Editorial Open Access
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 28, 2012; 18(12): 1279-1285
Published online Mar 28, 2012. doi: 10.3748/wjg.v18.i12.1279
Risk for gastric neoplasias in patients with chronic atrophic gastritis: A critical reappraisal
Lucy Vannella, Edith Lahner, Bruno Annibale, Dipartimento Medico-Chirurgico di Scienze Cliniche, Tecnobiomediche e Medicina Traslazionale, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome 00189, Italy
Author contributions: Vannella L contributed to the acquisition, analysis and interpretation of data and wrote the article; Lahner E critically revised the manuscript; Annibale B contributed to conception and design of the study and to final revision of the manuscript; all authors approved the version to be published.
Correspondence to: Bruno Annibale, Professor, Dipartimento Medico-Chirurgico di Scienze Cliniche, Tecnobiomediche e Medicina Traslazionale, Sant’Andrea Hospital, School of Medicine, University Sapienza, Rome 00189, Italy. bruno.annibale@uniroma1.it
Telephone: +39-6-4455292 Fax: +39-6-4455292
Received: August 15, 2011
Revised: November 15, 2011
Accepted: November 22, 2011
Published online: March 28, 2012

Abstract

Chronic atrophic gastritis (CAG) is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue (non-metaplastic atrophy) or by glandular structures inappropriate for location (metaplastic atrophy). Epidemiological data suggest that CAG is associated with two different types of tumors: Intestinal-type gastric cancer (GC) and type I gastric carcinoid (TIGC). The pathophysiological mechanisms which lead to the development of these gastric tumors are different. It is accepted that a multistep process initiating from Helicobacter pylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The TIGC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of TIGC. Thus, several events occur in the gastric mucosa before the development of intestinal-type GC and/or TIGC and these take several years. Knowledge of CAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors associated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias.

Key Words: Chronic atrophic gastritis; Gastric neoplasia; Intestinal-type gastric cancer; Type I gastric carcinoid; Prevalence; Incidence; Risk factors



INTRODUCTION

Chronic atrophic gastritis (CAG) is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue (non-metaplastic atrophy) or by glandular structures inappropriate for location (metaplastic atrophy)[1]. Epidemiological data suggest that CAG is associated with two different types of tumors: Intestinal-type gastric cancer (GC) and type I gastric carcinoid (TIGC). The pathophysiological mechanisms which lead to the development of these gastric tumors are different. It is accepted that a multistep process initiating from Helicobacter pylori (H. pylori)-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia, and finally leads to the development of GC[2]. TIGC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like (ECL) cells with their hyperplasia leading to the development of TIGC[3-5].

Considering that several events occur in the gastric mucosa before the development of GC and/or of TIGC, and that these events take several years, the knowledge of CAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors associated with the progression of this condition to gastric neoplasias are important issues.

EPIDEMIOLOGY OF CHRONIC ATROPHIC GASTRITIS

A recent systematic review was performed with the aim of evaluating the CAG incidence in patients free of CAG at moment of inclusion in the study[6]. From published studies, the authors selected only 14 follow-up studies in which CAG diagnosis was carefully made by histology (12 studies) or by serum pepsinogen (PG) levels (2 studies). The CAG incidence rates ranged from 0% to 10.9% per year. This wide CAG incidence range is explained by the particular settings in which the CAG diagnoses were made. In fact, the lowest incidence rates (0%) were found in patients with reflux esophagitis[7] and in patients successfully treated for H. pylori infection[8]. The highest incidence rate was observed in an older study conducted on patients who underwent vagotomy because of ulcer disease[9]. Regarding H. pylori infection, the CAG incidence rate was higher in H. pylori-positive patients than in H. pylori-negative ones[7,10-13] and the meta-analysis on the association between H. pylori infection and CAG incidence presented a rate ratio of 5 (95% CI: 3.1-8.3).

The prevalence of CAG was evaluated by serological screening using surrogate markers of gastric function (PG I or PG I/PG II ratio) or by gastroscopy/histology. In the vast majority of cases, the serological and histological screenings were both made in a general population. Serological studies reported CAG prevalence rates between 3% and 7%, which were lower than those reported by histological ones. Studies on CAG prevalence subdivided on the basis of diagnostic tools used for CAG diagnosis (histology or serology) are shown in Table 1[14-23]. The observed differences between serological and histological studies could be explained by the fact that it is likely that symptomatic patients accepted more easily to undergo gastroscopy. Higher rates of CAG prevalence found in the Asian countries may be justified by the fact that these areas are at higher risk of GC and by the fact that the definition of CAG diagnosis may be different between Western and Asian countries. In studies reporting from Asian countries, CAG diagnosis included all atrophic lesions irrespective of the atrophy localization in the gastric mucosa (antrum and/or corpus); in the vast majority of the studies conducted in Western countries, CAG diagnosis included only patients with a corpus atrophic involvement such as corpus-atrophic gastritis or a multifocal atrophic gastritis (i.e., patchy areas of atrophic-metaplastic changes in the antral and corpus mucosa), because it is maintained that only corpus atrophic changes can lead to the development of gastric cancer.

Table 1 Prevalence of chronic atrophic gastritis.
AuthorYearCountryStudy typePatientsAge (yr)CAG (%)
Serology
Sipponen et al[14]2003FinlandGeneral population12 252 (men)51-655.2
Green et al[15]2005New ZealandGeneral population466> 656.7
Weck et al[16]2007GermanyGeneral population944450-746
Telaranta-Keerle et al[17]2010FinlandGeneral population425618-923.5
Histology
Oksanen et al[18]2000FinlandEndoscopic cohort20719-83131
Borch et al[19]2000SwedenGeneral Population50135-859.42
Asaka et al[20]2001JapanGeneral Population2455< 20 to > 7055.53
Redéen et al[21]2003SwedenGeneral Population48837-859
Storskrubb et al[22]2008SwedenGeneral Population97620-806.64
Zou et al[23]2011ChinaGeneral Population102218-8063.83
ATROPHIC GASTRITIS AND GASTRIC CANCER

Nowadays, GC represents one of the most challenging tumors due to the fact that its diagnosis is often late and, in the advanced stage, the therapeutic options are scarce with consequent high rate of mortality[24]. In fact, although a reduction of global incidence for this neoplasm is reported, it remains the second cause of cancer-related death. The knowledge of precursor lesions for the development of intestinal-type GC could contribute to anticipating GC diagnosis at an early stage when surgery or chemotherapy offers a better prognosis. Several studies have estimated the risk of GC in patients with CAG[25-33]. Although the vast majority of these were performed on small numbers of patients and were based on older histological classifications, the progression rate of CAG to GC fluctuates from 0% to 10% with annual incidence (person-year) lower than 1% (Table 2). It is interesting to observe that, although the incidence rate of CAG in patients with superficial gastritis is higher in populations with higher risk of GC (Table 1), the progression rate of CAG towards GC is similar irrespective of different geographic areas.

Table 2 Incidence of gastric cancer in patients with chronic atrophic gastritis or pernicious anemia.
AuthorYearCountryStudy typePatientsAge, median or range (yr)GCAnnual incidence of GC, person-year (%)
Patients with chronic atrophic gastritis
Walker et al[25]1971AustraliaRetrospective4040-644 (10)0.6
Ectors et al[26]1986United KingdomRetrospective225-3 (1.3)0.1
Tatsuta et al[27]1993JapanRetrospective654-22 (3.4)0.2
You et al[28]1999ChinaProspective2082135-6419 (0.9)0.2
Whiting et al[29]2002United KingdomProspective1042> 4012 (11.5)1.1
Dinis-Ribeiro et al[30]2004PortugalRetrospective1771-4 (2.2)0.7
Lahner et al[31]2005ItalyProspective10622-741 (0.9)0.1
de Vries et al[32]2008NetherlandsRetrospective84 072265.71035 (1.2)0.2
Vannella et al[33]2010ItalyRetrospective30018-783 (1)0.2
Patients with pernicious anemia
Borch et al[34]1986SwedenProspective61-00
Kokkola et al[35]1998FinlandProspective6220-732 (3.2)1.10
Sjöblom et al[36]1993FinlandProspective5627-782 (3.5)1.20
Armbrecht et al[37]1990United KingdomProspective2726-8100
Bresky et al[38]2003SpainProspective68-00
Ye et al[39]2003SwedenRetrospective21 26574.3177 (0.8)0.10
Vannella et al[33]2010ItalyRetrospective12923-742 (1.5)0.30

Some studies have attempted to identify risk factors linked with the progression of precancerous lesions (CAG or intestinal metaplasia) towards GC to select those patients who should undergo endoscopic surveillance.

Age

Age has been identified as a possible risk factor in several studies. In the study by Leung et al[40], H. pylori-positive patients with intestinal metaplasia were followed up for 5 years to evaluate the progression or the improvement of histological lesions after H. pylori eradication treatment compared with placebo. At multivariate analysis, the presence of age > 45 years showed an approximate two-fold increased risk of progression of intestinal metaplasia compared to younger subjects[40]. This same age limit had already been identified in a screening survey performed on 3386 subjects from a rural Chinese population that showed an approximate three-fold increased risk of progression to GC[28]. In a large cohort study, increasing age at initial diagnosis was associated with higher hazard ratio (HR) for the progression to GC (for age > 55 years, HR > 2.38)[32]. In a recent work, patients with CAG who were aged > 50 years at the moment of initial diagnosis presented HR = 8.8 for the progression to gastric neoplastic lesions[33].

Pernicious anemia

Although the vast majority of the older studies on CAG included patients with pernicious anemia, the risk of GC in this particular clinical setting seems to be generally low (Table 2). In fact, this clinical condition is often associated with corpus-restricted gastritis and, as a consequence, with less extensive atrophy in the gastric mucosa. In a recent study, the presence of atrophic pangastritis increased the risk of progression to gastric neoplastic lesions by 4.5 times, in keeping with previous works[33,41,42]. The apparent contrast between older and more recent works about pernicious anemia can be explained by the difficulty in comparing studies with methodological differences linked to adopted gastritis classification or small number series. It is interesting to underline the fact that studies on the relationship between pernicious anemia and GC are lacking in Asian countries where the risk of GC is higher, thus it remains to be established whether pernicious anemia has low prevalence in the Asian geographic area or if this condition is overlooked.

Intestinal metaplasia

Parallel with more extensive atrophy in the gastric mucosa, the extensive replacement of this by intestinal metaplasia is considered a hallmark of severity of CAG. In the literature, the intestinal metaplasia extension was widely related to a higher risk of GC[32,33,40,42]. In particular, type III intestinal metaplasia was associated with an increased risk of GC in some studies[43,44], but subsequent studies showed conflicting findings[45,46], thus the clinical utility of different subtyping of intestinal metaplasia is limited.

Helicobacter pylori

The role of H. pylori infection in progression from CAG to GC is controversial. In the Leung study, H. pylori-positive patients who had not undergone eradication therapy had a progression rate of intestinal metaplasia higher than cured patients[40]. However, in this study, the vast majority of patients had only a superficial gastritis at baseline and, after 5 years of follow-up, the rate of patients with intestinal metaplasia increased significantly. It is maintained that the effect of eradication therapy on the progression to GC in patients with precancerous lesions is limited. A previous large prospective study demonstrated that H. pylori eradication may be beneficial in arresting the progression to GC only in patients without CAG or intestinal metaplasia[47]. Two recent meta-analyses showed a beneficial long-term effect of H. pylori eradication therapy on atrophic gastritis, but not on intestinal metaplasia[48,49]. Up till now, although the possibility of histological improvement of CAG is accepted after H. pylori cure, the efficacy of H. pylori eradication in reducing GC incidence needs to be demonstrated.

ATROPHIC GASTRITIS AND TYPE I GASTRIC NEUROENDOCRINE TUMOR

TIGC derives from ECL cells which are localized in the gastric fundus and corpus. ECL cells are specialized in the secretion of histamine that, in turn, stimulates acid secretion by parietal cells[50]. Gastric carcinoids have been classified into three subgroups, type I to type III, with different outcomes[51-53]. Type I lesions are associated with atrophic gastritis and constitute up to 80% of all gastric carcinoids[54]. Gastrin, released by G-cells in the gastric antrum, stimulates the release of histamine and produces trophic effects upon ECL cells[3]. In CAG, the loss of appropriate glands in the body leads to achlorhydria, and the consequent chronic hypergastrinemia stimulates ECL hyperplasia and sometimes the development of TIGC[4,5].

The prevalence rate of TIGC in patients with CAG is reported to be between 1% and 12.5% in different studies[36,37,55-58]. The wide range of the prevalence rates of TIGC among several studies can be explained by different settings where patients were selected, such as type of hospital (secondary, tertiary center) or symptoms/signs of presentation. CAG can have a wide range of clinical presentations such as dyspepsia, iron deficiency anemia or pernicious anemia[59]. In particular, in a recent observational study in which the TIGC incidence and prevalence were evaluated, pernicious anemia was present in almost 50% of patients, while previous studies included exclusively patients with this condition[60].

Long-term observational studies assessing incidence of TIGC in CAG patients are scarce[35,56,61]. We recently followed up a cohort of CAG patients for 1463 person-years reporting an annual incidence rate (person-year) for TIGC of 0.4%[60]. An old study by Kokkola et al[35] reported an annual incidence of 2%, observing 8 new cases of TIGC in 416 patient-years. Sjöblom et al[61] studied 196 patients with pernicious anemia and after 1397 patient-years, 2 new cases of TIGC were reported in hospital registries among the initial group of patients. This figure should correspond to an annual incidence rate of 0.1%, but in this study only 70 patients (35.7%) underwent gastroscopy and the incidence rate can only be obtained indirectly. Furthermore, although there are small fluctuations in the reported incidence rates, only a small group of CAG patients develop TIGC showing that factors other than gastrin are necessary for the progression of ECL cells to TIGC.

Few studies have attempted to identify risk factors associated with the development of TIGC. In a recent work, we found higher baseline levels of gastrin and chromogranin A in CAG patients with TIGC compared to those without TIGC. However, all patients with CAG present high plasma values of chromogranin A[62] and gastrin, thus these markers have limited clinical utility because of low specificity[63].

An accepted risk factor for TIGC is the presence of ECL dysplasia, which is often associated with TIGC. This lesion is considered as the true gastric carcinoid precursor lesion and it can represent the sign of a concomitant carcinoid lesion[56,64]. CAG patients with a diagnosis of ECL cell dysplasia could benefit from a shorter endoscopic follow-up time to exclude concomitant TIGC lesions or to identify newly arisen lesions in the gastric mucosa.

Although TIGC lesions can also be present on flat mucosa, in the vast majority of cases they are associated with the presence of body polyps. In CAG patients, hyperplastic or adenomatous polyps are very common; however, the presence of body polyps increases the risk of having a TIGC[60]. Unfortunately, no feature of endoscopic appearance of the gastric polyps (size, number, sessile/pedunculated presentation) seems useful to differentiate histology of polyps, thus all polyps should be removed and histologically examined[65,66].

CONCLUSION

The risk of development of GC or TIGC appears higher in CAG patients with respect to the general population. In geographic areas with low risk of GC, a surveillance program for all CAG patients may be not cost-effective considering that the vast majority of CAG patients will not develop a gastric neoplasm[67]. A subset of CAG patients at higher risk for GC should be identified allowing the selection of those CAG patients in whom gastroscopic/histologic surveillance may be warranted. Recently, an international consensus developed evidence-based guidelines on the management of precancerous conditions and lesions of the stomach, recommending an endoscopic surveillance every 3 years after diagnosis in all patients with extensive atrophy and/or intestinal metaplasia in the antrum and corpus[68]. New systems for histopathological staging (OLGA, OLGIM) have been developed with the aim of combining pathological findings with the risk of GC for the patient and to identify a subgroup of those at higher risk[69,70]. The OLGA system includes gastritis grading and staging[69]. Grading measures the severity of acute and chronic inflammatory infiltrate in the antrum and body. Staging refers to the extent of atrophy with or without intestinal metaplasia. The OLGIM system is based on intestinal metaplasia which is considered a more reproducible histopathological diagnosis with respect to atrophy diagnosis. Further studies are necessary to validate these new classifications and to establish their real clinical value. Regarding TIGC, although risk factors for its development have not been identified, ENETS guidelines suggest an endoscopic follow-up every 6-12 mo after TIGC diagnosis. This interval allows the identification of recurrent lesions or new lesions (incidence-case) at an early stage when they can easily be removed by polypectomy without complications[71]. This approach seems safe for TIGC, a neoplasm with an excellent outcome[60,72].

Footnotes

Peer reviewers: Giovanni Maconi, Professor, L.Sacco University Hospital, Via G.B.Grassi, 74, Milan 20157, Italy; Kazunari Murakami, Professor, Department of General Medicine, Oita University, 1-1 Idaigaoka, Hasama 879-5593, Japan

S- Editor Gou SX L- Editor Logan S E- Editor Xiong L

References
1.  Rugge M, Correa P, Dixon MF, Fiocca R, Hattori T, Lechago J, Leandro G, Price AB, Sipponen P, Solcia E. Gastric mucosal atrophy: interobserver consistency using new criteria for classification and grading. Aliment Pharmacol Ther. 2002;16:1249-1259.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 246]  [Cited by in F6Publishing: 255]  [Article Influence: 11.6]  [Reference Citation Analysis (0)]
2.  Correa P. Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992;52:6735-6740.  [PubMed]  [DOI]  [Cited in This Article: ]
3.  Dockray GJ, Varro A, Dimaline R, Wang T. The gastrins: their production and biological activities. Annu Rev Physiol. 2001;63:119-139.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 271]  [Cited by in F6Publishing: 243]  [Article Influence: 10.6]  [Reference Citation Analysis (0)]
4.  Creutzfeldt W. The achlorhydria-carcinoid sequence: role of gastrin. Digestion. 1988;39:61-79.  [PubMed]  [DOI]  [Cited in This Article: ]
5.  Bordi C, D'Adda T, Azzoni C, Pilato FP, Caruana P. Hypergastrinemia and gastric enterochromaffin-like cells. Am J Surg Pathol. 1995;19 Suppl 1:S8-19.  [PubMed]  [DOI]  [Cited in This Article: ]
6.  Adamu MA, Weck MN, Gao L, Brenner H. Incidence of chronic atrophic gastritis: systematic review and meta-analysis of follow-up studies. Eur J Epidemiol. 2010;25:439-448.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 68]  [Cited by in F6Publishing: 81]  [Article Influence: 5.8]  [Reference Citation Analysis (0)]
7.  Kuipers EJ, Lundell L, Klinkenberg-Knol EC, Havu N, Festen HP, Liedman B, Lamers CB, Jansen JB, Dalenback J, Snel P. Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication. N Engl J Med. 1996;334:1018-1022.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 514]  [Cited by in F6Publishing: 480]  [Article Influence: 17.1]  [Reference Citation Analysis (0)]
8.  Tepes B, Kavcic B, Zaletel LK, Gubina M, Ihan A, Poljak M, Krizman I. Two- to four-year histological follow-up of gastric mucosa after Helicobacter pylori eradication. J Pathol. 1999;188:24-29.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  Jönsson KA, Ström M, Bodemar G, Norrby K. Histologic changes in the gastroduodenal mucosa after long-term medical treatment with cimetidine or parietal cell vagotomy in patients with juxtapyloric ulcer disease. Scand J Gastroenterol. 1988;23:433-441.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 42]  [Cited by in F6Publishing: 41]  [Article Influence: 1.1]  [Reference Citation Analysis (0)]
10.  Ozasa K, Kurata JH, Higashi A, Hayashi K, Inokuchi H, Miki K, Tada M, Kawai K, Watanabe Y. Helicobacter pylori infection and atrophic gastritis: a nested case-control study in a rural town in Japan. Dig Dis Sci. 1999;44:253-256.  [PubMed]  [DOI]  [Cited in This Article: ]
11.  Carter M, Katz DL, Haque S, DeLuca VA. Does acid suppression by antacids and H2 receptor antagonists increase the incidence of atrophic gastritis in patients with or without H. pylori gastritis? J Clin Gastroenterol. 1999;29:183-187.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 7]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
12.  Klinkenberg-Knol EC, Nelis F, Dent J, Snel P, Mitchell B, Prichard P, Lloyd D, Havu N, Frame MH, Romàn J. Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa. Gastroenterology. 2000;118:661-669.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 395]  [Cited by in F6Publishing: 409]  [Article Influence: 17.0]  [Reference Citation Analysis (0)]
13.  Lundell L, Havu N, Miettinen P, Myrvold HE, Wallin L, Julkunen R, Levander K, Hatlebakk JG, Liedman B, Lamm M. Changes of gastric mucosal architecture during long-term omeprazole therapy: results of a randomized clinical trial. Aliment Pharmacol Ther. 2006;23:639-647.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 59]  [Cited by in F6Publishing: 58]  [Article Influence: 3.2]  [Reference Citation Analysis (0)]
14.  Sipponen P, Laxén F, Huotari K, Härkönen M. Prevalence of low vitamin B12 and high homocysteine in serum in an elderly male population: association with atrophic gastritis and Helicobacter pylori infection. Scand J Gastroenterol. 2003;38:1209-1216.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 59]  [Cited by in F6Publishing: 64]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
15.  Green TJ, Venn BJ, Skeaff CM, Williams SM. Serum vitamin B12 concentrations and atrophic gastritis in older New Zealanders. Eur J Clin Nutr. 2005;59:205-210.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Weck MN, Stegmaier C, Rothenbacher D, Brenner H. Epidemiology of chronic atrophic gastritis: population-based study among 9444 older adults from Germany. Aliment Pharmacol Ther. 2007;26:879-887.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 51]  [Cited by in F6Publishing: 58]  [Article Influence: 3.4]  [Reference Citation Analysis (0)]
17.  Telaranta-Keerie A, Kara R, Paloheimo L, Härkönen M, Sipponen P. Prevalence of undiagnosed advanced atrophic corpus gastritis in Finland: an observational study among 4,256 volunteers without specific complaints. Scand J Gastroenterol. 2010;45:1036-1041.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 38]  [Cited by in F6Publishing: 39]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
18.  Oksanen A, Sipponen P, Miettinen A, Sarna S, Rautelin H. Evaluation of blood tests to predict normal gastric mucosa. Scand J Gastroenterol. 2000;35:791-795.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 26]  [Cited by in F6Publishing: 28]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
19.  Borch K, Jönsson KA, Petersson F, Redéen S, Mårdh S, Franzén LE. Prevalence of gastroduodenitis and Helicobacter pylori infection in a general population sample: relations to symptomatology and life-style. Dig Dis Sci. 2000;45:1322-1329.  [PubMed]  [DOI]  [Cited in This Article: ]
20.  Asaka M, Sugiyama T, Nobuta A, Kato M, Takeda H, Graham DY. Atrophic gastritis and intestinal metaplasia in Japan: results of a large multicenter study. Helicobacter. 2001;6:294-299.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 146]  [Cited by in F6Publishing: 152]  [Article Influence: 6.6]  [Reference Citation Analysis (0)]
21.  Redéen S, Petersson F, Jönsson KA, Borch K. Relationship of gastroscopic features to histological findings in gastritis and Helicobacter pylori infection in a general population sample. Endoscopy. 2003;35:946-950.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 107]  [Cited by in F6Publishing: 116]  [Article Influence: 5.5]  [Reference Citation Analysis (0)]
22.  Storskrubb T, Aro P, Ronkainen J, Sipponen P, Nyhlin H, Talley NJ, Engstrand L, Stolte M, Vieth M, Walker M, Agréus L. Serum biomarkers provide an accurate method for diagnosis of atrophic gastritis in a general population: The Kalixanda study. Scand J Gastroenterol. 2008;43:1448-1455.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 81]  [Cited by in F6Publishing: 78]  [Article Influence: 5.2]  [Reference Citation Analysis (0)]
23.  Zou D, He J, Ma X, Liu W, Chen J, Shi X, Ye P, Gong Y, Zhao Y, Wang R. Helicobacter pylori infection and gastritis: the Systematic Investigation of gastrointestinaL diseases in China (SILC). J Gastroenterol Hepatol. 2011;26:908-915.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 15]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
24.  Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893-2917.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11128]  [Cited by in F6Publishing: 11720]  [Article Influence: 901.5]  [Reference Citation Analysis (4)]
25.  Walker IR, Strickland RG, Ungar B, Mackay IR. Simple atrophic gastritis and gastric carcinoma. Gut. 1971;12:906-911.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 112]  [Cited by in F6Publishing: 113]  [Article Influence: 2.1]  [Reference Citation Analysis (0)]
26.  Ectors N, Dixon MF. The prognostic value of sulphomucin positive intestinal metaplasia in the development of gastric cancer. Histopathology. 1986;10:1271-1277.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 60]  [Cited by in F6Publishing: 63]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
27.  Tatsuta M, Iishi H, Nakaizumi A, Okuda S, Taniguchi H, Hiyama T, Tsukuma H, Oshima A. Fundal atrophic gastritis as a risk factor for gastric cancer. Int J Cancer. 1993;53:70-74.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 80]  [Cited by in F6Publishing: 71]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
28.  You WC, Li JY, Blot WJ, Chang YS, Jin ML, Gail MH, Zhang L, Liu WD, Ma JL, Hu YR. Evolution of precancerous lesions in a rural Chinese population at high risk of gastric cancer. Int J Cancer. 1999;83:615-619.  [PubMed]  [DOI]  [Cited in This Article: ]
29.  Whiting JL, Sigurdsson A, Rowlands DC, Hallissey MT, Fielding JW. The long term results of endoscopic surveillance of premalignant gastric lesions. Gut. 2002;50:378-381.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 183]  [Cited by in F6Publishing: 178]  [Article Influence: 8.1]  [Reference Citation Analysis (0)]
30.  Dinis-Ribeiro M, Lopes C, da Costa-Pereira A, Guilherme M, Barbosa J, Lomba-Viana H, Silva R, Moreira-Dias L. A follow up model for patients with atrophic chronic gastritis and intestinal metaplasia. J Clin Pathol. 2004;57:177-182.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 67]  [Cited by in F6Publishing: 76]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
31.  Lahner E, Bordi C, Cattaruzza MS, Iannoni C, Milione M, Delle Fave G, Annibale B. Long-term follow-up in atrophic body gastritis patients: atrophy and intestinal metaplasia are persistent lesions irrespective of Helicobacter pylori infection. Aliment Pharmacol Ther. 2005;22:471-481.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 53]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
32.  de Vries AC, van Grieken NC, Looman CW, Casparie MK, de Vries E, Meijer GA, Kuipers EJ. Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands. Gastroenterology. 2008;134:945-952.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 483]  [Cited by in F6Publishing: 533]  [Article Influence: 33.3]  [Reference Citation Analysis (0)]
33.  Vannella L, Lahner E, Osborn J, Bordi C, Miglione M, Delle Fave G, Annibale B. Risk factors for progression to gastric neoplastic lesions in patients with atrophic gastritis. Aliment Pharmacol Ther. 2010;31:1042-1050.  [PubMed]  [DOI]  [Cited in This Article: ]
34.  Borch K. Epidemiologic, clinicopathologic, and economic aspects of gastroscopic screening of patients with pernicious anemia. Scand J Gastroenterol. 1986;21:21-30.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 45]  [Cited by in F6Publishing: 48]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
35.  Kokkola A, Sjöblom SM, Haapiainen R, Sipponen P, Puolakkainen P, Järvinen H. The risk of gastric carcinoma and carcinoid tumours in patients with pernicious anaemia. A prospective follow-up study. Scand J Gastroenterol. 1998;33:88-92.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 145]  [Cited by in F6Publishing: 124]  [Article Influence: 4.8]  [Reference Citation Analysis (0)]
36.  Sjöblom SM, Sipponen P, Järvinen H. Gastroscopic follow up of pernicious anaemia patients. Gut. 1993;34:28-32.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 66]  [Cited by in F6Publishing: 71]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
37.  Armbrecht U, Stockbrügger RW, Rode J, Menon GG, Cotton PB. Development of gastric dysplasia in pernicious anaemia: a clinical and endoscopic follow up study of 80 patients. Gut. 1990;31:1105-1109.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 38]  [Cited by in F6Publishing: 41]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
38.  Bresky G, Mata A, Llach J, Ginis MA, Pellisi M, Soria MT, Fernandez-Esparrach G, Mondelo F, Bordas JM. Endoscopic findings in a biennial follow-up program in patients with pernicious anemia. Hepatogastroenterology. 2003;50:2264-2266.  [PubMed]  [DOI]  [Cited in This Article: ]
39.  Ye W, Nyrén O. Risk of cancers of the oesophagus and stomach by histology or subsite in patients hospitalised for pernicious anaemia. Gut. 2003;52:938-941.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 78]  [Cited by in F6Publishing: 69]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
40.  Leung WK, Lin SR, Ching JY, To KF, Ng EK, Chan FK, Lau JY, Sung JJ. Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication. Gut. 2004;53:1244-1249.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 277]  [Cited by in F6Publishing: 293]  [Article Influence: 14.7]  [Reference Citation Analysis (0)]
41.  Miehlke S, Hackelsberger A, Meining A, Hatz R, Lehn N, Malfertheiner P, Stolte M, Bayerdörffer E. Severe expression of corpus gastritis is characteristic in gastric cancer patients infected with Helicobacter pylori. Br J Cancer. 1998;78:263-266.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 69]  [Cited by in F6Publishing: 74]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
42.  Cassaro M, Rugge M, Gutierrez O, Leandro G, Graham DY, Genta RM. Topographic patterns of intestinal metaplasia and gastric cancer. Am J Gastroenterol. 2000;95:1431-1438.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 183]  [Cited by in F6Publishing: 176]  [Article Influence: 7.3]  [Reference Citation Analysis (0)]
43.  Rokkas T, Filipe MI, Sladen GE. Detection of an increased incidence of early gastric cancer in patients with intestinal metaplasia type III who are closely followed up. Gut. 1991;32:1110-1113.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 164]  [Cited by in F6Publishing: 163]  [Article Influence: 4.9]  [Reference Citation Analysis (0)]
44.  Silva S, Filipe MI, Pinho A. Variants of intestinal metaplasia in the evolution of chronic atrophic gastritis and gastric ulcer. A follow up study. Gut. 1990;31:1097-1104.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 56]  [Cited by in F6Publishing: 68]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
45.  Conchillo JM, Houben G, de Bruïne A, Stockbrügger R. Is type III intestinal metaplasia an obligatory precancerous lesion in intestinal-type gastric carcinoma? Eur J Cancer Prev. 2001;10:307-312.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 31]  [Cited by in F6Publishing: 32]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
46.  Ramesar KC, Sanders DS, Hopwood D. Limited value of type III intestinal metaplasia in predicting risk of gastric carcinoma. J Clin Pathol. 1987;40:1287-1290.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 46]  [Cited by in F6Publishing: 55]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
47.  Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, Lai KC, Hu WH, Yuen ST, Leung SY. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004;291:187-194.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1015]  [Cited by in F6Publishing: 995]  [Article Influence: 49.8]  [Reference Citation Analysis (0)]
48.  Rokkas T, Pistiolas D, Sechopoulos P, Robotis I, Margantinis G. The long-term impact of Helicobacter pylori eradication on gastric histology: a systematic review and meta-analysis. Helicobacter. 2007;12 Suppl 2:32-38.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 144]  [Cited by in F6Publishing: 159]  [Article Influence: 9.4]  [Reference Citation Analysis (0)]
49.  Wang J, Xu L, Shi R, Huang X, Li SW, Huang Z, Zhang G. Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion. 2011;83:253-260.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 150]  [Cited by in F6Publishing: 151]  [Article Influence: 11.6]  [Reference Citation Analysis (0)]
50.  Burkitt MD, Pritchard DM. Review article: Pathogenesis and management of gastric carcinoid tumours. Aliment Pharmacol Ther. 2006;24:1305-1320.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 113]  [Cited by in F6Publishing: 106]  [Article Influence: 5.9]  [Reference Citation Analysis (0)]
51.  Rindi G, Bordi C, Rappel S, La Rosa S, Stolte M, Solcia E. Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology, and behavior. World J Surg. 1996;20:168-172.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 293]  [Cited by in F6Publishing: 259]  [Article Influence: 9.3]  [Reference Citation Analysis (0)]
52.  Rindi G, Luinetti O, Cornaggia M, Capella C, Solcia E. Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology. 1993;104:994-1006.  [PubMed]  [DOI]  [Cited in This Article: ]
53.  Mulkeen A, Cha C. Gastric carcinoid. Curr Opin Oncol. 2005;17:1-6.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 22]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
54.  Bordi C, D'Adda T, Azzoni C, Ferraro G. Pathogenesis of ECL cell tumors in humans. Yale J Biol Med. 1998;71:273-284.  [PubMed]  [DOI]  [Cited in This Article: ]
55.  Lehtola J, Karttunen T, Krekelä I, Niemelä S, Räsänen O. Gastric carcinoids with minimal or no macroscopic lesion in patients with pernicious anemia. Hepatogastroenterology. 1985;32:72-76.  [PubMed]  [DOI]  [Cited in This Article: ]
56.  Annibale B, Azzoni C, Corleto VD, di Giulio E, Caruana P, D'Ambra G, Bordi C, Delle Fave G. Atrophic body gastritis patients with enterochromaffin-like cell dysplasia are at increased risk for the development of type I gastric carcinoid. Eur J Gastroenterol Hepatol. 2001;13:1449-1456.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 82]  [Cited by in F6Publishing: 77]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
57.  Stockbrügger RW, Menon GG, Beilby JO, Mason RR, Cotton PB. Gastroscopic screening in 80 patients with pernicious anaemia. Gut. 1983;24:1141-1147.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 88]  [Cited by in F6Publishing: 81]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
58.  Borch K, Renvall H, Kullman E, Wilander E. Gastric carcinoid associated with the syndrome of hypergastrinemic atrophic gastritis. A prospective analysis of 11 cases. Am J Surg Pathol. 1987;11:435-444.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 56]  [Cited by in F6Publishing: 58]  [Article Influence: 1.6]  [Reference Citation Analysis (0)]
59.  Marignani M, Delle Fave G, Mecarocci S, Bordi C, Angeletti S, D'Ambra G, Aprile MR, Corleto VD, Monarca B, Annibale B. High prevalence of atrophic body gastritis in patients with unexplained microcytic and macrocytic anemia: a prospective screening study. Am J Gastroenterol. 1999;94:766-772.  [PubMed]  [DOI]  [Cited in This Article: ]
60.  Vannella L, Sbrozzi-Vanni A, Lahner E, Bordi C, Pilozzi E, Corleto VD, Osborn JF, Delle Fave G, Annibale B. Development of type I gastric carcinoid in patients with chronic atrophic gastritis. Aliment Pharmacol Ther. 2011;33:1361-1369.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 71]  [Cited by in F6Publishing: 74]  [Article Influence: 5.7]  [Reference Citation Analysis (0)]
61.  Sjöblom SM, Sipponen P, Miettinen M, Karonen SL, Jrvinen HJ. Gastroscopic screening for gastric carcinoids and carcinoma in pernicious anemia. Endoscopy. 1988;20:52-56.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 73]  [Cited by in F6Publishing: 73]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
62.  Borch K, Stridsberg M, Burman P, Rehfeld JF. Basal chromogranin A and gastrin concentrations in circulation correlate to endocrine cell proliferation in type-A gastritis. Scand J Gastroenterol. 1997;32:198-202.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 64]  [Cited by in F6Publishing: 66]  [Article Influence: 2.4]  [Reference Citation Analysis (0)]
63.  Peracchi M, Gebbia C, Basilisco G, Quatrini M, Tarantino C, Vescarelli C, Massironi S, Conte D. Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis, enterochromaffin-like cell lesions and gastric carcinoids. Eur J Endocrinol. 2005;152:443-448.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 77]  [Cited by in F6Publishing: 72]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
64.  Solcia E, Bordi C, Creutzfeldt W, Dayal Y, Dayan AD, Falkmer S, Grimelius L, Havu N. Histopathological classification of nonantral gastric endocrine growths in man. Digestion. 1988;41:185-200.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 253]  [Cited by in F6Publishing: 258]  [Article Influence: 7.2]  [Reference Citation Analysis (0)]
65.  Carmack SW, Genta RM, Graham DY, Lauwers GY. Management of gastric polyps: a pathology-based guide for gastroenterologists. Nat Rev Gastroenterol Hepatol. 2009;6:331-341.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 100]  [Cited by in F6Publishing: 101]  [Article Influence: 6.7]  [Reference Citation Analysis (0)]
66.  Goddard AF, Badreldin R, Pritchard DM, Walker MM, Warren B. The management of gastric polyps. Gut. 2010;59:1270-1276.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 151]  [Cited by in F6Publishing: 192]  [Article Influence: 13.7]  [Reference Citation Analysis (0)]
67.  Correa P, Piazuelo MB. The gastric precancerous cascade. J Dig Dis. 2012;13:2-9.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 355]  [Cited by in F6Publishing: 454]  [Article Influence: 37.8]  [Reference Citation Analysis (0)]
68.  Dinis-Ribeiro M, Areia M, de Vries AC, Marcos-Pinto R, Monteiro-Soares M, O'Connor A, Pereira C, Pimentel-Nunes P, Correia R, Ensari A. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy. 2012;44:74-94.  [PubMed]  [DOI]  [Cited in This Article: ]
69.  Rugge M, Meggio A, Pennelli G, Piscioli F, Giacomelli L, De Pretis G, Graham DY. Gastritis staging in clinical practice: the OLGA staging system. Gut. 2007;56:631-636.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 290]  [Cited by in F6Publishing: 318]  [Article Influence: 18.7]  [Reference Citation Analysis (0)]
70.  Capelle LG, de Vries AC, Haringsma J, Ter Borg F, de Vries RA, Bruno MJ, van Dekken H, Meijer J, van Grieken NC, Kuipers EJ. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71:1150-1158.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 301]  [Cited by in F6Publishing: 339]  [Article Influence: 24.2]  [Reference Citation Analysis (0)]
71.  Arnold R, Chen YJ, Costa F, Falconi M, Gross D, Grossman AB, Hyrdel R, Kos-Kudła B, Salazar R, Plöckinger U. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: follow-up and documentation. Neuroendocrinology. 2009;90:227-233.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 97]  [Cited by in F6Publishing: 88]  [Article Influence: 5.9]  [Reference Citation Analysis (0)]
72.  Borch K, Ahrén B, Ahlman H, Falkmer S, Granérus G, Grimelius L. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg. 2005;242:64-73.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 203]  [Cited by in F6Publishing: 180]  [Article Influence: 9.5]  [Reference Citation Analysis (0)]