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.
Abstract
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
Glycosylation is a common post-translational modification, and it has been reported that alterations in the glycosylation patterns on cells are related to cell proliferation, differentiation, tissue ...adhesion, and carcinogenesis. This study aimed to investigate the relationship between Helicobacter pylori infection and gastric mucosal glycosylation using a lectin microarray system.
Gastric mucosal samples were obtained from 10 Helicobacter pylori-non-infected patients, 10 H. pylori-infected patients, and 10 after H. pylori-eradicated patients who underwent gastric mucosal biopsy by endoscopy in our institute. The gastric gland cells which were isolated from formalin-fixed, paraffin-embedded gastric mucosal biopsy samples using laser capture microdissection were used for lectin microarray to obtain lectin-glycan interaction values.
Comparison of the lectin-glycan interaction values before and after eradication in the same patients showed significant increases for Ricinus communis agglutinin 120, Trichosanthes japonica agglutinin II, Euonymus europaeus lectin, jacalin, Amaranthus caudatus agglutinin, and Maclura pomifera agglutinin and significant decreases for Urtica dioica agglutinin, Lycopersicon esculentum lectin, Ulex europaeus agglutinin, Sambucus nigra agglutinin, Sambucus sieboldiana agglutinin, and Trichosanthes japonica agglutinin I. Furthermore, jacalin and MPA in the gastric antrum were significantly decreased with H. pylori infection compared with the without infection group and improved to the levels seen without infection as a result of eradication. Lycopersicon esculentum lectin, Sambucus nigra agglutinin, Sambucus sieboldiana agglutinin, and Trichosanthes japonica agglutinin I in the gastric body were significantly increased with H. pylori infection and improved to the level seen without infection as a result of eradication.
H. pylori infection changes the lectin binding state which is related to various cancers on the gastric mucosal cell. Furthermore, those changes are reversible by H. pylori eradication.
A 54-year-old man was treated with mycophenolate mofetil (MMF) after undergoing living donor renal transplantation. Two years later, he experienced repeated episodes of diarrhea, and his C-reactive ...protein (CRP) level was found to be 12.63 mg/dL. Ileocolonoscopy showed multiple deep, punched-out ulcers that were similar to Behçet's disease (BD) and cytomegalovirus (CMV) in the ileum. CMV infection was suspected. However, anti-cytomegalovirus agents were ineffective. The patient was subsequently diagnosed with gastrointestinal toxicity of MMF and MMF was switched to mizoribine. His symptoms improved immediately, and his CRP level normalized. Six months later, the patient's mucosa was healed.
Gastrointestinal Dieulafoy’s ulcer is a rare disease of unknown etiology. Dieulafoy’s ulcer often presents in the stomach and is thought to cause about 5% of all gastrointestinal bleeds in adults, ...but can be found in any part of the gastrointestinal tract. Dieulafoy’s ulcer corresponds to an arterial malformation in the submucosal space and can cause life-threatening hemorrhage. We report a case of the lower gastrointestinal bleeding from a cecal Dieulafoy’s ulcer that was successfully treated with endoscopic clips. An 82-year-old woman had been diagnosed with hypertension and cerebral infarction. She had been using aspirin to prevent recurrent infarction. She was admitted to our hospital with hematochezia. Urgent colonoscopy revealed a small, reddish vascular malformation in the cecum. The lesion was suggestive of Dieulafoy’s ulcer and was treated with endoscopic clips. The patient has since been discharged from our hospital without experiencing any further bleeding. Endoscopy is a useful method for diagnosing and treating Dieulafoy’s ulcer.
Background
Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2S), 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 H2S 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 H2S 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 H2S production, was the most frequently altered pathway. H pylori‐inoculated cells produced more endogenous H2S than control cells. Moreover, ATCC 43504‐inoculated cells produced less H2S than ATCC 51932‐inoculated cells.
Conclusions
H pylori infection modulates endogenous H2S production in AGS cells, suggesting that H2S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy.
Diagnoses reflect clear cell morphologies when tumor cells have clear cytoplasm in many organs, and the nature of such clear cells is typically identified. Colorectal tubular adenoma or ...adenocarcinoma, conversely, rarely show clear cells, the reason for which remains uncertain. We report 2 colon tumors with clear cell components (Case 1: adenoma; Case 2: adenocarcinoma) and investigate the nature of the clear cells.
Case 1 was a 75-year-old man with a superficial elevated polyp detected in the rectum for whom endoscopic submucosal dissection was performed. Microscopically, 10% of the tumor showed dysplastic columnar epithelium with clear cytoplasm forming tubular structures accompanied by conventional tubular adenoma. Case 2 was a 58-year-old man with a pedunculated polyp found in his sigmoid colon for which polypectomy was performed. Microscopically, 90% of the tumor showed dysplastic columnar epithelium with clear cytoplasm forming fused glands or cribriform structures adjacent to the ordinal tubular adenocarcinoma. In both cases, clear and ordinary tumor cells were negative for CK7 and positive for CK20 and CDX2, consistent with findings of colorectal origin. Different results were found for CEA and CD10 staining. CEA was positive on the luminal side of the conventional area in contrast diffuse cytoplasmic staining of the clear cell area in both cases. CD10 was only positive for the clear cell component of case 2. The clear cell components were negative for Periodic acid-Schiff (PAS), Alcian blue, and mucicarmine staining and AFP immunohistochemistry. An ultrastructural examination found multiple cytoplasmic lipid-like vacuoles in the clear cell component that were predominantly negative for adipophilin by immunoelectron microscopy.
We investigated tubular adenoma and tubular adenocarcinoma with clear cell components. The accompanying conventional tubular adenoma or adenocarcinoma cells helped us to evaluate the atypia of the clear cells. Diffuse cytoplasmic staining of CEA and CD10 suggested that the clear cell component might harbor malignant potential. We were unable to verify the well-known causes of clear cytoplasm, such as an accumulation of glycogen, lipid, or mucin and enteroblastic differentiation. The causes of clear cells in the colorectal region remain uncertain; however, possible explanations include autolysis and carbohydrate elution.
PDF
