Effect of Helicobacter pylori Eradication on Epigenetic Changes in Gastric Cancer-related Genes

It is known that gastric carcinogenesis results from the progressive changes from chronic gastritis to gastric atrophy, intestinal metaplasia, dysplasia, and invasive carcinoma. Several genetic and epigenetic alterations are involved in this process, and Helicobacter pylori (H. pylori) infection is believed to induce the initiation and progression of these steps. From an epigenetic point of view, H. pylori induces hypermethylation of genes involved in the development of gastric cancer and regulates the expression of various microRNAs (miRNAs). These H. pylori-related epigenetic changes are accumulated not only at the site of neoplasm but also in the adjacent non-cancerous gastric mucosa. Thereby, a state vulnerable to gastric cancer known as an epigenetic field defect is formed. H. pylori eradication can have an effective chemopreventive effect in gastric carcinogenesis. However, the molecular biological changes that occur in the stomach environment during H. pylori eradication have not yet been established. Several studies have reported that H. pylori eradication can restore infection-related changes, especially epigenetic alterations in gastric cancer-related genes, but some studies have shown otherwise. Simply put, it appears that the recovery of methylated gastric cancer-related genes and miRNAs during H. pylori eradication may vary among genes and may also differ depending on the histological subtype of the gastric mucosa. In this review, we will discuss the potential mechanism of gastric cancer prevention by H. pylori eradication, mainly from an epigenetic perspective.

The Family Type and Correct Family Attitude of Pregnant Diabetes Women / 임상당뇨병

What this social worker learned from more than a decade of training and counseling on anxiety, depression, and stress factors felt by pregnant women diagnosed with diabetes was that diabetes itself had a large impact on families as well, so the impact of diabetes could be classified as a "family disease," whether positive or negative. While training at the site (hospital), most of the time, rather than receiving direct questions from mothers or their families, social workers were told about the difficulties that mothers reported, which included that many people wanted to educate their families about their disease. In fact, most mothers who participated in education had big and small difficulties in these areas. Therefore, we learned that effective diabetes management requires active family cooperation and that positive interactions between pregnant women and their families are necessary.

Helicobacter pylori Eradication Can Reverse the Methylation-Associated Regulation of miR-200a/b in Gastric Carcinogenesis

Background/Aims@#Epigenetic change is one of the mecha-nisms that regulates the expression of microRNAs (miRNAs) and is known to play a role in Helicobacter pylori-associated gastric carcinogenesis. We aimed to evaluate the epigen-etic changes ofmiR-200a/b in H. pylori-associated gastric carcinogenesis and restoration after eradication. @*Methods@#The expression and methylation levels of miR-200a/b were evaluated in gastric cancer (GC) cell lines, human gastric mu-cosa of H. pylori-negative and -positive controls, and H. pyloripositive GC patients. Next, the changes in the expression and methylation levels of miR-200a/b were compared between H. pylori-eradication and H. pylori-persistence groups at 6 months. Real-time reverse transcription-polymerase chain reaction was conducted to investigate the miRNA expression levels, and MethyLight was performed to assess the meth-ylation levels. @*Results@#In the GC cell lines, the level ofmiR-200a/b methylation decreased and the level of expression increased after demethylation. In the human gastric mucosa, the miR-200a/b methylation levels increased in the following group order: H. pylori-negative control group, H. pylori-positive control group, and H. pylori-positive GC group. Conversely, the miR-200a/b expression levels decreased in the same order.In the H. pylori-persistence group, no significant changes were observed in the methylation and expression levels of miR-200a/b after 6 months, whereas the level of methyla-tion decreased and the level of expression of miR-200a/b increased significantly 6 months in the H. pylori-eradication group. @*Conclusions@#Epigenetic alterations ofmiR-200a/bmay be implicated in H. pylori-induced gastric carcinogen-esis. This field defect for cancerization is suggested to be improved by H. pylori eradication.

Helicobacter pylori Eradication after Endoscopic Resection of Gastric Epithelial Neoplasms

Endoscopic submucosal dissection is widely accepted as standard treatment for early gastric cancer; however, long-term management of metachronous gastric cancer after endoscopic resection is an important issue that is gaining much attention. Several prospective and retrospective studies have reported that Helicobacter pylori (H. pylori) eradication can reduce the risk of metachronous gastric cancer after endoscopic resection. Although there is lack of sufficient data regarding this subject, a few studies have reported histologically proven improvement in atrophic gastritis and intestinal metaplasia following H. pylori eradication in patients undergoing endoscopic resection. Therefore, treatment for H. pylori eradication should be considered in this patient population to reduce the incidence of metachronous gastric cancer and improve long-term outcomes.(

Continuous Use of Thienopyridine May Be as Safe as Low-Dose Aspirin in Endoscopic Resection of Gastric Tumors

BACKGROUND/AIMS: Current guidelines recommend withholding antiplatelets for 5–7 days before high-risk endoscopic procedures. We investigated whether this reduces post-endoscopic submucosal dissection (ESD) bleeding. METHODS: Gastric ESD cases with antiplatelets were retorospectively reviewed. Withholding antiplatelets for 5–7 days before ESD was defined as cessation and 0–4 days as continuation. The rate and risk of post-ESD bleeding according to the types and cessation of antiplatelets were assessed. RESULTS: Among the 215 patients (117 adenoma and 98 early gastric cancer), 161 patients were on single (94 aspirin, 56 thienopyridine, and 11 other agents), 51 on dual, and 3 on triple antiplatelets. Post-ESD bleeding rates were 12.8% in aspirin users, 3.6% in thienopyridine, 27.5% in dual, 33.3% in triple therapy, and 9.7% in the cessation and 15.0% in the continuation group. Multiple antiplatelets (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.01 to 5.76) and specimen size ≥ 5.5 cm (OR, 2.84; 95% CI, 1.04 to 7.73) were the risk of bleeding, while continuation of thienopyridine (OR, 0.23; 95% CI, 0.05 to 1.09) and antiplatelets (OR, 1.83; 95% CI, 0.68 to 4.94) did not increase the risk of bleeding. CONCLUSIONS: Continuing thienopyridine and aspirin did not increase the risk of post-ESD. Multiple antiplatelet therapy and a large specimen size were independent risk factors of post-ESD bleeding.

Associations Among Plasma Stress Markers and Symptoms of Anxiety and Depression in Patients with Breast Cancer Following Surgery

OBJECTIVE: The objective of present study is to analyze the prevalence of depression and anxiety following breast cancer surgery and to assess the factors that affect postoperative psychological symptoms. METHODS: The Hamilton Rating Scale for Depression (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Body Image Scale (BIS), and Rosenberg Self Esteem Scale (RSES) were used to assess the psychological states of patients who had been diagnosed with and had undergone surgery for breast cancer. Blood concentrations of the stress markers adrenocorticotropic hormone, cortisol, arginine-vasopressin, and angiotensin-converting enzyme were measured. Pearson’s correlation analysis and multilinear regression analysis were used to analyse the data. RESULTS: At least mild depressive symptoms were noted in 50.5% of patients, while 42.4% of patients exhibited at least mild anxiety symptoms. HAM-D score was positively correlated with HAM-A (r=0.83, p < 0.001) and BIS (r=0.29, p < 0.001) scores and negatively correlated with RSES score (r=-0.41, p < 0.001). HAM-A score was positively correlated with BIS score (r=0.32, p < 0.001) and negatively correlated with RSES score (r=-0.27, p < 0.001). There were no statistically significant associations between stress markers and depression/anxiety. CONCLUSION: Patients with breast cancer frequently exhibit postoperative depression and anxiety, which are related to low levels of self-esteem and distorted body image.

Association Between Anxiety and Depression and Gastroesophageal Reflux Disease: Results From a Large Cross-sectional Study

BACKGROUND/AIMS: The different clinical manifestations of gastroesophageal reflux disease (GERD) may be influenced by associated psychological factors. We evaluated the psychological status (anxiety and depression) according to each subtype of GERD. METHODS: Subjects who underwent esophagogastroduodenoscopy and completed a symptom questionnaire between January 2008 and December 2011 were analyzed. The subjects were classified into the following groups: erosive reflux disease (ERD), non-erosive reflux disease (NERD), asymptomatic erosive esophagitis (AEE), and controls. Anxiety and depression were assessed using the State-Trait Anxiety Inventory and Beck Depression Inventory, respectively. RESULTS: We analyzed 19 099 subjects: 16 157 (84.6%), 176 (0.9%), 1398 (7.3%), and 1368 (7.2%) in the control, ERD, NERD, and AEE groups, respectively. Multiple multinomial logistic regression revealed a significant association of increased state (adjusted OR, 1.89; 95% CI, 1.53–2.33) and trait anxiety (adjusted OR, 1.78; 95% CI, 1.34–2.35) and depression (adjusted OR, 2.21; 95% CI, 1.75–2.80) with NERD. ERD group showed a significant association only with state anxiety (adjusted OR, 2.20; 95% CI, 1.27–3.81) and depression (adjusted OR, 2.23; 95% CI, 1.18–4.22). The AEE group, however, did not show any significant association with psychological factors. CONCLUSION: This cross-sectional study revealed that anxiety and depression levels were significantly higher in subjects with GERD (notably in the NERD) than in controls.

Helicobacter pylori Is Associated with miR-133a Expression through Promoter Methylation in Gastric Carcinogenesis

BACKGROUND/AIMS: To investigate whether Helicobacter pylori eradication can reverse epigenetic silencing of microRNAs (miRNAs) which are associated with H. pylori-induced gastric carcinogenesis. METHODS: We examined expression and promoter methylation of miR-34b/c, miR-133a, let-7a, and let-7i in gastric cancer cell line, before/after demethylation. Among them, epigenetically controlled miRNAs were identified. Their expression and promoter methylation was examined in human tissues of H. pylori-positive gastric cancer (T), H. pylori-positive gastritis (H), and H. pylori-negative controls (C). We also compared changes of miRNA expression and promoter methylation in H. pylori-positive patients who were endoscopically treated for early gastric cancer, between baseline and 1 year later according to eradication status. RESULTS: In gastric cancer cell line, miR-34b/c and miR-133a showed epigenetic silencing. In human tissues, miR-34b/c and miR-133a showed serial increase of promoter methylation in order of C, H, and T (all, p < 0.01), and the miR-133a expression showed serial decrease (C vs H, p=0.02; H vs T, p=0.01; C vs T, p < 0.01) while miR-34b and miR-34c expressions did not. H. pylori eradication induced decrease of methylation (p < 0.01) and increase of miR-133a expression (p=0.03), compared with noneradication group. CONCLUSIONS: This result suggests H. pylori eradication could reverse methylation-silencing of miR-133a which is involved in H. pylori-induced gastric carcinogenesis.

Long-Term Effects of Helicobacter pylori Eradication on Metachronous Gastric Cancer Development

BACKGROUND/AIMS: Gastric mucosal atrophy and intestinal metaplasia due to Helicobacter pylori infection are the main precursor lesions of gastric cancer. The aim of this study was to evaluate the long-term effects of H. pylori eradication on the progression of precancerous lesions to metachronous cancer after endoscopic resection of early gastric cancer (EGC). METHODS: Patients who underwent endoscopic resection of EGC were retrospectively reviewed. Changes in precancerous lesions and development of metachronous cancer were compared according to H. pylori eradication and final infection status. RESULTS: In total, 565 patients were followed for over 5 years after endoscopic resection of EGC. The grade of atrophy on corpus was significantly lower in the H. pylori-eradicated group than in the persistent group during follow-up (p=0.029). In patients < 70 years of age, the cumulative incidence rate of metachronous cancer was significantly lower in the H. pylori-eradicated group than in the persistent group (p=0.018). Age was an independent risk factor for metachronous cancer development. CONCLUSIONS: H. pylori eradication might prevent the development of metachronous cancer in patients < 70 years of age by delaying the progression of precancerous lesions after endoscopic resection of EGC.

The Increased Level of Depression and Anxiety in Irritable Bowel Syndrome Patients Compared with Healthy Controls: Systematic Review and Meta-analysis

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) patients commonly experience psychiatric disorders, such as depression and anxiety. This meta-analysis sought to compare depression and anxiety levels between IBS patients and healthy controls. METHODS: We searched major electronic databases (PubMed, EMBASE, MEDLINE, and Cochrane library) to find comparative studies on IBS patients and healthy controls. The primary outcome was a standardized mean difference (SMD) of anxiety and depression levels; sub-group analyses were conducted according to IBS-subtypes. RESULTS: In total, 2293 IBS patients and 4951 healthy controls from 27 studies were included. In random effect analysis, depression and anxiety levels were significantly higher in IBS patients (pooled SMD = 0.76; 95% CI, 0.62–0.90; P < 0.001; I² = 77.2% and pooled SMD = 0.84; 95% CI, 0.67–1.01; P < 0.001; I² = 85.6%, respectively). Both analyses’ funnel plots showed symmetry. In meta-regression analysis, heterogeneity was due to the studied region and questionnaire type for both depression and anxiety. In sub-group analyses of IBS-subtype, the pooled SMDs of depression and anxiety levels (IBS with predominant constipation: 0.83 and 0.81, IBS with predominant diarrhea: 0.73 and 0.65, and IBS with mixed bowel habits: 0.62 and 0.75; P < 0.001, respectively) were significantly higher in all IBS-subtypes. CONCLUSIONS: The present meta-analysis showed depression and anxiety levels to be higher in IBS patients than in healthy controls, regardless of IBS-subtype. However, the gender effect on psychological factors among IBS patients could not be determined and should be evaluated in prospective studies.

The Effect of Helicobacter pylori Eradication on the Metachronous Neoplasm after Endoscopic Resection for Gastric Dysplasia / 대한소화기학회지

BACKGROUND/AIMS: Helicobacter pylori (Hp) infection is an important risk factor for gastric carcinogenesis. Although several studies have investigated the effect of Hp eradication on the development of metachronous neoplasm after endoscopic resection of the gastric dysplasia, the evidence is still insufficient to make a clear conclusion. The aims of this study was to evaluate the risk factors for the development of metachronous neoplasm after endoscopic resection of gastric dysplasia and to investigate the effect of Hp eradication. METHODS: Between 2005 and 2011, a total of 887 patients underwent endoscopic resection for gastric dysplasia. Among them, 521 patients who had undergone tests for Hp infection and been followed-up for at least one year were included in the final analyses. Of the 292 Hp-positive patients, 116 patients were successfully eradicated, while 176 failed or did not undergo eradication. RESULTS: During a mean follow-up of 59.1 months (range 12–125 months), metachronous neoplasm had developed in 63 patients (12.1%, dysplasia in 38, carcinoma in 25). In multivariate analyses, age ≥65 (hazard ratio [HR]=2.247, 95% confidence interval [CI] 1.297–3.895), tumor size (HR=1.283, 95% CI 1.038–1.585), synchronous lesion (HR=2.341, 95% CI 1.244–4.405), family history of gastric cancer (HR=3.240, 95% CI 1.776–5.912), and smoking (HR=1.016, 95% CI 1.003–1.029) were risk factors for metachronous neoplasm after endoscopic resection of gastric dysplasia. However, Hp eradication was not associated with metachronous neoplasm (HR=0.641, 95% CI 0.297–1.384). CONCLUSIONS: Hp eradication was not shown to be associated with the development of metachronous cancer after endoscopic resection of gastric dysplasia.

Management of Suspicious Mucosa-Associated Lymphoid Tissue Lymphoma in Gastric Biopsy Specimens Obtained during Screening Endoscopy

It is often difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from Helicobacter pylori-associated follicular gastritis, and thus, it becomes unclear how to manage these diseases. This study aimed to explore the management strategy for and the long-term outcomes of suspicious gastric MALT lymphoma detected by forceps biopsy during screening upper endoscopy. Between October 2003 and May 2013, consecutive subjects who were diagnosed with suspicious gastric MALT lymphomas by screening endoscopy in a health checkup program in Korea were retrospectively enrolled. Suspicious MALT lymphoma was defined as a Wotherspoon score of 3 or 4 upon pathological evaluation of the biopsy specimen. Of 105,164 subjects who underwent screening endoscopies, 49 patients with suspicious MALT lymphomas who underwent subsequent endoscopy were enrolled. Eight patients received a subsequent endoscopy without H. pylori eradication (subsequent endoscopy only group), and 41 patients received H. pylori eradication first followed by endoscopy (eradication first group). MALT lymphoma development was significantly lower in the eradication first group (2/41, 4.9%) than in the subsequent endoscopy only group (3/8, 37.5%, P = 0.026). Notably, among 35 patients with successful H. pylori eradication, there was only one MALT lymphoma patient (2.9%) in whom complete remission was achieved, and there was no recurrence during a median 45 months of endoscopic follow-up. H. pylori eradication with subsequent endoscopy would be a practical management option for suspicious MALT lymphoma detected in a forceps biopsy specimen obtained during screening upper endoscopy.

Characteristics and outcomes of endoscopically resected colorectal cancers that arose from sessile serrated adenomas and traditional serrated adenomas

BACKGROUND/AIMS: The efficacy and safety of endoscopic resection of colorectal cancer derived from sessile serrated adenomas or traditional serrated adenomas are still unknown. The aims of this study were to verify the characteristics and outcomes of endoscopically resected early colorectal cancers developed from serrated polyps. METHODS: Among patients who received endoscopic resection of early colorectal cancers from 2008 to 2011, cancers with documented pre-existing lesions were included. They were classified as adenoma, sessile serrated adenoma, or traditional serrated adenoma according to the baseline lesions. Clinical characteristics, pathologic diagnosis, and outcomes were reviewed. RESULTS: Overall, 208 colorectal cancers detected from 198 patients were included: 198 with adenoma, five with sessile serrated adenoma, and five with traditional serrated adenoma. The sessile serrated adenoma group had a higher prevalence of high-grade dysplasia (40.0% vs. 25.8%, P<0.001) than the adenoma group. During follow-up, local recurrence did not occur after endoscopic resection of early colorectal cancers developed from serrated polyps. In contrast, two cases of metachronous recurrence were detected within a short follow-up period. CONCLUSIONS: Cautious observation and early endoscopic resection are recommended when colorectal cancer from serrated polyp is suspected. Colorectal cancers from serrated polyp can be treated successfully with endoscopy.

Diagnosis and Treatment of Helicobacter Pylori Infection: Korean and Overseas Guidelines / 대한내과학회지

The Korean College of Helicobacter and Upper Gastrointestinal Research proposed revised guidelines for the diagnosis and treatment of Helicobacter pylori infection in 2013. These new guidelines were developed using an adaptation process, and addressed the revised recommendations especially in the changes of indication and treatment of H. pylori infection in Korea. They included 19 statements: 11 on the indications for tests and treatment, four for the diagnosis, and four for the treatment. A critical difference between the new and previous guidelines was that the proposed treatment regimen was more detailed, in consideration of the increasing resistance to antibiotics in Korea. Although clarithromycin-containing triple therapy was proposed as the first-line treatment option, per the previous guidelines, a bismuth-based quadruple regimen was also proposed as an effective alternative. In the case of treatment failure following bismuth quadruple therapy, second-line treatment should be based on two or more antibiotics that had not been used previously. Several overseas guidelines - from America, Europe, Canada, Japan, and the Asia-Pacific region - have been published concerning H. pylori infection; they indicate regional differences in epidemiology, antibiotic susceptibility, and national health insurance systems. This review compares the guidelines for H. pylori infection among these regions.

Recent Chemotherapy Reduces the Maximum-Standardized Uptake Value of 18F-Fluoro-Deoxyglucose Positron Emission Tomography in Colorectal Cancer

BACKGROUND/AIMS: The aim of this study was to evaluate the influence of recent chemotherapy on the patterns of the maximum-standardized uptake value (M-SUV) and sensitivity of 18F-fluoro-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in colorectal cancer. METHODS: We retrospectively analyzed the FDG-PET/CT of 509 patients who underwent surgery for colorectal cancer. Subgroup analysis was performed according to chemotherapy status; 401 patients were not treated with chemotherapy and 108 patients were treated with chemotherapy within 6 months prior to surgery. Pathologic analysis of the surgical specimen was used as the gold standard. RESULTS: The M-SUV was significantly lower in patients treated with chemotherapy than in those not treated with chemotherapy in pathologically confirmed same stages of disease. The difference in the sensitivity of the M-SUV according to chemotherapy status was greatest using a cutoff M-SUV value of 6.4 (p<0.001). The longest diameter of the primary tumor was the most important factor that correlated with M-SUV of the primary tumor irrespective of the chemotherapy effect (p<0.001). The M-SUV of the primary tumor was not an independent predictor of lymph node metastasis in colorectal cancer. CONCLUSIONS: The results indicate that the M-SUV of FDG-PET/CT should be interpreted in the context of concurrent chemotherapy.

Metastatic Recurrence of Small Bowel Cancer in Crohn's Disease / 대한소화기학회지

No abstract available.

Endoscopic Removal of a Migrated Coil after Embolization of a Splenic Pseudoaneurysm: A Case Report

Splenic artery pseudoaneurysms can be caused by pancreatitis, trauma, or operation. Traditionally, the condition has been managed through surgery; however, nowadays, transcatheter arterial embolization is performed safely and effectively. Nevertheless, several complications of pseudoaneurysm embolization have been reported, including coil migration. Herein, we report a case of migration of the coil into the jejunal lumen after transcatheter arterial embolization of a splenic artery pseudoaneurysm. The migrated coil was successfully removed by performing endoscopic intervention.

Prolonged Neutropenia after Sunitinib Treatment in a Patient with a Glucagonoma and Multiple Hepatic Metastases / 대한내과학회지

Pancreatic neuroendocrine tumors (PNET) are rare, with approximately 2.2 in 1,000,000 people affected annually. In the classification of neuroendocrine tumors, glucagonomas are a functional PNET and comprise 1.6% of PNET. Glucagonoma syndrome is a paraneoplastic syndrome that is characterized by necrolytic migratory erythema, weight loss, anemia, and diabetes mellitus. Metastatic disease at presentation is common, but is often limited to the liver and regional lymph nodes. Sunitinib malate improves the progression-free and overall survival of PNET. This report presents a 45-year-old Asian woman with prolonged neutropenia after sunitinib treatment of a glucagonoma with multiple hepatic metastases. The severity of the neutropenia after the sunitinib treatment fluctuated from grade 1 to 4 repeatedly, with a non-febrile pattern. Ultimately, the patient did not recover from the neutropenia, even after stopping the sunitinib.

A Case of Gastroduodenal Mucosa-associated Lymphoid Tissue Lymphoma Regression after Eradication of Helicobacter pylori

Mucosa-associated lymphoid tissue (MALT) lymphoma is a neoplasm with low-grade malignancy that arises from the MALT of various organs. Among the various MALT lymphomas, gastric MALT lymphoma is the most frequently reported, and it has been correlated with Helicobacter pylori infection. In contrast, duodenal MALT lymphoma is very rare, and a relationship with H. pylori has not been established. This case report describes a very rare case of MALT lymphoma arising in both the stomach and duodenum that regressed after eradication of H. pylori.

A Case of Immune Thrombocytopenic Purpura Associated with Preexisting Ulcerative Colitis Treated with Colectomy and Splenectomy

Ulcerative colitis is a chronic inflammatory bowel disease of unknown etiology, associated with extraintestinal manifestations, including the rarely reported immune thrombocytopenic purpura. Here, we present a case of immune thrombocytopenic purpura associated with preexisting ulcerative colitis. The patient was diagnosed with ulcerative colitis 13 years ago. Two years after diagnosis, he presented with hematochezia and active ulcerative colitis. Despite steroid use, the platelet count gradually decreased to 21,000/mm3. Hematochezia and the platelet count recovered after the administration of cyclosporine, and ulcerative colitis was in near complete remission for 11 years. However, the patient was re-admitted for hematochezia and thrombocytopenia persisting over a month. Medical management including increased doses of steroids in combination with cyclosporin failed to control hematochezia and thrombocytopenia. Immune thrombocytopenic purpura was suspected on the basis of normocellular marrow with a normal number of megakaryocytes. To treat uncontrolled colitis and steroid-refractory thrombocytopenia, total proctocolectomy with ileal pouch-anal anastomosis and splenectomy were performed. The patient was followed up for 10 months after surgery and was found to be in good health with a normal platelet count. Therefore, colectomy alone or in combination with splenectomy should be considered in cases of life-threatening ulcerative colitis complicated with steroid-refractory immune thrombocytopenic purpura.