Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study.

BACKGROUND: Although eradication therapy for chronic Helicobacter pylori (H. pylori) reduces the risk of gastric cancer (GC), its effectiveness is not complete. Therefore, it is also critically important to identifying those patients who remain at high risk after H. pylori eradication therapy. Accumulation of protein methylation is strongly implicated in cancer, and recent study showed that dimethylation of eEF1A lysine 55 (eEF1AK55me2) promotes carcinogenesis in vivo. We aimed to investigate the relationship between eEF1A dimethylation and H. pylori status, efficacy of eradication therapy, and GC risk in H. pylori-eradicated mucosa, and to reveal the potential downstream molecules of eEF1A dimethylation. METHODS: Records of 115 patients (11 H. pylori-negative, 29 H. pylori-positive, 75 post-eradication patients) who underwent upper gastrointestinal endoscopy were retrospectively reviewed. The eEF1A dimethyl level was evaluated in each functional cell type of gastric mucosa by immunofluorescent staining. We also investigated the relationship between eEF1AK55me2 downregulation by CRISPR/Cas9 mediated deletion of Mettl13, which is known as a dimethyltransferase of eEF1AK55me2. RESULTS: The level of eEF1A dimethylation significantly increased in the surface and basal areas of H. pylori-positive mucosa compared with the negative mucosa (surface, p = 0.0031; basal, p = 0.0036, respectively). The eEF1A dimethyl-levels in the surface area were significantly reduced by eradication therapy (p = 0.005), but those in the basal area were maintained even after eradication therapy. Multivariate analysis revealed that high dimethylation of eEF1A in the basal area of the mucosa was the independent factor related to GC incidence (odds ratio = 3.6611, 95% confidence interval = 1.0350-12.949, p = 0.0441). We also showed the relationship between eEF1A dimethylation and expressions of reprogramming factors, Oct4 and Nanog, by immunohistochemistry and in vitro genome editing experiments. CONCLUSIONS: The results indicated that H. pylori infection induced eEF1A dimethylation in gastric mucosa. The accumulation of dimethyl-eEF1A in the basal area of the mucosa might contribute to GC risk via regulation of reprograming factors in H. pylori eradicated-gastric mucosa.

Gastric mucosal changes, and sex differences therein, after Helicobacter pylori eradication: A long-term prospective follow-up study.

BACKGROUND AND AIM: Improvement of atrophic gastritis and intestinal metaplasia (IM) is considered to reduce the gastric cancer risk, but whether it can be achieved by H. pylori eradication (HPE) remains controversial. To evaluate the effect of HPE, we observed the gastric mucosa for up to17 years after HPE and sex differences in gastric mucosa. METHODS: In total, 172 patients (94 males, 78 females) with HPE were enrolled. Annual histological evaluations were performed for up to 17 years. The grades of mononuclear cells, neutrophils, atrophy, IM in the antrum and corpus were evaluated using the updated Sydney system. RESULTS: Relative to the pre-HPE period, atrophy had improved significantly 1 year after HPE in the antrum (1.50 ± 0.75 vs. 1.21 ± 1.25, P < 0.01) and corpus (0.59 ± 0.75 vs. 0.18 ± 0.52, P < 0.05). IM showed no significant change during 17 years after HPE at either biopsy site. Atrophy scores did not differ significantly between males and females. IM scores were significantly higher in males than in females before eradication (antrum, 0.67 ± 0.94 vs. 0.44 ± 0.77, P = 0.003, corpus, 0.20 ± 0.62 vs. 0.047 ± 0.21, P = 0.0027) and at most observation timepoints. CONCLUSIONS: During 17 years after HPE, atrophy, but not IM, improved significantly at the greater curvatures of the antrum and corpus. IM was significantly more severe in males than in females. Careful follow-up after HPE based on sex differences in gastric mucosal characteristics is important.

Helicobacter pylori infection modulates endogenous hydrogen sulfide production in gastric cancer AGS cells.

BACKGROUND: Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2 S), a gaseous biological transmitter, has been implicated in both the physiological functions of the gastrointestinal tract and its diseases. To understand gastric epithelial cell response against H pylori infection, we investigated the metabolic changes of gastric cancer cells co-cultured with H pylori and observed the modulation of endogenous H2 S production. MATERIALS AND METHODS: Gastric cancer AGS cells were co-cultured with an H pylori standard strain possessing bacterial virulence factor CagA (ATCC 43504) and a strain without CagA (ATCC 51932). Three hours after inoculation, the cells were subjected to metabolomics analysis using gas chromatography-tandem mass spectrometry (GC-MS/MS). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and pathway analysis were performed. In addition, intracellular H2 S levels were measured by using HSip-1 fluorescent probe. RESULTS: Results of OPLS-DA showed a significant difference between the metabolism of untreated control cells and cells inoculated with the H pylori strains ATCC 51932 or ATCC 43504, mainly due to 45 metabolites. Pathway analysis with the selected metabolites indicated that methionine metabolism, which is related to H2 S production, was the most frequently altered pathway. H pylori-inoculated cells produced more endogenous H2 S than control cells. Moreover, ATCC 43504-inoculated cells produced less H2 S than ATCC 51932-inoculated cells. CONCLUSIONS: H pylori infection modulates endogenous H2 S production in AGS cells, suggesting that H2 S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy.

Influence of acotiamide on 13C-urea breath test for Helicobacter pylori diagnosis.

The Helicobacter pylori infection and functional dyspepsia are often coexisted. The effect of acotiamide, a drug for functional dyspepsia, on the result of Helicobacter pylori diagnosis has yet to be studied. We evaluated the influence of acotiamide on the results of Helicobacter pylori diagnosis in the 13C-urea breath test. Twenty patients with Helicobacter pylori-positive functional dyspepsia were treated with 100 mg of acotiamide three times a day for two weeks. Changes in 13C-urea breath test were investigated before and after administration, and two weeks after administration as the follow-up period. The 13C-urea breath test and the medical questionnaire of modified frequency scale for the symptoms of gastroesophageal reflux disease were conducted at every period. Nineteen patients were included for analysis. No patients showed negative in 13C-urea breath test at Weeks 2 and 4. On the symptom scale, dyspepsia and total scores decreased from Week 0 to Week 2 and increased from Week 2 to Week 4, and the improvement rates of the dyspepsia score at Week 2 was 63%. In conclusion, we confirmed that acotiamide is unlikely to influence the result of 13C-urea breath test and it may improve the symptoms of functional dyspepsia during Helicobacter pylori eradication treatment.

Differences in Helicobacter pylori and CagA antibody changes after eradication between subjects developing and not developing gastric cancer.

We evaluated serological Helicobacter pylori and cytotoxin-associated gene A (CagA) antibodies and endoscopic atrophy after eradication to identify factors predicting post-eradication gastric cancer development. Thirty-five patients with successful eradiation were divided into the post-eradication gastric cancer (13 cases) and non-gastric cancer (22 cases) groups. Serum Helicobacter pylori and CagA antibody titers and endoscopic atrophy before and six years after eradication were examined. Median Helicobacter pylori antibody titers had decreased significantly from baseline at 0.5-2 years after eradication in both groups (gastric cancer group, from 39.0 to 11.0 U/ml, p = 0.011; non-gastric cancer group, from 29.6 to 4.97 U/ml, p<0.001), but were significantly higher in the gastric cancer than in the non-gastric cancer group (p = 0.029). Median serum CagA antibody titers had also decreased significantly at 0.5-2 years after eradication (gastric cancer group, from 6.35 to 3.23 U/ml, p = 0.028; non-gastric cancer group, from 9.88 to 1.21 U/ml, p = 0.0045). Serum CagA in each group showed no significance. Endoscopic atrophy improved significantly after eradication in the non-gastric cancer, but not the gastric cancer, group (p = 0.0007). In conclusion, changes in Helicobacter pylori and CagA antibody titers and endoscopic atrophy after eradication might be useful as predictive factors for post-eradication gastric cancer.

Endoscopic gastric mucosal atrophy as a predictor of colorectal polyps: a large scale case-control study.

Although some studies have indicated a correlation between Helicobacter pylori infection and the risk of colorectal neoplasms, these findings have not been consistent and are controversial. This case-control study aimed to investigate the association between endoscopic gastric mucosal atrophy and colorectal polyp occurrence. Records of 7,394 participants who underwent colonoscopy examinations from August 2008 to July 2018 were reviewed retrospectively. A total of 2,404 subjects were registered; 1,565 (65.1%) were in the gastric mucosal atrophy-positive group and 1,138 (47.3%) had colorectal polyps. The multivariate analysis adjusted by age, sex, smoking habits, alcohol habits, hemoglobin A1c, and systolic blood pressure indicated that patients in the gastric mucosal atrophy-positive group more frequently had colorectal polyps compared with patients in the gastric mucosal atrophy-negative group (odds ratio, 3.27; 95% confidence interval, 2.68-4.01; p<0.001). An analysis of the association between gastric mucosal atrophy degree and colorectal polyp status indicated that, compared with mild gastric mucosal atrophy, severe gastric mucosal atrophy was associated with a higher risk of proximal colon polyps (odds ratio, 1.47; 95% confidence interval, 1.05-2.07; p = 0.024) and two or more colorectal polyps (odds ratio, 1.80; 95% confidence interval, 1.30-2.49; p<0.001). In conclusion, gastric mucosal atrophy found during esophagogastroduodenoscopy may be an indication for complete colon screening.

Experience-Related Factors in the Success of Beginner Endoscopic Ultrasound-Guided Biliary Drainage: A Multicenter Study.

Endoscopic ultrasound-guided biliary drainage (EUS-BD) has become comparable to endoscopic retrograde cholangiopancreatography and is now considered a first-line intervention for certain biliary obstructions. Although analysis of experience-related factors may help achieve better outcomes and contribute to its wider adoption, no concrete evidence exists regarding the required operator or institutional experience levels. This study aimed to analyze experience-related factors at beginner multicenters. Patients who underwent EUS-BD using self-expandable metal stents and/or dedicated plastic stents during the study period (up to the first 25 cases since introducing the technique) were retrospectively enrolled from seven beginner institutions and operators. Overall, 90 successful (technical success without early adverse events) and 22 failed (technical failure and/or early adverse events) cases were compared. EUS-BD-related procedures conducted at the time of applicable EUS-BD by each institution/operator were evaluated. The number of institution-conducted EUS-BD procedures (≥7) and operator-conducted EUS screenings (≥436), EUS-guided fine-needle aspirations (FNA) (≥93), and EUS-guided drainages (≥13) significantly influenced improved EUS-BD outcomes (p = 0.022, odds ratio [OR], 3.0; p = 0.022, OR, 3.0; p = 0.022, OR, 3.0; and p = 0.028, OR, 2.9, respectively). Our threshold values, which significantly divided successful and failed cases, were assessed using receiver operating characteristic curve analysis and may provide useful approximate indications for successful EUS-BD.

Rectal varix treated with endoscopic cyanoacrylate injection therapy.

There is no established treatment for rectal varices. Although endoscopic cyanoacrylate (N-butyl 2-cyanoacrylate) injection therapy is the standard treatment for gastric varices, there are few reports of its use for rectal varices. We present a case of rectal varix that was successfully treated with endoscopic cyanoacrylate injection therapy. An 80-year-old man with cirrhosis was treated for rectal varices with interventional radiology 2 years earlier. At his current presentation, he underwent colonoscopy for hematochezia and anemia, which showed recurrence of rectal varix. We performed endoscopic cyanoacrylate injection therapy for the lesion. However, since we observed bleeding from the treated varix the next day, additional cyanoacrylate was injected. Thereafter, there was no re-bleeding and no recurrence was observed at the 3-year follow-up. According to the previous reports, interventional radiology (IVR), endoscopic sclerotherapy (EIS), and endoscopic variceal ligation (EVL) have been mainly used to treat rectal varices; however, there are few reports of endoscopic cyanoacrylate injection therapy. Our case suggests that endoscopic cyanoacrylate injection therapy might be a useful and safe treatment option for rectal varices.

Examine the Availability and Safety of Mucosal Cutting Biopsy Technique for Diagnosis of Gastric Submucosal Tumor.

OBJECTIVES: Differentiating gastrointestinal stromal tumor (GIST) from other submucosal tumors (SMTs) is important in diagnosing SMT. GIST is an immunohistological diagnosis that cannot be made from images alone. Tissue sampling of tumor sites is thus becoming increasingly important. In this study, the utility and associated complications of mucosal cutting biopsy (MCB) for gastric SMTs were investigated. METHODS: This was a case series study. The subjects were patients aged ≥20 years old in whom an SMT was seen on esophagogastroduodenography and who underwent MCB between January 2012 and December 2016. Patient information, endoscopy findings, gastric SMT size, pathological diagnosis, and other information were gathered from medical records. The SMT size was the maximum diameter that could be visualized on EUS. The pathological diagnosis was made with hematoxylin-eosin staining, with immunostaining added to diagnose GIST. The endpoint was the histopathological diagnostic yield. Risk assessment using the Miettinen classification and modified Fletcher classification was also done for GISTs treated with surgery. RESULTS: The mean tumor diameter was 15.4 mm. The tumor diameter was ≥20 mm in seven patients and <20 mm in 23 patients. The tissue-acquiring rate was 93.3%. A histological diagnosis could not be made in two patients. The only complication was that bleeding required endoscopic hemostasis during the procedure in one patient, but no subsequent bleeding or no postoperative bleeding was seen. CONCLUSIONS: MCB is an appropriate and safe procedure in the diagnosis of gastric SMTs. Many hospitals will be able to perform MCB if they have the environment, including skills and equipment, to perform endoscopic submucosal dissection.

Infrared radiation has potential antidepressant and anxiolytic effects in animal model of depression and anxiety.

BACKGROUND: Bright light therapy has been shown to have antidepressant and anxiolytic effects in humans. OBJECTIVE: The antidepressant and anxiolytic effects of infrared radiation were evaluated using an experimental animal model. METHODS: Rats were randomly assigned to either an acutely or chronically exposed infrared radiation group or to a nonexposed control group. Acutely exposed rats were treated with an infrared radiation machine for one session, whereas chronically exposed animals were treated with an infrared radiation for 10 sessions. Control group rats were exposed to the sound of the infrared radiation machine as a sham treatment. After infrared radiation or control exposure, rats underwent behavioral evaluation, including elevated plus maze test, light/dark box, and forced swim test. RESULTS: Chronic infrared radiation exposure decreased indicators of depression- and anxiety-like behavior. No significant effect on general locomotor activity was observed. The number of BrdU-positive cells in CA1 of the hippocampus was significantly increased in both acutely and chronically exposed infrared radiation groups compared with the control group. CONCLUSIONS: These results indicate that chronic infrared radiation might produce antidepressant- and anxiolytic-like effects.