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Background/Aims@#Drugs that stabilize intestinal motility may improve the efficacy of nonabsorbable antibiotics, such as rifaximin, against small intestinal bacterial overgrowth (SIBO). We compared the efficacy of rifaximin alone with that of its combination with trimebutine maleate against SIBO. @*Methods@#We performed a randomized double-blind placebo-controlled trial (https://cris.nih.go.kr, no. KCT0004836) that included patients with functional bloating, no constipation, and SIBO using the hydrogen (H2 )–methane (CH4 ) glucose breath test (GBT). Patients were randomized into 2 groups in a 1:1 ratio, namely rifaximin (1200 mg/day) + trimebutine maleate (600 mg/day) group and rifaximin + placebo group, for 2 weeks. Patients completed a symptom questionnaire and underwent a GBT at baseline and at 1 month after treatment withdrawal. The primary outcome was SIBO eradication. The secondary outcomes included changes in the concentrations of exhaled gases, symptoms, and presence of adverse events. @*Results@#The complete eradication rate of SIBO was 35.9% (14/39) in the rifaximin group, and 34.1% (14/41) in the combined group with no significant differences. In both groups, no significant differences were observed in GBT profiles before and after the treatment, respectively. However total breath H2 and CH4 concentration were conspicuously decreased in the combined group after treatment.The combined group exhibited substantial relief of bloating. The adverse events were similar in the 2 groups. @*Conclusion@#While the combination therapy was not superior over rifaximin alone for SIBO eradication, it improves the symptom of bloating with numerically reducing the concentration of breath H2 /CH4 .

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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.

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Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the gastrointestinal tract, particularly gastric MiNENs are rare, and a gastric adenoma that occurs concomitant with a neuroendocrine carcinoma (and not gastric adenocarcinoma) is extremely rare. The clinicopathologic and pathogenetic features of MiNENs remain unclear, and treatment guidelines are currently unavailable. A 75-year-old man patient was referred to our hospital for management of a gastric adenoma. Endoscopy revealed an elevated mucosal lesion (10 mm×10 mm) at the greater curvature of the lower gastric body. The patient underwent endoscopic submucosal dissection for removal of the gastric neoplasm. Histopathological evaluation revealed mixed epithelial dysplasia, low and partly high grade and a neuroendocrine tumor (grade 1). Immunohistochemical analysis showed neoplastic cells with immunopositivity for CD56, synaptophysin, and INSM1, and Ki-67 showed 2.2%. Therefore, the patient was diagnosed with a low-grade gastric MiNEN. We present a rare case of gastric MiNENs (adenoma-neuroendocrine tumor) together with a literature review.

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Background@#We evaluated the protective effects of melatonin against high-fat diet (HFD)-induced deterioration of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT). @*Methods@#Four-week-old male C57BL/6 mice were divided into control (chow diet group), HFD, and HFD + melatonin-administered groups. Mice were sacrificed after 14 weeks, and the right femur was extracted. The microskeletal structure of the femur was analyzed using SkyScan1173 (version 1.6). A 3-dimensional image was reconstructed using the Nrecon (version 1.7.0.4) program. @*Results@#Bone volume (BV) was significantly increased in the HFD group compared with that in the normal diet group, and that of the melatonin group also increased significantly compared with BV of the normal diet group (p<0.05). Percent BV/total volume [TV] and bone surface/BV were significantly higher in both the HFD and melatonin groups than in the normal diet group (p<0.05), and the melatonin group had the highest BV/total volume (TV). BMD was lower in the HFD than in the normal diet group and was the highest in the melatonin group. @*Conclusions@#This study shows that melatonin inhibited the deterioration of microarchitecture induced by a HFD. A better understanding of the protective effect of melatonin on bone microarchitecture and mechanisms could provide fracture prevention for people who are obese.

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Background/Aims@#Lactase deficiency, which has many similarities with small intestinal bacterial overgrowth (SIBO), causes various gastrointestinal symptoms. We estimate the prevalence of SIBO in patients with intestinal symptoms from dairy products and investigate the association between lactase deficiency (LD) and SIBO. @*Methods@#This prospective study included patients with functional intestinal symptoms from dairy product indigestion. A questionnaire on gastrointestinal symptoms, a hydrogen (H 2 )-methane glucose breath test (GBT) for SIBO, and lactose intolerance quick test (LQT) for LD using upper gastrointestinal endoscopy were performed. @*Results@#A total of 88 patients, 29 (33.0%) with severe and 36 (40.9%) with mild LD were included. Sixteen patients (18.2%) were GBT positive. Patients with LQT negativity indicating severe LD showed a higher positivity to GBT or GBT (H 2 ) than the historic controls (27.6% vs 6.7%, P = 0.032). There was no difference in the items on the symptom questionnaire according to the presence of LD or SIBO, except for higher symptom scores for urgency in GBT-positive patients. There were more LQT-negative patients in the GBT (H 2 )-positive group than in the other groups (27.6% vs 10.2%, P = 0.036). Moreover, only GBT (H 2 )-positivity was significantly associated with a higher risk of LQT negativity in multivariate analysis (OR, 4.19; P = 0.029). @*Conclusions@#SIBO producing H 2is common in patients with severe LD suspected lactose intolerance. SIBO may be a new therapeutic target for managing intestinal symptoms in patients with lactose intolerance.

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Background/Aims@#Small intestinal bacterial overgrowth (SIBO) is expected in children and adolescents with functional abdominal pain disorders (FAPDs). This study is conducted to estimate the prevalence of SIBO and to investigate the role of SIBO in children and adolescents with FAPDs. @*Methods@#This prospective study enrolled children with FAPDs fulfilling the Rome IV criteria. A hydrogen-methane glucose breath test was used to diagnose SIBO. A survey of bowel symptoms using questionnaires, birth history, types of feeding, and the presence of allergy was conducted. @*Results@#Sixty-eight children and adolescents (range, 6-17 years; median, 12.5 years) were enrolled. SIBO was detected in 14 patients (20.6%). Age (≥ 12 years) (P < 0.003) and loose stool (P = 0.048) were significantly more common in children with SIBO than in children without SIBO. However, the history of allergies (P = 0.031) was less common in children with SIBO than those without SIBO. No significant differences were observed in other demographic findings. In multivariate analysis, age (≥ 12 years) was the independent factor predicting SIBO in children with FAPDs. @*Conclusions@#SIBO is not uncommon in children and adolescents with FAPDs. Among children aged above 12 years and diagnosed with FAPDs, SIBO is a suspected clinical target for treatment to relieve intestinal symptoms. A further study to investigate the association between intestinal bacteria and history of allergy is needed.

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Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was noted to cause coronavirus disease 2019 (COVID-19) in 2019, there have been many trials to develop vaccines against the virus. Messenger ribonucleic acid (mRNA) vaccine as a type of the vaccine has been developed and commercialized rapidly, but there was not enough time to verify the long-term safety. An 82-year-old female patient was admitted to the emergency room with dyspnea accompanied by stridor three days after the 3rd COVID-19 mRNA vaccination (Comirnaty, Pfizer-BioNTech, USA). The patient was diagnosed with bilateral vocal fold paralysis (VFP) by laryngoscope. Respiratory distress was improved after the intubation and tracheostomy in sequence. The brain, chest, and neck imaging tests, serological tests, cardiological analysis, and immunological tests were performed to evaluate the cause of bilateral VFP. However, no definite cause was found except for the precedent vaccination.Because bilateral VFP can lead to a fatal condition, a quick evaluation is necessary in consideration of VFP when dyspnea with stridor occurs after vaccination.

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Choristoma, also known as a hairy polyp, is a rare benign mass that commonly occurs in the nasopharynx and oropharynx in the head and neck region. It is usually diagnosed in children and has rarely been reported in adults. In this study, we describe a nasopharyngeal choristoma in an adult man. The mass was located at the lateral nasopharyngeal wall, and the patient expressed intermittent nasal stuffiness and ear fullness. The mass was successfully removed using an endoscopic approach. Since nasopharyngeal choristoma in adults is rare, it is important to distinguish it from other benign tumors located in the nasopharynx or nasal cavity. In this report, we describe the radiologic characteristics of nasopharyngeal choristoma and summarize the importance of differential diagnosis from other benign masses.

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Background/Aims@#Helicobacter pylori eradication may prevent the recurrence of gastric epithelial neoplasia after endoscopic treatment. However, H. pylori eradication therapy is unlikely to prevent gastric cancer. This study determined the longterm results and clinical outcomes of patients with gastric epithelial neoplasia based on H. pylori infection status and microsatellite stability (MSS). @*Methods@#Patients diagnosed with gastric epithelial neoplasia who underwent an endoscopic mucosal resection or submucosal dissection between 2004 and 2010 were included in this retrospective study. During the follow-up period (range, 4 to 14 years), disease recurrence was monitored, and tissue examinations were conducted for seven sets of microsatellite loci initially linked to the tumour suppressor gene locus. When H. pylori infection was identified, patients underwent eradication therapy. @*Results@#The patients (n = 120) were divided into three groups: H. pylori-negative with MSS, H. pylori-positive with MSS, and microsatellite instability (MSI). After H. pylori eradication, the rate of metachronous recurrence was significantly different in the MSI (28.2%) and MSS groups (3.7%, p < 0.01). The mean duration of recurrence was 77 months (range, 24 to 139) in the MSI group. There was no recurrence after eradication therapy in patients who were positive for H. pylori in the MSS group. @*Conclusion@#H. pylori eradication could help prevent gastric cancer recurrence in patients with stable microsatellite loci. Careful, long-term monitoring is required in patients with unstable microsatellite loci.

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Background/Aims@#This study aimed to investigate the possibility of in situ diagnosis of Helicobacter pylori (H. pylori) infection during endoscopic examination. The predictive infection value was estimated using the endoscopic Kyoto scoring system (EKSS), and specific endoscopic findings were evaluated for diagnosing H. pylori infection in H. pylori naïve patients and those with a eradication history. @*Materials and Methods@#A total of 836 patients with H. pylori infection were analyzed. The state of the infection was predicted using the EKSS and specific endoscopic findings. @*Results@#Patients were classified into two groups: the H. pylori naïve group and the group with a the bacterial eradication history. The area under the curve (AUC) on receiver operating characteristics analysis was 0.90 for EKSS in H. pylori naïve patients and 0.83 for the other group patients. For patients with open type atrophy and/or intestinal metaplasia, EKSS (24.4%; 95% CI, 12.4~0.3%) and regular arrangement of collecting venules (RAC) (46.3%; 95% CI, 30.7~62.9%) showed low specificities. Mucosal swelling (66.2%; 95% CI, 62.5~69.7%) and sticky mucus (80.5%; 95% CI, 74.8~85.2%) presented relatively high positive predictive values for H. pylori infection in naïve patients, whereas reflux esophagitis, hematin, red streak, and duodenitis exhibited high negative predictive values in patients with a H. pylori eradication history (98.0%; 95% CI, 96.4~99.1%). @*Conclusions@#EKSS and RAC are excellent tools for predicting H. pylori infection. However, they have a limited role in patients with open type atrophy and/or intestinal metaplasia. Specific endoscopic findings could help predict the infection state.

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Background/Aims@#The treatment of gastric cancer remains unsatisfactory. We aimed to investigate the prognostic value of immunohistochemical staining in gastric cancer. @*Methods@#We analyzed 505 (279 early staged, 226 advanced-staged) gastric cancer tissues from patients who underwent radical gastric resection between January 2014 and December 2016. Available surgical specimens immunohistochemically stained for p53, epidermal growth factor receptor (EGFR), human EGFR 2 (HER-2), E-cadherin, and Ki-67 were reviewed. We evaluated the association between positivity to various biomarkers and disease recurrence, disease-free survival, lymph node metastasis, and microscopic lymphovascular invasion. @*Results@#The median follow-up duration was 32.5 months (range, 7 to 70). Advanced gastric cancer cases showed high Ki-67 expression; other cases showed unremarkable expression. Concerning disease recurrence, lymphatic invasion, and disease-free interval, all biomarkers had no prognostic effects. HER-2-positive stage I gastric cancer tended to occur in old patients and in the upper one-third of the stomach (p = 0.01). HER-2 positivity was significantly correlated with disease recurrence (p = 0.01), lymphatic invasion (p = 0.03), and vascular invasion (p = 0.03) in stage I cases. @*Conclusions@#Only HER-2 was associated with the recurrence of stage I gastric cancer. HER-2-positive stage I gastric cancer requires additional therapy despite curative resection.

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Gastric cancer is one of the leading causes of cancer-related deaths worldwide. The increased expression of cyclooxygenase (COX)-2 has been implicated in the development and progression of gastric cancers. A number of recent studies have been published evaluating the chemopreventive effect of aspirin and non steroidal anti inflammatory drungs (NSAIDs) against gastric cancer. Aspirin and NSAIDs use may reduce the risk of gastric cancer incidence and death, whereas other studies have reported contradictory results. Therefore, further study should be needed to clarify the role of aspirin and NSAIDs in the chemoprevention of gastric cancer.

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A 49-year-old woman was referred to our hospital for further treatment due to the suspicion of a submucosal tumor in a routine screening colonoscopy. On colonoscopy, a 1-cm sized subepithelial mass with normal overlying mucosa in the hepatic flexure was found. Endoscopic ultrasonography (EUS) showed a homogenous hypoechoic lesion arising from the second and third layer. We were unable to make a final diagnosis because the lesion showed a small tumor with atypical macroscopic morphology including EUS findings. Therefore, endoscopic submucosal dissection was performed for the diagnostic treatment of the tumor. Submucosal dissection was performed just above the muscle layer, and the tumor was removed completely and reliably without any acute complications such as perforation. Based on histopathological findings, we diagnosed a benign, calcifying fibrous tumor (CFT). The present case is the first report of successful endoscopic diagnosis and treatment of colonic CFT mimicking a submucosal tumor.

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Background/Aims@#Local and systemic factors, such as diabetes, obesity, and hyperlipidemia, are considered risk factors for the recurrence of choledocholithiasis after successful endoscopic clearance. Local factors include the presence of bile sludge, common bile duct (CBD) diameter, and CBD angulation. Among them, it is unclear if acute CBD angulation is preferable to the recurrence of a CBD stone. @*Methods@#PubMed, EMBASE, CINAHL, the Cochrane Library databases, and google website were searched for randomized controlled trials reported in English and undertaken until August 2019. Meta‐analysis was performed on all randomized controlled trials for the recurrence of CBD stones between the patients with acute CBD angulation. @*Results@#Eight randomized trials (1,776 patients) were identified, and the total recurrent rate of CBD stones was 18.8% (334/1,776). A CBD angle ≤145° was significantly associated with an increased risk of recurrent CBD stone (OR=2.65, p<0.01). In two prospective studies, acute CBD angulation was not proven to be associated with a recurrence (p=0.39). @*Conclusions@#Approximately 20% of patients with a CBD stone showed recurrence after the complete clearance of the CBD stone, and a CBD angle ≤145° could increase the risk of recurrence. Overall, a large-scale prospective study should be necessary.

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Background/Aims@#It is still unknown whether cytochrome P450 (CYP) 2C19 polymorphisms influence Helicobacter pylori (H. pylori) eradication, especially in eastern Asia. We aimed to evaluate how changes in proton pump inhibitor (PPI) strategies could be used to overcome the effects of CYP2C19 polymorphism on H. pylori eradication rate when it is used as the second-line regimen after the failure of standard triple therapy. @*Materials and Methods@#We performed a retrospective observation study of 675 patients in whom standard triple therapy for H. pylori infection was not effective between January 2009 to December 2018. All patients underwent a classic bismuth-containing quadruple therapy (10 to 14-day regimen), and their eradication rates were evaluated for several years. We compared the eradication rates in patients with or without the second-line PPI switch. Further, we assessed differences in eradication rates with or without the strategy using esomeprazole and rabeprazole, which are not influenced significantly by CYP2C19 genetic polymorphism. @*Results@#The eradication rate was 81.0% in individuals who received the second-line PPI switch, but it was 74.8% without switching (P=0.14). In the strategy using esomeprazole and rabeprazole, the eradication rate was 84.6%, compared to 76.5% in the control group (P=0.03). Finally, in the group of patients who switched to rabeprazole, the eradication rates were 85.6%, compared to 77.6% in the group who switched to pantoprazole (P=0.05). @*Conclusions@#Switching to PPI, which is not influenced by CYP2C19 genetic polymorphism, increases the efficiency of eradication after the failure of standard triple therapy.

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Background/Aims@#This study examined the clinical features and prognosis of patients with mucinous gastric carcinoma (MGC), non-mucinous gastric carcinoma (NMGC), and signet ring cell gastric carcinoma (SRC). @*Methods@#A retrospective cohort study was performed, enrolling 65 patients with MGC from January 2007 to December 2016.During the same period, 1,814 patients with histologically proven gastric cancers underwent curative or palliative operations. One hundred and ninety-five NMGC patients were selected as the 1:3 age- and sex-matched control groups. In addition, 200 SRC patients were identified. This study evaluated the demographic features of the patients, pathologic features of the tumor, and the predictive factors, such as the recurrence-free survival and overall survival. @*Results@#The recurrence rates were significantly high in MGC than in NMGC or SRC (both p<0.01). The proportion of early gastric cancer was lower in the MGC group than in the other groups (p<0.01). In addition, metastatic lymph nodes were found more frequently in the MGC group (p<0.01), and the proportion of initial pT4, M1 stage, was highest in the MGC group. The recurrence-free survival and overall survival in the MGC group were significantly lower than those in the NMGC or SRC. Subgroup analysis showed that patients with the same American Joint Committee on Cancer (AJCC) stage of each cancer group showed a similar prognosis. @*Conclusions@#MGC frequently presents an advanced stage with an unfavorable prognosis compared to NMGC or SRC. On the other hand, MGC of the same AJCC stage had a similar prognosis to NMGC and SRC.

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Gastric cancer is one of the leading causes of cancer-related deaths worldwide. The increased expression of cyclooxygenase (COX)-2 has been implicated in the development and progression of gastric cancers. A number of recent studies have been published evaluating the chemopreventive effect of aspirin and non steroidal anti inflammatory drungs (NSAIDs) against gastric cancer. Aspirin and NSAIDs use may reduce the risk of gastric cancer incidence and death, whereas other studies have reported contradictory results. Therefore, further study should be needed to clarify the role of aspirin and NSAIDs in the chemoprevention of gastric cancer.

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Background/Aims@#This study examined the clinical features and prognosis of patients with mucinous gastric carcinoma (MGC), non-mucinous gastric carcinoma (NMGC), and signet ring cell gastric carcinoma (SRC). @*Methods@#A retrospective cohort study was performed, enrolling 65 patients with MGC from January 2007 to December 2016.During the same period, 1,814 patients with histologically proven gastric cancers underwent curative or palliative operations. One hundred and ninety-five NMGC patients were selected as the 1:3 age- and sex-matched control groups. In addition, 200 SRC patients were identified. This study evaluated the demographic features of the patients, pathologic features of the tumor, and the predictive factors, such as the recurrence-free survival and overall survival. @*Results@#The recurrence rates were significantly high in MGC than in NMGC or SRC (both p<0.01). The proportion of early gastric cancer was lower in the MGC group than in the other groups (p<0.01). In addition, metastatic lymph nodes were found more frequently in the MGC group (p<0.01), and the proportion of initial pT4, M1 stage, was highest in the MGC group. The recurrence-free survival and overall survival in the MGC group were significantly lower than those in the NMGC or SRC. Subgroup analysis showed that patients with the same American Joint Committee on Cancer (AJCC) stage of each cancer group showed a similar prognosis. @*Conclusions@#MGC frequently presents an advanced stage with an unfavorable prognosis compared to NMGC or SRC. On the other hand, MGC of the same AJCC stage had a similar prognosis to NMGC and SRC.

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Addressing the increasing antibiotic resistance, including clarithromycin resistance, which affects Helicobacter pylori (H. pylori) eradication therapy, is a challenge for clinicians. Antibiotic resistance is the main reason for H. pylori eradication failure and the resistance rate for clarithromycin may drastically increase, up to 38.5%, due to 23S ribosomal RNA point mutations. Therefore, the standard triple regimen is no longer suitable as the first-line treatment in most regions. However, there is a growing interest in personalized care for patients. Increased eradication rates of tailored therapy based on antibiotic susceptibility have been reported using nucleic acid-based techniques for clarithromycin resistance with a focus on the first-line eradication therapy of H. pylori infection. Herein, we discuss the eradication therapy for H. pylori, with a diagnostic test and appropriate treatment for clarithromycin resistance.

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BACKGROUND/AIMS: Fecal calprotectin (FC) is known to correlate with disease activity and can be used as a predictor for relapse or treatment response in inflammatory bowel disease (IBD). We evaluated the usefulness of FC as a biomarker for disease activity in patients with IBD using both enzyme-linked immunosorbent assay (ELISA) and a quantitative point-of-care test (QPOCT). METHODS: Fecal samples and medical records were collected from consecutive patients with IBD. FC levels were measured by both ELISA and QPOCT and patient medical records were reviewed for clinical, laboratory, and endoscopic data. RESULTS: Ninety-three patients with IBD were enrolled, 55 with ulcerative colitis (UC) and 38 with Crohn's disease (CD). The mean FC-ELISA levels were 906.3 ± 1,484.9 μg/g in UC and 1,054.1 ± 1,252.5 μg/g in CD. There was a strong correlation between FC-ELISA level and clinical activity indices (p < 0.05). FC-ELISA level was significantly lower in patients with mucosal healing (MH) compared to those without MH in UC (85.5 ± 55.6 μg/g vs. 1,503.7 ± 2,129.9 μg/g, p = 0.005). The results from the QPOCT corresponded well to those from ELISA. A cutoff value of 201.3 μg/g for FC-ELISA and 150.5 μg/g for FC-QPOCT predicted endoscopic inflammation (Mayo endoscopic subscore ≥ 1) in UC with a sensitivity of 81.8% and 85.8%, respectively, and a specificity of 100% for both. CONCLUSIONS: FC was strongly associated with disease activity indices, serologic markers, and endoscopic activity in patients with IBD. QPOCT can be used more conveniently than ELISA to assess FC in clinical practice.

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