[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.

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.

Endoscopic features and treatments of gastric cystica profunda.

BACKGROUND: Gastric cystica profunda (GCP) represents a rare condition characterized by cystic dilation of gastric glands within the mucosal and/or submucosal layers. GCP is often linked to, or may progress into, early gastric cancer (EGC). AIM: To provide a comprehensive evaluation of the endoscopic features of GCP while assessing the efficacy of endoscopic treatment, thereby offering guidance for diagnosis and treatment. METHODS: This retrospective study involved 104 patients with GCP who underwent endoscopic resection. Alongside demographic and clinical data, regular patient follow-ups were conducted to assess local recurrence. RESULTS: Among the 104 patients diagnosed with GCP who underwent endoscopic resection, 12.5% had a history of previous gastric procedures. The primary site predominantly affected was the cardia (38.5%, n = 40). GCP commonly exhibited intraluminal growth (99%), regular presentation (74.0%), and ulcerative mucosa (61.5%). The leading endoscopic feature was the mucosal lesion type (59.6%, n = 62). The average maximum diameter was 20.9 ± 15.3 mm, with mucosal involvement in 60.6% (n = 63). Procedures lasted 73.9 ± 57.5 min, achieving complete resection in 91.3% (n = 95). Recurrence (4.8%) was managed via either surgical intervention (n = 1) or through endoscopic resection (n = 4). Final pathology confirmed that 59.6% of GCP cases were associated with EGC. Univariate analysis indicated that elderly males were more susceptible to GCP associated with EGC. Conversely, multivariate analysis identified lesion morphology and endoscopic features as significant risk factors. Survival analysis demonstrated no statistically significant difference in recurrence between GCP with and without EGC (P = 0.72). CONCLUSION: The findings suggested that endoscopic resection might serve as an effective and minimally invasive treatment for GCP with or without EGC.

Strategies of Helicobacter pylori in evading host innate and adaptive immunity: insights and prospects for therapeutic targeting.

Helicobacter pylori (H. pylori) is the predominant pathogen causing chronic gastric mucosal infections globally. During the period from 2011 to 2022, the global prevalence of H. pylori infection was estimated at 43.1%, while in China, it was slightly higher at approximately 44.2%. Persistent colonization by H. pylori can lead to gastritis, peptic ulcers, and malignancies such as mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas. Despite eliciting robust immune responses from the host, H. pylori thrives in the gastric mucosa by modulating host immunity, particularly by altering the functions of innate and adaptive immune cells, and dampening inflammatory responses adverse to its survival, posing challenges to clinical management. The interaction between H. pylori and host immune defenses is intricate, involving evasion of host recognition by modifying surface molecules, manipulating macrophage functionality, and modulating T cell responses to evade immune surveillance. This review analyzes the immunopathogenic and immune evasion mechanisms of H. pylori, underscoring the importance of identifying new therapeutic targets and developing effective treatment strategies, and discusses how the development of vaccines against H. pylori offers new hope for eradicating such infections.

Robot-assisted gastric endoscopic submucosal dissection significantly improves procedure time at challenging dissection locations.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early malignant stomach lesions. However, this procedure is technically demanding and carries a high complication risk. The level of difficulty in performing ESD is influenced by the location of the lesion. In our study, we aimed to investigate and analyze the effectiveness of robot-assisted ESD for lesions situated in challenging locations within the stomach. METHODS: We developed a gastric simulator that could be used to implement various gastric ESD locations. An EndoGel (Sunarrow, Tokyo, Japan) was attached to the simulator for the dissection procedures. Robot-assisted or conventional ESD was performed at challenging or easy locations by two ESD-trainee endoscopists. RESULTS: The procedure time was remarkably shorter for robotic ESD than conventional dissection at challenging locations (6.2 vs. 10.2 min, P < 0.05), mainly due to faster dissection (220.3 vs. 101.9 mm2/min, P < 0.05). The blind dissection rate was significantly lower with robotic ESD than with the conventional method (17.6 vs. 35.2%, P < 0.05) at challenging locations. CONCLUSION: The procedure time was significantly shortened when robot-assisted gastric ESD procedures were performed at challenging locations. Therefore, our robotic device provides simple, effective, and safe multidirectional traction for endoscopic submucosal dissection at challenging locations, thereby reducing difficulty of the procedure.

Molecular docking, characterization, ADME/toxicity prediction, and anti-ulcer activity of new quercetin derivatives on indomethacin-induced gastric ulcer in mice.

Gastric ulcer (GU) is a serious upper gastrointestinal tract disorder that affects people worldwide. The drugs now available for GU treatment have a high rate of relapses and drug interactions, as well as mild to severe side effects. As a result, new natural therapeutic medications for treating GU with fewer negative side effects are desperately needed. Because of quercetin's (QCT) diverse pharmacological effects and unique structural features, we decided to semi-synthesize new QCT derivatives and test them for antiulcer activity. Docking assays were performed on the synthesized compounds to determine their affinity for TLR-4/MD-2, MyD88/TIR, and NF-κB domains, an important inflammatory pathway involved in GU development and progression. Mice were given oral famotidine (40 mg/kg/day), QCT, QCT pentamethyl (QPM), or QCT pentaacetyl (QPA) (50 mg/kg/day) for 5 days before GU induction by a single intraperitoneal injection of indomethacin (INDO; 18 mg/kg). QPM and QPA have a stronger binding affinity for TLR-4/MD-2, MyD88/TIR and NF-κB domains than QCT. In comparison, they demonstrated the greatest reduction in ulcer score and index, gastric MDA and nitric oxide (NO) contents, MyD88 and NF-κB expressions, and gastric TLR-4 immunostaining. They also enhanced the levels of GSH, CAT, COX-1, and COX-2 in the gastric mucosa, as well as HO-1 and Nrf2 expression, with histological regression in gastric mucosal lesions, with QPA-treated mice demonstrating the best GU healing. QPA is safe against all of the target organs and adverse pathways studied, with good ADME properties. However, further in vitro experiments are necessary to demonstrate the inhibitory effects of QPM and QPA on the protein targets of interest. In addition, preclinical research on its bioavailability and safety is essential before clinical management can be undertaken. Overall, the new QPA derivative could one day serve as the basis for a new class of potential antiulcer drugs.

Diagnosis by combination of endoscopic findings helps differentiate non-Helicobacter pylori Helicobacter-infected gastritis from Helicobacter pylori-infected gastritis.

BACKGROUND: The characteristic endoscopic findings of non-Helicobacter pylori Helicobacter (NHPH) gastritis, including white marbled appearance and crack-like mucosa, have been reported. However, these findings can also manifest in H. pylori (HP)-infected gastritis. This study compared NHPH gastritis and mild atrophic HP gastritis to identify features that may enhance NHPH diagnosis. MATERIALS AND METHODS: A total of 2087 patients underwent upper gastrointestinal endoscopy and were histologically evaluated by multiple gastric mucosal biopsies according to the updated Sydney System (USS) at Shinshu University Hospital between 2005 and 2023. Among them, nine patients were classified into the NHPH group and 134 patients with HP infection and mild atrophy were classified into the HP group for retrospective comparisons of endoscopic findings and clinicopathological characteristics. RESULTS: All nine patients in the NHPH group (eight males [89%], median ± standard deviation [SD] age: 49 ± 13.0 years) were infected with H. suis. The 134 patients in the HP group contained 70 men (52%) and had a median ± SD age of 35 ± 19.9 years. Endoscopic findings were statistically comparable for white marbled appearance (three patients [33%] in the NHPH group and 37 patients [31%] in the HP group) and crack-like mucosa (three patients [33%] and 27 patients [20%], respectively). Diffuse redness was significantly less frequent in the NHPH group (one patient [14%] vs. 97 patients [72%], p < 0.001). White marbled appearance or crack-like mucosa without diffuse redness was significantly more common in the NHPH group (56% vs. 13%, p = 0.004), with a sensitivity and specificity of 56% and 87%, respectively. Mean USS neutrophil infiltration and Helicobacter density scores were significantly higher in the HP group (both p < 0.01), which might have influenced the endoscopic findings of diffuse redness. CONCLUSIONS: When endoscopic findings of white marbled appearance or cracked-like mucosa are present, evaluation for diffuse redness may contribute to a more accurate diagnosis of NHPH gastritis.

Histopathological and Immunohistochemical Mechanisms of Bone Marrow-Derived Mesenchymal Stem Cells in Reversion of Gastric Precancerous Lesions.

BACKGROUND: Gastric cancer (GC) stands as one of the most prevalent cancer types worldwide, holding the position of the second leading cause of cancer-related deaths. Gastric lesions represent pathological alterations to the gastric mucosa, with an elevated propensity to advance to gastric cancer. Limited research has explored the potential of stem cells in the treatment of gastric lesions. METHODS: This study aimed to explore the potential of intravenous transplantation of labeled bone marrow-derived mesenchymal stem cells (BMMSCs) to inhibit the progression of precancerous gastric lesions. RESULTS: In the gastric lesion disease model group, the rat tissue exhibited noteworthy mucosal atrophy, intestinal metaplasia, dysplasia, and inflammatory cell infiltration. Following the infusion of BMMSCs, a notable decrease in gastric lesions was found, with atrophic gastritis being the sole remaining lesion, which was confirmed by morphological and histological examinations. BMMSCs that were colonized at gastric lesions could differentiate into epithelial and stromal cells, as determined by the expression of pan-keratin or vimentin. The expression of vascular endothelial growth factor was significantly elevated following BMMSC transplantation. BMMSCs could also upregulate the production of humoral immune response cytokines, including interleukin (IL)-4 and IL-10, and downregulate the production of IL-17 and interferon-gamma, which could be highly associated with the cellular immune response and inflammation severity of the lesions. CONCLUSIONS: BMMSC transplantation significantly reduced inflammation and reversed gastric lesion progression.

Curative criteria for endoscopic treatment of gastric cancer.

Endoscopic treatment, particularly endoscopic submucosal dissection, has become the primary treatment for early gastric cancer. A comprehensive optical assessment, including white light endoscopy, image-enhanced endoscopy, and magnification, are the cornerstones for clinical staging and determining the resectability of lesions. This paper discusses factors that influence the indication for endoscopic resection and the likelihood of achieving a curative resection. Our review stresses the critical need for interpreting the histopathological report in accordance with clinical guidelines and the imperative of tailoring decisions based on the patients' and lesions' characteristics and preferences. Moreover, we offer guidance on managing complex scenarios, such as those involving non-curative resection. Finally, we identify future research avenues, including the role of artificial intelligence in estimating the depth of invasion and the urgent need to refine predictive scores for lymph node metastasis and metachronous lesions.

Management of high risk T1 gastric adenocarcinoma following endoscopic resection.

Endoscopic submucosal dissection has revolutionized the treatment of early gastric cancer. However, cases that do not meet the curability criteria have a higher risk of lymph node metastasis and salvage surgery is still considered the next treatment approach to increase the chance of cure. Nevertheless, not all high-risk resections entail the same level of risk, emphasizing the utmost importance of individualized stratification for further treatment. In this review, we aim to examine the current evidence concerning the management following a high-risk non-curative resection, highlighting the existing approaches, while also presenting upcoming strategies that attempt to improve patient outcomes, minimize adverse events, and provide a tailored management.

Clinicopathological features and mucosal microbiota in gastric mucosal damage between nodular and non-nodular gastritis in children with Helicobacter pylori infection.

AIMS: Nodular gastritis (NG) represents a frequently observed clinical presentation of Helicobacter pylori (H. pylori) infection in pediatric patients. This investigation aimed to explore the microbiota and histological features of the gastric mucosa in children with H. pylori colonized NG. MAIN METHODS: The current investigation examined a sample of 120 children who underwent gastroscopy due to symptoms of gastrointestinal distress, which showed that 64 were patients with H. pylori infection. Endoscopic procedures were conducted to acquire mucosal biopsies for the purpose of DNA extraction and histopathological analysis. The 16S rRNA profiling was utilized to examine the gastric mucosal microbiota. KEY FINDINGS: In conjunction with endoscopic evaluation, 26 of 64 patients were diagnosed with NG. The NG group had significantly higher inflammation scores and activity scores on histological assessment than the non-NG group. The NG group exhibited a significant reduction in the richness levels of the five genera. In terms of the predicted functions, the pathways of synthesis and degradation of ketone bodies and phagosome in the NG group were less abundant compared with the non-NG group, while the Wnt signaling pathway was significantly enriched. NG does not increase a microbial community that possesses genotoxic potential within the gastric mucosa. SIGNIFICANCE: In conclusion, NG group exhibited significant severe inflammation and reduced abundance levels of several bacterial genera compared to the non-NG group. However, individuals with NG did not have a dysregulated microbial community with genotoxic potential.

A puzzling case report of well-differentiated neuroendocrine tumor mixed with gastric adenocarcinoma of the fundic gland type associated with autoimmune gastritis.

Gastric adenocarcinoma of the fundic gland type (GA-FG) is a rare gastric neoplasm. We present a unique case of multiple GA-FG that coexisted with the well-differentiated neuroendocrine tumors in a patient with autoimmune gastritis. To our knowledge, this is the first documented instance of such a co-occurrence and the molecular mechanism of their origin has been reviewed systematically. A 47-year-old male presented to our hospital with abdominal distension for over 10 years. Gastroscopy revealed multiple gastric eminence lesions (0.2-1.5 cm). After endoscopic mucosal resection, the pathological morphology showed mixed tumor components infiltrating into the submucosa with puzzling similarity. One with uniform-sized tumor cells arranged in nests or tubes and the other a well-differentiated tubular adenocarcinoma with irregular branching and visible gland fusion. Immunohistochemistry findings revealed the first component expressed typical markers of neuroendocrine tumor, whereas the second component expressed pepsinogen and mucin-6, indicating the presence of oxyntic gland adenocarcinoma. Due to the tumors' proximity to the surgical margins, the patient underwent laparoscopic subtotal gastrectomy three months after the diagnosis without any tumor residue and showed no recurrence or metastasis occurred in the following regular checkups.

High frequency electrocoagulation resection effect analysis and prognosis observation in the treatment of patients with gastric polyps under painless gastroscopy.

To explore high frequency electrocoagulation resection effect in treatment of patients with gastric polyps under painless gastroscopy. Sixty-four patients with gastric polyps were randomly divided into experimental group (32 cases) and control group (32 cases). Experimental group received basic treatment drugs for 8 weeks, and then treated with painless gastroscope high-frequency electrocoagulation resection. Control group was also given basic treatment drugs for 8 weeks, and then received high-frequency electrocoagulation resection under ordinary gastroscope. The patients in both groups were given rabeprazole sodium enteric coated capsules for 4 weeks. The improvement of symptom score, postoperative gastric mucosal healing and comprehensive curative effect of the 2 groups were observed after treatment. The patients with polyps cured under gastroscopy were subjected to a 6-month follow-up period during which gastroscopy was performed to assess the recurrence of polyps. Symptom scores comparison after treatment showed that experimental group had obvious advantages in improving epigastric fullness, fatigue and loose stool in patients with gastric polyps (P < .01 or P < .05). Gastric mucosa healing in experimental group was better at 2 weeks after operation (P < .05), showing no difference 4 weeks after operation (P > .05). Comprehensive curative effect comparison showed that the experimental group was better (P < .01), showing no difference in long-term efficacy (P > .05). In treating patients with gastric polyps, painless endoscopic high-frequency electrocoagulation resection effect is better, which not only promotes postoperative rehabilitation in patients but also reduces complications incidence, demonstrating a high level of safety. Therefore, it is highly recommended for widespread adoption and application.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

BEST-J Score: Validation of a Predicting Model for Delayed Bleeding After Gastric Endoscopic Submucosal Dissection on a European Sample.

BACKGROUND: Delayed bleeding (DB) is a possible adverse event following gastric endoscopic submucosal dissection (ESD). The BEST-J score was created as a risk prediction model for DB following gastric ESD, but is yet to be validated in Western populations. AIMS: We aimed to validate the BEST-J score on a European sample and to perform a subgroup analysis according to histological classification. METHODS: Retrospective study of all consecutive patients undergoing gastric ESD on a European Endoscopic Unit. DB was defined as hemorrhage with clinical symptoms and confirmed by emergency endoscopy from the time of completion to 28 days after ESD. BEST-J score was calculated in each patient and confronted with the outcome (DB). RESULTS: Final sample included 161 patients. From these, 10 (6.2%) presented DB following ESD, with a median time to bleeding of 7 days (IQR 6.8). BEST-J score presented an excellent accuracy predicting DB in our sample, with an AUC = 0.907 (95%CI 0.801-1.000; p < 0.001). Subgroup analysis by histological classification proved that the discriminative power was still excellent for each grade: low-grade dysplasia-AUC = 0.970 (p < 0.001); high-grade dysplasia-AUC = 0.874 (p < 0.001); early gastric cancer-AUC = 0.881 (p < 0.001). The optimal cut-off value to predict DB was a BEST-J score ≥ 3, which matches the cut-off value for high-risk of bleeding in the original investigation. CONCLUSIONS: The BEST-J score still presents excellent accuracy in risk stratification for post-ESD bleeding in European individuals. Thus, this score may help to guide which patients benefit the most from prophylactic therapies following gastric ESD in this setting.

RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates.

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.