Fundic Research Articles

SOX9 is regulated by AURKA in response to Helicobacter pylori infection via EIF4E-mediated cap-dependent translation

Helicobacter pylori (H. pylori) infection is the main risk factor for gastric cancer. The SRY-Box Transcription Factor 9 (SOX9) serves as a marker of stomach stem cells. We detected strong associations between AURKA and SOX9 expression levels in gastric cancers. Utilizing in vitro and in vivo mouse models, we demonstrated that H. pylori infection induced elevated levels of both AURKA and SOX9 proteins. Notably, the SOX9 protein and transcription activity levels were dependent on AURKA expression. AURKA knockdown led to a reduction in the number and size of gastric gland organoids. Conditional knockout of AURKA in mice resulted in a decrease in SOX9 baseline level in AURKA-knockout gastric glands, accompanied by diminished SOX9 induction following H. pylori infection. We found an AURKA-dependent increase in EIF4E and cap-dependent translation with an AURKA-EIF4E-dependent increase in SOX9 polysomal RNA levels. Immunoprecipitation assays demonstrated binding of AURKA to EIF4E with a decrease in EIF4E ubiquitination. Immunohistochemistry analysis on tissue arrays revealed moderate to strong immunostaining of AURKA and SOX9 with a significant correlation in gastric cancer tissues. These findings elucidate the mechanistic role of AURKA in regulating SOX9 levels via cap-dependent translation in response to H. pylori infection in gastric tumorigenesis.

Outcomes following duodenectomy in patients with familial adenomatous polyposis.

Background and study aims Some patients with familial adenomatous polyposis (FAP) and extensive duodenal polyposis or cancer require total duodenectomy. Regular postoperative endoscopic surveillance of the remaining jejunum and stomach is recommended, but little is known about the outcomes after this surgery. Patients and methods Patients with FAP who underwent either pancreatoduodenectomy (PD) or pancreas-preserving total duodenectomy (PPTD) were identified at two expert centers. Data about postoperative endoscopic surveillance outcomes were collected, as well as survival outcomes. Results Overall, 119 patients (50% female) underwent duodenectomy (86 PD and 33 PPTD); 100 for benign duodenal polyposis and 19 for duodenal or ampullary cancer. Details of postoperative endoscopic surveillance were available for 88 patients (74%). During a median follow-up of 106 months, 36 patients (41%) were diagnosed with jejunal adenomas after duodenectomy, with a significantly higher proportion in patients who underwent PPTD compared with patients who underwent PD (log-rank, P < 0.01). Two patients developed jejunal cancer (2%). Twenty-six patients (30%) were diagnosed with a total of 66 gastric adenomas, of which 61% were located in the fundus/body and 39% in the antrum. Five patients (6%) developed gastric cancer after a median of 15 years (range 6-23 years), all but one within carpeting fundic gland polyposis. Patients who underwent surgery for cancer had worse survival than patients with benign disease and all but one patient with postoperative gastric/jejunal cancer died. Conclusions After duodenectomy in FAP, a considerable risk of developing adenomas and cancer in the stomach and jejunum exists with poor cancer prognosis, highlighting the need for close postoperative endoscopic surveillance.

Changes in growth, morphology, and levels of digestive enzymes and growth-related hormones in early ontogeny of black scraper, Thamnaconus modestus

IntroductionThe black scraper, Thamnaconus modestus, is a highly valued marine fish species, but its output has gradually decreased in recent years, which may be due to its low survival rate during early ontogenesis.MethodsTherefore, in this study, we assessed the changes in growth, morphology, digestive enzymes, and hormone levels in T. modestus from 0–60 days post-hatching (dph) and revealed growth turning points by morphological measurement and determination of digestive enzyme activities and hormone levels. We found that ontogenesis could be divided into the larval (0–20 dph) and juvenile (20–60 dph) stages. Acid and alkaline protease activity significantly increased and decreased, respectively, from 12–25 dph, likely due to the development of stomach and gastric glands. Acid phosphatase levels significantly increased at 0 and 4 dph, which may be related to the regulation of metabolism and immune protection. A sharp increase in alkaline phosphatase levels at 20 and 25 dph was observed and was likely due to the development of the brush border membrane of enterocytes. The amylase level was significantly higher at 25, 30, and 35 dph, possibly due to better digestion and absorption during the transition from consuming Artemia to compound feed. In newly hatched larvae, the level of thyroid hormones triiodothyronine (T3) and thyroxine (T4) gradually increased and peaked at 35 dph, highlighting the importance of these hormones during the development of T. modestus. Growth hormone (GH) levels first increased from 0–8 dph, with a plateau at 8–20 dph, and then increased at 25–30–35 dph. For insulin-like growth factor 1 (IGF-1), a significant increase with a subsequent plateau was observed between 8 and 20 dph, followed by a substantial decrease between 30 and 35 dph. These results suggest that the regulating functions of GH and IGF-1 are synchronised. Digestive enzyme activity and hormone levels of abnormal fry at 30 dph were lower than those of normal fish, highlighting the importance of specific hormones, especially T4 and IGF-1, in the development of T. modestus.

Clinicopathologic and endoscopic characteristics of ten patients with gastric hamartomatous inverted polyp: a single center case series

BackgroundGastric hamartomatous inverted polyps (GHIPs) are not well characterized and remain diagnostically challenging due to rarity. Therefore, this study aims to investigate the clinicopathologic and endoscopic characteristics of patients with GHIP.MethodsWe retrospectively reviewed clinicopathologic and endoscopic features of ten patients with GHIP who were admitted to Beijing Friendship Hospital from March 2013 to July 2022. All patients were treated successfully by endoscopic resection.ResultsGHIPs were usually asymptomatic and found incidentally during gastroscopic examination. They may be sessile or pedunculated, with diffuse or local surface redness or erosion. On endoscopic ultrasonography, the sessile submucosal tumor-type GHIP demonstrated a heterogeneous lesion with cystic areas in the third layer of the gastric wall. Histologically, GHIPs were characterized by a submucosal inverted proliferation of cystically dilated hyperplastic gastric glands accompanied by a branching proliferation of smooth muscle bundles. Inflammatory cells infiltration was observed in the stroma, whereas only one patient was complicated with glandular low-grade dysplasia. Assessment of the surrounding mucosa demonstrated that six patients (60%) had atrophic gastritis or Helicobacter pylori–associated gastritis, and four patients (40%) had non-specific gastritis. Endoscopic resection was safe and effective.ConclusionsGHIPs often arise from the background of abnormal mucosa, such as atrophic or H.pylori-associated gastritis. We make the hypothesis that acquired inflammation might lead to the development of GHIPs. We recommend to make a full assessment of the background mucosa and H. pylori infection status for evaluation of underlying gastric mucosal abnormalities, which may be the preneoplastic condition of the stomach.

White ring sign is useful for differentiating between fundic gland polyp and gastric adenocarcinoma of fundic gland type

Background: Gastric adenocarcinoma of fundic gland type (GA-FG) is characterized by an elevated lesion with vessel dilation exhibiting branching architectures (DVBA). However, this feature is also found in fundic gland polyp (FGP), posing a challenge in their differentiation. In this study, we aimed to investigate the clinicopathological features of gastric elevated lesions with DVBA and assess the efficacy of the white ring sign (WRS) as a novel marker for distinguishing between FGP and GA-FG. Methods: We analyzed 159 gastric elevated lesions without DVBA and 51 gastric elevated lesions with DVBA, further dividing the latter into 39 in the positive-WRS group and 12 in the negative-WRS group. The clinicopathological features, diagnostic accuracy, and inter-rater reliability were analyzed. Results: Univariate and multivariate analyses for gastric elevated lesions with DVBA identified the histological type consistent with FGP and GA-FG, along with the presence of round pits in the background gastric mucosa, as independent predictors. FGPs were present in 92.3% (36/39) of the positive-WRS group and GA-FGs were observed in 50.0% (6/12) of the negative-WRS group. Positive- and negative-WRS exhibited high diagnostic accuracy, with 100% sensitivity, 80.0% specificity, and 94.1% accuracy for FGP, and 100% sensitivity, 86.7% specificity, and 88.2% accuracy for GA-FG. Kappa values of WRS between experts and nonexperts were 0.891 and 0.841, respectively, indicating excellent agreement. Conclusions: Positive- and negative-WRS demonstrate high diagnostic accuracy and inter-rater reliability for FGP and GA-FG, respectively, suggesting that WRS is a useful novel marker for distinguishing between FGP and GA-FG.

Convergent gene losses and pseudogenizations in multiple lineages of stomachless fishes

The regressive evolution of independent lineages often results in convergent phenotypes. Several teleost groups display secondary loss of the stomach, and four gastric genes, atp4a, atp4b, pgc, and pga2 have been co-deleted in agastric (stomachless) fish. Analyses of genotypic convergence among agastric fishes showed that four genes, slc26a9, kcne2, cldn18a, and vsig1, were co-deleted or pseudogenized in most agastric fishes of the four major groups. kcne2 and vsig1 were also deleted or pseudogenized in the agastric monotreme echidna and platypus, respectively. In the stomachs of sticklebacks, these genes are expressed in gastric gland cells or surface epithelial cells. An ohnolog of cldn18 was retained in some agastric teleosts but exhibited an increased non-synonymous substitution when compared with gastric species. These results revealed novel convergent gene losses at multiple loci among the four major groups of agastric fish, as well as a single gene loss in the echidna and platypus.

Histopathological staging and differential diagnosis of marginal zone lymphoma of gastric mucosa-associated lymphoid tissue

The purpose of this study was to explore the histopathological staging and differential diagnosis of marginal zone lymphoma in gastric mucosa-associated lymphoid tissue (MALT lymphoma). We performed detailed histomorphology and immunohistochemistry investigations as well as genetic testing on endoscopic biopsy and endoscopic mucosal resection specimens from 18 patients with gastric MALT lymphoma. We found that gastric MALT lymphoma typically begins as a small, isolated area outside the lymphoid follicular mantle zone or proliferates in a multifocal, patchy manner, gradually spreads to the interfollicular zone, forming diffuse proliferation, invades the gastric mucosal glands, and infiltrates or proliferates into the center of peripheral reactive lymphoid follicles. Abnormally proliferating lymphocytes invade the surrounding lymphoid follicles, resulting in damage, atrophy, and disappearance of their normal follicles as well as of the gastric mucosa glands, forming diffuse proliferation. Redifferentiation and proliferation lead to the transformation of lymphocytes; that is, MALT transitions into highly invasive lymphoma. Based on our findings in this study, we propose the following five stages in the process of development and progression of gastric MALT lymphoma: the stage of cell proliferation outside the lymphoid follicular mantle zone; the stage of heterogeneous proliferative lymphoepithelial lesion; the stage of reactive lymphoid follicular implantation; the stage of lymphoid follicular clonal proliferation; and the stage of MALT transforming into highly invasive lymphoma. We examined the differential diagnosis of histopathological features at each stage. The clinicopathological staging of gastric MALT lymphoma can help clinicians provide accurate treatment and track malignant cell transformation, thus playing a significant role in controlling its development and progression.

Comparison of Prognosis and Metachronous Gastric Tumor Rates After Endoscopic Submucosal Dissection Between Gastric Neoplasm of Fundic Gland Type Neoplasms and Conventional Gastric Adenocarcinoma.

Gastric neoplasm of the fundic gland type (GNFG) is a tumor with a good prognosis. However, since it has not been compared with conventional gastric adenocarcinoma (CGA), it is unknown whether it has a good prognosis or requires surveillance after treatment. The purpose of this study was to determine the prognosis and metachronous gastric tumor rates compared with those of CGA. We conducted a single-center, retrospective, matched-cohort study using our database from January 2010 to December 2021. We extracted GNFG data from the endoscopic submucosal dissection (ESD) database and matched patients with conventional early gastric cancer as controls in a 1:4 ratio by age and sex. GNFG and CGA were compared for the overall survival (OS), disease-specific survival, progression-free survival, and metachronous gastric tumor rates. Overall, 43 lesions were GNFG and 164 CGAs were matched. There were three deaths in the GNFG group and 11 deaths in the CGA group. There was no significant difference in the OS between the two groups (P=0.81). The five-year OS rates for the GNFG and CGA groups were 90.9% and 92.9%, respectively. No disease-specific deaths or recurrences were observed in either group. There was no significant difference in the cumulative metachronous gastric tumor rate between the two groups (P=0.17). The cumulative five-year metachronous gastric tumor rates for the GNFG and CGA groups were 6.6% and 2.5%, respectively. The prognosis for GNFG is good, however, not better than that for CGA. The metachronous gastric tumor rate after ESD in GNFG was not lower than that in CGA. Therefore, after ESD, GNFGmay need to be managed in the same way as CGA.

Pathologic significance of peribiliary capillary plexus in gallbladder neoplasm

AimsSignificance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), precursors of gallbladder carcinoma, and to differentiate invasive carcinoma from pseudo-invasive lesions in gallbladder walls, referring to PCP. Materials and methodsHigh-grade BilIN (38 cases), PGA (5 cases), and ICPN (25 cases) were examined using capillary immunostaining. Non-neoplastic gallbladders were used as controls. ResultsIn non-neoplastic gallbladders, a single layer of regularly dotted capillaries (PCP) was located beneath lining epithelia and around non-neoplastic glands (NNGs), including Rokitansky-Aschoff sinus (RAS), presenting a two-layer of lining epithelia and PCP. Intra-luminal components of all cases of high-grade BilIN and PGA and one-third of ICPNs presented a two-layer pattern. In the remaining ICPNs, capillaries were irregular and sparse in intraluminal neoplastic components presenting irregular and complicated lesions. Neoplastic glands in gallbladder walls of high-grade BilIN and ICPN were classifiable into 2 types: glands that were underlain by densely dotted capillaries and those that were not, with the latter suggestive of invasive carcinoma, while the former suggestive of non-invasive neoplasms involving NNGs intraepithelially and/or showing an expanding growth into gallbladder wall (pseudo-invasion). ConclusionA two-layer pattern of lining epithelia and underlining capillaries were preserved in all cases of high-grade BilIN and PGA and one-third of ICPN cases. Presence or absence of dotted capillaries around neoplastic glands may be able to be added as a new pathologic feature to differentiate invasive carcinomas from pseudo-invasion in gallbladder wall.

Endoscopic submucosal dissection (ESD) for gastritis cystica profunda (GCP) with early gastric cancer: A propensity score matching analysis

Background and aimCystic dilatation of the gastric glands within the mucosal layer is the hallmark of the rare condition known as gastritis cystica profunda (GCP). Although it has been proved that GCP is the precursor lesion for early gastric cancer (EGC), the management strategy of GCP-related EGC is not well established.The purpose of this research was to determine if ESD is effective and safe for GCP-related EGC. MethodsPatients with EGC who had ESD at Beijing Friendship Hospital between January 2015 and May 2023 were retrospectively included. All patients were divided into two groups: those with GCP-related EGC, and those with EGC alone. The two groups were matched 1:1 using the propensity score matching (PSM) method. Curative resection rate, postoperative adverse outcome rate (bleeding, perforation, stricture), and recurrence rate were the primary measures used to evaluate the efficacy and safety of ESD. ResultsThere were a total of 386 participants (44 with GCP and 342 with EGC alone). Following PSM, 44 patients were paired and analyzed separately. Except for the presence of cysts in EUS (multiple/single/none cyst: 12/2/5 versus 1/0/25, P < 0.0001), there was no change in baseline characteristics, EUS appearance, or histology results between groups. Overall, there was no significant difference in curative resection rates between the GCP group (70.5 %) and the control group (81.8 %) (P = 0.211). Postoperative complications were comparative (9/44 vs 5/44, P = 0.244), as were rates of local recurrence (1/44 vs 0/44, P = 1.0), metachronous gastric cancer (1/44 vs 0/44, P = 1.0), and mortality (0/44 vs 0/44, P = 1.0). ConclusionsExistence of cysts in EUS is a characteristic presentation to distinguish GCP-related EGC from EGC-alone lesions. ESD might be a safe and effective therapy for patients with GCP-related EGC.

Developing efficient feeding and weaning protocols for Betta splendens informed by larval digestive physiology

Betta splendens, also known as the Siamese fighting fish, is an anabantoid native to Southeast Asia and is among the top ten freshwater ornamental fish species imported into the USA for the aquarium trade. Although B. splendens is a staple in the ornamental aquaculture industry, larval production continues to rely heavily on the use of Artemia spp. nauplii. Digestive physiology data can be used to minimize the use of costly live feeds during larval production by indicating when larvae can digest complex feeds like microdiets (MDs). A 30-day trial was conducted to determine the timing of the maturation of the digestive tract. Standard microplate assays were conducted to quantify pepsin, trypsin, and lipase activities and histology was used to describe digestive tract morphology. Pepsin activity and the development of gastric glands indicated the presence of a functional stomach between 15 and 18 DPH (days post-hatch). Next, a 42-day dietetics trial was conducted to determine which of three commercially available MDs best promoted growth and survival in larval B. splendens compared to an Artemia spp. reference diet. Survival was statistically similar for larvae fed Gemma Micro compared to the Artemia spp. reference diet and all MD treatments yielded significantly higher growth compared with the reference diet. Finally, a 25-day weaning trial was conducted where MD was introduced at three timepoints surrounding the development of the digestive tract. Larvae were subjected to one of five treatments: Artemia spp. reference diet, MD from first-feeding, or MD introduction at 12, 15, or 18 DPH. MD introduction at 15 and 18 DPH yielded similar survival and growth compared to the Artemia spp. reference diet. MD from first-feeding yielded statistically lower survival and growth compared to all other treatments. These results suggest that B. splendens can transition to a MD as early as 15 DPH without reducing growth or survival.

Altered glycosylation in secreting cells of the gastric glands of aquaporin-4-deficient mice.

Aquaporins (AQPs) are important for water transport in the gastrointestinal tract. Changes in their expression and/or localization could cause in disorders and be used as therapeutic targets. Aquaporin-4 (AQP4) is expressed predominantly on the basolateral membrane of the parietal cells in the corpus of the murine gastric glands. Although the secretion of gastric juice is not affected in AQP4-deficient knockout, we evaluated by light microscopy whether the lack of AQP4 affects the glycopatterns of secreting gastric cells. Wild type (WT) and AQP4-deficient knockout mice (KO) were fed a standard diet ad libitum before sacrifice. Segments of stomach corpus were collected, fixed in buffered formalin, and embedded in paraffin wax. Sections, 5-μm thick, were analyzed by histochemical methods (Periodic acid-Schiff, Alcian Blue pH 2.5), and binding of lectins specific to GalNAc (SBA, DBA), Gal (PNA) GlcNAc (WGA, GSAII) mannose and/or glucose (ConA), and fucose (UEA-I, AAA, LTA). Immunohistochemical methods such as anti-Muc6 for neck cells and anti- β- H+/K+-ATPase for parietal cells were also performed. Compared to WT mice, in the mucous cells of KO lower amounts of glycans with galactosyl/galactosaminylated, glycosyl/glycosaminylated, and fucosylated residues were observed; lower fucosylation resulted also in the parietal cells. The observed differences of KO in respect to WT could lead to severer pathological conditions. RESEARCH HIGHLIGHTS: Glycopatterns in gastric glands were compared between wild type (WT) and AQP4-deficient knockout (KO) mice by histochemical and lectin-binding methods. In the mucous cells of KO lower amounts of glycans with galactosyl/galactosaminylated, glycosyl/glycosaminylated and fucosylated residues were observed. In the parietal cells lower fucosylation also resulted. AQP4-deficiency affects glycosylation and could result in altered functionality and pathological conditions.

A case of young male with recurrent acute pancreatitis caused by an intrapancreatic gastric duplication cyst

Gastric duplication cyst (GDC) is a rare gastrointestinal malformation that frequently occurs in the greater curvature of the gastric antrum or corpus. Herein, we reported a case of intrapancreatic GDC found as a result of recurring pancreatitis. A 15-year-old man experienced repeated episodes of acute pancreatitis and was found to have a cystic lesion in the pancreatic tail. Contrast-enhanced computed tomography revealed a 20-mm cystic lesion with an enhanced thick wall. Endoscopic ultrasonography revealed an anechoic cyst with a three-layered wall. Magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography (ERP) revealed a connection between the cyst and the main pancreatic duct (MPD), and the duplication of the MPD. ERP showed the pancreatic duct stenosis downstream of the cyst. Although preoperative diagnosis was difficult, distal pancreatectomy was performed to prevent recurrence of pancreatitis. Pathological examination revealed that the cystic lesion was circumferentially surrounded by the pancreatic parenchyma. The epithelial lining of the cyst was crypt epithelium containing the fundic or pyloric glands and surrounded by a smooth muscle layer. The final diagnosis was intrapancreatic GDC.

A Natural Peptide from A Traditional Chinese Medicine Has the Potential to Treat Chronic Atrophic Gastritis by Activating Gastric Stem Cells.

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF-EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment.

Clinicopathological and endoscopic features of Helicobacter pylori infection-negative gastric cancer in Japan: a retrospective study.

Helicobacter pylori infection-negative gastric cancer (HPNGC) has not been systematically investigated in consecutive patients. Hence, this study aimed to investigate the clinicopathological and endoscopic features of HPNGC. This single-center retrospective study selected participants from patients with gastric cancer who were treated at the Fukuoka University Chikushi Hospital between January 2013 and December 2021. Only patients diagnosed with HPNGC were enrolled, and their clinicopathological and endoscopic features were analyzed in detail. The prevalence of HPNGC in the present study was 2.6% (54/2112). The types of HPNGC observed in each gastric region were as follows: advanced gastric cancer was observed in the cardia; gastric adenocarcinoma of fundic-gland differentiation, gastric adenocarcinoma of foveolar-type presenting with whitish elevation and raspberry-like foveolar-type gastric adenocarcinoma, gastric adenocarcinoma arising in polyposis, and gastric adenocarcinoma with autoimmune gastritis were observed in the fundic gland region ranging from the gastric fornix to the gastric body; signet-ring cell carcinoma was observed in the gastric-pyloric transition region ranging from the lower gastric body to the gastric angle; and well-differentiated tubular adenocarcinoma with low-grade atypia was observed in the antrum. This study revealed that tumors from each gastric region exhibited distinct macroscopic and histological types in HPNGC.

Abstract 1140: A spatially mapped gene expression signature for intestinal stem-like cells identifies high-risk precursors of gastric cancer

Abstract Gastric intestinal metaplasia (GIM) is a precursor lesion for the intestinal subtype of gastric cancer (GC). A risk stratification tool is the Operative Link on GIM (OLGIM), a system that relies on histopathologic annotation of gastric biopsies. Advanced OLGIM (stages III and IV) have the highest risk of progression to GC. Molecular biomarkers for advanced OLGIM are lacking. We explored transcriptomics biomarkers for advanced OLGIM to aid risk assessment efforts among GC precursors.We used clinical and genomic data from four cohorts: 1) GAPS, a cohort of OLGIM-staged patients (N=303); 2) a subset of confirmed intestinal-type GC from The Cancer Genome Atlas (TCGA, N=198); 3) a compilation of scRNA-seq data (N=40), and 4) a spatial transcriptomics cohort (N=5) with annotated H&amp;E-stained histopathology slides from GC or OLGIM-staged patients.We separated the GAPS bulk RNAseq gene expression dataset into independent discovery (N=88) and validation (N=215) sets. Through a combination of differential expression analysis and co-expression analysis, we identified a discrete set of 100 significantly upregulated genes characterizing advanced OLGIM that were confirmed in the validation set. Importantly, these genes were overexpressed both in the corpus and antrum of the stomach. We leveraged spatial transcriptomics assays to refine this signature to genes overexpressed specifically in GIM foci. We interrogated the TCGA dataset and confirmed these genes to be also expressed in gastric tumors. The final high-risk signature included 26 genes. Single-cell RNAseq analysis revealed these genes to be expressed by aberrant intestinal-like lineages. Further, reference-mapping identified cells resembling mature enterocytes and goblet cells that expressed 16 of these genes, whereas 10 genes from the high-risk signature pinpoint immature intestinal stem-like cells at varying stages of differentiation (duodenum stem cells, duodenum differentiating stem cells, and duodenum transit amplifying cells). Finally, we confirmed expression of 12 of these genes by single-molecule fluorescence in situ hybridization (smFISH), that distinguish differentiated from stem-like lineages in metaplasia and are absent in normal gastric glands in intact tissue sections from GC precursors.Our study identified as signature of 26 genes that are: i) characteristically over-expressed in advanced OLGIM stages, ii) localize specifically to metaplasia, iii) are expressed in gastric tumors, and iv) distinguish differentiated from stem-like cells in GIM. These results provide transcriptomics biomarkers that indicate the establishment and expansion of intestinal stem-like cells in advanced OLGIM, with profound translational implications, as these cells may harbor and expand mutations that predispose advanced OLGIM patients to GC. Citation Format: Ignacio A. Wichmann, Robert J. Huang, Andrew Su, Anuja Sathe, Miranda V. Shum, Susan M. Grimes, Rithika Meka, Alison Almeda, Xiangqi Bai, Jeanne Shen, Quan Nguyen, Manuel Amieva, Joo Ha Hwang, Hanlee P. Ji. A spatially mapped gene expression signature for intestinal stem-like cells identifies high-risk precursors of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1140.

Morphological analysis of the digestive tract of Antillean manatee (Trichechus manatus manatus, Linnaeus, 1758) in northeast Brazil

Morphological studies of the digestive tract are relevant to know the biology and understand the eating habits to conserve species. Our objective was to analyze macroscopically and microscopically the digestive tract of Antillean manatee (Trichechus manatus manatus). Samples were collected from 20 animals found dead stranded on the coast of northeastern Brazil or that died during the rehabilitation process in captivity between July 1995 and March 2017. The macroscopic analysis of the gastrointestinal tract was carried out from the in loco monitoring of the two necropsies. For microscopic evaluation, tissue fragments were collected during necropsy, fixed with 10% buffered formaldehyde and subjected to routine histological processing, with 5 μm thick slices, and subsequently submitted to the Hematoxylin-Eosin staining method, the Verhoeff method, and the periodic acid-Schiff method. Macroscopically, neonates and adults have the same digestive tract structures, namely esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, and rectum. The microscopic analysis demonstrated that the digestive tract is formed by four histological layers (mucosa, submucosa, muscularis, and serosa or adventitia). In the esophagus, esophageal glands are absent and there are elastic fibers in the submucosal layer and between the external muscle and adventitial layers. The stomach has a structure called the cardiac gland, which microscopically presents ontogenetic differences regarding the depth of the lining epithelium and the orderly distribution of cells along the gastric gland. In the duodenal ampulla and in the diverticula, duodenal glands were identified in the submucosa. The luminal portion of the mucous layer of the cecal ampulla, colon, and rectum is lined by keratinized stratified squamous epithelium. The digestive tract of the species Antillean manatee is similar to what has been reported for the order Sirenia.

Gastric hamartomatous inverted polyps: a clinicopathological analysis of five cases

Objective: To investigate the endoscopic and histopathological features, diagnosis and differential diagnosis of gastric hamartomatous inverted polyp (GHIP). Methods: Five cases of GHIP were collected at the University Town Hospital of Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China, from May 2021 to May 2023. The endoscopic, pathological and immunohistochemical features of the 5 GHIP cases were analyzed. The relevant literature was reviewed. Results: There were 3 males and 2 females, aged from 49 to 60 years, with a mean age of 56 years. The lesions were located in the fundus and body of the stomach, and presented as polyps or masses under endoscopy. Microscopically, the lesions were mainly in the submucosa and consisted of lobulated or clustered gastric glandular epithelium surrounded by hyperplastic smooth muscle. In some areas, there were differentiated glandular elements mimicking the normal gastric mucosa. The irregularly dilated glandular elements in the center were lined by hyperplastic foveolar epithelium, while the glands in the periphery were fundic or pyloric glands. In addition, in some areas, the glands showed cystic expansion, disordered arrangement and lack of differentiation. The hyperplastic glandular epithelium included foveolar epithelium, fundic gland and pyloric gland. There were scattered neuroendocrine cells and smooth muscle bundles in the stroma. Immunohistochemically, the tumor cells were positive for MUC5AC, MUC6, Pepsinogen Ⅰ and H+/K+ ATPase β, but negative for MUC2. The scattered neuroendocrine cells were positive for synaptophysin, and the desmin stain highlighted hyperplastic smooth muscle bundles. One case was classified as type 2 gastric inverted polyp, and 4 cases were classified as type 3. Conclusions: GHIP is a rare gastric polyp with unique histological features. It should be distinguished from inverted hyperplastic polyp, gastritis cystica profunda, adenomyoma, hyperplastic polyps and well-differentiated gastric tubular adenocarcinoma, etc. Improving the understanding of its pathogenesis and diagnostic features can help avoid misdiagnoses.

Feasibility and efficacy of endoscopy with blue laser imaging for the detection and diagnosis of cardia polyps: A single-center randomized controlled study.

To compare the detection rate and diagnostic accuracy of cardia polyps using endoscopy with blue laser imaging (BLI) and white-light imaging (WLI). Patients were randomly divided into the BLI group and WLI group according to the endoscopic procedures. BLI followed by WLI was conducted in the BLI group, whereas WLI followed by BLI examination was conducted in the WLI group. The number, size, microstructure, and microvascular patterns of cardia polyps detected were recorded. Biopsy of the polyps was then performed. The detection rate of cardia polyps in the BLI group was higher than that in the WLI group (7.87% vs 4.22%, P = 0.018). The rate of overlooked lesions in the BLI group was lower than in the WLI group (0.64% vs 3.38%, P = 0.003). The diagnostic coincidence rate between magnifying BLI and histopathology was 88.16%. The sensitivity, specificity, positive predictive value and negative predictive value for the diagnosis of neoplastic lesions by magnifying endoscopy with BLI were 90.91%, 87.69%, 55.56%, and 98.28%, respectively. The most remarkable patterns for predicting inflammatory polyps were the prolonged and fine network patterns (sensitivity 71.43%, specificity 93.75%). Small round combined with honeycomb patterns were the most common among fundic gland polyps (sensitivity 80.00%, specificity 98.48%). Neoplastic lesions presented as villous or ridge-like combined with core vascular or unclear pattern for both microvascular and microstructure patterns. BLI is more effective than WLI in the detection and diagnosis of cardia polyps, and magnifying endoscopy with BLI may help diagnose such lesions.

Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid.

Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts-both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG.