Case analysis of 24 cases of Oxyntic gland neoplasm of the stomach

Case analysis of 24 cases of Oxyntic gland neoplasm of the stomach | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Case analysis of 24 cases of Oxyntic gland neoplasm of the stomach Xinyuan Xie, Yahan Zhang, Jianhui Sun, Yangcheng Liu, Gang Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4150295/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Stomach oxyntic gland neoplasms such as oxyntic gland adenoma (OGA) and gastric adenocarcinoma of fundic gland type (GA-FG) have been included in the World Health Organization's List of Digestive System-related Malignancies in 2019. Due to the rare occurrence of the disease, some patients have been diagnosed incorrectly in certain clinical settings. This study aimed to investigate the clinicopathological aspects of Stomach oxyntic gland neoplasms by retrospectively examining clinical features, endoscopic evidence, and pathological findings to aid future clinical diagnosis. Materials and methods: A total of 45 patients with verified diagnoses of OGA and GA-FG, as well as other benign lesions were collected from a similar time duration. Patients were divided into three groups and their clinical course was studied both prospectively and retrospectively. Clinical information, including endoscopic characteristics, pathological appearance, and immunohistochemistry for MUC5AC, MUC6, CDX2, KI-67, and P53, SYN, and CgA, were analyzed in detail. Materials and methods: A total of 45 patients with verified diagnoses of OGA and GA-FG, as well as other benign lesions from the same time period, were collected from the researchers and separated into three groups, with the clinical course of all patients being studied prospectively and retrospectively. This involved comparing and analyzing available clinical information, endoscopic characteristics, pathological appearance, and immunohistochemistry for MUC5AC, MUC6, CDX2, KI-67, and P53, SYN, and CgA. Results: The 45 patients' clinical and pathologic data were divided into three groups, 18 OGA patients, 6 GA-FG patients, and 21 patients with other benign lesions. All lesions were multi-evidence confirmed. Narrow-band imaging endoscopy characterized GA-FG with the absence of clear margins. Fluorescent stain of MUC6 positively, MUC2 negatively expressed specimens further confirmed OGA and GA-FG cases. In our comparison of the three groups, gender, Hp infection, and endoscopic subepithelial changes were statistically significant among the three groups. We also observed the expression differences between groups in some hall markers. While there was no overexpression of P53, and the Ki-67 labeling index varied between 4.6% and 8% in GA-FG and OGA cases. In addition, lymphatic and vascular infiltration confirmed metastasis and recurrence were not detected in any of the cases. Conclusion: Overall, this study reports 24 cases of Stomach oxyntic gland neoplasms. While most clinical variables align with previous reports, a few of them, such as gender bias, were observed among the three groups in this study. Other key features, such as endoscopy, the hall marker stating, and treatment methods, were characterized throughout this study. Health sciences/Medical research Health sciences/Oncology Gastric adenocarcinoma of the fundic gland type Endoscopic diagnosis Endoscopic submucosal dissection Pathological diagnosis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Stomach oxyntic gland neoplasms, comprising of oxyntic gland adenoma (OGA) and gastric adenocarcinoma of fundic gland type (GA-FG), are fundic glandular tumors. The two types of Stomach oxyntic gland neoplasms exhibit minimal heterogeneity and closely resemble non-neoplastic gastric fundus gland cells[1]). The 2019 WHO Oncology Classification identifies gastric acid-secreting gland-type tumors as a novel and rare form of stomach neoplasm. It categorizes acid-secreting adenomas as non-invasive to the submucosal layer, whereas gastric fundus adenocarcinomas are characterized by submucosal infiltration( 2 ). GA-FG, a highly differentiated fundic glandular gastric cancer, occurs with a frequency of 0.98–1.6%( 3 ). GA-FG is classified into three histopathological subtypes: chief cell predominant, parietal cell predominant, and mixed phenotype( 4 ). Tumor cells in GA-FG are tightly packed, forming "endless glands", which may exhibit cytological structural heterogeneity. However, cellular heterogeneity, characterized by larger nuclei, is uncommon( 5 ). While GA-FG presents a low risk of malignancy and invasiveness, with no instances of lymphatic or venous invasion, most tumors infiltrate the submucosal layer( 3 , 4 , 6 ). In a ten-year follow-up case of GA-FG, Okumura et al observed that the tumor formed a central depressed area( 7 ). Most tumor cells in the mucosa and superficial submucosa resembled neck mucosa cells. These cells formed isolated tubular glands, extensively infiltrating the muscularis propria and subserosa. Tubular adenocarcinomas tend to exhibit a gradual transition zone between the muscularis propria and subserosa, characterized by poorly differentiated components( 7 ). GA-FG lesions originate primarily from the deep mucous layer. The lesions are covered by normal epithelium on the surface. They develop predominantly in the deep mucous layer, with one side infiltrating the submucous layer and the other side expanding throughout the entire layer. A typical characteristic of this lesion is its small size and susceptibility to infiltration of the submucosal layer. These signals reveal the rare growth pattern and submucosal infiltration in GA-FG. Together, it is suggested that GA-FG may originate in the atrophic gastric mucosa, provided the fundic glands are preserved, eventually evolving into invasive carcinoma with lymph node (LN) metastasis( 8 ). Hence, additional cases are necessary to fully understand the physiological and clinical characteristics of GA-FG. GA-FG is a well-differentiated adenocarcinoma. It is characterized by the presence of light gray-blue, basophilic columnar cells with mild nuclear heterogeneity. Immunohistochemical staining of GA-FGs shows positive pepsinogen-I (chief cell marker) and/or H + K + ATPase (parietal cell marker)( 9 ). This subtype represents a novel form of gastric cancer not associated with H. pylori ( Hp ) infection( 4 , 10 ). Although the detection rate of GA-FG has increased, many cases remain undiagnosed due to diagnostic challenges. Unlike conventional gastric cancer, GA-FG is considered to have a lower risk of metastasis, and therefore most patients undergo endoscopic submucosal dissection (ESD) only, rather than radical resection. The low occurrence of this disease results in misdiagnosis or underdiagnosis. In this study, we report a retrospective examination of 24 SOGN cases to further enhance our understanding of this disease. Materials and Methods I Clinical data This study analyzed data from 45 patients diagnosed with OGA, GA-FG, and other Benign lesions at The First Affiliated Hospital of Kunming Medical University. The research includes both prospective and retrospective analyses of clinicopathological features. II Statistical Analysis Overview of Statistical Approaches This study analyzed patient datasets with a wide range of diagnostic indicators, including categorical and continuous variables. A comprehensive statistical approach was used for accurate analysis of each data type. For categorical variables, such as smoking history, subepithelial appearance (SEL-like), history of gastroscopy, and utilization of magnifying endoscopy, chi-square tests were applied to assess distributional differences across various pathological diagnostic groups (cancer, adenoma, and others). Additionally, Fisher's exact test was considered for binary variables to enhance accuracy in a small sample size. For continuous variables, such as age and tumor size, Analysis of Variance (ANOVA) was utilized to compare the difference of means across different pathological diagnostic categories. In instances where the data did not pass the normality test, non-parametric Mann-Whitney U tests were employed to assess intergroup differences. Data Processing and Analytical Software All statistical analyses were conducted using SPSS Statistics v.29 (IBM SPSS Statistics). Data were subjected to necessary preprocessing, including handling of missing values, outlier detection, and transformation, prior to analysis. Significance Levels and Reporting In this study, all statistical tests were two-tailed, and the significance level was set at 0.05. Statistically significant findings are reported in detail in the Results section. Significant labels are indicated correspondingly under figure captions. III Methods of Pathologic Evaluation HE staining was performed using the HE staining kit (Solarbio, G1120). Briefly, specimens were fixed in a 4% neutral formaldehyde solution. Post-ESD excision, biopsy specimens were sampled at 2 mm intervals, followed by routine dehydration, paraffin embedding, and sectioning at 4 µm for HE staining. These images were obtained using Nikon’s confocal microscope (Nikon, Japan). IV Immunohistochemical assay Immunohistochemical staining was conducted via the EnVision two-step method. Antibodies targeting MUC5AC, MUC6, CDX2, KI-67, and P53 were purchased from Cell Signaling Technology (Beverly, MA, USA). Appropriate negative and positive controls were used for these markers. V Ethical Statement We hereby declare that our clinical research protocol strictly adheres to the CFDA/GCP guidelines and the Declaration of Helsinki.Additionally, this research protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Kunming Medical University, and we have obtained the corresponding approval documents.Furthermore, we have recruited human volunteers for this study and have obtained signed informed consent documents from all participants. V Data availability Data is provided within the manuscript and supplementary information files Results Clinical manifestations In this study, clinical and pathological data were collected from a total of 45 patients. One lesion sample was collected from each patient, in a total 45 lesions (Table 1). This included 18 patients with OGA (2 male, 16 female), 6 patients with GA-FG (2 male, 4 female), and 21 patients with other benign lesions (11 male, 10 female), all of whom had no family history of tumor. Notably, gender (P = 0.049) played a significant role in pathological classification, suggesting potential gender-related predispositions in the distribution (Fig. 1 ). The mean age in this study was 50.7 years for OGA patients, 56.3 years for GA-FG patients, and 55.7 years for other patients, with no statistically significant difference between the three groups. The history of alcoholism was not significant between the three groups. Although smoking history was significantly related to the benign group (P = 0.015), it may be due to the small sample size. Another important variable is the infection history of Hp (Fig. 1 ). The presence of previous infection was significantly correlated with the diagnostic categories (P = 0.0219). Only 1 of the 6 patients in GA-FG had an infection history, none of the 18 patients in OGA had an infection history, whereas 6 patients in the benign group had an infection history. Our finding here is in line with previous literature, underscoring its potential role in the etiology of gastric lesions( 11 , 12 ). Table.1 Baseline patient characteristics Characteristics GA-FG OGA Other P value n 6 18 21 Gender, n (%) 0.049* Female 4(66.67) 16(88.89) 11(52.38) Man 2(33.33) 2(11.11) 10(47.62) Age, mean ± sd 56.333 ± 10.211 50.722 ± 10.145 55.667 ± 13.044 0.3088 Smoking History, n (%) 0.015* - 4(66.67) 17(94.44) 21(100.00) + 2(33.33) 1(5.56) 0(0.00) Alcohol Consumption History, n (%) 0.464 - 6(100.00) 17(94.44) 21(100.00) + 0(0.00) 1(5.56) 0(0.00) Helicobacter pylori (Hp), n (%) 0.049* - 5(83.33) 18(100.00) 15(71.43) + 1(16.67) 0(0.00) 6(28.57) Size (mm), mean ± sd 7.33 ± 2.94 5.22 ± 2.82 5.10 ± 2.39 0.18 Color Tone (Fading, Reddening), n (%) 0.176 Fading 6(100.00) 10(55.56) 14(66.67) Reddening 0(0.00) 6(33.33) 7(33.33) Yello 0(0.00) 2(11.11) 0(0.00) Location, n (%) fundus 4 (8.9%) 9 (20%) 10 (22.2%) body 2 (4.4%) 9 (20%) 11 (24.4%) Subepithelial Manifestation (SEL-like), n (%) < 0.001*** - 0(0.00) 10(55.56) 21(100.00) + 6(100.00) 8(44.44) 0(0.00) MUC6, n (%) 0.371 - 0(0.00) 3(21.43) 0(0.00) + 6(100.00) 11(78.57) 2(100.00) ki-67, mean ± sd 0.05 ± 0.05 0.05 ± 0.04 0.08 ± 0.15 0.860 syn, n (%) 0.291 - 0(0.00) 4(28.57) 0(0.00) + 6(100.00) 10(71.43) 1(100.00) CgA, n (%) 0.575 - 6(100.00) 12(85.71) 1(100.00) + 0(0.00) 2(14.29) 0(0.00) * p < 0.05 ***p < 0.001 Features of the endoscope Endoscopic equipment, such as white light endoscopy (WLE), chromoendoscopy, magnifying endoscopy, endomicroscopy, narrow band imaging (NBI), and endoscopic molecular imaging, have improved in recent decades thanks to new technology. Recent significant developments in narrow-band imaging technology and magnifying endoscopy have made it possible to diagnose stomach cancers early( 13 ). Characteristic endoscopic alterations can potentially offer valuable insights during the diagnosis. Based on our observations, all lesions were found in the gastric body and fundus, and the lesions for Stomach oxyntic gland neoplasms were all solitary, whereas other benign lesions were observed with multiple lesions. Five of the six GA-FG patients (83.3%) had magnifying endoscopy. All (100%) GA-FG patients were observed with positive boundaries, microstructures, and microvessels, compared to 63.6% in the OGA group, and only 17% in the benign group. In this study, positive borders, positive microstructures, and positive microvessels were the most common endoscopic symptoms of GA-FG. The proportion of patients with OGA who were positive for these symptoms was 63.6%, compared to only 17% of the benign group. Endoscopic signs of GA-FG included fading tone, vasodilation of the tumor surface, and a submucosal tumor-like (SMT-like) appearance( 14 ). Based on our observations, the endoscopic features of GA-FG (white light) can be summarized as: SMT morphology, white or faded tone, dendritic vasodilatation, and background mucosa that was mainly devoid of Hp infection or did not atrophy (Fig. 2 ). GA-FG in ME-NBI, on the other hand, was distinguishable by the absence of defined edges, larger glandular apertures, enlarged inter-fossa regions, and the absence of irregular microvessels. The subepithelial lesion (SELs) of the gastrointestinal tract refers to an elevated lesion, mass, or bulge within the lumen that is usually covered by normal-appearing mucosa( 15 ). The majority of gastric SELs are benign lesions such as smooth muscle tumors and pancreatic lesions, or tumors with malignant potential, such as gastrointestinal stromal tumors (GISTs) and carcinoid tumors( 16 ). In our data statistics, all GA-FG patients(100%)had subepithelial manifestations, 8 cases of OGA had subepithelial manifestations༈44.4%), while none of the patients in the benign group had subepithelial alterations, resulting a statistically significant difference between the three groups(Fig. 3 ). It indicated that subepithelial manifestations can be useful in the diagnosis of GA-FG. Pathomorphological and immunohistochemistry Previous studies have found that GA-FG tumor tissue is located in the lamina propria and is covered by normal concave epithelium( 17 ). The glands appeared twisted, angular, cystically dilated, and anastomosed in an "endless gland" pattern. Tumor heterogeneous cells, which consisted of two types of cells, were found to be uncommon. The first type was similar to chief cells, characterized by a columnar shape and slightly basophilic cytoplasm. This type constituted the major component of the tumor. The other type was made up of ovoid or triangular parietal cells with eosinophilic and finely granular cytoplasm. This type constituted the minor component of the tumor( 3 , 18 ). Because of the characteristics of this cell, GA-FG has more submucosal invasion than cells confined within the OGA. In our investigation, all six GA-FG tumor cells penetrated the submucosal layer, which has a thickness ranging from 100 µm to 900 µm (mean 263 µm), after breaking through the mucosal muscle layer. Also, none of the 24 Stomach oxyntic gland neoplasms showed signs of intestinal chemotaxis, lymphovascular invasion, atrophy, or vascular invasion. There was no statistically significant difference observed in the sizes of the mass between the three groups: GA-FG measured 7.33 ± 2.94 (mm), OGA measured 5.22 ± 2.82 (mm), and the benign group measured 5.10 ± 2.39 (mm). In clinical practice, immunohistochemical staining is the most widely used method for diagnosing malignancies. In this study, immunohistochemical staining was utilized for both the GA-FG and OGA specimens for diagnosis and differentiation (Fig. 4 ). Fourteen OGA specimens were stained with MUC6, and out of which, 11 were diffusely positive. In the GA-FG group, all specimens were MUC6 positive. Ki-67 labeling index was expressed equally in both groups with 0.05. 4 of the 10 OGA specimens were positive for Syn, but all GA-FG specimens were positive for Syn. And 12 of the 14 OGA specimens were positive for CgA, but for GA-FG there were no specimen showed positive expression of CgA. The immunohistochemical staining results agreed with positive and negative MUC2 reports in past literature( 19 ). Treatment and prognosis Due to the rare occurrence of Stomach oxyntic gland neoplasms, additional research is needed to delve deeper into the treatment strategies. Endoscopic removal of mucosal lesions that are tiny and confined is feasible. Therefore, in this study, most of the patients were treated with ultrasound endoscopy (Fig. 5 ). However, the operator may not trust traditional biopsy forceps for excision and expects persistent lesions. Endoscopic resection is a suitable initial treatment strategy for oxyntic gland adenoma and GA-FG. For individuals who have been misdiagnosed as polypectomized, additional endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is advised, and for smaller lesions, at least EMR or loop excision followed by EMR laparotomy is recommended. Direct ESD is recommended for the complete excision of relatively big lesions, and surgical therapy is preferred in situations of large lesions with possible lymphovascular and vascular metastases from SM infiltration. In this study, 12 OGA patients were treated with ESD, and 4 patients underwent biopsy. In GA-FG, four patients were given ESD and two were given EMR (Fig. 6 ). Follow-up visits are still ongoing. Discussion Reviews focusing on the clinical aspects of GA-FG remain limited despite the increasing number of recorded cases. According to the 2019 WHO Classification of Gastric Tumors, the typical onset age for GA-FG is 60–70 years( 6 ). In Japan, the reported average age of GA-FG is 67.7 years (range 42–82 years)( 20 ). In our study, OGA patients had an average age of 50.7 years, while GA-FG patients averaged 56.3 years, and 55.7 years for other patients. Additionally, a gender bias is present in our cases, where a global male-to-female ratio of 2.2 was observed, whereas in Japanese GA-FG cases, the ratio is 1.4 ( 20 ). In contrast, the male-to-female ratio for GA-FG is 1:2 in our study, possibly limited by the small-sample-size and single-center nature of this study. GA-FG initially presents in Hp-negative and non-atrophic mucosa and is classified as an Hp-negative gastric cancer. Numerous studies have reported GA-FG as Hp infection irrelevant. However, some studies propose a positive correlation between fundic gland polyps and fundic adenocarcinoma, even in patients without a history of continuous proton pump inhibitor (PPI) use or Hp infection/eradication( 21 ). Their rationale is that the prevalence of Hp infections has risen concurrently with the increase in these cases. Differentiated adenocarcinomas are believed to arise from intestinal metaplasia, which is often associated with Hp infection. Most FG-GA originates in the non-atrophic fundic gland area, they found that in 15 out of 20 patients, lesions predominantly occurred in the non-atrophic gastric mucosa, regardless of Hp positivity or eradication status( 6 ). Currently, it remains unclear how Hp influences GA-FG progression and severity. Mucosal atrophy and Hp infection status may not be primary factors in GA-FG development( 18 ). In this study, none of the GA-FG patients had an Hp infection, aligning with previous research findings. In terms of GA-FG tumor size, most reported tumors have a diameter of less than 1 cm, though some reach up to 8.5 cm( 18 ). The risk of GA-FG transplantation and invasion increases with tumor diameter due to greater submucosal invasion. Sarcomeric GA-FG cancers are most commonly 0-IIa lesions, followed by 0-IIb, with 0-IIc and 0-I lesions being less frequent. Most lesions showed submucosal (SM) infiltration, predominantly SM1 infiltration. Fewer lesions exhibited SM2 or deeper infiltration, with intramucosal lesions being less common. The disease's clinical presentation often includes frequent SM infiltration, even in lesions of a few millimeters in size( 6 ). Some studies note that GA-FG can be identified through various methods( 19 ). As the tumor evolves, the fundic glandular type may transform into variants like the undifferentiated or tiny concave types, which possess a greater malignancy potential than GA-FG's predominantly cellular differentiation. In our study, the average size of GA-FG was 0.73 cm, and OGA was 0.53 cm. This is consistent with previous reports. It is uncommon to find multiple GA-FG lesions, as most of them are solitary. Although our study focused on single lesions, we did notice reports of patients with two simultaneous lesions in the non-atrophic zones of Hp active atrophic gastritis( 21 ). Typical endoscopic diagnosis signals of GA-FG include discolored tones, tumor surface vasodilation, and an SMT-like appearance. In a previous Janapnese report( 22 ), discolored lesions, as the hallmark of GA-FG, were noted in 52 out of 67 (77.6%) under endoscopy. Additionally, vascular dilation of the tumor surface was observed in 49 out of 67 cases (73.1%) in the same report. It is important to differentiate between vasodilation caused by Stomach oxyntic gland neoplasms and that caused by MALT lymphomas( 23 ), neuroendocrine tumors, and carcinomas. Stomach oxyntic gland neoplasms and neuroendocrine tumors share similar morphological characteristics, making it difficult to distinguish between the two. Stomach oxyntic gland neoplasms are typically found in Hp -negative environments and originate in the deep mucosal layer of tumor bulging type lesions with SMT-like changes, while neuroendocrine tumors originate in the deep mucosal layer and extend to the submucosal layer, also with SMT-like changes. Both ultrasound endoscopy and white light endoscopy can only show as deep as submucosal hypoechoic occupations, which makes ultrasound endoscopy difficult to distinguish between the two, and white light endoscopy is even worse. Gastric fundic gland polyp is originated in the epithelial layer, with a clear boundary and visible elevation, and the surface microstructure is the regular structure of the gastric fundus gland. In contrast, GA-FG has poorly defined borders, uneven microstructural expansion, extended epithelium at the crypt margins, and crypt middle region enlargement. As a result, biopsy or excision for pathologic distinction is the most effective method. Consequently, vasodilation on the tumor surface is an indication of lesions in the deep mucosal/submucosal layers, which is common to fundic glandular gastric cancers proliferating in the submucosa, but not exclusive to GA-FG. Lesions, primarily located in the mid to deep mucosa and covered by normal superficial mucosa, are similar to SMT. SMTs are appropriately described as subepithelial tumors, as they are named after their predominant location in the submucosal layer. NBI endoscopic magnification reveals features of GA-FG with indistinct boundaries, expanded glandular apertures, increased interfollicular areas, and the absence of asymmetric microvessels. In our study, all solitary tumors were located in the fundus and body of the stomach. Magnified endoscopy on 14 patients of OGA and GA-FG showed negative boundaries, positive microstructure, and negative microvessels, attributed to surface discoloration, filamentous erythematous changes, and clear capillary dilation. Subepithelial symptoms were observed in all GA-FG patients and in seven cases of OGA. White light endoscopy revealed that most GA-FG lesions exhibited an elevated morphology, similar to an SMT. In our cases, OGA and GA-FG lesions were predominantly yellow, discolored, and reddish, consistent with high-grade lesions (Fig. 3 ). GA-FG cells largely express MUC6, while MUC5AC-positive cells, indicative of indurated epithelium, are rare, showing scant P53 expression and a low Ki-67 index (average 3.6%)( 24 ). Consequently, GA-FG cells exhibit minimal invasiveness and low proliferative activity( 5 ). In our study, Fourteen OGA specimens were stained with MUC6, and out of which, 11 were diffusely positive. In the GA-FG group, all specimens were MUC6 positive. Ki-67 labeling index was expressed equally in both groups with 0.05. 4 of the 10 OGA specimens were positive for Syn, but all GA-FG specimens were positive for Syn. And 12 of the 14 OGA specimens were positive for CgA, but for GA-FG there were no specimen showed positive expression of CgA. The immunohistochemical staining results agreed with positive and negative MUC2 reports in past literature. Consequently, it is challenging to examine changes in the stomach's deepest layers, where GA-FG and OGA tumor components reside. Therefore, magnification endoscopy is not a reliable diagnostic tool, but rather a supplementary evaluation method. Conversely, magnified NBI identified some GA-FG lesions, along with typical mucosal vascular pattern (MVP) and mucosal surface pattern (MSP). Abnormal MSP and MVP observed under magnification staining may indicate GA-FG( 14 ). Chiba et al. monitored ten GA-FG lesions and found no morphologic changes after 16 months( 6 ). GA-FG tumors typically exhibit slow growth, low malignancy potential, and minimal invasiveness. Although the submucosa is frequently involved, most GA-FG tumors are benign. The GCTG recommends local excision or gastrectomy with lymph node dissection for typical gastric cancers( 24 ). Treatment decisions consider tumor size, histologic type, and estimated depth of invasion. In recent years, most GA-FG cases have been treated with surgical resection via ESD( 24 ). Overall, this study reports 24 cases of stomach oxyntic gland neoplasms. While most clinical variables align with previous reports, a few of them, such as gender bias, were observed among the three groups in this study. Other key features, such as endoscopy, the hall marker stating, and treatment methods, were characterized throughout this study. We believe our findings provide valuable insights into the clinical and pathological characteristics of stomach oxyntic gland neoplasms, contributing to the understanding and management of this rare gastric cancer subtype. Declarations Author Contribution Yangcheng Liu and Gang Yang performed the colonoscopy procedures. Xinyuan Xie collected patient data and drafted the manuscript,.Yahan Zhang conducted the statistical analysis of the data, and Jianhui Sun created the tables and organized the figures. Acknowledgement Thanks to our group.I am also grateful to my colleagues, Professor. Gang Yang, Miss Xinyuan Xie, and Miss Yahan Zhang for their invaluable assistance. Data Availability Data is provided within the manuscript and supplementary information files References Yamada S, Yamanoi K, Sato Y, Nakayama J. 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Diagn Pathol. 2020;15(1):131. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4150295","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":298931939,"identity":"bd14a99d-fea0-4394-b06c-31b4baad8d2c","order_by":0,"name":"Xinyuan Xie","email":"","orcid":"","institution":"First Affiliated Hospital of Kunming Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xinyuan","middleName":"","lastName":"Xie","suffix":""},{"id":298931941,"identity":"598fb697-95aa-4257-b91a-f083e40413c9","order_by":1,"name":"Yahan Zhang","email":"","orcid":"","institution":"First Affiliated Hospital of Kunming Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yahan","middleName":"","lastName":"Zhang","suffix":""},{"id":298931945,"identity":"877db584-01d9-4b40-a603-76539e46b402","order_by":2,"name":"Jianhui Sun","email":"","orcid":"","institution":"Fifth Hospital In Wuhan","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jianhui","middleName":"","lastName":"Sun","suffix":""},{"id":298931949,"identity":"abc70406-9a6f-4479-bb02-08fa77e6c5a8","order_by":3,"name":"Yangcheng Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYBACfobzDx9+qLCpZ2NvIFKLZOMZZmOJM2kJ/DwHiNRicPgMmwRv2+EEyRkJxLrs2NkDEpJtaXkGNx9vvMFQYxNNUAdjz7kEg4JzNsUGt9OKLRiOpeU2ENLCLHHAIEGiLI1xw+0cMwnGhsOEtbDJPzA4wMN2mHHDzTNEauFhOGPYwNN2OHHmDB4itUgwHEtmBgayMT8P0C8JxPjF/sDh4z+BUSnHxn54440PNTaEtSADA4kEUpRDtJCqYxSMglEwCkYGAABmqUWBZnvCLwAAAABJRU5ErkJggg==","orcid":"","institution":"First Affiliated Hospital of Kunming Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yangcheng","middleName":"","lastName":"Liu","suffix":""},{"id":298931951,"identity":"4a13095e-b1aa-46e7-9f01-8d9e430db421","order_by":4,"name":"Gang Yang","email":"","orcid":"","institution":"First Affiliated Hospital of Kunming Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gang","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2024-03-22 14:01:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4150295/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4150295/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56044211,"identity":"eaf0506c-4036-4b0e-a2b0-2f0987fd3f77","added_by":"auto","created_at":"2024-05-07 20:29:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":48932,"visible":true,"origin":"","legend":"\u003cp\u003eBar graphs of gender-related, \u003cem\u003eHp\u003c/em\u003e infection and Smoking history: A. Sex-associated differences: sex-associated differences in three groups: oxyntic gland adenoma (OGA), gastric adenocarcinoma of fundic gland type (GA-FG), and others (other benign lesions). There was a significant difference between the three groups (*P\u0026lt;0.05). B. \u003cem\u003eHp\u003c/em\u003e infection detection-associated differences: Hp infection-associated differences in three groups, there was a significant difference between the three groups (*P\u0026lt;0.05). C. Smoking history-associated differences: Smoking history-associated differences in three groups, there was a significant difference between the three groups (*P\u0026lt;0.05).\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-4150295/v1/429466487af61c5bcae61bd1.png"},{"id":56044604,"identity":"95b75d3d-5ad1-4eaa-826f-53c1f9885ef3","added_by":"auto","created_at":"2024-05-07 20:37:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1525746,"visible":true,"origin":"","legend":"\u003cp\u003eExamples of the characteristic endoscopic changes of reddening, faded tone and yellow at endoscopy: Reddening (A. endoscopy, D. magnifying endoscopy), Faded tone (B. endoscopy, E. magnifying endoscopy), Yellow (C. endoscopy, F. magnifying endoscopy).\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-4150295/v1/8fa483d719685c439b58f8d0.png"},{"id":56044215,"identity":"d09598e2-c459-4cf2-a01c-ebbad8f3f948","added_by":"auto","created_at":"2024-05-07 20:29:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":414507,"visible":true,"origin":"","legend":"\u003cp\u003eSubepithelial lesion (SEL)-like in endoscopic view: A. endoscopic view showing NO subepithelial lesion. B. endoscopic view showing subepithelial lesion. C.S (SEL)-like -associated differences: (SEL)-like -associated differences in three groups, there was a significant difference between the three groups (*P\u0026lt;0.05, **P\u0026lt;0.01).\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-4150295/v1/26778ed5a1632ce7797d619b.png"},{"id":56044212,"identity":"dcb1bfb3-0a57-44f1-9560-ad9f1d59dba1","added_by":"auto","created_at":"2024-05-07 20:29:19","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1810664,"visible":true,"origin":"","legend":"\u003cp\u003eTypical examples of pathology detection: OGA :(A) Lesin with white light endoscopic. (B). (B) HE staining; magnification, ×200. GA-FG: (C) Lesin with white light endoscopic. (D) HE staining; magnification, ×200.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-4150295/v1/390e7403040423eb9ca8715d.png"},{"id":56044798,"identity":"b3cd5853-e160-46e4-8e8d-3ee98281b17c","added_by":"auto","created_at":"2024-05-07 20:45:20","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":496387,"visible":true,"origin":"","legend":"\u003cp\u003eEndoscopic ultrasonography: A. Lesin with white light endoscopic B. Endoscopic ultrasonography for Lesin\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-4150295/v1/123ad6d5bf41b3b4d52e1908.png"},{"id":56044216,"identity":"438b0241-6644-46fe-96fc-fc1e107f4c5d","added_by":"auto","created_at":"2024-05-07 20:29:19","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1761136,"visible":true,"origin":"","legend":"\u003cp\u003eEndoscopic view of the procedure of ESD: A. Under white light endoscope. B. Circumferential incision. C. Submucosal dissection. D. Observation of wound. E. Clipping. F. ESD specimen.\u003c/p\u003e","description":"","filename":"image6.png","url":"https://assets-eu.researchsquare.com/files/rs-4150295/v1/c80dd09dabda43980991cf90.png"},{"id":58389131,"identity":"f4e74c48-b39f-4d49-b44c-f095b0cfa4d9","added_by":"auto","created_at":"2024-06-14 19:46:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8708029,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4150295/v1/20f8f3ba-47df-4319-8a1b-254f254389ab.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Case analysis of 24 cases of Oxyntic gland neoplasm of the stomach","fulltext":[{"header":"Introduction","content":"\u003cp\u003eStomach oxyntic gland neoplasms, comprising of oxyntic gland adenoma (OGA) and gastric adenocarcinoma of fundic gland type (GA-FG), are fundic glandular tumors. The two types of Stomach oxyntic gland neoplasms exhibit minimal heterogeneity and closely resemble non-neoplastic gastric fundus gland cells[1]). The 2019 WHO Oncology Classification identifies gastric acid-secreting gland-type tumors as a novel and rare form of stomach neoplasm. It categorizes acid-secreting adenomas as non-invasive to the submucosal layer, whereas gastric fundus adenocarcinomas are characterized by submucosal infiltration(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). GA-FG, a highly differentiated fundic glandular gastric cancer, occurs with a frequency of 0.98\u0026ndash;1.6%(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). GA-FG is classified into three histopathological subtypes: chief cell predominant, parietal cell predominant, and mixed phenotype(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Tumor cells in GA-FG are tightly packed, forming \"endless glands\", which may exhibit cytological structural heterogeneity. However, cellular heterogeneity, characterized by larger nuclei, is uncommon(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). While GA-FG presents a low risk of malignancy and invasiveness, with no instances of lymphatic or venous invasion, most tumors infiltrate the submucosal layer(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In a ten-year follow-up case of GA-FG, Okumura \u003cem\u003eet al\u003c/em\u003e observed that the tumor formed a central depressed area(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Most tumor cells in the mucosa and superficial submucosa resembled neck mucosa cells. These cells formed isolated tubular glands, extensively infiltrating the muscularis propria and subserosa. Tubular adenocarcinomas tend to exhibit a gradual transition zone between the muscularis propria and subserosa, characterized by poorly differentiated components(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGA-FG lesions originate primarily from the deep mucous layer. The lesions are covered by normal epithelium on the surface. They develop predominantly in the deep mucous layer, with one side infiltrating the submucous layer and the other side expanding throughout the entire layer. A typical characteristic of this lesion is its small size and susceptibility to infiltration of the submucosal layer. These signals reveal the rare growth pattern and submucosal infiltration in GA-FG. Together, it is suggested that GA-FG may originate in the atrophic gastric mucosa, provided the fundic glands are preserved, eventually evolving into invasive carcinoma with lymph node (LN) metastasis(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Hence, additional cases are necessary to fully understand the physiological and clinical characteristics of GA-FG.\u003c/p\u003e \u003cp\u003eGA-FG is a well-differentiated adenocarcinoma. It is characterized by the presence of light gray-blue, basophilic columnar cells with mild nuclear heterogeneity. Immunohistochemical staining of GA-FGs shows positive pepsinogen-I (chief cell marker) and/or H\u0026thinsp;+\u0026thinsp;K\u0026thinsp;+\u0026thinsp;ATPase (parietal cell marker)(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). This subtype represents a novel form of gastric cancer not associated with \u003cem\u003eH. pylori\u003c/em\u003e (\u003cem\u003eHp\u003c/em\u003e) infection(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Although the detection rate of GA-FG has increased, many cases remain undiagnosed due to diagnostic challenges. Unlike conventional gastric cancer, GA-FG is considered to have a lower risk of metastasis, and therefore most patients undergo endoscopic submucosal dissection (ESD) only, rather than radical resection. The low occurrence of this disease results in misdiagnosis or underdiagnosis. In this study, we report a retrospective examination of 24 SOGN cases to further enhance our understanding of this disease.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eI Clinical data\u003c/h2\u003e \u003cp\u003eThis study analyzed data from 45 patients diagnosed with OGA, GA-FG, and other Benign lesions at The First Affiliated Hospital of Kunming Medical University. The research includes both prospective and retrospective analyses of clinicopathological features.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eII Statistical Analysis\u003c/h2\u003e \u003cp\u003eOverview of Statistical Approaches\u003c/p\u003e \u003cp\u003eThis study analyzed patient datasets with a wide range of diagnostic indicators, including categorical and continuous variables. A comprehensive statistical approach was used for accurate analysis of each data type.\u003c/p\u003e \u003cp\u003eFor categorical variables, such as smoking history, subepithelial appearance (SEL-like), history of gastroscopy, and utilization of magnifying endoscopy, chi-square tests were applied to assess distributional differences across various pathological diagnostic groups (cancer, adenoma, and others). Additionally, Fisher's exact test was considered for binary variables to enhance accuracy in a small sample size.\u003c/p\u003e \u003cp\u003eFor continuous variables, such as age and tumor size, Analysis of Variance (ANOVA) was utilized to compare the difference of means across different pathological diagnostic categories. In instances where the data did not pass the normality test, non-parametric Mann-Whitney U tests were employed to assess intergroup differences.\u003c/p\u003e \u003cp\u003eData Processing and Analytical Software\u003c/p\u003e \u003cp\u003eAll statistical analyses were conducted using SPSS Statistics v.29 (IBM SPSS Statistics). Data were subjected to necessary preprocessing, including handling of missing values, outlier detection, and transformation, prior to analysis.\u003c/p\u003e \u003cp\u003eSignificance Levels and Reporting\u003c/p\u003e \u003cp\u003eIn this study, all statistical tests were two-tailed, and the significance level was set at 0.05. Statistically significant findings are reported in detail in the \u003cspan refid=\"Sec9\" class=\"InternalRef\"\u003eResults\u003c/span\u003e section. Significant labels are indicated correspondingly under figure captions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eIII Methods of Pathologic Evaluation\u003c/h2\u003e \u003cp\u003eHE staining was performed using the HE staining kit (Solarbio, G1120). Briefly, specimens were fixed in a 4% neutral formaldehyde solution. Post-ESD excision, biopsy specimens were sampled at 2 mm intervals, followed by routine dehydration, paraffin embedding, and sectioning at 4 \u0026micro;m for HE staining. These images were obtained using Nikon\u0026rsquo;s confocal microscope (Nikon, Japan).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eIV Immunohistochemical assay\u003c/h2\u003e \u003cp\u003eImmunohistochemical staining was conducted via the EnVision two-step method. Antibodies targeting MUC5AC, MUC6, CDX2, KI-67, and P53 were purchased from Cell Signaling Technology (Beverly, MA, USA). Appropriate negative and positive controls were used for these markers.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eV Ethical Statement\u003c/h2\u003e \u003cp\u003e We hereby declare that our clinical research protocol strictly adheres to the CFDA/GCP guidelines and the Declaration of Helsinki.Additionally, this research protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Kunming Medical University, and we have obtained the corresponding approval documents.Furthermore, we have recruited human volunteers for this study and have obtained signed informed consent documents from all participants.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eV Data availability\u003c/h2\u003e \u003cp\u003e Data is provided within the manuscript and supplementary information files\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eClinical manifestations\u003c/h2\u003e \u003cp\u003eIn this study, clinical and pathological data were collected from a total of 45 patients. One lesion sample was collected from each patient, in a total 45 lesions (Table\u0026nbsp;1). This included 18 patients with OGA (2 male, 16 female), 6 patients with GA-FG (2 male, 4 female), and 21 patients with other benign lesions (11 male, 10 female), all of whom had no family history of tumor. Notably, gender (P\u0026thinsp;=\u0026thinsp;0.049) played a significant role in pathological classification, suggesting potential gender-related predispositions in the distribution (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe mean age in this study was 50.7 years for OGA patients, 56.3 years for GA-FG patients, and 55.7 years for other patients, with no statistically significant difference between the three groups. The history of alcoholism was not significant between the three groups. Although smoking history was significantly related to the benign group (P\u0026thinsp;=\u0026thinsp;0.015), it may be due to the small sample size. Another important variable is the infection history of \u003cem\u003eHp\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The presence of previous infection was significantly correlated with the diagnostic categories (P\u0026thinsp;=\u0026thinsp;0.0219). Only 1 of the 6 patients in GA-FG had an infection history, none of the 18 patients in OGA had an infection history, whereas 6 patients in the benign group had an infection history. Our finding here is in line with previous literature, underscoring its potential role in the etiology of gastric lesions(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable.1 Baseline patient characteristics\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGA-FG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOGA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.049*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(66.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(88.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11(52.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(11.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(47.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.333\u0026thinsp;\u0026plusmn;\u0026thinsp;10.211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.722\u0026thinsp;\u0026plusmn;\u0026thinsp;10.145\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55.667\u0026thinsp;\u0026plusmn;\u0026thinsp;13.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.3088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking History, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.015*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(66.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(94.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(5.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol Consumption History, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(94.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(5.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHelicobacter pylori (Hp), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.049*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(83.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15(71.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(16.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(28.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSize (mm), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.22\u0026thinsp;\u0026plusmn;\u0026thinsp;2.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.10\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColor Tone (Fading, Reddening), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.176\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(55.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14(66.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReddening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(33.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYello\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(11.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003efundus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e10 (22.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ebody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e11 (24.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubepithelial Manifestation (SEL-like), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(55.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e21(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(44.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMUC6, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.371\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(21.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(78.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eki-67, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.860\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esyn, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.291\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(28.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(71.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCgA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.575\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(85.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1(100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(14.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 ***p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eFeatures of the endoscope\u003c/h2\u003e \u003cp\u003eEndoscopic equipment, such as white light endoscopy (WLE), chromoendoscopy, magnifying endoscopy, endomicroscopy, narrow band imaging (NBI), and endoscopic molecular imaging, have improved in recent decades thanks to new technology. Recent significant developments in narrow-band imaging technology and magnifying endoscopy have made it possible to diagnose stomach cancers early(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Characteristic endoscopic alterations can potentially offer valuable insights during the diagnosis. Based on our observations, all lesions were found in the gastric body and fundus, and the lesions for Stomach oxyntic gland neoplasms were all solitary, whereas other benign lesions were observed with multiple lesions. Five of the six GA-FG patients (83.3%) had magnifying endoscopy. All (100%) GA-FG patients were observed with positive boundaries, microstructures, and microvessels, compared to 63.6% in the OGA group, and only 17% in the benign group. In this study, positive borders, positive microstructures, and positive microvessels were the most common endoscopic symptoms of GA-FG. The proportion of patients with OGA who were positive for these symptoms was 63.6%, compared to only 17% of the benign group. Endoscopic signs of GA-FG included fading tone, vasodilation of the tumor surface, and a submucosal tumor-like (SMT-like) appearance(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Based on our observations, the endoscopic features of GA-FG (white light) can be summarized as: SMT morphology, white or faded tone, dendritic vasodilatation, and background mucosa that was mainly devoid of Hp infection or did not atrophy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). GA-FG in ME-NBI, on the other hand, was distinguishable by the absence of defined edges, larger glandular apertures, enlarged inter-fossa regions, and the absence of irregular microvessels.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe subepithelial lesion (SELs) of the gastrointestinal tract refers to an elevated lesion, mass, or bulge within the lumen that is usually covered by normal-appearing mucosa(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The majority of gastric SELs are benign lesions such as smooth muscle tumors and pancreatic lesions, or tumors with malignant potential, such as gastrointestinal stromal tumors (GISTs) and carcinoid tumors(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In our data statistics, all GA-FG patients(100%)had subepithelial manifestations, 8 cases of OGA had subepithelial manifestations༈44.4%), while none of the patients in the benign group had subepithelial alterations, resulting a statistically significant difference between the three groups(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). It indicated that subepithelial manifestations can be useful in the diagnosis of GA-FG.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePathomorphological and immunohistochemistry\u003c/h2\u003e \u003cp\u003ePrevious studies have found that GA-FG tumor tissue is located in the lamina propria and is covered by normal concave epithelium(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The glands appeared twisted, angular, cystically dilated, and anastomosed in an \"endless gland\" pattern. Tumor heterogeneous cells, which consisted of two types of cells, were found to be uncommon. The first type was similar to chief cells, characterized by a columnar shape and slightly basophilic cytoplasm. This type constituted the major component of the tumor. The other type was made up of ovoid or triangular parietal cells with eosinophilic and finely granular cytoplasm. This type constituted the minor component of the tumor(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBecause of the characteristics of this cell, GA-FG has more submucosal invasion than cells confined within the OGA. In our investigation, all six GA-FG tumor cells penetrated the submucosal layer, which has a thickness ranging from 100 \u0026micro;m to 900 \u0026micro;m (mean 263 \u0026micro;m), after breaking through the mucosal muscle layer. Also, none of the 24 Stomach oxyntic gland neoplasms showed signs of intestinal chemotaxis, lymphovascular invasion, atrophy, or vascular invasion. There was no statistically significant difference observed in the sizes of the mass between the three groups: GA-FG measured 7.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.94 (mm), OGA measured 5.22\u0026thinsp;\u0026plusmn;\u0026thinsp;2.82 (mm), and the benign group measured 5.10\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39 (mm).\u003c/p\u003e \u003cp\u003eIn clinical practice, immunohistochemical staining is the most widely used method for diagnosing malignancies. In this study, immunohistochemical staining was utilized for both the GA-FG and OGA specimens for diagnosis and differentiation (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Fourteen OGA specimens were stained with MUC6, and out of which, 11 were diffusely positive. In the GA-FG group, all specimens were MUC6 positive. Ki-67 labeling index was expressed equally in both groups with 0.05. 4 of the 10 OGA specimens were positive for Syn, but all GA-FG specimens were positive for Syn. And 12 of the 14 OGA specimens were positive for CgA, but for GA-FG there were no specimen showed positive expression of CgA. The immunohistochemical staining results agreed with positive and negative MUC2 reports in past literature(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eTreatment and prognosis\u003c/h2\u003e \u003cp\u003eDue to the rare occurrence of Stomach oxyntic gland neoplasms, additional research is needed to delve deeper into the treatment strategies. Endoscopic removal of mucosal lesions that are tiny and confined is feasible. Therefore, in this study, most of the patients were treated with ultrasound endoscopy (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). However, the operator may not trust traditional biopsy forceps for excision and expects persistent lesions. Endoscopic resection is a suitable initial treatment strategy for oxyntic gland adenoma and GA-FG. For individuals who have been misdiagnosed as polypectomized, additional endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is advised, and for smaller lesions, at least EMR or loop excision followed by EMR laparotomy is recommended. Direct ESD is recommended for the complete excision of relatively big lesions, and surgical therapy is preferred in situations of large lesions with possible lymphovascular and vascular metastases from SM infiltration. In this study, 12 OGA patients were treated with ESD, and 4 patients underwent biopsy. In GA-FG, four patients were given ESD and two were given EMR (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Follow-up visits are still ongoing.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eReviews focusing on the clinical aspects of GA-FG remain limited despite the increasing number of recorded cases. According to the 2019 WHO Classification of Gastric Tumors, the typical onset age for GA-FG is 60\u0026ndash;70 years(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In Japan, the reported average age of GA-FG is 67.7 years (range 42\u0026ndash;82 years)(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In our study, OGA patients had an average age of 50.7 years, while GA-FG patients averaged 56.3 years, and 55.7 years for other patients. Additionally, a gender bias is present in our cases, where a global male-to-female ratio of 2.2 was observed, whereas in Japanese GA-FG cases, the ratio is 1.4 (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In contrast, the male-to-female ratio for GA-FG is 1:2 in our study, possibly limited by the small-sample-size and single-center nature of this study.\u003c/p\u003e \u003cp\u003eGA-FG initially presents in Hp-negative and non-atrophic mucosa and is classified as an Hp-negative gastric cancer. Numerous studies have reported GA-FG as Hp infection irrelevant. However, some studies propose a positive correlation between fundic gland polyps and fundic adenocarcinoma, even in patients without a history of continuous proton pump inhibitor (PPI) use or \u003cem\u003eHp\u003c/em\u003e infection/eradication(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Their rationale is that the prevalence of \u003cem\u003eHp\u003c/em\u003e infections has risen concurrently with the increase in these cases. Differentiated adenocarcinomas are believed to arise from intestinal metaplasia, which is often associated with \u003cem\u003eHp\u003c/em\u003e infection. Most FG-GA originates in the non-atrophic fundic gland area, they found that in 15 out of 20 patients, lesions predominantly occurred in the non-atrophic gastric mucosa, regardless of Hp positivity or eradication status(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Currently, it remains unclear how \u003cem\u003eHp\u003c/em\u003e influences GA-FG progression and severity. Mucosal atrophy and \u003cem\u003eHp\u003c/em\u003e infection status may not be primary factors in GA-FG development(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In this study, none of the GA-FG patients had an Hp infection, aligning with previous research findings.\u003c/p\u003e \u003cp\u003eIn terms of GA-FG tumor size, most reported tumors have a diameter of less than 1 cm, though some reach up to 8.5 cm(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The risk of GA-FG transplantation and invasion increases with tumor diameter due to greater submucosal invasion. Sarcomeric GA-FG cancers are most commonly 0-IIa lesions, followed by 0-IIb, with 0-IIc and 0-I lesions being less frequent. Most lesions showed submucosal (SM) infiltration, predominantly SM1 infiltration. Fewer lesions exhibited SM2 or deeper infiltration, with intramucosal lesions being less common. The disease's clinical presentation often includes frequent SM infiltration, even in lesions of a few millimeters in size(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Some studies note that GA-FG can be identified through various methods(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). As the tumor evolves, the fundic glandular type may transform into variants like the undifferentiated or tiny concave types, which possess a greater malignancy potential than GA-FG's predominantly cellular differentiation. In our study, the average size of GA-FG was 0.73 cm, and OGA was 0.53 cm. This is consistent with previous reports. It is uncommon to find multiple GA-FG lesions, as most of them are solitary. Although our study focused on single lesions, we did notice reports of patients with two simultaneous lesions in the non-atrophic zones of \u003cem\u003eHp\u003c/em\u003e active atrophic gastritis(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTypical endoscopic diagnosis signals of GA-FG include discolored tones, tumor surface vasodilation, and an SMT-like appearance. In a previous Janapnese report(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), discolored lesions, as the hallmark of GA-FG, were noted in 52 out of 67 (77.6%) under endoscopy. Additionally, vascular dilation of the tumor surface was observed in 49 out of 67 cases (73.1%) in the same report. It is important to differentiate between vasodilation caused by Stomach oxyntic gland neoplasms and that caused by MALT lymphomas(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), neuroendocrine tumors, and carcinomas. Stomach oxyntic gland neoplasms and neuroendocrine tumors share similar morphological characteristics, making it difficult to distinguish between the two. Stomach oxyntic gland neoplasms are typically found in \u003cem\u003eHp\u003c/em\u003e-negative environments and originate in the deep mucosal layer of tumor bulging type lesions with SMT-like changes, while neuroendocrine tumors originate in the deep mucosal layer and extend to the submucosal layer, also with SMT-like changes. Both ultrasound endoscopy and white light endoscopy can only show as deep as submucosal hypoechoic occupations, which makes ultrasound endoscopy difficult to distinguish between the two, and white light endoscopy is even worse. Gastric fundic gland polyp is originated in the epithelial layer, with a clear boundary and visible elevation, and the surface microstructure is the regular structure of the gastric fundus gland. In contrast, GA-FG has poorly defined borders, uneven microstructural expansion, extended epithelium at the crypt margins, and crypt middle region enlargement. As a result, biopsy or excision for pathologic distinction is the most effective method.\u003c/p\u003e \u003cp\u003eConsequently, vasodilation on the tumor surface is an indication of lesions in the deep mucosal/submucosal layers, which is common to fundic glandular gastric cancers proliferating in the submucosa, but not exclusive to GA-FG. Lesions, primarily located in the mid to deep mucosa and covered by normal superficial mucosa, are similar to SMT. SMTs are appropriately described as subepithelial tumors, as they are named after their predominant location in the submucosal layer. NBI endoscopic magnification reveals features of GA-FG with indistinct boundaries, expanded glandular apertures, increased interfollicular areas, and the absence of asymmetric microvessels. In our study, all solitary tumors were located in the fundus and body of the stomach. Magnified endoscopy on 14 patients of OGA and GA-FG showed negative boundaries, positive microstructure, and negative microvessels, attributed to surface discoloration, filamentous erythematous changes, and clear capillary dilation. Subepithelial symptoms were observed in all GA-FG patients and in seven cases of OGA. White light endoscopy revealed that most GA-FG lesions exhibited an elevated morphology, similar to an SMT. In our cases, OGA and GA-FG lesions were predominantly yellow, discolored, and reddish, consistent with high-grade lesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGA-FG cells largely express MUC6, while MUC5AC-positive cells, indicative of indurated epithelium, are rare, showing scant P53 expression and a low Ki-67 index (average 3.6%)(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Consequently, GA-FG cells exhibit minimal invasiveness and low proliferative activity(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In our study, Fourteen OGA specimens were stained with MUC6, and out of which, 11 were diffusely positive. In the GA-FG group, all specimens were MUC6 positive. Ki-67 labeling index was expressed equally in both groups with 0.05. 4 of the 10 OGA specimens were positive for Syn, but all GA-FG specimens were positive for Syn. And 12 of the 14 OGA specimens were positive for CgA, but for GA-FG there were no specimen showed positive expression of CgA. The immunohistochemical staining results agreed with positive and negative MUC2 reports in past literature. Consequently, it is challenging to examine changes in the stomach's deepest layers, where GA-FG and OGA tumor components reside. Therefore, magnification endoscopy is not a reliable diagnostic tool, but rather a supplementary evaluation method. Conversely, magnified NBI identified some GA-FG lesions, along with typical mucosal vascular pattern (MVP) and mucosal surface pattern (MSP). Abnormal MSP and MVP observed under magnification staining may indicate GA-FG(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Chiba et al. monitored ten GA-FG lesions and found no morphologic changes after 16 months(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGA-FG tumors typically exhibit slow growth, low malignancy potential, and minimal invasiveness. Although the submucosa is frequently involved, most GA-FG tumors are benign. The GCTG recommends local excision or gastrectomy with lymph node dissection for typical gastric cancers(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Treatment decisions consider tumor size, histologic type, and estimated depth of invasion. In recent years, most GA-FG cases have been treated with surgical resection via ESD(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOverall, this study reports 24 cases of stomach oxyntic gland neoplasms. While most clinical variables align with previous reports, a few of them, such as gender bias, were observed among the three groups in this study. Other key features, such as endoscopy, the hall marker stating, and treatment methods, were characterized throughout this study. We believe our findings provide valuable insights into the clinical and pathological characteristics of stomach oxyntic gland neoplasms, contributing to the understanding and management of this rare gastric cancer subtype.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYangcheng Liu and Gang Yang performed the colonoscopy procedures. Xinyuan Xie collected patient data and drafted the manuscript,.Yahan Zhang conducted the statistical analysis of the data, and Jianhui Sun created the tables and organized the figures.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThanks to our group.I am also grateful to my colleagues, Professor. Gang Yang, Miss Xinyuan Xie, and Miss Yahan Zhang for their invaluable assistance.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is provided within the manuscript and supplementary information files\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYamada S, Yamanoi K, Sato Y, Nakayama J. Diffuse MIST1 expression and decreased α1,4-linked N-acetylglucosamine (αGlcNAc) glycosylation on MUC6 are distinct hallmarks for gastric neoplasms showing oxyntic gland differentiation. Histopathology. 2020;77(3):413\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76(2):182\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiyazawa M, Matsuda M, Yano M, Hara Y, Arihara F, Horita Y, et al. Gastric adenocarcinoma of fundic gland type: Five cases treated with endoscopic resection. World J Gastroenterol. 2015;21(26):8208\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenedict MA, Lauwers GY, Jain D. Gastric Adenocarcinoma of the Fundic Gland Type: Update and Literature Review. Am J Clin Pathol. 2018;149(6):461\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng XY, Yang G, Dong CJ, Zheng RY. Gastric adenocarcinoma of the fundic gland: A review of clinicopathological characteristics, treatment and prognosis. Rare Tumors. 2021;13:20363613211060171.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiba T, Kato K, Masuda T, Ohara S, Iwama N, Shimada T, et al. Clinicopathological features of gastric adenocarcinoma of the fundic gland (chief cell predominant type) by retrospective and prospective analyses of endoscopic findings. Dig Endosc Off J Jpn Gastroenterol Endosc Soc. 2016;28(7):722\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkumura Y, Takamatsu M, Ohashi M, Yamamoto Y, Yamamoto N, Kawachi H, et al. Gastric Adenocarcinoma of Fundic Gland Type with Aggressive Transformation and Lymph Node Metastasis: a Case Report. J Gastric Cancer. 2018;18(4):409\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUeo T, Yonemasu H, Ishida T. Gastric adenocarcinoma of fundic gland type with unusual behavior. Dig Endosc Off J Jpn Gastroenterol Endosc Soc. 2014;26(2):293\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUeyama H, Yao T, Akazawa Y, Hayashi T, Kurahara K, Oshiro Y, et al. Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type. J Gastroenterol. 2021;56(9):814\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUeyama H, Yao T, Nakashima Y, Hirakawa K, Oshiro Y, Hirahashi M, et al. Gastric adenocarcinoma of fundic gland type (chief cell predominant type): proposal for a new entity of gastric adenocarcinoma. Am J Surg Pathol. 2010;34(5):609\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTohda G, Osawa T, Asada Y, Dochin M, Terahata S. Gastric adenocarcinoma of fundic gland type: Endoscopic and clinicopathological features. World J Gastrointest Endosc. 2016;8(4):244\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan K, Brown IS, Kyle T, Lauwers GY, Kumarasinghe MP. Chief cell-predominant gastric polyps: a series of 12 cases with literature review. Histopathology. 2016;68(6):825\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHayee B, Inoue H, Sato H, Santi EG, Yoshida A, Onimaru M, et al. Magnification narrow-band imaging for the diagnosis of early gastric cancer: a review of the Japanese literature for the Western endoscopist. Gastrointest Endosc. 2013;78(3):452\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatsumoto K, Ueyama H, Yao T, Iwano T, Yamamoto M, Utsunomiya H, et al. Endoscopic Features of Gastric Epithelial Neoplasm of Fundic Gland Mucosa Lineage. Diagnostics. 2022;12(11):2666.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGong EJ, Kim DH. Endoscopic Ultrasonography in the Diagnosis of Gastric Subepithelial Lesions. Clin Endosc. 2016;49(5):425\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong JH, Kim SG, Chung SJ, Kang HY, Yang SY, Kim YS. Risk of progression for incidental small subepithelial tumors in the upper gastrointestinal tract. Endoscopy. 2015;47(8):675\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsukamoto T, Yokoi T, Maruta S, Kitamura M, Yamamoto T, Ban H, et al. Gastric adenocarcinoma with chief cell differentiation. Pathol Int. 2007;57(8):517\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNomura R, Saito T, Mitomi H, Hidaka Y, Lee S yong, Watanabe S, et al. GNAS mutation as an alternative mechanism of activation of the Wnt/β-catenin signaling pathway in gastric adenocarcinoma of the fundic gland type. Hum Pathol. 2014;45(12):2488\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIwamuro M, Kusumoto C, Nakagawa M, Kobayashi S, Yoshioka M, Inaba T, et al. Endoscopic resection is a suitable initial treatment strategy for oxyntic gland adenoma or gastric adenocarcinoma of the fundic gland type. Sci Rep. 2021;11:7375.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManabe S, Mukaisho KI, Yasuoka T, Usui F, Matsuyama T, Hirata I, et al. Gastric adenocarcinoma of fundic gland type spreading to heterotopic gastric glands. World J Gastroenterol. 2017;23(38):7047\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang M, Sun X, Chen Y, Yang P. Twenty cases of gastric adenocarcinoma of the fundic gland type. Scand J Gastroenterol. 2023;58(7):744\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKino H, Nakano M, Kanamori A, Suzuki T, Kaneko Y, Tsuchida C, et al. Gastric Adenocarcinoma of the Fundic Gland Type after Endoscopic Therapy for Metachronous Gastric Cancer. Intern Med Tokyo Jpn. 2018;57(6):795\u0026ndash;800.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakigawa H, Masaki S, Naito T, Yuge R, Urabe Y, Tanaka S, et al. Helicobacter suis infection is associated with nodular gastritis-like appearance of gastric mucosa‐associated lymphoid tissue lymphoma. Cancer Med. 2019;8(9):4370\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi C, Wu X, Yang S, Yang X, Yao J, Zheng H. Gastric adenocarcinoma of the fundic gland type: clinicopathological features of eight patients treated with endoscopic submucosal dissection. Diagn Pathol. 2020;15(1):131.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Gastric adenocarcinoma of the fundic gland type, Endoscopic diagnosis, Endoscopic submucosal dissection, Pathological diagnosis","lastPublishedDoi":"10.21203/rs.3.rs-4150295/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4150295/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eStomach oxyntic gland neoplasms such as oxyntic gland adenoma (OGA) and gastric adenocarcinoma of fundic gland type (GA-FG) have been included in the World Health Organization's List of Digestive System-related Malignancies in 2019. Due to the rare occurrence of the disease, some patients have been diagnosed incorrectly in certain clinical settings. This study aimed to investigate the clinicopathological aspects of Stomach oxyntic gland neoplasms by retrospectively examining clinical features, endoscopic evidence, and pathological findings to aid future clinical diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and methods:\u003c/strong\u003e A total of 45 patients with verified diagnoses of OGA and GA-FG, as well as other benign lesions were collected from a similar time duration. Patients were divided into three groups and their clinical course was studied both prospectively and retrospectively. Clinical information, including endoscopic characteristics, pathological appearance, and immunohistochemistry for MUC5AC, MUC6, CDX2, KI-67, and P53, SYN, and CgA, were analyzed in detail.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and methods: \u003c/strong\u003eA total of 45 patients with verified diagnoses of OGA and GA-FG, as well as other benign lesions from the same time period, were collected from the researchers and separated into three groups, with the clinical course of all patients being studied prospectively and retrospectively. This involved comparing and analyzing available clinical information, endoscopic characteristics, pathological appearance, and immunohistochemistry for MUC5AC, MUC6, CDX2, KI-67, and P53, SYN, and CgA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe 45 patients' clinical and pathologic data were divided into three groups, 18 OGA patients, 6 GA-FG patients, and 21 patients with other benign lesions. All lesions were multi-evidence confirmed. Narrow-band imaging endoscopy characterized GA-FG with the absence of clear margins. Fluorescent stain of MUC6 positively, MUC2 negatively expressed specimens further confirmed OGA and GA-FG cases. In our comparison of the three groups, gender, \u003cem\u003eHp\u003c/em\u003e infection, and endoscopic \u0026nbsp;subepithelial changes were statistically significant among the three groups. \u0026nbsp;We also observed the expression differences between groups in some hall \u0026nbsp;markers. While there was no overexpression of P53, and the Ki-67 labeling index \u0026nbsp;varied between 4.6% and 8% in GA-FG and OGA cases. In addition, lymphatic and \u0026nbsp;vascular infiltration confirmed metastasis and recurrence were not detected in \u0026nbsp;any of the cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eOverall, this study reports 24 cases of Stomach oxyntic gland \u0026nbsp;neoplasms. While most clinical variables align with previous reports, a few of \u0026nbsp;them, such as gender bias, were observed among the three groups in this study. \u0026nbsp;Other key features, such as endoscopy, the hall marker stating, and treatment \u0026nbsp;methods, were characterized throughout this study.\u003c/p\u003e","manuscriptTitle":"Case analysis of 24 cases of Oxyntic gland neoplasm of the stomach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-07 20:29:15","doi":"10.21203/rs.3.rs-4150295/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"430e408f-f794-4d41-8a3b-35e7ad1d66f2","owner":[],"postedDate":"May 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":31536852,"name":"Health sciences/Medical research"},{"id":31536853,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2024-06-14T19:38:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-07 20:29:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4150295","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4150295","identity":"rs-4150295","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}