Efficacy of Endoscopic and Surgical Treatments for Gastroesophageal Reflux Disease: A Systematic Review and Network Meta-Analysis

Although various endoscopic and surgical procedures are available for the treatment of gastroesophageal reflux disease (GERD), the comparative efficacy of these treatments has not been fully elucidated. This study aimed to comprehensively evaluate the efficacy of various endoscopic and surgical treatments for GERD. All relevant randomized controlled trials published through August 2021 that compared the efficacy of endoscopic and surgical GERD treatments, including radiofrequency energy delivery, endoscopic plication, reinforcement of the lower esophageal sphincter (LES), and surgical fundoplication, were searched. A network meta-analysis was performed to analyze treatment outcomes, including the requirement of proton pump inhibitor (PPI) continuation and GERD-health-related quality of life questionnaire score (GERD-HRQL). As such, 25 studies with 2854 patients were included in the analysis. Endoscopic plication, reinforcement of the LES, and surgical fundoplication were effective in reducing the requirement of PPI continuation compared to PPI therapy (pooled risk ratio (RR) (95% confidence interval [CI]): endoscopic plication, 0.34 (0.21-0.56); reinforcement of LES, 0.32 (0.16-0.63), and surgical fundoplication, 0.16 (0.06-0.42)). Radiofrequency energy delivery tended to reduce the requirement of PPI continuation compared to PPI therapy (RR (95% CI): 0.55 (0.25-1.18)). In terms of GERD-HRQL, all endoscopic and surgical treatments were superior to PPI therapy. In conclusion, all endoscopic or surgical treatments, except radiofrequency energy delivery, were effective for discontinuation of PPI medication, especially surgical fundoplication. Quality of life, measured by GERD-HRQL, also improved in patients who underwent endoscopic or surgical treatment compared to those who received PPI therapy.ope

Effect of β-caryophyllene from Cloves Extract on Helicobacter pylori Eradication in Mouse Model

New antibacterial treatments against Helicobacter pylori are needed as H. pylori is acquiring antibiotic resistance. β-caryophyllene is a natural bicyclic sesquiterpene, with anti-inflammatory and antimicrobial effects. This study investigates the effects of H-002119-00-001 from β-caryophyllene on the eradication of H. pylori in a mouse model, and its effects on the inflammation of the gastric mucosa. To evaluate the anti-H.pylori efficacy of β-caryophyllene, a total of 160 mice were divided into eight groups (n = 10 each) and were administered different treatments for 2 and 4 weeks. H. pylori eradication was assessed using a Campylobacter-like organism (CLO) test and H. pylori qPCR of the gastric mucosa. The levels of inflammation of gastric mucosa were assessed using histology and immunostaining. H-002119-00-001 decreased bacterial burden in vitro. When H-002119-00-001 was administered to mice once daily for 2 weeks, cure rates shown by the CLO test were 40.0%, 60.0%, and 70.0% in groups 6, 7, and 8, respectively. H. pylori levels in gastric mucosa decreased dose-dependently after H-002119-00-001 treatment. H-002119-00-001 also reduced levels of inflammation in gastric mucosa. H-002119-00-001 improved inflammation and decreased bacterial burden in H. pylori-infected mouse models. H-002119-00-001 is a promising and effective therapeutic agent for the treatment of H. pylori infection.ope

The Effect of Trimebutine on the Overlap Syndrome Model of Guinea Pigs

Background/Aims: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common gastrointestinal (GI) disorders and these patients frequently overlap. Trimebutine has been known to be effective in controlling FD co-existing diarrhea-dominant IBS, however its effect on overlap syndrome (OS) patients has not been reported. Therefore, we investigated the effect of trimebutine on the model of OS in guinea pigs. Methods: Male guinea pigs were used to evaluate the effects of trimebutine in corticotropin-releasing factor (CRF) induced OS model. Different doses (3, 10, and 30 mg/kg) of trimebutine were administered orally and incubated for 1 hour. The next treatment of 10 μg/kg of CRF was intraperitoneally injected and stabilized for 30 minutes. Subsequently, intragastric 3 mL charcoal mix was administered, incubated for 10 minutes and the upper GI transit analyzed. Colonic transits were assessed after the same order and concentrations of trimebutine and CRF treatment by fecal pellet output assay. Results: Different concentrations (1, 3, and 10 μg/kg) of rat/human CRF peptides was tested to establish the OS model in guinea pigs. CRF 10 μg/kg was the most effective dose in the experimental OS model of guinea pigs. Trimebutine (3, 10, and 30 mg/kg) treatment significantly reversed the upper and lower GI transit of CRF induced OS model. Trimebutine significantly increased upper GI transit while it reduced fecal pellet output in the CRF induced OS model. Conclusions: Trimebutine has been demonstrated to be effective on both upper and lower GI motor function in peripheral CRF induced OS model. Therefore, trimebutine might be an effective drug for the treatment of OS between FD and IBS patients.ope

lncRNAs UC.145 and PRKG1-AS1 Determine the Functional Output of DKK1 in Regulating the Wnt Signaling Pathway in Gastric Cancer

DKK1 inhibits the canonical Wnt signaling pathway that is known to be involved in various cancers. However, whether DKK1 acts as an oncogene or tumor suppressor gene remains controversial. Furthermore, the DKK1-regulating mechanism in gastric cancer has not yet been defined. The aim of this study was to explore whether the ultraconserved region UC.145 regulates epigenetic changes in DKK1 expression in gastric cancer. Microarray analysis revealed that UC.145 exhibited the highest binding affinity to EZH2, a histone methyltransferase. The effects of UC.145 inactivation were assessed in gastric cancer cell lines using siRNA. The results indicated that UC.145 triggers DKK1 methylation via interaction with EZH2 and is involved in the canonical Wnt signaling pathway. Additionally, interaction between UC.145 and another long non-coding RNA adjacent to DKK1, PRKG1-AS1, induced a synergistic effect on Wnt signaling. The regulation of these three genes was closely associated with patient overall survival. Inactivation of UC.145 induced apoptosis and inhibited the growth and migratory, invasive, and colony-forming abilities of gastric cancer cells. The study findings provide insights into Wnt signaling in gastric cancer and support UC.145 as a potential novel predictive biomarker for the disease.ope

Endoscopic Resection of Early Gastric Cancer in Elderly

With the aging of the society, the proportion of elderly patients with gastric cancer is increasing and the chances of encountering elderly patients with early gastric cancer (EGC) are increasing. Because elderly patients have more comorbidities, and lower life expectancy than younger patients, the treatment strategy for elderly patients with EGC is not standardized. Therefore, it is necessary to identify risk factors related to survival of elderly patients with EGC and to establish treatment strategies according to prognosis in elderly patients with EGC.ope

Early Detection is Important to Reduce the Economic Burden of Gastric Cancer

Purpose: Early detection of gastric cancer is important to improve prognosis. Early detection enables local treatment, such as endoscopic submucosal dissection (ESD). Therefore, we investigated whether early detection of gastric cancer could reduce healthcare costs by comparison according to stage and treatment modalities. Materials and Methods: Medical care costs were investigated according to tumor stage and initial treatment modality in 1,188 patients newly diagnosed with gastric cancer at 7 medical institutions from December 2011 to June 2012. Total medical care costs during the first-year after diagnosis (total first-year costs) were examined, including the costs of initial treatment, post-initial treatment, and inpatient and outpatient visits. Results: Stage I (75.3%) was the most common cancer stage. ESD was the second most common treatment following surgery. Total first-year costs increased significantly from stages I to IV. The costs of initial treatment and post-initial treatment were lowest in patients with stage I cancer. Among patients with stage I cancer, total first-year costs were significantly lower when treated by ESD; in particular, initial ESD treatment costs were much lower than others. Conclusions: The cost of healthcare has increased significantly with increasing cancer stages. ESD can greatly reduce medical care costs of gastric cancer. Thus, early detection of gastric cancer is important to reduce healthcare costs.ope

Guidelines for Nonvariceal Upper Gastrointestinal Bleeding

Nonvariceal upper gastrointestinal bleeding (NVUGIB) refers to bleeding that develops in the gastrointestinal tract proximal to the ligament of Treitz. NVUGIB requires hospitalization and is associated with significant morbidity and mortality. Although European and Asian-Pacific guidelines have been published, there have been no previous guidelines regarding management of NVUGIB in Korea. Korea has a high prevalence of Helicobacter pylori infections, and patients have easy accessibility to endoscopy. Therefore, we believe that guidelines regarding management of NVUGIB in Korea are essential. The Korean Society of Gastroenterology reviewed the recent evidence and recommends practical management guidelines on NVUGIB in Korea.ope

Association of Long-term Use of Proton Pump Inhibitors with Mortality

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Guidelines for Non-variceal Upper Gastrointestinal Bleeding

Non-variceal upper gastrointestinal bleeding (NVUGIB) refers to bleeding that develops in the gastrointestinal tract proximal to the ligament of Treitz. NVUGIB is an important cause for visiting the hospital and is associated with significant morbidity and mortality. Although European and Asian-Pacific guidelines have been published, there has been no previous guidelines regarding management of NVUGIB in Korea. Korea is a country with a high prevalence of Helicobacter pylori infection and patients have easy accessibility to receive endoscopy. Therefore, we believe that guidelines regarding management of NVUGIB are mandatory. The Korean Society of Gastroenterology reviewed recent evidence and recommends practical management guidelines on NVUGIB in Korea.ope

Optimal Endoscopy Timing in Patients With Acute Variceal Bleeding: A Systematic Review and Meta-Analysis

Although current guidelines recommend performing endoscopy within 12 hours for acute variceal bleeding (AVB), the optimal timing remains controversial. This study aimed to assess the effect of endoscopy timing on the mortality and rebleeding rates in AVB through a systematic review and meta-analysis of all eligible studies. PubMed, Cochrane Library, and Embase were searched for relevant publications up to January 2019. Overall mortality, rebleeding rate, and other clinical outcomes were determined. For the non-randomized studies, the risk of bias assessment tool was used to assess the methodological quality of the included publications. The Mantel-Haenszel random-effects model of the RevMan software (Cochrane) and the inverse variance method were used to analyse binary end points and continuous outcomes, respectively. This meta-analysis included five studies with 854 and 453 participants who underwent urgent (≤12 hours) and non-urgent endoscopies (>12 hours), respectively. All the included studies were retrospective in nature, because of obvious ethical issues. No significant differences in the severity indexes were found between the urgent and non-urgent groups. Three studies showed 6-week mortality and the others in-hospital mortality as main outcomes. No significant difference in overall mortality rate was found between the groups (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.36-1.45, p = 0.36). The rebleeding rate was similar between the two groups (OR: 1.21, 95% CI: 0.76-1.93, p = 0.41). Other outcomes such as successful haemostasis, need for salvage therapy, length of hospital stay, and number of blood transfusions were also similar between the groups. We demonstrated that endoscopy timing does not affect the mortality or rebleeding rate of patients with AVB. Therefore, an appropriate timing of endoscopy would be more important than an urgent endoscopy depending on each patient's condition.ope