Deep learning based ECG segmentation for delineation of diverse arrhythmias.

Accurate delineation of key waveforms in an ECG is a critical step in extracting relevant features to support the diagnosis and treatment of heart conditions. Although deep learning based methods using segmentation models to locate P, QRS, and T waves have shown promising results, their ability to handle arrhythmias has not been studied in any detail. In this paper we investigate the effect of arrhythmias on delineation quality and develop strategies to improve performance in such cases. We introduce a U-Net-like segmentation model for ECG delineation with a particular focus on diverse arrhythmias. This is followed by a post-processing algorithm which removes noise and automatically determines the boundaries of P, QRS, and T waves. Our model has been trained on a diverse dataset and evaluated against the LUDB and QTDB datasets to show strong performance, with F1-scores exceeding 99% for QRS and T waves, and over 97% for P waves in the LUDB dataset. Furthermore, we assess various models across a wide array of arrhythmias and observe that models with a strong performance on standard benchmarks may still perform poorly on arrhythmias that are underrepresented in these benchmarks, such as tachycardias. We propose solutions to address this discrepancy.

Effector Function Characteristics of Exhausted CD8+ T-cell in Microsatellite Stable and Unstable Gastric Cancer.

Purpose: Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors (ICIs), presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential. Materials and Methods: We explored the molecular characteristics of CD8+ T cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis. Results: In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T (MAIT) cell and NKT cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The IFN-γ signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer. Conclusion: Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.

Identification of New Pathogenic Variants of Hereditary Diffuse Gastric Cancer.

Purpose: Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression. Materials and Methods: Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing (WES) on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation and enrichment analysis were performed. Results: As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the RhoaR129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked RhoAR129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families. Conclusion: The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

RNA expression of 6 genes from metastatic mucosal gastric cancer serves as the global prognostic marker for gastric cancer with functional validation.

BACKGROUND: Molecular analysis of advanced tumors can increase tumor heterogeneity and selection bias. We developed a robust prognostic signature for gastric cancer by comparing RNA expression between very rare early gastric cancers invading only mucosal layer (mEGCs) with lymph node metastasis (Npos) and those without metastasis (Nneg). METHODS: Out of 1003 mEGCs, all Npos were matched to Nneg using propensity scores. Machine learning approach comparing Npos and Nneg was used to develop prognostic signature. The function and robustness of prognostic signature was validated using cell lines and external datasets. RESULTS: Extensive machine learning with cross-validation identified the prognostic classifier consisting of four overexpressed genes (HDAC5, NPM1, DTX3, and PPP3R1) and two downregulated genes (MED12 and TP53), and enabled us to develop the risk score predicting poor prognosis. Cell lines engineered to high-risk score showed increased invasion, migration, and resistance to 5-FU and Oxaliplatin but maintained sensitivity to an HDAC inhibitor. Mouse models after tail vein injection of cell lines with high-risk score revealed increased metastasis. In three external cohorts, our risk score was identified as the independent prognostic factor for overall and recurrence-free survival. CONCLUSION: The risk score from the 6-gene classifier can successfully predict the prognosis of gastric cancer.

Distribution of Perigastric Station 4d Lymph Nodes in Vascularized Gastroepiploic Lymph Node Transfer: An Anatomic Study and Case Series.

BACKGROUND: Vascularized gastroepiploic lymph node transfer (VGLNT) is a well-accepted surgical treatment for restoring physiological function in chronic lymphedema. However, the inclusion of substantial lymph nodes (LNs) in the flap remains uncertain. This study aimed to identify the anatomical basis for reliable flap harvest for VGLNT. PATIENTS AND METHODS: The anatomy of perigastric station 4d LNs was studied in healthy cadavers (n = 15) and patients with early gastric cancer (EGC) (n = 27). The omentum was divided into three segments: proximal, middle, and distal from the origin of the right gastroepiploic vessels. The flap dimension, number, location, size of LNs, and caliber of the vessels were reviewed. Eight patients underwent VGLNT for upper/lower limb lymphedema. RESULTS: The mean numbers of LNs in the proximal, middle, and distal segment were 2.5, 1.4, 0.5 in the cadavers, and 4.9, 2.7, 0.7 in the gastrectomy specimens, respectively. The proximal third included a significantly greater number of LNs than the distal third in the cadaveric (p = 0.024) and ECG (p = 0.016) specimens. A total of 95% of the LNs were located within proximal two-thirds of the flap from the vessel origin both in the cadavers (21.0 × 5.0 cm) and in the gastrectomy specimens (20 × 3.5 cm). In VGLNT, the transferred flap was 25.5 ± 6.9 × 4.1 + 0.7 cm in dimension, containing a mean number of 6.5 ± 1.9 LNs. At postoperative 6 months, the volumetric difference was significantly reduced by 22.8 ± 9.2% (p < 0.001). CONCLUSIONS: This study provides a distinct distribution pattern of station 4d LNs. Inclusion of the proximal two-thirds of the flap, which carries majority of the LNs, is recommended for VGLNT.

Long-term impact of weight loss in people with class II obesity on the overall burden of disease: Evidence from the National Health Screening Cohort in Korea.

BACKGROUND: Obesity is known to increase overall disease burden but does obesity management actually help reduce disease burden? OBJECTIVES: To investigate the effects of weight loss on disease burden in people with obesity using the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in Korea. SETTING: Pure longitudinal observational study using Nationwide cohort database. METHODS: Out of 514,866 NHIS-HEALS cohort, participants with class II obesity in Asia-Pacific region (30 ≤ body mass index [BMI] < 35) who underwent health check-up provided by NHIS during 2003-2004 (index date) were included. All final participants continued to receive a total of 5 biennial health check-ups over the next 10 years without missing. A group-based trajectory model (GBTM) was used to categorize subjects based on 10-year BMI change patterns. The changes of co-morbidities, healthcare resource utilization, and medical cost were analyzed. RESULTS: The final study subjects (9857) were categorized into 3 trajectory clusters based on the pattern of BMI (kg/m2) change: maintenance (57.35%) with an average change of -.02 ± .06, loss (38.65%) with -.04 ± .08, and substantial loss (4.0%) with -.10 ± .18. The annual increases in the number of co-morbidities per subject in each cluster were .18, .18, and .16 (all P < .001), respectively. The increase of healthcare resource utilization over time was lowest for the substantial loss compared to maintenance and loss. With each passing year, the average annual total healthcare cost increased by ₩21,200 ($16.48, P = .034) and ₩10,500 ($8.16, P = .498) in the maintenance and loss, respectively, but decreased by ₩62,500 ($48.59, P = .032) in the substantial loss. CONCLUSIONS: Weight loss in people with obesity was associated with a reduced burden of disease, as evidenced by lower co-morbidity, healthcare resource utilization rate, and decreased medical costs. This study highlights the potential positive long-term impact on Korean society when actively managing weight in individuals with obesity.

Long-Term Outcome of Proximal Gastrectomy for Upper-Third Advanced Gastric and Siewert Type II Esophagogastric Junction Cancer Compared With Total Gastrectomy: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to investigate the oncologic long-term safety of proximal gastrectomy for upper-third advanced gastric cancer (AGC) and Siewert type II esophagogastric junction (EGJ) cancer. METHODS: The study enrolled patients who underwent proximal gastrectomy (PG) or total gastrectomy (TG) with standard lymph node (LN) dissection for pathologically proven upper-third AGC and EGJ cancers between January 2007 and December 2018. Propensity score-matching with a 1:1 ratio was performed to reduce the influence of confounding variables such as age, sex, tumor size, T stage, N stage, and tumor-node-metastasis (TNM) stage. Kaplan-Meier survival analysis was performed to analyze oncologic outcome. The prognostic factors of recurrence-free survival (RFS) were analyzed using the Cox proportional hazard analysis. RESULTS: Of the 713 enrolled patients in this study, 60 received PG and 653 received TG. Propensity score-matching yielded 60 patients for each group. The overall survival rates were 61.7 % in the PG group and 68.3 % in the TG group (p = 0.676). The RFS was 86.7 % in the PG group and 83.3 % in the TG group (p = 0.634). The PG group showed eight recurrences (1 anastomosis site, 1 paraaortic LN, 1 liver, 1 spleen, 1 lung, 1 splenic hilar LN, and 2 remnant stomachs). In the multivariate analysis, the operation method was not identified as a prognostic factor of tumor recurrence. CONCLUSION: The patients who underwent PG had a long-term oncologic outcome similar to that for the patients who underwent TG for upper-third AGC and EGJ cancer.

Targeting Stem Cells and Dysplastic Features With Dual MEK/ERK and STAT3 Suppression in Gastric Carcinogenesis.

BACKGROUNDS & AIMS: Precancerous metaplasia progression to dysplasia can increase the risk of gastric cancers. However, effective strategies to specifically target these precancerous lesions are currently lacking. To address this, we aimed to identify key signaling pathways that are upregulated during metaplasia progression and critical for stem cell survival and function in dysplasia. METHODS: To assess the response to chemotherapeutic drugs, we used metaplastic and dysplastic organoids derived from Mist1-Kras mice and 20 human precancerous organoid lines established from patients with gastric cancer. Phospho-antibody array analysis and single-cell RNA-sequencing were performed to identify target cell populations and signaling pathways affected by pyrvinium, a putative anticancer drug. Pyrvinium was administered to Mist1-Kras mice to evaluate drug effectiveness in vivo. RESULTS: Although pyrvinium treatment resulted in growth arrest in metaplastic organoids, it induced cell death in dysplastic organoids. Pyrvinium treatment significantly downregulated phosphorylation of ERK and signal transducer and activator of transcription 3 (STAT3) as well as STAT3-target genes. Single-cell RNA-sequencing data analyses revealed that pyrvinium specifically targeted CD133+/CD166+ stem cell populations, as well as proliferating cells in dysplastic organoids. Pyrvinium inhibited metaplasia progression and facilitated the restoration of normal oxyntic glands in Mist1-Kras mice. Furthermore, pyrvinium exhibited suppressive effects on the growth and survival of human organoids with dysplastic features, through simultaneous blocking of the MEK/ERK and STAT3 signaling pathways. CONCLUSIONS: Through its dual blockade of MEK/ERK and STAT3 signaling pathways, pyrvinium can effectively induce growth arrest in metaplasia and cell death in dysplasia. Therefore, our findings suggest that pyrvinium is a promising chemotherapeutic agent for reprogramming the precancerous milieu to prevent gastric cancer development.

Surgical Outcomes of Laparoscopic-assisted Distal Gastrectomy Versus Totally Laparoscopic Distal Gastrectomy Billroth I for Gastric Cancer.

OBJECTIVE: The present study aimed to compare intraoperative and postoperative outcomes of laparoscopic-assisted distal gastrectomy versus totally laparoscopic distal gastrectomy (TLDG) Billroth I (BI) for gastric cancer and to assess the impact of the initial introduction phase of TLDG BI anastomosis. PATIENTS AND METHODS: The study analyzed the prospectively collected data of patients who underwent laparoscopic distal gastrectomy BI from 2014 to 2021 at Seoul National University Hospital. RESULTS: Among 1116 patients, laparoscopic-assisted distal gastrectomy BI was performed in 566 patients and TLDG BI was performed in 550 patients. The total laparoscopic arm had a faster mean operative time (190 vs 208 min; P < 0.001) and a shorter postoperative hospital stay (7.4 vs 7.9 d; P < 0.001). Local complications were higher in the total laparoscopic group (17.6% vs 9.9%; P = 0.008) during the early introduction phase. CONCLUSION: The total laparoscopic approach for BI reconstruction is safe and effective with faster operative time, shorter hospital stays, and less wound infection, but it may be associated with an increase in postoperative surgical complications and hospital stay in the early introduction phase.

Feasibility and safety of pure single-incision laparoscopic total and proximal gastrectomy for early gastric cancer: propensity score-matched comparison to multiport totally laparoscopic approach.

BACKGROUND: There have been few studies regarding the feasibility and safety of pure single-incision laparoscopic total gastrectomy (SITG) or proximal gastrectomy (SIPG) for early gastric cancer (EGC). The purpose of this study was to analyze the surgical outcome of all consecutive SITG or SIPG cases compared with multiport laparoscopic total gastrectomy (MLTG) or proximal gastrectomy (MLPG) for EGC. METHODS: We analyzed all consecutive SITG or SIPG cases with double-tract reconstruction for ECG, including the initial case, between March 2013 and December 2021. SITG/SIPG was performed on patients without significant systemic comorbidities through a 3-4 cm vertical transumbilical incision. SITG/SIPG was matched to multiport laparoscopic total or proximal gastrectomy (MLTG/MLPG) cases performed in the same period using a 1:3 propensity score matching, including sex, body mass index (BMI), age and type of resection, year of operation, and institution as covariates. We compared perioperative clinicopathological characteristics and early postoperative morbidity within 1 month after surgery between the SITG/SIPG and MLTG/MLPG groups. RESULTS: In total, 21 patients with SITG and 15 patients with SIPG were compared with those with MLTG (n = 264) and MLPG (n = 220). No conversion to an open or multiport approach occurred in the SITG/SIPG group. After matching, operation time was similar between SITG/SIPG and MLTG/MLPG (223.9 ± 63.5 min vs 234.8 ± 68.7 min, P = 0.402). Length of stay was not significantly different between SITG/SIPG and MLTG/MLPG (11.9 ± 15.4 days vs 8.4 ± 5.0 days, P = 0.210). The average number of retrieved lymph nodes was not significantly different between SITG and MLTG (53.1 ± 16.3 vs 63.2 ± 27.5, P = 0.115), but it was significantly higher in SIPG than MLPG (59.6 ± 27.2 vs 46.0 ± 19.7, P = 0.040). The overall complication rate (30.6% vs 25.9%, P = 0.666) and Clavien-Dindo grade III or higher complication rates (13.9% vs 6.5%, P = 0.175) were not significantly different between the SITG/SIPG and MLTG/MLPG groups. CONCLUSION: Cautious adoption of SITG/SIPG procedures for EGC is feasible and safe.

Can prospective monitoring improve complication rates after gastrectomy? Experience of Billroth I reconstruction at a high-volume tertiary center.

INTRODUCTION: Prospective database is imperative in surgical outcome monitoring and has shown success in providing a comprehensive complication index to monitor surgical quality. This study aims to review whether prospective monitoring has an effect on postoperative complication rates, especially leakage after Billroth I (BI) anastomosis and to identify risk factors of anastomosis leakage after BI anastomosis. MATERIALS AND METHODS: Patients who underwent distal gastrectomy with BI reconstruction at Seoul National University Hospital between January 2018 and April 2021 were enrolled. Clinicopathological characteristics and perioperative variables were retrieved. The risk factor that was statistically significant in univariate analysis was further analyzed by binomial logistic regression analysis. RESULTS: BI leakage rate in three years has declined by half on a yearly basis from 5.7% to 1.8%. The leakage group patients were predominantly male (100%) when compared to the non-leakage group (67.6%) (p = 0.04). The BMI (25.00 ± 1.42 vs. 24.16 ± 3.15, p = 0.048) and CRP measured on POD#2 (16.47 ± 5.64 vs. 9.99 ± 5.42, p < 0.001) showed significant differences between the two groups. POD#2 CRP greater than 12.7 mg/dL was able to predict risk of anastomosis leak with sensitivity 73.3% and specificity 73.1%. CONCLUSION: Understanding variations in outcomes is important for improvements in surgical care, and through prospective monitoring and intra-departmental feedback, it is possible to reduce complication rates after gastrectomy. This study shows that age, gender and BMI are risk factors to BI leakage and POD#2 CRP greater than 12.7 mg/dL can be used to suspect leakage after BI anastomosis.

Organoid-Based Human Stomach Micro-Physiological System to Recapitulate the Dynamic Mucosal Defense Mechanism.

Several stomach diseases are attributed to the dysregulation of physiological function of gastric mucosal barrier by pathogens. Gastric organoids are a promising tool to develop treatment strategies for gastric infections. However, their functional features of in vivo gastric mucosal barrier and host-microbe interactions are limited due to the lack of physiological stimuli. Herein, a human stomach micro-physiological system (hsMPS) with physiologically relevant gastric mucosal defense system is described based on the combination of organoid and MPS technology. A fluid flow enhanced epithelial-mesenchymal interaction in the hsMPS enables functional maturation of gastric epithelial cells, which allows for the recreation of mesh-like mucus layer containing high level of mucus protective peptides and well-developed epithelial junctional complexes. Furthermore, gastroprotection mechanisms against Helicobacter pylori (H. pylori) are successfully demonstrated in this system. Therefore, hsMPS represents a new in vitro tool for research where gastric mucosal defense mechanism is pivotal for developing therapeutic strategies.

Long-term outcomes of a phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumors of the stomach.

BACKGROUND: Neoadjuvant treatment is recommended for large GISTs due to their friability and risk of extensive operations; however, studies on the indications and long-term results of this approach are lacking. METHODS: Patients with large (≥ 10 cm) gastric GISTs were enrolled from multiple centers in Korea and Japan after a pathologic confirmation of c-KIT ( +) GISTs. Imatinib (400 mg/d) was given for 6-9 months preoperatively, and R0 resection was intended. Postoperative imatinib was given for at least 12 months and recommended for 3 years. RESULTS: A total of 56 patients were enrolled in this study, with 53 patients receiving imatinib treatment at least once and 48 patients undergoing R0 resection. The 5-year overall survival and progression-free survival rates were 94.3% and 61.6%, respectively. Even patients with stable disease by RECIST criteria responded well to preoperative imatinib treatment and could undergo R0 resection, with most being evaluated as partial response by CHOI criteria. The optimal reduction in tumor size was achieved with preoperative imatinib treatment for 24 weeks or more. No resumption of imatinib treatment was identified as an independent prognostic factor for recurrence after R0 resection. No additional size criteria for a higher risk of recurrence were identified in this cohort with a size of 10 cm or more. CONCLUSIONS: Neoadjuvant imatinib treatment is an effective treatment option for gastric GISTs 10 cm or larger. Postoperative imatinib treatment is recommended even after R0 resection to minimize recurrence.

Erratum: Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach.

This corrects the article on p. 3 in vol. 23, PMID: 36750993.

Cross-phenotype association analysis of gastric cancer: in-silico functional annotation based on the disease-gene network.

BACKGROUND: A gene or variant has pleiotropic effects, and genetic variant identification across multiple phenotypes can provide a comprehensive understanding of biological pathways shared among different diseases or phenotypes. Discovery of genetic loci associated with multiple diseases can simultaneously support general interventions. Several meta-analyses have shown genetic associations with gastric cancer (GC); however, no study has identified associations with other phenotypes using this approach. METHODS: Here, we applied disease network analysis and gene-based analysis (GBA) to examine genetic variants linked to GC and simultaneously associated with other phenotypes. We conducted a single-nucleotide polymorphism (SNP) level meta-analysis and GBA through a systematic genome-wide association study (GWAS) linked to GC, to integrate published results for the SNP variants and group them into major GC-associated genes. We then performed disease network and expression quantitative trait loci (eQTL) analyses to evaluate cross-phenotype associations and expression levels of GC-related genes. RESULTS: Seven genes (MTX1, GBAP1, MUC1, TRIM46, THBS3, PSCA, and ABO) were associated with GC as well as blood urea nitrogen (BUN), glomerular filtration rate (GFR), and uric acid (UA). In addition, 17 SNPs regulated the expression of genes located on 1q22, 24 SNPs regulated the expression of PSCA on 8q24.3, and rs7849820 regulated the expression of ABO on 9q34.2. Furthermore, rs1057941 and rs2294008 had the highest posterior causal probabilities of being a causal candidate SNP in 1q22, and 8q24.3, respectively. CONCLUSIONS: These findings identified seven GC-associated genes exhibiting a cross-association with GFR, BUN, and UA.

High-throughput multi-gate microfluidic resistive pulse sensing for biological nanoparticle detection.

A microfluidic resistive pulse sensing technique offers a simple method for detecting and analysing microparticles in various fields, yet it has challenges such as the noise during detection and low throughput as the signal obtained from a small single sensing aperture and particle position is nonuniform. This study presents a microfluidic chip with multiple detection gates in the main channel to enhance the throughput while maintaining a simple operational system. A hydrodynamic sheathless particle focusing on a detection gate by modulation of the channel structure and measurement circuit with a reference gate to minimize the noise during detection is used for detecting resistive pulses. The proposed microfluidic chip can analyse the physical properties of 200 nm polystyrene particles and exosomes from MDA-MB-231 with high sensitivity with an error of <10% and high-throughput screening of more than 200 000 exosomes per seconds. The proposed microfluidic chip can analyse the physical properties with high sensitivity, so that it can be potentially used for exosome detection in biological and in vitro clinical applications.

Genetic and immune microenvironment characterization of HER2-positive gastric cancer: Their association with response to trastuzumab-based treatment.

BACKGROUND: We aimed to determine the molecular and immune microenvironment characteristics of HER2-positive gastric cancer (GC) related to the patient's response to first-line trastuzumab-based treatment. METHODS: Eighty-three cases of HER2-positive advanced gastric adenocarcinoma patients treated with trastuzumab were enrolled. Targeted deep sequencing and transcriptome analysis were performed on selected 21 cases (exploration cohort) along with two post-treatment samples. The results were compared between patients progressed before 6 months (Group 2) and others (Group 1), and were validated by FISH and immunohistochemistry in total cohort. Tumor-infiltrating immune cells were evaluated using RNA sequencing data and multiplex immunohistochemistry. Progression-free survival (PFS) analysis was performed. RESULTS: Group 1 showed frequent amplification of G1/S cell cycle checkpoint-related genes and upregulated KEGG pathways related to cell proliferation. In contrast, Group 2 had more frequent EGFR, HER3, and MET amplification and higher RNA expression in immune-related KEGG pathways than Group 1. In total cohort, significant predictors of better PFS were cell cycle-related including CCNE1 amplification, Cyclin A and PLK1 overexpression, and decreased Cyclin D3 and HER3 expression (p < 0.05), or immune-related including high density of CD3- CD57+ NK cells and PD-L1 combined positive score ≥5 (p < 0.05). The best prognostic predictors were a combination of Cyclin A, Cyclin E, p21, and HER3 (p < 0.001). CONCLUSION: HER2-positive GC with favorable response to trastuzumab were characterized by cell cycle-related gene alterations and increased CD3- CD57+ NK cell infiltration. These findings would be helpful to the fine modulation of therapeutic strategies for patients with HER2-positive GC.

Clinical Outcomes of Resectional Roux-en-Y Gastric Bypass, Compared to Sleeve Gastrectomy for Severe Obesity.

PURPOSE: Resectional Roux-en-Y gastric bypass (RRYGB) is considered an alternative bariatric surgery in countries with a high incidence of stomach cancer because there is no excluded stomach after RRYGB. This study aimed to evaluate the efficacy and safety of RRYGB. MATERIALS AND METHODS: This study included patients who underwent RRYGB and sleeve gastrectomy (SG) between 2011 and 2021. Surgical complications and metabolic and nutritional profiles were compared between the patients preoperatively and at 1, 6, and 12 months after surgery. RESULTS: Twenty and seventy-six patients underwent RRYGB and SG, respectively; 7 in the SG group were lost to follow-up within 1 year. Surgical complications and baseline characteristics were comparable between two groups, except for diabetes (90.0% vs. 44.7%, p < 0.001). The decrease of HbA1c levels and incidence of reflux esophagitis were lower in the RRYGB group compared to that of SG at 1-year postoperative (-3.0% vs. -1.8%, p = 0.014; 0% vs. 26.7%, p = 0.027). The percentage of total weight loss at 1- year postoperative and incidence of dumping syndrome were comparable between the two groups. The RRYGB group had significantly lower total cholesterol level (161.9 mg/dl vs. 196.4 mg/dl, p < 0.001), but higher incidence of vitamin B12 deficiency (30.0% vs. 3.6%, p = 0.003) at 1 year postoperative compared to those of the SG group. CONCLUSIONS: The RRYGB group had better postoperative outcomes for diabetes and dyslipidemia without increasing surgical complications compared to that of the SG group. Thus, RRYGB can be considered a safe and effective alternative in areas where gastric cancer is prevalent.