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Gastric cancer (GC) is recognized as the fifth most prevalent malignant tumor worldwide. It is characterized by diverse clinical symptoms, treatment responses, and prognoses. In GC prognosis, the promotion of epithelial-mesenchymal transition (EMT) fosters cancer cell invasion and metastasis, thereby triggering the dissemination of tumor cells. This study proposes a nucleic acid amplification circuit-based hydrogel (NACH) assay for identifying exosomal miRNA derived from metastatic GC. The NACH assay employs the rolling circle amplification method and targets miRNA-21, a tumor-related oncogene, and miRNA-99a, which promotes EMT. Specific amplification probes for each target are immobilized within the hydrogel, enabling a streamlined, one-step amplification reaction. The NACH assay exhibits a detection limit of 1 fm for miRNA-21 and miRNA-99a, thereby enabling rapid and highly sensitive on-site detection. Performance evaluation using exosomal miRNA extracted from cell culture media, mouse plasma, and human plasma revealed fluorescence intensity patterns similar to those obtained in qRT-PCR. Furthermore, deploying a custom-developed portable fluorometer for the NACH assay allows for diagnostic performance assessment and point-of-care testing using clinical samples from GC patients. These findings emphasize the potential of the NACH assay to be used as a robust tool for the genetic diagnosis of GC based on exosome detection., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Endoscopic submucosal dissection (ESD) plays a pivotal role in treating early gastric cancer (EGC). Some patients require additional gastrectomy because of non-curative ESD. This study aimed to analyze the clinical factors associated with non-curative ESD and to re-evaluate the role of ESD according to its indication criteria. Altogether, 134 patients who had undergone additional gastrectomy with lymphadenectomy for non-curative ESD based on the pathological results of ESD specimens were included. Their data including pre-ESD diagnosis, reasons for requesting additional gastrectomy, and surgical outcomes were analyzed retrospectively. Of the 134 patients with EGC in the final pathology of ESD specimens, 56 underwent staging ESD for a diagnostic approach, of whom 28 were diagnosed with atypical glands and 28 with high-grade dysplasia (HGD) prior to ESD. The remaining 78 patients of the 134 were identified to have EGC and received ESD for therapy. Based on the pathological results of ESD specimens, additional gastrectomy was commissioned with non-curative ESD because of one or more causes such as deep submucosal invasion, lymphatic invasion, positive vertical margin, undifferentiated histology, positive lateral margin, and venous invasion. Regarding surgical specimens, 13 patients had lymph node metastasis (LNM) and 9 had local residual tumor; one of them had both LNM and a local residual tumor. In patients with atypical glands, 4 had LNM and 3 had a local residual tumor; one of them had both LNM and a local residual tumor, and then died of multiple organ metastasis. In patients with HGD, 4 had LNM and 1 had a local residual tumor. Additionally, 4 patients who were absolutely indicated for ESD had LNM, of whom 2 had atypical glands, and the other 2 had HGD. Similarly, in 6 patients with a local residual tumor absolutely indicated for ESD, 2 had atypical glands and 1 had HGD. Positive vertical margin, lymphatic invasion, and deep submucosal invasion were identified as independent risk factors for LNM. ESD may play diagnostic and therapeutic roles in determining the optimal treatment of EGC when the diagnosis is equivocal or insufficient in endoscopic assessments for gastric cancer screening., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Endoscopic resection (ER)-a minimal invasive procedure, compared to surgical gastrectomy, with the advantage of preserving the entire stomach and maintaining the patient's quality of life-is a widely used curative treatment for early gastric cancers (EGCs). Despite its advantages, such as the preservation of the whole stomach, a large area of the gastric mucosa with histologic changes such as atrophy and intestinal metaplasia remains after ER, and so does the risk of metachronous gastric cancers (MGCs). Therefore, regular surveillance endoscopy after curative ER of EGCs is important so that MGCs are detected early and so minimally invasive ER remains a treatment option. To date, the optimal interval for surveillance endoscopy after curative ER of EGCs has not been established. Therefore, this review summarizes the results of the published studies on this topic with the aim of establishing the optimal surveillance interval for early identification of MGCs. Based on my review, the median timing of MGC occurrence is within 3 years, and reports suggest biannual endoscopy during the first 3 years; however, the evidence suggests that individual patient characteristics may influence the risk of MGCs. Therefore, stratified endoscopic strategies for surveillance based on patient characteristics, such as age, family history of gastric cancer, synchronous gastric lesions, and corpus intestinal metaplasia, should be applied.

Backgrounds: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). The authors performed an RCT to confirm if TLDG is different from LADG., Methods: The KLASS-07 trial is a multi-centre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enroled from 21 cancer care centres in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was quality of life (QoL) for 1 year. This trial is registered at ClinicalTrials.gov (NCT03393182)., Results: Four hundred forty-two patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P= 0.006; and 0.5% vs. 4.3%, P= 0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P< 0.05). However, these QoL differences were resolved at 1 year., Conclusions: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complications but has the advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

I read with interest the paper by Matsuo et al [...].

Background: This study aimed to evaluate the clinical outcomes and efficacy of enhanced recovery after surgery (ERAS) protocol in patients undergoing distal gastrectomy for gastric cancer (GC)., Methods: Patients were randomly assigned to the ERAS group (EG) and the conventional care group (CG) by stratified randomization according to age and sex. The primary endpoint was adjusted postoperative hospital stay, calculated using discharge criteria developed to evaluate recovery. Nutritional data and quality of life (QoL) (European Organisation for Research and Treatment of Cancer [EORTC] C30 and STO22) during the perioperative period were also analyzed., Results: We enrolled 198 eligible patients with GC for the study between June 2017 and January 2019. A total of 147 patients were finally enrolled in this study (full analysis set) and were assigned to EG (n = 71) and CG (n = 76). First flatus was faster significantly in EG (3.6 ± 1.5 vs 4.1 ± 1.2 days, P = .019). EG showed a faster start of the sips and soft diet than CG (1.3 ± 0.7 vs 3.1 ± 0.4 days, P < .001; 2.4 ± 0.9 vs 5.2 ± 0.7 days, P < .001) according to the protocol. The recorded hospital stay was not significantly different; however, adjusted hospital stay was significantly shorter in EG than in CG (6.5 ± 3.1 vs 7.8 ± 2.1 days, P = .005). There was no difference in morbidity, and no mortality occurred in both groups. EG did not show significant superiority in nutritional outcome and QoL improvement, except for pain scale in EORTC-STO22., Conclusion: The application of the ERAS protocol could reduce the adjusted hospital stay without an increase in postoperative complications. There was no significant difference in long-term nutritional outcome and QoL of the 2 groups., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: The trastuzumab biosimilar CT-P6 is approved for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), metastatic breast cancer (MBC), and metastatic gastric cancer (MGC). The objective of this post-marketing surveillance (PMS) study was to evaluate the real-world safety and effectiveness of CT-P6 in patients with HER2-positive cancers., Research Design and Methods: This open-label, observational, prospective, PMS study collected data via investigator surveys from 35 centers in the Republic of Korea (5 October 2018-4 October 2022). Eligible patients with HER2-positive EBC, MBC, or MGC started CT-P6 treatment during routine clinical practice, followed by 1-year observation. Evaluations included adverse events (AEs), adverse drug reactions (ADRs), and effectiveness., Results: Safety was analyzed in 642 patients (494 EBC, 94 MBC, 54 MGC). Overall, 325 (50.6%) patients experienced 1316 AEs, and 550 ADRs occurred in 199 (31.0%) patients. Unexpected ADRs occurred in 62 (9.7%) patients. Unexpected ADRs and ADRs of special interest did not raise any new safety signals. Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response., Conclusions: In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies.

Atractylodes macrocephala Koidz (AMK) is a traditional herbal medicine used for thousands of years in East Asia to improve a variety of illnesses and conditions, including cancers. This study explored the effect of AMK extract on apoptosis and tumor-grafted mice using AGS human gastric adenocarcinoma cells. We investigated the compounds, target genes, and associated diseases of AMK using the Traditional Chinese Medical Systems Pharmacy (TCMSP) database platform. Cell viability assay, cell cycle and mitochondrial depolarization analysis, caspase activity assay, reactive oxygen species (ROS) assay, and wound healing and spheroid formation assay were used to investigate the anti-cancer effects of AMK extract on AGS cells. Also, in vivo studies were conducted using subcutaneous xenografts. AMK extract reduced the viability of AGS cells and increased the sub-G1 cell fraction and the mitochondrial membrane potential. Also, AMK extract increased the production of ROS. AMK extract induced the increased caspase activities and modulated the mitogen-activated protein kinases (MAPK). In addition, AMK extract effectively inhibited AGS cell migration and led to a notable reduction in the growth of AGS spheroids. Moreover, AMK extract hindered the growth of AGS xenograft tumors in NSG mice. Our results suggest that AMK has anti-cancer effects by promoting cell cycle arrest and inhibiting the proliferation of AGS cancer cells and a xenograft model through apoptosis. This study could provide a novel approach to treat gastric cancer.

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: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC., Methods: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan)., Results: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy., Conclusions: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression., Trial Registration: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732)., (© 2024. The Author(s).)

Background: Gastric cancer is a common cause of global mortality, with significant challenges during treatment due to side effects and complications. Traditional herbal medicine (THM) has emerged as a potential adjuvant therapy to enhance cancer treatment by reducing side effects and bolstering the immune response. This study conducted a meta-analysis to assess the efficacy and safety of THM as an adjuvant therapy in post-surgical gastric cancer patients., Methods: PubMed, Cochrane Library, EMBASE, CNKI, CiNii, KMBASE, KISS, OASIS, RISS, and ScienceON databases were searched from inception through December, 2021. The outcomes considered in this analysis encompassed tumor response, quality of life (QoL), side effects, and tumor markers. Additionally, a frequency analysis of the most commonly used herbs in the included studies was conducted. A total of 36 randomized controlled trials (RCTs) were included, and data were extracted according to study design. The analysis compared groups receiving chemotherapy alone with those receiving both chemotherapy and THM treatment., Results: The group receiving both chemotherapy and THM showed substantial improvement in tumor response compared to the chemotherapy-only control group (RR 1.25, 95% CI [1.09, 1.45]). QoL also significantly increased in the THM-treated group. Most drug adverse reactions displayed statistical significance, except for platelet reduction. Tumor markers CEA, CA19-9, and CA72-4 exhibited significant improvements, but CA125 did not. The 1, 2, and 3-year survival rates improved, with RR values of 1.08 (95% CI [1.02, 1.14]), 1.32 (95% CI [1.19, 1.47]), and 1.42 (95% CI [1.12, 1.79]) respectively. However, some publication bias was indicated., Conclusion: THM may offer potential benefits as a complementary approach to post-surgical anticancer therapy in gastric cancer patients. Improved tumor response, quality of life, and survival rates were reported. However, it is important to exercise caution due to the possibility of publication bias, and further research is needed to confirm these findings.Registration:PROSPERO CRD 42022354133., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Backgrounds: This study aimed to compare the incidence of bile reflux, quality of life (QoL), and nutritional status among Billroth II (BII), Billroth II with Braun anastomosis (BII-B), and Roux-en-Y (RY) reconstruction after laparoscopic distal gastrectomy (LDG)., Materials and Methods: We reviewed the prospective data of 397 patients from a multicentre database who underwent LDG for gastric cancer between 2018 and 2020 at 20 tertiary teaching hospitals in Korea. Postoperative endoscopic findings, QoL surveys using the European Organization for Research and Treatment of Cancer questionnaire (C30 and STO22), and nutritional and surgical outcomes were compared among groups., Results: In endoscopic findings, bile reflux was the lowest in the RY group ( n =67), followed by the BII-B ( n =183) and BII groups ( n =147) at 1 year (3.0 vs. 67.8 vs. 84.4%, all P <0.05). The anti-reflux capability of BII-B was statistically better than that of BII, but not as perfect as that of RY. From the perspective of QoL, BII-B was not inferior to RY, but better than BII reconstruction in causing fewer STO22 reflux symptoms at 6 and 12 months. However, only RY caused fewer C30 nausea symptoms than BII at 6 and 12 months, but not BII-B. Nutritional status and morbidities were similar among the three groups, and the operative time did not differ between the BII-B and RY groups., Conclusions: BII-B cannot substitute for RY in preventing bile reflux, shortening the operative time, or reducing morbidities. Regarding short-term QoL, BII-B was sufficient to reduce STO22 reflux symptoms but failed to reduce C30 nausea symptoms postoperatively., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Previous studies have focused on the non-inferiority of RPG compared with conventional port gastrectomy (CPG); however, we assumed that some candidates might derive more significant benefit from RPG over CPG., Methods: We retrospectively analyzed the clinicopathological and perioperative parameters of 1442 patients with gastric cancer treated by gastrectomy between 2009 and 2022. The C-reactive protein level on postoperative day 3 (CRPD3) was used as a surrogate parameter for surgical trauma. Patients were grouped according to the extent of gastrectomy [subtotal gastrectomy (STG) or total gastrectomy (TG)] and lymph node dissection (D1+ or D2). The degree of surgical trauma, bowel recovery, and hospital stay between RPG and CPG was compared among those patient groups., Results: Of 1442 patients, 889, 354, 129, and 70 were grouped as STGD1+, STGD2, TGD1+, and TGD2, respectively. Compared with CPG, RPG significantly decreased CRPD3 only among patients in the STGD1+ group (CPG: n = 653, 84.49 mg/L, 95% CI 80.53-88.45 vs. RPG: n = 236, 70.01 mg/L, 95% CI 63.92-76.09, P < 0.001). In addition, the RPG method significantly shortens bowel recovery and hospital stay in the STGD1+ (P < 0.001 and P < 0.001), STGD2 (P < 0.001 and P < 0.001), and TGD1+ (P = 0.026 and P = 0.007), respectively. No difference was observed in the TGD2 group (P = 0.313 and P = 0.740)., Conclusions: The best candidates for RPG are patients who undergo STGD1+, followed by STGD2 and TG D1+, considering the reduction in CRPD3, bowel recovery, and hospital stay., (© 2023. The Author(s).)

Securing an appropriate proximal resection margin (PRM) is crucial for oncological safety in treating gastric cancer. This study investigated the clinicopathological characteristics of patients with incomplete PRM length of <2 cm in early gastric cancer. Clinicopathological data of 1,493 patients who underwent subtotal gastrectomy for early gastric cancer in 2012 to 2021 were retrospectively reviewed. Patients were divided into the PRM length of <2 cm and ≥2 cm groups based on pathological results. Univariate and multivariate analyses evaluated factors for incomplete PRM length. Factors related to patients with a relative PRM positive were also analyzed. The proportion of patients with a PRM length of <2 cm was 17.9% (267/1,493). Multivariate regression analysis revealed that age <50, preoperative endoscopic size of ≥3 cm, size discrepancy of ≥2 cm, and midbody tumor with a lesser curvature significantly contributed to the PRM length of <2 cm. Twenty-four patients had a relative PRM positive (24/1493, 1.6%). An incomplete PRM was the only risk factor for a positive relative PRM. Surgical treatment for early gastric cancer requires an accurate preoperative endoscopic tumor size and location evaluation. A more aggressive resection is recommended for patients with age <50, preoperative endoscopic size of ≥3 cm, size discrepancy of ≥2 cm, and midbody tumor with a lesser curvature., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Owing to the rising number of screening endoscopies and instrumental advances in endoscopic ultrasound (EUS), colorectal subepithelial tumors (SETs) are being increasingly detected. We aimed to determine the feasibility of endoscopic resection (ER) and the impact of EUS-based surveillance on colorectal SETs., Methods: The medical records of 984 patients with incidentally detected colorectal SETs between 2010 and 2019 were retrospectively reviewed. Overall, 577 colorectal SETs underwent ER, and 71 colorectal SETs underwent serial colonoscopy for > 12 months., Results: The mean tumor size (± standard deviation) of 577 colorectal SETs for which ER was performed was 7.0 ± 5.7 (median, 55; range, 1-50) mm; 475 tumors were located in the rectum and 102, in the colon. En bloc resection was achieved in 560/577 treated lesions (97.1%), and complete resection was achieved in 516/577 (89.4%). ER-related adverse events occurred in 15/577 (2.6%) patients. SETs originating from the muscularis propria showed a higher risk of ER-related adverse events and perforation than SETs arising from the mucosal or submucosal layer (odds ratio [OR] 19.786, 95% confidence interval [CI] 4.556-85.919; P = 0.002 and OR 141.250, 95% CI 11.596-1720.492; P = 0.046, respectively). Seventy-one patients were followed up after EUS without any treatment for > 12 months, during which three showed progression; eight, regression; and sixty, no changes., Conclusions: ER for colorectal SETs showed excellent efficacy and safety. Additionally, colorectal SETs without high-risk features in surveillance with colonoscopy showed an excellent prognosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: The eCura system, a scoring model for stratifying the lymph node metastasis risk after noncurative endoscopic resection for early gastric cancer (EGC), has been internally validated, primarily for differentiated-type EGC. We aimed to externally validate this model for undifferentiated-type EGC., Methods: This multicenter, retrospective cohort study included 634 patients who underwent additional surgery (radical surgery group, n=270) or were followed up without additional treatment (no additional treatment group, n=364) after noncurative endoscopic resection for undifferentiated-type EGC between 2005 and 2015. The lymph node metastasis and survival rates were compared according to the risk categories., Results: For the radical surgery group, the lymph node metastasis rates were 2.6%, 10.9%, and 14.8% for the low-, intermediate-, and high-risk eCura categories, respectively (p for trend=0.003). For the low-, intermediate-, and high-risk categories in the no additional treatment group, the overall survival (92.7%, 68.9%, and 80.0% at 5 years, respectively, p<0.001) and cancer-specific survival rates (99.7%, 94.7%, and 80.0% at 5 years, respectively, p<0.001) differed significantly. In the multivariate analysis, the hazard ratios (95% confidence interval) in the no additional treatment group relative to the radical surgery group were 3.18 (1.41 to 7.17; p=0.005) for overall mortality and 2.60 (0.46 to 14.66; p=0.280) for cancer-specific mortality in the intermediate-to-high risk category. No such differences were noted in the low-risk category., Conclusions: The eCura system can be applied to undifferentiated-type EGC. Close follow-up without additional treatment might be considered for low-risk patients, while additional surgery is recommended for intermediate- and high-risk patients.

Background: Gastric cancer (GC) is among the most common types of gastrointestinal cancers and has a high incidence and mortality around the world. To suppress the progression of GC, it is essential to develop diagnostic markers. MicroRNAs regulate GC development, but a clearer insight into their role is needed before they can be applied as a molecular markers and targets., Methods: In this study, we assessed the diagnostic value of differentially expressed microRNAs as potential diagnostic biomarkers for GC using data for 389 tissue samples from the Cancer Genome Atlas (TCGA) and 21 plasma samples from GC patients., Results: The expression of hsa-miR-143-3p (also known as hsa-miR-143) was significantly downregulated in GC according to the TCGA data and plasma samples. The 228 potential target genes of hsa-miR-143-3p were analyzed using a bioinformatics tool for miRNA target prediction. The target genes correlated with extracellular matrix organization, the cytoplasm, and identical protein binding. Furthermore, the pathway enrichment analysis of target genes showed that they were involved in pathways in cancer, the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, and proteoglycans in cancer. The hub genes in the protein-protein interaction (PPI) network, were matrix metallopeptidase 2 (MMP2), CD44 molecule (CD44), and SMAD family member 3 (SMAD3)., Conclusions: This study suggests that hsa-miR-143-3p may be used as a diagnostic marker for GC, contributing via the pathways involved in the development of GC., (© 2023. The Author(s).)

Gastric cancer (GC) is a complex disease influenced by multiple genetic and epigenetic factors. Chronic inflammation caused by Helicobacter pylori infection and dietary risk factors can result in the accumulation of aberrant DNA methylation in gastric mucosa, which promotes GC development. Tensin 4 (TNS4), a member of the Tensin family of proteins, is localized to focal adhesion sites, which connect the extracellular matrix and cytoskeletal network. We identified upregulation of TNS4 in GC using quantitative reverse transcription PCR with 174 paired samples of GC tumors and adjacent normal tissues. Transcriptional activation of TNS4 occurred even during the early stage of tumor development. TNS4 depletion in GC cell lines that expressed high to moderate levels of TNS4, i.e., SNU-601, KATO III, and MKN74, reduced cell proliferation and migration, whereas ectopic expression of TNS4 in those lines that expressed lower levels of TNS4, i.e., SNU-638, MKN1, and MKN45 increased colony formation and cell migration. The promoter region of TNS4 was hypomethylated in GC cell lines that showed upregulation of TNS4. We also found a significant negative correlation between TNS4 expression and CpG methylation in 250 GC tumors based on The Cancer Genome Atlas (TCGA) data. This study elucidates the epigenetic mechanism of TNS4 activation and functional roles of TNS4 in GC development and progression and suggests a possible approach for future GC treatments.

Background: Duodenal stump leakage (DSL) is a serious complication after gastrectomy. In this study, we developed a novel prevention technique using a falciform ligament patch (FLP) to prevent DSL among high-risk patients after gastrectomy. Materials and Methods: From January 2019 to July 2021, 14 patients who were judged to be at high risk for DSL during preoperative examinations or surgery were included in this retrospective study, and the FLP was applied to the duodenal stump. The falciform ligament was separated from the liver after duodenal transection during gastrectomy; the end part was used to cover the duodenal stump and was fixed using nonabsorbable polypropylene sutures. Results: In total, 14 patients who underwent FLP had one or two risk factors that were identified: 5 patients, gastric cancer duodenal invasion; 4 patients, gastric outlet obstruction (GOO); 1 patient, cancer involving the distal resection margin; 1 patient, duodenal gastrointestinal stromal tumor involving the distal resection margin; 1 patient, gastric cancer duodenal invasion and GOO; and 2 patients, cancer involving the distal resection margin and GOO. FLP construction was successful, and no patient developed complications of DSL. The average hospital stay was 11.9 days, and the patients were discharged without any morbidities after surgery. Conclusions: Therefore, the FLP can be used to prevent DSL among high-risk patients after gastrectomy.

Background/aims: Endoscopic submucosal dissection is a widely used treatment for gastric epithelial neoplasms. Accurate delineation of the horizontal margins is necessary for the complete resection of gastric epithelial neoplasms. Recently, image-enhanced endoscopy has been used to evaluate horizontal margins of gastric epithelial neoplasms. The aim of this study was to investigate whether I-SCAN-optical enhancement (I-SCAN-OE) is superior to chromoendoscopy in evaluating the horizontal margin of gastric epithelial neoplasms., Methods: This was a multicenter, prospective, and randomized trial. The participants were divided into two groups: I-SCAN-OE and chromoendoscopy. For both groups, we first evaluated the horizontal margins of early gastric cancer or high-grade dysplasia using white-light imaging, and then evaluated, the horizontal margins using I-SCAN-OE or chromoendoscopy. We devised a unique scoring method based on the pathological results obtained after endoscopic submucosal dissection to accurately evaluate the horizontal margins of gastric epithelial neoplasms. The delineation scores of both groups were compared, as were the ratios of positive/negative horizontal margins., Results: In total, 124 patients were evaluated for gastric epithelial neoplasms, of whom 112 were enrolled in the study. A total of 112 patients participated in the study, and 56 were assigned to each group (1:1). There was no statistically significant difference in the delineation scores between the groups (chromoendoscopy, 7.80±1.94; I-SCAN-OE, 8.23±2.24; p=0.342)., Conclusions: I-SCAN-OE did not show superiority over chromoendoscopy in delineating horizontal margins of gastric epithelial neoplasms.

Importance: Patients undergoing proximal gastrectomy (PG) with double-tract reconstruction (DTR) have been reported to have an incidence of reflux esophagitis that is as low as that observed after total gastrectomy (TG). It is unclear whether PG has an advantage over TG for the treatment of patients with upper early gastric cancer (GC)., Objective: To evaluate the effect of laparoscopic PG with DTR (LPG-DTR) vs laparoscopic TG (LTG) on levels of hemoglobin and vitamin B12 supplementation required among patients with clinically early GC in the upper third of the stomach (upper-third early GC)., Design, Setting, and Participants: This multicenter open-label superiority randomized clinical trial was conducted at 10 institutions in Korea. A total of 138 patients with upper-third cT1N0M0 GC were enrolled between October 27, 2016, and September 9, 2018. Follow-up ended on December 3, 2020., Interventions: Patients were randomized to undergo either LPG-DTR or LTG., Main Outcomes and Measures: The primary co-end points were change in hemoglobin level and cumulative amount of vitamin B12 supplementation at 2 years after LPG-DTR or LTG. The secondary end points included morbidity, postoperative reflux esophagitis, quality of life, overall survival, and disease-free survival. Quality of life outcomes were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) 30-item core questionnaire (C30) and the EORTC QLQ stomach cancer-specific questionnaire at 3 months, 12 months, and 24 months., Results: Among 138 patients (mean [SD] age, 60.0 [10.9] years; 87 men [63.0%]; all of Asian race and Korean ethnicity), 68 (mean [SD] age, 56.7 [10.4] years; 39 men [57.4%]) were randomized to receive LPG-DTR and 69 (mean [SD] age, 61.3 [11.3] years; 48 men [69.6%]) were randomized to receive LTG. The mean (SD) changes in hemoglobin levels from baseline to month 24 were -5.6% (7.4%) in the LPG-DTR group and -6.9% (8.3%) in the LTG group, for an estimated difference of -1.3% (95% CI, -4.0% to 1.4%; P = .35). The mean (SD) cumulative amount of vitamin B12 supplementation was 0.4 (1.3) mg in the LPG-DTR group and 2.5 (3.0) mg in the LTG group, for an estimated difference of 2.1 mg (95% CI, 1.3-2.9 mg; P < .001). The late complication rates in the LPG-DTR and LTG groups were 17.6% and 10.1%, respectively (P = .31). The incidence of reflux esophagitis was not different between the LPG-DTR and LTG groups (2.9% vs 2.9%; P = .99). Compared with the LTG group, the LPG-DTR group had better physical functioning scores (85.2 [15.6] vs 79.9 [19.3]; P = .03) and social functioning scores (89.5 [17.9] vs 82.4 [19.4]; P = .03) on the EORTC QLQ-C30. Two-year overall survival (98.5% vs 100%; P = .33) and disease-free survival (98.5% vs 97.1%; P = .54) did not significantly differ between the LPG-DTR vs LTG groups., Conclusions and Relevance: In this study, patients with upper-third early GC who received LPG-DTR required less vitamin B12 supplementation than those who received LTG, with no increase in complication rates and no difference in overall and disease-free survival rates. There was no difference in change in hemoglobin level between groups. In addition, the LPG-DTR group had better physical and social functioning than the LTG group. These findings suggest that LPG-DTR may be as safe as LTG and may be a function-preserving procedure for the treatment of patients with upper-third early GC., Trial Registration: ClinicalTrials.gov Identifier: NCT02892643.

Background: Endoscopic submucosal dissection (ESD) is not as tiresome as gastrectomy, but it is a time-consuming procedure. One-step knife (OSK) is a novel knife that combines a knife for ESD and an injection needle into one sheath. In this study, we aimed to compare the insulated tip type of OSK and conventional knife (CK) in terms of procedure time and complication rate., Methods: Medical records of patients with ESD using CK between February and September 2020 were retrospectively reviewed. Subsequently, data from patients who underwent ESD using OSK by September 2021 were prospectively collected. Total procedure time, procedure time by location and complication rate in the OSK and CK group were compared., Results: In the study period, a total of 203 patients (OSK, 102 patients; CK, 101 patients) were analyzed. On multivariate analysis, using CK, body location, resection size ≥ 40 mm, and submucosal fibrosis were associated with longer procedure time. The total procedure time was statistically significantly reduced in the OSK group (median 11 vs. 17 min, p < 0.01). The procedure time for each location was more reduced in the body (median 14 vs. 19 min p < 0.01) than the antrum (median 10 vs. 14 min, p = 0.01) in the OSK group. There was no significant difference in post-ESD bleeding and perforation in the two groups (3.9 vs. 3.9%, p = 0.99 and 1.0 vs. 2.0%, p = 0.56)., Conclusions: OSK significantly reduced the total procedure time of ESD. OSK could be an effective and safe knife for gastric ESD, especially for body lesions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Subepithelial tumors (SETs) in the upper gastrointestinal (GI) tract are frequently discovered during upper endoscopy, and their management is determined based on size and histopathological diagnosis. We aimed to evaluate the diagnostic performance of endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) in upper GI SETs of 2-5 cm in size., Methods: We included 63 patients who underwent EUS-FNB for upper GI SETs of 2-5 cm in size between January 2013 and February 2020. The diagnostic yield of EUS-FNB, ability of EUS-FNB in discriminating malignant from non-malignant lesions, and histopathological concordance between EUS-FNB specimens and resected specimens were evaluated., Results: Successful acquisition of macroscopic tissue cores was possible in all 63 cases, and the diagnostic yield of EUS-FNB was 92.1% (58/63). The sensitivity, specificity, and accuracy of EUS-FNB in discriminating malignant from non-malignant lesions were 100% (95% confidence interval [CI] 85.3-100%), 87.8% (95% CI 79.9-87.8%), and 92.1% (95% CI 81.8-92.1%), respectively. Of the 26 SETs that were endoscopically or surgically resected after EUS-FNB, the histopathological concordance rate between the EUS-FNB specimens and resected specimens was 100% (24/24), except in two cases of inadequate results with EUS-FNB specimens., Conclusion: EUS-FNB provides high diagnostic yield and high capability in discriminating malignant from non-malignant lesions in upper GI SETs of 2-5 cm in size., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Underwater endoscopic mucosal resection (UW-EMR) has been recently introduced as an effective technique for rectal third layer subepithelial tumors. Therefore, we aimed to assess the safety, efficacy, and procedure time of UW-EMR for upper gastrointestinal subepithelial tumors (SETs) originating from the deep mucosal and/or submucosal layers., Methods: Between August 2018 to July 2022, a total of 17 SETs (7 duodenal SETs, 6 gastric SETs, and 4 esophageal SETs) were included in this study. On endoscopic ultrasound examinations, the tumors were found to be embedded in the submucosa without muscularis propria invasion. All SETs were resected successfully using UW-EMR. The characteristics of the tumors and their R0 resection rate, adverse event rate, and recurrence rate were evaluated retrospectively., Results: The mean tumor size was 0.9 cm (range, 0.3-1.5 cm). En bloc resection and complete resection rates were 100%, respectively. The patients showed no complications such as perforation or bleeding. Histologic assessments of the resected tumors revealed 9 neuroendocrine tumors (7 on the duodenum, 2 on the stomach), 2 gastric cystica profunda, 1 gastric follicular lymphoma, 1 gastric fibromyxoma, 3 esophageal granular cell tumors, and 1 esophageal adenoid cystic carcinoma. The mean procedural time was 3.2 min (range, 1.3-8.7 minutes). The overall en bloc and complete resection rates were 100%, respectively. No recurrence was observed during the follow-up period., Conclusion: UW-EMR is a safe and effective treatment for upper gastrointestinal SETs embedded in the submucosal layer. Further studies are needed to compare other endoscopic resection techniques., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The goal of this study was to identify the clinical outcomes of uncut Roux-en-Y reconstruction in patients who underwent totally laparoscopic distal gastrectomy (TLDG) over 3-year follow-up., Methods: From January 2016 to December 2017, 269 patients who underwent TLDG were enrolled in the study and analyzed retrospectively. They were classified into two groups according to the reconstruction method: uncut Roux-en-Y reconstruction (uncut RY) (n = 154) and Billroth II with Braun anastomosis (B-II/Braun) (n = 115). Postoperative endoscopic findings (residual food, bile reflux, gastritis, and esophagitis) and nutritional status (body weight, serum hemoglobin, total protein, and albumin levels) were assessed every 6 months for 3 years., Results: Residual food was less frequent in the uncut RY group in the 6th month after TLDG (p = 0.022), but there were no differences between the two groups for the rest of the study period. The incidence of bile reflux and gastritis was low in the uncut RY group during all postoperative periods (all p &lt; 0.001). In the B-II/Braun group, the frequency of reflux esophagitis was high in the 30th and 36th months after TLDG (both p &lt; 0.001), and there were no differences between the two groups during the preceding periods. No significant differences were found with respect to nutritional status, such as body weight, serum hemoglobin, total protein, and albumin levels during all postoperative periods., Conclusions: Three-year follow-up outcomes showed that uncut RY can effectively reduce the incidence of bile reflux and gastritis in the remnant stomach compared to B-II/Braun after TLDG., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Extragastric recurrence after radical resection of stage I gastric cancer is very rare. We investigated the incidence of extragastric recurrence and risk factors in patients who underwent surgical resection of stage I gastric cancer and evaluated the value of abdominal CT as a surveillance tool. This retrospective study enrolled 914 patients with stage I gastric cancer who underwent surgical resection at a single tertiary hospital. We investigated extragastric recurrence during the follow-up period, and disease-free survival (DFS) was assessed. Over a median follow-up period of 39 months, the overall incidence of extragastric recurrence was 2.2% (20/914). Risk factors for extragastric recurrence included deep submucosal invasion (SM2-3), muscularis propria invasion, and lymph node metastasis (hazard ratio [HR]=10.37, 28.101, and 6.843; P = .028, .002, and .001, respectively). Based on the number of risk factors, patients were stratified into 3 subgroups: low-risk (pT1aN0, pT1b(SM1)N0, 496/914), moderate-risk (pT1aN1, pT1b(SM1)N1, pT1b(SM2-3)N0, pT2N0, 369/914), and high-risk (pT1b(SM2-3)N1, 49/914). DFS was significantly longer in the low-risk group, followed by the moderate-risk and high-risk groups. We propose that postoperative CT surveillance should be omitted for stage 1A cases involving the mucosa and SM1 because of the extreme rarity of extragastric recurrence., Competing Interests: The authors have no conflicts of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

MicroRNAs (miRNAs) are important diagnostic and prognostic biomarkers for various tumors. Currently, many diagnostic systems have been developed to detect miRNAs, but simple techniques for detecting miRNAs are still required. Recently, we reported that the expression of miRNA-135b is upregulated in gastric epithelial cells during gastric inflammation and carcinogenesis. Our aim was to develop an in vitro diagnostic platform to analyze the expression of gastric cancer-related biomarkers in the blood. The diagnostic platform comprised an isothermal amplification-based lateral flow biosensor (IA-LFB) that enables easy diagnosis of gastric cancer through visual observation. In this platform, trace amounts of biomarkers are isothermally amplified through rolling circle amplification (RCA), and the amplified product is grafted to the LFB. The performance of the IA-LFB was confirmed using RNAs extracted from in vitro and in vivo models. The platform could detect target miRNAs within 3 h with excellent sensitivity and selectivity. In particular, the IA-LFB could detect the overexpression of gastric cancer-related markers (miRNA-135b and miRNA-21) in RNAs extracted from the blood of patients with various stages (stages 1-4) of gastric cancer compared to that in healthy volunteers. Therefore, IA-LFB is a simple and sensitive in vitro diagnostic system for detecting gastric cancer-related biomarkers and can contribute to the early diagnosis and prognosis monitoring of gastric cancer. Furthermore, this technology can be applied to systems that can detect multiple biomarkers related to various diseases (such as infectious and genetic diseases)., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Human immunodeficiency virus (HIV) infection management has recently become more successful. While the life expectancy of HIV-infected patients increased, the prevalence of non-acquired immunodeficiency syndrome-defining cancers, such as gastric cancer, also increased. Helicobacter pylori is associated with gastric cancer, the most common cancer and the fourth leading cause of cancer-related deaths in South Korea, which has the highest incidence of chronic gastric mucosa inflammation. Here, the seroprevalence and risk factors of H. pylori infection in Korean HIV-infected patients were evaluated., Methods: Three hundred HIV-infected patients attending the Outpatient Department of Pusan National University Hospital were prospectively enrolled from October 2018 to February 2019. Socio-demographic information was evaluated using questionnaires, and the serological status of H. pylori infection was analyzed for anti-H. pylori IgG antibodies., Results: The overall seropositivity of H. pylori was 32.7%, and 254 patients (84.7%) were male. The risk factors significantly associated with H. pylori seropositivity were: age of 40-49 years (odds ratio [OR] = 5.00; 95% confidence interval [CI] 1.30-19.17), age of 50-59 years (OR = 3.93; 95% CI 1.05-14.73), CD4 cell counts of 350-500/μL (OR = 4.23; 95% CI 1.53-11.65), CD4 cell counts ≥500/μL (OR = 2.78; 95% CI 1.15-6.72), and a weekly average alcohol consumption of at least one alcoholic beverage (OR = 1.78; 95% CI 1.05-2.99)., Conclusions: The seroprevalence of H. pylori is significantly associated with alcohol consumption, high CD4 cell count, and the age group of 40-59 years., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer deaths around the world. Chemotherapy is one of the most effective treatments for cancer patients, and has remarkably enhanced survival rates. However, it has many side effects. Recently, microRNAs (miRNAs) have been intensively studied as potential biomarkers for cancer diagnosis and treatment monitoring. However, definitive biomarkers in chemotherapy-induced peripheral neuropathy (CIPN) are still lacking. The aim of this study was to identify the factors significant for neurological adverse events in GC patients receiving XELOX (oxaliplatin and capecitabine) chemotherapy. The results show that XELOX chemotherapy induces changes in the expression of hsa-miR-200c-3p, hsa-miR-885-5p, and hsa-miR-378f. Validation by qRT-PCR demonstrated that hsa-miR-378f was significantly downregulated in CIPN. Hsa-miR-378f was identified as showing a statistically significant correlation in GC patients receiving XELOX chemotherapy according to the analysis of differentially expressed (DE) miRNAs. Furthermore, 34 potential target genes were predicted using a web-based database for miRNA target prognostication and functional annotations. The identified genes are related to the peptidyl-serine phosphorylation and regulation of alternative mRNA splicing with enrichment in the gastric cancer, neurotrophin, MAPK, and AMPK signaling pathways. Collectively, these results provide information useful for developing promising strategies for the treatment of XELOX-chemotherapy-induced peripheral neuropathy.

Background: For successful treatment of early gastric cancers (EGCs), it is crucial to define the horizontal border of the lesion with high accuracy. Acetic acid-indigo carmine (AI) chromoendoscopy has been used to determine the horizontal border in EGCs, but this technique is less potent in certain situations. Mucin phenotype in gastric cancers refers to biological differences in precursor lesions and differences in histopathologic findings, and it might affect AI chromoendoscopy findings. We aimed to investigate the association between mucin phenotype and AI chromoendoscopy findings in EGCs., Methods: We prospectively evaluated 126 lesions in 126 patients with endoscopically diagnosed EGCs. Conventional endoscopy and AI chromoendoscopy findings of these lesions before treatment were prospectively analyzed. The border distinction between the lesion and surrounding mucosa was classified as distinct or indistinct on conventional endoscopy and AI chromoendoscopy, respectively. Mucin phenotypes were classified as gastric, intestinal, gastrointestinal, or null type by immunohistochemistry., Results: The lesion borders were distinct in 46.8% (59/126) of the lesions assessed using conventional endoscopy and in 73.0% (92/126) of those assessed with AI chromoendoscopy (p < 0.001). The border distinction rate of differentiated-type cancers on AI chromoendoscopy was significantly higher than that on conventional endoscopy (66/71 [93.0%] vs. 34/71 [47.9%], p < 0.001), but the border distinction rate of undifferentiated-type cancers on AI chromoendoscopy was not different from that on conventional endoscopy (26/55 [47.3%] vs. 25/55 [45.5%], p = 0.848). Compared with conventional endoscopy, AI chromoendoscopy identified borders in a significantly higher percentage of gastric, intestinal, and gastrointestinal mucin types; however, there was no difference in AI chromoendoscopy findings according to the mucin phenotype (p = 0.271)., Conclusion: AI chromoendoscopy was effective in horizontal border delineation in differentiated-type EGCs, but not in undifferentiated-type EGCs. Mucin phenotype had no effect on border distinction using AI chromoendoscopy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment., Methods: We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared., Results: Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively., Conclusions: ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Total laparoscopic distal gastrectomy for early gastric cancer has been widely accepted; however, reduced-port laparoscopic distal gastrectomy has not gained the same popularity because of technical difficulties and oncologic safety issues. This study aimed to analyze the oncologic safety and short-term surgical outcomes of patients who underwent reduced-port laparoscopic distal gastrectomy (RpLDG) for gastric cancer., Methods: Consecutive patients who underwent surgical treatment between January 2016 and May 2018 were included in this study. Of the 833 patients enrolled, 158 underwent RpLDG and were propensity-matched with 158 patients who underwent conventional port laparoscopic distal gastrectomy (CpLDG). The groups were compared in terms of short-term outcomes and disease-free and overall survival rates., Results: The RpLDG group had shorter operation times (161.8 min vs. 189.0 min, p < 0.00) and shorter postoperative hospital stays (7.6 days vs. 9.1 days, p = 0.04) compared to the CpLDG group. Estimated blood loss was lower in the RpLDG group than in the CpLDG group (52.6 mL vs. 73.7 mL, p < 0.00), while hospital costs incurred by the RpLDG group were lower than those of the CpLDG group (10,033.7 vs. 11,016.8 USD, p < 0.00). No statistical differences were found regarding overall morbidity and occurrence of surgical complications of grade III or higher, as defined by the Clavien-Dindo classification. Furthermore, no significant differences between RpLDG and CpLDG were found in 3-year disease-free (99.4% vs. 98.1%; p = 0.42) and 3-year overall survival rates (98.7% vs. 96.8%; p = 0.25)., Conclusion: Patients who underwent RpLDG had better short-term surgical outcomes than those who underwent CpLDG in terms of operation time, estimated blood loss, duration of hospital stay, and hospital costs. The oncologic safety of RpLDG was satisfactory., (© 2021. The Society for Surgery of the Alimentary Tract.)

Background: Patients who received endoscopic resection (ER) for early gastric cancer (EGC) or high-grade dysplasia (HGD) are at high risk for the subsequent development of metachronous gastric cancer (MGC). This study aims to compare the detection rate and stage of MGC between biannual and annual endoscopic surveillance after ER of EGC or HGD., Methods: From September 2009 to August 2019, 859 patients who underwent ER for the treatment of EGC or HGD were analyzed, retrospectively. Patients received endoscopic surveillance twice a year (high-intensity group) or annually (low-intensity group) for 3 years., Results: A total of 521 patients were enrolled in this study (267 patients in the high-intensity group and 254 patients in the low-intensity group). During a mean follow-up of 5.3 ± 1.6 years, MGCs were found in 27 patients (16.9%) in the high-intensity group and 18 patients (7.1%) in the low-intensity group (P = 0.219). In patients with moderate to severe atrophy (Kimura-Takemoto grade C3 ~ O3), detection rates of MGC during 3 years from were 8.4% (16/191) and 2.2% (4/186), respectively (P = 0.007). Forty-four patients who received treatment for MGC, including endoscopic or surgical resection, were stage IA. Only one patient in the low-intensity group was diagnosed as stage IIIA advanced gastric cancer., Conclusions: There was no significant difference in the detection rate of MGC between biannual and annual endoscopic surveillance after ER of EGC or HGD. However, biannual surveillance showed a higher detection rate during the first 3 years, especially for patients with moderate to severe gastric atrophy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC); however, its curative resection rate is low for undifferentiated-type EGC. We developed and externally validated a prediction model for curative ESD of undifferentiated-type EGC., Methods: In this cross-sectional study, we included 448 patients who underwent ESD for undifferentiated-type EGC at 18 hospitals in Korea between 2005 and 2015 in the development cohort and 1342 patients who underwent surgery at two hospitals in the validation cohort. A prediction model was developed using the logistic regression model., Results: Endoscopic tumor size 1-2 cm (odds ratio [OR], 2.40; 95% confidence interval [CI] 1.54-3.73), tumor size > 2 cm (OR, 14.00; 95% CI 6.81-28.77), and proximal tumor location from the lower to upper third of the stomach (OR, 1.45; 95% CI 1.03-2.04) were independent predictors of non-curative ESD. A six-score prediction model was developed by assigning points to endoscopic tumor size > 2 cm (five points), tumor size 1-2 cm (two points), upper third location (two points), and middle third location (one point). The rate of curative ESD ranged from 70.6% (score 0) to 11.6% (score 5) with an area under the receiver operating characteristic curve (AUC) of 0.720 (95% CI 0.673-0.766). The model also showed good performance in the validation cohort (AUC, 0.775; 95% CI 0.748-0.803)., Conclusions: This six-score prediction model may help in predicting curative ESD and making informed decisions about the treatment selection between ESD and surgery for undifferentiated-type EGC., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Subepithelial tumors (SETs) are commonly encountered during upper gastrointestinal endoscopy, especially during national gastric cancer screening programs in Korea. Although the majority of SETs are benign, endoscopists harbor concerns regarding whether a SET is benign or malignant because the diagnosis cannot be established on the basis of routine endoscopic biopsy findings. The differential diagnosis of SETs is important, beginning with meticulous endoscopic examination, including the evaluation of the location, macroscopic shape, color, surface characteristics, mobility, consistency, and size of the tumors. The yield of endoscopic biopsy increases with the use of the bite-on-bite technique for SETs without the rolling or tenting sign, with large openings, and with erosion or ulceration. In this review, a systematic approach for the diagnosis of gastric SETs during conventional endoscopy is introduced.

Early gastric cancers (EGCs) are defined as gastric cancers confined to the mucosa or submucosa, regardless of regional lymph node metastasis. The proportion of EGCs has been increasing due to the increase in screening endoscopy for gastric cancers; therefore, the paradigm shift from surgical resection to endoscopic resection as a treatment modality for selected EGCs is accelerating. For successful endoscopic resection of EGCs, it is important to detect EGCs at an early stage and to accurately predict the histological type, depth of invasion, and horizontal margins of the tumor. The diagnostic process of EGCs can be divided into three steps: presence diagnosis, qualitative diagnosis, and quantitative diagnosis. The presence diagnosis of EGCs is mainly based on two endoscopic findings: a well-demarcated lesion and irregularity in the color/surface pattern. Qualitative diagnosis refers to the prediction of histological type, which is mainly possible based on the macroscopic shape and color of the lesion. Quantitative diagnosis of EGCs consists of predicting the depth of invasion by detailed examination of the macroscopic morphology and determining horizontal margins using chromoendoscopy. Although advanced diagnostic modalities, such as endosonography or magnifying endoscopy, are helpful for the qualitative and quantitative diagnosis of EGCs, these modalities are not available in most hospitals. Therefore, it is still very important to evaluate EGCs systematically during conventional endoscopy for successful endoscopic treatment.

Proton pump inhibitors (PPIs) are used worldwide to treat of acid-related disorders such as peptic ulcer and gastroesophageal reflux disease and to prevent gastroduodenal injuries due to nonsteroidal anti-inflammatory drugs. PPIs are the most potent inhibitors of gastric acid secretion currently available, and they are one of the most commonly prescribed classes of drugs because of their high efficacy and low toxicity. However, long-term PPI use causes histopathological changes such as parietal cell protrusion into the gland lumen, cystic dilation of gastric fundic glands, and foveolar epithelial hyperplasia. These changes can manifest on endoscopic examination as fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like mucosa, or black spots. Clinicians must be aware of PPI-induced endoscopic features in patients with chronic long-term PPI use. Conversely, identifying patients with long-term PPI use based on their endoscopic findings is important. Recently, potassium-competitive acid blockers (P-CABs), a new class of acid suppressants that inhibit gastric acid secretion more strongly than PPIs, have recently been introduced clinically. Further long-term prospective studies on these gastric mucosal lesions in patients with either PPI or P-CAB use are required to investigate their association with histopathological changes and to establish the clinical significance of these findings.

Background/aims: This study examined the long-term outcomes of undifferentiated-type early gastric cancer (UD EGC) with positive horizontal margins (HMs) after endoscopic resection (ER) and compared them between additional surgery and nonsurgical management., Methods: From 2005 to 2015, a total of 1,124 patients with UD EGC underwent ER at 18 tertiary hospitals in Korea. Of them, 92 patients with positive HMs as the only noncurative factor (n=25) or with both positive HMs and tumor size >2 cm (n=67) were included. These patients underwent additional surgery (n=40), underwent additional endoscopic treatment (n=6), or were followed up without further treatment (n=46)., Results: No lymph node (LN) metastasis was found in patients who underwent additional surgery. During a median follow-up of 57.7 months (interquartile range, 27.6 to 68.8 months), no LN or distant metastases or gastric cancer-related deaths occurred in the overall cohort. At baseline, the residual cancer rate was 57.8% (26/45) after additional surgery or ER. The 5-year local recurrence rate was 33.6% among patients who were followed up without additional treatment. The 5-year overall survival rates were 95.0% and 87.8% after additional surgery and nonsurgical management (endoscopic treatment or close follow-up), respectively (log-rank p=0.224). In the multivariate Cox regression analysis, nonsurgical management was not associated with an increased risk of mortality., Conclusions: UD EGC with positive HMs after ER may have favorable long-term outcomes and a very low risk of LN metastasis. Nonsurgical management may be suggested as an alternative, particularly for patients with old age or chronic illness.

Background: Few studies have presented evidence pertaining to the adequate minimum number of adjuvant chemotherapy (AC) cycles required to achieve an oncologic benefit for gastric cancer., Methods: From January 2012 to December 2013, data from patients who underwent curative radical gastrectomy and consequently received AC for pathologic stage 2 or 3 gastric cancer at 27 institutions in South Korea were analyzed., Results: The study enrolled 925 patients, 661 patients (71.5%) who completed 8 cycles of AC and 264 patients (28.5%) who did not. Compared with the mean disease-free survival (DFS) of the patients who completed 8 AC cycles (69.3 months), the mean DFS of patients who completed 6 AC cycles (72.4 months; p = 0.531) and those who completed 7 AC cycles (63.7 months; p = 0.184) did not differ significantly. However, the mean DFS of the patients who completed 5 AC cycles (48.2 months; p = 0.016) and those who completed 1-4 AC cycles (62.9 months; p = 0.036) was significantly lower than the DFS of those who completed 8 AC cycles. In the multivariate Cox proportional hazards analysis, the mean DFS was significantly affected by advanced stage, large tumor size, positive vascular invasion, and number of completed AC cycles (1-5 cycles: hazard ratio 1.45; 95% confidence interval 1.01-2.08; p = 0.041)., Conclusion: The current multicenter observational cohort study showed that the mean DFS for 6 or 7 AC cycles was similar to that for 8 AC cycles as an adjuvant treatment for gastric cancer.

Objective: This study applied network analyses to illustrate patterns of associations between cancer-related physical and psychological symptoms (CPPS) and quality of life (QOL) before and after surgery., Methods: Participants consisted of 256 gastric cancer patients admitted for curative section surgery at the surgical department in a teaching hospital in Korea between May 2016 and November 2017. Participants completed the survey, including MD Anderson Symptom Inventory, Hospital Anxiety and Depression Scale, and Functional Assessment of Cancer Therapy-Gastric Cancer before surgery (T0), 1 week after surgery (T1), and 3-6 months after surgery (T2)., Results: Three networks featured several salient connections with varying magnitudes between CPPS and QOL across all time points. Particularly, anxiety was tightly connected to emotional wellbeing (EWB) across all time points and physical wellbeing (PWB) at T1. On the other hand, depression was connected to functional wellbeing at T0 and T2, gastric cancer concerns (CS) at T1, and PWB at T2. Distress and sadness were the most central symptoms in the three networks. Other central symptoms included shortness of breath at T0, fatigue at T0 and T1, and PWB and CS at T2. Anxiety, depression, and EWB served as bridges connecting CPPS to QOL across all time points with varying degrees of importance, as did PWB at T1 and T2., Conclusions: Treating psychological distress and enhancing EWB and PWB can be high impact intervention targets throughout the cancer trajectory., (© 2021 John Wiley & Sons Ltd.)

Resistance to anticancer therapeutics occurs in virtually every type of cancer and becomes a major difficulty in cancer treatment. Although 5-fluorouracil (5FU) is the first-line choice of anticancer therapy for gastric cancer, its effectiveness is limited owing to drug resistance. Recently, altered cancer metabolism, including the Warburg effect, a preference for glycolysis rather than oxidative phosphorylation for energy production, has been accepted as a pivotal mechanism regulating resistance to chemotherapy. Thus, we investigated the detailed mechanism and possible usefulness of antiglycolytic agents in ameliorating 5FU resistance using established gastric cancer cell lines, SNU620 and SNU620/5FU. SNU620/5FU, a gastric cancer cell harboring resistance to 5FU, showed much higher lactate production and expression of glycolysis-related enzymes, such as lactate dehydrogenase A (LDHA), than those of the parent SNU620 cells. To limit glycolysis, we examined catechin and its derivatives, which are known anti-inflammatory and anticancer natural products because epigallocatechin gallate has been previously reported as a suppressor of LDHA expression. Catechin, the simplest compound among them, had the highest inhibitory effect on lactate production and LDHA activity. In addition, the combination of 5FU and catechin showed additional cytotoxicity and induced reactive oxygen species (ROS)-mediated apoptosis in SNU620/5FU cells. Thus, based on these results, we suggest catechin as a candidate for the development of a novel adjuvant drug that reduces chemoresistance to 5FU by restricting LDHA.

Background and Aims: Endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD EGC) has debate due to the risk of lymph node metastasis. We investigated the outcomes of ESD compared to those of surgery for the UD EGC within expanded indication., Methods: We reviewed 971 UD EGC patients performed ESD across 18 hospitals in Korea and 1812 patients who underwent surgical resection in two hospitals between February 2005 and May 2015. Of these cases, we enrolled a curative resected ESD group of 328 patients and surgery group of 383 cases within an expanded indication. Overall outcomes and one-to-one propensity score-matched (218 ESD group vs 218 surgery group cases) outcomes for these two groups were analyzed., Results: Over the 75.6 month median follow-up period for the 711 enrolled cases, recurrences occurred in 22 patients (6.7%) in the ESD group but not in the surgery group. Overall survival (OS) was higher in the surgery group (p = 0.0316) in all cases, but there was no significant difference after propensity score matching (p = 0.069). According to the histologic type in propensity score matching, the OS of signet ring cell carcinoma and poorly differentiated carcinoma patients did not differ between the ESD and surgery groups (p = 0.1189 and p = 0.3087, respectively). In the surgery group involving expanded criteria, lymph node metastasis was found in six cases (1.56%)., Conclusions: Although ESD shows comparable outcomes to surgery for the UD EGC within expanded indications, appropriate patient selection is needed for the ESD due to the possibility of lymph node metastasis.

Alisol B 23‑acetate (AB23A) is a natural triterpenoid isolated from Alismatis rhizoma , which exhibits a number of pharmacological activities. In the present study, AB23A‑induced anticancer efficacy was examined in AGS gastric cancer cells. Cell viability assay, cell cycle analysis, caspase activity assay, western blotting and reactive oxygen species (ROS) assay were used to investigate the anticancer effects of AB23A on AGS cells. AB23A reduced the viability of AGS cells, increased the sub‑G1 cell fraction and depolarized the mitochondrial membrane. Notably, AB23A‑induced cell death was associated with downregulation of the B‑cell lymphoma 2 and survivin proteins, and upregulation of the Bax protein. In addition, AB23A increased caspase‑3 and ‑9 activities, and regulated the activation of mitogen‑activated protein kinases (MAPK). Moreover, AB23A increased the production of reactive oxygen species. These results suggested that AB23A may induce apoptosis through cell cycle arrest and the mitochondrial pathway, accompanied by the caspase and MAPK signaling cascades. In conclusion, AB23A may have potential as a novel anticancer drug for the treatment of gastric cancer.

The anti-cancer effects of Alisma canaliculatum extracts (ACE) were identified in AGS gastric cancer cells. Our results showed that ACE inhibited the growth of AGS cells, increased the proportion of sub-G1 phase cells, and depolarized the membrane potential of mitochondria. ACE-induced gastric cancer cell death was associated with Bcl-2, survivin and Bax level changes, and it activated caspase-3 and -9. In addition, it was involved in the activation of MAPKs and increased the reactive oxygen species (ROS). These results suggest that ACE induces apoptosis in AGS gastric cancer cells, and therefore, ACE may have the potential to treat gastric cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)