Gastric Corpus Research Articles

Gastric Organoids: Progress and Remaining Challenges.

The stomach is a complex and physiologically necessary organ, yet large differences in physiology between mouse and human stomachs have impeded translation of physiological discoveries and drug screens performed using murine gastric tissues. Gastric cancer (GC) is a global health threat, with a high mortality rate and limited treatment options. The heterogeneous nature of GC makes it poorly suited for current “one size fits all” standard treatments. In this review, we discuss the rapidly evolving field of gastric organoids, with a focus on studies expanding cultures from primary human tissues and describing the benefits of mouse organoid models. We introduce the differing methods for culturing healthy gastric tissue from adult tissues or pluripotent stem cells, discuss the promise these systems have for preclinical drug screens, and highlight applications of organoids for precision medicine. Finally, we discuss the limitations of these models and look to the future to present potential ways gastric organoids will advance treatment options for patients with GC.

Gastric antrum stenosis caused by accidental ingestion of concentrated hydrogen peroxide.

Hydrogen peroxide (HP) is an oxidizing agent that has since long been used for medical purposes, such as wound irrigation, dental irrigation, and enema. However, its routine use is limited by many toxic effects such as portal gas embolism1 and proctitis.2 Accidental ingestion of concentrated HP is not common and has been reported to cause an extensive portal gas embolism, esophagitis, gastritis,3 and even result in death. However, reports of gastric corpus stenosis caused by accidental ingestion of HP are rare. A 60-year-old man ingested a mouthful of HP (30%), thinking it was water after a family member filled the water jar with HP on February 23, 2020, when most households in the region used HP as a disinfectant because of the Covid-19 pandemic. He felt epigastric pain, burning sensation in the chest area, had attacks of persistent vomiting, and non-bloody foaming in the mouth and was immediately presented to a county hospital 30 min later. Upon arrival to the emergency department, his vital signs were stable, the abdomen was soft but tender, and he was neurologically intact. A computerized tomography scan of the abdomen was performed and revealed gas in the portal vein throughout the liver (Fig. 1). After gastric lavage, the patient's symptoms were not relieved, and then he was transferred to a provincial hospital. The patient was then treated with proton pump inhibitors and parenteral nutrition for more than 2 months and was allowed a liquid diet (less than 100 ml). He felt abdominal distension, repeatedly vomited white sticky gastric juice, and lost 11 kg weight. Endoscopy was performed on April 27, demonstrating cardiac stenosis, esophagitis, diffuse gastritis with multiple petechiae, and white exudate; gastric stenosis (Fig. 2) and gastroenterography performed on May 27 revealed gastric antrum stenosis and gastric retention. Jejunostomy was performed on May 12, and the patient was treated with continuous enteral nutrition, which provided 2000 kcal daily, through a jejunostomy tube for the following 3 months, and he gained 5 kg weight. The patient was then readmitted, and gastroenterography (Fig. 3) performed on September 6 indicated gastric retention and gastric antrum stenosis, so gastrojejunostomy (Roux-en-Y) was performed on September 22. The patient was discharged on October 9, when he recovered to a regular diet. The patient remained well during 3 months follow-up. The three main mechanisms involved in HP toxicity damage include oxygen gas formation, corrosive damage, and lipid peroxidation.4 The toxic effect of HP seems to be related to the ingested concentration and quantity. Ingestion of low concentration of HP (3%) has been reported to be usually asymptomatic or resulted in mild symptoms such as nausea and vomiting.5 Complications such as gastritis, hemorrhagic gastritis, gastric ulcers, and gas in the portal vein have also been reported.1-3 Accidental ingestion of concentrated HP (35%) is more likely to result in serious complications such as hemorrhagic gastritis, portal venous gas embolism, acute myocardial infarction, neurological impairment, and death.1, 4, 6-8 Our patient presented with a rare case of accidental ingestion of HP associated with the portal vein gas embolism, gastritis, and gastric antrum stenosis, which hindered the patient's intake of food and resulted in malnutrition. Waiting for a certain period before the surgical treatment of gastric antral stenosis is recommended because the stabilization of the pathological process of gastric injury takes time. Accordingly, appropriate nutrition methods should be adopted to maintain the nutrition of patients during the waiting period. All data generated appear in the submitted article. Shi-lian Le: Data curation; supervision; writing – review and editing. Long-xin Xiong: Resources; validation; writing – review and editing. Peng Deng: Formal analysis; project administration; writing – original draft; writing – review and editing.

Helicobacter pylori-naive Subject with Spotty Redness in the Gastric Corpus

Helicobacter pylori-naive Subject with Spotty Redness in the Gastric Corpus

Systematic Review and Meta-analysis of Histological Gastric Biopsy Aspects According to the Updated Sydney System in Children.

A descriptive and comparative study of gastric histological aspects according to the updated Sydney classification (USC), obtained from Helicobacter pylori-positive versus H pylori-negative children referred for upper gastrointestinal endoscopy. The Prisma method was used to perform a systematic review and meta-analysis. Selection criteria were based on following key words USC, H pylori, children, endoscopy, or biopsy. Publication biases were assessed according to the Newcastle-Ottawa Scale, and a meta-regression analysis was done. The study was registered on the PROSPERO platform. Between 1994 and 2017, 1238 references were found; 97 studies were retained for the systematic review with a total number of 25,867 children; 75 studies were selected for the meta-analysis concerning 5990 H pylori-infected and 17,782 uninfected children.H pylori-positive versus H pylori-negative children, according to the USC, showed significantly higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, and of lymphoid follicles, and gastric mucosa atrophy, whereas, intestinal metaplasia showed a significantly higher RR only in antral biopsies. The meta-regression analysis showed that H pylori-positive versus H pylori-negative children had significantly higher risk only for corpus activity according to age, recurrent abdominal pain, and geographical area of low H pylori prevalence. H pylori infection in children was associated with higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, lymphoid follicles, and rare gastric mucosa atrophy, whereas, rare intestinal metaplasia was only significantly higher in the antral area.

The gastric microbiota in patients with Crohn\u2019s disease; a preliminary study

The gastric microbiota in Crohn’s disease (CD) has not been studied. The purpose of the study was to evaluate differences of stomach microbiota between CD patients and controls. DNA was extracted from gastric mucosal and fluid samples, from 24 CD patients and 19 controls. 16S rRNA gene sequencing identified 1511 operational taxonomic units (OTUs), of which 239 passed the low abundance and low variance filters. All but one CD patients were HP negative. Fifteen bacterial phyla were identified in at least one mucosal or fluid site. Of these, Bacteroidota and Firmicutes accounted for 70% of all phyla. Proteobacteria, Actinobacteriota, and Fusobacteriota combined accounted for 27%. There was significant difference in the relative abundance of Bacteroidota, Proteobacteria, Fusobacteriota, and Campilobacterota between CD patients and controls only in gastric corpus samples. In gastric liquid, there was a significant difference only in Actinobacteriota. Pairwise comparison identified 67 differentially abundant OTUs in at least one site. Of these, 13 were present in more than one comparison, and four differentiating OTUs (Neisseriaceae, Neisseria, Absconditabacteriales, and Microbacteriaceae) were identified at all tested sites. The results reveal significant changes in gastric microbial profiles (beta diversity, phylum, and individual taxa levels) between H. pylori-negative CD patients and controls.

A Rare case of Menetrier’s disease presenting with Protein Losing Gastropathy Mimicking Carcinoma Stomach

Ménétrier's disease (MD) (also known as giant hypertrophic gastritis or hypoproteinemic hypertrophic gastropathy) is a rare premalignant entity characterized by markedly hypertrophied mucosal folds of the fundus and the gastric corpus typically associated with , hypochlorhydria, protein losing enteropathy causing hypoalbuminemia and anemia. However, the natural history of MD in adults remains unclear and is rarely reported in the literature. Its constellation of classic symptoms includes nausea, vomiting, abdominal pain and peripheral edema, and it is associated with increased risk of gastric cancer. Nevertheless, its pathophysiology is not yet fully understood and clinical and endoscopic diagnosis can be difficult to establish. Malignant transformation in MD should not be overlooked, and regular monitoring of the gastric mucosa via endoscopy is necessary.

Unacceptable Antibiotic Resistance Rates for Helicobacter pylori in Turkey: Something Must Change.

It is known that clarithromycin resistance has increased over the years (success rate 60%). The aim of the study was to investigate the importance of regional antimicrobial resistance rates for full accuracy of both diagnosis and treatment of Helicobacter pylori infection. This study was carried out in the University Hospital Department of Gastroenterology. A total of 116 patients were evaluated with upper gastrointestinal endoscopy. Gastric antrum and corpus biopsy samples were taken for the rapid urease test (RUT), culture, and antimicrobial susceptibility testing for the presence of H. pylori. Antimicrobial susceptibilities of isolated H. pylori strains for clarithromycin and levofloxacin were determined by the epsilometer test (E-test). Minimal inhibitory concentration values for clarithromycin and levofloxacin were ≥1 and >1 μg/mL, respectively. H. pylori infection was considered clinically positive in 93 (80.2%) patients with either the RUT, culture, or histopathological examination. Seventy (60.3%) of the patients had RUT positivity. Sixty (85.7%) of these 70 patients had RUT positivity within the first 20 min. Among the 90 patients, who had a histopathological examination, HLO was positive in 76 (84.4%) patients. Fifty-two (44.8%) out of 116 patients were culture positive. Resistance rates for both clarithromycin and levofloxacin were high. In these 52 culture-positive patients, resistance rates determined for clarithromycin and levofloxacin were 26.9% and 25.5%, respectively. Clarithromycin or levofloxacin-based treatment regimen may not be an ideal alternative therapy for Turkish patients regardless of culture.

WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury

WAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis with the use of preneoplastic metaplasia models. Three spasmolytic polypeptide-expressing metaplasia (SPEM) models were established in both wild-type and Wfdc2-knockout mice with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777-treated gastric corpus specimens. Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development. WFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis.

LGR5-Expressing Cells in the Healing Process of Post-ESD Ulcers in Gastric Corpus.

LGR5 is a promising stem cell marker in gastric pylorus, but there are few reports on its expression in human gastric corpus. To investigate the involvement of LGR5 expression in gastric corpus ulcer regeneration in humans. LGR5 expression was analyzed in five post-ESD ulcers during the healing process of regenerating epithelial cells of the gastric corpus. LGR5 expression was detected by mRNA in situ hybridization using an RNA scope kit. Immunohistochemistry of MUC6, HIK1083, and pepsinogen 1 (PG1) was performed to identify cell differentiation. We defined MUC6+/HIK1083-/PG1-, MUC6+/HIK1083+/PG1-, MUC6+/HIK1083+/PG1+, MUC6+/HIK1083-/PG1+, and MUC6-/HIK1083-/PG1+cells as pseudopyloric mucosa (PPM) phase 1 (PPM1), PPM phase 2 (PPM2), PPM phase 3 (PPM3), immature chief cells (ICC), and mature chief cells (MCC) in order from the ulcer center, respectively. In the regenerated mucosa around post-ESD ulcers, LGR5 expression was observed throughout the gland in PPM1-PPM3, but it was limited to the bottom of the gland in ICC and MCC. Furthermore, LGR5 expression was not identified in the normal gastric corpus. The H-score of PPM2 was significantly higher than that of PPM3 (P = 0.0313). The H-score of PPM3 was significantly higher than that of ICC (P = 0.0313). The LGR5 H-score was higher at the immature stage, which decreased gradually with progression of the differentiation stage. LGR5 expression appears to contribute to mucosal regeneration in the human gastric corpus. The application of LGR5 expression analysis to mucosal regeneration and fundic gland-type gastric tumors is expected.

Association of status of mismatch repair protein expression and EB virus infection with clinicopathological parameters in 886 gastric adenocarcinoma patients

Objective: To analyze the expression of mismatch repair (MMR) protein and the EB virus infection in gastric adenocarcinoma, and to examine the association of MMR expression and EB virus infection with clinicopathological parameters. Methods: A case-control study was performed. Clinicopathological data of patients who was pathologically diagnosed as gastric adenocarcinoma, received radical gastrectomy and had complete clinicopathological data from August 2017 to April 2020 in Tianjin Medical University Cancer Institute and Hospital were retrospectively collected and analyzed. The immunohistochemistry (IHC) of MMR proteins and in situ hybridization (ISH) of Epstein-Barr virus encoded RNA (EBER) were reviewed. The associations of MMR and EBER results with clinicopathological parameters were analyzed. The main observations of the study were MMR and EBER expression, and association of MMR and EBER results with clinicopathological parameters. Results: Eight hundred and eighty-six patients were enrolled, including 98 patients who received preoperative neoadjuvant chemoradiotherapy. Of 886 patients, 613 (69.2%) were males and the median age was 60 (22-83) years; 831 (93.8%) were mismatch repair proficiency (pMMR), and 55 (6.2%) were mismatch repair deficiency (dMMR). In dMMR group, 47 cases (85.5%) had the deficiency of both MLH1 and PMS2, 1 case (1.8%) had the deficiency of both MSH2 and MSH6, 4 cases (7.3%) had the deficiency only in PMS2, 2 cases (3.6%) had the deficiency only in MSH6, and 1 case (1.8%) had the deficiency only in MSH2. The deficiency rates of PMS2, MLH1, MSH6 and MSH2 were 5.8% (51/886), 5.3% (47/886), 0.3% (3/886) and 0.2% (2/886), respectively. Among the 871 cases with EBER results, 4.9% (43/871) were positive EBER. Univariate analysis showed that dMMR was more frequently detected in female patients (χ(2)=10.962, P=0.001), cancer locating in the antrum (χ(2)=9.336,P=0.020), Lauren intestinal type (χ(2)=9.718, P=0.018), stage T3 (χ(2)=25.866, P<0.001) and TNM stage II (χ(2)=15.470, P=0.002). The ratio of dMMR was not significantly associated with age, tumor differentiation, histological type, lymph node metastasis, distant metastasis or Her-2 immunohistochemical score (all P>0.05). Compared with negative EBER, positive EBER was more frequent in male patients (χ(2)=9.701, P=0.002), cancer locating in gastric fundus and corpus (χ(2)=17.964, P<0.001), gastric cancer with lymphoid stroma (χ(2)=744.073, P<0.001) and poorly differentiated cancer (χ(2)=13.739, P=0.010). Positive EBER was not significantly associated with age, depth of invasion, lymph node metastasis, distant metastasis, TNM stage or Her-2 immunohistochemical score (all P>0.05). In addition, all dMMR cases were EBER negative, and all cases of positive EBER were pMMR. Conclusions: The positive EB virus status is mutually exclusive with dMMR, indicating that different molecular subtypes of gastric adenocarcinoma are involved in different molecular pathways in tumorigenesis and progression. The overlapping of dMMR or positive EBER status and positive Her-2 expression is found in some cases of gastric adenocarcinoma. Patients with gastric adenocarcinoma after radical surgery should be tested for MMR status if they are female, the tumor locates in gastric antrum, the TNM staging is stage II or T3, or if the Lauren classification is intestinal type. And if patients are male, the tumor locates in the gastric fundus and corpus, the cancer is lymphoid stroma, or poor differentiated, the expression of EBER should be detected. Results of our study may provide evidence for further decision-making of clinical treatment.

Simultaneous gastric cancer and breast cancer metastases to the stomach with lymph node collision tumor: a case report

BackgroundWhile double primary cancers are common in breast cancer patients, co-existence of primary gastric cancer and gastric metastases of breast cancer is exceedingly rare.Case presentationA 51-year-old woman receiving chemotherapy for breast cancer presented with melena and presyncope. A circumferential thickening of the pylorus and small submucosal tumor-like lesions in the gastric fundus and corpus were confirmed on endoscopy. Immunohistochemistry of biopsies revealed that the former was composed of poorly differentiated gastric cancer cells, while the latter were breast cancer metastases. Distal gastrectomy was performed. Pathological evaluation of the resected specimen revealed gastric adenocarcinoma in the pyloric lesion and breast countless cancer metastases throughout the remainder of the stomach, with positive margins. One lymph node had evidence of both stomach cancer and breast cancer metastases, forming a collision tumor. Despite a successful surgery, the patient died 6 months later due to progression of breast cancer.ConclusionWe report a case of synchronous primary gastric adenocarcinoma and gastric metastases of breast cancer. Inter-disciplinary collaboration is crucial in determining the optimal treatment in double cancers.

Updated Kimura-Takemoto classification of atrophic gastritis.

BACKGROUNDThe Updated Sydney system for visual evaluation of gastric mucosal atrophy via endoscopic observation is subject to sampling error and interobserver variability. The Kimura-Takemoto classification system was developed to overcome these limitations. AIMTo compare the morphological classification of atrophic gastritis between the Kimura-Takemoto system and the Updated Sydney system.METHODSA total of 169 patients with atrophic gastritis were selected according to diagnosis by the visual endoscopic Kimura-Takemoto method. Following the Updated Kimura-Takemoto classification system, one antrum biopsy and five gastric corpus biopsies were taken according to the visual stages of the Kimura-Takemoto system. The Updated Kimura-Takemoto classification system was then applied to each and showed 165 to have histological mucosal atrophy; the remaining 4 patients had no histological evidence of atrophy in any biopsy. The Updated Kimura-Takemoto classification was verified as a reference morphological method and applied for the diagnosis of atrophic gastritis. Adding one more biopsy from the antrum to the six biopsies according to the Updated Kimura-Takemoto classification, constitutes the updated combined Kimura-Takemoto classification and Sydney system. RESULTSThe sensitivity for degree of mucosal atrophy assessed by the Updated Sydney system was 25% for mild, 36% for moderate, and 42% for severe, when compared with the Updated Kimura-Takemoto classification of atrophic gastritis for morphological diagnosis. Four types of multifocal atrophic gastritis were identified: sequential uniform (type 1; in 28%), sequential non-uniform (type 2; in 7%), diffuse uniform (type 3; in 23%), diffuse non-uniform (type 4; in 24%), and "alternating atrophic – non-atrophic" (type 5; in 18%). The pattern of the spread of atrophy, sequentially from the antrum to the cardiac segment of the stomach, which was described by the Updated Kimura-Takemoto system, was histologically confirmed in 82% of cases evaluated.CONCLUSIONThe Updated Sydney system is significantly inferior to the Updated Kimura-Takemoto classification for morphological verification of atrophic gastritis.

Effect of Electrical Stimulation on Gastrointestinal Symptoms in Lung Cancer Patients during Chemotherapy: A Randomized Controlled Trial

Objective:The objective was to evaluate the effects of transcutaneous acupoint electric stimulation (TAES) and gastric electrical stimulation (GES) on cancer patients with chemotherapy-induced gastrointestinal (GI) symptoms.Methods:A total of 122 lung cancer patients receiving chemotherapy were assigned randomly to the following two groups: control group (usual care group, n = 61) and intervention group (TAES plus GES, n = 61). TAES involved two acupoints such as Neiguan (PC6) and Zusanli (ST36). GES was performed at gastric pacing sites on the body surface such as the places of projection of gastric antrum and corpus on the body surface. GES was performed on these sites for 14 days continuously (25 min every time, once daily). The effects of TAES and GES on GI symptoms were assessed using the Memorial Symptom Assessment Scale on the day prior to chemotherapy (time point 1) and days 14 (time point 2) and 28 (time point 3) after chemotherapy.Results:No significant differences in the demographic and disease-related variables were detected between the two groups. Differences in symptom occurrence and severity at time point 1 were not statistically significant between the two groups (both P > 0.05). At time points 2 and 3, GI symptoms such as loss of appetite, nausea, vomiting, diarrhea, and constipation in the stimulation group had statistically significantly improved compared with the control group (all P < 0.05).Conclusions:TAES and GES were efficacious in relieving GI discomfort in lung cancer patients after chemotherapy. TAES combined with GES is a safe and easy-to-use tool to manage GI symptoms in practice.

Prevalence, clinical features, and esophagogastroduodenoscopy (EGD) findings of non‐Helicobacter pylori Helicobacter infection: A study of 50 cases at a single facility in Japan

There are only a few reports of non-Helicobacter pylori Helicobacter (NHPH) gastritis in Japanese patients. We aimed to examine its prevalence, clinical features, and esophagogastroduodenoscopy (EGD) findings based on 50 patients encountered in one facility. Subjects were all patients who had undergone gastric mucosal biopsy endoscopically at Kenwakai Hospital for approximately 10years. NHPH infection was diagnosed by microscopic findings of Giemsa staining performed on all specimens. PCR analysis of urease genes was performed to detect and identify NHPH, when informed consent was obtained. Helicobacter pylori-diagnostic tests were also performed. NHPH-infected patients were questioned about symptoms and animal contact. NHPH gastritis was found in 50 of 3847 patients (1.30%). The percentage increased to 3.35% (30 of 896 patients) in the latter 2years and 4months with increasing recognition of its characteristic endoscopic findings by endoscopists. PCR analysis, performed in 30 patients, detected NHPH in 28 patients: 26 as Helicobacter suis and 2 as Helicobacter heilmanii/Helicobacter ailurogastricus. Helicobacter pylori-diagnostic tests were almost negative. However, anti-H. pylori antibody showed high-negative titer (3.0-9.9U/ml) in 12. Of 50 patients (consisting of 49 men and 1 woman), almost all were asymptomatic, and 25 were keeping pets. Regarding EGD findings, in all 50 patients, "crack-like mucosa" and/or nodular gastritis was noted in gastric antrum, and regular arrangement of collecting venules (RAC) was noted in gastric corpus. None of the patients infected with NHPH were co-infected with H. pylori. The prevalence was finally estimated to be approximately 3.35%. Helicobacter suis was the most common NHPH species. "Crack-like mucosa" and/or nodular gastritis in gastric antrum, RAC in gastric corpus, and H. pylori-negativity by H. pylori-diagnostic tests especially containing a high-negative titer of anti-H. pylori antibody may indicate NHPH infection.

Alterations in mucosa-associated microbiota in the stomach of patients with gastric cancer

PurposeThe purpose of this study was to characterize alterations in mucosa-associated microbiota in different anatomical locations of the stomach during gastric cancer progression and to identify associations between Helicobacter pylori infection and gastric microbial changes in patients with gastric cancer.MethodsTwenty-five H. pylori negative subjects with chronic gastritis and thirty-four subjects with gastric cancer were recruited, including H. pylori negative and positive patients with tumors in the antrum and the corpus. Gastric mucosa-associated microbiota were determined by 16S ribosomal RNA gene sequencing using a 454 sequencing platform.ResultsWe found that individuals with chronic gastritis from three different anatomical sites exhibited different microbiota compositions, although the microbial alpha diversity, richness and beta diversity were similar. Compared to patients with chronic gastritis, the gastric microbiota compositions were significantly different at the order level in the antrum and the corpus of patients with gastric cancer, which was dependent on the H. pylori infection status. Microbial alpha diversity and species richness, however, were similar between chronic gastritis and gastric cancer cases and independent of H. pylori status. The microbial community structure in patients with gastric cancer was distinct from that in patients with chronic gastritis. In addition, we found that the presence of H. pylori markedly altered the structure in gastric corpus cancer, but only mildly affected the antrum.ConclusionOur data revealed distinct niche-specific microbiota alterations during the progression from gastritis to gastric cancer. These alterations may reflect adaptions of the microbiota to the diverse specific environmental habitats in the stomach, and may play an important, as yet undetermined, role in gastric carcinogenesis.

Proteomics signature of autoimmune atrophic gastritis: towards a link with gastric cancer

BackgroundAutoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins whose expression levels are altered in this disease and also in GC.MethodsUsing two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5, P < 0.01) were selected and identified by LC–MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with Helicobacter pylori infection) and from GC patients and unaffected first-degree relatives of GC patients.Results2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC–MS/MS identified these as 53 distinct proteins. The most significant (adjusted P < 0.01) biological process associated with the less abundant proteins was “tricarboxylic acid cycle”. Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of H. pylori infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (PDIA3, GSTP gene products) and four less abundant proteins (ATP5F1A, PGA3, SDHB, PGC).ConclusionThis study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC.

Conservative Therapy of Reflux Disease and its Limits

Gastrooesophageal reflux disease (GORD) is common. Proton pump inhibitors (PPI) are regarded as first line therapy for all clinical manifestations. However, their efficacy is inadequate for at least 30% of patients and they are occasionally poorly tolerated. Moreover, some patients would prefer an alternative therapy. Alginate cause mechanical reflux inhibition by forming a gelatinous layer in the so-called acid pocket, an acid reservoir that forms on the surface of the chyme in the gastric corpus immediately after food intake. They may be used an alternative to treat the symptoms of uncomplicated GORD and as an add-on to PPIs if these do not improve symptoms adequately. If the reflux symptoms persist or if reflux oesophagitis does not heal, differentiated diagnostic testing must be performed, using endoscopy and functional analysis. Extraoesophageal manifestations of GORD include cough, compulsive clearing of the throat, problems with the voice and globus sensation. These often do not respond to antireflux therapy. Recent data indicate that these are complex hypersensitivity syndromes and that reflux is only one of several possible triggers.

Changes in Gastric Corpus Microbiota With Age and After Helicobacter pylori Eradication: A Long-Term Follow-Up Study.

Helicobacter pylori infection changes gastric microbiota profiles. However, it is not clear whether H. pylori eradication can restore the healthy gastric microbiota. Moreover, there has been no study regarding the changes in gastric microbiota with aging. The objective of this study was to investigate the changes in gastric corpus microbiota with age and following H. pylori eradication. Changes in corpus mucosa-associated microbiota were evaluated in 43 individuals with endoscopic follow-up > 1 year, including 8 H. pylori-uninfected and 15 H. pylori-infected subjects with no atrophy/metaplasia by histology and pepsinogen I/II ratio > 4.0; 17 H. pylori-infected subjects with atrophy/metaplasia and pepsinogen I/II ratio < 2.5; and 3 subjects with atrophy/metaplasia, no evidence of active H. pylori infection, negative for anti-H. pylori immunoglobulin G (IgG) antibody testing, and no previous history of H. pylori eradication. Successful H. pylori eradication was achieved in 21 patients. The gastric microbiota was characterized using an Illumina MiSeq platform targeting 16S ribosomal DNA (rDNA). The mean follow-up duration was 57.4 months (range, 12–145 months), and median follow-up visit was 1 (range, 1–3). Relative abundance of Lactobacillales and Streptococcus was increased with atrophy/metaplasia. In H. pylori-uninfected subjects (n = 8), an increase in Proteobacteria (Enhydrobacter, Comamonadaceae, Sphingobium); a decrease in Firmicutes (Streptococcus, Veillonella), Fusobacteria (Fusobacterium), Nocardioidaceae, Rothia, and Prevotella; and a decrease in microbial diversity were observed during the follow-up (p trend < 0.05). In 10 of 21 subjects (47.6%), H. pylori eradication induced restoration of microbial diversity; however, a predominance of Acinetobacter with a decrease in microbial diversity occurred in 11 subjects (52.3%). The presence of atrophy/metaplasia at baseline and higher neutrophil infiltration in the corpus were associated with the restoration of gastric microbiota after successful eradication, whereas a higher relative abundance of Acinetobacter at baseline was associated with the predominance of Acinetobacter after H. pylori eradication (p < 0.05). To conclude, in H. pylori-uninfected stomach, relative abundance of Proteobacteria increases, relative abundance of Firmicutes and Fusobacteria decreases, and microbial diversity decreases with aging. H. pylori eradication does not always restore gastric microbiota; in some individuals, gastric colonization by Acinetobacter species occurs after anti-Helicobacter treatment.

IgG4-related gastric disease with plasma cell-rich obliterative arteritis accompanied by early-stage gastric cancer: a case report

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is an immune-mediated inflammatory disorder that can involve multiple organs. It is characterized by IgG4-positive plasma cell-rich storiform fibrosis and obliterative phlebitis associated with a high serum IgG4 level. There are few reports of gastric IgG4-RD, especially those detected prior to systemic or other organ involvement.Case presentation: A 70-year-old man was diagnosed with type 0–IIc gastric cancer at the anterior wall of the gastric corpus by upper gastrointestinal endoscopy. In addition, a submucosal tumor (SMT) 7 mm in diameter was found at the greater curvature of the angulus. Laparoscopic distal gastrectomy with regional lymph node dissection was performed. Pathology revealed a poorly differentiated adenocarcinoma in the type 0–IIc lesion and storiform fibrosis with infiltration of a large number of IgG4-positive plasma cells in the SMT. Postoperative laboratory testing showed elevation of serum IgG4 levels; thus, we diagnosed the SMT as IgG4-RD. Intriguingly, the gastric IgG4-RD lesion demonstrated IgG4-positive plasma cell-rich arteritis as well as typical obstructive phlebitis. The patient has been followed for 2 years after surgery without recurrence of cancer, but skin lesions of IgG4-RD have appeared.ConclusionWe report a rare case of IgG4-RD presenting as a gastric SMT, accompanied by early-stage gastric cancer. Our case may support a newly proposed relationship between IgG4-RD and malignancies. The gastric IgG4-RD lesion showed arteritis as well as obliterative phlebitis, potentially providing novel insight into IgG4-related vascular lesions.

The Effect of Dried Amnion Membrane Application in the Expression of Platelet Derived Growth Factors in the Healing Process of Stomach Stab Wound (Study on New Zealand Rabbit)

Background: Management of penetrating abdominal trauma, especially those affecting the stomach, keepsdeveloping. Although the technology in the field of surgery is getting more advanced, the risk of complications dueto leakage is still common. A lot of research is being done to improve the tissue healing process, including a varietyof surgical techniques and material uses. The amniotic membrane is a material that is widely used to help stimulatethe healing process. The amniotic membrane contains growth factors, one of which is platelet-derived growth factor(PDGF). PDGF is a major player in the wound healing process.Purpose: To investigate the differences in PDGF levels in gastric rupture repair with dry amniotic membrane asa biological dressing compared to primary repair of gastric rupture without using dry amniotic membrane.Method: This research was an experimental analytical study, using 42 samples of rabbits which were groupedinto 2 groups, namely the control and treatment groups. Stab wound of 2 cm by 0.5 cm wide with a depth entire gastricwall in gastric corpus was done and repaired with 4-6 interrupted suture using 5/0 polypropylene monofilament. Inthe control group, the wound was only sutured and the treatment group, dry amniotic membrane was applicatedbefore suturing. The expression of PDGF was examined from the suture tissue on day-7.Result: Intensity score was obtained in the treatment group with the highest score of 2 with a sample of 11(52.4%) as well as in the control group as many as 13 (61.9%) samples who had a score of 2. The extensionscore was obtained in the treatment group with the highest score of 1 with a total sample size of 10 (47.6%)while the control group had the highest score with a score of 0.5 as much as 14 (66.7%). After obtaining thePDGF intensity and extension values, then these two values are multiplied to get the PDGF expression. Fromthe results of the comparison test using the Mann Whitney test, it was found that the difference in PDGFexpression was significant between the treatment group and the control group with p = 0.008 (p &lt;0.05).Conclusion: Applying dry amniotic membrane to the wound on the stomach will increase the expression ofPDGF in the wound area.