Your privacy, your choice

We use essential cookies to make sure the site can function. We also use optional cookies for advertising, personalisation of content, usage analysis, and social media.

By accepting optional cookies, you consent to the processing of your personal data - including transfers to third parties. Some third parties are outside of the European Economic Area, with varying standards of data protection.

See our privacy policy for more information on the use of your personal data.

for further information and to change your choices.
Skip to main content
Download PDF

Relationship between gastric mucosal atrophy, cystic dilatation, and histopathological characteristics

BMC Gastroenterology volume 25, Article number: 92 (2025) Cite this article

Abstract

Objective

This study aims to elucidate the relationship between gastric mucosal atrophy, cystic dilatation, and their associated histopathological characteristics.

Methods

A comprehensive analysis was conducted on endoscopic biopsy specimens from 527 cases exhibiting gastric mucosal cystic dilatation. Detailed histological observations and immunohistochemical analysis were performed.

Results

This study included 527 endoscopic biopsy and ESD samples, with a male predominance of 313 cases (59.4%) and 214 female cases (40.6%). The age distribution was as follows: 207 cases (39.3%) were ≤ 60 years, while 320 cases (60.7%) were > 60 years. Regarding cystic dilatation types, 287 cases (54.5%) were identified as simple cystic dilatation, and 240 cases (45.5%) were classified as compound cystic dilatation. Gastric mucosal atrophy was observed in all cases of cystic dilatation, with the atrophic process initially disrupting the structural integrity of the gastric glands. This led to increased interstitial tissue and widening of glandular septa, followed by compensatory hyperplasia and cystic cavity formation. Simple cystic dilatation (54.5%) and compound cystic dilatation (45.5%) were distinguished based on the extent of cellular and structural changes. Simple cystic dilatation could progress to early gastric cancer, presenting as gastric papillary cystadenocarcinoma, while compound cystic dilatation could lead to tubular papillary adenocarcinoma. The progression from simple to complex lesions involved low- and high-grade intraepithelial neoplasia, ultimately resulting in mixed cystadenocarcinoma-glandular tube papillary carcinoma, indicative of early-stage gastric cancer.

Conclusion

The classification, grading, and histopathological characteristics of cystic dilatation in the gastric mucosa are crucial for guiding clinicians in precise treatment and vigilant monitoring of malignant transformation. This approach is significant for the prevention and control of gastric cancer progression.

Peer Review reports

Introduction

Gastric cancer represents about 6% of all cancers globally, making it the fifth most common malignancy and the fourth leading cause of cancer-related deaths, with its highest incidence observed in Asia and Eastern Europe [1,2,3]. Despite a decrease in the prevalence of gastric cancer, patient prognosis remains poor, primarily because most cases are diagnosed at a middle to advanced stage. Even with perioperative or adjuvant chemotherapy, survival rates for these patients remain low [4,5,6]. Chronic atrophic gastritis is widely considered a precursor to gastric cancer. Gastrointestinal pathologists distinguish the types of atrophy histologically based on glandular loss, intestinal metaplasia, and non-intestinal metaplasia [7, 8]. Intestinal metaplasia atrophic gastritis refers to the phenomenon of intestinal metaplasia when the inherent glands of the gastric mucosa atrophy. Non-intestinal metaplasia atrophic gastritis is mainly due to the atrophy of the inherent glands of the gastric mucosa, but there is no pathological change of intestinal metaplasia. Intestinal metaplastic atrophic gastritis is associated with a higher risk of progression to dysplasia and cancer than non-intestinal metaplastic atrophic gastritis [9]. Research indicates a correlation between the risk of developing gastric cancer and the grade of mucosal atrophy [10, 11]. Previous studies have demonstrated that atrophy may progress to intestinal metaplasia, a condition that tends to become more pronounced with advancing age. In individuals over 50 years of age, there is a notable variation in both the quantity and quality of mucus secretion. This mucus often contains different levels of sialic acid mucus and/or sulfate mucus, which are highly susceptible to carcinogenesis [12].

Factors such as Helicobacter pylori infection, chemical irritation, and immune responses can lead to gastric mucosal atrophy and subsequent development of gastric cancer. Notably, even after the successful eradication of H. pylori, patients with moderate to severe gastric mucosal atrophy remain at high risk of developing gastric cancer [13,14,15,16]. Although the link between gastric mucosal atrophy and gastric cancer is well recognized, the morphological changes leading to carcinogenesis are infrequently reported in the literature. Gastric mucosal atrophy does not directly progress into gastric adenocarcinoma but instead undergoes a series of histomorphological changes during the transformation process. Our previous research revealed that H. pylori infection disrupts stem cell proliferation in the proliferative area of the gastric mucosa. This disruption results in extensive segmental papillomatous hyperplasia, caused by the excessive upward migration of the proliferative area, and extensive segmental gland atrophy in the lamina propria, due to insufficient downward migration [17].

Subsequent studies introduced the terminology for gastric mucosal atrophy lesions and identified the histopathological characteristics of different types of atrophy [18, 19]. Persistent gastric mucosal atrophy has been shown to disrupt the normal physiological regularity and polarity of stem cells in the proliferative area, leading to the formation of abnormal proliferative structures. In addition to glandular atrophy, compensatory proliferative atrophy, intestinal metaplastic atrophy, and smooth muscle proliferative atrophy in the lamina propria, stem cell atrophy in the proliferative area has also been identified as a key feature [20].

It is worth mentioning that cystic dilatation is regarded as a precursor or an intermediate stage in the development of gastric cancer [21]. From the perspective of histopathological features, there are obvious differences between cystic dilatation and other forms of mucosal atrophy areas. In the area of cystic dilatation, cystic structures will appear in the submucosa or muscular layer of the stomach, with varying sizes of the cystic cavities. The surrounding gastric wall tissues are often accompanied by structural disorders to different extents, such as irregular cell arrangement and changes in intercellular connections [22]. Compared with simple glandular atrophy and other situations, the mucosal barrier function in the area of cystic dilatation is often weaker, which makes it easier for harmful factors to invade and act on cells, thereby increasing the possibility of abnormal changes such as gene mutations in cells and also enhancing the potential for malignant development [23]. Moreover, cystic dilatation is usually accompanied by a more intense chronic inflammatory response. Inflammatory cells release a large number of inflammatory mediators, which will not only directly damage the DNA of cells but also create a microenvironment conducive to the growth and proliferation of tumor cells, further promoting the process of its malignant transformation [24].

This article further explores the relationship between cystic dilatation of the gastric mucosa and mucosal atrophy, as well as the associated histopathological characteristics. Through the analysis of 527 cases of gastric mucosal cystic dilatation, we propose that this condition originates from gastric mucosal atrophy and can progress into two distinct types of lesions: simple cystic dilatation and compound cystic dilatation, each with distinct histological features. A thorough understanding of these characteristics is crucial for clinicians to provide targeted treatment and monitor the malignant transformation of cells, which is vital for managing the development and progression of gastric cancer.

Materials and methods

Materials

A total of 527 cases of cystic dilatation of the gastric mucosa, histopathologically diagnosed through gastroscopic biopsy between February 2022 and February 2024, were collected from multiple institutions: Peking University Shenzhen Hospital (135 cases), Xuchang Central Hospital (132 cases), Weifang 80th Group Army Hospital of the Chinese People’s Liberation Army (94 cases), Longgang District People’s Hospital (85 cases) of Shenzhen, and Shenzhen Longgang Fourth People’s Hospital (81 cases). This study was conducted with approval from the Ethics Committee of The Fourth People’s Hospital of Longgang District and in accordance with the declaration of Helsinki. From each patient, between three and five mucosal tissue samples were collected. These samples were subsequently fixed in 10% neutral formalin, dehydrated through standard procedures, embedded in paraffin, and then meticulously sliced into 4-micron thick sections. These sections served as the basis for both hematoxylin and eosin (HE) staining and immunohistochemical analysis.

A total of 527 cases were identified through gastric mucosal biopsy screenings at Peking University Shenzhen Hospital, Xuchang Central Hospital, Weifang 80th Army Group Hospital, Shenzhen Longgang District People’s Hospital, and The Fourth People’s Hospital of Longgang District. The diagnosis of cystic dilatation was confirmed through histopathological analysis. The condition was characterized by compensatory hyperplastic glandular structures of varying sizes within the gastric mucosa due to atrophy, subsequently forming two types of dilatation: simple cystic dilatation and complex cystic dilatation.

Immunohistochemical staining

Using the EnVision two-step method, the tissue sections were first dewaxed, hydrated, and rinsed with distilled water. The sections were then immersed in TBS (Tris-buffered saline) for 10 min, followed by the blocking of endogenous peroxidase activity for 5 min. After another 10-minute TBS wash, each primary antibody (including CDX2, MUC5AC, MUC6, p53, and ki-67) was incubated with the sections for 30 min at room temperature. The sections were then washed in TBS for 10 min before being incubated with the EnVision™ reagent. Following a 10-minute TBS wash, the secondary antibody was applied for 10 min.

Subsequently, the sections were treated with the chromogenic substrate solution for 10 min and then rinsed with distilled water. DAB (3,3’-diaminobenzidine) was used for color development, and the sections were counterstained with hematoxylin. Known gastric mucosal sections were used as positive controls, while PBS buffer replaced the primary antibodies for the negative controls. All working solutions were sourced from Fuzhou Maixin Biotech Co., Ltd., and the procedures were carried out strictly according to the manufacturer’s instructions.

Results

Clinical characteristics

This study included a total of 527 endoscopic biopsy and ESD samples. Among these, 313 cases (59.4%) were male, and 214 cases (40.6%) were female. The age distribution was as follows: 207 cases (39.3%) were aged ≤ 60 years while 320 cases (60.7%) were aged > 60 years. In terms of cystic dilatation types, 287 cases (54.5%) were identified as simple cystic dilatation, and 240 cases (45.5%) were classified as compound cystic dilatation (Table 1). Among these 527 cases, 20 instances of cystic dilatation with high-grade intramucosal neoplasia and 1 case of gastric mixed intramucosal carcinoma underwent endoscopic submucosal dissection (ESD). The remaining 506 cases underwent biopsy procedures. Of the 506 biopsy cases, tissue samples were taken from various regions of the stomach: 89 from the gastric angle, 319 from the gastric antrum, 98 from the gastric body, 54 from the gastric fundus, and 78 from the cardia.

Table 1 Correlation between simple and compound cystic dilatation and clinical parameters
Full size table

Relationship between gastric mucosal atrophy and cystic dilatation, its occurrence and development

In all 527 cases of gastric mucosal cystic dilatation, varying degrees of gastric mucosal atrophy were observed. The atrophic process initially disrupts the structural integrity of the deep gastric pits, gland isthmus, and glandular neck, resulting in increased interstitial tissue and widening of glandular septa. This disruption is evident in the proliferative areas and mucosa lamina propria, where surface epithelium is present. Focal atrophy of the pyloric, fundic, or cardia glands occurs, followed by compensatory hyperplasia, leading to the formation of cystic cavities of varying sizes. Over time, this process may evolve into two distinct types of lesions: simple cystic dilatation, characterized by less complex cystic changes, and compound cystic dilatation, involving more complex cystic formations and often presenting with varying degrees of cellular and structural atypia. These lesions are collectively referred to as cystic dilated lesions of the gastric mucosa and are characterized by their neoplastic hyperplasia nature (Fig. 1).

Fig. 1
figure 1

Correlation between gastric mucosal atrophy and cystic dilatation and the flow chart of its occurrence and development

Full size image

Stages and histopathological characteristics of simple and compound cystic dilatation

This study proposes two types of cystic dilatation lesions: simple cystic dilatation and composite cystic dilatation. Simple cystic dilatation involves a histological structure consisting of a single type of cystic dilation, whereas composite cystic dilatation is characterized by the combination of cystic dilation and glandular papillary structures. Both types can progress through various stages, including focal, widespread, proliferative, low-grade, and high-grade lesions, ultimately evolving into gastric mixed mucosal cancer (cystadenocarcinoma-papillary adenocarcinoma). The chart in Fig. 2 illustrates the distribution and proportion of these types and stages, highlighting the frequency of simple cystic dilatation at each stage. Focal simple cystic dilatation is the most prevalent, accounting for 32.8%, followed by widespread cystic dilatation at 19.2%. Other stages, such as proliferative cystic dilatation and those with intraepithelial neoplasia, are observed in lower frequencies.

Fig. 2
figure 2

Histogenesis and comparison of simple cystic dilatation and complex cystic dilatation. The data on the vertical axis of Fig. 2 represents the percentage of each group

Full size image

Simple cystic dilatation involves several histomorphological changes related to a single type of cystic dilatation, including: (1) Focal simple cystic dilatation, characterized by approximately 5 dilated glands associated with gastric mucosal atrophy (Fig. 3a); (2) Extensive simple cystic dilatation, referring to multifocal cystic dilatations or those measuring ≥ 5 mm in length (Fig. 3b); (3) Proliferative and transformative simple cystic dilatation, where the dilated glands show increased cellular size, small nucleoli, and heightened mitosis (Fig. 3c); (4) Simple cystic dilatation with low-grade intraepithelial neoplasia, marked by cystic dilated glands with changes indicative of low-grade intraepithelial neoplasia (Fig. 3d); (5) Simple cystic dilatation with high-grade intraepithelial neoplasia, where cystic dilated glands present with characteristics of high-grade intraepithelial neoplasia (Fig. 3e); and (6) Gastric papillary cystadenocarcinoma (early gastric cancer) with cystic dilated glands exhibiting features of papillary cystadenocarcinoma (Fig. 3f).

Fig. 3
figure 3

Simple cystic dilatation includes several stages: (a) Focal simple cystic dilatation, where hyperplastic fundic glands form cyst cavities of varying sizes, often ranging greatly in size (indicated by the arrow); (b) Extensive simple cystic dilatation, where the lesion extends beyond 5 mm into the fundic gland area (indicated by the arrow); (c) Proliferative and transformative simple cystic dilatation, characterized by glandular epithelial cells arranged in single or multilayered patterns with enlarged, irregularly round or oval nuclei (indicated by the arrow); (d) Simple low-grade intraepithelial neoplasia, with glandular epithelial cells arranged in single or multilayered patterns, and nuclei enlarged to 2–3 times the size of normal fundic gland nuclei (indicated by the arrow); (e) Simple high-grade intraepithelial neoplasia, where glandular epithelial cells transform from columnar to cubic, showing large nuclei with an increased nucleus-to-cytoplasm ratio, and enlarged nucleoli present in about 30-50% of nuclei (indicated by the arrow); (f) Gastric papillary cystadenocarcinoma - early gastric cancer, with large nuclei, an increased nucleus-to-cytoplasm ratio, enlarged and obvious nucleoli in ≥ 50% of nuclei, and mitosis occurring in 3–8 cells per HPF (indicated by the arrow)

Full size image

Compound cystic dilatation features structural elements of tubular papillae in the upper area of isolated cystic dilatation, with the following stages: (1) Focal compound cystic dilatation, which shows focal papillary hyperplasia originating from the surface epithelium in the upper part of the cystic dilatation (Fig. 4a); (2) Extensive compound cystic dilatation, characterized by widespread papillary hyperplasia of the surface epithelium in the upper part of cystic dilatation (Fig. 4b); (3) Compound proliferative cystic dilatation, where glandular epithelial cells proliferate in a stratified manner, with increased nucleus size and small nucleoli (Fig. 4c); (4) Compound low-grade intraepithelial neoplasia, featuring stratified proliferation of glandular epithelial cells with elongated nuclei, mild to moderate atypia, increased nuclear chromatin, and nucleoli present in about 20 − 30% of the nuclei (Fig. 4d); (5) Compound high-grade intraepithelial neoplasia, showing glandular epithelial cell transformation from columnar to cubic forms, with large nuclei, an increased nucleus-to-cytoplasm ratio, and enlarged nucleoli in 30 − 50% of nuclei (Fig. 4e); (6) Compound tubular papillary adenocarcinoma (early gastric cancer), where glandular epithelial cells exhibit large nuclei, an increased nucleus-to-cytoplasm ratio, and nucleoli in ≥ 50% of nuclei, with mitotic activity observed in 3–8 cells per high-power field (HPF) (Fig. 4f); and (7) Gastric mixed cystadenocarcinoma - glandular tube papillary carcinoma (early gastric cancer), characterized by tubular papillary adenocarcinoma changes in the upper glands of cystic dilatation, with large nuclei, an increased nucleus-to-cytoplasm ratio, nucleoli present in ≥ 50% of nuclei, and mitotic activity in 3–8 cells per HPF (Fig. 4g). The histological diagnostic criteria for these stages are detailed in Table 2.

Fig. 4
figure 4

Compound cystic dilatation includes several stages: (a) Focal compound cystic dilatation, where focal hyperplasia or papillary structures form in the upper isthmus of the cystic dilatation or in the regional proliferative area of the glandular neck (indicated by the arrow); (b) Extensive compound cystic dilatation, characterized by lesions extending beyond 5 mm into the fundic gland area in the upper isthmus or regional proliferative area (indicated by the arrow); (c) Proliferative and transformative compound cystic dilatation, where the glands in the upper area of cystic dilatation show tubular papillary hyperplasia, with glandular epithelial cells proliferating in a stratified manner and exhibiting increased nucleus size and small nucleoli (indicated by the arrow); (d) Compound low-grade intraepithelial neoplasia, where some glands retain their original cystic dilatation forms while others proliferate in a tubular papillary manner, forming a tubular papillary structure with mild to moderate atypia and increased nuclear chromatin, and nucleoli visible in about 20 − 30% of nuclei (indicated by the arrow); (e) Compound high-grade intraepithelial neoplasia, where some glands retain their original cystic dilatation forms while others proliferate into irregular branching tubular papillary structures, with enlarged and obvious nucleoli in about 30 − 50% of nuclei (indicated by the arrow); (f) Compound tubular papillary adenocarcinoma - early gastric cancer, where the glands in the upper area show changes of tubular papillary adenocarcinoma, with large nuclei, an increased nucleus-to-cytoplasm ratio, and enlarged and obvious nucleoli in ≥ 50% of nuclei (indicated by the arrow); (g) Gastric mixed intramucosal carcinoma/early gastric cancer (cystadenocarcinoma-glandular tube papillary carcinoma), characterized by tubular papillary adenocarcinoma in the upper part and papillary cystadenocarcinoma in the lower part (indicated by the arrow)

Full size image
Table 2 Histopathological characteristics of simple-compound cystic dilatation
Full size table

Immunohistochemical staining results of cystic dilatation

MUC5AC and MUC6 exhibited partially weak positive expression in the lesion areas of both simple and compound cystic dilatation (Fig. 5a and b). CDX2 and p53 were negative in the focal and extensive stages of simple and compound cystic dilatation, and either negative or weakly positive in the proliferation and transformation stages. However, they showed positive expression in the intraepithelial neoplasia and adenocarcinoma stages (Fig. 5c). The number of Ki-67 positive cells demonstrated an increasing trend across the lesion areas of both simple and compound cystic dilatation (Fig. 5d).

Fig. 5
figure 5

(a) The immunophenotype of cystic dilatation of gastric mucosa includes: in compound high-grade intraepithelial neoplasia, positive expression of MUC5AC in some glands of cystic dilatation (indicated by the arrow); (b) in compound tubular papillary adenocarcinoma (early gastric cancer), positive expression of MUC6 (indicated by the arrow); (c) in cystic dilatation with high-grade intraepithelial neoplasia, positive expression of CDX2 (indicated by the arrow); (d) and in cystic dilatation with high-grade intraepithelial neoplasia, a significant increase in the number of Ki-67 positive cells (indicated by the arrow)

Full size image

Discussion

In normal gastric mucosa, each gastric pit connects to 3–5 glands, forming the basic structural unit known as a gastric unit. Each unit comprises a gastric pit and a gastric gland, which is further divided into the isthmus, glandular neck, and base. The upper regions of the deep gastric pit, gland isthmus, and glandular neck constitute the proliferative area or zone. This area is characterized by small, low columnar cells and is primarily composed of proliferating stem cells. Some stem cells migrate upwards to differentiate into surface mucus cells, while others remain localized or migrate downward to develop into various fundic gland cells [25,26,27,28].

Analysis of 527 cases of gastric mucosal cystic dilatation in this study revealed that these lesions originate from gastric mucosal atrophy. Contributing factors such as infection, chemical stimuli, immune responses, and genetic influences impair the normal differentiation and migration of stem cells in the proliferative area of the gastric mucosa, leading to atrophy. Initially, the proliferative regions of the deep gastric pit, gland isthmus, and glandular neck exhibit structural disruption or absence, characterized by increased interstitial tissue and widened glandular septa. This results in focal atrophy of the pyloric, fundic, and cardia glands, accompanied by compensatory hyperplasia and the formation of cystic cavities of varying sizes, ranging from 0.1 to 0.6 mm in size. The cystic dilatation often presents with a single-layered, flattened, cubic, or columnar epithelium with non-atypical glandular epithelial cells. The dilated glands may include pyloric, fundic, cardiac glands, or gastric pit glands. As cystic dilatation progresses to more proliferative and transformative stages, it can develop into gastric adenocarcinoma. Consequently, cystic dilatation of the gastric mucosa is considered a significant precancerous lesion, emphasizing the importance of early detection and intervention to manage and understand its progression.

Few reports specifically address cystic dilatation of gastric mucosal glands. It has been noted that conditions such as gastric polyps or portal adenomas may exhibit cystic dilatation, often characterized by glandular submucosal proliferation and cystic changes. In such cases, the polyp surface may be covered with fundic or pyloric gland gastric mucosa, with the submucosal cystic component potentially connected to the overlying mucosa through defects in the muscular mucosae. This suggests that these lesions might originate from the ectopic downward growth of mucosal glands into the submucosa [29, 30]. Additionally, prolonged use of proton pump inhibitors (PPIs) has been associated with histopathological changes, including protrusion of parietal cells into the glandular lumen, cystic dilatation of fundic glands, and foveolar epithelial hyperplasia [31, 32].

Currently, the mechanisms underlying the formation of cystic dilatation of gastric mucosal glands remain unclear. Recent research mainly points out the following aspects: Inflammatory Factors: The observed transformation of gastric mucosal atrophy into cystic dilatation and subsequent neoplasia is likely influenced by inflammatory and molecular disruptions, as suggested by Kuester et al. [33] Their findings demonstrate that Helicobacter pylori infection, combined with deficiencies in protease pathways such as cathepsin x/z, induces premalignant host responses. These insights highlight potential molecular mechanisms underlying the progression of atrophic lesions to cystic dilations and gastric adenocarcinoma, reinforcing the need for further exploration into host-pathogen interactions in gastric cancer pathogenesis. Autoimmune Factors: In autoimmune gastritis, anti-parietal cell antibodies and others destroy parietal cells, affecting gastric acid secretion and vitamin B₁₂ absorption. The glands atrophy, and immune cells release cytokines that inhibit the proliferation of epithelial cells and induce apoptosis, worsening the damage. Subsequently, the foveolar epithelium undergoes compensatory hyperplasia and finally forms cystic dilation. Pathologically, disordered mucosal structures and cystic structures can be seen [34]. Gene Mutations: For example, the mutation of the CDH1 gene in hereditary diffuse gastric cancer syndrome, although it does not directly drive the transformation from atrophy to cystic dilation, can affect cell-cell adhesion and indirectly participate in this process [35]. Signaling Pathways: When the Wnt/β-catenin signaling pathway is stimulated, key molecules are dysregulated, and β-catenin accumulates abnormally, promoting excessive cell proliferation, which may lead to cystic dilation. Pathologically, enhanced proliferative activity can be manifested [36]. The TGF-β signaling pathway is abnormally activated or inhibited under pathological conditions, affecting cell growth inhibition and the balance of the extracellular matrix, which is conducive to the formation of cystic dilation, and an increase in matrix components can be observed [37].

In this study, through the examination of 527 cases of gastric mucosal cystic dilatation, distinct characteristics of these lesions were identified. Two types of cystic dilatation were proposed: simple cystic dilatation, which involves a single type of histological structure, and compound cystic dilatation, which includes both cystic dilatation and papillary glandular tube structures. Both types undergo various stages including focal, extensive, proliferative, and low- to high-grade lesions, potentially evolving into gastric mixed intramucosal carcinoma (cystadenocarcinoma-glandular tube papillary carcinoma). This study outlines the types and stages of cystic dilatation based on histological structures and cell morphological changes, providing a framework for clinical pathological reporting. By incorporating these classifications into clinical reports, pathologists can assist clinicians in offering targeted treatment and monitoring malignant cell transformation, thereby playing a crucial role in controlling the occurrence and progression of gastric cancer.

Gastric cancer (GC) remains a leading cause of death globally, with primary prevention efforts centered on the detection and eradication of H. pylori, a significant environmental risk factor. In regions with high-incidence rates, secondary prevention increasingly involves endoscopic or radiological screening of asymptomatic populations [38, 39]. H. pylori infection can lead to atrophic gastritis (AG), which may progressively evolve into gastric cancer. Literature indicates that most gastric cancers originate from long-standing AG, suggesting that gastric atrophy (GA) serves as a precursor to gastric adenocarcinoma (GAC) [40, 41]. Our previous research has demonstrated that H. pylori infection induces gastric pit epithelial hyperplasia and atrophic foveolar epithelial hyperplasia, which can potentially lead to foveolar epithelial neoplasia and signet-ring cell carcinoma [42, 43].

The histopathological changes of cystic dilation are closely related to early gastric cancer. Current research considers that the following relationships exist: Cellular Atypia: In cystic dilation, affected by multiple factors, the epithelial cells of the gastric mucosa will undergo morphological and functional changes during cystic dilation. For example, the cells may vary in size, have an imbalance in the ratio of nucleus to cytoplasm, and show irregular nuclei. The cells are arranged in a disorderly manner, with an increase in the number of layers and a loss of polarity, being in a “precancerous state”. Connection with early gastric cancer: Taking papillary cystadenocarcinoma as an example, it also has the feature of cellular atypia in its early stage. If the cellular atypia in the cystic dilation area worsens, such as more obvious pleomorphism and an abnormal increase in mitotic figures, it indicates an increased risk of papillary cystadenocarcinoma, reflecting that the cell proliferation is out of control and is developing towards malignancy [44]. Invasiveness: In cystic dilation, with its further development, there will be invasive manifestations such as destruction of the cyst wall and infiltration of surrounding tissues, which may damage the tissue barrier. Moreover, an increase in the infiltration of inflammatory cells will form a vicious cycle. Connection with early gastric cancer: Early gastric cancer has the characteristic of invasiveness. If cystic dilation shows similar invasive manifestations and the situation continues to progress, it suggests an increased possibility of gastric cancer occurrence. The degree of invasiveness can also reflect the malignancy degree and progression speed of early gastric cancer, facilitating early intervention [45]. Other Connections: During cystic dilation, the glands undergo deformation, dilation, and fusion, which disrupts their normal architecture. In early gastric cancers, such as differentiated adenocarcinomas, similar alterations in glandular structure can be observed. Additionally, the mucus-secreting function of epithelial cells may be impaired, with some early gastric cancers, like mucinous adenocarcinomas, displaying mucus-related characteristics. These abnormalities in both glandular structure and mucus secretion may serve as important clues for the early prediction of gastric cancer [46].

This study identifies cystic dilatation of the gastric mucosa as a precancerous lesion for gastric cancer, proposing a link between the development of early gastric cancer gastric mucosal cystic dilatation. We have detailed the mechanisms involved and introduced a histopathological classification system for cystic dilatations, including those with low-grade and high-grade intraepithelial neoplasia, as well as specific types of early gastric cancer: gastric papillary cystadenocarcinoma, compound tubular papillary adenocarcinoma, and gastric mixed cystadenocarcinoma-glandular tube papillary carcinoma. The study also provides detailed histopathological diagnostic criteria and immunophenotypic characteristics for each stage, offering new insights for research into early gastric cancer. For patients with compound cystic dilation, doctors need to comprehensively consider various factors such as the specific characteristics of the lesion (such as its size, the degree of cellular atypia, the presence or absence of invasive manifestations, etc.), the individual conditions of the patient (age, physical condition, mental state, etc.), and medical resources. They should weigh the advantages and disadvantages of more frequent monitoring and early intervention in order to formulate the most personalized treatment plan suitable for the patient.

Conclusion

In summary, this study proposes that cystic dilatation of the gastric mucosa originates from gastric mucosal atrophy and represents a significant precancerous lesion. Cystic dilatation can evolve into two categories: simple cystic dilatation and compound cystic dilatation. By analyzing histological structures and cellular morphological changes in the gastric mucosa, as well as patterns of disease occurrence and progression, this study defines the histopathological characteristics of both types. It suggests that including the type and stage of cystic dilatation in clinical pathological reports will aid clinicians in providing targeted treatment and monitoring malignant cell transformation, which is crucial for managing the onset and progression of gastric cancer. The development of cystic dilatation is a gradual process, and its progression to cancer will be monitored through genetic studies and long-term follow-up, with further research planned at the molecular biological level.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

H.pylori:

Helicobacter pylori

AG:

Gastritis

GC:

Gastric cancer

GAC:

Adenocarcinoma of the stomach

GA:

Gastric atrophy

PPIs:

Proton pump inhibitor

References

  1. Xia JY, Aadam AA. Advances in screening and detection of gastric cancer. J Surg Oncol. 2022;125(7):1104–9. https://doi.org/10.1002/jso.26844.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Tong Y, Cheng PSW, Or CS, Yue SSK, Siu HC, Ho SL, Law SYK, Tsui WY, Chan D, Ma S, Lee SP, Chan ASY, Chan AS, Yun SW, Hui HS, Yuen ST, Leung SY, Yan HHN. Escape from cell-cell and cell-matrix adhesion dependence underscores disease progression in gastric cancer organoid models. Gut. 2023;72(2):242–55. https://doi.org/10.1136/gutjnl-2022-327121.

    Article  CAS  PubMed  Google Scholar 

  3. Gullo I, Grillo F, Mastracci L, Vanoli A, Carneiro F, Saragoni L, Limarzi F, Ferro J, Parente P, Fassan M. Precancerous lesions of the stomach, gastric cancer and hereditary gastric cancer syndromes. Pathologica. 2020;112(3):166–85. https://doi.org/10.32074/1591-951X-166.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Norwood DA, Montalvan-Sanchez E, Dominguez RL, Morgan DR. Gastric Cancer: emerging trends in Prevention, diagnosis, and treatment. Gastroenterol Clin North Am. 2022;51(3):501–18. https://doi.org/10.1016/j.gtc.2022.05.001.

    Article  PubMed  Google Scholar 

  5. Costa G, Younes H, Kourie HR, Kattan J. The rapidly evolving landscape of advanced gastric cancer therapy. Future Oncol. 2022;18(12):1413–6. https://doi.org/10.2217/fon-2021-1499.

    Article  CAS  PubMed  Google Scholar 

  6. Wu HJ, Dai WW, Wang LB, Zhang J, Wang CL. Comprehensive analysis of the molecular mechanism for gastric cancer based on competitive endogenous RNA network. World J Tradit Chin Med. 2023;9:29–42. https://doi.org/10.4103/2311-8571.364415.

    Article  CAS  Google Scholar 

  7. Matysiak-Budnik T, Camargo MC, Piazuelo MB, Leja M. Recent guidelines on the management of patients with gastric atrophy: common points and controversies. Dig Dis Sci. 2020;65(7):1899–903. https://doi.org/10.1007/s10620-020-06272-9.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kinoshita H, Hayakawa Y, Koike K. Metaplasia in the stomach-precursor of gastric Cancer? Int J Mol Sci. 2017;18(10):2063. https://doi.org/10.3390/ijms18102063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Drnovsek J, Homan M, Zidar N, Smid LM. Pathogenesis and potential reversibility of intestinal metaplasia - a milestone in gastric carcinogenesis. Radiol Oncol. 2024;58(2):186–95. https://doi.org/10.2478/raon-2024-0028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kishikawa H, Ojiro K, Nakamura K, Katayama T, Arahata K, Takarabe S, Miura S, Kanai T, Nishida J. Previous Helicobacter pylori infection-induced atrophic gastritis: a distinct disease entity in an understudied population without a history of eradication. Helicobacter. 2020;25(1):e12669. https://doi.org/10.1111/hel.12669.

    Article  CAS  PubMed  Google Scholar 

  11. Vannella L, Lahner E, Annibale B. Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal. World J Gastroenterol. 2012;18(12):1279–85. https://doi.org/10.3748/wjg.v18.i12.1279.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wang YK, Shen L, Yun T, Yang BF, Zhu CY, Wang SN. Histopathological classification and follow-up analysis of chronic atrophic gastritis. World J Clin Cases. 2021;9(16):3838–47. https://doi.org/10.12998/wjcc.v9.i16.3838.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Shichijo S, Hirata Y. Characteristics and predictors of gastric cancer after Helicobacter pylori eradication. World J Gastroenterol. 2018;24(20):2163–72. https://doi.org/10.3748/wjg.v24.i20.2163.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Toyoshima O, Nishizawa T, Koike K. Endoscopic Kyoto classification of Helicobacter pylori infection and gastric cancer risk diagnosis. World J Gastroenterol. 2020;26(5):466–77. https://doi.org/10.3748/wjg.v26.i5.466.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Quach DT, Hiyama T. Assessment of Endoscopic gastric atrophy according to the Kimura-Takemoto classification and its potential application in Daily Practice. Clin Endosc. 2019;52(4):321–7. https://doi.org/10.5946/ce.2019.072.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Dilaghi E, Dottori L, Pivetta G, Dalla Bella M, Esposito G, Ligato I, Pilozzi E, Annibale B, Lahner E. Incidence and predictors of gastric neoplastic lesions in Corpus-Restricted Atrophic gastritis: a single-Center Cohort Study. Am J Gastroenterol. 2023;118(12):2157–65. https://doi.org/10.14309/ajg.0000000000002327.

    Article  CAS  PubMed  Google Scholar 

  17. Wang YK, Zhou JL, Meng NL, Zhu CY, Wang SN, Chen XD. How does Helicobacter pylori infection cause gastric mucosal atrophy. Infect Drug Resist. 2022;15:3619–29. https://doi.org/10.2147/IDR.S355981.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wang Y, Zhou J, Meng N, Yang B, Zhu C, Jiang B, Wang S, Chen X. The occurrence, progression and development of four types of gastric mucosal atrophic lesions and their histopathological characteristics. Gastric Cancer. 2023;26(5):721–33. https://doi.org/10.1007/s10120-023-01400-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang YK, Ran DM, Li YY, Zhu CY, Zhang RB, Jiang B, Wang SN. Histopathological features of glandular atrophy of the lamina propria of the gastric mucosa during its occurrence and development. BMC Gastroenterol. 2023;23(1):395. https://doi.org/10.1186/s12876-023-03033-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang YK, Li YY, Wang B, Ran DM, Zhu CY, Li P, Jiang B, Wang SN. Histopathological staging of atrophic lesions of gastric mucosa. Heliyon. 2024;10(6):e27845. https://doi.org/10.1016/j.heliyon.2024.e27845.

    Article  PubMed  PubMed Central  Google Scholar 

  21. González Díaz I, Méndez MC, Tavecchia M, Amor Costa C, Amiama Roig C, Burgos García A. Gastritis Cystica profunda in a western population without previous gastric surgery. Rev Esp Enferm Dig. 2024 Sep;5. https://doi.org/10.17235/reed.2024.10633/2024.

  22. Dong N, Meng F, Yue B, Hou J. Clinicopathologic and endoscopic characteristics of ten patients with gastric hamartomatous inverted polyp: a single center case series. BMC Gastroenterol. 2024;24(1):139. https://doi.org/10.1186/s12876-024-03233-8.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hata M, Kinoshita H, Hayakawa Y, Konishi M, Tsuboi M, Oya Y, Kurokawa K, Hayata Y, Nakagawa H, Tateishi K, Fujiwara H, Hirata Y, Worthley DL, Muranishi Y, Furukawa T, Kon S, Tomita H, Wang TC, Koike K. GPR30-Expressing gastric Chief cells do not dedifferentiate but are eliminated via PDK-Dependent Cell Competition during Development of Metaplasia. Gastroenterology. 2020;158(6):1650–e166615. https://doi.org/10.1053/j.gastro.2020.01.046.

    Article  CAS  PubMed  Google Scholar 

  24. Salvatori S, Marafini I, Laudisi F, Monteleone G, Stolfi C. Helicobacter pylori and GacancerCapathogeneticemechanismsanisms. Int J Mol Sci. 2023;24(3):2895. https://doi.org/10.3390/ijms24032895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Russi S, Calice G, Ruggieri V, Laurino S, La Rocca F, Amendola E, Lapadula C, Compare D, Nardone G, Musto P, De Felice M, Falco G, Zoppoli P. Gastric normal adjacent mucosa Versus Healthy and Cancer tissues: distinctive transcriptomic profiles and Biological features. Cancers (Basel). 2019;11(9):1248. https://doi.org/10.3390/cancers11091248.

    Article  CAS  PubMed  Google Scholar 

  26. Souza SM, Valiente AEF, Sá KM, Juanes CC, Rodrigues BJ, Farias ACC, Campelo CC, Silva PGB, Almeida PRC. Immunoexpression of LGR4 and Β-Catenin in gastric Cancer and normal gastric mucosa. Asian Pac J Cancer Prev. 2019;20(2):519–27. https://doi.org/10.31557/APJCP.2019.20.2.519.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tarnawski AS, Ahluwalia A. Increased susceptibility of aging gastric mucosa to injury and delayed healing: clinical implications. World J Gastroenterol. 2018;24(42):4721–7. https://doi.org/10.3748/wjg.v24.i42.4721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Heidari Z, Mahmoudzadeh-Sagheb H, Narouei M. Quantitative changes of gastric mucosa during carcinogenesis using stereological methods. J BUON. 2017 Jul-Aug;22(4):905–10.

  29. Pezhouh MK, Park JY. Gastric pyloric gland adenoma. Arch Pathol Lab Med. 2015;139(6):823–6. https://doi.org/10.5858/arpa.2013-0613-RS.

    Article  CAS  PubMed  Google Scholar 

  30. Itoh K, Tsuchigame T, Matsukawa T, Takahashi M, Honma K, Ishimaru Y. Unusual gastric polyp showing submucosal proliferation of glands: case report and literature review. J Gastroenterol. 1998;33(5):720–3. https://doi.org/10.1007/s005350050161.

    Article  CAS  PubMed  Google Scholar 

  31. Takahari K, Haruma K, Ohtani H, Kiyoto S, Watanabe A, Kamada T, Manabe N, Hatano Y. Proton pump inhibitor induction of gastric cobblestone-like lesions in the stomach. Intern Med. 2017;56(20):2699–703. https://doi.org/10.2169/internalmedicine.7964-16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kim GH. Proton Pump inhibitor-related gastric mucosal changes. Gut Liver. 2021;15(5):646–52. https://doi.org/10.5009/gnl20036.

    Article  PubMed  Google Scholar 

  33. Krueger S, Bernhardt A, Kalinski T, Baldensperger M, Zeh M, Teller A, Adolf D, Reinheckel T, Roessner A, Kuester D. Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice. PLoS ONE. 2013;8(7):e70242. https://doi.org/10.1371/journal.pone.0070242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Toh BH, Alderuccio F, Chan J. Cutting edge: autoimmune gastritis: using the mouse to understand the human disease. J Immunol. 2000;164(4):1537–40.

    Google Scholar 

  35. Oliveira C, Seruca R, Carneiro F. Genetics, pathology, and clinics of familial gastric cancer. Int J Surg Pathol. 2006;14(1):21–33. https://doi.org/10.1177/106689690601400105.

    Article  CAS  PubMed  Google Scholar 

  36. Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012;149(6):1192–205. https://doi.org/10.1016/j.cell.2012.05.012.

    Article  CAS  PubMed  Google Scholar 

  37. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. https://doi.org/10.1016/j.cell.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  38. Huang RJ, Laszkowska M, In H, Hwang JH, Epplein M. Controlling Gastric Cancer in a world of heterogeneous risk. Gastroenterology. 2023;164(5):736–51. https://doi.org/10.1053/j.gastro.2023.01.018.

    Article  PubMed  Google Scholar 

  39. Shah SC, Piazuelo MB, Kuipers EJ, Li D, AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis. Expert Rev Gastroenterol. 2021;161(4):1325–e13327. https://doi.org/10.1053/j.gastro.2021.06.078.

    Article  CAS  Google Scholar 

  40. Honing J, Keith Tan W, Dieninyte E, O’Donovan M, Brosens L, Weusten B, di Pietro M. Adequacy of endoscopic recognition and surveillance of gastric intestinal metaplasia and atrophic gastritis: a multicentre retrospective study in low incidence countries. PLoS ONE. 2023;18(6):e0287587. https://doi.org/10.1371/journal.pone.0287587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Nakamura K, Kakukgawa Y, Sekiguchi M, Tsuruki ES, Matsumoto M, Hisada I, Mizuguchi Y, Takamaru H, Sakamoto T, Saito Y, Kobayashi N, Matsuda T. Chronological Trend of opportunistic endoscopic screening for gastric Cancer and atrophic gastritis. Asian Pac J Cancer Prev. 2024;25(4):1247–55. https://doi.org/10.31557/APJCP.2024.25.4.1247.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Wang Y, Li Y, Wang B, Ran D, Zhu C, Li P, Jiang B, Wang S. Early onset, development and histological features of gastric signet-ring cell carcinoma. Front Oncol. 2023;13:1166549. https://doi.org/10.3389/fonc.2023.1166549.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Wang Y, Shen L, Zhao G, Li B, Bu J, Zhu C, Jiang B, Wang S. Histomorphological characteristics and pathological types of hyperproliferation of gastric surface epithelial cells. Gastroenterol Res Pract. 2021;2021:8828326. https://doi.org/10.1155/2021/8828326.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Loe AKH, Rao-Bhatia A, Wei Z, Kim JE, Guan B, Qin Y, Hong M, Kwak HS, Liu X, Zhang L, Wrana JL, Guo H, Kim TH. YAP targetome reveals activation of SPEM in gastric pre-neoplastic progression and regeneration. Cell Rep. 2023;42(12):113497. https://doi.org/10.1016/j.celrep.2023.113497.

    Article  CAS  PubMed  Google Scholar 

  45. Christodoulidis G, Koumarelas KE, Kouliou MN. Revolutionizing gastric cancer treatment: the potential of immunotherapy. World J Gastroenterol. 2024;30(4):286–9. https://doi.org/10.3748/wjg.v30.i4.286.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Rubio CA, Slezak P, Ohman U, Emås S. The histological classification of early gastric cancer (micro-invasive carcinoma of the stomach). Acta Pathol Microbiol Immunol Scand A. 1982;90(5):311–6. https://doi.org/10.1111/j.1699-0463.1982.tb00099_90a.x.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was funded by the Shenzhen Longgang District Medical and Health Technology Research and Development Plan Project (Grant Number: 20231229). The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Author information

Author notes

  1. Yang-Kun Wang and Ping Li contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, The Fourth People’s Hospital of Longgang District, No.2 Jinjian Road, Nanwan Street, Longgang District, Shenzhen, 518123, Guangdong Province, China

    Yang-Kun Wang, Hai-Ying He & Si-Liang Xu

  2. Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong Province, China

    Ping Li

  3. Department of Pathology, Xuchang Central Hospital, Xuchang, 461000, Henan Province, China

    Fa-Shun Zhang

  4. Department of Pathology, 80th Army Group Hospital, Weifang, 261021, Weifang, Shandong Province, China

    Xiao-Ling Jiang

  5. Department of Pathology, Shenzhen Longgang District People’s Hospital, Shenzhen, 518172, Guangdong Province, China

    Ren-Bing Zhang

  6. Shenzhen Polytechnic University, Xili Lake, Xilihu Town, Nanshan District, Shenzhen, 518055, Guangdong Province, China

    Su-Nan Wang

Authors
  1. Yang-Kun Wang
    View author publications

    Search author on:PubMed Google Scholar

  2. Ping Li
    View author publications

    Search author on:PubMed Google Scholar

  3. Hai-Ying He
    View author publications

    Search author on:PubMed Google Scholar

  4. Fa-Shun Zhang
    View author publications

    Search author on:PubMed Google Scholar

  5. Xiao-Ling Jiang
    View author publications

    Search author on:PubMed Google Scholar

  6. Ren-Bing Zhang
    View author publications

    Search author on:PubMed Google Scholar

  7. Su-Nan Wang
    View author publications

    Search author on:PubMed Google Scholar

  8. Si-Liang Xu
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Yang-Kun Wang: Conceptualization, Funding acquisition, Writing– review & editing. Ping Li: Conceptualization, Data curation, Writing– original draft. Hai-Ying He: Data curation, Formal Analysis, Visualization. Fa-Shun Zhang: Data curation, Formal Analysis, Software. Xiao-Ling Jiang: Data curation, Formal Analysis. Ren-Bing Zhang: Data curation, Formal Analysis, Software. Su-Nan Wang: Conceptualization, Project administration, Writing– original draft. Si-Liang Xu: Conceptualization, Validation, Writing– review & editing. All authors read and approved the final draft.

Corresponding authors

Correspondence to Su-Nan Wang or Si-Liang Xu.

Ethics declarations

Ethics approval and consent to participate

This study was conducted with approval from the Ethics Committee of The Fourth People’s Hospital of Longgang District. This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, YK., Li, P., He, HY. et al. Relationship between gastric mucosal atrophy, cystic dilatation, and histopathological characteristics. BMC Gastroenterol 25, 92 (2025). https://doi.org/10.1186/s12876-025-03662-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12876-025-03662-z

Keywords

BMC Gastroenterology

ISSN: 1471-230X

Contact us