Clinical Practice Guideline for Gastritis in Korea.

Gastritis is a disease characterized by inflammation of the gastric mucosa. It is very common and has various classification systems such as the updated Sydney system. As there is a lot of evidence that Helicobacter pylori infection is associated with the development of gastric cancer and that gastric cancer can be prevented by eradication, H. pylori gastritis has been emphasized recently. The incidence rate of gastric cancer in Korea is the highest in the world, and due to the spread of screening endoscopy, atrophic gastritis and intestinal metaplasia are commonly diagnosed in the general population. However, there have been no clinical guidelines developed in Korea for these lesions. Therefore, this clinical guideline has been developed by the Korean College of Helicobacter and Upper Gastrointestinal Research for important topics that are frequently encountered in clinical situations related to gastritis. Evidence-based guidelines were developed through systematic review and de novo processes, and eight recommendations were made for eight key questions. This guideline needs to be periodically revised according to the needs of clinical practice or as important evidence about this issue is published in the future.

Prediction model for curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC); however, its curative resection rate is low for undifferentiated-type EGC. We developed and externally validated a prediction model for curative ESD of undifferentiated-type EGC. METHODS: In this cross-sectional study, we included 448 patients who underwent ESD for undifferentiated-type EGC at 18 hospitals in Korea between 2005 and 2015 in the development cohort and 1342 patients who underwent surgery at two hospitals in the validation cohort. A prediction model was developed using the logistic regression model. RESULTS: Endoscopic tumor size 1-2 cm (odds ratio [OR], 2.40; 95% confidence interval [CI] 1.54-3.73), tumor size > 2 cm (OR, 14.00; 95% CI 6.81-28.77), and proximal tumor location from the lower to upper third of the stomach (OR, 1.45; 95% CI 1.03-2.04) were independent predictors of non-curative ESD. A six-score prediction model was developed by assigning points to endoscopic tumor size > 2 cm (five points), tumor size 1-2 cm (two points), upper third location (two points), and middle third location (one point). The rate of curative ESD ranged from 70.6% (score 0) to 11.6% (score 5) with an area under the receiver operating characteristic curve (AUC) of 0.720 (95% CI 0.673-0.766). The model also showed good performance in the validation cohort (AUC, 0.775; 95% CI 0.748-0.803). CONCLUSIONS: This six-score prediction model may help in predicting curative ESD and making informed decisions about the treatment selection between ESD and surgery for undifferentiated-type EGC.

Long-term outcomes of endoscopic resection followed by additional surgery after non-curative resection in undifferentiated-type early gastric cancer: a nationwide multi-center study.

BACKGROUND: Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment. METHODS: We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared. RESULTS: Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively. CONCLUSIONS: ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC.

Clinical outcomes of endoscopic resection for undifferentiated intramucosal early gastric cancer larger than 2 cm.

BACKGROUND: This study investigated the long-term clinical outcomes of endoscopic resection (ER) for undifferentiated-type (UD) early gastric cancer (EGC), with tumor size > 2 cm as the only non-curative factor. METHODS: From among 1123 patients who underwent ER for UD EGC at 18 tertiary hospitals in Korea between 2005 and 2014, we identified 216 patients with UD intramucosal EGC > 2 cm, which was completely resected, with negative resection margins, and absence of ulceration and lymphovascular invasion. The patients were divided into the additional surgery (n = 40) or observation (n = 176) groups, according to post-ER management and were followed up for a median duration of 59 months for recurrence and 90 months for overall survival. RESULTS: Lymph node (LN) or distant metastasis or cancer-related mortality was not observed in the surgery group. In the observation group, two (1.1%) patients developed LN or distant metastasis with a 5-year cumulative risk of 0.7%, and one (0.6%) patient died of gastric cancer. The 5- and 8-year overall survival rates were 94.1% and 89.9%, respectively, in the observation group and 100.0% and 95.2%, respectively, in the surgery group (log-rank P = 0.159). Cox regression analysis did not reveal an association between the observation group and increased mortality. CONCLUSION: The risk of LN or distant metastasis was not negligible, but as low as 1% for patients undergoing non-curative ER for UD EGC, with tumor size > 2 cm as the only non-curative factor. Close observation may be an alternative to surgery, especially for older patients or those with poor physical status.

Comparison between endoscopic submucosal resection and surgery for the curative resection of undifferentiated-type early gastric cancer within expanded indications: a nationwide multi-center study.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD EGC) has debate due to the risk of lymph node metastasis. We investigated the outcomes of ESD compared to those of surgery for the UD EGC within expanded indication. METHODS: We reviewed 971 UD EGC patients performed ESD across 18 hospitals in Korea and 1812 patients who underwent surgical resection in two hospitals between February 2005 and May 2015. Of these cases, we enrolled a curative resected ESD group of 328 patients and surgery group of 383 cases within an expanded indication. Overall outcomes and one-to-one propensity score-matched (218 ESD group vs 218 surgery group cases) outcomes for these two groups were analyzed. RESULTS: Over the 75.6 month median follow-up period for the 711 enrolled cases, recurrences occurred in 22 patients (6.7%) in the ESD group but not in the surgery group. Overall survival (OS) was higher in the surgery group (p = 0.0316) in all cases, but there was no significant difference after propensity score matching (p = 0.069). According to the histologic type in propensity score matching, the OS of signet ring cell carcinoma and poorly differentiated carcinoma patients did not differ between the ESD and surgery groups (p = 0.1189 and p = 0.3087, respectively). In the surgery group involving expanded criteria, lymph node metastasis was found in six cases (1.56%). CONCLUSIONS: Although ESD shows comparable outcomes to surgery for the UD EGC within expanded indications, appropriate patient selection is needed for the ESD due to the possibility of lymph node metastasis.

Risk factors of lymph node metastasis after non-curative endoscopic resection of undifferentiated-type early gastric cancer.

BACKGROUND: This study aimed to investigate risk factors for lymph node (LN) or distant metastasis after non-curative endoscopic resection (ER) of undifferentiated-type early gastric cancer (EGC). METHODS: Of 1124 patients who underwent ER for undifferentiated-type gastric cancer at 18 tertiary hospitals across six geographic areas in Korea between 2005 and 2014, 634 with non-curative ER beyond the expanded criteria were retrospectively enrolled. According to the treatment after ER, patients were divided into additional surgery (n = 270) and follow-up (n = 364) groups. The median follow-up duration was 59 months for recurrence and 84 months for mortality. RESULTS: LN metastasis was found in 6.7% (18/270) of patients at surgery. Ulcer [odds ratio (OR) 3.83; 95% confidence interval (CI) 1.21-12.13; p = 0.022] and submucosal invasion (OR 10.35; 95% CI 1.35-79.48; p = 0.025) were independent risk factors. In the follow-up group, seven patients (1.9%) developed LN or distant recurrence. Ulcer [hazard ratio (HR) 7.60; 95% CI 1.39-35.74; p = 0.018], LVI (HR 6.80; 95% CI 1.07-42.99; p = 0.042), and positive vertical margin (HR 6.71; 95% CI 1.28-35.19; p = 0.024) were independent risk factors. In the overall cohort, LN metastasis rates were 9.6% in patients with two or more risk factors and 1.2% in those with no or one risk factor. CONCLUSIONS: LVI, ulcer, submucosal invasion, and positive vertical margin are independently associated with LN or distant metastasis after non-curative ER of undifferentiated-type EGC. Surgical resection is strongly recommended for patients with two or more risk factors.

Sleep disorders in patients with functional dyspepsia: A multicenter study from the Korean Society of Neurogastroenterology and Motility.

BACKGROUND AND AIM: The few studies concerning the association between sleep disorders and functional dyspepsia (FD) have yielded inconsistent results. We compared the prevalence of sleep disorders in patients with FD and healthy controls, and evaluated whether FD was independently associated with sleep disorders, and the risk factors for sleep disorders in patients with FD. METHODS: This prospective, multicenter, cross-sectional study was conducted from August 2014 to December 2017 at 12 hospitals in South Korea. The inclusion criterion was the presence of FD (for ≥18 years) according to the Rome III criteria. Healthy controls were recruited from among patients who visited the Health Examination Center for check-ups. RESULTS: In total, 526 subjects were prospectively enrolled in this study (201 with FD and 325 healthy controls). The prevalence of sleep disorders was significantly higher among the patients with FD than among the healthy controls (41.8% vs 18.8%, P = 0.000). In a multivariate analysis, FD (odds ratio [OR] = 1.851; 95% confidence interval [CI] 1.194-2.870; P = 0.006), female sex (OR = 1.672; 95% CI 1.063-2.628; P = 0.026), and anxiety (OR = 3.325; 95% CI 2.140-5.166; P = 0.000) were independent risk factors for sleep disorders in the overall cohorts. In patients with FD only, low body mass index, heartburn, and anxiety were independent risk factors for sleep disorders in a further multivariate analysis. CONCLUSION: Sleep disorders were common in patients with FD. FD was significantly associated with sleep disorders in our patient population, irrespective of the presence of heartburn or psychiatric disorders.

Potential involvement of adiponectin in obesity-associated erosive esophagitis.

A strong causal relationship between obesity and erosive esophagitis has been proposed. Obesity may affect the pathogenesis of erosive esophagitis through adipokines as well as acid reflux. We evaluated the involvement of adiponectin in obesity-associated erosive esophagitis. In total, 1,902 patients who underwent endoscopy during medical check-ups were selected for study. Variables including the body mass index (BMI) and adiponectin level were compared between subjects with erosive esophagitis and normal controls. The subjects were classified by quartiles (Qs) of adiponectin level. Q4 was the reference group. The median adiponectin level differed by gender (men, 5.3 µg/ml vs women, 9.3 µg/ml; p<0.001). As the severity of erosive esophagitis increased in men, the BMI increased (p<0.001) while the adiponectin level decreased (p = 0.026). The multivariate odds ratio for erosive esophagitis was 1.79 for Q1, 1.73 for Q2, 2.34 for obesity, and 27.40 for hiatal hernia in men. When classified by obesity, the multivariate odds ratio for erosive esophagitis was 1.94 for Q1, 2.10 for Q2, and 18.47 for hiatal hernia only in obese men. In women, there were no trends in BMI, adiponectin levels, or severity of erosive esophagitis. We demonstrated that low adiponectin levels are involved in obesity-associated erosive esophagitis in men but not women.

Gender Specific Differences in Prevalence and Risk Factors for Gastro-Esophageal Reflux Disease.

BACKGROUND: Gender-related factors might play an important role in the development of reflux esophagitis (RE) and symptomatic gastro-esophageal reflux disease (GERD). We aimed to evaluate the prevalence and risk factors for RE and symptomatic GERD and determine whether gender specific differences exist. METHODS: This study was conducted on a health cohort consisting of 10,158 participants who underwent comprehensive health screening. Lifestyles and gastrointestinal symptoms were investigated using a self-reported structured questionnaire. Questionnaires about menstrual status were added for the women. RESULTS: The prevalence of RE in men was significantly higher than that in women (10.6% vs. 2.0%, P < 0.001); however, symptomatic GERD showed predominance in women (6.2% vs. 2.5%, P < 0.001). Although the prevalence of RE gradually increased with the duration of menopause stratified by decade (P = 0.007), that of symptomatic GERD rapidly increased across the menopausal transit in women. Apart from common risk factors of obesity and current smoking for RE, over 70 years of age in women and hiatal hernia and hypertriglyceridemia in men were significant risk factors. In symptomatic GERD, high somatization was a common risk factor. Excessive alcohol drinking was a significant risk factor in men, but not in women. CONCLUSION: This study showed a predominance of RE in men, but a predominance of symptomatic GERD in women. In women, dynamic increase in the prevalence of GERD is closely related to the menopause conditions and its duration. There are specific risk factors for RE and symptomatic GERD according to gender differences.

Triple therapy versus sequential therapy for the first-line Helicobacter pylori eradication.

BACKGROUND: The eradication rate of Helicobacter pylori (H. pylori) with triple therapy which was considered as standard first-line treatment has decreased to 70-85%. The aim of this study is to compare 7-day triple therapy versus 10-day sequential therapy as the first line treatment. METHODS: Data of 1240 H. pylori positive patients treated with triple therapy or sequential therapy from January 2013 to December 2015 were analyzed retrospectively. The patients who had undertaken previous H. pylori eradication therapy or gastric surgery were excluded. RESULTS: There were 872 (74.3%) patients in the triple therapy group, and 302 (25.7%) patients in the sequential therapy group. There was no significant difference between the two groups regarding age, residence, comorbidities or drug compliance, but several differences were noted in endoscopic characteristics and indication for the treatment. The eradication rate of H. pylori by intention to treat analysis was 64.3% in the triple therapy group, and 81.9% in the sequential therapy group (P = 0.001). In per protocol analysis, H. pylori eradication rate in the triple therapy and sequential therapy group was 81.9 and 90.3%, respectively (P = 0.002). There was no significant difference in overall adverse events between the two groups (P = 0.706). For the rescue therapy, bismuth-containing quadruple therapy showed comparable treatment efficacy after sequential therapy, as following triple therapy. CONCLUSIONS: The eradication rate of triple therapy was below the recommended threshold. Sequential therapy could be effective and tolerable candidate for the first-line H. pylori eradication therapy.

Multidisciplinary Approach to Refractory Upper Gastrointestinal Bleeding: Case Series of Angiographic Embolization.

Although medical and endoscopic hemostasis is now considered as the first-line therapy for nonvariceal upper gastrointestinal (UGI) bleeding, refractory bleeding still occurs in 5%-10% of the patients. In these patients, transcatheter arterial embolization (TAE) or surgery is required, but research on embolization for unmanageable UGI bleeding in Korea is scanty. We reviewed the medical records of 518 patients who underwent endoscopic hemostasis during 4 years. Among these subjects, 8 patients who required embolization due to failure of endoscopic hemostasis were enrolled. Mean patient age was 74.00 ± 8.25 years, and rebleeding occurred in 4 patients within 48 hours after TAE. Three patients with duodenal rebleeding underwent surgery, and the other patient with a gastric ulcer underwent endoscopic hemostasis. Nonvariceal UGI bleeding remains a serious clinical challenge, especially in older patients. A multidisciplinary approach including endoscopists, interventional radiologists, and surgeons may be important for the treatment of nonvariceal UGI bleeding.

Importance of Patients' Knowledge of Their Prescribed Medication in Improving Treatment Adherence in Inflammatory Bowel Disease.

GOALS: To investigate the association between treatment nonadherence and patients' knowledge of the prescribed medication among individuals with inflammatory bowel disease (IBD), and evaluate the impact of nonadherence on relapse. BACKGROUND: The patient's knowledge of the prescribed medication has been identified as an important predictor of treatment adherence in chronic diseases. However, this association has not been examined in IBD. STUDY: In this prospective study, at baseline, 138 patients with IBD completed a self-reported survey on demographic data, knowledge of the prescribed medication, and candidate factors related to the degree of treatment adherence. To investigate the impact of nonadherence among patients in remission, relapse was analyzed for 18 months after enrollment. RESULTS: Nonadherence was observed in 50 (36.2%) of the 138 subjects. In multivariate analysis, nonadherence was significantly associated with younger age (less than 30 y) at participation [odds ratio (OR), 5.88; 95% confidence interval (CI), 1.51-22.94; P=0.011], longer intervals between outpatient clinic visits (≥3 mo) (OR, 30.31; 95% CI, 3.06-300.17; P=0.004), and limited knowledge of the prescribed medication (OR, 5.61; 95% CI, 1.60-19.67; P=0.038). Nonadherent patients had a significantly greater risk of relapse of IBD than adherent patients (relative risk, 2.9; 95% CI, 2.25-3.79; P=0.045). CONCLUSION: Younger age, longer intervals between outpatient clinic visits, and limited knowledge of the prescribed medication tended to be associated with nonadherence to treatment, which consequently also affects the risk of relapse.

Significance of calcium-sensing receptor expression in gastric cancer.

OBJECTIVE: The calcium-sensing receptor (CaSR) is known to have differential expression in various carcinomas and normal tissues. It has been shown to be involved in carcinogenesis or tumor suppression. However, its role in gastric cancer remains unknown. This study was performed to determine the CaSR expression level in gastric cancer and non-tumor gastric tissues and to examine the related clinicopathological factors. MATERIALS AND METHODS: Thirty-one pairs of gastric cancer tissues and matched non-tumor gastric tissues were obtained from surgical tissues after gastrectomy. Using real-time polymerase chain reaction, we measured CaSR mRNA expression. We evaluated the association between CaSR mRNA expression and clinicopathological variables based on the downregulation or upregulation of CaSR mRNA expression in gastric cancer tissues compared to those of matched non-tumor gastric tissues. By immunohistochemistry, we confirmed CaSR expression levels in gastric cancer tissues. RESULTS: Downregulation of CaSR mRNA was observed in 77.4% of gastric cancer tissues compared to their matched normal tissues. Downregulated CaSR was associated with a tendency for deeper invasion into the proper muscle (p = 0.028) and more advanced stage (II-IV; p = 0.012). CONCLUSION: We conclude that downregulation of CaSR may contribute to the prevention or suppression of tumor outgrowth.

Epstein-Barr virus infection serves as an independent predictor of survival in patients with lymphoepithelioma-like gastric carcinoma.

BACKGROUND: The pathogenesis and clinicopathologic characteristics of Epstein-Barr virus (EBV)-negative lymphoepithelioma-like gastric carcinoma (LELC) are still unclear. In addition, it remains controversial whether EBV infection itself affects the prognosis of LELC. METHODS: Between 1995 and 2011, 145 LELC patients (124 patients with EBV infection and 21 patients without EBV infection) underwent radical gastrectomy with D2 lymph node dissection. The clinicopathologic features and prognosis of EBV-negative LELC cases were compared with those of EBV-positive LELC cases. The median duration of follow-up after surgery was 55 months. Microsatellite instability (MSI) analysis was performed on 20 EBV-negative LELC cases. RESULTS: EBV-negative LELC accounted for 14.5 % of the total LELC cases. EBV-negative LELC was significantly associated with older age, female sex, advanced T stage, and advanced American Joint Committee on Cancer (AJCC) tumor stage compared with EBV-positive LELC. In univariate analysis, patients with EBV-negative LELC had significantly shorter overall, disease-specific, and recurrence-free survival than those with EBV-positive LELC. The 5-year overall survival rates were 81.0 % for patients with EBV-negative LELC and 96.2 % for patients with EBV-positive LELC. In a Cox proportional hazards model, EBV infection, age, and AJCC tumor stage were identified as independent predictors of overall survival. MSI-high, MSI-low, and microsatellite-stable tumors accounted for 25, 10, and 65 % of EBV-negative LELC cases, respectively. MSI status did not affect the prognosis of EBV-negative LELC cases. CONCLUSIONS: EBV infection serves as an independent predictor of survival in patients with LELC. EBV-negative LELC exhibited clinicopathologic features and prognosis distinct from those of EBV-positive LELC.

EYA4 Acts as a New Tumor Suppressor Gene in Colorectal Cancer.

A previous genome-wide methylation array for colorectal cancer (CRC) identified aberrant promoter methylation of eyes absent 4 (EYA4). However, the correlations between EYA4 methylation and gene expression, the role played by EYA4 protein in colorectal carcinogenesis, and results of the gene-enrichment and functional annotation analysis have not yet been established. We analyzed the EYA4 methylation status and found EYA4 promoter methylation in CRC cell lines (100%), CRC tissues (93.5%) and advanced adenoma tissues (50.7%), compared with normal mucosa (32.6%). There was a significant inverse correlation between EYA4 methylation and expression. EYA4 transfection led to inhibition of cell proliferation in colony assays and xenograft studies. On performing the gene-enrichment and functional annotation analysis, we observed that the differentially expressed genes have been associated with the Wnt and MAPK signaling pathways. Our results demonstrate that EYA4 is under epigenetic regulation in CRC. It is a candidate tumor suppressor gene that acts by inducing up-regulation of DKK1 and inhibiting the Wnt signaling pathway. In addition, EYA4 methylation may be identified in stool samples and it serves as a potential stool biomarker for detection of advanced adenoma and CRC.

The use of low-volume polyethylene glycol containing ascorbic acid versus 2 L of polyethylene glycol plus bisacodyl as bowel preparation for colonoscopy.

OBJECTIVE: Low-volume polyethylene glycol (PEG) bowel preparations have been developed to improve compliance for colonoscopy. Our study aimed to compare the efficacy and tolerability of low-volume PEG containing ascorbic acid for colonoscopy against 2 L of PEG plus bisacodyl. METHODS: We prospectively enrolled consecutive inpatients who had not undergone polypectomy at the index colonoscopy and were subsequently referred for polypectomy at our hospital. A total of 62 patients were randomized to receive either low-volume PEG containing ascorbic acid (n = 31) or 2 L of PEG plus bisacodyl (n = 31) as a split-dose regimen in inpatients. The efficacy of preparation was determined using the Ottawa Bowel Preparation Score (OBPS) and a 4-point scale. Adverse events, tolerability, and willingness were evaluated using a questionnaire. RESULTS: Based on the OBPS and 4-point scale, we determined that the efficacy of low-volume PEG containing ascorbic acid was comparable to that of the 2 L of PEG plus bisacodyl (p = 0.071 for OBPS, p = 0.056 for the 4-point scale). Adverse events were comparable between the two groups (p = 1.000). A greater proportion of patients in the low-volume PEG containing ascorbic acid (90.6%) and the 2L of PEG plus bisacodyl (96.9%) were willing to repeat the same preparation for subsequent colonoscopy. CONCLUSION: Low-volume PEG containing ascorbic acid had comparable efficacy and tolerability to 2 L of PEG plus bisacodyl, when given as a split dose, for colonoscopy in inpatients. Split-dose low-volume PEG containing ascorbic acid is a good alternative for bowel preparation for colonoscopy in inpatients.

Is endoscopic resection an alternative to surgery for early low-risk submucosal gastric cancers: analysis of a large surgical database.

BACKGROUND: Although endoscopic resection (ER) for early gastric cancers (EGCs) has become popular with the development of endoscopic instruments and skillful endoscopists, the risk of lymph node metastasis (LNM) is still an obstacle in performing ER. In this study, we aimed to identify the risk factors of LNM and validated the expanded criteria, with the goal of suggesting modified criteria for ER in submucosal EGCs. METHODS: Of patients who underwent gastrectomy with LN dissection and were diagnosed as EGCs with depth of invasion such as sm1, sm2 or ≤ 500 µm from 1999 to 2008, 318 EGCs with submucosal invasion ≤ 500 µm were enrolled through pathologic evaluations. To identify the risk factors of LNM, a multivariate analysis of clinicopathologic factors was performed. By combining the independent risk factors of LNM, the risk of LNM was analyzed. RESULT: LNM were detected in 35 cases (11.0 %). Tumors >30 mm in size and with lymphatic invasion were identified as an independent risk factor for LNM in EGCs with depth of invasion ≤ 500 µm. Among 94 cases meeting the expanded criteria, two cases (2.1 %) were found to have LNM. Based on the submucosal invasion <300 µm, there was no LNM in EGCs with a size ≤ 30 mm and no lymphovascular invasion, regardless of differentiation grade. CONCLUSION: To exclude the possibility of LNM, applying the modified criteria based on the submucosal invasion <300 µm in performing ER might be worthwhile.

Involvement of adiponectin in early stage of colorectal carcinogenesis.

BACKGROUND: Although altered levels of adiponectin have been reported as a potential risk factor in colorectal cancer (CRC), the importance of the role played by adiponectin in colorectal carcinogenesis has not been established. We sought to examine the expression pattern of adiponectin and adiponectin receptors (AdipoRs) in the normal-adenoma-carcinoma sequence and to assess the implications of adiponectin in colorectal carcinogenesis. METHODS: Serum adiponectin concentrations, and the mRNA and protein expression of adiponectin and AdipoRs were examined using serum and tissues from patients with CRC, advanced adenoma, and a normal colon. mRNA expression of AdipoRs and epithelial-mesenchymal transition regulators including E-cadherin, cyclooxygenase-2 (COX-2) and T-cadherin were examined in HCT116 cells treated with adiponectin. RESULTS: Serum adiponectin concentrations in patients with advanced adenoma and CRC were lower than those in controls. Adiponectin mRNA was not detected in colonic tissue, whereas AdipoRs mRNA was lower in advanced adenoma and CRC than that in normal colon tissues. Immunohistochemical staining demonstrated that adiponectin was expressed in spindle-shaped cells of the subepithelial layer in normal colon tissues, whereas ill-defined overexpression of adiponectin was seen in the stroma of advanced adenoma and CRC tissues. AdipoRs expression was strong in normal epithelium, but weak to negative in the epithelia of CRC tissues. Adiponectin downregulated COX-2 mRNA expression in vitro, but upregulated T-cadherin in HCT116 cells. CONCLUSIONS: Systemic adiponectin and local AdipoRs expression in the colon may be associated with anti-tumorigenesis during the early stages of CRC. These findings offer new insight into understanding the relationship between adiponectin and colorectal carcinogenesis.

Clinical Trial: Efficacy of Mosapride Controlled-release and Nortriptyline in Patients With Functional Dyspepsia: A Multicenter, Double-placebo, Double-blinded, Randomized Controlled, Parallel Clinical Study.

Background/Aims: Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Methods: Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. Results: One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Conclusion: Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Efficacy of Tegoprazan in Patients With Functional Dyspepsia: A Prospective, Multicenter, Single-arm Study.

Background/Aims: Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD. Methods: FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean (NDI-K), and gastroesophageal reflux disease-health-related quality of life (GERD-HRQL). The main outcome was satisfactory symptom relief rates at 8 weeks. Results: In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study. Conclusion: Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.