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Gastric subepithelial lesions (SELs) are often detected incidentally during upper gastrointestinal endoscopy. Although most SELs are benign, endoscopic differentiation between malignant and benign lesions is important. Endoscopy is useful to determine the location, color, consistency, mobility, surface characteristics, and approximate size of gastric SELs. EUS can distinguish between intraluminal lesions and extraluminal compression and confirm the exact size, layer of origin, echogenicity, and homogeneity of SELs. Accurate understanding of the endoscopic and EUS features of gastric SELs is useful to effectively design an appropriate management plan and thereby minimize the rate of unnecessary surveillance or overtreatment.
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Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common type of extranodal non-Hodgkin lymphoma. Endoscopic findings are nonspecific and variable; therefore, differentiation of this malignancy from early gastric cancer is challenging during endoscopy. Although an endoscopic biopsy is the gold standard for diagnosis, a biopsy may not conclusively establish the diagnosis in all cases. Diagnostic confirmation requires interpretation of the biopsy specimen findings by an experienced histopathologist, and an additional immunoglobulin heavy chain (IgH) rearrangement test may aid with accurate diagnosis. We present a case of gastric MALT lymphoma that histopathologically mimicked signet ring cell carcinoma (SRCC) on evaluation of repeat endoscopic biopsies. Following endoscopic submucosal dissection (ESD), we confirmed the final diagnosis of gastric MALT lymphoma based on histopathological findings of prominent lymphoid infiltrates accompanied by lymphoepithelial lesions and results of the monoclonal IgH rearrangement test. Notably, a few carcinoma-like signet ring cells (SRCs) in the specimen were attributed to a reactive change. Clinicians should be mindful of possible SRCs in gastric MALT lymphoma specimens to avoid misdiagnosis of SRCC in patients with gastric MALT lymphoma. Confirmatory ESD may be useful for accurate diagnosis and appropriate management of such lesions.
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Foreign body ingestion is commonly seen in children. However, occasionally it may also be seen among adults and is often associated with intellectual disability, psychiatric disorders, and alcoholism. Ingestion of a magnetic foreign body may cause complications such as gastrointestinal tract perforation, wherein emergency endoscopic removal of the foreign body is generally required. Here, we report a rare case of a 59-year-old male with an intellectual disability and psychiatric disorder in whom metallic objects in the stomach cavity were accidentally discovered during abdominal CT. Esophagogastroduodenoscopy revealed several metallic objects attached to two magnets, which had been ingested several years before and had remained in the stomach cavity. The magnets and metallic objects were safely removed endoscopically using rat-tooth forceps without complications.
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The fundic gland type (GA-FG) of gastric adenocarcinoma is a rare variant of gastric cancer recently included in the 5th edition of the World Health Organization’s classification of digestive system tumors. Five patients with GA-FG underwent an endoscopic resection at our institution. None of the patients had a Helicobacter pylori infection. Four lesions were located in the upper third of the stomach, and one was in the lower third. Three lesions had a IIa shape, while two resembled a subepithelial tumor. An endoscopic submucosal dissection was performed in four patients and endoscopic mucosal resection in one. Tumor cells were composed of well-differentiated columnar cells mimicking fundic gland cells, and the median tumor size was 10 mm. Three lesions exhibited submucosal invasion. No lymphatic or venous invasion was observed. Tumor cells were positive for MUC6 in all five cases; one case was focally positive for MUC5AC. No recurrence was observed during a median follow-up period of 13 months. An endoscopic resection can be a safe treatment modality for GA-FG, considering its small size and low risk of recurrence or metastasis. (Korean J Gastroenterol 2023;81:259-264)
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Esophageal subepithelial tumors (SETs) are commonly encountered during screening endoscopy, and leiomyomas are the most common SET of the esophagus. Almost all patients with esophageal leiomyomas are asymptomatic; however, some present with dysphagia, depending on the size of the tumor and the extent to which it encroaches on the lumen. The typical endosonographic features of esophageal leiomyomas include well-demarcated, homogeneously hypoechoic lesions with echogenicity similar to that of the surrounding proper muscle layer, but without cystic changes. Histopathologically, esophageal leiomyomas do not undergo cystic or myxoid degeneration. This report presents a case involving a 65-year-old man with a symptomatic esophageal SET and endosonographic features indicative of malignant neoplasms, who was diagnosed with esophageal leiomyoma with cystic and myxoid degeneration following surgical resection.
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Background/Aims@#Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008. @*Methods@#This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed. @*Results@#The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p<0.001), aspiration pneumonia (aHR, 3.92; 95% CI, 2.38 to 6.48; p<0.001), and mortality (aHR, 1.68; 95% CI, 1.44 to 1.94; p<0.001). Esophageal cancer carried the highest mortality risk (aHR, 8.82; 95% CI, 2.35 to 33.16; p=0.001), while pneumonia had the highest non-cancer mortality risk (aHR, 2.28; 95% CI, 1.31 to 3.96; p=0.004). @*Conclusions@#In this nationwide study, achalasia was associated with increased risk of mortality.Esophageal cancer and pneumonia were the most common comorbidities and the major causes of death in patients with achalasia.
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Background@#Patients with esophageal squamous cell carcinoma (ESCC) have a poor prognosis and there are no effective clinical biomarkers. Recently, stable microRNAs detected in the blood have been suggested as potential biomarkers in various cancers. Therefore, we investigated whether plasma microRNAs could be feasible biomarkers for ESCC. @*Methods@#Peripheral blood samples were obtained from 16 healthy volunteers and 66 ESCC patients before treatment between May 2016 and April 2021. Plasma miR-18b, miR-21, miR-31, and miR-375 expression levels were measured using reverse transcription-quantitative polymerase chain reaction. @*Results@#Compared with those in healthy controls, the expression levels of plasma miR-21 were significantly higher (P = 0.022) and those of plasma miR-31 and miR-375 were significantly lower in ESCC patients (both P < 0.001). Plasma miR-18b expression levels increased in ESCC patients, but the difference was not significant (P = 0.164). The sensitivities and specificities of miR-21, miR-31, and miR-375 for differentiating ESCC patients from healthy controls were 87.5% and 61.9%, 87.5% and 98.4%, and 87.5% and 100%, respectively. There was no difference in expression levels of plasma miR-21, miR-31, and miR-375 according to clinicopathological characteristics of sex, age, tumor size and location, histologic grade, and tumor-node-metastasis stage. @*Conclusion@#Our study demonstrated that plasma miR-21, miR-31, and miR-375 could be potential biomarkers for the diagnosis of ESCC. Particularly, plasma miR-31 and miR-375 showed high sensitivity and specificity for differentiating ESCC patients from healthy controls.
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Purpose@#While the incidence of Barrett’s neoplasia has been increasing in Western countries, the disease remains rare in Asian countries. Therefore, very few studies have investigated the endoscopic treatment for Barrett’s neoplasia in Korea. Endoscopic submucosal dissection (ESD) enables en bloc and complete resection of gastrointestinal neoplastic lesions. This study aimed to evaluate the therapeutic outcomes of ESD for Barrett’s neoplasia in a single center in Korea and to examine the predictive factors for incomplete resection. @*Materials and Methods@#We conducted a retrospective observational study of 18 patients who underwent ESD for superficial Barrett’s neoplasia (dysplasia and early cancer) between January 2010 and December 2019 at Pusan National University Hospital. The therapeutic outcomes of ESD and procedure-related complications were analyzed. @*Results@#En bloc resection, complete resection, and curative resection were performed in 94%, 72%, and 61% of patients, respectively. Histopathology (submucosal or deeper invasion of the tumor) was a significant predictive factor for incomplete resection (P=0.047). Procedure-related bleeding and stenosis were not observed, whereas perforation occurred in one case. During the median follow-up period of 12 months (range, 6–74 months), local recurrence occurred in 2 patients with incomplete resection, one patient underwent repeat ESD, and the other patient received concurrent chemoradiotherapy. The 3-year overall and disease-specific survival rates were 73% and 93%, respectively. @*Conclusions@#ESD seems to be an effective and safe treatment for superficial Barrett’s neoplasia in Korea. Nevertheless, the suitability of ESD for Barrett’s cancer cases should be determined considering the high risk of deep submucosal invasion.
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Epstein-Barr virus-associated gastric carcinoma (EBVaGC) comprises approximately 10% of all gastric cancers and is now defined as one of the four subtypes of gastric cancer according to the molecular classification proposed by the Cancer Genome Atlas project. EBVaGC has characteristic genetic profiles that harbor a DNA methylation phenotype, frequent mutations in PIK3CA and ARID1A, and amplification of JAK2 and programmed death-ligand (PD-L)1/PD-L2. Therefore, EBVaGC shows several distinct clinicopathological features, including a male predominance, proximal stomach location, gastric carcinoma with lymphoid stroma histology, low risk of lymph node metastasis, and favorable prognosis. In clinical practice, patients with early EBVaGC might be good candidates for endoscopic resection or minimally invasive surgery since the rate of lymph node metastasis is very low, even with deep submucosal invasion. Furthermore, in the case of advanced EBVaGC, the applicability of immunotherapy has been investigated based on its increased expression of PD-L1 and high immunogenicity. In conclusion, EBV can serve as a biomarker in gastric cancer, and further identification of other molecular characteristics of EBVaGC is essential for new potential therapeutic targets.
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Background/Aims@#Esophageal high-resolution manometry (HRM) enables the comprehensive evaluation of the esophageal motor function. However, protocols are not uniform and clinical practices vary widely among institutions. This study aims to understand the current HRM practice in Korea. @*Methods@#The survey was sent via email through the Korean Society of Neurogastroenterology and Motility. The questions covered descriptive information, preparation, techniques, analysis, and reporting of esophageal HRM. @*Results@#The survey was completed in 32 (74.4%) out of 43 centers, including 24 tertiary and 8 secondary referral centers. Of the 32 centers, 25 (78.1%) performed HRM in a sitting position, while 7 centers (21.9%) reported performing HRM in a supine position. All the centers utilized single wet swallows as a standard, but the volume, frequency, and interval between swallows varied widely. Sixteen centers (50.0%) applied adjunctive tests, including multiple rapid swallows (n = 16) and rapid drink challenges (n = 9). Parameters assessed and documented in the report were similar. In addition to the assessment of the esophagogastric junction and esophageal body, 27 centers (84.8%) and 18 centers (56.3%) included measurements for the upper esophageal sphincter and the pharynx, respectively, in the HRM protocol. @*Conclusions@#We found a variation in the available HRM practice among centers, even though they broadly agreed in the data analysis. Efforts are needed to develop a standardized protocol for HRM measurement.
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Background/Aims@#Achalasia is an esophageal motor disorder that leads to functional esophageal obstruction. Food stasis and bacterial fermentation can predispose an individual to esophageal mucosal inflammation, causing multifocal dysplasia and increasing the risk of developing esophageal squamous cell carcinoma. We aimed to evaluate esophageal mucosal alterations in achalasia patients and determine clinical factors associated with the histopathological findings. @*Methods@#From 2009 to 2013, we obtained endoscopic biopsies from the lower and middle esophagus of 22 patients with achalasia and 17 controls. Patients’ clinical data and histological severity of esophagitis were retrospectively analyzed. Additionally, immunohistochemical staining for CD3, CD20, Ki-67, and p53 was conducted. @*Results@#The median age of achalasia patients was 49.5 years (range, 27 to 82 years), and there were nine males (40.9%). The median symptom duration was 5.8 years (range, 1 to 33.5 years), and 10 patients (45%) underwent previous treatment (nine, balloon dilation; one, botulinum toxin injection). Achalasia patients had significantly more severe esophagitis than did controls (p=0.001, lower esophagus; p=0.008, middle esophagus), and the number of CD3-positive lymphocytes exceeded that of CD20-positive lymphocytes (p<0.001). Achalasia patients also had a higher esophageal Ki-67 proliferation index (p=0.048). Although statistically nonsignificant, p53 expression was only observed in achalasia patients. There was no association between the histological severity of esophagitis and other clinicopathological findings. @*Conclusions@#Achalasia patients showed significantly severe histological esophagitis and a high Ki-67 proliferation index, indicating an increased risk of neoplastic progression. Therefore, careful endoscopic inspection is necessary for the early detection of superficial neoplasia in these patients.
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Background/Aims@#This study examined the long-term outcomes of undifferentiated-type early gastric cancer (UD EGC) with positive horizontal margins (HMs) after endoscopic resection (ER) and compared them between additional surgery and nonsurgical management. @*Methods@#From 2005 to 2015, a total of 1,124 patients with UD EGC underwent ER at 18 tertiary hospitals in Korea. Of them, 92 patients with positive HMs as the only noncurative factor (n=25) or with both positive HMs and tumor size >2 cm (n=67) were included. These patients underwent additional surgery (n=40), underwent additional endoscopic treatment (n=6), or were followed up without further treatment (n=46). @*Results@#No lymph node (LN) metastasis was found in patients who underwent additional surgery. During a median follow-up of 57.7 months (interquartile range, 27.6 to 68.8 months), no LN or distant metastases or gastric cancer-related deaths occurred in the overall cohort. At baseline, the residual cancer rate was 57.8% (26/45) after additional surgery or ER. The 5-year local recurrence rate was 33.6% among patients who were followed up without additional treatment. The 5-year overall survival rates were 95.0% and 87.8% after additional surgery and nonsurgical management (endoscopic treatment or close follow-up), respectively (log-rank p=0.224). In the multivariate Cox regression analysis, nonsurgical management was not associated with an increased risk of mortality. @*Conclusions@#UD EGC with positive HMs after ER may have favorable long-term outcomes and a very low risk of LN metastasis. Nonsurgical management may be suggested as an alternative, particularly for patients with old age or chronic illness.
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Background/Aims@#Unlike other gastrointestinal tract cancers, there are relatively few reports on the clinical significance of circulating tumor cells (CTCs) and TWIST, a marker of epithelial-mesenchymal transition, in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the clinical significance of TWIST expression in CTCs in patients with ESCC. @*Methods@#Peripheral blood samples for CTC analyses were prospectively obtained from 52 patients with ESCC prior to treatment between September 2017 and September 2019. CTCs were detected using a centrifugal microfluidic system based on a fluid-assisted separation technique, and CTCs positive for TWIST on immunostaining were defined as TWIST (+) CTCs. @*Results@#Of the 52 patients with ESCC, CTCs and TWIST (+) CTCs were detected in 44 patients (84.6%) and 39 patients (75.0%), respectively. The CTC and TWIST (+) CTC counts were significantly higher in patients aged >65 years and those who had a large tumor (>3 cm) thanin those aged ≤65 years and those who had a small tumor (≤3 cm), respectively. There were nodifferences in CTC and TWIST (+) CTC counts according to tumor location, histologic grade, or TNM stage. TWIST (+) CTCs were significantly associated with histologic grade; a proportion of TWIST (+) CTCs ≥0.5 was significantly associated with advanced histologic grade. Other clini-copathologic characteristics such as sex, age, tumor location, tumor size, and TNM stages were not significantly associated with TWIST (+) CTCs. @*Conclusions@#Our study showed that TWIST (+) CTCs were frequently detected in patients with ESCC, and a high proportion of TWIST (+) CTCs was associated with poor differentiation
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Epstein-Barr virus-associated gastric carcinoma (EBVaGC) comprises approximately 10% of all gastric cancers and is now defined as one of the four subtypes of gastric cancer according to the molecular classification proposed by the Cancer Genome Atlas project. EBVaGC has characteristic genetic profiles that harbor a DNA methylation phenotype, frequent mutations in PIK3CA and ARID1A, and amplification of JAK2 and programmed death-ligand (PD-L)1/PD-L2. Therefore, EBVaGC shows several distinct clinicopathological features, including a male predominance, proximal stomach location, gastric carcinoma with lymphoid stroma histology, low risk of lymph node metastasis, and favorable prognosis. In clinical practice, patients with early EBVaGC might be good candidates for endoscopic resection or minimally invasive surgery since the rate of lymph node metastasis is very low, even with deep submucosal invasion. Furthermore, in the case of advanced EBVaGC, the applicability of immunotherapy has been investigated based on its increased expression of PD-L1 and high immunogenicity. In conclusion, EBV can serve as a biomarker in gastric cancer, and further identification of other molecular characteristics of EBVaGC is essential for new potential therapeutic targets.
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Background/Aims@#Esophageal high-resolution manometry (HRM) enables the comprehensive evaluation of the esophageal motor function. However, protocols are not uniform and clinical practices vary widely among institutions. This study aims to understand the current HRM practice in Korea. @*Methods@#The survey was sent via email through the Korean Society of Neurogastroenterology and Motility. The questions covered descriptive information, preparation, techniques, analysis, and reporting of esophageal HRM. @*Results@#The survey was completed in 32 (74.4%) out of 43 centers, including 24 tertiary and 8 secondary referral centers. Of the 32 centers, 25 (78.1%) performed HRM in a sitting position, while 7 centers (21.9%) reported performing HRM in a supine position. All the centers utilized single wet swallows as a standard, but the volume, frequency, and interval between swallows varied widely. Sixteen centers (50.0%) applied adjunctive tests, including multiple rapid swallows (n = 16) and rapid drink challenges (n = 9). Parameters assessed and documented in the report were similar. In addition to the assessment of the esophagogastric junction and esophageal body, 27 centers (84.8%) and 18 centers (56.3%) included measurements for the upper esophageal sphincter and the pharynx, respectively, in the HRM protocol. @*Conclusions@#We found a variation in the available HRM practice among centers, even though they broadly agreed in the data analysis. Efforts are needed to develop a standardized protocol for HRM measurement.
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Background/Aims@#Achalasia is an esophageal motor disorder that leads to functional esophageal obstruction. Food stasis and bacterial fermentation can predispose an individual to esophageal mucosal inflammation, causing multifocal dysplasia and increasing the risk of developing esophageal squamous cell carcinoma. We aimed to evaluate esophageal mucosal alterations in achalasia patients and determine clinical factors associated with the histopathological findings. @*Methods@#From 2009 to 2013, we obtained endoscopic biopsies from the lower and middle esophagus of 22 patients with achalasia and 17 controls. Patients’ clinical data and histological severity of esophagitis were retrospectively analyzed. Additionally, immunohistochemical staining for CD3, CD20, Ki-67, and p53 was conducted. @*Results@#The median age of achalasia patients was 49.5 years (range, 27 to 82 years), and there were nine males (40.9%). The median symptom duration was 5.8 years (range, 1 to 33.5 years), and 10 patients (45%) underwent previous treatment (nine, balloon dilation; one, botulinum toxin injection). Achalasia patients had significantly more severe esophagitis than did controls (p=0.001, lower esophagus; p=0.008, middle esophagus), and the number of CD3-positive lymphocytes exceeded that of CD20-positive lymphocytes (p<0.001). Achalasia patients also had a higher esophageal Ki-67 proliferation index (p=0.048). Although statistically nonsignificant, p53 expression was only observed in achalasia patients. There was no association between the histological severity of esophagitis and other clinicopathological findings. @*Conclusions@#Achalasia patients showed significantly severe histological esophagitis and a high Ki-67 proliferation index, indicating an increased risk of neoplastic progression. Therefore, careful endoscopic inspection is necessary for the early detection of superficial neoplasia in these patients.
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Background/Aims@#This study examined the long-term outcomes of undifferentiated-type early gastric cancer (UD EGC) with positive horizontal margins (HMs) after endoscopic resection (ER) and compared them between additional surgery and nonsurgical management. @*Methods@#From 2005 to 2015, a total of 1,124 patients with UD EGC underwent ER at 18 tertiary hospitals in Korea. Of them, 92 patients with positive HMs as the only noncurative factor (n=25) or with both positive HMs and tumor size >2 cm (n=67) were included. These patients underwent additional surgery (n=40), underwent additional endoscopic treatment (n=6), or were followed up without further treatment (n=46). @*Results@#No lymph node (LN) metastasis was found in patients who underwent additional surgery. During a median follow-up of 57.7 months (interquartile range, 27.6 to 68.8 months), no LN or distant metastases or gastric cancer-related deaths occurred in the overall cohort. At baseline, the residual cancer rate was 57.8% (26/45) after additional surgery or ER. The 5-year local recurrence rate was 33.6% among patients who were followed up without additional treatment. The 5-year overall survival rates were 95.0% and 87.8% after additional surgery and nonsurgical management (endoscopic treatment or close follow-up), respectively (log-rank p=0.224). In the multivariate Cox regression analysis, nonsurgical management was not associated with an increased risk of mortality. @*Conclusions@#UD EGC with positive HMs after ER may have favorable long-term outcomes and a very low risk of LN metastasis. Nonsurgical management may be suggested as an alternative, particularly for patients with old age or chronic illness.
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Background/Aims@#Unlike other gastrointestinal tract cancers, there are relatively few reports on the clinical significance of circulating tumor cells (CTCs) and TWIST, a marker of epithelial-mesenchymal transition, in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the clinical significance of TWIST expression in CTCs in patients with ESCC. @*Methods@#Peripheral blood samples for CTC analyses were prospectively obtained from 52 patients with ESCC prior to treatment between September 2017 and September 2019. CTCs were detected using a centrifugal microfluidic system based on a fluid-assisted separation technique, and CTCs positive for TWIST on immunostaining were defined as TWIST (+) CTCs. @*Results@#Of the 52 patients with ESCC, CTCs and TWIST (+) CTCs were detected in 44 patients (84.6%) and 39 patients (75.0%), respectively. The CTC and TWIST (+) CTC counts were significantly higher in patients aged >65 years and those who had a large tumor (>3 cm) thanin those aged ≤65 years and those who had a small tumor (≤3 cm), respectively. There were nodifferences in CTC and TWIST (+) CTC counts according to tumor location, histologic grade, or TNM stage. TWIST (+) CTCs were significantly associated with histologic grade; a proportion of TWIST (+) CTCs ≥0.5 was significantly associated with advanced histologic grade. Other clini-copathologic characteristics such as sex, age, tumor location, tumor size, and TNM stages were not significantly associated with TWIST (+) CTCs. @*Conclusions@#Our study showed that TWIST (+) CTCs were frequently detected in patients with ESCC, and a high proportion of TWIST (+) CTCs was associated with poor differentiation
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Korean guidelines for nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer were previously developed in 2009 with the collaboration of the Korean College of Helico-bacter and Upper Gastrointestinal Research and Korean So-ciety of Gastroenterology. However, the previous guidelines were based mainly upon a review of the relevant literature and expert opinion. Therefore, the guidelines need to be revised. We organized a guideline Development Commit-tee for drug-related peptic ulcer under the auspices of the Korean College of Helicobacter and Upper Gastrointestinal Research in 2017 and developed nine statements, includ-ing four for NSAIDs, three for aspirin and other antiplatelet agents, and two for anticoagulants through a de novo process founded on evidence-based medicine that included a literature search and a meta-analysis, A consensus was reached through the application of the modified Delphi method. The primary target of these guidelines is adult pa-tients undergoing long-term treatment with NSAIDs, aspirin or other antiplatelet agents and anticoagulants. The revised guidelines reflect the expert consensus and is intended to assist clinicians in the management and prevention of druginduced peptic ulcer and associated conditions.
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Background/Aims@#Although acid suppressants are widely used for the prevention or treatment of drug-induced upper gastrointestinal bleeding (GIB), evidence regarding the prevention of anticoagulant-related GIB is scarce. The aim of this study was to evaluate the protective effect of acid suppressants against anticoagulant-related GIB. @*Methods@#A systematic review was conducted of studies that evaluated the protective effect of acid suppressants against anticoagulant-related GIB found in PubMed, the Cochrane library, Embase, and KoreaMed from the date of database inception to April 2018. Random effect model meta-analyses with sensitivity analyses were conducted. The methodological quality of each included publication was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies. Publication bias was assessed. @*Results@#In total, six nested case-control or cohort studies were identified and analyzed. Proton-pump inhibitors (PPI) had a protective effect against upper GIB in patients on dicumarinics (risk ratio [RR], 0.56; 95% confidence interval [CI], 0.38 to 0.83; I2, 0%); however, the histamine-2 receptor antagonist did not have the same effect (RR, 0.97; 95% CI, 0.52 to 1.81; I2, 0%). Acid suppressants did not have a protective effect against GIB in patients on dabigatran (hazard ratio, 0.78; 95% CI, 0.44 to 1.37; I2, 81.8%). @*Conclusions@#The protective effect of PPIs against dicumarinics-related upper GIB was clear, while there was no evidence supporting the protective effect of acid suppressants against dabigatran-related GIB. However, in the absence of randomized trials demonstrating a lack of bias, solid conclusions cannot be drawn.