Fundal atrophic gastritis as a risk factor for gastric cancer

Tatsuta, Masaharu; Nakaizumi, Akihiko; Okuda, Shujiro; Taniguchi, Haruo; Hiyama, Tomohiko; Tsukuma, Hideaki; Oshima, Akira

doi:10.1002/ijc.2910530114

Cited by 107 publications

(92 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several previous studies have demonstrated that the more advanced the stage of H. pylori-related CAG, the greater the cancer risk. 31,32,[40][41][42][43][44] Subjects with metaplastic gastritis, an end result of long-lasting H. pylori infection, are thus considered to be at particularly high risk of gastric cancer. Indeed, our previous longitudinal cohort study found that a group of middle-aged male subjects with metaplastic gastritis based on 2 serum tests-negative results for H. pylori antibody and positive results on the PG test-displayed an annual cancer incidence rate of about 0.87%, meaning that 1 cancer developed in 11.5 subjects during every 10-year period.…”

Section: Discussionmentioning

confidence: 99%

Preventive effects of etodolac, a selective cyclooxygenase‐2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori‐negative precancerous lesion

Yanaoka

Oka

Yoshimura

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

The present study investigated the preventive effects of etodolac, a selective cyclo-oxygenase (COX)-2 inhibitor, on metachronous cancer development after endoscopic resection of early gastric cancer. Among 267 early gastric cancer patients who underwent endoscopic resection, 47 patients with extensive metaplastic gastritis were selected based on endoscopic findings and our previously described criteria of serum pepsinogen (PG) test-positive and Helicobacter pylori antibodynegative conditions. Nonrandomized etodolac treatment (300 mg/day) was administered to 26 patients (Group A), while the remaining 21 patients were untreated (Group B). No significant differences in age, sex distribution, lifestyle factors or extent of metaplastic gastritis at baseline were identified between groups. Patients were followed for metachronous cancer development with endoscopy every 6-12 months for up to 5 years. Mean (standard deviation) follow-up period was 4.2 (0.9) years. In Group B, 5 cancers developed (incidence rate 5 6,266/100,000 person-years), significantly more than the 1 cancer in Group A (incidence rate 5 898/100,000 person-years; p < 0.05). Long-term etodolac treatment did not influence the extent of metaplastic gastritis as revealed by endoscopic findings or by serum PG levels, but effectively reduced metachronous cancer development in patients with extensive metaplastic gastritis. These results strongly suggest that chemoprevention of cancer in the metaplastic stomach is possible by controlling COX-2 expression.Helicobacter pylori triggers chronic inflammation of the infected stomach mucosa and is considered a major risk factor for gastric cancer and associated precursor lesions. 1 As postulated in the multistep model of gastric cancer development by Correa, long-lasting inflammation in the stomach mucosa leads to a cascade of molecular and morphological changes of stomach carcinogenesis, representing the gastritisatrophy-metaplasia-dysplasia-cancer sequence. 2 This sequence of stomach carcinogenesis is now widely accepted to be strongly promoted by H. pylori and is affected by a variety of genetic and environmental factors that may act synergistically. 3 H. pylori eradication thus appears to be the most promising approach for the control of gastric cancer development, and the results of animal experiments have revealed that eradication of H. pylori, especially in the early stage, is effective for preventing stomach carcinogenesis. [4][5][6] However, current data indicate that H. pylori eradication does not lead to complete eradication of gastric cancer 7-12 and might be effective only in subjects without chronic atrophic gastritis (CAG) together with intestinal metaplasia. 7,10 Moreover, patients with extensive intestinal metaplasia-that is, metaplastic gastritis-should not be treated with eradication

show abstract

Section: Discussionmentioning

confidence: 99%

Preventive effects of etodolac, a selective cyclooxygenase‐2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori‐negative precancerous lesion

Yanaoka

Oka

Yoshimura

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…As several studies dealing with endoscopic biopsies or chromoendoscopic testing have found that progression of chronic atrophic gastritis (CAG) increases the risk of cancer (Meister et al, 1979;Sipponen et al, 1985;Siurala et al, 1966;Tatsuta et al, 1993;Testoni et al, 1987), accurate and reliable evaluation of the extent of CAG is considered important for identifying individuals at high risk of cancer. However, accurately diagnosing the extent of CAG based on a few biopsy samples is difficult, because CAG together with intestinal metaplasia is a multifocal process.…”

Section: Serum Pg Testmentioning

confidence: 99%

Gastric Cancer Risk Diagnosis and Prevention in Subjects with Helicobacter pylori-related Chronic Gastritis

Enomoto¹,

Watanabe²,

Mukoubayashi³

et al. 2011

Gastritis and Gastric Cancer - New Insights in Gastroprotection, Diagnosis and Treatments

View full text Add to dashboard Cite

GC risk diagnosis based on the natural history of HP-related chronic gastritisNovel risk markers to identify GC high-risk groups based on a detailed natural history of HP-related chronic gastritis have long been awaited. In this section, we discuss the emerging significance of serum PG as a GC risk marker for more precise identification of GC high-risk groups. Serum PG testHP-related chronic gastritis usually starts in the antrum and expands proximally towards the body of the stomach (Kimura, 1972;Tatsuta et al., 1973). As several studies dealing with endoscopic biopsies or chromoendoscopic testing have found that progression of chronic atrophic gastritis (CAG) increases the risk of cancer (Meister et al., 1979;Sipponen et al., 1985;Siurala et al., 1966;Tatsuta et al., 1993;Testoni et al., 1987), accurate and reliable evaluation of the extent of CAG is considered important for identifying individuals at high risk of cancer. However, accurately diagnosing the extent of CAG based on a few biopsy samples is difficult, because CAG together with intestinal metaplasia is a multifocal process. Furthermore, histological diagnosis of gastric atrophy depends on subjective judgment without a gold standard (Guarner et al., 1999;Plummer et al., 1997). A test for CAG progression that is more convenient, free of discomfort or risk, economical and based on objective parameters is needed. PG is the inactive precursor of pepsin, a digestive enzyme specifically produced in the stomach. Immunologically, two isozymes exist (Kageyama, 2003). PGI is produced by chief cells and mucus neck cells of the gastric fundic glands. In contrast, PGII is produced not only by chief cells and mucus neck cells, but also in cardiac glands, pyloric glands, and Brunner's glands, with localization of producing cells in a wide range from the stomach to the duodenum. The majority of PG produced (about 99%) is secreted in the stomach lumen and functions as a digestive enzyme. However, a small amount of PG (about 1%) is also present in blood and can be evaluated by measuring serum PG levels. Serum PG levels are generally agreed to reflect the morphological and functional status of the stomach mucosa (Hirschowitz, 1957;Samloff et al., 1982). In an endoscopic study with Congo red staining, we have shown a strong correlation between an increase in glandular boundary, associated with diagnosed progression of gastric mucosal atrophy, and stepwise reductions in serum PGI levels and the PGI/PGII ratio ( Fig. 1) (Miki et al., 1987). In other words, by measuring serum PGI and the PGI/II ratio, the progression of CAG, which is involved in GC carcinogenesis, can be objectively evaluated (Ichinose et al., 2001). In addition, during HP infection, serum PGI and PGII increase, and the PG I/II ratio decreases. These findings are improved after eradication treatment (Furuta et al., 1997) and are useful as gastric mucosal inflammatory markers. Several criteria are used in the serum PG test. As criteria for GC screening, the combination of PGI ≤70 ng/ml and PGI/II ratio ≤3.0...

show abstract

“…CAG of the antrum and corpus are independent risk factors for gastric cancer, and the risk increases exponentially with the increase in grade and severity of atrophy (6,7). The progression of severe fundal atrophic gastritis to gastric cancer was documented to be ~3% from a total of 654 patients in the Japan (8). Annual surveillance of patients with IM or atrophic gastritis detected a higher percentage of gastric cancer, at 11% (9).…”

Section: Introductionmentioning

confidence: 99%

Serum pepsinogen and gastrin-17 as potential biomarkers for pre-malignant lesions in the gastric corpus

et al. 2017

View full text Add to dashboard Cite

Abstract. There is a lack of non-invasive screening modalities to diagnose chronic atrophic gastritis (CAG) and intestinal metaplasia (IM). Thus, the aim of the present study was to determine the sensitivity and specificity of serum pepsinogen I (PGI), PGI:II, the PGI:II ratio and gastrin-17 (G-17) in diagnosing CAG and IM, and the correlations between these serum biomarkers and pre-malignant gastric lesions. A cross-sectional study of 72 patients (82% of the calculated sample size) who underwent oesophageal-gastro-duodenoscopy for dyspepsia was performed in the present study. The mean age of the participants was 56.2±16.2 years. Serum PGI:I, PGI:II, G-17 and Helicobacter pylori antibody levels were measured by enzyme-linked immunosorbent assay. Median levels of PGI:I, PGI:II, the PGI:II ratio and G-17 for were 129.9 µg/l, 10.3 µg/l, 14.7 and 4.4 pmol/l, respectively. Subjects with corpus CAG/IM exhibited a significantly lower PGI:II ratio (7.2) compared with the control group (15.7; P<0.001). Histological CAG and IM correlated well with the serum PGI:II ratio (r=-0.417; P<0.001). The cut-off value of the PGI:II ratio of ≤10.0 demonstrated high sensitivity (83.3%), specificity (77.9%) and area under the receiver operating characteristic curve of 0.902 in detecting the two conditions. However, the sensitivity was particularly low at a ratio of ≤3.0. The serum PGI:II ratio is a sensitive and specific marker to diagnose corpus CAG/IM, but at a high cut-off value. This ratio may potentially be used as an outpatient, non-invasive biomarker for detecting corpus CAG/IM.

show abstract

Fundal atrophic gastritis as a risk factor for gastric cancer

Cited by 107 publications

References 17 publications

Preventive effects of etodolac, a selective cyclooxygenase‐2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori‐negative precancerous lesion

Preventive effects of etodolac, a selective cyclooxygenase‐2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori‐negative precancerous lesion

Gastric Cancer Risk Diagnosis and Prevention in Subjects with Helicobacter pylori-related Chronic Gastritis

Serum pepsinogen and gastrin-17 as potential biomarkers for pre-malignant lesions in the gastric corpus

Contact Info

Product

Resources

About