Fundic Research Articles

Prenatal Histomorphological and Histochemical Study of Stomach in Indigenous Rabbit (Oryctolagus cuniculus)

The present study was designed to investigate the normal histological features of the stomach at the prenatal stage from ten healthy pregnant rabbits at the third period of pregnancy. The stomach appeared as J-shaped situated at the left part of the abdominal cavity. It found in the front part entirely within the rib. The non-glandular region act as a reservoir, the septa prevented ingesta reflux into the esophagus. Histologically the stomach in both periods composed of four tunics', which were mucosa, tunica submucosa, tunica muscularis and tunica serosa. The stomach also has different regions cardiac, fundic and pyloric regions, glands in the cardiac region were coiled branched tubular gland and almost present of the mucous cells with a few chief cells. In the fundic region the glands in this part were long and simple tubular. There are four secretory cell types: mucous cells, chief cells, parietal cells and endocrine cells, glands in the pyloric region were branched coiled tubular glands which opened at the pits of the pyloric part. The mucous-secreting cell always persists, the pyloric sphincter muscle found as thickened muscle in the pyloric duodenal junction. With PAS stain reaction gave a positive reaction for Cardiac and pyloric glands secretion which indicates the present of neutral mucopolysaccharides. In conclusion, it was found that the histomorphological features of the stomach in prenatal period embryos at the third stage of pregnancy of rabbit it was changed according to the age and food intake after birth.

Morphological digital assessment and transcripts of gastric and duodenal visfatin in growing piglets fed with increasing amounts of polyphenols from olive mill waste extract.

Visfatin is an adipokine with mediatory effects on inflammation. It is expressed at low levels in the pig stomach, but its role in the gastrointestinal (GI) tract is not well understood. This study explored visfatin expression and localization in the stomach and duodenum of piglets fed varying levels of polyphenols derived from olive mill waste extract, known for their antioxidant and immunomodulatory properties. Twenty-seven piglets were assigned to three dietary groups: control (commercial feed), low polyphenol (120 ppm), and high polyphenol (240 ppm) groups. After 14 days of feeding, samples from the glandular stomach and duodenum were collected from 13 piglets. Immunohistochemistry (IHC), digital image analysis (DIA) using QuPath software, and double-label immunofluorescence were performed to detect visfatin-positive cells and co-localize them with serotonin. Additionally, relative gene expression of visfatin was assessed via RT-qPCR. Visfatin-positive cells were identified in 5 out of 13 piglets, localized mainly in the basal portion of gastric and intestinal glands. The morphology of those cells was consistent with neuroendocrine cells and confirmed by co-localization of visfatin and serotonin. No significant differences were found in cell positivity or morphology between dietary groups or between tissues. However, visfatin transcript levels increased with the dose of polyphenolic extract. These findings suggest that dietary polyphenols may modulate visfatin gene expression in the GI tract. The study also highlights the value of digital anatomy for enhancing the accuracy and reproducibility of anatomical research. Further studies are needed to elucidate the functional role of visfatin transcript and protein in the porcine GI tract.

Single-cell integration reveals metaplasia in inflammatory gut diseases

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease3. Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn’s disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner’s glands. Although previously linked to mucosal healing4, we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases.

Endoscopic features of the duodenal pyloric gland adenoma: A case series of 14 patients.

Pyloric gland adenoma (PGA) is a distinct subtype of duodenal adenoma. PGA has been increasingly recognized as a histologically and molecularly distinct entity; however, its endoscopic features have not been precisely described. This study aims to investigate the endoscopic characteristics of duodenal PGA, including the association of their putative precursors, Brunner's gland hyperplasia (BGH), and gastric epithelial heterotopia/metaplasia (GEM/H). This study was a single-center, retrospective case series. Fourteen consecutive patients with duodenal PGA were retrieved from the pathological database. PGA was diagnosed according to the World Health Organization classification. The median tumor size was 22.5 mm (range: 12-40 mm), and 79% of cases were located in the first part of the duodenum. Six PGAs demonstrated high-grade dysplasia. PGA could be classified into two subtypes based on their appearance: villous lobulated type and smoothly protruding type. BGH and GEM/H were identified in the background mucosa in 28% and 7% of the cases, respectively. BGH was more abundant in the background mucosa of the PGA group than in the control group (p < 0.05). Six PGAs (43%) exhibited high-grade dysplasia, and no significant difference was observed in the endoscopic findings between low- and high-grade dysplasia. The 14 patients with PGA demonstrated characteristic endoscopic findings. BGH and GEM/H might be precursors of PGA.

A Pathological Assessment of the Microvasculature of Biliary Tract Neoplasms Referring to Pre-Existing Blood Vessels and Vessel Co-Option.

There are several types of microvasculature supplying neoplasms: "newly formed blood vessels" (neoangiogenesis), which are a component of the tumor microenvironment (TME) of invasive carcinoma with wound healing-like reaction; and "pre-existing blood vessels", which are used as tumor-supplying vessels by neoplasms (co-option vessels) and are likely to develop in hypervascularized organs. We herein review the microvasculature of neoplasms of biliary tract with reference to pre-existing vessels and vessel co-options. In the hepatobiliary system, intrahepatic large and extrahepatic bile ducts (large bile ducts) and the gallbladder as well as hepatic lobules are highly vascularized regions. In large bile ducts, the biliary lining epithelia and underlining capillaries (peribiliary capillary plexus [PCP]) form the biliary epithelia-PCP alignment, whereas the hepatocyte-sinusoid alignment composes hepatic lobules. Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are the main biliary tract carcinomas. CCA is subdivided into distal (d/CCA), perihilar (pCCA), and intrahepatic (iCCA), and iCCA is subdivided into small duct type (SD-iCCA) and large duct type (LD-iCCA). High-grade biliary intraepithelial neoplasm (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN) have recently been proposed as the precursors of LD-iCCA, p/dCCA, and GBC. In the large bile ducts and gallbladder, all cases of high-grade BilIN and PGA, about half of IPNB, and one-third of ICPN with less-complicated structure were found to have hijacked the PCP as their supporting vessels (vessel co-option), while p/dCCA, LD-iCCA, and GBC were supplied by neo-angiogenetic vessels associated with fibrous stroma. The intraluminal components of the remaining cases of ICPN and IPNB with complicated structure presented sparse capillaries without fibrous stroma, a unique microvasculature different from that of co-option or neoangiogenesis. Regarding iCCA showing invasion into the hepatic lobules, some SD-iCCAs replaced hepatocytic cords and used pre-existing sinusoids as co-opted vessels. Visualization of pre-existing vessels could be a new pathological tool for the evaluation of malignant progression and of vascular supply in CCAs and its precursors.

Regulatory Effects of Copper on Ghrelin Secretion in Rat Fundic Glands.

Copper (Cu) is an effective additive in feed for promoting growth. Growth dan axis comprising growth hormone (GH), somatostatin (SS) and GH-releasing hormone (GHRH), with ghrelin regulating their release. The growth-promoting effects of Cu are closely related to ghrelin, but the specific mechanism behind the relationship remains unknown. We investigated the adjustment of ghrelin synthesis and secretion by Cu. Sprague-Dawley rats were fed basal diets with an addition of 0, 120 or 240 mg/kg Cu sulfate for 28 day to establish a growth-promoting model. Signalling molecules relevant to ghrelin synthesis and secretion were detected and mechanistically explored using enzyme-linked immunosorbent assay, quantitative reverse-transcription polymerase chain reaction and Western blot analysis. The 120 mg/kg supplement improved growth performance; significantly increased the serum levels of ghrelin, ghrelin O-acyltransferase (GOAT), acylated ghrelin (AG), GH, and reactive oxygen species (ROS) and decreased those of SS; significantly increased the mRNA and protein expression of ghrelin, GOAT, ghrelin receptor (GHS-R1α), and activator protein 1 (AP-1); increased the phosphorylation ratio of JNK and p38 MAPK; and inhibited the mRNA and protein expression of SS and SS receptor subtype 2 (SSTR2) in gastric fundic gland tissues. Thus, Cu may affect gastric ghrelin synthesis at the transcriptional level by activating the JNK/p38 MAPK pathway through increased ROS levels and regulating the activation of the downstream redox-sensitive transcription factor AP-1. SS plays a crucial determinant role in ghrelin regulation via intragastric Cu. Cu promotes GOAT activity and ghrelin secretion by inhibiting SS secretion, affecting AG levels, and promoting ghrelin acylation through ghrelin/GOAT/GHS-R1α system, modulating ghrelin secretion.

Endoscopic and pathological features of neoplastic transformation of gastric hyperplastic polyps: Retrospective study of 4010 cases.

Hyperplastic polyps, which represent 30%-93% of all gastric epithelial polyps, are the second most common type of gastric polyps after fundic gland polyps. They were previously considered to have no risk of neoplastic transformation. Recently, an increasing number of cases of gastric hyperplastic polyps (GHPs) combined with neoplastic changes have been reported; however, the specific mechanism underlying their transformation has not been thoroughly explored. To investigate the clinical, endoscopic, and pathological characteristics of the neoplastic transformation of GHPs and explore the risk factors. A retrospective analysis was performed on 4010 cases of GHPs diagnosed by gastroscopy and pathological examination at the hospital from 2005 to 2021. In total, 3874, 119, and 17 cases were in the group without intraepithelial neoplasia (IN), with low-grade IN, and with high-grade IN, respectively. The data analysis examined the association of endoscopic and pathological features with risk factors for neoplastic transformation. Factors with significant differences were entered into univariate logistic regression, followed by multivariate logistic regression analysis. Univariate analysis revealed diameter, multiple polyp presence, redness, rough surface, lobulation, erosion, Yamada classification, location, and gastric mucosa were risk factors for neoplastic transformation. Multivariate analysis showed that age > 65 years [odds ratio (OR) = 1.789; 95% confidence interval (CI): 1.227-2.609; P = 0.003], male sex (OR = 1.680; 95%CI: 1.158-2.438; P = 0.006), multiple polyps (OR = 1.851; 95%CI: 1.230-2.784; P = 0.003), pedunculated or semi-pedunculated shape (OR = 2.722; 95%CI: 1.689-4.388; P < 0.001), and polyp diameter were significantly associated with GHPs that demonstrated neoplastic transformation. Compared with chronic superficial gastritis, autoimmune gastritis, atrophic gastritis, and gastritis with IN were independent risk factors for neoplastic transformation [(OR = 2.672; 95%CI: 1.559-4.579; P < 0.001), (OR = 1.876; 95%CI: 1.134-3.103; P = 0.014), and (OR = 5.299; 95%CI: 3.173-8.849; P < 0.001), respectively]. Male sex, age > 65 years, multiple polyps, pedunculated or semi-pedunculated shape, polyp size > 1 cm, and specific background gastric mucosa are key indicators for predicting neoplastic transformation of GHPs.

Effects of Medication Period and Gastrin Levels on Endoscopic Gastric Mucosal Changes in Long-Term Proton Pump Inhibitor Users.

Background/Objectives: Proton pump inhibitor (PPI) use has increased worldwide, including in continuous and longer-term users. Recent reports highlight PPI-related endoscopic gastric mucosal changes, including fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cracked and cobblestone-like mucosa (CCLM), and black spots. PPI use elevates gastrin levels because of acid inhibition, and hypergastrinemia might be relevant to these findings. In this cross-sectional study, we retrospectively examined gastric mucosal changes in long-term PPI users, focusing on medication period and gastrin levels. Methods: We enrolled 57 patients who received a PPI (>1 year) at two clinics between January 2021 and March 2022. Participants were classified according to medication period: 1 < 5, 5-10, and ≥10 years. Gastrin levels were categorized as low, middle, and high (<250, 250-500, and ≥500 pg/mL, respectively). Odds ratios (OR) were estimated to assess the risk of endoscopic findings. Results: Of the 57 patients, 6 (10.5%), 25 (43.9%), and 26 (45.6%) were PPI users of 1 < 5, 5-10, and ≥10 years, respectively. There were no significant differences in the incidence of endoscopic findings among the medication periods. Low, middle, and high gastrin groups included 21 (36.8%), 21 (36.8%), and 15 (26.3%) patients, respectively. CCLM incidence was significantly elevated in higher gastrin level groups: middle (OR, 6.60; 95% confidence interval [CI], 1.46-29.75; p = 0.014) and high (OR, 9.00; 95% CI, 1.79-45.23; p = 0.0008) (p-trend = 0.0171). No significant differences were observed for other findings. Conclusions: No elevated risk of PPI-related gastric epithelial changes in long-term PPI users was observed time-dependently. Notably, higher gastrin levels were positively associated with CCLM development, irrespective of the medication period.

OGC SO26 - Double tract reconstruction post total gastrectomy enables duodenal surveillance in familial polyposis: Case report

Abstract Background Familial polyposis syndromes such as Juvenille polyposis syndrome (JPS) and Familial adenomatous polyposis (FAP) are associated with ∼21% and ∼11% lifetime risk of foregut carcinoma respectively. In patients effected, routine oesophago-gastro-duodenoscopy (OGD) is recommended every 1-3 years, in JPS from 15 years old and in FAP from 25 years old. In patients with malignant transformation traditional resection with Roux-en-Y reconstruction inhibits future duodenoscopy. Method Between April and July 2024 two patients presented requiring total gastrostomy with familial polyposis syndromes. In both cases laparoscopic total gastrectomy with double tract reconstruction was decided upon to enable future duodenal surveillance. Results Case 1: 45 year old female with JPS (germline SMAD 4 mutation). Surveillance detected a massive circumferential proximal gastric polyp comprising ∼30% of total gastric mucosa, too large for endoscopic therapy. Biopsies showed JPS polyps. Patient had no early complications following laparoscopic total gastrectomy and a post operative barium swallow showed clear passage of contrast down the double tract. Case 2: 61 year old male with FAP (germline APC mutation). Surveillance detected innumerable fundic gland polyps with histology demonstrating multifocal high grade dysplasia. Previous subtotal colectomy Planned for laparoscopic total gastrectomy with double tract reconstruction in July 2024 Conclusion Roux-en-Y reconstruction is the most common reconstruction following total gastrectomy. However, in patients with familial polyposis syndromes ongoing lifelong duodenal surveillance is critical. In such patients double-tract reconstruction instead of Roux-en-Y may be preferable allowing future duodenoscopy and acceptable remnant foregut function.

Immune cell changes in Helicobacter pylori infection-induced glandular epithelial cell damage of the gastric mucosa

Objective The purpose of this study was to investigate the relationship between Helicobacter pylori (H. pylori) infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and the histopathological characteristics of these changes. Methods We performed a detailed histomorphometry and immunohistochemical analysis of a total of 1635 H. pylori-infected gastric mucosal specimens. Results Stage-wise features were as follows: Early stage of infection: H. pylori was colonized in the mucous layer, and very few neutrophils were visible in the layer. Gastric surface epithelial cell infection stage: H. pylori specifically and selectively adhered to the cytoplasm of the surface mucous cells, with the presence of a small number of neutrophils, eosinophils, and lymphocytes infiltration, which is termed early immune response. Compensatory mucous neck cell hyperplasia stage: proliferation of stem cells in the deep gastric pit and infiltration of a large number of lymphocytes in the superficial layer of lamina propria were observed, which is termed immune cell mobilization counterinsurgency. Lamina propria lesion stage: excessive upward migration of the proliferative area. Infiltration of a large number of lymphocytes, plasma cells, monocytes, macrophages, and other immune cells was observed in the whole layer of the gastric mucosa, which is termed automatic replication of immune cells. Abnormal proliferative transformation stage: presence of intranuclear milky globular body cells or signet-ring cell-like heterotypic cells at the junction of the gastric pit and the gastric gland, with proliferation of large numbers of immune cells and vacuolar degeneration of immune cells, which is termed the proliferation and degeneration of immune cells. Intraepithelial neoplasia stage: clonal hyperplasia of epithelial cells and immunosuppression. Conclusion For controlling the occurrence and development of gastric cancer and effective immune intervention, it is essential to grasp the relationship between H. pylori infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and its histopathological characteristics.

Molecular, pathological and immunohistochemical investigation of Helicobacteraceae in the abomasum of dairy cattle and sheep in Northern Italy

Although several Helicobacter species have been associated with gastric disease in humans and animals, their role in domestic ruminants is still unclear. This study aimed to investigate the prevalence of H. pylori, “Candidatus H. bovis” and other Helicobacteraceae in the abomasum of dairy cattle and sheep reared in Northern Italy, to shed light on their role as potential reservoir of H. pylori for humans and to evaluate the involvement of Helicobacter spp. in the gastric pathology of these animal species. Abomasa from 25 dairy cows and 24 sheep were collected at slaughter. Following macroscopic examination, samples of fundic and pyloric mucosa were analysed by a screening PCR for Helicobacteraceae, followed by specific PCRs (H. pylori, “Candidatus H. bovis”, and Wolinella spp.), histological examination, and immunohistochemistry for Helicobacter spp. Overall, 96% of the bovine and 42% of the ovine abomasa tested positive for Helicobacteraceae. No samples tested positive for H. pylori, while 68% of bovine samples tested positive for “Candidatus H. bovis”, mostly in the pyloric mucosa. Immunohistochemistry showed colonisation by Helicobacter spp. only in the pyloric glands of 11 bovine abomasa (44%), while in ovine abomasa colonisation was not detected. Our results confirmed that "Candidatus H. bovis" is the most common Helicobacteraceae in the bovine abomasum and specifically colonises bovine pyloric glands. No association was found between Helicobacter spp. infection status and abomasal inflammation, suggesting a high degree of adaptation to the bovine host. The role of cattle and sheep as potential source of H. pylori for humans appears to be negligible.

Detached pyloric gland adenoma of gallbladder: A case report and review of literature.

Vigilant intraoperative inspection is crucial during gallbladder surgery to detect any abnormal tissue including the rare pyloric gland adenomas, which can be easily missed. Thorough examination and removal of unusual lymph nodes or thickened tissues are essential to prevent the risk of malignant transformation and ensure comprehensive patient care. Pyloric gland adenomas are uncommon tumors that can be discovered in various organs such as the stomach, gallbladder, and pancreas. Typically lacking noticeable symptoms, these tumors are categorized into subtypes, with the pyloric variant being the most frequent. The term "intracholecystic papillary-tubular neoplasms (ICPN)" is used to emphasize growth patterns and associated risks. In a discussed case, a detached pyloric gland adenoma was identified incidentally during a cholecystectomy procedure. A 58-year-old obese male presented with upper abdominal pain, nausea, and vomiting. He was diagnosed with early cholecystitis caused by gallstones. Subsequently, during a laparoscopic cholecystectomy, a detached adenoma was discovered. Vigilant screening is crucial, as the identification of gallbladder pyloric gland adenomas is a rare occurrence that might be missed during gallbladder surgery. Any unusual lymph nodes or thickened tissues found in association with the gallbladder ought to be carefully removed, as they could potentially indicate detached gallbladder adenomas with a significant risk of becoming malignant. Failing to consider this possibility may subject the patient to prolonged risks if not meticulously examined.

Meloxicam-amino acids salts/ion pair complexes with advanced solubility, dissolution, and gastric safety

Amino acids have attracted attention as a potential functional excipient for optimizing biopharmaceutics characteristics of poorly soluble drugs. The amino acids are a diverse class with many functional groups, natural compounds, biocompatible, and low-molecular-weight substances. Two amino acids serine and arginine were investigated with meloxicam. Meloxicam has extremely low solubility; being NSAIDs, gastric upset, and ulcer are common side effects. Solid dispersions were produced by precipitation and physical mixing techniques. The produced combinations underwent in vitro dissolution, docking, DSC, FTIR, XRD, solubility, and gastric ulcer formation studies. Docking indicated ion pair/salt formation between the basic amino acid arginine and meloxicam. Both solubility and dissolution rates were increased by up to 3000-fold and 12-fold, respectively. DSC, FTIR an XRD supported these findings. Rats treated with meloxicam showed loss of surface gastric epithelium integrity and ulceration. The animal group received meloxicam: arginine showed intact gastric mucosa with the surface epithelium and gastric glands well organized and nearly similar to the untreated control. Arginine with the guanidine group that was capable of preserving gastric mucosa after repeated administration for 10 days. This study highlighted the role of arginine as a functional excipient that did not only improve solubility and dissolution rates but ameliorated the long-standing gastric side effects attributed to meloxicam.

A New Diagnosis of Intestinal Metaplasia in Gastric Mucosa: Convolutional Neural Network Based on Visual Auxiliary Method

Abstract Introduction/Objective Intestinal metaplasia (IM) is a common lesion observed in chronic gastric disease and is thought to be associated with the development of gastric cancer. One of the characteristics of IM is the presence of goblet cells. However, differentiating these inconspicuous goblet cells from glandular cavities and gastric mucus cells using traditional algorithms is inefficient. This paper proposes an interpretable auxiliary diagnosis method for gastric mucosal intestinal metaplasia based on a convolutional neural network(CNN). Methods/Case Report The overall flow chart of the algorithm is shown in Figure 1A. The self-constructed gastric mucosa dataset is utilized in this paper for IM. To improve performance, some modifications are applied to the U-Net. The auxiliary diagnosis process incorporates R34W and R34U for segmenting the glands and IM regions. The R34W represents a dual-resolution input network structure (Figure 1B). For the initial stage of the auxiliary diagnosis, the convolutional neural network calculates patches with both large and small fields for gland region segmentation. Then, the IM glands segmentation network is used to classify regions with and without IM lesions. Results (if a Case Study enter NA) The result of the WSI level mask generated after post-processing is shown in Figure 2A. R34W Net offers significant advantages in differentiating open epithelial structures and proper glands. This network effectively differentiates between proper glands and epithelial regions while maintaining precise segmentation, leveraging high-resolution features in a small visual field. The quantitative indexes of gland segmentation networks are shown in Figure 2B. As part of auxiliary diagnosis, the classification of proper glands with intestinal metaplasia achieves the highest accuracy of 0.95 and AUC of 0.975 in the test datasets (Figure 2C). The area proportion of IM regions generated by CNN is shown in Figure 2D. Conclusion This paper provides a visual auxiliary method based on a CNN for the pathological diagnosis of intestinal metaplasia. The goal is to enhance the speed and accuracy of pathologists in performing this diagnosis. Additionally, we propose a CNN with a dual-resolution input structure, which is utilized for segmenting gastric proper glands.

Gastric Epithelial Neoplasm of Fundic-Gland Mucosa Lineage: Showed the Same Genetic Lineage and Ki67 May Help in Their Identification

Abstract Introduction/Objective Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare form of gastric tumors that encompasses oxyntic gland adenoma (OGA), gastric adenocarcinoma of the fundic-gland type (GA-FG), and gastric adenocarcinoma of the fundic-gland mucosa type (GA-FGM). There is no consensus on the clinicopathologica and molecular characteristics of GEN-FGMLs, and misdiagnosis is common because of similarities in symptoms. Methods/Case Report The NGS and immunohistochemical staining were performed on 37 cases diagnosed with GEN-FGMLs with a thorough histological evaluation. Gene alternations were analysed and compared across histological subtypes. we used an artificial intelligence approach for the recognition of the Ki67 immunohistochemistry stained. Results (if a Case Study enter NA) The patient’s ages ranged from 42 to 79 years, with a median age of 60. 17 were male and 20 were female. Morphologically, 19 OGAs, 16 GA-FGs, and two GA-FGMs were identified. Histopathological similarities exist between GEN-FGMLs. The tumors demonstrated well-formed glands, expanding with dense growth patterns comprising pale, blue-grey columnar cells with mild nuclear atypia. The normal gastric pit epithelium covered the entire surface of the OGA and GA-FG, but the dysplasia pit epithelium covered the GA-FGM. Compared with OGA, GA-FG and GA-FGM were more prominent in the macroscopic view (p&amp;lt;0.05) and had larger sizes (p&amp;lt;0.0001). Additionally, GA-FG and GA-FGM exhibited higher Ki67 indices than OGA (p&amp;lt;0.0001). The heterogeneity of mutational signatures, somatic mutations, and copy number variations was revealed across histological subtypes. The top five mutational signatures in OGA were ROS1, CTNNA1, GNAS, BRCA2, and ZFHX3. The top five mutational signatures in GA-FG and GA-FGM were GNAS, MLL3, BRAF, MSH3, and EGFR. GNAS were both found in OGA, GA-FG and GA-FGM. Compared with well-differencent gastric adenocarcinoma, The top five mutational signatures in GEN-FGMLs were GNAS, BRAF, ROS1, MLL3, and MSH3. Recurrently mutated key signaling pathways across tumor types in GEN-FGML were Wnt signaling pathways. Conclusion GEN-FGMLs are a group of well-differentiated gastric tumors with favourable biological behaviours. Compared with OGA, GA-FG and GA-FGM have larger sizes and higher Ki67 proliferation indices, indicating that they play a critical role in the identification of GEN-FGML. GEN-FGMLs showed the same genetic lineage, the Wnt signalling pathway plays a role in the development and progression of GEN-FGMLs.

Mutational Landscape of Gastric Adenocarcinoma of the Fundic Gland Type Revealed by Whole Genome Sequencing.

Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described variant of gastric adenocarcinoma with lack of knowledges regarding its genetic features. We performed whole-genome sequencing (WGS) in formalin-fixed paraffin-embedded (FFPE) tumor tissues and matched adjacent noncancerous specimens from 21 patients with GA-FG, and integrated published datasets from 1105 patients with traditional gastric adenocarcinoma with the purpose of dissecting genetic determinants both common to conventional gastric adenocarcinoma and unique to GA-FG disease. We characterized the genomic architecture of GA-FG disease, revealing the predominant proportion of C > T substitution among the six types of SNVs. GNAS was the most significantly mutated driver gene (14.29%). 42.8% of samples harbored "Kataegis." Distinct genomic alterations between GA-FG and conventional gastric cancer were identified. Specifically, low mutational burden and relatively moderate mutational frequencies of significantly mutated driver genes, coupled with the absence of non-silent alterations of formerly well-known drivers such as TP53, PIK3CA and KRAS were identified in GA-FG patients. Oncogenic signaling pathway analysis revealed mutational processes associated with focal adhesions and proteoglycans in cancer, highlighting both common and specific procedures during the development of GA-FG and conventional gastric cancer. Our study is the first to comprehensively depict the genomic landscape highlighting the multidimensional perturbations in GA-FG patients. These discoveries offered mechanistic insights for novel diagnostic and therapeutic strategies for patients with such disease.

Características genéticas y manifestaciones fenotípicas extracolónicas en pacientes con poliposis adenomatosa familiar

IntroductionFamilial adenomatous polyposis (FAP) is a hereditary disease caused by mutations in the APC gene, which is also associated with extracolonic manifestations. The objective was to characterize the extracolonic manifestations in a cohort of patients with classic FAP and the possible genotype-phenotype association. Materials and methodsThe study design was observational and descriptive. Demographic, clinical, and genetic variables were collected based on the type of mutation (frameshift, nonsense, splicing, rearrangement, and others). ResultsWe included 45 patients with FAP (mean age 47years, range 21-78; 51% female), belonging to 21 families, with a median of 2 (range 0-6) manifestations per patient. Eighty percent (n=36) had upper digestive tract involvement, with duodenal adenomas (73%), fundic gland polyposis (56%), and ampullary adenoma (36%) being the most frequent findings. The most common extraintestinal manifestations were desmoid tumors (16%) and papillary thyroid carcinoma (13%). Thirty eight percent of the patients presented an aggressive phenotype (SpigelmanIII-IV, high-grade dysplasia, invasive neoplasia, desmoid tumor, and papillary thyroid carcinoma). The most common genetic mutations were frameshift (56%), nonsense (26%), and splicing (16%), primarily located in exon15 (50%). No significant correlation was found between the type of genetic mutation and the severity or location of phenotypic manifestations. ConclusionsOne-third of patients with FAP present an aggressive phenotype, without a demonstrated correlation between the type of genetic alteration and the phenotypic manifestations.

S2321 Visibility evaluation of Gastric Epithelial Neoplasm of Fundic Gland Mucosa Lineage in a New Image Enhanced Endoscopy; Texture and Color Enhancement Imaging

S2321 Visibility evaluation of Gastric Epithelial Neoplasm of Fundic Gland Mucosa Lineage in a New Image Enhanced Endoscopy; Texture and Color Enhancement Imaging

S4131 Catching a Wolf in Sheep’s Clothing: Successful Endoscopic Mucosal Resection of a Large Duodenal Pyloric Gland Adenoma

S4131 Catching a Wolf in Sheep’s Clothing: Successful Endoscopic Mucosal Resection of a Large Duodenal Pyloric Gland Adenoma

Gastric dysplasia arising from a submucosal heterotopic gastric gland.

A submucosal heterotopic gastric gland (SHGG) is characterized by benign ectopic gastric tissue within the submucosa. Neoplasms arising from SHGGs are rare, and their definitive diagnosis via endoscopic biopsy is often challenging. We report the case of a 74-year-old man undergoing screening esophagogastroduodenoscopy, which revealed a subepithelial lesion with a central orifice in the upper body of the stomach. Endoscopic submucosal dissection (ESD) was performed because the endoscopic biopsy revealed a suspected pyloric gland adenoma. Pathological examination of the resected specimen confirmed SHGG with focal dysplasia. The patient recovered uneventfully and remained free of recurrence over a 5-year follow-up period. This case highlights the utility of ESD in both the treatment and accurate pathological diagnosis of neoplasms arising from SHGGs.