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To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant.

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Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype-phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398-1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.

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OBJECTIVES: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. METHODS: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. RESULTS: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and an irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogen+ously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HPs and PPI-Ls were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). CONCLUSION: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

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ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia coriaria (Jacq.) Willd is widely used as a traditional medinal plant in Mexico for protective and healing purposes and the treatment of gastrointestinal diseases. AIM OF THE STUDY: To investigate the gastroprotective effect of extract of Caesalpinia coriaria pods against ethanol-induced and indomethacin-induced gastric lesion models, its anti-inflammatory and antioxidative activities, and its main compounds through LC-MS analysis. MATERIALS AND METHODS: Male Wistar rats were orally administered a methanol extract obtained from the pods of C. coriaria at doses of 10, 30, 100, and 300 mg/kg prior to inducing gastric lesions with ethanol or indomethacin. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations. Determination of prostaglandin E2 (PGE2), alpha tumor necrosis factor (TNF-α), leukotriene B4 (LTB4), nitrites/nitrates, superoxide dismutase (SOD), and H2S gastric levels were investigated. Its main compounds of the active extract through LC-MS analysis. RESULTS: Phenolic compounds were identified as major components of methanol extract. LC-MS analysis identified 15 constituents, and the significant compounds were gallic acid, 3-O-galloylquinic acid, digalloylglucose, tetragalloylglucose, valoneic acid dilactone, pentagalloylglucose, digalloylshikimic acid, and ellagic acid. Pretreatment with the extract at doses of 100 and 300 mg/kg significantly reduced gastric ulcer lesions in both models. Compared with the reference drugs (omeprazole or ranitidine, respectively), no significant difference was found (p < 0.05). The extract's gastroprotective effect was accompanied by significant decreases in leukocyte recruitment, and gastric levels of TNF-α and LTB4 by two to fourfold (p < 0.05). Also, gastric levels of PGE2 gastric levels were maintained and the antioxidant enzyme activities of SOD and nitrate/nitrite in the gastric tissue were improved (p < 0.05). The LC-MS analysis indicated the presence of hydrolyzable tannins (mainly gallic acid derivatives). CONCLUSION: The results suggest that the gastroprotective effect of the methanol extract of C. coriaria pods occurs through anti-inflammatory, antioxidant, and NO modulation properties, and gallic acid derivatives may be the main possible compounds responsible for its actions.

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BACKGROUND: Early detection of gastric cancer (GC) remains challenging. We aimed to examine urine proteomic signatures and identify protein biomarkers that predict the progression of gastric lesions and risk of GC. METHODS: A case-control study was initially designed, covering subjects with GC and gastric lesions of different stages. Subjects were aged 40-69 years, without prior diagnosis of renal or urological diseases. We enrolled a total of 255 subjects, with 123 in the discovery stage from Linqu, China, a high-risk area for GC and 132 in the validation stage from Linqu and Beijing. A prospective study was further designed for a subset of 60 subjects with gastric lesions, which were followed for 297-857 days. FINDINGS: We identified 43 differentially expressed urine proteins in subjects with GC vs. mild or advanced gastric lesions. Baseline urinary levels of ANXA11, CDC42, NAPA and SLC25A4 were further positively associated with risk of gastric lesion progression. Three of them, except for SLC25A4, also had higher expression in GC than non-GC tissues. Integrating these four proteins showed outstanding performance in predicting the progression of gastric lesions (AUC (95% CI): 0.92 (0.83-1.00)) and risk of GC (AUC (95% CI): 0.81 (0.73-0.89) and 0.84 (0.77-0.92) for GC vs. mild or advanced gastric lesions respectively). INTERPRETATION: This study revealed distinct urine proteomic profiles and a panel of proteins that may predict the progression of gastric lesions and risk of GC. These biomarkers in a non-invasive approach may have translational significance for defining high-risk populations of GC and its early detection. FUNDING: Funders are listed in the Acknowledgement.

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BACKGROUND: The Sydney system offers a standard biopsy protocol for detection and follow-up of gastric preneoplastic lesions such as intestinal metaplasia (IM). The highest frequency of cardia-type gastric adenocarcinoma (GA) in Iran has been documented in the north-western part of the country. This study aims to investigate the effect of the addition of mucosal biopsies of gastric cardia to the standard Sydney protocol on the rate of detection of IM in the asymptomatic residents of this high-risk region for proximal gastric cancer. METHODS: A retrospective new analysis was performed on the previous data obtained in cross-sectional endoscopic screening in 2000 as well as a biopsy study of 508 asymptomatic volunteer residents in Meshkinshahr district, Ardabil province. The screening study was conducted in a group of residents aged 40 years and older who did not have any previous GI or hemodynamic problems. RESULTS: Intestinal metaplasia at the Sydney protocol sampling sites was detected in 107 samples belonging to 76 of the 508 (14.99%) volunteers. Twenty-one patients had IM at the cardia. Of these, five patients had IM-cardia (IM only at the cardia). Therefore, adding a cardia biopsy to the set of biopsies diagnosed five more IM cases which were not diagnosed on the standard Sydney protocol (P=0.062). CONCLUSION: The addition of a biopsy from the cardia to the Sydney protocol biopsy set does not seem to improve the frequency of detection of IM in the residents of this high-risk geographic area for proximal gastric carcinoma.

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The aim of this study was to improve the solubility and prevent the ulcerogenic effect of flurbiprofen. Initially, binary and ternary solid dispersions (BSDs and TSDs) of flurbiprofen were prepared by using non-ordered mesoporous silica and gelucire. After preformulation testing (solubility, flow properties, % yield, and entrapment efficiency), four formulations were selected for further detailed studies. Solid-state characterization of optimized formulations (S1, S6, S7, and S12) showed successful drug incorporation in the solid dispersion at the molecular state without any noticeable interactions. The in vitro solubility and release study showed an increase in solubility and 98-100% of drug release in 30-45 min. The in vivo gastro-protective effect of the optimized formulations containing flurbiprofen and silica (1:1) with 25% w/w gelucire (S6 and S12) showed a reduction in the gastric lesion index (GLI) after four days of treatment. Moreover, histological images of the stomach lining (S6 and S12) illustrated normal epithelial cells and a partially protected mucosal membrane. Thus, TSD exhibited a significant increase in solubility and the dissolution rate and reduced the gastric ulceration. Therefore, TSDs are dubbed as efficacious carriers to enhance the bioavailability of flurbiprofen while simultaneously reducing its side effects.

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Rationale: Gastric cancer (GC) is preceded by a stepwise progression of precancerous gastric lesions. Distinguishing individuals with precancerous gastric lesions that have progression potential to GC is an important need. Perturbated lipid metabolism, particularly the dysregulation of de novo lipogenesis, is involved in gastric carcinogenesis. We conducted the first prospective lipidomics study exploring lipidomic signatures for the risk of gastric lesion progression and early GC. Methods: Our two-stage study of targeted lipidomics enrolled 400 subjects from the National Upper Gastrointestinal Cancer Early Detection Program in China, including 200 subjects of GC and different gastric lesions in the discovery and validation stages. Of validation stage, 152 cases with gastric lesions were prospectively followed for the progression of gastric lesions for a median follow-up of 580 days (interquartile range 390-806 days). We examined the lipidomic signatures associated with the risk of advanced gastric lesions and their progression to GC. Our published tissue proteomic data were referred to further investigate highlighted lipids with their biologically related protein expression in gastric mucosa. Results: We identified 11 plasma lipids significantly inversely associated with the risk of gastric lesion progression and GC occurrence. These lipids were integrated as latent profiles to identify 5 clusters of lipid expression that had distinct risk of gastric lesion progression. The latent profiles significantly improved the ability to predict the progression potential of gastric lesions (AUC: 0.82 vs 0.68, Delong's P = 4.6×10-4) and risk of early GC (AUC: 0.81 vs 0.55, P = 6.3×10-5). Significant associations were found between highlighted lipids, their biologically correlated proteins and the risk of GC, supporting the role of the pathways involving monocarboxylic acid metabolism and lipid transport and catabolic process in GC. Conclusions: Our study revealed the lipidomic signatures associated with the risk of gastric lesion progression and GC occurrence, exhibiting translational implications for GC prevention.

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Peptic ulcers are lesions that affect the gastrointestinal tract and that can be triggered by external factors such as alcohol use. This study investigated the gastroprotective role of two anthocyanidins, malvidin and cyanidin chloride, in an ethanol-induced gastric ulcer model in male and female mice (ovariectomized and supplemented with 17ß-estradiol or not) and aimed to evaluate the effectiveness of anthocyanidins in preventing the formation of lesions and to identify the underlying mechanisms, while considering hormonal differences. Moreover, in silico comparative analysis was performed to predict the properties and biological behaviors of the molecules. We observed that the hormonal status did not interfere with the gastroprotective action of malvidin, although antioxidant mechanisms were modulated differently depending on sex. On the other hand, cyanidin showed gastroprotective activity at different doses, demonstrating that, for the same experimental model, there is a need to adjust the effective dose depending on sex. In silico analysis showed that, despite being structurally similar, the interaction with receptors and target proteins in this study (myeloperoxidase, superoxide dismutase, catalase, and reduced glutathione) differed between the two molecules, which explains the difference observed in in vivo treatments.

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Gastric duplication cysts are rare congenital malformation with a potential neoplastic progression and they may represent a challenge in differential diagnosis with exophytic pancreatic cyst neoplasm. We describe a case of a 38-year old man, complaining of recurrent epigastric pain due to a large abdominal mass, referred to our Hospital for EUS evaluation. Differential diagnosis was between gastric duplication cyst and exophytic pancreatic cyst because of FNA pointed out amylase 1280 UI/L and CEA 593.33 ng/mL. Despite antibiotic prophylaxis, an overinfection of the lesion occurred after the FNA, likely due to the technical failure to drain the cyst completely. Afterwards, the patient was referred to surgery and the pathologist confirmed the diagnosis of gastric duplication cyst. In this setting, EUS procedure has gained a leading play, complementary to traditional imaging tests, although its role has been not yet standardized in the reported literature. Here, we describe and discuss our demanding case, and we propose an algorithm to simplify and standardize the diagnostic workup.

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We redefined Robert's prototypical cytoprotection model, namely the intragastric administration of 96% alcohol in order to generate a general peripheral and central syndrome similar to that which occurs when major central or peripheral veins are occluded in animal models. With this redefinition, we used Robert's model to examine the cytoprotective effects of the stable gastric pentadecapeptide BPC 157. The intragastric administration of alcohol induced gastric lesions, intracranial (superior sagittal sinus) hypertension, severe brain swelling and lesions, portal and vena caval hypertension, aortal hypotension, severe thrombosis, inferior vena cava and superior mesenteric vein congestion, azygos vein failure (as a failed collateral pathway), electrocardiogram disturbances, and heart, lung, liver and kidney lesions. The use of BPC 157 therapy (10 µg/kg or 10 ng/kg given intraperitoneally 1 min after alcohol) counteracted these deficits rapidly. Specifically, BPC 157 reversed brain swelling and superior mesenteric vein and inferior vena caval congestion, and helped the azygos vein to recover, which improved the collateral blood flow pathway. Microscopically, BPC 157 counteracted brain (i.e., intracerebral hemorrhage with degenerative changes of cerebral and cerebellar neurons), heart (acute subendocardial infarct), lung (parenchymal hemorrhage), liver (congestion), kidney (congestion) and gastrointestinal (epithelium loss, hemorrhagic gastritis) lesions. In addition, this may have taken place along with the activation of specific molecular pathways. In conclusion, these findings clarify and extend the theory of cytoprotection, offer an approach to its practical application, and establish BPC 157 as a prospective cytoprotective treatment.

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OBJECTIVE: We aimed to establish a standardized procedure for white light gastroscopy (WLG) to screen gastric lesions including early gastric cancer (EGC) in China and to verify its efficacy and feasibility in clinical practice. METHODS: A standardized WLG procedure for outpatients at nine tertiary hospitals in Beijing was established. Clinical information of the participants and details of the endoscopic procedures were recorded. RESULTS: A total of 1051 participants were enrolled in a baseline conventional endoscopic survey between March 2014 and December 2015, while 2156 patients were enrolled in the standardized WLG operation from January 2016 to June 2017. The procedure time of the standardized procedure was significantly longer than that of the baseline conventional procedure (P = 0.003). More images were obtained during the standardized procedure compared with the baseline conventional procedure (P < 0.001). The overall detection rate of gastric lesions in the standardized procedure group was significantly higher than that in the baseline procedure group (52.5% vs 38.4%, P < 0.01). The satisfaction scores of both participants and endoscopists in the standardized procedure group were significantly higher than in the baseline procedure group. CONCLUSIONS: Compared with the conventional procedure, standardized WLG procedure significantly improves the detection rate of gastric lesions as well as the satisfaction score of participants and endoscopists despite its longer procedure time. It is effective and feasible in clinical practice in China for the use of currently available endoscopic equipment.

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BACKGROUND AND AIM: The fruit of Garcinia is a rich and valuable source of bioactive compounds and is traditionally used for treating wounds and ulcers. The present study was carried out to investigate the protective effect of chromatographically standardized fruit extract of Garcinia cowa (GCE) on ethanol-induced gastric lesions in rats and its possible mechanisms. METHODS: The effect of GCE (200 and 400 mg/kg body weight) was evaluated by determining various gastric ulcer parameters like gastric wall mucus, non-protein sulfhydryls (NP-SH) content, microvascular permeability, endogenous antioxidant enzyme, and gastric histopathological study. RESULTS AND CONCLUSIONS: Oral administration of GCE at doses of 200 and 400 mg/kg exhibited significant (p < .01) dose-dependent inhibition of ulcer index by 18.94-44.02%, respectively. Pre-treatment of rats with GCE (400 mg/kg) significantly restored the depleted gastric wall mucus level by 34.09% and NP-SH content by 33.35% induced by ethanol administration. In addition, GCE (400 mg/kg) showed a significant decrease in microvascular permeability of Evans Blue by 47.43%, rationalizing its protective effect. Furthermore, a significant increase in oxidative enzyme levels with reduction in malondialdehyde level and elevation of superoxide dismutase (SOD) activity was observed in the GCE treated group as compared to the ulcer control group. The histopathological assessment also confirmed the protective nature of GCE. HPTLC analysis showed the presence of 0.27%, 0.11% w/w gallic acid, and amentoflavone, respectively in GCE. The content of α-mangostin and xanthochymol in the G. cowa extract sample quantified by HPLC-PDA method was 0.72 and 8.46%, respectively. The results obtained indicate that the protective effect of GCE against gastric ulcers in rats through multiple actions confirmed by the reduction of oxidative stress and restoration of adhered gastric mucus, NP-SH content, and histological architecture.KEY MESSAGESEthanol is the most typical ulcerogenic agent and has been shown to extend the risk of ulcer in humans.Natural products are promising alternative medication for the development of new drugs to regulate gastrointestinal diseases.Garcinia cowa protects the gastric mucosa through multiple actions that include restoration of adhered gastric mucus and inhibition of lipid peroxidation.

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This article analyses the literature regarding the value of computer-assisted systems in esogastroduodenoscopy-quality monitoring and the assessment of gastric lesions. Current data show promising results in upper-endoscopy quality control and a satisfactory detection accuracy of gastric premalignant and malignant lesions, similar or even exceeding that of experienced endoscopists. Moreover, artificial systems enable the decision for the best treatment strategies in gastric-cancer patient care, namely endoscopic vs surgical resection according to tumor depth. In so doing, unnecessary surgical interventions would be avoided whilst providing a better quality of life and prognosis for these patients. All these performance data have been revealed by numerous studies using different artificial intelligence (AI) algorithms in addition to white-light endoscopy or novel endoscopic techniques that are available in expert endoscopy centers. It is expected that ongoing clinical trials involving AI and the embedding of computer-assisted diagnosis systems into endoscopic devices will enable real-life implementation of AI endoscopic systems in the near future and at the same time will help to overcome the current limits of the computer-assisted systems leading to an improvement in performance. These benefits should lead to better diagnostic and treatment strategies for gastric-cancer patients. Furthermore, the incorporation of AI algorithms in endoscopic tools along with the development of large electronic databases containing endoscopic images might help in upper-endoscopy assistance and could be used for telemedicine purposes and second opinion for difficult cases.

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The present study investigated the effects of Shilajit extract on aspirin-induced gastric lesions in rats. We evaluated macroscopic and histopathological lesions in the stomach, measured the activity of oxidative stress enzymes in gastric tissue homogenates, and assessed serum electrolytes and parameters of kidney and liver function. Forty-five male rats were allocated to five groups: Normal control, positive control, omeprazole treatment, Shilajit treatment, and Shilajit control. The treatment period lasted for four consecutive days. The size and number of gastric lesions were significantly reduced in the Shilajit and omeprazole groups compared to the positive control group, indicating a reduction in mucosal damage and the severity of edema and leukocyte infiltration in tissue sections. A significant increase was observed in the levels of all oxidative stress parameters, except malondialdehyde, in rats treated with Shilajit and omeprazole compared to those in the positive control group. The effect of the aqueous extract of Shilajit was comparable to that of omeprazole. These results indicated the protective effects of Shilajit against aspirin-induced gastric lesions.

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At present, the application of artificial intelligence (AI) based on deep learning in the medical field has become more extensive and suitable for clinical practice compared with traditional machine learning. The application of traditional machine learning approaches to clinical practice is very challenging because medical data are usually uncharacteristic. However, deep learning methods with self-learning abilities can effectively make use of excellent computing abilities to learn intricate and abstract features. Thus, they are promising for the classification and detection of lesions through gastrointestinal endoscopy using a computer-aided diagnosis (CAD) system based on deep learning. This study aimed to address the research development of a CAD system based on deep learning in order to assist doctors in classifying and detecting lesions in the stomach, intestines, and esophagus. It also summarized the limitations of the current methods and finally presented a prospect for future research.

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The use of bisphosphonates constitutes the gold-standard therapy for the control and treatment of bone diseases. However, its long-term use may lead to gastric problems, which limits the treatment. Thus, this study aimed to formulate a nanostructured system with biodegradable polymers for the controlled release of alendronate sodium. The nanoparticles were characterized, and its gastric toxicity was investigated in rats. The synthesis process proved to be effective for encapsulating alendronate sodium, exhibiting nanoparticles with an average size of 51.02 nm and 98.5% of alendronate sodium incorporation. The release tests demonstrated a controlled release of the drug in 420 min, while the morphological analyzes showed spherical shapes and no apparent roughness. The biological tests demonstrated that the alendronate sodium nanoformulation reversed the gastric lesions, maintaining the normal levels of malondialdehyde and myeloperoxidase. Also, the encapsulated alendronate sodium showed no toxicity in murine osteoblastic cells, even at high concentrations.

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BACKGROUND: Technological and operative advancements have allowed laparoscopic intragastric surgery (LIGS) to be applied in the treatment of superficial gastric or submucosal lesions. The aim of this study was to evaluate short- and long-term outcomes following LIGS. METHODS: From 2000 to 2013, 25 LIGSs were performed for superficial gastric lesions. Clinical records were reviewed retrospectively for peri-operative course and long-term outcomes with particular attention to the oncological follow-up for patients with malignant lesions. RESULTS: Nineteen (76%) lesions were located close to the EGJ, three (12%) in the lesser curvature, two (8%) in the posterior wall and one (4%) in the prepyloric-antral region. A multiport technique was used in 15 (60%) patients and a single-access approach in 10 (40%) patients. The median operative time was 140 (50-210) minutes. No conversion to open or conventional laparoscopic surgery was needed. Mortality was nil, and severe morbidity occurred in one (4%) patient. The median length of stay was 6 (3-10) days. Indications of LIGS were adenocarcinoma in 11 (44%) patients, gastrointestinal stromal tumors (GISTs) in 6 (24%) patients and benign lesions in eight (32%) patients. En bloc resection was obtained in 24 (96%) patients with R0 margins in 23 (92%) patients. After a median follow-up of 76 (26-171) months, recurrence was detected in 4 (36%) patients with advanced malignant adenocarcinoma. CONCLUSION: LIGS provides an interesting alternative to major gastric and EGJ resection when endoscopic resection is not suitable for highly selected patients with superficial gastric lesions.

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