 1.06; 95% CI, 0.98-1.16).
Prevalence of IM by Location Of the 810,821 patients, 614,093 (75.7%) had biopsies from the antrum; among these, 56,494 had IM (9.2%); 337,817 (41.7%) had biopsies from the corpus, with 26,586 cases of IM (7.9%). Among those who had biopsies exclusively from the corpus (80,424 patients, or 9.9%), only 3912 (4.9%) had IM. These latter patients were 5.5% East Asians, who represented only 2.5% of the study population; of the 1375 East Asians who had cor-
pus biopsies only, 215 (15.6%) had IM, in contrast to 3697 (4.7%) of the 79,049 non-East Asians who had corpus biopsies only (OR 3.81; 95% CI, 3.28-4.43).
Clinical Presentation To determine whether patients with IM were more or less likely to present with certain clinical manifestations, and whether the background on which the metaplasia occurred was associated with certain presentation, we analyzed the frequency of the most common complaints stated as the reason for the EGD. Compared with patients without IM, those with IM were more likely to present with dyspepsia (9.6% vs. 7.8%; OR 1.26; 95% CI, 1.23-1.30; P < 0.001) and with anemia (9.9% vs. 7.4%; OR 1.37; 95% CI, 1.34-1.41; P < 0.001). In contrast, both vomiting (10.3% vs. 8.3%; OR 0.79; 95% CI, 0.77-0.82; P < 0.001) and gastroesophageal reflux (47.0% vs. 43.7%; OR 0.88; 95% CI, 0.86-0.89) were more common in subjects without metaplasia. Epigastric pain was reported equally in the 2 groups. Among patients with IM, anemia was present in 21.8% of patients who had concurrent extensive atrophy, likely reflecting the presence of autoimmune gastritis but in only 8.0% to 11.8% of patients with other histopathologic associations. These patients also had the lowest reported rates of gastroesophageal reflux (32.7%) compared with an average of 43.7% for the entire group.
TABLE 2. Relative Prevalence of H. pylori Gastritis (H. pylori+), Helicobacter-negative Chronic Active Gastritis (Hp-Neg-CAG), Chronic Inactive Gastritis With No H. pylori (CIG), Reactive Gastropathy (RG), Atrophy, and Mild or Minimal Inflammatory or Reactive Changes in Patients With (Top) and Without (Bottom) IM Stratified By Age Group Age Group IM (+) < 18 18-30 31-45 46-60 61-75 >75 IM () < 18 18-30 31-45 46-60 61-75 >75
Total
H. pylori (+) (%)
Hp-Neg-CAG (%)
CIG (%)
RG (%)
Atrophy (%)
Mild Changes (%)
184 1674 6588 19,582 26,448 13,728
1.7 10.9 20.0 23.4 21.0 18.0
3.3 2.5 2.3 2.2 2.4 2.9
13.3 14.9 15.2 14.8 17.5 20.6
12.7 17.9 17.5 17.1 17.0 18.1
0.55 1.13 2.41 3.02 5.23 6.61
53.0 38.0 30.0 27.4 26.0 23.6
9202 58,870 131,979 242,160 220,752 79,654
3.6 8.4 11.7 10.6 8.9 8.5
2.2 1.7 1.5 1.4 1.4 1.8
5.0 5.7 5.3 4.4 4.5 5.7
5.1 11.7 14.0 16.8 20.4 22.0
0.01 0.03 0.08 0.13 0.30 0.58
39.2 22.5 17.0 15.4 15.5 15.2
In each group, we have depicted the percentage of patients with each condition.
702 | www.ajsp.com
Copyright
r
2015 Wolters Kluwer Health, Inc. All rights reserved.
Am J Surg Pathol
Volume 39, Number 5, May 2015
FIGURE 2. Proportion of patients in each age group with one of the main categories of mucosal background phenotype. In this depiction, the category “H. pylori-related” includes both active infection and chronic inactive gastritis, a condition believed to be related to past H. pylori infection in the vast majority of cases.
DISCUSSION In this study of >800,000 subjects who had gastric biopsies in endoscopy practices throughout the United States, 8.4% had IM. As expected, the prevalence of IM increased with age, from
