Duloxetine protected indomethacin-induced gastric mucosal injury by increasing serotonin-dependent RANTES expression and activating PI3K-AKT-VEGF pathway.

Antidepressant duloxetine has been shown protective effect on indomethacin-induced gastric ulcer, which was escorted by inflammation in the gastric mucosa. Cytokines are the principal mediators of inflammation. Thus, by screening the differential expression of cytokines in the gastric mucosa using cytokine array at 3 h after indomethacin exposure, when the gastric ulcer began to format, we found that indomethacin increased cytokines which promoted inflammation responses, whereas duloxetine decreased pro-inflammatory cytokines increased by indomethacin and increased RANTES expression. RANTES was consistently increased by pretreated with both 5 mg/kg and 20 mg/kg duloxetine at 3 h and 6 h after indomethacin exposure in male rats. Selective blockade of RANTES-CCR5 axis by a functional antagonist Met-RANTES or a CCR5 antagonist maraviroc suppressed the protection of duloxetine. Considering the pharmacologic action of duloxetine on reuptake of monoamine neurotransmitters, we examined the serotonin (5-HT), norepinephrine and dopamine contents in the blood and discovered 20 mg/kg duloxetine increased 5-HT levels in platelet-poor plasma, while treatment with 5-HT promoted expression of RANTES in the gastric mucosa and alleviated the indomethacin-induced gastric injury. Furthermore, duloxetine activated PI3K-AKT-VEGF signaling pathway, which was regulated by RANTES-CCR5, and selective inhibitor of VEGF receptor axitinib blocked the prophylactic effect of duloxetine. Furthermore, duloxetine also protected gastric mucosa from indomethacin in female rats, and RANTES was increased by duloxetine after 6 h after indomethacin exposure too. Together, our results identified the role of cytokines, particularly RANTES, and the underlying mechanisms in gastroprotective effect of duloxetine against indomethacin, which advanced our understanding in inflammatory modulation by monoamine-based antidepressants.

Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis.

Background: The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated. Purpose: This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism. Methods: The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins. Results: The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin. Conclusion: Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.

Triple-drug combination therapy versus six-month proton pump inhibitor monotherapy in non-Helicobacter pylori Helicobacter eradication, and hyperacid environment preference of Helicobacter suis: a clinical study.

BACKGROUND: At present, eradication regimens for non-Helicobacter pylori Helicobacter (NHPH) have not been established yet. We investigated effectiveness of the standard triple-drug combination therapy for Helicobacter pylori eradication and of a proton pump inhibitor (PPI) monotherapy in eradication of NHPH. METHODS: Subjects were the patients who were diagnosed with NHPH-infected gastritis based on microscopic findings, helical-shaped organisms obviously larger than Helicobacter pylori, in the gastric mucosal specimens using Giemsa staining at Kenwakai Hospital between November 2010 and September 2021, whose NHPH species were identified by polymerase chain reaction (PCR) analysis of urease genes in endoscopically-biopsied samples, and who consented to NHPH eradication with either the triple-drug combination therapy for one week or a PPI monotherapy for six months. Six months after the completion of eradication, its result was determined with esophagogastroduodenoscopy, microscopic examination, and PCR analysis. In cases of unsuccessful eradication, a second eradication with the other therapy was suggested to the patient. RESULTS: PCR analysis detected NHPH in 38 patients: 36 as Helicobacter suis and two as Helicobacter heilmannii/Helicobacter ailurogastricus. Fourteen Helicobacter suis-infected and one Helicobacter heilmannii/Helicobacter ailurogastricus-infected patients requested eradication therapy. The triple-drug combination therapy succeeded in four of five patients, while the PPI monotherapy succeeded in five of 10 patients. Three of five patients who had been unsuccessful with the latter therapy requested the triple-drug combination therapy as the second eradication and all three were successful. In total, the triple-drug combination therapy succeeded in seven out of eight (87.5%) attempted cases, while the PPI monotherapy in five out of 10 (50%) attempted cases. CONCLUSIONS: In NHPH eradication, the triple-drug combination therapy was considered to be effective to some extent and to become the first-line therapy. While, although less successful, PPI monotherapy appeared to be a potentially promising option particularly for patients with allergy or resistance to antibiotics. Effectiveness of PPI monotherapy may be attributed to hyperacid environment preference of Helicobacter suis and PPI's acid-suppressive effect. Additionally, male predominance in NHPH-infected gastritis patients may be explained by gender difference in gastric acid secretory capacity. However, further evidence needs to be accumulated. STUDY REGISTRATION: This study was approved by the Research Ethics Committee of Kenwakai Hospital (No. 2,017,024).

Machine learning models to predict submucosal invasion in early gastric cancer based on endoscopy features and standardized color metrics.

Conventional endoscopy is widely used in the diagnosis of early gastric cancers (EGCs), but the graphical features were loosely defined and dependent on endoscopists' experience. We aim to establish a more accurate predictive model for infiltration depth of early gastric cancer including a standardized colorimetric system, which demonstrates promising clinical implication. A retrospective study of 718 EGC cases was performed. Clinical and pathological characteristics were included, and Commission Internationale de l'Eclariage (CIE) standard colorimetric system was used to evaluate the chromaticity of lesions. The predicting models were established in the derivation set using multivariate backward stepwise logistic regression, decision tree model, and random forest model. Logistic regression shows location, macroscopic type, length, marked margin elevation, WLI color difference and histological type are factors significantly independently associated with infiltration depth. In the decision tree model, margin elevation, lesion located in the lower 1/3 part, WLI a*color value, b*color value, and abnormal thickness in enhanced CT were selected, which achieved an AUROC of 0.810. A random forest model was established presenting the importance of each feature with an accuracy of 0.80, and an AUROC of 0.844. Quantified color metrics can improve the diagnostic precision in the invasion depth of EGC. We have developed a nomogram model using logistic regression and machine learning algorithms were also explored, which turned out to be helpful in decision-making progress.

Mitochondrial Dysfunction by FADDosome Promotes Gastric Mucosal Injury in Portal Hypertensive Gastropathy.

Mucosal epithelial death is an essential pathological characteristic of portal hypertensive gastropathy (PHG). FADDosome can regulate mucosal homeostasis by controlling mitochondrial status and cell death. However, it remains ill-defined whether and how the FADDosome is involved in the epithelial death of PHG. The FADDosome formation, mitochondrial dysfunction, glycolysis process and NLRP3 inflammasome activation in PHG from both human sections and mouse models were investigated. NLRP3 wild-type (NLRP3-WT) and NLRP3 knockout (NLRP3-KO) littermate models, critical element inhibitors and cell experiments were utilized. The mechanism underlying FADDosome-regulated mitochondrial dysfunction and epithelial death in PHG was explored. Here, we found that FADD recruited caspase-8 and receptor-interacting serine/threonine-protein kinase 1 (RIPK1) to form the FADDosome to promote Drp1-dependent mitochondrial fission and dysfunction in PHG. Also, FADDosome modulated NOX2 signaling to strengthen Drp1-dependent mitochondrial fission and alter glycolysis as well as enhance mitochondrial reactive oxygen species (mtROS) production. Moreover, due to the dysfunction of electron transport chain (ETC) and alteration of antioxidant enzymes activity, this altered glycolysis also contributed to mtROS production. Subsequently, the enhanced mtROS production induced NLRP3 inflammasome activation to result in the epithelial pyroptosis and mucosal injury in PHG. Thus, the FADDosome-regulated pathways may provide a potential therapeutic target for PHG.

Revealing the pathogenesis of gastric intestinal metaplasia based on the mucosoid air-liquid interface.

BACKGROUND: Gastric intestinal metaplasia (GIM) is an essential precancerous lesion. Although the reversal of GIM is challenging, it potentially brings a state-to-art strategy for gastric cancer therapeutics (GC). The lack of the appropriate in vitro model limits studies of GIM pathogenesis, which is the issue this work aims to address for further studies. METHOD: The air-liquid interface (ALI) model was adopted for the long-term culture of GIM cells in the present work. This study conducted Immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), transcriptomic sequencing, and mucoproteomic sequencing (MS) techniques to identify the pathways for differential expressed genes (DEGs) enrichment among different groups, furthermore, to verify novel biomarkers of GIM cells. RESULT: Our study suggests that GIM-ALI model is analog to the innate GIM cells, which thus can be used for mucus collection and drug screening. We found genes MUC17, CDA, TRIM15, TBX3, FLVCR2, ONECUT2, ACY3, NMUR2, and MAL2 were highly expressed in GIM cells, while GLDN, SLC5A5, MAL, and MALAT1 showed down-regulated, which can be used as potential biomarkers for GIM cells. In parallel, these genes that highly expressed in GIM samples were mainly involved in cancer-related pathways, such as the MAPK signal pathway and oxidative phosphorylation signal pathway. CONCLUSION: The ALI model is validated for the first time for the in vitro study of GIM. GIM-ALI model is a novel in vitro model that can mimic the tissue micro-environment in GIM patients and further provide an avenue for studying the characteristics of GIM mucus. Our study identified new markers of GIM as well as pathways associated with GIM, which provides outstanding insight for exploring GIM pathogenesis and potentially other related conditions.

Tamarix aphylla derived metabolites ameliorate indomethacin-induced gastric ulcers in rats by modulating the MAPK signaling pathway, alleviating oxidative stress and inflammation: In vivo study supported by pharmacological network analysis.

Nature has proven to be a treasure resource of bioactive metabolites. In this regard, Tamarix aphylla (F. Tamaricaceae) leaves crude extract was investigated for its gastroprotective effect against indomethacin-induced damage to the gastric mucosa. Additionally, phytochemical investigation of the methanolic extract afforded eight flavonoids' derivatives (1-8). On pharmacology networking study, the isolated compounds identified 123 unique targets where only 45 targets were related to peptic ulcer conditions, these 45 targets include 11 targets specifically correlate to gastric ulcer. The protein-protein interaction defined the PTGS2 gene as one of the highly interacted genes and the complete pharmacology network defined the PTGS2 gene as the most represented gene. The top KEGG signaling pathways according to fold enrichment analysis was the EGFR tyrosine kinase inhibitor resistance pathway. As a result, these findings highlighted the significance of using T. aphylla leaves crude extract as an anti-gastric ulcer candidate, which provides a safer option to chemical antisecretory medicines, which are infamous for their negative side effects. Our findings have illuminated the potent anti-inflammatory and antioxidant effects of T. aphylla, which are likely mediated by suppressing IL-1ß, IL-6, TNF-α, and MAPK signaling pathways, without compromising gastric acidity.

Helicobacter pylori disrupts gastric mucosal homeostasis by stimulating macrophages to secrete CCL3.

BACKGROUND: Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis. METHODS: The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry. RESULTS: After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased. CONCLUSIONS: In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.

MISP Is Overexpressed in Intestinal Metaplasia and Gastric Cancer.

Gastric cancer is the fifth most common cancer and the fourth cause of global cancer mortality. The identification of new biomarkers and drug targets is crucial to allow the better prognosis and treatment of patients. The mitotic spindle positioning (MISP) protein has the function of correcting mitotic spindle positioning and centrosome clustering and has been implicated in the cytokinesis and migration of cancer cells. The goal of this work was to evaluate the expression and clinical relevance of MISP in gastric cancer. MISP expression was evaluated by immunohistochemistry in a single hospital series (n = 286) of gastric adenocarcinomas and compared with normal gastric mucosa and intestinal metaplasia, a preneoplastic lesion. MISP was detected on the membrane in 83% of the cases, being overexpressed in gastric cancer compared to normal gastric mucosa (n = 10). Its expression was negatively associated with diffuse and poorly cohesive types. On the other hand, it was strongly expressed in intestinal metaplasia where it was associated with MUC2 and CDX2 expression. Furthermore, when we silenced MISP in vitro, a significant decrease in the viability of gastric carcinoma cells was observed. In conclusion, MISP is overexpressed in gastric cancer, being associated with an intestinal phenotype in gastric carcinogenesis and having a role in cellular proliferation.

Drug-induced mucosal alterations observed during esophagogastroduodenoscopy.

Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract, i.e., the esophagus, stomach, and duodenum. These include pill-induced esophagitis, desquamative esophagitis, worsening of gastroesophageal reflux, chemotherapy-induced esophagitis, proton pump inhibitor-induced gastric mucosal changes, medication-induced gastric erosions and ulcers, pseudomelanosis of the stomach, olmesartan-related gastric mucosal inflammation, lanthanum deposition in the stomach, zinc acetate hydrate tablet-induced gastric ulcer, immune-related adverse event gastritis, olmesartan-asso-ciated sprue-like enteropathy, pseudomelanosis of the duodenum, and lanthanum deposition in the duodenum. For endoscopists, acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions. This minireview aims to provide essential information on drug-induced mucosal alterations observed on esophagogastroduodenoscopy, along with representative endoscopic images.

Ferulic acid nanoemulsion as a promising anti-ulcer tool: in vitro and in vivo assessment.

OBJECTIVE: Ferulic acid (FA) is a promising nutraceutical molecule which exhibits antioxidant and anti-inflammatory properties, but it suffers from poor solubility and bioavailability. In the presented study, FA nanoemulsions were prepared to potentiate the therapeutic efficacy of FA in prevention of gastric ulcer. METHODS: FA nanoemulsions were prepared, pharmaceutically characterized, and the selected nanoemusion was tested for its ulcer-ameliorative properties in rats after induction of gastric ulcer using ethanol, by examination of stomach tissues, assessment of serum IL-1ß and TNF-α, assessment of nitric oxide, prostaglandin E2, glutathione, catalase and thiobarbituric acid reactive substance in stomach homogenates, as well as histological and immunohistochemical evaluation. RESULTS: Results revealed that the selected FA nanoemulsion showed a particle size of 90.43 nm, sustained release of FA for 8 h, and better in vitro anti-inflammatory properties than FA. Moreover, FA nanoemulsion exhibited significantly better anti-inflammatory and antioxidant properties in vivo, and the gastric tissue treated with FA nanoemulsion was comparable to the normal control upon histological and immunohistochemical evaluation. CONCLUSION: Findings suggest that the prepared ferulic acid nanoemulsion is an ideal anti-ulcer system, which is worthy of further investigations.

Exploring non-curative endoscopic submucosal dissection: Current treatment optimization and future indication expansion.

The increasing popularity of endoscopic submucosal dissection (ESD) as a treatment for early gastric cancer has highlighted the importance of quality assessment in achieving curative resections. This article emphasizes the significance of evaluating ESD quality, not only for curative cases but also for non-curative ones. Postoperative assessment relies on the endoscopic curability (eCura) classification, but management strategies for eCuraC-1 tumour with a positive horizontal margin are unclear. Current research primarily focuses on comparing additional surgical procedures in high-risk patients, while studies specifically targeting eCuraC-1 patients are limited. Exploring management strategies and follow-up outcomes for such cases could provide valuable insights. Furthermore, the application of molecular imaging using near-infrared fluorescent tracers holds promise for precise tumour diagnosis and navigation, potentially impacting the management of early-stage gastric cancer patients. Advancing research in these areas is essential for improving the overall efficacy of endoscopic techniques and refining treatment indications.

Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

[Pyloric gland adenoma - a rare tumor of the upper gastrointestinal tract with a high risk of malignancy]. / Adenoma piloricheskikh zhelez ­ redkaya opukhol' verkhnikh otdelov zheludochno-kishechnogo trakta s vysokim riskom malignizatsii.

BACKGROUND: Pyloric gland adenomas (PGA) are rare neoplasms of the gastrointestinal tract. According to the literature, these lesions may be underdiagnosed, and their true frequency of occurrence is underestimated. OBJECTIVE: Clinical and morphological analysis of eight PGA cases of the upper gastrointestinal tract. MATERIAL AND METHODS: The study included 8 cases of detection of PGA. In 7 out of 8 cases, the tumor was diagnosed by examining endoscopic biopsies, in 1 case, PGA was an accidental finding in the surgical material after proximal gastric resection. RESULTS: 6 out of 8 patients were female, the median age was 65 years (minimum 36 years and maximum 78 years). In 6 cases, PDA was localized in the stomach, in 1 - in the esophagus and in 1 - in the duodenum The size of the tumors ranged from 0.6 cm to 7.5 cm. 4 out of 6 stomach tumors appeared on the background of confirmed autoimmune gastritis, 1 - on the background of lymphocytic gastritis. 4 tumors were found in the body of the stomach, 1 - in the cardia, 1 - in the bottom of the stomach. In 2 out of 8 cases, there were signs of malignancy of the tumor with the transition to a highly differentiated adenocarcinoma. According to the results of the IHC study, the absence of a p53 mutation was noted in these cases. CONCLUSION: PGA should be considered as neoplasms with a high risk of transformation into invasive adenocarcinoma. Increasing the recognition of PGA among pathologists and further understanding of the molecular mechanisms involved in their neoplastic transformation will improve the diagnosis and treatment of this pathology.

[Therapeutic efficacy analysis of endoscopic combined with serological diagnosis strategy and endoscopic in G1 and G2 gastric neuroendocrine neoplasms].

Objective: To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Methods: This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment. Results: Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P＜0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P＜0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P＜0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P＜0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions: The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.

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

BACKGROUND: Gastric 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. METHODS: We 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. RESULTS: GHIPs 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. CONCLUSIONS: GHIPs 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.