Efficacy of fexuprazan compared with rebamipide in Korean patients with gastritis: A matching-adjusted indirect comparison.

BACKGROUND: Gastritis is one of the most frequently diagnosed diseases requiring medical treatment in South Korea. Fexuprazan, a novel potassium-competitive acid blocker, has been approved for treating gastritis and erosive esophagitis. Meanwhile, rebamipide is the most commonly used mucoprotective agent for acute and chronic gastritis in real-world settings in South Korea. However, there have been no studies comparing the efficacy of these two drugs yet. AIM: To compare the efficacy of fexuprazan with that of rebamipide for acute and chronic gastritis. METHODS: This was a matching-adjusted indirect comparison. Individual patient data from a phase III study of fexuprazan (10 mg BID) were compared with cumulative data from two matching studies of rebamipide (100 mg TID). Erosion improvement and healing rates were compared between two weeks of fexurapan, two weeks of rebamipide, and four weeks of rebamipide. The two main outcome variables were presented as percentages, and the risk differences (RD) and 95% confidence intervals (CI) were calculated for the relative treatment effects. RESULTS: In the primary analysis, the erosion improvement and healing rates after a two-week treatment with fexuprazan were 64.5% and 53.2%, respectively, while a two-week treatment with rebamipide resulted in erosion improvement and healing rates of 43.6% (RD: 21.0%; 95%CI: 9.6-32.3; P < 0.01) and 35.6% (RD: 17.6%; 95%CI: 6.1-29.2; P = 0.003), respectively. In the additional analysis, the erosion improvement and healing rates for the two-week fexuprazan treatment (64.2% and 51.2%, respectively) were similar to those obtained during a four-week treatment with rebamipide (60.6%; RD: 3.6%; 95%CI: -9.8, 17.0; P = 0.600 and 53.5%; RD: -2.3%; 95%CI: -16.1, 11.5; P = 0.744, respectively). CONCLUSION: The two-week fexuprazan treatment was superior to the two-week rebamipide treatment and similar to the four-week rebamipide treatment for patients with gastritis.

Randomized, Double-blind, Active-controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan compared to Esomeprazole in Erosive Esophagitis.

INTRODUCTION: Zastaprazan is a potent potassium-competitive acid blocker (P-CAB) developed to treat gastroesophageal reflux disease. This study aims to evaluate the efficacy and safety of zastaprazan compared to esomeprazole in patient with erosive esophagitis (EE). METHODS: A phase III, multicenter, randomized, double-blind, non-inferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary endpoint was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate at week 4, symptom response and quality of life assessment. Safety profiles and serum gastrin levels were also assessed. RESULTS: In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) (P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than esomeprazole group (95.14% (137/144) vs. 87.68% (121/138); P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the two groups (P = 0.047), but both decreased after treatment. DISCUSSION: An 8-week therapy of zastaprazan 20 mg is non-inferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study.

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

Ranitidine Use and Incident Cancer in a Multinational Cohort.

Importance: Ranitidine, the most widely used histamine-2 receptor antagonist (H2RA), was withdrawn because of N-nitrosodimethylamine impurity in 2020. Given the worldwide exposure to this drug, the potential risk of cancer development associated with the intake of known carcinogens is an important epidemiological concern. Objective: To examine the comparative risk of cancer associated with the use of ranitidine vs other H2RAs. Design, Setting, and Participants: This new-user active comparator international network cohort study was conducted using 3 health claims and 9 electronic health record databases from the US, the United Kingdom, Germany, Spain, France, South Korea, and Taiwan. Large-scale propensity score (PS) matching was used to minimize confounding of the observed covariates with negative control outcomes. Empirical calibration was performed to account for unobserved confounding. All databases were mapped to a common data model. Database-specific estimates were combined using random-effects meta-analysis. Participants included individuals aged at least 20 years with no history of cancer who used H2RAs for more than 30 days from January 1986 to December 2020, with a 1-year washout period. Data were analyzed from April to September 2021. Exposure: The main exposure was use of ranitidine vs other H2RAs (famotidine, lafutidine, nizatidine, and roxatidine). Main Outcomes and Measures: The primary outcome was incidence of any cancer, except nonmelanoma skin cancer. Secondary outcomes included all cancer except thyroid cancer, 16 cancer subtypes, and all-cause mortality. Results: Among 1 183 999 individuals in 11 databases, 909 168 individuals (mean age, 56.1 years; 507 316 [55.8%] women) were identified as new users of ranitidine, and 274 831 individuals (mean age, 58.0 years; 145 935 [53.1%] women) were identified as new users of other H2RAs. Crude incidence rates of cancer were 14.30 events per 1000 person-years (PYs) in ranitidine users and 15.03 events per 1000 PYs among other H2RA users. After PS matching, cancer risk was similar in ranitidine compared with other H2RA users (incidence, 15.92 events per 1000 PYs vs 15.65 events per 1000 PYs; calibrated meta-analytic hazard ratio, 1.04; 95% CI, 0.97-1.12). No significant associations were found between ranitidine use and any secondary outcomes after calibration. Conclusions and Relevance: In this cohort study, ranitidine use was not associated with an increased risk of cancer compared with the use of other H2RAs. Further research is needed on the long-term association of ranitidine with cancer development.

Efficacy and safety of intragastric balloon for obesity in Korea.

BACKGROUND/AIMS: Intragastric balloon (IGB) is the only available endoscopic bariatric and metabolic therapy in Korea. End-ball (Endalis) has the longest history of clinical use among the IGBs available in Korea. However, little clinical data on this system have been reported. In this study, we aimed to evaluate the efficacy and safety of End-ball in Korea. METHODS: We performed a retrospective cohort study of patients who underwent IGB insertion (End-ball) from 2013 to 2019. Demographic and anthropometric data were collected. The efficacy and safety of IGB treatment were analyzed. RESULTS: In total, 80 patients were included. Mean age was 33.7 years and 83.8% were female. Initial body mass index was 34.48±4.69 kg/m2. Body mass index reduction was 3.72±2.63 kg/m2 at the time of IGB removal. Percent of total body weight loss (%TBWL) was 10.76%±6.76%. Percentage excess body weight loss was 43.67%±27.59%. Most adverse events were minor, and 71.4% of participants showed nausea, vomiting, or abdominal pain. CONCLUSION: IGB treatment showed good efficacy and safety profile in Korean patients with obesity. In terms of %TBWL and percentage excess body weight loss, the efficacy was similar to that in the Western population.

Triple Therapy-Based on Tegoprazan, a New Potassium-Competitive Acid Blocker, for First-Line Treatment of Helicobacter pylori Infection: A Randomized, Double-Blind, Phase III, Clinical Trial.

Background/Aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication. Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)- based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases. Results: In total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences. Conclusions: TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier NCT03317223).

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.

Low insertion of cystic duct increases risk for common bile duct stone recurrence.

BACKGROUND: Common bile duct (CBD) stone is one of the most frequent biliary diseases. Recurrence after the complete removal of CBD stones is high, and we aim to evaluate the rate and risk factors for symptomatic recurrence of CBD stones after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We, retrospectively, reviewed the database of patients who underwent ERCP for CBD stones and subsequent cholecystectomy between January 2015 and December 2017 at a tertiary hospital. The recurrence of symptomatic CBD stones was defined as the presence of a CBD stone with related symptoms at least 6 months after the ERCP procedure. The primary outcomes were recurrence of symptomatic CBD stones and its risk factors. RESULTS: Among the 362 enrolled patients, 60 experienced a symptomatic recurrence of CBD stones between 6 months and 5 years after the procedure. The mean duration of follow-up was 32.3 ± 8.1 months. The patients with recurrences were older and had a longer follow-up duration. Low insertion of the cystic duct (HR = 2.893, p = 0.016), distal CBD angulation (HR = 1.015, p = 0.034), maximum CBD diameter (HR = 1.070, p = 0.012), number of ERCP sessions at first admission (HR = 1.558, p = 0.032), and cannulation time (HR = 1.030, p = 0.008) were the independent risk factors for symptomatic recurrent CBD stones. CONCLUSIONS: Patients with risk factors, especially those with low cystic duct insertion, are more prone to symptomatic recurrent CBD stones and should be followed more carefully.

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.

Rates and Risk Factors for Interval Gastric Cancers at Screening Gastroscopy.

BACKGROUNDS/AIMS: Interval gastric cancers (GCs) can be encountered during screening gastroscopy. This study investigated the rate of interval GCs and their risk factors. MATERIALS AND METHODS: We retrospectively investigated subjects who underwent screening gastroscopy from 2005 to 2017 in a university hospital and were diagnosed with GC. Subjects were grouped based on their endoscopic images and descriptive results into interval GC and initially diagnosed GC groups. Interval GCs were defined when endoscopic results within the previous 3 years were negative for GC. The clinico-pathological characteristics of the groups and risk factors for interval GCs were evaluated. RESULTS: Of 54 724 subjects who underwent screening gastroscopy, 234 were diagnosed with GC, of which 43 were interval GCs. The rate of interval GCs was 18.4% (43/234, mean age 61.6 years). Interval GCs were smaller than initially diagnosed GCs (1.6 vs 1.9 cm, P = .011). They were located in the low-to-mid-body in 44.2%, antrum in 48.8%, and high body and cardia in 7%. Their observation time was shorter (248.74 vs 410.64 sec, P = .032). In multivariate analysis, they were associated with short observation time (odds ratio [OR] 0.99, 95% CI 0.994-0.998, P < .001) and location in the low-to-mid-body (OR 2.12, 95% CI 1.071-4.181, P = .031), although differentiation, ulcerated type, metaplasia, Helicobacter pylori infection, and endoscopists' experience were not associated with interval GCs. CONCLUSIONS: The rate of interval GCs was significant during screening gastroscopy. They might be reduced by increasing observation time, focusing on smaller lesions, and observing the low-to-mid-body of the stomach more carefully.

Prevalence and clinical characteristics of antibiotics associated drug induced liver injury.

BACKGROUND: The use of antibiotics increases recently. Accordingly, the incidence of antibiotics associated with drug induced liver injury (DILI) also increases. The purpose of this study is to evaluate the proportion and the clinical characteristics of antibiotic associated with DILI. METHODS: This study is a retrospective study of analyzed adult patients who were referred to the department of hepatology for the elevation of liver function tests and the frequency of elevated liver enzyme of patients with prescribed antibiotics during the same period at outpatient setting as a validation set. RESULTS: Antibiotics associated with DILI (64.0%) are the most common reason agent among consulting to hepatology department. Rheumatoid arthritis related drugs (11.0%), health supplements (5.0%), herbal medicines (4.0%), anti-viral drugs, anti-inflammatory analgesics/acetaminophen and lipid-lowering agents (3.0%) were next common causative drug for DILI in inpatients setting (training set). The frequency of antibiotics associated with DILI was high in order of flomoxef, cetrazole, ceftriaxone, vancomycin, piperacillin/tazobactam and amoxicillin/clavulanate. In the same period, 32% of the patients who prescribed flomoxef showed elevated liver enzyme levels above the upper normal limit. The prevalence of flomoxef induced DILI (>3 folds of ALT) was 13% and liver enzyme levels were five times higher than upper normal limits in 5% of flomoxef groups. Hypertension or diabetes was the risk factor of flomoxef associated with DILI. CONCLUSIONS: The Prevalence of antibiotics associated with DILI was 2-14%. Co-morbidity with diabetes and hypertension was the risk factor of flomoxef associated with DILI.

Long-term Outcomes of Undifferentiated-Type Early Gastric Cancer with Positive Horizontal Margins after Endoscopic Resection.

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.

Efficacy and Safety of Rebamipide versus Its New Formulation, AD-203, in Patients with Erosive Gastritis: A Randomized, Double-Blind, Active Control, Noninferiority, Multicenter, Phase 3 Study.

Background/Aims: : The mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of MucostaⓇ (rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in treating erosive gastritis. Methods: This double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups: AD-203 twice daily or MucostaⓇ thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; MucostaⓇ, n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; MucostaⓇ, n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated. Results: According to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and MucostaⓇ-treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and MucostaⓇ-treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was -4.01% (95% confidence interval [CI], -13.09% to 5.06%) in the ITT analysis and -4.44% (95% CI, -13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 MucostaⓇ-treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates. Conclusions: The new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (MucostaⓇ) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.

Is There Pathological Uniformity between the Periphery and Center of a Gastrointestinal Stromal Tumor?

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors and have some malignant potential. Mitotic count is important for predicting the malignant potential of GISTs. Proper treatment of GISTs requires accurate pathological diagnosis. In general, endoscopic ultrasound-guided fine-needle aspiration and deep biopsy are used for pathological diagnosis of GIST before making decisions about surgery. This study sought to evaluate the pathological uniformity of gastric GISTs for mitotic index of the center and periphery of the GIST. METHODS: We retrospectively reviewed the data of 37 gastric GIST patients who underwent wedge resection at Hanyang University Hospital. We used Armed Forces Institute of Pathology criteria to classify gastric GISTs. To determine the pathological uniformity of gastric GISTs, we compared GIST risk stratification between the center and periphery of GISTs. RESULTS: The mean size of GISTs was 3.56 ± 2.10 cm. Three lesions were located in the antrum, 11 in the fundus, 9 in the cardia, and 14 in the body. The mean age of patients was 58.65 ± 9.44 years; 18 patients were male and 19 were female. Thirty-five patients (94.6%) showed the same level of risk stratification between the center and periphery of gastric GISTs, while two patients (5.4%) presented different levels of risk between the two sites. No significant difference in mitotic count was observed between the two sites (kappa value = 0.863; p = 0.001). CONCLUSIONS: Mitotic index category (either more than five mitoses per high-power field or five or fewer mitoses per high-power field) of GISTs showed good concurrence between the center and periphery.

Diagnostic Performance of Serum Asialo α1-Acid Glycoprotein Levels to Predict Liver Cirrhosis.

Background/Aims: To date, studies on various noninvasive techniques have been suggested to evaluate the degree of liver fibrosis. We aimed to investigate the diagnostic performance of serum asialo α1-acid glycoprotein (AsAGP) in the diagnosis of liver cirrhosis compared with chronic hepatitis for clinically useful result. Methods: We conducted a case-control study of 96 patients with chronic liver disease. Chronic hepatitis was defined as the presence of chronic liver disease on ultrasonography, with a liver stiffness of less than 5.0 kPa as shown on magnetic resonance elastography (MRE). Liver cirrhosis was defined as liver stiffness of more than 5.0 kPa on MRE. The serum AsAGP concentration was compared between the two groups. Results: Serum AsAGP levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis (1.83 µg/mL vs 1.42 µg/mL, p<0.001). Additionally, when comparing patients in each cirrhotic group (Child-Pugh grades A, B, and C) to those with chronic hepatitis, AsAGP levels were significantly higher in all the cirrhotic groups (p<0.05, p<0.01, p<0.001, respectively). The sensitivity and specificity of AsAGP for detecting cirrhosis were 79.2% and 64.6%, respectively, and the area under the curve value was 0.733. The best diagnostic cutoff to predict cirrhosis was 1.4 µg/mL. AsAGP and bilirubin were found to be independent risk factors for the prediction of cirrhosis in the logistic regression analysis. Conclusions: Serum AsAGP showed an acceptable diagnostic performance in predicting liver cirrhosis.

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.