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Background: Checking Helicobacter pylori susceptibility tests in the clinical setting before first-line treatment is considered difficult. We compared susceptibility-guided therapy (SGT) with empirical therapy (ET) as a first-line treatment containing clarithromycin and investigated the eradication rate using antimicrobial susceptibility testing (AST)., Methods: 257 patients with H. pylori infection, with AST, performed before the eradication of clarithromycin-containing regimens were enrolled and divided into two groups: the SGT and ET groups., Results: Eradication rates in the SGT and ET groups were 85.4% and 58.4% ( P < 0.01), respectively. In triple therapy (TT), eradication rates of the SGT and ET groups were 85.1% and 56.6% ( P < 0.01), respectively. In sequential therapy (SET), eradication rates of the SGT and ET groups were 86.2% and 65.6% ( P = 0.06), respectively. According to AST, TT had an eradication rate of 84.6% with strains susceptible to clarithromycin and amoxicillin and 11.1% with strains resistant to both. SET had an eradication rate of 89.5% with strains susceptible to clarithromycin, amoxicillin, and metronidazole, whereas it was 0% with strains resistant to clarithromycin and metronidazole., Conclusions: SGT as first-line treatment improved eradication rates of TT and SET by 28.5 ( P < 0.01) and 20.6 ( P = 0.06) percent points, respectively, compared with ET.

Background: Bismuth-containing quadruple therapy is an effective alternative first-line therapy for Helicobacter pylori infection. We evaluated the efficacy and safety of a modified twice-a-day bismuth quadruple regimen (BQT-2) with low-dose (1000 mg total) metronidazole as first-line therapy for the eradication of H pylori., Materials and Methods: In this prospective pilot study, patients diagnosed with H pylori infection and naïve to eradication therapy were included. The modified BQT-2 therapy consisted of rabeprazole 20 mg, amoxicillin 1 g, metronidazole 500 mg, and tripotassium dicitrato bismuthate 600 mg (elemental bismuth 240 mg) twice daily, given 30 minutes before morning and evening meals for 14 days. H pylori eradication was assessed by 13 C-urea breath test conducted at least 4 weeks after therapy completion., Results: In 66 patients who received the modified BQT-2 regimen, the compliance rate was 100% and the H pylori eradication rate was 77.3%. H pylori was successfully cultured in 50 (75.8%) patients. The resistance rates to metronidazole and clarithromycin were 30.0% and 22.0%, respectively. Eradication rates were not significantly different according to the resistance to metronidazole (metronidazole-susceptible: 74.3% [26/35], metronidazole-resistant: 73.3% [11/15]; P > .99). Most of the adverse events were mild, with 20 (30%) patients developing nausea, epigastric soreness, loose stool, asthenia, skin rash, dizziness, taste perversion, headache, or dyspepsia., Conclusions: Twice-a-day modified BQT-2 regimen with low-dose metronidazole was suboptimal as an alternative first-line therapy for eradicating H pylori, despite high patient compliance., (© 2020 John Wiley & Sons Ltd.)

Background: The development of the endoscopic technique has resulted in an increasing number of patients undergoing percutaneous endoscopic gastrostomy (PEG) insertion; however, the protocols for increasing the volume of feeding formula after PEG insertion have not been established. Therefore, we compared the clinical outcomes of patients receiving low- and high-volume increase in enteral feeding formula., Methods: A total of 215 patients who underwent PEG insertion between January 2016 and March 2019 were included. They were divided into 2 groups according to the increase in volume of feeding formula: the low-volume group (n = 135) received ≤150 mL/d, and the high-volume group (n = 80) received ≥300 mL/d. Patient characteristics, procedure, and feeding-related clinical outcomes were retrospectively reviewed using medical records., Results: The adverse events of the feeding protocol did not significantly differ between the 2 groups. The number of days needed to attain the calorie targets was significantly lower in the high-volume group than in the low-volume group (5.4 ± 3.0 vs 2.4 ± 1.5; P < .001). The duration of supplemental parenteral nutrition and the length of hospitalization were also significantly lower in the high-volume group (3.9 ± 3.3 vs 1.2 ± 2.2; P < .001 and 5.8 ± 2.7 vs 4.6 ± 2.6; P = .007, respectively)., Conclusion: To rapidly attain the calorie targets in appropriately selected patients with PEG insertion, a high-volume increase in daily feeding can safely be recommended given the favorable outcomes., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Background and Aim: There are few cases of duodenal mucosa-associated lymphoid tissue (MALT) lymphoma reported in the literature, and little is known about the clinical course of this disease. Here, we aimed to characterize the clinical features of duodenal MALT lymphoma by comparison with gastric MALT lymphoma., Methods: Thirteen patients diagnosed with duodenal MALT lymphoma at Asan Medical Center from March 1997 to February 2017 were included in this retrospective study, along with patients with gastric MALT lymphoma, matched by age and sex at a 1:10 ratio., Results: Median age of patients with duodenal MALT lymphoma was 49 (range 20-72) years, and 53.8% (7/13) were male. Comparison of patient characteristics indicated that Helicobacter pylori infection (46.2% vs 90.8%, P < 0.001) and lymph node metastasis (23.1% vs 5.4%, P = 0.049) rates differed between patients with duodenal and gastric MALT lymphoma. Overall complete remission (61.5% vs 86.2%, P = 0.021) and complete remission after initial H. pylori eradication therapy (50% vs 87.7%, P = 0.037) were significantly lower in patients with duodenal than gastric MALT lymphoma. Complications including bleeding, stricture, and transformation to high-grade lymphoma occurred in a total of seven patients (4.9%), with a higher incidence in patients with duodenal than gastric MALT lymphoma (38.5% vs 1.5%, P < 0.001)., Conclusions: Duodenal MALT lymphoma is very rare, and treatment outcomes appear to be inferior to those of gastric MALT lymphoma., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Obesity, along with its comorbidities, has become a significant public health concern worldwide. Bariatric surgery is considered the most effective treatment modality; however, only 2% of patients with obesity undergo bariatric surgery. Endoscopic bariatric and metabolic therapies (EBMTs) are emerging alternatives to traditional bariatric surgery for patients who are not eligible for or do not prefer surgical treatment. EBMTs are generally categorized as space-occupying, gastric restrictive, aspiration, and small bowel therapies. We aimed to review various non-balloon and non-gastroplasty devices with available clinical data and discuss the possible mechanisms of action, efficacy, and safety profile of these EMBTs.

Signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) are two representative transcription factors that play a critical role in inflammation-associated tumorigenesis through multi-level cooperation. Unlike other types of tumors, breast carcinomas have shown a significant dependency on the non-classical NF-κB pathway as well as the classical one. The α subunit of the inhibitor of the κB kinase (IKK) complex, IKKα, is involved in both classical and non-classical activation of NF-κB. Although the cross-talk between STAT3 and NF-κB has been suggested in several studies, the interplay between STAT3 and the regulators of NF-κB including IKKα has not been fully clarified yet. In this study, we observed overexpression and co-localization of IKKα and STAT3 in human breast cancer tissues as well as in H- Ras transformed human breast epithelial (H- Ras MCF-10A) and breast cancer (MDA-MB-231) cells. By utilizing small interfering RNA (siRNA) technology, we were able to demonstrate that STAT3 up-regulated IKKα, but not IKKβ or IKKγ, in these cells. This was attributable to direct binding to and subsequent stabilization of IKKα protein by blocking the ubiquitin-proteasome system. Notably, we identified the lysine 44 residue of IKKα as a putative binding site for STAT3. Moreover, siRNA knockdown of IKKα attenuated viability, anchorage-independent growth and migratory capabilities of H- Ras MCF-10A cells. Taken together, these findings propose a novel mechanism responsible for NF-κB activation by STAT3 through stabilization of IKKα, which contributes to breast cancer promotion and progression. Thus, breaking the STAT3-IKKα alliance can be an alternative therapeutic strategy for the treatment of breast cancer.

Recent studies report that nuclear factor-erythroid-2-related factor 2 (Nrf2) facilitates tumor progression through metabolic reprogramming in cancer cells. However, the molecular mechanism underlying the oncogenic functions of Nrf2 is not yet well understood. Some of the pentose phosphate pathway (PPP) enzymes are considered to play a role in the cancer progression. The present study was intended to explore the potential role of phosphogluconate dehydrogenase (PGD), one of the PPP enzymes, in the proliferation and migration of human hepatoma HepG2 cells. Genetic ablation of Nrf2 attenuated the expression of PGD at both transcriptional and translational levels. Notably, Nrf2 regulates the transcription of PGD through direct binding to the antioxidant response element in its promoter region. Nrf2 overexpression in HepG2 cells led to increased proliferation, survival, and migration, and these events were suppressed by silencing PGD . Interestingly, knockdown of the gene encoding this enzyme not only attenuated the proliferation and clonogenicity of HepG2 cells but also downregulated the expression of Nrf2. Thus, there seems to exist a positive feedback loop between Nrf2 and PGD which is exploited by hepatoma cells for their proliferation and survival. Treatment of HepG2 cells with ribulose-5-phosphate, a catalytic product of PGD, gave rise to a concentration-dependent upregulation of Nrf2. Collectively, the current study shows that Nrf2 promotes hepatoma cell growth and progression, partly through induction of PGD transcription.

Background and Aims: Minimally invasive therapies for obesity are a bridge between lifestyle interventions and bariatric surgery. We developed a novel device to reduce weight gain rate and evaluated its safety and efficacy in juvenile pigs., Methods: The intragastric satiety-inducing device (ISD) comprises a self-expandable esophageal metal stent connected to a star-shaped disc placed in the stomach fundus. Eight juvenile pigs were randomized into ISD (n = 5) and control (n = 3) groups. Body weight and serum ghrelin hormone were monitored weekly for 6 weeks. One pig was followed up for 4 additional weeks (rebound pig) after ISD removal. Histological examination and immunohistochemistry for the interstitial cells of Cajal (ICCs) were performed., Results: ISD placement was successful in all pigs. Two ISDs (40%) migrated at 4 and 5 weeks after placement. Weight gain rates were significantly lower in the ISD group than in the control group from week 1 to 6 but were higher in the rebound pig than in a control pig from week 7 to 10. Mean ghrelin hormone level was higher in the control group than in the ISD group from week 1 to 6. ISD induced reversible inflammatory changes in the esophagus and stomach fundus. The number of ICCs was lesser in ISD pigs than in control and rebound pigs., Conclusions: ISD placement is feasible and safe in juvenile pigs. It decreases weight gain rate but induces reversible inflammatory reaction and tissue hyperplasia. Its mechanism may be related to pressure exertion on the stomach fundus or gastric motility alteration.

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the conversion of oncogenic prostaglandin E 2 to non-tumerigenic 15-keto prostaglandin E 2 . In the present study, we found that curcumin, a yellow coloring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), induced expression of 15-PGDH at the both transcriptional and translational levels in normal rat gastric mucosal cells. By using deletion constructs of 15-PGDH promoter, we were able to demonstrate that activator protein-1 (AP-1) is the principal transcription factor responsible for regulating curcumin-induced 15-PGDH expression. Curcumin enhanced the expression of c-Jun and c-Fos that are functional subunits of AP-1, in the nuclear fraction of cells. Silencing of c-Jun suppressed curcumin-induced expression of 15-PGDH. Moreover, the chromatin immunoprecipitation assay revealed curcumin-induced binding of c-Jun to the AP-1 consensus sequence present in the 15-PGDH promoter. Curcumin increased phosphorylation of ERK1/2 and JNK, and pharmacologic inhibition of these kinases abrogated the curcumin-induced phosphorylation of c-Jun and 15-PGDH expression. In contrast, tetrahydrocurcumin which lacks the α,β-unsaturated carbonyl group failed to induce 15-PGDH expression, suggesting that the electrophilic carbonyl group of curcumin is essential for its induction of 15-PGDH expression. Curcumin restored the expression of 15-PGDH which is down-regulated by Helicobacter pylori through suppression of DNA methyltransferase 1. In addition, oral administration of curcumin increased the expression of 15-PGDH and its regulators such as p-ERK1/2, p-JNK, and c-Jun in the mouse stomach. Taken together, these findings suggest that curcumin-induced upregulation of 15-PGDH may contribute to chemopreventive effects of this phytochemical on inflammation-associated gastric carcinogenesis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/aims: Percutaneous endoscopic gastrostomy (PEG) is usually performed on patients with chronic underlying diseases in the general ward (GW). This study evaluated the clinical outcomes of PEG performed on patients in the surgical intensive care unit (SICU) compared with those of PEG performed in the GW., Methods: The medical records of 27 patients in the SICU and 263 in the GW, who underwent PEG between January 2013 and July 2017, were retrospectively reviewed., Results: The median age of the 27 SICU patients was 66 years, and their median body mass index was 21.1 kg/m2. In the SICU group, the median baseline Sequential Organ Failure Assessment (SOFA) score was 4, and the median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 16. The median interval between surgery and PEG in SICU patients was 30 days, with a PEG failure rate of 3.7%. Acute complications in SICU patients included bleeding (7.4%) and ileus (11.1%), while chronic complications included aspiration pneumonia (7.4%) and tube obstruction (3.7%). The rates of acute and chronic complications did not differ significantly between the SICU and GW groups. The 30-day mortality rate was 14.8% in SICU patients and 5.3% in GW patients (p=0.073)., Conclusion: PEG is a safe and feasible method of enteral feeding for critically ill patients who require ICU care after surgery.

Chemotherapy is commonly used as a major therapeutic option for breast cancer treatment, but its efficacy is often diminished by disruption of patient's anti-tumor immunity. Chemotherapy-generated tumor cell debris could hijack accumulated tumor-associated macrophages (TAMs), provoking tumor recurrence. Therefore, reprogramming TAMs to acquire an immunocompetent phenotype is a promising strategy to potentiate therapeutic efficacy. In this study, we analyzed the proportion of immune cells in the breast cancer patients who received chemotherapy. To validate our findings in vivo, we used a syngeneic murine breast cancer (4T1) model. Chemotherapy generates an immunosuppressive tumor microenvironment in breast cancer. Here, we show that phagocytic engulfment of tumor cell debris by TAMs reduces chemotherapeutic efficacy in a 4T1 breast cancer model. Specifically, the engulfment of tumor cell debris by macrophages reduced M1-like polarization through heme oxygenase-1 (HO-1) upregulation. Conversely, genetic or pharmacologic inhibition of HO-1 in TAMs restored the M1-like polarization. Our results demonstrate that tumor cell debris-induced HO-1 expression in macrophages regulates their polarization. Inhibition of HO-1 overexpression in TAMs may provoke a robust anti-tumor immune response, thereby potentiating the efficacy of chemotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Gastric heterotopic pancreas (GHP) is generally asymptomatic and rarely features complications such as pancreatitis, pseudocysts, gastric outlet obstruction, bleeding, obstructive jaundice, or intussusception. However, the treatment of complicated GHP is challenging and often requires surgical resection., Aim: To investigate the clinical outcomes of endoscopic submucosal dissection (ESD) as alternative to surgical resection for complicated GHP., Methods: This is a single-center, retrospective study. Between January 2013 and December 2017, a total of 5 patients underwent ESD for complicated GHP at Asan Medical Center. Patients who were diagnosed with complicated GHP were treated conservatively as with general practice for acute pancreatitis. After conservative management for resolving the acute phase of pancreatitis, ESD was performed as definitive treatment for complicated GHP. ESD was performed using the conventional method under conscious sedation. The clinical features of patients and tumors, procedure-related characteristics, and long-term outcomes were investigated., Results: The age of the 5 patients ranged from 28-43 years. Two of the patients were males. All lesions were located in the greater curvature of the antrum. On endoscopic ultrasonography during the pain episode, all lesions were located across the muscularis mucosa, submucosa, and proper muscle layers. The median lesion size was 20 [interquartile range (IQR), 18-35] during the pain episode at the time of the diagnosis of complicated GHP, and 15 mm (IQR, 9-33) at the time of ESD after conservative treatment. The procedure time ranged from 15-120 min. There were no procedure-related adverse events such as perforation or bleeding. The length of hospital stay after the procedure ranged from 2-4 d. All patients were symptom free during the median follow-up period of 46.0 mo (IQR, 39-60)., Conclusion: ESD appears to be a feasible and effective treatment option for complicated GHP based on the favorable clinical outcomes., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Aims: Isolation of Helicobacter pylori is considered difficult because of the requirement of the additional biopsy tissue and the effort involved in the isolation of the bacterium. We investigated whether H pylori can be cultured from tissue samples used for the rapid urease test (RUT)., Methods: Totally, 174 specimens from 87 patients referred for endoscopy were prospectively included. During endoscopy, two biopsy specimens were obtained, one each from the gastric antrum and the corpus, and were placed into a commercially available RUT kit. After detection of urease activity, H pylori was cultured using tissue leftover in the RUT, regardless of the result., Results: H pylori was successfully isolated using leftover tissue in 72.4% (63/87) of the patients. In 32 patients, H pylori was isolated from both specimens, while in 31 patients, it was isolated from either antrum or corpus. Eighty-one H pylori strains were isolated from 141 specimens with positive RUT results (57.4%), whereas 14 strains were isolated from 33 specimens with negative RUT results (42.4%). The median interval between tissue acquisition and inoculation onto the isolation media was 3.6 hours (range: 0.5-27.5 hours) in cases with successful cultures, compared to 23.5 hours (range: 0.5-76.0 hours) in cases with failed cultures. Among the positive RUT tissues, 80.4% (45/56) were cultured successfully when the tissue was inoculated within 4 hours of the biopsy., Conclusions: RUT kits can be used as transport media for H pylori, and this media is most efficient when used within 4 hours of the test., (© 2020 John Wiley & Sons Ltd.)

In inflammation-associated carcinogenesis, COX-2 is markedly overexpressed, resulting in accumulation of various prostaglandins. 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ) is one of the terminal products of COX-2-catalyzed arachidonic acid catabolism with oncogenic potential. Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their polarity and adhesiveness, and thereby gain migratory and invasive properties. Treatment of human breast cancer MCF-7 cells with 15d-PGJ 2 induced EMT as evidenced by increased expression of Snail and ZEB1, with concurrent down-regulation of E-cadherin. Nuclear extract from 15d-PGJ 2 -treated MCF-7 cells showed the binding of Snail and ZEB1 to E-box sequences present in the E-cadherin promoter, which accounts for repression of E-catherin expression. Unlike 15d-PGJ 2 , its non-electrophilic analogue 9,10-dihydro-15d-PGJ 2 failed to induce EMT, suggesting that the α,β-unsaturated carbonyl group located in the cyclopentenone ring of 15d-PGJ 2 is essential for its oncogenic function. Notably, the mRNA level of interleukin-8 (IL-8)/CXCL8 was highly elevated in 15d-PGJ 2 -stimulated MCF-7 cells. 15d-PGJ 2 -induced up-regulation of IL-8/CXCL8 expression was abrogated by silencing of Snail short interfering RNA. Treatment of normal fibroblast with conditioned medium obtained from cultures of MCF-7 cells undergoing EMT induced the expression of activated fibroblast marker proteins, α-smooth muscle actin and fibroblasts activation protein-α. Co-culture of normal fibroblasts with 15d-PGJ 2 -stimulated MCF-7 cells also activated normal fibroblast cells to cancer associated fibroblasts. Taken together, above findings suggest that 15d-PGJ 2 induces EMT through up-regulation of Snail expression and subsequent production of CXCL8 as a putative activator of fibroblasts, which may contribute to tumor-stroma interaction in inflammatory breast cancer microenvironment., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed., (Copyright © 2020 Korean Society of Cancer Prevention.)

Helicobacter pylori (H. pylori) infection is considered as one of the principal risk factors of gastric cancer. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated gastric carcinogenesis. In the canonical STAT3 pathway, phosphorylation of STAT3 on Tyr705 is a major event of STAT3 activation. However, recent studies have demonstrated that STAT3 phosphorylated on Ser727 has an independent function in mitochondria. In the present study, we found that human gastric epithelial AGS cells infected with H. pylori resulted in localization of STAT3 phosphorylated on Ser727 (P-STAT3 Ser727 ), predominantly in the mitochondria. Notably, H. pylori-infected AGS cells exhibited the loss of mitochondrial integrity and increased expression of the microtubule-associated protein light chain 3 (LC3), the autophagosomal membrane-associated protein. Treatment of AGS cells with a mitophagy inducer, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), resulted in accumulation of P-STAT3 Ser727 in mitochondria. In addition, the elevated expression and mitochondrial localization of LC3 induced by H. pylori infection were attenuated in AGS cells harboring STAT3 mutation defective in Ser727 phosphorylation (S727A). We also observed that both P-STAT3 Ser727 expression and LC3 accumulation were increased in the mitochondria of H. pylori-inoculated mouse stomach.

Aberrant activation of H-Ras is often associated with tumor aggressiveness in breast cancer. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1  (Pin1) is a unique enzyme that interacts with phosphorylated serine or threonine of a target protein and isomerizes the adjacent proline residue. Pin1 is prevalently overexpressed in human cancers, and its overexpression correlates with poor prognosis. Nuclear factor E2-related factor 2 (Nrf2) is a master regulator of cellular redox homeostasis. The sustained activation/accumulation of Nrf2 has been observed in many different types of human malignancies, conferring an advantage for growth and survival of cancer cells. The activated form of H-Ras (GTP-H-Ras) is highly overexpressed in human breast cancer tissues. In our present study, silencing of H-Ras decreased the invasiveness of MDA-MB-231 human breast cancer cells and abrogated the interaction between Pin1 and Nrf2 in these cells. Pin1 knockdown blocked the accumulation of Nrf2, thereby suppressing proliferation and clonogenicity of MCF10A-Ras human mammary epithelial cells. We found that Pin1 binds to Nrf2 which stabilizes this transcription factor by hampering proteasomal degradation. In conclusion, H-Ras activation in cooperation with the Pin1-Nrf2 complex represents a novel mechanism underlying breast cancer progression and constitutive activation of Nrf2 and can be exploited as a therapeutic target., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: There are various patterns in determining the choice of the first-line antithrombotic agent for acute stroke with non-valvular atrial fibrillation. We investigated the efficacy and safety of non-vitamin K oral anticoagulants as first-line antithrombotics for patients with acute stroke and non-valvular atrial fibrillation., Materials and Methods: Patients with non-valvular atrial fibrillation and ischemic stroke or transient ischemic attack within 24 h from stroke onset were included. On the basis of the first regimen used and the regimen within 7 days after admission, the study population was divided into three groups: 1) antiplatelet switched to warfarin (A-W), 2) antiplatelet switched to NOAC (A-N), and 3) NOAC only (N only). We compared the occurrence of early neurologic deterioration, symptomatic intracranial hemorrhage, systemic bleeding, and poor functional outcome at 90 days., Results: Of 314 included patients, 164, 53, and 97 were classified into the A-W, A-N, and N only groups, respectively. Early neurologic deterioration was most frequently observed in the A-W group (9.1%), followed by the A-N (5.7%) and N only (1.0%) groups (p = 0.017). Multivariable analysis adjusting for potential confounders demonstrated that the N only group was independently associated with a lower rate of early neurologic deterioration (odds ratio [OR] 0.104, 95% CI 0.013-0.831) or poor functional outcome at 90 days (OR 0.450, 95% CI 0.215-0.940) than the A-W group. However, the rate of symptomatic intracranial hemorrhage or any systemic bleeding event did not differ among the groups., Conclusion: Using non-vitamin K oral anticoagulants as the first-line regimen for acute ischemic stroke may help prevent early neurologic deterioration without increasing the bleeding risk., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The proviral integration site for Moloney murine leukemia virus (PIM) family of serine/threonine-specific kinases consist of three isoforms, that regulate proliferation, apoptosis, metabolism, invasion, and metastasis of cancer cells. Among these, abnormally elevated kinase activity of PIM-1 contributes to the progression of gastric cancer and predicts poor prognosis and a low survival rate in gastric cancer patients. In the present study, we found that resveratrol, one of the representative chemopreventive and anticarcinogenic phytochemicals, directly binds to PIM-1 and thereby inhibits its catalytic activity in human gastric cancer SNU-601 cells. This resulted in suppression of phosphorylation of the proapoptotic Bad, a known substrate of PIM-1. Resveratrol, by inactivating PIM-1, also inhibited anchorage-independent growth and proliferation of SNU-601 cells. To understand the molecular interaction between resveratrol and PIM-1, we conducted docking simulation and found that resveratrol directly binds to the PIM-1 at the ATP-binding pocket. In conclusion, the proapototic and anti-proliferative effects of resveratrol in gastric cancer cells are likely to be mediated through suppression of PIM-1 kinase activity, which may represent a novel mechanism underlying its chemopreventive and anticarcinogenic actions., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Treatment of locally recurrent gastric neoplasms after endoscopic resection remains challenging. We investigated the efficacy and safety of treatment options for recurrent gastric neoplasms localized to the scar of previous endoscopic submucosal dissection (ESD)., Methods: The clinicopathological characteristics and treatment outcomes of patients who underwent endoscopic treatment or surgery for recurrent gastric neoplasms between June 2010 and May 2017 were retrospectively reviewed., Results: Of the 92 patients included, 74 underwent endoscopic treatment (51 redo ESD, 23 argon plasma coagulation [APC] ablation) and 18 underwent surgery. The redo ESD procedure time was significantly longer than that of the primary ESD (31.0 versus 22.0 min, p = 0.018). Overall, adverse events occurred in 11 patients (12.0%), with the incidence being significantly higher in the surgery group (27.8% versus 8.1% in the endoscopic treatment group, p = 0.036). Local recurrence-free survival rates were 81.1% for the endoscopic treatment group (86.3% and 69.6% for redo ESD and APC groups, respectively) and 100% for the surgery group (log rank p = 0.033). Logistic regression analysis showed that tumor size > 12.5 mm (odds ratio [OR] 5.14, 95% confidence interval [CI] 1.25-26.9, p = 0.032) and tumors located in the upper two-thirds of the stomach (OR 4.43, 95% CI 1.27-16.8, p = 0.023) were associated with non-curative resection after redo ESD., Conclusions: Endoscopic treatment could be an effective and safe alternative to surgery for selected patients with gastric neoplasms recurring at the scar of previous ESD. Especially, patients having small lesions located in the distal part of the stomach could be a good candidate for redo ESD.

Background: Esophageal bolus transit can be assessed using esophagogram or high-resolution impedance manometry (HRIM). The three-dimensional volume of inverted impedance (VII) has been developed to quantify the residual bolus between each swallow through spatiotemporal analysis. However, this novel metric has not been validated against simultaneous esophagogram., Methods: A total of nine healthy volunteers (Seven males, aged 19-45 years) were prospectively evaluated with HRIM and barium esophagogram. In addition, 21 symptomatic patients (12 males, aged 20-85 years) without major motility disorder were also included. The VII was estimated from HRIM data using MATLAB program and was compared with residual bolus volume in the esophagus estimated from simultaneous esophagogram., Key Results: A total of 80 swallows (24 in controls and 56 in patients) were analyzed. Results from the VII method were concordant with the bolus transit pattern estimated from the esophagogram in 91.3% (73/80) of swallows. The correlation between quantitative data from VII and the volume of residual bolus estimated from esophagogram was strong in both groups with a Pearson's correlation coefficient of 0.805 for healthy volunteers and 0.730 for symptomatic patients. The intraclass correlation coefficient of VII between the three swallows within a subject was 0.901 in healthy subjects and 0.705 in patients, indicating a modest reliability of this method., Conclusions and Inferences: The newly developed VII method is a reliable method in assessing residual bolus volume in the esophagus based on comparison with bolus volume estimated from simultaneous esophagogram., (© 2020 John Wiley & Sons Ltd.)

15-Deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), an endogenous ligand for PPARγ, has differential effects on cancer cell proliferation and survival depending on the dose and the type of cells. In the present study, we have investigated the effects of 15d-PGJ 2 on apoptosis of the Ha- ras transformed human breast epithelial (MCF10A- ras ) cells. When MCF10A- ras cells were treated with 15d-PGJ 2 (10 μM) for 24 hours, they underwent apoptosis as evidenced by characteristic morphological features, an increased proportion of sub-G 0 /G 1 cell population, a typical pattern of annexin V/propidium iodide staining, perturbation of mitochondrial transmembrane potential (Δψ m ), and cleavage of caspase-3 and its substrate PARP. A pan-caspase inhibitor, Z-Val-Ala-Asp (OCH 3 )-fluoromethyl ketone attenuated cytotoxicity and proteolytic cleavage of caspase-3 induced by 15d-PGJ 2 . The 15d-PGJ 2 -induced apoptosis was accompanied by enhanced intracellular accumulation of reactive oxygen species (ROS), which was abolished by the antioxidant N -acetyl-L-cysteine (NAC). 15d-PGJ 2 inhibited the DNA binding activity of NF-κB which was associated with inhibition of expression and catalytic activity of IκB kinase β (IKKβ). 15d-PGJ 2 -mediated inhibition of IKKβ and nuclear translocation of phospho-p65 was blocked by NAC treatment. 9,10-Dihydro-PGJ 2 , a non-electrophilic analogue of 15d-PGJ 2 , failed to produce ROS, to inhibit NF-κB DNA binding, and to induce apoptosis, suggesting that the electrophilic α,β-unsaturated carbonyl group of 15d-PGJ 2 is essential for its pro-apoptotic activity. 15d-PGJ 2 -induced inactivation of IKKβ was also attributable to its covalent thiol modification at the cysteine 179 residue of IKKβ. Based on these findings, we propose that 15d-PGJ 2 inactivates IKKβ-ΝF-κB signaling through oxidative or covalent modification of IKKβ, thereby inducing apoptosis in Ha- ras transformed human breast epithelial cells., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed., (Copyright © 2020 Korean Society of Cancer Prevention.)

Introduction: High resolution vessel wall MRI (VW-MRI) has enabled to characterize intracranial atherosclerosis (ICAS). We studied to identify the factors for enhancement of ICAS in VW-MRI in patients with acute ischemic stroke. Methods: Consecutive patients with acute ischemic stroke or TIA who underwent VW-MRI between January 2017 and December 2017 were included. Enhancement on VW-MRI was defined as an increase in intensity on contrast-enhanced T1-weighted sequence. We compared the clinical and the radiologic findings between patients with wall enhancement and those without wall enhancement. Results: Of the 48 patients with ICAS, 28 patients revealed enhancement on VW-MRI. Patients with enhancement were more likely to have severe stenotic lesions and higher levels of total cholesterol, triglycerides, low-density cholesterol, Apo (b), and Apo (b)/Apo (a) lipoprotein ratio ( p < 0.05). Multivariable analysis demonstrated that total cholesterol (OR: 5.378, 95% CI, 1.779-16.263), triglycerides (OR: 3.362, 95% CI, 1.008-11.209), low density lipoprotein cholesterol (OR: 4.226, 95% CI, 1.264-14.126), Apo (b) lipoprotein (OR: 3639.641, 95% CI, 17.854-741954.943) levels, and Apo (b)/Apo (a) lipoprotein ratio (OR, 65.514; 95% CI, 1.131-3680.239) were independently associated with enhancement of ICAS. High-density lipoprotein cholesterol and Apo (a) lipoprotein levels were not significantly different between the patients with wall enhancement and those without wall enhancement. Conclusions: The presence and severity of enhancement of ICAS was significantly associated with dyslipidemic conditions. These results suggest that strict lipid modification should be achieved for the management of ICAS., (Copyright © 2020 Woo, Na, Heo, Nam, Choi, Ahn, Choi, Lee, Lee, Cha and Kim.)

Background: The increasing prevalence of antimicrobial resistance, together with the lack of novel treatment options, negatively affects successful eradication of Helicobacter pylori . The aim of this study was to investigate genetic mutations in the 23S rRNA genes, which is associated with clarithromycin resistance, and to determine the clinical impact of genotype on phenotypic antimicrobial resistance., Methods: A total of 46 H. pylori strains were obtained from 13 patients, before and after unsuccessful eradication with clarithromycin-based triple therapy. The phenotypic resistance of each H. pylori strain was determined by minimum inhibitory concentration against clarithromycin using the serial two-fold agar dilution method. The genomic sequences of 23S rRNA genes were identified through next-generation sequencing, and nucleotide variants were determined based on comparison with genome sequences of the reference strain H. pylori 26695., Results: Clarithromycin resistance was found in 9 of 13 subjects before treatment and all subjects after unsuccessful eradication. Whole-genome sequencing of the 23S rRNA genes detected 42 mutations on 40 nonidentical loci, including 2147A>G (formerly 2143A>G) and 2146A>G (formerly 2142A>G). All strains with clarithromycin-resistant phenotype had either 2147A>G or 2146A>G mutation. When comparing genotype and phenotype for clarithromycin resistance, there was a significant association between 2147A>G mutation and clarithromycin-resistant phenotype., Conclusions: All clarithromycin-resistant strains had either 2146A>G or 2147A>G mutation, suggesting that tests targeting these two mutations may be enough for the prediction of clarithromycin resistance in this population.

Aim: The number of elderly patients with superficial esophageal neoplasms has steadily increased, but few studies have focused on the clinical outcomes of esophageal endoscopic submucosal dissection in these patients. Therefore, the aim of our study was to investigate the feasibility and safety of endoscopic submucosal dissection among elderly patients with superficial esophageal neoplasms., Methods: Patients who underwent endoscopic submucosal dissection for superficial esophageal neoplasms between December 2005 and December 2017 were eligible. The patients were divided into two groups according to age: Not-old (<75 years, n = 369) and Old (≥75 years, n = 44). Clinical features and treatment outcomes were retrospectively investigated by reviewing medical records., Results: In total, 413 patients with 459 lesions were enrolled in to this study. Comorbidities, except for a previous history of malignancy, were not significantly different between the two groups. Procedure-related characteristics and the rate of adverse events were similar in the two groups. During a median follow-up period of 33.4 months, the overall survival rate was lower in the Old group (P = 0.046), and the cumulative recurrence rate did not differ significantly between the two groups (P = 0.334)., Conclusion: Based on these favorable outcomes, endoscopic submucosal dissection is as feasible and effective for the treatment of superficial esophageal neoplasms among elderly patients as it is among non-elderly patients. Geriatr Gerontol Int 2020; 20: 430-435., (© 2020 Japan Geriatrics Society.)

Korean Red Ginseng (KRG) exerts chemopreventive effects on experimentally induced carcinogenesis through multiple mechanisms. In this study, we investigated effects of KRG on dextran sulfate sodium (DSS)-induced colitis and azoxymethane (AOM) plus DSS-induced colon carcinogenesis in mice. Male C57BL/6J mice were fed diet containing 1% KRG or a standard diet throughout the experiment. The mouse colitis was induced by administration of 3% DSS in drinking water for 1 week. DSS caused body weight loss, diarrhea, rectal bleeding and colon length shortening, and all these symptoms were ameliorated by KRG treatment. KRG inhibited DSS-induced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by suppressing activation of nuclear factor-kappa B (NF-κB) and signal transducer and activation of transcription 3 (STAT3). In another experiment, colon carcinogenesis was initiated by single intraperitoneal injection of AOM (10 mg/kg) and promoted by 2% DSS in drinking water. KRG administration relieved the symptoms of colitis and reduced the incidence, the multiplicity and the size of colon tumor. The up-regulation of COX-2, iNOS, c-Myc and Cyclin D1 by AOM plus DSS was attenuated in KRG fed mice which was associated with suppression of NF-κB and STAT3 activation. These results suggest that KRG is a potential candidate for chemoprevention of inflammation-associated cancer in the colon., Competing Interests: The authors declare no conflicts of interest in this work/, (© 2020 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Background: The association between Helicobacter pylori and reflux esophagitis (RE) remains controversial. This study aimed to prospectively evaluate the effect of H. pylori eradication on RE and gastroesophageal reflux (GERD) symptoms in H. pylori-positive patients who underwent endoscopic resection of gastric neoplasm., Methods: Of the 244 patients enrolled in this study, 173 H. pylori-positive patients underwent follow-up at least once. We evaluated the prevalence of RE and GERD symptoms in these patients following H. pylori eradication., Results: There were 75.7% (131/173), 78.6% (125/159), and 78.9% (105/133) subjects who were successfully eradicated after 6, 12, and 18-24 months, respectively. During the 2-year follow-up period, the eradication of H. pylori did not increase the incidence of RE (OR 0.93; 95% CI, 0.49-1.77, p = 0.828). H. pylori status was also not associated with the development of GERD symptoms (OR 1.12; 95% CI, 0.47-2.95, p = 0.721). In the univariate analysis for RE, present smoking history (OR 4.79; 95% CI 1.98-11.60, p = 0.001), present alcohol consumption history (OR 2.18; 95% CI 1.03-4.63, p = 0.041), and diabetes mellitus (OR 2.44; 95% CI 1.02-5.86, p = 0.045) were found to be associated with RE. Multivariate analysis showed that present smoking history (OR 4.54; 95% CI 1.84-11.02, p = 0.001) was a significant risk factor for RE., Conclusions: H. pylori eradication did not increase the incidence of RE or GERD symptoms in patients who underwent endoscopic resection of gastric neoplasm.

The present study was aimed to investigate the effects of curcumin, a representative chemopreventive phytochemical with pronounced antioxidant and anti-inflammatory properties, on activation of Nrf2 and expression of its target protein heme oxygenase-1 (HO-1) in mouse skin in vivo and in cultured murine epidermal cells. Treatment of mouse epidermal JB6 cells with curcumin resulted in the induction of HO-1 expression, and this was abrogated in cells transiently transfected with Nrf2 siRNA. While curcumin treatment increased protein expression of Nrf2, it did not alter the steady-state level of the Nrf2 mRNA transcript. Treatment of cells with curcumin stabilized Nrf2 by inhibiting ubiquitination and subsequent 26S proteasomal degradation of this transcription factor. Tetrahydrocurcumin, a non-electrophilic analogue of curcumin that lacks the α,β-unsaturated carbonyl group, failed to induce HO-1 expression as well as nuclear translocation of Nrf2 and its binding to the antioxidant/electrophile response elements. Cells transfected with a mutant Keap1 protein in which cysteine 151 (Cys151) is replaced by serine exhibited marked reduction in curcumin-induced Nrf2 transactivation. Mass spectrometric analysis revealed that curcumin binds to Keap1 Cys151, supporting that this amino acid is a critical target for curcumin modification of Keap1, which facilitates the liberation of Nrf2. Thus, it is likely that the α,β-unsaturated carbonyl moiety of curcumin is essential for its binding to Keap1 and stabilization of Nrf2 by hampering ubiquitination and proteasomal degradation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aims: We aimed to investigate the safety and efficacy of endoscopic resection (ER) compared with surgical resection (SR) of gastric GI stromal tumors (GISTs)., Methods: This study included 51 and 403 patients who underwent ER and SR, respectively, for ≤5 cm GISTs in the stomach between June 2005 and August 2017. After propensity score matching (1:1) using age, sex, tumor size, mitotic count, and comorbidities, the oncologic outcomes were compared with 48 patients each from ER and SR groups., Results: The ER group had significantly shorter hospital stay (4.4 ± 2.9 vs 6.6 ± 3.6 days, P < .001) and procedure time (38.3 ± 24.2 vs 66 ± 33.3 min, P < .001). The R0 resection rate was 62.7% in the ER group and 98.5% in the SR group. In the ER group, macroperforation occurred in 6 patients (11.8%) with a tumor located in the fundus (4/6, 66.7%) or body (2/6, 33.3%). All cases of perforation were cured with conservative treatment. In the SR group, postoperative adverse events such as stricture and leakage occurred in 7 patients (1.7%) with a tumor located in the antrum (4/7, 57.1%) or cardia (3/7, 42.9%). After matching, the overall mean follow-up period was 47.9 ± 37.8 months in the ER group and 41.3 ± 22.6 months in the SR group. No recurrence or distant metastasis occurred in either group during the follow-up period., Conclusions: ER is an effective and safe therapeutic method that might be comparable with SR for treating small-sized (≤5 cm) gastric GISTs. Selecting the resection method according to the tumor location seems appropriate., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background: In cases of subepithelial tumors (SETs) located in the cardiac area, a preoperative histologic diagnosis might be helpful in determining the requirement of surgery., Aim: To investigate the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in gastric SETs located in the cardia., Methods: The data of 107 patients who underwent EUS-FNB, from 2012 to 2017, for tissue sampling of gastric SETs located in the cardia were collected. The clinicopathological data, EUS-related parameters, and surgical outcomes were retrospectively reviewed., Results: The EUS-FNB results were diagnostic in 86.9% (93/107) and nondiagnostic in 13.1% (14/107) of the patients. Immunostaining of the FNB specimens led to the diagnosis of gastrointestinal stromal tumor (GIST) in 25 SETs (23.4%), leiomyoma in 62 SETs (57.9%), heterotopic pancreas in 3 SETs (2.8%), and schwannoma in 2 SETs (1.9%). In the multivariate analysis, patients with GISTs showed significantly more inhomogeneous echogenicity [odds ratio (OR), 8.867], more cystic foci (OR, 26.98), and older age (OR, 1.087). In 26 patients who underwent surgical resection, the agreement between EUS-FNB and surgical pathological findings was 100% with respect to the diagnosis of GISTs (n = 20) and leiomyoma (n = 7). Among these cases, the proportion of high-risk GISTs was 20.0% (4/20), and no leiomyosarcoma was detected., Conclusions: Although a majority of the subepithelial lesions in the cardia of the stomach are benign, 20% of the cases diagnosed with GIST have a high malignant potential. Preoperative EUS-FNB might be a useful tool for decision-making regarding the ultimate management and outcomes of these lesions.

Background: Upper gastrointestinal bleeding (UGIB) is one of the major manifestations of gastrointestinal stromal tumor (GIST) of the stomach. Several studies have reported that GIST bleeding is associated with poor prognosis. However, only case reports have reported hemostasis modalities for treating hemorrhagic gastric GIST. To identify clinical outcome of gastric GIST bleeding, we analyzed risk factors and prognosis of hemorrhagic GIST evaluating hemostasis methods., Methods: Total 697 patients histopathologically diagnosed with primary gastric GIST between January 1998 and May 2015 were enrolled to the study, retrospectively., Results: Of 697 total patients, 46 (6.6%) patients had UGIB. Endoscopic intervention, transarterial embolization, or surgical intervention was performed for initial hemostasis in 15, 2, and 1, respectively. Over a median of 68 months of follow-up, 16 patients in bleeding group and 88 patients in non-bleeding group died; the 5-year survival rate was 79.4% in bleeding group and 91.8% in non-bleeding group (p = 0.004). Multivariate analysis showed that significant risk factors for gastric GIST bleeding included the maximal tumor diameter > 5 cm and Ki-67 positivity. Age ≥ 60 [hazard ratio (HR) = 8.124, p = 0.048], necrosis (HR = 5.093, p = 0.027), and bleeding (HR 5.743, p = 0.034) were significant factors for overall survival of gastric GIST patients., Conclusions: Bleeding risk of gastric GIST was higher when tumor had diameter > 5 cm or Ki-67 positivity. In addition, tumor bleeding, necrosis, and age ≥ 60 years were associated with poor overall survival. Endoscopic intervention can be considered as an effective method for initial hemostasis of hemorrhagic gastric GIST.

Prostaglandin E 2 (PGE 2 ) plays a key role in inflammation-associated carcinogenesis. NAD + -dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S)-hydroxyl group of PGE 2 to generate 15-keto PGE 2 . 15-PGDH has been known as a tumor suppressor in various malignancies including colon cancer. However, the molecular mechanisms underlying the tumor-suppressive function of 15-PGDH remain largely unresolved. In this study, we found that 15-keto PGE 2 upregulated the expression of heme oxygenase-1 (HO-1), a representative antioxidative and anti-inflammatory enzyme, at both transcriptional and translational levels, in human colon epithelial CCD 841 CoN cells. A redox-sensitive transcription factor, NF-E2-related factor (Nrf2) plays a critical role in the regulation of HO-1 and other cytoprotective proteins. 15-Keto PGE 2 induced translocation of Nrf2 into the nucleus and antioxidant response element-driven luciferase activity. Furthermore, the silencing of the Nrf2 gene abolished 15-keto PGE 2 -induced HO-1 expression in CCD 841 CoN cells. 15-Keto PGE 2 activated AKT signaling, and the pharmacological AKT inhibitor, LY294002 suppressed the 15-keto PGE 2 -induced HO-1 expression. 15-Keto PGE 2 generates the reactive oxygen species which is suppressed by the general antioxidant N-acetyl-l-cysteine. N-acetyl-l-cysteine treatment attenuated the 15-keto PGE 2 -induced phosphorylation of GSK3β, transcriptional activity of Nrf2, and subsequently HO-1 expression. However, 13,14-dihydro-15-keto PGE 2 lacking the α,β-unsaturated carbonyl moiety failed to induce intracellular production of reactive oxygen species, HO-1 expression and nuclear translocation of Nrf2. In conclusion, 15-keto PGE 2 induces HO-1 expression through Nrf2 activation in human colon epithelial cells., (Copyright © 2019. Published by Elsevier Inc.)

Recently, growing attention has been given to new classes of bioactive lipid mediators derived from ω-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), especially in the context of their role as endogenous signal modulators. One such molecule is 17-oxo-DHA, generated from DHA by the action of COX2 and a dehydrogenase. The redox-sensitive transcription factor, Nrf2 plays a key role in cellular stress responses. In the present study, the effects of 17-oxo-DHA on Nrf2-mediated expression of cytoprotective enzymes were examined in mouse skin in vivo and cultured murine epidermal JB6 cells. Topical application of 17-oxo-DHA markedly elevated the nuclear localization of Nrf2 and expression of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 in hairless mouse skin. In contrast to 17-oxo-DHA, the non-electrophilic metabolic precursor 17-hydroxy-DHA was a much weaker inducer of Nrf2 activation and its target protein expression. Likewise, 17-oxo-DHA significantly enhanced nuclear translocation and transcriptional activity of Nrf2 with concomitant upregulation of HO-1 expression in cultured JB6 cells. 17-Oxo-DHA was a much stronger inducer of Nrf2-mediated antioxidant response than its parent molecule, DHA. HO-1 expression was abolished in Nrf2 knockdown JB6 cells or embryo fibroblasts from Nrf2 knock out mice. 17-Oxo-DHA also markedly reduced the level of Keap1 protein by inducing ubiquitination. Mutation of Cys151 and Cys273 in Keap1 abrogated 17-oxo-DHA-induced ubiquitination and proteasome-mediated degradation of Keap1 as well as HO-1 expression, suggesting that these cysteine residues are putative sites for 17-oxo-DHA binding. Further, Keap1 degradation stimulated by 17-oxo-DHA coincided with accumulation of the autophagy substrate, p62/SQSTM1., (Copyright © 2019. Published by Elsevier Inc.)

Objective: Considering the clinical heterogeneity of temporal lobe epilepsy with amygdala enlargement (TLE-AE), identifying distinct prognostic subgroups of TLE-AE has clinical implications. Until now, baseline volume of the enlarged amygdala (EAV) has consistently failed to predict prognosis in TLE-AE. Based on studies suggesting that patients responsive to antiepileptic drugs (AEDs) exhibit remission of AE on follow-up imaging, we investigated whether reduction rate of EAV is predictive of long-term prognosis in TLE-AE., Methods: Sixty-one consecutive patients with two separate magnetic resonance imaging (MRI) scans were enrolled. To utilize longitudinally measured biomarkers in prediction, the period beyond the first MRI acquisition was split into two periods: the "observation window" (period between the two MRIs) and "prediction window" (follow-up period beyond the second MRI). Patients were classified according to their AED responsiveness during the observation window, and AED-responsive patients were further subdivided by initial seizure frequency: (a) AED-responsive patients presenting with low-frequency seizures (<5 seizures/3 mo; Group A, n = 25), (b) high-frequency seizures (≥5 seizures/3 mo; Group B, n = 23), and (c) patients with poor initial treatment response (Group C, n = 13). Multivariate logistic regression models were constructed for identification of prognostic factors. Along with factors obtained at baseline, factors derived from the observation window (annual percentage change of EAV [APCEAV] and initial AED responsiveness) were also considered as potential predictors., Results: Favorable initial treatment response and faster volume reduction rate (APCEAV ≤ -5.0%/y) were identified as factors predictive of achieving overall seizure freedom. Among the AED-responsive patients, Group A (low-frequency seizures) showed slower remission of AE and higher rate of seizure recurrence, whereas Group B (high-frequency seizures) exhibited faster remission of AE and lower rate of seizure recurrence., Significance: Faster recuperation of AE in patients with initial high-frequency seizures may be indicative of seizure-induced changes. As volume reduction rate serves as a prognostic marker in TLE-AE, short-term MRI follow-up may be useful in prognostication., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Background/aims: Acid suppression therapy is thought to be associated with the topography of Helicobacter pylori and associated gastritis, leading to corpus-predominant gastritis. This study was aimed to investigate the influence of proton pump inhibitor (PPI) treatment on the distribution of H. pylori and associated gastritis in patients with atrophic change., Methods: Patients who underwent endoscopic resection for gastric neoplasms and received PPI for 2 months were prospectively analyzed. Biopsy specimens were obtained from 5 areas in the stomach before, during, and after the treatment with PPI. Histological examination was -performed using the updated Sydney system, and -bacterial density of H. pylori was further graded by immunohistochemistry (ClinicalTrials.gov registration number NCT02449941)., Results: A total of 15 patients were analyzed, of whom 7 had H. pylori infection. The degree of activity and inflammation were greater in patients with H. pylori infection than in those without H. pylori infection. During the PPI treatment, the density of H. pylori decreased not only in the antrum but also in the corpus. The degree of activity and inflammation improved significantly in the antrum, particularly in the presence of H. pylori infection, while the corpus gastritis was not affected by PPI use. Atrophy and intestinal metaplasia remained unchanged in both regions of the stomach. The observed changes reverted following the discontinuation of PPI treatment., Conclusion: PPI treatment decreased H. pylori both in the antrum and the corpus in patients with atrophic gastritis. Antral gastritis improved during PPI treatment, whereas no changes were found in the corpus., (© 2019 S. Karger AG, Basel.)

Background/aims: Spontaneous retrograde migration of nasoenteral feeding tubes is common in clinical practice. The aim of the present study was to evaluate the effectiveness of nasoenteral feeding tube tip fixation with hemoclips to prevent tube dislodgement., Methods: We retrospectively reviewed patients who underwent insertion of an endoscopic nasoenteral feeding tube with or without tube tip fixation with hemoclips at the Asan Medical Center in Korea from January 2016 to December 2017. We compared the incidence of tube dislodgment and procedure-related complications between the two groups., Results: Of the total 225 procedures, 72 were performed using the clip-assisted method, while 153 were performed using the standard non-clip-assisted method. Tube dislodgement occurred in two (2.8%) cases in the clipping group and in 26 (17.0%) in the non-clipping group (p = 0.003). Non-clipping group had a sevenfold higher risk of tube dislodgement compared to clipping group after adjustments in multivariable logistic regression (adjusted OR 7.97, 95% CI 1.82-35.00). The procedure time was not significantly different between the two groups (17.6 ± 8.5 min in the clipping group vs. 17.8 ± 9.4 min in the non-clipping group, p = 0.872). In addition, procedure-related complications, such as bleeding, aspiration pneumonia, Mallory-Weiss tear, ileus, and tube obstruction, were not different between the two groups. Achieving target calorie intake took 10.4 ± 10.5 days in the clipping group and 7.9 ± 7.9 days in the non-clipping group (p = 0.293)., Conclusion: Clip-assisted fixation of nasoenteral feeding tube was effective in preventing tube dislodgement.

Background and Aims: Endoscopic treatment for duodenal neoplasms is associated with a high risk of perforation. This study aimed to determine the feasibility of endoscopic treatment for sporadic nonampullary duodenal adenoma (SNDA)., Methods: Consecutive patients undergoing endoscopic treatment for SNDA between January 2005 and December 2015 were included in the study. Clinical characteristics and endoscopic outcomes were analyzed using medical records. Long-term outcome was assessed in patients whose follow-up period was >12 months >1 year., Results: A total of 95 lesions (92 patients) were treated with argon plasma coagulation (APC) ablation (n = 25), endoscopic mucosal resection (EMR, n = 59), or endoscopic submucosal dissection (ESD, n= 11). The median age was 54.9 years, and 63% were male. In patients who underwent EMR and ESD, the en bloc resection rate was 83.1 and 90.0% (p > 0.99); and the complete resection rate was 81.4 and 80% (p > 0.99), respectively. Perforation occurred in 8 patients (8.7%), 4 of whom required surgery. The ESD group showed a significantly higher perforation rate than APC or EMR group (45.5 vs. 0 and 5.1%; p < 0.001). During the median follow-up period of 19 months (range 12-137 months), one patient in the APC ablation group experienced recurrence; no recurrences were seen among EMR and ESD groups., Conclusions: Favorable long-term outcomes indicate that endoscopic treatment is an effective approach for the treatment of SNDA. Considering the high risk of perforation associated with ESD, APC, or EMR may be an acceptable alternative., (© 2020 S. Karger AG, Basel.)

Objectives: This study aimed to investigate the efficacy of prophylactic steroid administration in preventing post-endoscopic submucosal dissection (ESD) esophageal stricture and to determine risk factors for these strictures., Methods: Patients who underwent ESD for superficial esophageal neoplasms with a mucosal defect affecting >75% of the esophageal circumference between January 2011 and August 2016 were eligible. Patients were classified into three groups, including ESD-alone group (n = 22), oral steroid group (n = 25) and intralesional steroid injection group (n = 6). Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors for esophageal stricture., Results: The stricture rate was 50.0%, 20.0% and 33.3% in the ESD-alone group, oral steroid group and steroid injection group, respectively. Patients treated with steroids had a significantly lower stricture rate than the ESD-alone group (22.6% vs 50.0%, P = 0.046). Additionally, oral steroid group had a significantly lower stricture rate than the ESD-alone group (P = 0.037). Multivariate analysis revealed that the extent of the circumferential mucosal defect was a significant risk factor for post-ESD strictures (odds ratio [OR] 13.015, 95% confidence interval [CI] 2.257-76.077, P = 0.004). The administration of steroids (OR 0.108, 95% CI 0.020-0.578, P = 0.009), specifically oral steroids (OR 0.109, 95% CI 0.019-0.622, P = 0.013), was associated with prevention of post-ESD strictures., Conclusion: Oral steroid prophylaxis appears to be a safe and effective treatment in preventing post-ESD stricture and improving patients' quality of life., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background/aims: The epidemiology and pathogenesis of eosinophilic esophagitis (EoE) remain unclear in Asian countries. We investigated clinicopathological characteristics and diagnostic trends of EoE, and evaluated 3 tissue biomarkers for correlation with disease activity and treatment response in Korean patients with EoE., Methods: We retrospectively reviewed 25 271 esophageal biopsies performed during upper endoscopies between 2006 and 2017. We diagnosed EoE based on ≥ 15 eosinophils/high-power field (HPF) and, symptoms of esophageal dysfunction. We performed immunohistochemical analysis for tryptase, eosinophilic derived neurotoxin (EDN), and eotaxin-3., Results: We diagnosed EoE in 72 patients (53 men and 19 women; mean age, 46.2 years) with presenting symptoms of, dysphagia (15.3%), epigastric pain (31.9%), and heartburn (30.6%). The diagnostic rate of EoE considerably increased between 2006 and 2017, from 0.29 diagnoses to 7.99 diagnoses per 1000 esophageal biopsies ( P < 0.001). The mean peak eosinophil count (PEC) was 56.0 (± 77.8)/HPF. Whereas the EDN (rho = 0.667, P < 0.001) and eotaxin-3 levels (rho = 0.465, P < 0.001) correlated with PEC, tryptase and PEC were weakly correlated (rho = 0.291, P = 0.013). EDN (rho = 0.279, P = 0.017), and tryptase (rho = 0.279, P = 0.033) correlated with the inflammatory score of Eosinophilic Esophagitis Endoscopic Reference Score. Immunohistochemical analysis and changes in tryptase, EDN, and eotaxin-3 levels were associated with histologic and endoscopic improvements., Conclusions: EoE incidence considerably increased during the 12-year period, regardless of endoscopic esophageal biopsy rate. Tryptase, EDN, and eotaxin-3 levels in esophageal biopsy specimens could be promising biomarkers for disease activity, symptom, and endoscopic response in Korea.

Background and Aim: Guidelines for selecting the eradication regimen for Helicobacter pylori reinfection remain unclear. This study aimed to evaluate the eradication rate of H. pylori reinfection in patients with a previous infection successfully eradicated with index triple therapy., Methods: This was a single-center, retrospective case-control study. A total of 10 468 H. pylori-infected patients treated with proton-pump inhibitor-based triple eradication therapy at a tertiary medical institution between 2005 and 2016 were enrolled. We reviewed the medical records of the enrolled patients and compared the treatment outcomes in those with H. pylori reinfection after a successful eradication., Results: Helicobacter pylori infection was successfully eradicated with the index triple therapy in 7770 patients (74.2%). Among 3567 patients followed up for > 1 year, H. pylori reinfection occurred in 420 (11.8%; 3.06% per person-year) during a median follow-up of 39.1 months (interquartile range, 23.5-58.7 months). Of these patients, 164 received eradication therapy for reinfection (triple therapy in 102 and quadruple therapy in 62) and had follow-up data. Triple therapy showed an eradication rate of 78.4% for H. pylori reinfection, which was not significantly different from that of the index triple therapy (P = 0.394). Quadruple therapy for reinfection exhibited a better eradication rate (87.1%) than triple therapy but without statistical significance (P = 0.237)., Conclusions: Retreatment with triple therapy for H. pylori reinfection after successful eradication of prior infection showed comparable outcomes to the index triple therapy. Bismuth-containing quadruple therapy for reinfection tended to have a better eradication rate than did triple therapy., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Abnormal upregulation of prostaglandin E 2 (PGE 2 ) is considered to be a key oncogenic event in the development and progression of inflammation-associated human colon cancer. It has been reported that 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme catabolizing PGE 2 , is ubiquitously downregulated in human colon cancer. 15-Deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), a peroxisome proliferator-activated receptor γ ligand, has been shown to have anticarcinogenic activities. In this study, we investigate the effect of 15d-PGJ 2 on expression of 15-PGDH in human colon cancer HCT116 cells., Methods: HCT116 cells were treated with 15d-PGJ 2 analysis. The expression of 15-PGDH in the treated cells was measured by Western blot analysis and RT-PCR. In addition, the cells were subjected to a 15-PGDH activity assay. To determine which transcription factor(s) and signaling pathway(s) are involved in 15d-PGJ 2 -induced 15-PGDH expression, we performed a cDNA microarray analysis of 15d-PGJ 2 -treated cells. The DNA binding activity of AP-1 was measured by an electrophoretic mobility shift assay. To determine whether the AP-1 plays an important role in the 15d-PGJ 2 -induced 15-PGDH expression, the cells were transfected with siRNA of c-Jun, a major subunit of AP-1. To elucidate the upstream signaling pathways involved in AP-1 activation by 15d-PGJ 2 , we examined its effect on phosphorylation of Akt by Western blot analysis in the presence or absence of kinase inhibitor., Results: 15d-PGJ 2 (10 μM) significantly upregulated 15-PGDH expression at the mRNA and protein levels in HCT-116 cells. 15-PGDH activity was also elevated by 15d-PGJ 2 . We observed that genes encoding C/EBP delta, FOS-like antigen 1, c-Jun, and heme oxygenase-1 (HO-1) were most highly induced in the HCT116 cells following 15d-PGJ 2 treatment. 15d-PGJ 2 increased the DNA binding activity of AP-1. Moreover, transfection with specific siRNA against c-Jun significantly reduced 15-PGDH expression induced by 15d-PGJ 2 . 15d-PGJ 2 activates Akt and a pharmacological inhibitor of Akt, LY294002, abrogated 15d-PGJ 2 -induced 15-PGDH expression. We also observed that an inhibitor of HO-1, zinc protoporphyrin IX, also abrogated upregulation of 15-PGDH and down-regulation of cyclooxygenase-2 expression induced by 15d-PGJ 2 ., Conclusions: These finding suggest that 15d-PGJ 2 upregulates the expression of 15-PGDH through AP-1 activation in colon cancer HCT116 cells., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed., (Copyright © 2019 Korean Society of Cancer Prevention.)

Introduction: One of the most common sleep disorders, insomnia is a significant public health concern. Several psychiatric disorders, such as anxiety disorders and depression, have shown strong relationships with insomnia. However, the clinical impact of the combination of these two conditions on insomnia severity and sleep quality remains unknown. We investigated the relationship between sleep disturbance and psychiatric comorbidities in subjects with high risk for insomnia. Methods: We analyzed data from a nation-wide cross-sectional survey of Korean adults aged 19 ~ 69 years conducted from November 2011 to January 2012. The survey was performed via face-to-face interviews using a structured questionnaire. We used the insomnia severity index (ISI) to evaluate insomnia and defined respondents with ISI scores of ≥10 were considered to be at high risk for insomnia. To diagnose anxiety and depression, we used the Goldberg anxiety scale (GAS) and Patient Health Questionnaire-9 (PHQ-9), respectively. Results: Of the 2,762 respondents, 290 (10.5%) were classified as subjects with high risk for insomnia; anxiety [odds ratio (OR), 9.8; 95% confidence interval (CI), 7.3-13.1] and depression (OR, 19.7; 95% CI, 13.1-29.6) were more common in this population than in participants without insomnia. Of the participants with insomnia, 152 (52.4%) had neither anxiety nor depression, 63 (21.7%) only had anxiety, 21 (7.2%) only had depression, and 54 (18.6%) had both anxiety and depression. The group with both anxiety and depression was associated with worse scores on sleep-related scales than the other groups [high ISI, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale]. The relationship between outcome measures (ISI and PSQI) and psychiatric problems was significant only when anxiety and depression were present. The PSQI has a significant mediation effect on the relationship between psychiatric comorbidities and insomnia severity. Conclusion: Among the respondents with insomnia, psychiatric comorbidities may have a negative impact on daytime alertness, general sleep quality, and insomnia severity, especially when the two conditions are present at the same time. Clinicians should, therefore, consider psychiatric comorbidities when treating insomnia.

Objective: To assess potential mechanisms of cortical superficial siderosis (cSS), a central MRI biomarker in cerebral amyloid angiopathy (CAA), we performed a collaborative meta-analysis of APOE associations with cSS presence and severity., Methods: We pooled data from published studies reporting APOE genotype and MRI assessment of cSS in 3 distinct settings: (1) stroke clinic patients with symptomatic CAA (i.e., lobar intracerebral hemorrhage, transient focal neurologic episodes) according to the Boston criteria; (2) memory clinic patients; and (3) population-based studies. We compared cSS presence and severity (focal or disseminated vs no cSS) in participants with ε2+ or ε4+ genotype vs the ε3/ε3 genotype, by calculating study-specific and random effects pooled, unadjusted odds ratios (ORs)., Results: Thirteen studies fulfilled inclusion criteria: 7 memory clinic cohorts (n = 2,587), 5 symptomatic CAA cohorts (n = 402), and 1 population-based study (n = 1,379). There was no significant overall association between APOE ε4+ and cSS presence or severity. When stratified by clinical setting, APOE ε4+ was associated with cSS in memory clinic (OR 2.10; 95% confidence interval [CI] 1.11-3.99) but not symptomatic CAA patients. The pooled OR showed significantly increased odds of having cSS for APOE ε2+ genotypes (OR 2.42, 95% CI 1.48-3.95) in both patient populations. This association was stronger for disseminated cSS in symptomatic CAA cohorts. In detailed subgroup analyses, APOE ε2/ε2 and APOE ε2/ε4 genotypes were most consistently and strongly associated with cSS presence and severity., Conclusion: CAA-related vasculopathic changes and fragility associated with APOE ε2+ allele might have a biologically meaningful role in the pathophysiology and severity of cSS., (© 2019 American Academy of Neurology.)

Background: Baicalein is a bioactive flavone that is originally extracted from the root of Scutellaria baicalensis Georgi. This plant has long served as Chinese herbal medicine in the management of multiple diseases including inflammatory bowel diseases. Although it has been revealed that baicalein inhibits experimental colitis in mice, the molecular mechanisms still remain largely unrecognized., Methods: The experimental colitis was induced in mice by 3% dextran sulfate sodium (DSS) in drinking water. The mice were given baicalein (10 or 25 mg/kg) by gavage for 7 days before and after DSS administration. Expression of COX-2 and inducible nitric oxide synthase (iNOS) and molecules involved in NF-κB signaling, such as inhibitor of κBα (IκBα), pIκBα, p65, and phospho-p65 was examined by Western blot analysis in the tissue of the mouse colon. Activity of IκB kinase β (IKKβ) was assessed by measuring the relative amount of radioactive γ-phosphate of ATP transferred to the IκBα substrate protein. The expression and phosphorylation of STAT3 and its target gene cyclin D1 were also measured., Results: Baicalein prominently mitigated the severity of DSS-induced colitis in mice. It inhibited the expression of COX-2 and iNOS. Moreover, baicalein attenuated activity and phosphorylation of IKKβ and subsequent degradation of IκBα. Baicalein suppressed the phosphorylation and nuclear translocation of p65, resulting in a reduced DNA binding activity of NF-κB. Baicalein also suppressed the phosphorylation of STAT3 and expression of cyclin D1. Baicalein exhibited the synergistic effect on inhibition of COX-2 induced by DSS with curcumin, an ingredient of turmeric., Conclusions: Protective effects of baicalein on DSS-induced colitis are associated with suppression of NF-κB and STAT3 signaling pathways, which may contribute to its cancer preventive effects on colon carcinogenesis., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.

Purpose: To evaluate the technical feasibility, safety, and efficacy of a novel full sense device (FSD) for the treatment of obesity in a porcine model., Materials and Methods: The novel FSD comprised a self-expanding metallic esophageal stent connected to a star-shaped nitinol disk. Three types of FSD were used: fully covered (type A), fully covered with barbs (type B), and uncovered with barbs (type C). Nine juvenile pigs were divided into two groups: FSD (n = 6) and control (n = 3). FSD type A was placed in the FSD group. In case of migration, either FSD type B or type C was then randomly placed. Food intake was monitored daily. Weight changes and ghrelin hormone levels were monitored weekly for 12 weeks., Results: FSD placement was technically successful in all pigs. All FSDs except one migrated to the stomach within 1 week after placement. The pig in which the FSD was retained showed decreased food intake in the first week after FSD placement, and there was a difference in the final weight between the FSD pig and control pigs. The percentage of weight gain was 116.6% in the control group and 105.3% in the FSD pig., Conclusion: FSD placement under fluoroscopic and endoscopic guidance is technically feasible and safe in a porcine model. The uncovered FSD appears to decrease food intake and reduce the rate of weight gain. However, the high FSD migration rate is not encouraging.

Overproduction of prostaglandin E 2 (PGE 2 ) has been linked to enhanced tumor cell proliferation, invasiveness and metastasis as well as resistance to apoptosis. 15-Keto prostaglandin E 2 (15-keto PGE 2 ), a product formed from 15-hydroxyprostaglandin dehydrogenase-catalyzed oxidation of PGE 2 , has recently been shown to have anti-inflammatory and anticarcinogenic activities. In this study, we observed that 15-keto PGE 2 suppressed the phosphorylation, dimerization and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in human mammary epithelial cells transfected with H-ras (MCF10A-ras). 15-Keto PGE 2 inhibited the migration and clonogenicity of MCF10A-ras cells. In addition, subcutaneous injection of 15-keto PGE 2 attenuated xenograft tumor growth and phosphorylation of STAT3 induced by breast cancer MDA-MB-231 cells. However, a non-electrophilic analogue, 13,14-dihydro-15-keto PGE 2 failed to inhibit STAT3 signaling and was unable to suppress the growth and transformation of MCF10A-ras cells. These findings suggest that the α,β-unsaturated carbonyl moiety of 15-keto PGE 2 is essential for its suppression of STAT3 signaling. We observed that the thiol reducing agent, dithiothreitol abrogated 15-keto PGE 2 -induced STAT3 inactivation and disrupted the direct interaction between 15-keto PGE 2 and STAT3. Furthermore, a molecular docking analysis suggested that Cys251 and Cys259 residues of STAT3 could be preferential binding sites for this lipid mediator. Mass spectral analysis revealed the covalent modification of recombinant STAT3 by 15-keto PGE 2 at Cys259. Taken together, thiol modification of STAT3 by 15-keto PGE 2 inactivates STAT3 which may account for its suppression of breast cancer cell proliferation and progression., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Backgrounds/aim: We aimed to evaluate the feasibility of endoscopic treatment for gastric epithelial neoplasm in the remnant stomach after distal gastrectomy and compared the clinical outcomes by tumor location and endoscopic treatment modality., Methods: We reviewed the data of patients who underwent endoscopic treatment for gastric epithelial neoplasms in the remnant stomach after distal gastrectomy between January 1996 and August 2013. The treatments included endoscopic resection or argon plasma coagulation., Results: Herein, 107 patients (median age, 65.1 years; 92 men) encompassing 117 cases of gastric neoplasms in the remnant stomach after distal gastrectomy were endoscopically treated. Forty of these lesions were located at anastomotic sites; they were treated with endoscopic resection in 29 cases (72.5%) and argon plasma coagulation in 11 cases (27.5%). For 77 lesions located on the non-anastomotic site, endoscopic resection was performed in 68 cases (88.4%) and argon plasma coagulation was performed in nine cases (11.7%; p = 0.031). The mean endoscopic resection duration was significantly longer in the anastomotic site group than in the non-anastomotic site group (43.6 vs. 26.3 min, p = 0.018). Recurrence was observed in five (12.8%) patients in the former and in one (1.3%) in the latter (p = 0.015); all the patients were successfully retreated with endoscopic resection or APC., Conclusions: Endoscopic treatment for gastric epithelial neoplasm in a remnant stomach after distal gastrectomy is effective and safe. However, closely monitoring for recurrence should be conducted, particularly when the tumor is located at the anastomotic site., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)