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Background and Aims: The incidence of gastric and duodenal neuroendocrine tumors (GNET and DNET, respectively) is increasing, however associated factors of these diseases are not well known. Here, we investigated the factors associated with GNET and DNET., Methods: Patients with GNET and DNET presenting at eight tertiary referral centers between 2001 and 2020 were included and compared with healthy controls who underwent upper endoscopic screening. Clinical factors and laboratory data were analyzed to determine associated factors of GNET and DNET., Results: Overall, 396 patients with GNET and 193 patients with DNET were included and compared with 1725 healthy controls. Multivariate analysis showed that age (odds ratio [OR] 0.98), diabetes (OR 1.72), hypertension (OR 1.97), low serum high-density lipoprotein cholesterol (HDL-C) levels (OR 2.54), and past/present H. pylori infection (OR 1.46) were significantly associated with GNET. In contrast, DNET was significantly associated with diabetes (OR 1.80), hypertension (OR 1.68), low serum HDL-C levels (OR 2.29), and past/present H. pylori infection (OR 5.42). In the sex-based subgroup analysis in GNET, current smoking was strongly associated in women (OR 9.85), but not in men., Conclusions: This study identified several common metabolic factors associated with GNET and DNET. Additionally, some factors had sex-specific associations., Competing Interests: Conflict of interest The authors have no conflict of interest regarding this article., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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.

Background/aims: Endoscopic technologies have recently advanced to optimize the detection and diagnosis of gastric lesions. Endocytoscopy aids in the virtual realization of histology. Herein, we aimed to investigate gastric lesions using single-stain endocytoscopy and compare them using magnifying endoscopy with narrow-band imaging (ME-NBI) in terms of diagnostic yield in vivo., Methods and Methods: In the present prospective study, we registered 24 patients with gastric neoplasms and retrospectively reviewed their images. Three endoscopists reviewed the images of gastric neoplasms using white light, ME-NBI, and endocytoscopy. The diagnostic yield of endocytoscopy in early gastric cancer (EGC) was assessed using histopathology as the gold standard., Results: Endocytoscopy was performed in 24 patients with gastric neoplasms. Of these, 15 patients had adenocarcinomas, while nine patients had low-grade dysplasia. The sensitivity, specificity, and accuracy of endocytoscopy for EGC detection were reported as 80.0% [95% confidence interval (CI), 51.9-95.7], 66.7% (95% CI, 58.4-91.9), and 75.0% (95% CI, 53.3-90.2) by endoscopist A; 80.0% (95% CI, 51.9-95.7), 44.4% (95% CI, 13.7-78.8), and 66.7% (95% CI, 44.7-84.4) by endoscopist B; and 93.3% (95% CI, 68.1-99.8), 55.6% (95% CI, 21.2-86.3), and 79.2% (95% CI, 57.9-92.8) by endoscopist C; these findings were not inferior to NBI. The inter-observer agreement, κ statistic = 0.67 (95% CI, 0.43-0.90) was favorable., Conclusion: Endocytoscopy aid in the diagnosis of EGC because of its better sensitivity and accuracy compared to NBI or white-light imaging. However, further large-scale studies are required to confirm our findings., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: This study evaluated the efficacy of fibrin glue for preventing postendoscopic submucosal dissection (ESD) bleeding in high-risk patients for bleeding (expected iatrogenic ulcer size ≥40 mm or receiving antithrombotic therapy)., Methods: A multicenter, open-label, randomized controlled trial was performed at 4 tertiary medical centers in South Korea between July 1, 2020, and June 22, 2022. Patients with gastric neoplasm and a high risk of post-ESD bleeding were enrolled and allocated at 1:1 to a control group (standard ESD) or a fibrin glue group (fibrin glue applied to iatrogenic ulcers after standard ESD). The primary outcome was overall bleeding events within 4 weeks. The secondary outcomes were acute bleeding (within 48 hours post-ESD) and delayed bleeding (48 hours to 4 weeks post-ESD)., Results: In total, 254 patients were randomized, and 247 patients were included in the modified intention-to-treat population (125 patients in the fibrin glue group and 122 patients in the control group). Overall bleeding events occurred in 12.0% (15/125) of the fibrin glue group and 13.1% (16/122) of the control group ( P = 0.791). Acute bleeding events were significantly less common in the fibrin glue group than in the control group (1/125 vs 7/122, P = 0.034). Delayed bleeding events occurred in 11.2% (14/125) in the fibrin glue group and 7.3% (9/122) in the control group ( P = 0.301)., Discussion: This trial failed to show a preventive effect of fibrin glue on overall post-ESD bleeding in high-risk patients. However, the secondary outcomes suggest a potential sealing effect of fibrin glue during the acute period., (Copyright © 2023 by The American College of Gastroenterology.)

Objective: Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota., Design: Microbiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year., Results: The microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation., Conclusion: Major histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The authors declare that they have no conflict of interests.

Background and Aim: Bleeding after endoscopic submucosal dissection (ESD) is a main adverse event. To date, although there have been several studies about risk factors for post-ESD bleeding, there has been few predictive model for post-ESD bleeding with large volume cases. We aimed to design a prediction model for post-ESD bleeding using a classification tree model., Methods: We analyzed a prospectively established cohort of patients with gastric neoplasms treated with ESD from 2007 to 2016. Baseline characteristics were collected for a total of 5080 patients, and the bleeding risk was estimated using variable statistical methods such as logistic regression, AdaBoost, and random forest. To investigate how bleeding was affected by independent predictors, the classification and regression tree (CART) method was used. The prediction tree developed for the cohort was internally validated., Results: Post-ESD bleeding occurred in 262 of 5080 patients (5.1%). In multivariate logistic regression, ongoing antithrombotic use during the procedure, cancer pathology, and piecemeal resection were significant risk factors for post-ESD bleeding. In the CART model, the decisive variables were ongoing antithrombotic agent use, resected specimen size ≥49 mm, and patient age <62 years. The CART model accuracy was 94.9%, and the cross-validation accuracy was 94.8%., Conclusions: We developed a simple and easy-to-apply predictive tree model based on three risk factors that could help endoscopists identify patients at a high risk of bleeding. This model will enable clinicians to establish precise management strategies for patients at a high risk of bleeding and to prevent post-ESD bleeding., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Goals: We assessed the efficacy of polaprezinc plus proton pump inhibitor (PPI) treatment for endoscopic submucosal dissection (ESD)-induced ulcer healing compared with rebamipide plus PPI treatment., Background: ESD has been widely used as a local treatment option that cures gastric neoplasms. However, it causes large and deep artificial ulcers, and there are no guidelines with regard to the optimal treatment durations and drug regimens for ESD-induced ulcers. Polaprezinc is effective for promoting ulcer healing and helps enhance the quality of ulcer healing., Study: Two hundred ten patients with ESD-induced ulcers were randomly allocated to treatment with polaprezinc (150 mg/d) plus pantoprazole (40 mg/d) or treatment with rebamipide (300 mg/d) plus pantoprazole (40 mg/d). We evaluated the ulcer healing rate and condition of the ulcer at 4 weeks after dissection. The χ2 or Fisher exact test and the Student t test were used., Results: The ulcer healing rates at 4 weeks after dissection in the polaprezinc plus pantoprazole treatment group were not inferior compared with those in the rebamipide plus pantoprazole treatment group, both in the intention-to-treat analysis (90.3% and 91.4%, respectively, P=0.523) and per-protocol analysis (89.9% and 91.1%, respectively, P=0.531). The short procedure time was an independent predictive factor for a high ulcer healing rate (odds ratio: 0.975; 95% confidence interval: 0.958-0.993; P=0.006)., Conclusion: The polaprezinc plus PPI treatment showed noninferiority to rebamipide plus PPI treatment in the ulcer healing rate at 4 weeks after ESD., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background/aims: Endoscopic vacuum-assisted closure (EVAC) has been attempted as new nonsurgical treatment for anastomotic leakage. We aimed to evaluate the clinical outcomes of EVAC and compare its efficacy with the self-expandable metallic stent (SEMS) for postgastrectomy leakage., Methods: Between January 2007 and February 2018, 39 patients underwent endoscopic treatment for anastomotic leakage after gastric cancer surgery. Of them, 28 patients were treated with SEMS, seven with EVAC after SEMS failure, and four with EVAC. We retrospectively compared the clinical characteristics and therapeutic outcomes between EVAC (n=11) and SEMS (n=28)., Results: The median followup duration was 17 months (interquartile range, 9 to 26 months) in both groups. In comparison of clinical characteristics between two groups, only the median size of the leak was larger in the EVAC group than in the SEMS group (2.1 cm vs 1.0 cm; p<0.001). All EVAC cases healed successfully; however, two cases (7.1%) failed to heal in the SEMS group. Anastomotic stricture occurred one case (9.1%) in EVAC and four cases (14.3%) in SEMS within 1 year after endoscopic treatment. The median treatment duration of EVAC was shorter than that of SEMS (15 days vs 36 days; p<0.001). Median weight loss after therapy was similar in both groups (8.0 kg in EVAC vs 9.0 kg in SEMS; p=0.356)., Conclusions: EVAC can be effective endoscopic treatment for postgastrectomy anastomotic leakage. Substantial leakage could be an important clinical factor for considering EVAC as a treatment option. Large randomized controlled trials are needed to confirm the efficacy of EVAC.

Background and Aim: This study investigated the usefulness of near-focus narrowband imaging (NF-NBI) for determining gastric tumor margins compared with indigo carmine chromoendoscopy (ICC) before endoscopic submucosal dissection (ESD)., Methods: This prospective randomized controlled trial was conducted at seven teaching hospitals in Korea. Patients with gastric adenoma or differentiated adenocarcinoma undergoing ESD were enrolled and randomly assigned to the NF-NBI or ICC group. A marking dot was placed on the most proximal margin of the tumor before ESD. The primary endpoint was delineation accuracy, which was defined as presence of marking dots within 1 mm of the tumor margin under microscopic observation., Results: A total of 200 patients in the NF-NBI group and 195 patients in the ICC group were included. The delineation accuracy rate was 84.5% in the NF-NBI group and 81.0% in the ICC group (P = 0.44). However, the distance from the marking dot to the margin of the tumor was significantly shorter in the NF-NBI group than in the ICC group (0.8 ± 0.8 vs 1.2 ± 1.3 mm, P < 0.01). Even after adjustment of other clinicopathological factors that are associated with difficulty of tumor delineation, NF-NBI did not show significant association with accurate delineation (odds ratio of 0.86, P = 0.60)., Conclusions: This prospective multicenter study showed that NF-NBI is not superior to ICC in terms of accurately delineating gastric tumors (NCT02661945)., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Purpose: To evaluate the safety and efficacy of preoperative chemotherapy (CTx) followed by chemoradiotherapy (CCRT) for high-risk gastric cancer (GC)., Methods and Materials: The inclusion criteria were as follows: (1) Borrmann type 4; (2) large Borrmann type 3 (≥8 cm); (3) single bulky (≥3 cm × 1) or multiple lymph nodes (≥1.5 cm × 3). Patients received two 21-day courses of induction CTx of TS-1 (35 mg/m 2 , p.o, twice daily on days 1-14), docetaxel (30 mg/m 2 , i.v., days 1 and 8), and cisplatin (30 mg/m 2 , i.v., days 1 and 8) followed by CCRT (two courses of TS-1 and cisplatin in combination with 45 Gy radiation)., Results: Forty-two patients were enrolled between March 2014 and February 2016, and 39 of these completed sequential CTx and CCRT. Among the 33 patients who underwent R0 resection, the pathologic response rate was 39.4% [no residual carcinoma (n = 5, 15.2%), with 1-10% residual carcinoma (n = 8, 24.2%)]. Overall, 4 patients (12.1%) were pathologic stage 0, 7 (21.2%) were stage I, 10 (30.3%) were stage II, and 12 (36.4%) were stage III. The overall survival rate at 3 years was 77.9% for stages 0 and I, 66.8% for stages II-III, and 33.3% for unresectable cases (P = 0.001). Toxicity was mild to moderate with grade 4 neutropenia (n = 1) and neutropenic fever (n = 1) as the most prominent side-effects., Conclusions: Sequential CTx and CCRT prior to surgery are feasible and effective for high-risk GC., Trial Registration Number: NCT02495493., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aim: Adequate tissue acquisition is important in making treatment decisions for patients with upper gastrointestinal subepithelial tumors (SETs). This study aimed to compare the outcomes of endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) with those of the unroofing biopsy technique., Methods: This study was a single-center, prospective comparative study conducted at Severance Hospital, Yonsei University College of Medicine. A total of 39 patients with SETs ≥15 mm were enrolled between January 2016 and August 2017., Results: Of the 39 patients, 28 underwent biopsy with both techniques (4 underwent only unroofing and 7 underwent only EUS-FNB). Histological diagnosis was made with EUS-FNB in 64.3% and unroofing biopsy in 78.6% (p = 0.344), and immunohistochemical diagnosis was made with EUS-FNB in 46.4% and unroofing biopsy in 67.9% (p = 0.180). In the subgroup analysis (28 patients), there was no significant difference in diagnostic yield between the 2 methods The mean procedural time with EUS-FNB was shorter than that with unroofing biopsy (p < 0.001). The larger SET (≥ 20 mm) (p = 0.035) and satisfaction of procedure (p = 0.019) were positively associated with successful histological diagnosis by EUS-FNB., Conclusions: There was no significant difference in the histological diagnostic yield for SETs between the EUS-FNB and unroofing biopsy techniques (CinicalTrials.gov. identifier NCT02646241)., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to analyze long-term clinical and oncologic outcomes in patients with early-stage adenocarcinoma of the esophagogastric junction (AEG) managed with either endoscopic resection (ER) or surgery., Methods: The inclusion criteria were AEG, meeting classic or expanded indications for ER of early gastric cancer, and complete resection. A total of 66 patients with Siewert type II AEG were included (ER group, n = 38; vs. surgery group, n = 28)., Results: The mean age of the ER group was greater than that of the surgery group (mean ± SD, 66.9 ± 9.7 vs. 58.5 ± 10.4 years, respectively; p = 0.001). Compared to the ER group, macroscopically flat or depressed-type lesions were more common (47.4 vs. 89.3%; p = 0.001), and mean lesion size was larger in the surgery group (13.3 ± 8.4 vs. 18.6 ± 11.0 mm; p = 0.039). One intensive care unit admission and subsequent surgery-related death occurred in the surgery group (1/28 vs. 0/38 in the ER group; p = 0.424). During follow-up, recurrence was detected in both groups (4/38 vs. 1/28; p = 0.385). Overall survival and 5-year disease-free survival did not differ between the groups (93.3 vs. 92.9%; p  = 0.282 and 88.0 vs. 100.0%; p = 0.066)., Conclusions: Once complete resection is achieved in patients with AEG who met the expanded criteria for endoscopic submucosal dissection of gastric cancer, there was no significant difference in clinical outcomes between ER and surgery.

Background and Aims: We aimed to evaluate long-term outcomes with noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and surveillance strategies such as the optimal time for additional endoscopic treatment in patients with noncurative ESD., Methods: Of 2527 patients who underwent gastric ESD for EGC, 512 (20.3%) patients with noncurative resection were reviewed. Noncurative resection is defined as positive resected margins on histology, lymphovascular infiltration, or beyond the expanded criteria for ESD., Results: The mean ± standard deviation follow-up duration was 79.0 ± 55.7 months. A total of 264 patients (51.6%) and 50 patients (9.8%) underwent surgery and endoscopic treatment after noncurative resection, respectively, whereas 198 patients (38.7%) were observed. Cancer-specific survival and disease-free survival rates were significantly different among the surgery, other endoscopic treatment, and observation groups (96.7%, 86.8%, and 86.2%, respectively; P =.030; and 92.5%, 73.6%, and 63.0%, respectively; P < .001). When patients who underwent surgery were excluded, the disease-free survival rate of recurrence was not significantly different between the endoscopic treatment and observation groups (73.6% vs 63.0%; P = .548). To exclude the potential for the presence of lymph node metastasis, we further analyzed disease-free survival of local recurrence by comparing the patients with only a positive lateral resection margin. The disease-free survival rate was higher in the endoscopic treatment group than in the observation group (89.2% vs 69.1%; P = .023). Moreover, additional endoscopic treatment within 3 months showed significant associations with lower risk of local recurrence on multivariate analysis (hazard ratio, 0.017; 95% confidence interval, 0.002-0.260; P = .003)., Conclusions: In patients with noncurative ESD, additional surgery showed a better long-term outcome; moreover, when a positive lateral resection margin was the only noncurative factor, additional endoscopic treatment within 3 months could be considered to improve disease-free survival., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The treatment of intramucosal early gastric cancer with undifferentiated-type histologies (UD-EGCs) using endoscopic submucosal dissection (ESD) is controversial. This study aimed to compare the clinical and oncologic long-term outcomes of ESD and surgery for UD-EGCs., Methods: A prospectively collected database of patients who underwent ESD or surgery between January 2006 and December 2012 was established. Patients who diagnosed with UD-EGC and satisfied the expanded indications of ESD were included. Clinical data from 111 patients treated with ESD and 382 patients underwent surgery were analyzed, and 1-1 propensity score-matched 81 pairs of patients were also compared., Results: In both groups, two-thirds of the UD-EGCs had signet ring cell (SRC)-type histology and about 90% of UD-EGCs were flat or depressed types. The mean size of tumors was smaller in ESD group (9.7 vs. 13.2 mm; P < 0.001). After propensity score-matched, case-matching covariates were not significantly different between the groups. Disease-free survival (DFS) was significantly shorter in the ESD group, but overall survival (OS) was not different between the two groups both in overall comparison (DFS; P < 0.001 and OS; P = 0.078) and propensity score-matched analysis (DFS; P < 0.001 and OS; P = 0.850). According to histologic type, OS of SRC histology was not different between the group, both in overall comparison and propensity score-matched analysis (P = 0.286 and P = 0.210). On the other hands, OS of poorly differentiated adenocarcinoma was significantly shorter in ESD group in overall comparison (P = 0.007), but was not as so in propensity score-matched analysis (P = 0.088)., Conclusions: ESD might be a complementary option for the treatment of UD-EGCs, especially in those with SRC-type histology based on strict expanded indications. Nonetheless, close endoscopic surveillance is required because of a high incidence of intragastric recurrence.

Background: Endoscopic submucosal dissection (ESD) is accepted as a standard treatment in patients with early gastric cancer (EGC) who have a negligible risk of lymph node metastasis. The aim of this study was to compare the short-term and long-term outcomes between ESD and surgery in patients with EGC that fulfilled the expanded indication of ESD on their final pathologic report., Methods: We reviewed the clinical data of patients who underwent gastric ESD and surgery between January 2007 and December 2012. Patients with pathologically confirmed EGC that fulfilled the expanded indication of ESD on their final pathologic report were analyzed., Results: Among 2023 patients, 817 (40.4%) underwent ESD and 1206 (59.6%) underwent surgery. The proportion of cases meeting the absolute indication was significantly higher in the ESD group than in the surgery group (66.0 vs. 26.2%). Lesions on the middle third, >3 cm in size, flat or depressed, and of undifferentiated histology were significantly more common in the surgery group than in the ESD group. The ESD group showed lower acute complication rates [8.1% (66 of 817) vs. 18.1% (218 of 1206), P ≤ 0.001] and procedure-related mortality [0 vs. 0.3% (4 of 1206), P = 0.153] than the surgical group. The annual incidence of recurrent gastric cancer was 2.18% in the ESD group and 0.19% in the surgery group. The 5-year overall and disease-specific survival rates were not significantly different between the ESD group and the surgery group (overall survival: 96.4 vs. 97.2%, P = 0.423; disease-specific survival: 99.6 vs. 99.2%, P = 0.203)., Conclusions: Although EGC lesions had poorer features in the surgery group than in the ESD group, ESD was comparable to surgery for EGCs that fulfilled the expanded indication of ESD, with lower rates of acute complication and comparable overall survival.

Background and Aims: No well-established treatment strategies exist for lateral margin positivity (LM+) alone after endoscopic resection (ER) of early gastric cancer (EGC). Thus, we aimed to clarify a treatment strategy for non-curative resection (non-CR) with LM+ alone after ER in EGC., Methods: Among 2065 patients with EGC treated by ER, 76 (3.6%) with only LM+ after non-CR of EGC were reviewed retrospectively. Of these, 28 underwent gastrectomy, 25 underwent argon plasma coagulation (APC), and 23 underwent repeat ER (re-ER). We analyzed the clinicopathologic characteristics of all patients and compared those who underwent additive surgery, APC, or re-ER., Results: Of the 76 patients, 28 (36.8%) fulfilled the absolute criteria and 48 (63.2%) the expanded criteria for ER. Among the latter patients, the proportion undergoing additive surgery was 75.0%, higher than that of patients in the former group (P = .014). Residual cancer cells were observed in 70.6% of patients after additive surgery or re-ER. Residual cancer cells were observed significantly more often in patients with undifferentiated-type than in those with differentiated-type EGC (P = .02). However, no lymph node metastasis was observed in any patient after additive surgery., Conclusions: Our results suggest that endoscopic treatment may be a sufficient additive therapy for patients with LM+ alone after ER, irrespective of whether the absolute or expanded ER criteria are used. However, as complete ablation of remnant cells cannot be guaranteed, re-ER is a better additive treatment than APC., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background/aims: Few studies have evaluated the effect of Helicobacter pylori infection on the prognosis of patients diagnosed with gastric cancer (GC) after curative surgery. We investigated the association between the H. pylori infection status and clinical outcome after surgery., Methods: We assessed the H. pylori status of 314 patients who underwent curative resection for GC. The H. pylori status was examined using a rapid urease test 2 months after resection. Patients were followed for 10 years after surgery., Results: An H. pylori infection was observed in 128 of 314 patients. The median follow-up period was 93.5 months. A Kaplan-Meier analysis indicated that patients with H. pylori had a higher cumulative survival rate than those who were negative for H. pylori . Patients with stage II cancer who tested negative for H. pylori were associated with a poor outcome. In a multivariate analysis, H. pylori -negative status was a significant independent prognostic factor for poor overall survival., Conclusions: Having a negative H. pylori infection status seems to indicate poor prognosis for patients with GC who have undergone curative resection. Further prospective controlled studies are needed to evaluate the mechanism by which H. pylori affects GC patients after curative surgery in Korea.

We tested the clinical utility of combined profiling of Ion Torrent PGM based next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to molecularly targeted therapies. A consecutive cohort of 93 patients with advanced/metastatic GC who underwent palliative chemotherapy between March and December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53 protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay). Treatment was based on availability of targeted agents at the time of molecular diagnosis. Among the 81 cases with available tumor samples, complete NGS and IHC profiles were successfully achieved in 66 cases (81.5%); only IHC results were available for 15 cases. Eight cases received matched therapy based on sequencing results; ERBB2 amplification, trastuzumab (n = 4); PIK3CA mutation, Akt inhibitor (n = 2); and FGFR2 amplification, FGFR2b inhibitor (n = 2). Eleven cases received matched therapy based on IHC; ERBB2 positivity, trastuzumab (n = 5); PTEN loss (n = 2), PI3Kβ inhibitor; MMR deficiency (n = 2), PD-1 inhibitor; and EGFR positivity (n = 2), pan-ERBB inhibitor. A total of 19 (23.5%) and 62 (76.5%) cases were treated with matched and non-matched therapy, respectively. Matched therapy had significantly higher overall response rate than non-matched therapy (55.6% vs 13.1%, P = 0.001). NGS and IHC markers provide complementary utility in identifying patients who may benefit from targeted therapies.

Background: Patients with early gastric cancer (EGC) who have undergone noncurative endoscopic resection (ER) generally require additional surgery due to the possibility of lymph node metastasis (LNM). This study aimed to develop a reliable risk-stratification system to predict LNM after noncurative ER for EGC., Methods: A total of 2368 patients had a diagnosis of EGC and underwent ER. The study analyzed 321 patients who underwent additive gastrectomy and lymph node dissection after noncurative ER. Independent risk factors for LNM were identified and used to develop a risk-stratification system to estimate the relative risk of LNM., Results: Of the 321 patients, 23 (7.2%) had LNM. A logistic regression analysis showed that female sex, lymphovascular invasion (LVI), and a positive vertical margin were significantly associated with LNM. The authors established a risk-stratification system using sex, LVI, and positive vertical margin (area under the receiver-operating characteristic [AUROC] curve, 0.811). The high-risk LNM group (score, ≥ 2 points) showed a significantly higher risk of LNM than the low-risk LNM group (score, <2 points) (14.0 vs 1.2%). No LNM was found in patients with a risk score of zero. After internal and external validation, the AUROC curve for predicting LNM was 0.788 and 0.842, respectively., Conclusions: The risk-stratification system developed in this study will facilitate identification of patients who should undergo LN dissection after noncurative ER. Although additive surgery should be performed after noncurative ER for patients with a high risk of LNM, a close follow-up visit could be considered for low-risk patients with multiple comorbidities or high operative risks.

Background and Aim: We evaluated probe-based confocal laser endomicroscopy (pCLE) in the margin delineation of early gastric cancer (EGC) for endoscopic submucosal dissection in comparison with white-light imaging with chromoendoscopy (CE)., Methods: We conducted a prospective, randomized controlled study from November 2013 to October 2014 in a tertiary referral hospital. A total of 101 patients scheduled for endoscopic submucosal dissection due to differentiated EGC were randomized into pCLE and CE groups (pCLE 51, CE 50). Markings were made by electrocautery at the proximal and distal tumor margins, as determined by either pCLE or CE. The distance from the marking to the tumor margin was measured in the resected specimen histopathologically and was compared between the two groups by a linear mixed model., Results: Among 104 lesions, 80 lesions with 149 markings (pCLE 68, CE 81) were analyzed after excluding undifferentiated EGCs (n = 8) and unidentifiable markings (n = 13). Although the complete resection rate showed no difference between the groups (94.6% vs 93.2%, P = 1.000), the median distance from the marking to the margin was shorter in the pCLE group (1.3 vs 1.8 mm, P = 0.525) and the proportion of the distance <1 mm was higher (43.9% vs 27.6%, P = 0.023) in the pCLE group. Finally, subgroup analysis with superficial flat lesions (18 lesions, 31 marking dots) showed a significantly decreased distance in the pCLE group (0.5 vs 3.1 mm, P = 0.007)., Conclusions: Among EGCs with superficial flat morphology, in which the accurate evaluation of lateral extent is difficult with CE, pCLE would be useful for more precise margin delineation., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aims: Endoscopic submucosal dissection (ESD) is a useful method for complete resection of early gastric cancer (EGC). However, there are still some patients who undergo additional gastrectomy after ESD because of non-curative resection. There is no model that can accurately predict non-curative resection of ESD. We aimed to create a model for predicting non-curative resection of ESD in patients with EGC., Patients and Methods: We reviewed the medical records, including all gross findings of EGC, of patients who underwent ESD for EGCs. We divided the patients into a non-curative resection group and a curative resection group. The clinicopathologic characteristics were compared between the groups to identify the risk factors for non-curative resection of ESD. We created a scoring system based on logistic regression modeling and bootstrap validation., Results: Of 1639 patients who had undergone ESD for EGCs, 272 were identified as being treated non-curatively with ESD. A large tumor size (≥20 mm), tumor location in the upper body of the stomach, the presence of ulcer, fusion of gastric folds, the absence of mucosal nodularity, spontaneous bleeding, and undifferentiated tumor histology were associated with non-curative resection of ESD. Points of risk scores were assigned for these variables based on the β coefficient as follows: tumor size (≥20 mm), 2 points; tumor location in the upper body of the stomach, 1 point; ulcer, 2 points; fusion of gastric folds, 2 points; absence of mucosal nodularity, 1 point; spontaneous bleeding, 1 point; and undifferentiated histology, 2 points. Our risk scoring model showed good discriminatory performance on internal validation (bootstrap-corrected area under the receiver operating characteristic curve, 0.7004; 95% confidence interval, 0.6655-0.7353)., Conclusions: We developed a validated prediction model that can be used to identify patients who will undergo non-curative resection of ESD. Our prediction model can provide useful information for making decisions about the treatment of EGC before performing ESD., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims: Endoscopic resection (ER) is accepted as a curative treatment option for selected cases of early gastric cancer (EGC). Although additional surgery is often recommended for patients who have undergone non-curative ER, clinicians are cautious when managing elderly patients with GC because of comorbid conditions. The aim of the study was to investigate clinical outcomes in elderly patients following non-curative ER with and without additive treatment., Patients and Methods: Subjects included 365 patients (>75 years old) who were diagnosed with EGC and underwent ER between 2007 and 2015. Clinical outcomes of three patient groups [curative ER (n = 246), non-curative ER with additive treatment (n = 37), non-curative ER without additive treatment (n = 82)] were compared., Results: Among the patients who underwent non-curative ER with additive treatment, 28 received surgery, three received a repeat ER, and six experienced argon plasma coagulation. Patients who underwent non-curative ER alone were significantly older than those who underwent additive treatment. Overall 5-year survival rates in the curative ER, non-curative ER with treatment, and non-curative ER without treatment groups were 84, 86, and 69 %, respectively. No significant difference in overall survival was found between patients in the curative ER and non-curative ER with additive treatment groups. The non-curative ER groups were categorized by lymph node metastasis risk factors to create a high-risk group that exhibited positive lymphovascular invasion or deep submucosal invasion greater than SM2 and a low-risk group without risk factors. Overall 5-year survival rate was lowest (60 %) in the high-risk group with non-curative ER and no additive treatment., Conclusions: Elderly patients who underwent non-curative ER with additive treatment showed better survival outcome than those without treatment. Therefore, especially with LVI or deep submucosal invasion, additive treatment is recommended in patients undergoing non-curative ER, even if they are older than 75 years.

Purpose: Gastric cancer is the third-leading cause of cancer-related death in Korea. As the Korean population is ageing, the number of extremely old patients with this disease is increasing. This study examined the clinicopathological characteristics of gastric cancer in extremely old (over 85 years) patients who received treatment or conservative observations and compared the treatment outcomes according to the treatment modality., Materials and Methods: A total of 170 patients over 85 years of age were diagnosed with gastric cancer. Of these, 81 underwent treatment for gastric cancer and 89 received conservative observations. The clinicopathological characteristics of the treatment and conservative groupswere compared., Results: The mean age of the patients was 86.5 years. The conservative group included significantly more patients with older ages, macroscopically advanced cancer and upper-middle located cancer. The overall survival rate of the treatment group was significantly higher than that of the conservative group. The disease-specific mortality rate was significantly lower in the treatment group than in the conservative group. Multivariate analysis revealed the clinical course, alarm sign, and macroscopic classification to be independent prognosis factors., Conclusion: By itself, the chronological age should not be used as a strategy to determine whether treatmentwill be administered for gastric cancer. Patients who have early gastric cancer or lower-risk preexisting comorbidities should not be discouraged from treatment, even if they are older than 85 years., Competing Interests: relevant to this article was not reported.

Introduction: Perforation is one of the major complications of endoscopic submucosal dissection (ESD). In the present study, we investigated the clinical outcomes of and management strategies for ESD-related perforations., Methods: Between February 2010 and April 2014, a total of 3821 patients who underwent ESD for an upper gastrointestinal epithelial neoplasm were analyzed using the Yonsei University Severance Hospital database. Clinical outcomes of and management strategies for perforations in 90 patients (2.4 %) were analyzed. The risk factors for the development of perforation were also investigated., Results: The mean age of our subjects was 64.7 ± 12.2 years (male to female ratio, 3.2:1), and the mean size of the resected specimens was 39.4 ± 12.5 mm. Endoscopically visible perforations (visible perforation group) were noted in 74 of the 90 patients (82.2 %), and clinically suspected perforations (suspected perforation group) were noted in 16 patients (17.8 %). Immediate closure with endoclips was attempted in cases with a visible perforation and was successful in 72 (97.3 %) cases. Two patients in whom endoscopic closure failed underwent surgery. Conservative care, including fasting and intravenous antibiotic administration, was attempted in the suspected perforation group, and all the patients were treated successfully without surgery. The mean durations of fasting, antibiotic treatment, and hospital stay were 3.8 ± 3.1, 6.8 ± 4.2, and 8.7 ± 5.3 days, respectively. Subgroup analysis of perforation type (visible perforation vs. suspected perforation) revealed no significant difference in the clinical course. Tumor location at the upper or middle third of the stomach was significantly associated with perforation., Conclusion: Most of the ESD-related perforations in upper gastrointestinal epithelial neoplasm could be managed successfully in a non-surgical manner under strict monitoring.

Background: The role of endoscopic ultrasonography (EUS) in gastric cardia cancer should be further evaluated because the accuracy of EUS depends on tumor location. We aimed to identify a specific role of EUS for therapeutic decision-making in patients with gastric cardia cancer., Methods: Initial EUS examinations for treatment-naïve gastric cancer that were followed by endoscopic resection or surgery were included in the study. Lesions were classified as cardiac and non-cardiac cancer according to tumor location. The diagnostic performance of EUS in predicting invasion depth was compared between the two groups., Results: The overall accuracy of EUS in predicting invasion depth did not differ between the cardiac and non-cardiac cancer groups (44.4 vs. 52.3 %, P = 0.259). The underestimation rate was higher in the cardiac cancer group than in the non-cardiac cancer group (37.0 vs. 18.5 %, P = 0.001). When the depth of invasion was predicted to be deeper than the mucosa (submucosal or deeper) by EUS, the positive predictive value was 82.1 [95 % confidence interval (CI), 66.5-92.5 %] and 62.9 % (95 % CI, 60.5-66.9 %) in the cardiac and non-cardiac cancer groups, respectively (P = 0.015). In multivariable analysis, tumor location in the cardia was found to be an independent factor for the underestimation of invasion depth [odds ratio (95 % CI) = 2.242 (1.156-4.349)]., Conclusions: The underestimation rate in predicting invasion depth was significantly higher for cardiac cancers than for non-cardiac cancers. Therefore, selection of the treatment method for gastric cardia cancer via EUS should be done carefully.

Background and Aims: The aim of this study was to identify the incidence of recurrent lesions after endoscopic submucosal dissection (ESD) and to determine whether scheduled endoscopic surveillance might control their development and treatment., Methods: We reviewed the clinical data of patients who underwent gastric ESD between March 2007 and April 2014., Results: A total of 1347 patients who underwent curative ESD for early gastric cancer that met the expanded indication for ESD were analyzed. Of these, recurrence at the previous ESD site occurred in 39 patients, whereas recurrence in the stomach at a site other than the ESD site occurred in 102 patients. Older age, intestinal metaplasia, flat or depressed lesions, and ESD criteria were associated with recurrence in the stomach in places other than the ESD site. The annual incidence was .84% for recurrence at the previous ESD site and 2.48% for recurrence in the stomach at other than the ESD site. In cases of local recurrence and metachronous lesions, there was a significant difference between the short- and long-surveillance interval group (≤12 months vs >12 months) in the proportions of recurrent adenocarcinoma (31.9% vs 60.9%, P = .021), additional gastrectomy (7.1% vs 46.2%, P = .033), and size (8.92 ± 4.17 mm vs 18.08 ± 10.47 mm, P = .010)., Conclusions: Scheduled endoscopy surveillance is necessary for detecting recurrent lesions. In addition, scheduled endoscopy surveillance might help to detect recurrent lesions at a stage early enough for a curative resection., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Screening endoscopies in individuals 40 years or older in regions where gastric cancer is prevalent increase the diagnosis of gastric cancer at an early stage. However, the benefits of screening endoscopies in a young population (<40 years) have not been evaluated., Methods: We reviewed data from patients less than 40 years old who underwent endoscopic submucosal dissection or surgery for initial-onset gastric cancer. We also administered a questionnaire to gather information concerning periodic endoscopic inspections and the period from the penultimate endoscopy to diagnosis., Results: Of the 564 patients in this study, 101 (17.9%) patients underwent screening endoscopy within 24 months of their gastric cancer diagnosis. Lesion size was significantly smaller in the ≤24 months group than in the >24 month group (23.8 mm [standard deviation, 22.2 mm] vs. 30.5 mm [standard deviation, 23.1 mm], P = 0.008). However, the proportion of patients with early gastric cancer did not differ between the two groups (≤24 months vs. >24 months group; 67.6% vs. 65.7%, P = 0.712). On multivariable analysis, periodic endoscopies did not influence the early diagnosis of gastric cancer (with >24 months as the reference group: ≤24 months, odds ratio = 0.939, 95% confidence interval = 0.583-1.513)., Conclusion: Although periodic endoscopies aided in the detection of gastric cancer when lesions were smaller in size, they seemed not to increase the proportion of patients with early gastric cancer in young patients diagnosed with resectable gastric cancer.

Gastric cancer (GC) is a leading cause of death. We aim to establish a clinically relevant assay that encompasses recent molecular classifications and provides useful clinical information in a large cohort of GC patients. A consecutive series of 438 GC patients that underwent palliative chemotherapy between 2014 and 2015 were assessed using 10 GC panels: EBER in-situ hybridization, immunohistochemistry for mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (RTKs; HER2, EGFR, and MET), PTEN, and p53 protein. With a median of one aberration, 3.3 % of samples analyzed were Epstein-Barr virus (EBV)-positive; 4.8%, MMR-deficient. RTKs were overexpressed in 218 patients; EGFR was most commonly overexpressed (39.9%), followed by HER2 (13.5%) and MET (12.1%). Furthermore, 2.5 % and 10.7 % of cases had simultaneous overexpression of three and two RTKs, respectively. p53 overexpression/null tumors were identified in 259 patients (59.1%), and PTEN loss was identified in 89 patients (20.3%). EBV-positivity was mutually exclusive with MMR-deficiency, predominantly identified in male patients, and these tumors were undifferentiated with proximal location. p53 mutant type was significantly found predominantly in the EBV-negative (60.6% vs 14.3%, P=0.001) and HER2-positive (78.0% vs 56.2%, P=0.002) groups. We described a molecular spectrum of distinct GC subtypes using clinically applicable assay. This assay will provide a convenient screening tool and facilitate the development of targeted agents in clinical trials., Competing Interests: The authors have no potential conflicts of interest to disclose.

Background: Endoscopic resection is performed in undifferentiated-type early gastric cancer (UD-EGC), including poorly differentiated (PD) adenocarcinoma and signet ring cell (SRC) carcinoma. We previously found that different approaches are needed for PD adenocarcinoma and SRC carcinoma for curative resection. However, according to the 2010 WHO classification, diffuse-type PD adenocarcinoma and SRC carcinoma are categorized in the "poorly cohesive carcinomas." Thus, we assessed whether the WHO classification is helpful when endoscopic resection is performed for treatment of UD-EGC., Methods: We analyzed clinicopathological features of 1295 lesions with SRC carcinoma and PD adenocarcinoma treated by open surgery. We recategorized them into intestinal-type PD adenocarcinomas and poorly cohesive carcinomas (SRC carcinoma, diffuse-type PD adenocarcinoma). We also recategorized 176 lesions treated by endoscopic resection into intestinal-type PD adenocarcinomas and poorly cohesive carcinomas., Results: According to the open surgery data, the rates of lymph node metastasis (LNM) and lymphovascular invasion were significantly lower in SRC carcinoma than in diffuse-type and intestinal-type PD adenocarcinomas. The rates of LNM and lymphovascular invasion were significantly higher in diffuse-type PD adenocarcinoma than in SRC carcinoma. Endoscopic resection data showed no recurrence if the carcinoma was curatively resected. However, the commonest cause of noncurative resection was different in SRC carcinoma and PD adenocarcinoma. A positive lateral margin was the commonest cause in SRC carcinoma versus a positive vertical margin in both intestinal-type and diffuse-type PD adenocarcinoma., Conclusions: The clinical behavior differs in diffuse-type PD adenocarcinoma and SRC carcinoma. On the basis of LNM and outcomes of endoscopic resection, the recent WHO classification may not be helpful when endoscopic resection is performed for treatment of UD-EGC.

Background: For patients who undergo gastrectomy for gastric cancer, systematic follow-up evaluation to detect recurrent lesions is recommended, although the benefits of a surveillance program using short-term imaging studies have not been evaluated., Methods: This study reviewed the clinical data of patients who underwent curative surgery for gastric cancer using a prospective database. Patients with recurrence were classified according to surveillance interval as follows: ≤3, 3-6, and 6-12 months., Results: Of the 2785 patients who underwent curative surgery for gastric cancer, 376 (13.5 %) had intraabdominal recurrences, excluding the stomach. Multivariable analysis showed that a short surveillance interval did not increase the post-recurrence survival duration (with 6-12 months as the reference: ≤3 months: hazard ratio [HR] 0.954; 95 % confidence interval [CI] 0.689-1.323; 3-6 months: HR 0.994, 95 % CI 0.743-1.330). In addition, short surveillance intervals did not increase overall survival (with 6-12 months as the reference: ≤3 months: HR 0.969; 95 % CI 0.699-1.342; 3-6 months: HR 0.955; 95 % CI 0.711-1.285). In contrast to the surveillance interval, age, cancer stage, symptoms at recurrence, and recurrence time after gastrectomy were factors associated with both post-recurrence survival and overall survival., Conclusions: Although the detection of recurrence before symptoms helped to prolong both post-recurrence survival and overall survival, shortening the surveillance interval to less than 6 months did not improve either the patient's post-recurrence survival or overall survival. Hence, it is not recommended that asymptomatic patients undergo surveillance involving imaging studies more often than once a year.

Background: Gastric cancer with undifferentiated histology has different clinicopathologic characteristics compared to differentiated type gastric cancer. We aimed to compare the risk of synchronous or metachronous tumors after curative resection of early gastric cancer (EGC) via endoscopic submucosal dissection (ESD), according to the histologic differentiation of the primary lesion., Methods: Clinicopathological data of patients with initial-onset EGC curatively resected via ESD between January 2007 and November 2014 in a single institution were reviewed. We analyzed the incidence of synchronous or metachronous tumors after ESD with special reference to the differentiation status of the primary lesion., Results: Of 1,560 patients with EGC who underwent curative resection via ESD, 1,447 had differentiated type cancers, and 113 had undifferentiated type cancers. The cumulative incidence of metachronous or synchronous tumor after ESD was higher in the differentiated cancer group than in the undifferentiated cancer group (P = 0.008). Incidence of metachronous or synchronous tumor was 4.8% and 1.2% per person-year in the differentiated and undifferentiated cancer groups, respectively. The Cox proportional hazard model revealed that undifferentiated cancers were associated with a low risk of synchronous or metachronous tumors after adjusting for confounding variables (hazard ratio [95% confidence interval] = 0.287 [0.090-0.918])., Conclusions: The rate of synchronous or metachronous tumors after curative ESD was significantly lower for undifferentiated cancers compare to differentiated cancers. These findings suggest that ESD should be actively considered as a possible treatment for undifferentiated type EGCs.

Background: The ABCD screening method was developed for risk stratification of gastric cancer. It is unclear whether the ABCD method can predict the risk of gastric neoplasms, including gastric adenomas, as observed for gastric cancer. We aimed to devise a modified ABCD method for predicting gastric neoplasms., Methods: We reviewed 562 patients who had undergone upper gastrointestinal tract endoscopy and whose serum IgG anti-Helicobacter pylori antibody, gastrin, and pepsinogen (PG) I and PG II data were available. Patients were classified into the following four groups: H. pylori antibody negative and normal PG level (group A), H. pylori antibody positive and normal PG level (group B), H. pylori antibody positive and low PG level (group C), and H. pylori antibody negative and low PG level (group D)., Results: The PG I/PG II ratio was lower in patients with gastric neoplasms than in patients without these lesions (gastric adenoma vs gastric cancer vs no neoplasm, 3.7 ± 2.0 vs 3.8 ± 1.8 vs 4.9 ± 2.1, P < 0.001). The optimal cutoff values of the PG I/PG II ratio for predicting gastric neoplasms were 3.1 for H. pylori antibody negative patients and 4.1 for H. pylori antibody positive patients. A higher group grade was associated with a significantly higher proportion of gastric neoplasms [odds ratio (95 % confidence interval), group A, reference; group B, 1.783 (1.007-3.156); group C, 3.807 (2.382-6.085); and group D, 5.862 (2.427-14.155)]., Conclusions: The modified ABCD method using two different cutoff values according to the H. pylori antibody status was useful for predicting the presence of gastric neoplasms. This method might be a supplementary screening tool for both gastric adenoma and gastric cancer. However, further studies will be required to provide a definitive conclusion.

Background: Synchronous gastric neoplasms are not infrequently detected, thus endoscopic submucosal dissection (ESD) for multiple early gastric neoplasia is occasionally considered. However, there have been few investigations of the safety and feasibility of simultaneous ESD for multiple gastric lesions. This study aims to evaluate the safety and feasibility of simultaneous ESD for multiple gastric neoplasia., Methods: A total of 1823 patients who underwent ESD for 1929 gastric adenomas or early gastric cancers were retrospectively reviewed in this study. Two hundred gastric adenomas or early gastric cancers among 94 patients were treated by ESD simultaneously (multiple group), and 1729 patients were treated with ESD for a single lesion (single group)., Results: En bloc resection (P = 0.060), complete resection (P = 0.362) and curative resection (P = 0.108) rates did not differ between the two groups. Rates of adverse events including bleeding (P = 0.317), perforation (P = 0.316) and aspiration pneumonia (P = 0.563) were not higher in the multiple group. Long-term follow-up showed more frequent local recurrence (P < 0.001), synchronous neoplasia (P = 0.041) and metachronous neoplasia (P < 0.001) per patient in the multiple group; however, local recurrence per lesion did not differ between the two groups (P = 0.103)., Conclusions: Simultaneous ESD for multiple synchronous gastric neoplasms is safe and feasible compared to single ESD. However, thorough examination for local recurrence and synchronous and metachronous neoplasia is required.

Purpose: There is insufficient data about the role of eradication of H. pylori after endoscopic resection (ER) for gastric dysplasia. The aim was to investigate the benefit of H. pylori eradication after ER in patients with gastric dysplasia to prevent metachronous gastric neoplasms., Materials and Methods: We retrospectively reviewed 1872 patients who underwent ER of gastric dysplasia. We excluded patients with a follow-up period of <2 years or who had not undergone tests for active H. pylori infection. A total of 282 patients were enrolled. The patients were categorized into those without active H. pylori infection (H. pylori-negative group, n = 124), those who successfully underwent H. pylori eradication (eradicated group, n = 122), and those who failed or did not undergo H. pylori eradication (persistent group, n = 36)., Results: Metachronous recurrence was diagnosed in 36 patients, including 19 in the H. pylori-negative group, 10 in the eradicated group, and 7 in the persistent group. The cumulative incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group in comparison with either of the H. pylori-persistent (non-eradicated or failed) groups (p = 0.039). Similarly, the incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group compared with the H. pylori-negative group (p = 0.041)., Conclusion: Successful H. pylori eradication may reduce the development of metachronous gastric neoplasms after ER in patients with gastric dysplasia.

Background: Although gastric gastrointestinal stromal tumors (GISTs) are usually identified by endoscopic examinations, the diagnostic value of endoscopy has not been fully evaluated. We assessed the diagnostic performance of endoscopy for gastric GISTs according to lesion characteristics. Furthermore, the benefits of periodic endoscopy prior to diagnosis of gastric GISTs were evaluated., Methods: We reviewed patients who underwent surgery for gastric GISTs at Severance Hospital, Seoul, Korea, between January 2008 and April 2014. In addition, we administered a questionnaire to determine the usage of periodic endoscopic inspection and the period from the penultimate endoscopy to the diagnosis., Results: Of 174 included patients, 109 (62.4 %) showed intraluminally growing GISTs and 65 (37.4 %) showed extraluminally growing GISTs. The proportions of lesions that were initially diagnosed via endoscopy were 99.1 % for intraluminally growing GISTs and 49.2 % for extraluminally growing GISTs (P < 0.001). In patients with intraluminally growing GISTs, patients who had undergone endoscopy within 3 years prior to the diagnosis showed smaller tumor sizes (P = 0.015) and fewer tumors with ulceration (7.1 vs. 28.4 %, P = 0.021). The proportion of GISTs with a high mitotic index did not differ according to the usage of periodic endoscopy (P = 0.639). In contrast, lesion characteristics of the extraluminally growing GISTs did not differ according to whether an endoscopy was performed within 3 years prior to the diagnosis., Conclusions: Endoscopic examinations had a limited role in the diagnosis of extraluminally growing GISTs. However, periodic endoscopy was associated with relatively earlier detection of growth in intraluminal gastric GISTs.

Background: Palliative chemotherapy is used to prolong survival among elderly patients with inoperable gastric cancer (GC). We analyzed differences between single and combination first-line palliative chemotherapy among these patients., Methods: Included patients were >70 years old and were treated for GC at four clinical centers of the Catholic University of Korea. Baseline characteristics, the first-line chemotherapy regimen, treatment responses, toxicities, progression-free survival (PFS), and overall survival (OS) were evaluated., Results: Between 2005 and 2012, 178 > 70-year-old patients with GC received palliative chemotherapy using single or combination regimens. Median ages were 77 years (range 71-89) in the single regimen group (SG, 70 patients) and 73 years (range 71-81) in the combination group (CG, 108 patients). Patients in the SG received S-1 or capecitabine. The most common regimen in the CG was platinum combined with fluorouracil. The most common response in both groups was stable disease (SG, 45.7 %; CG, 48.1 %). In the SG and CG, median PFS times were 4.4 months (95 % confidence interval [CI] 2.85-5.95) and 4.1 months (95 % CI 2.62-5.57; P = 0.295), respectively; median OS times were 6.6 months (95 % CI 4.17-9.08) and 7.6 months (95 % CI 5.50-9.69; P = 0.782), respectively. Hematologic (P < 0.001) and non-hematologic toxicities (P < 0.001) were more frequent in the CG. The most common causes of chemotherapy cessation were disease progression in the SG and decreased performance status in the CG., Conclusions: Single-agent treatment should be considered a first-line palliative chemotherapy option for elderly patients with GC.

Background: Safety of endoscopic resection (ER) for early gastric cancers (EGC) with mixed histology predominantly of differentiated type has not been securely established, since those lesions tend to exhibit lymph node metastasis, compared to pure differentiated type. The purpose of this study was to evaluate clinicopathologic characteristics, therapeutic outcomes, and risk for lymph node metastasis in predominantly differentiated mixed EGC treated by ER., Methods: A total of 1,016 patients with 1,039 EGCs underwent ER between January 2007 and June 2013. Enrolled lesions were divided into groups of either pure differentiated (n = 1,011) or predominantly differentiated mixed (n = 28), according to the presence of mixed histology predominantly of differentiated type in ER specimen., Results: Mixed histology predominantly of differentiated type was diagnosed in 2.7% of lesions. Larger size, mid-third location, and moderately differentiated histology on forceps biopsy were independent risk factors for the predominantly differentiated mixed histologic type of EGC in multivariate analysis. En bloc resection rate tended to be lower, and complete and curative resection rates were significantly lower in the predominantly differentiated mixed group. The rate of lymph node metastasis in the lesions with additional operation tended to be higher, in this mixed histology group., Conclusions: Larger size, mid-third location, and moderately differentiated histology on forceps biopsy carry the significant risk for mixed histology predominantly of differentiated type. EGC with predominantly differentiated mixed histologic type affects therapeutic outcomes and consequent clinical course accompanied by possibly higher risk for lymph node metastasis. The safety of ER for predominantly differentiated mixed EGC should be validated by further prospective investigation.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are most commonly found in the stomach. Although GISTs can spread to the liver and peritoneum, metastasis to the skeletal muscle is very rare and only four cases have previously been reported. These cases involved concurrent skeletal metastases of primary GISTs or liver metastases. Here, we report the first case of a distant recurrence in the brachialis muscle after complete remission of an extra-luminal gastric GIST following a wedge resection of the stomach, omental excision, and adjuvant imatinib therapy for one year. Ten months after therapy completion, the patient presented with swelling and tenderness in the left arm. Magnetic resonance imaging revealed a large mass in the brachialis muscle, which showed positivity for c-kit and CD34 upon pathologic examination. This is the first reported case of a solitary distant recurrence of a GIST in the muscle after complete remission had been achieved.

Background: There is controversy about the effect of Helicobacter pylori (H. pylori) eradication on the prevention of metachronous gastric cancer after endoscopic resection (ER)., Aims: The aim of this study was to systematically evaluate the effect of H. pylori eradication on the prevention of metachronous gastric lesions after ER of gastric neoplasms., Methods: We performed a systematic search of PubMed, EMBASE, the Cochrane Library, and MEDLINE that encompassed studies through April 2014. Our meta-analysis consisted of 10 studies, which included 5881 patients who underwent ER of gastric neoplasms., Results: When we compared the incidence of metachronous lesions between H. pylori-eradicated and non-eradicated groups, H. pylori eradication significantly lowered the risk of metachronous lesions after ER of gastric neoplasms (five studies, OR = 0.392, 95% CI 0.259 - 0.593, P < 0.001). When we compared H. pylori-eradicated and persistent groups, again, H. pylori eradication significantly lowered the incidence of metachronous lesions after ER of gastric neoplasms (six studies, OR = 0.468, 95% CI 0.326 - 0.673, P < 0.001). There was no obvious heterogeneity across the analyzed studies., Conclusions: This meta-analysis suggests a preventive role for H. pylori eradication for metachronous gastric lesions after ER of gastric neoplasms. Thus, H. pylori eradication should be considered if H. pylori infection is confirmed during ER.

Background: EUS is an operator-dependent procedure and requires more technical and cognitive skills than a routine endoscopic procedure. The learning curve for the staging of gastric cancer, however, has not been evaluated., Objective: To evaluate the threshold number of EUS examinations for gastric cancer T staging., Design: Retrospective study., Setting: University-affiliated tertiary care hospital in the Republic of Korea., Patients: Four trainees with no previous EUS experience., Intervention: Analyzing performance of EUS trainees in gastric cancer T staging by using cumulative sum (CUSUM) analysis., Main Outcome Measurements: CUSUM plot and a minimal number of procedures for reaching a plateau., Results: A total of 553 initial EUS examinations for treatment-naïve gastric cancers, performed by trainees, were enrolled in the study. The final T stage was determined by experts by using EUS in 332 gastric cancer cases, whereas the T stage of the other 221 lesions was determined by trainees by using EUS. The accuracy of EUS examinations performed by trainees and experts was 72.6% and 84.3%, respectively. The number of EUS examinations required to reach the first plateau in each trainee was 20, 41, 60, and 65., Limitations: Retrospective study with a relatively small number of trainees., Conclusion: The CUSUM scores of all of 4 trainees in the study reached a plateau by the 65th examination., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background/aims: Interval gastric cancer (IGC) is defined as cancer that is diagnosed between the time of screening and postscreening esophagogastroduodenoscopy (EGD). Un-fortunately, little is known about the characteristics of IGC in Korea, a country with a high incidence of gastric cancer. The aim of this study was to evaluate the clinicopathologic char-acteristics of IGCs in Korea., Methods: From January 2006 to July 2011, a total of 81,762 subjects underwent screening EGD at Yonsei University Health Promotion Center, Seoul, Ko-rea. We defined missed cancer as cancer diagnosed within 1 year of screening EGD and latent cancer as cancer diag-nosed more than 1 year after EGD., Results: A total of 16 IGC patients (17 lesions; three missed cancers and 14 latent can-cers) were identified, with a mean age of 60.68 years and a mean interval time of 19.64 months. IGCs tended to be undifferentiated (12/17, 70.6%), located in the lower body of the stomach (12/17, 70.6%) and exhibited flat/depressed endoscopic morphology (11/17, 64.7%). The patients with missed cancer were generally younger than the patients with latent cancer (51.3 years vs 62.8 years, p=0.037), and the patients with undifferentiated cancer were significantly younger than those with differentiated cancer (57.0 years vs 68.8 years, p=0.008)., Conclusions: IGCs tended to be undif-ferentiated, located in the lower body of the stomach, and exhibited flat/depressed endoscopic morphology. (Gut Liver, 2015;9167-173).

Background: Although pain is a common complication of endoscopic submucosal dissection (ESD), management strategies are inadequate. The aim of this study was to evaluate the efficacy of topical bupivacaine and triamcinolone acetonide for abdominal pain relief and as a potential method of pain control after ESD for gastric neoplasia., Methods: In this randomized, double-blind, placebo-controlled trial, 111 eligible patients with early gastric neoplasm were randomized into one of three groups: bupivacaine (BV) only, bupivacaine with triamcinolone (BV-TA), or placebo. The present pain intensity (PPI) score and the Short-Form McGill Pain Questionnaire (SF-MPQ) were used to evaluate pain at 0, 6, 12, and 24 h after ESD., Results: The mean values for the 6-hour PPI in the BV-TA and BV groups were lower than those of the placebo group (1.57 ± 1.09 and 1.97 ± 1.09 vs. 2.63 ± 0.98, p < 0.001). The 12-hour PPI of the BV-TA group (1.20 ± 0.83) was the lowest among the three groups (p = 0.001). The total 6-hour SF-MPQ score, especially in the sensory domain, was higher in the placebo group than in BV and BV-TA groups. The 12-hour SF-MPQ score was the lowest in the BV-TA group. Multivariate analysis demonstrated that BV-TA injection protocol, fibrosis, and size of residual ulcer were independently associated with the PPI score at 6 h., Conclusion: Bupivacaine after ESD was effective for pain relief at 6 h postoperatively. Particularly, topical infiltration of bupivacaine mixed with triamcinolone acetonide was helpful for producing a more long-lasting benefit of pain relief after gastric ESD.

Background: Self-expandable metal stent (SEMS) placement and palliative gastrojejunostomy (GJJ) are palliative treatment options for malignant gastric outlet obstruction., Objective: To compare clinical outcomes of palliative treatments for gastric outlet obstruction caused by unresectable gastric cancer., Design: Retrospective study., Setting: University-affiliated tertiary-care hospital in the Republic of Korea., Patients: Two hundred fifty-six patients with gastric outlet obstruction caused by unresectable gastric cancer., Intervention: SEMS placement and palliative GJJ., Main Outcome Measurements: Patency duration and overall survival duration., Results: In total, 217 and 39 patients underwent SEMS placement and palliative GJJ, respectively, as an initial palliative treatment. Treatment modality affected reobstruction after clinical success (hazard ratio [HR] [95% confidence interval {CI}], 0.5 [0.3-0.8] of palliative GJJ). In addition, carcinomatosis with ascites was an independent associated factor of clinical success and reobstruction (HR [95% CI], 0.3 [0.1-0.7] and 1.4 [1.0-2.0], respectively). In a subgroup of patients with good performance who had neither carcinomatosis nor ascites, patency duration and overall survival duration did not differ between the 2 groups (P = .079 and P = .290, respectively). In patients with good performance who had carcinomatosis without ascites, patency duration was longer in the palliative GJJ group than in the SEMS placement group (P = .016). Overall survival, however, did not differ between the 2 groups (P = .062). In a subgroup of patients with good performance who had carcinomatosis with ascites, both patency duration and overall survival were longer in the palliative GJJ group than in the SEMS placement group (P = .007 and P = .012, respectively)., Limitations: Nonrandomized, retrospective study., Conclusion: Long-term clinical outcomes of the palliative treatment modality for gastric outlet obstruction caused by unresectable gastric cancer were affected by carcinomatosis and ascites status., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: In early gastric cancer (EGC) and gastric adenoma, residual tumors may develop despite complete endoscopic resection (ER). To improve the chance of curative resection, we investigated the risk factors of residual tumor development in completely resected gastric epithelial neoplasia after ER., Methods: In total, 3,879 gastric epithelial neoplasms showing complete resection after ER were examined; 46 (1.2 %) residual tumors were found upon follow-up endoscopy. Clinicopathological characteristics were evaluated between those with and without residual tumors., Results: For gastric adenoma, high-grade dysplasia and severe intestinal metaplasia (IM) in the background mucosa were significantly associated with residual tumors. For EGC, poorly differentiated adenocarcinoma (PD), signet ring cell carcinoma (SRC), having a minimum lateral safety margin of <3 mm, and localization in the upper third of the stomach were significantly associated with residual tumors. Multivariate analysis revealed that a lateral safety margin of <3 mm (OR 13.8; p < 0.001), PD (OR 16.3; p = 0.014), and SRC (OR 9.8; p = 0.009) among EGC patients, and severe IM in the background mucosa (OR 9.0; p = 0.024) among gastric adenoma patients, were significantly associated with residual tumors., Conclusions: For neoplasms with undifferentiated histology (PD or SRC), short-term endoscopic follow-up may help to detect residual tumors that form after complete resection via ER. For EGC, the lateral margin may be considered safe if greater than 3 mm. However, the possibility of satellite lesions should be investigated when the gastric adenoma to be resected is surrounded by severe IM.

Background: Quality indicators of screening esophagogastroduodenoscopy are essential to improve the detection rate of gastric cancer. However, a reliable, practical indicator of the performance of endoscopists in screening esophagogastroduodenoscopy has not yet been identified., Aims: We aimed to identify quality indicators of esophagogastroduodenoscopy for the detection of early gastric neoplasms, including gastric dysplasia and early gastric cancer, focusing on the endoscopic findings., Methods: The records of 54,889 individuals who underwent esophagogastroduodenoscopy for gastric cancer screening at the Yonsei University Severance Hospital Health Promotion Center, Seoul, Korea, between February 2006 and July 2013 were analyzed. The detection rates for various gastric lesions including early gastric neoplasms were analyzed for each endoscopist., Results: Gastric dysplasia, early gastric cancer, and advanced gastric cancer were detected in 97 (0.18 %), 54 (0.10 %), and 21 (0.04 %) of 54,889 individuals, respectively. Multivariate analysis showed that the detection rates of gastric subepithelial lesions and gastric diverticuli were independent factors associated with the detection rate of early gastric neoplasms (regression coefficients of 0.096 and 0.532, respectively). A quality score formula was deduced using these regression coefficients to predict the ability of an endoscopist to detect early gastric neoplasms. A trend test confirmed that the group of endoscopists with a higher quality score showed a significantly higher rate of early gastric neoplasm detection (P < 0.001)., Conclusions: The detection rates of gastric subepithelial lesions and gastric diverticuli are well correlated with that of early gastric neoplasms. In addition, the proposed quality scoring system could be a good quality indicator for the detection of early gastric neoplasms.

Background and Aim: Metachronous recurrence often occurs after endoscopic submucosal dissection for early gastric cancer, and a method for preventing recurrence is unknown. We aimed to identify risk factors for metachronous lesions, and the effects of aspirin use and Helicobacter pylori eradication on preventing recurrence., Methods: A total of 1041 consecutive patients who underwent endoscopic submucosal dissection for early gastric cancer between January 2007 and December 2011 were retrospectively analyzed. Every patient was examined endoscopically at 2, 6, and 12 months after endoscopic submucosal dissection, and then annually. Patients were classified into the metachronous group or non-metachronous group according to the existence of metachronous lesions and subdivided by Helicobacter pylori status into three groups: not infected, eradicated after infection, and not eradicated., Results: At 39 months' median follow-up, metachronous gastric lesions had developed in 35 patients (3.4%), including 16 with dysplasia and 19 cancers. Metachronous group were significantly older than non-metachronous group (P = 0.02). Although non-metachronous group took aspirin more frequently than metachronous group (15.5% vs 5.7%), the difference was statistically insignificant (P = 0.11). In the not eradicated group, the odds ratio of metachronous lesion was 7.762 compared with the not infected group (95% confidence interval, 1.483-60.854; P = 0.02). In the eradicated group, the odd ratio of metachronous lesion was 8.120 compared with not infected group (95% confidence interval, 1.950-58.985; P = 0.01)., Conclusion: Helicobacter pylori infection was an independent risk factor for metachronous gastric lesions. However, eradication of Helicobacter pylori alone does not prevent all metachronous lesions in an inflamed stomach., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background: Several studies have shown that the neutrophil to lymphocyte ratio (NLR) in peripheral blood is a prognostic factor of various cancers. However, there is limited information on the clinical and prognostic significance of NLR in patients with metastatic advanced gastric cancer (AGC). Therefore, we examined whether the NLR can be used as a prognostic marker for predicting chemotherapeutic response and survival outcomes in metastatic AGC patients who are receiving palliative chemotherapy., Method: A total of 268 patients diagnosed with metastatic AGC were enrolled. NLR was calculated from complete blood cell count taken before the first chemotherapy treatment. Patients were divided into two groups according to the median value of NLR: a high NLR group and a low NLR group., Result: The median follow-up period was 340 days (range 72-1796 days) and median NLR was 3.06 (range 0.18-18.16). The high NLR group (NLR >3.0) contained 138 patients and the low NLR group (NLR ≤3.0) contained 130 patients. Low NLR group patients had a significantly higher chemotherapeutic disease control rate (90.0 % vs. 80.4; P = 0.028), and longer progression-free survival (PFS) and overall survival (OS) than the high NLR group patients (186 vs. 146 days; P = 0.001; 414 vs. 280 days; P < 0.001, respectively). In multivariate analysis, NLR showed a significant association with PFS (HR 1.478; 95 % CI 1.154-1.892; P = 0.002) and OS (HR 1.569; 95 % CI 1.227-2.006; P < 0.001)., Conclusion: Pretreatment NLR is a useful prognostic marker in patients with metastatic AGC who are undergoing palliative chemotherapy.

Background: Endoscopic submucosal dissection is applied in selected cases of signet ring cell early gastric cancer. However, factors related to curability of signet ring cell early gastric cancer with this method have not been fully evaluated. Our aim was to evaluate factors related to incomplete resection in signet ring cell early gastric cancer with endoscopic submucosal dissection., Methods: A retrospective analysis was performed on a total of 126 consecutive patients with signet ring cell early gastric cancer who had undergone endoscopic submucosal dissection at the Severance Hospital in Korea, between March 2007 and March 2012. The clinical outcomes were reviewed and factors related to incomplete resection were analysed., Results: Multivariate analysis showed that large tumour size was the only significant factor related to incomplete resection (P=0.006; hazard ratio, 1.040; 95% confidence interval, 1.101-1.084). In addition, large tumour size was the only significant factor related to endoscopic size underestimation (P<0.001; hazard ratio, 1.391; 95% confidence interval, 1.221-1.586). The rate of endoscopic size underestimation was significantly higher in tumours with a size ≥20mm (P<0.001)., Conclusions: To improve the curability of signet ring cell early gastric cancer with endoscopic submucosal dissection, larger tumours (especially tumour with a size ≥20mm) should be resected with a larger margin., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)