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Abstract Background The current gastric cancer staging system relies on the number of metastatic lymph nodes (MLNs) for nodal stage determination. However, incorporating additional information such as topographic status may help address uncertainties. This study evaluated the appropriateness of the current staging system and relative significance of MLNs based on their anatomical location. Methods Patients who underwent curative gastrectomy for gastric cancer between 2000 and 2019 at six Catholic Medical Center-affiliated hospitals were included. Lymph node-positive patients were classified into the perigastric (stations 1–6, group P) or extragastric (stations 7–12) groups. The extragastric group was further subdivided into the near-extragastric (stations 7–9, group NE) and far-extragastric (stations 10–12, group FE) groups. Results We analyzed the data of 3,591 patients with positive lymph node metastases. No significant survival differences were found between group P and the extragastric group in each N stage. However, in N1 and N2, group FE showed significantly worse survival than the other groups (p = 0.013 for N1, p

Abstract Background Weight changes after gastrectomy affect not only quality of life but also prognosis and survival. However, it remains challenging to predict the weight changes of individual patients. Using clinicopathological variables, we built a user-friendly tool to predict weight change after curative gastrectomy for gastric cancer. Methods The clinical data of 984 patients who underwent curative gastrectomy between 2009 and 2013 were retrospectively reviewed and analyzed. Multivariate logistic regression was performed to identify variables predictive of postoperative weight change. A nomogram was developed and verified via bootstrap resampling. Results Age, sex, performance status, body mass index, extent of resection, pathological stage, and postoperative weight change significantly influenced postoperative weight recovery. Postoperative levels of hemoglobin, albumin, ferritin and total iron-binding capacity were significant covariates. The nomogram performed well (concordance index = 0.637); calibration curves indicated appropriate levels of agreement. We developed an online weight prediction calculator based on the nomogram ( http://gc-weightchange.com/en/front/ ). Conclusions The novel, Web-calculator based on the predictive model allows surgeons to explore patient weight patterns quickly. The model identifies patients at high risk for weight loss after gastrectomy; such patients require multidisciplinary medical support.

Abstract Background We sought to assess the prognostic significance of lymph node ratio (LNR) and N stage in patients undergoing D2 gastrectomy and adjuvant chemotherapy, S-1, and XELOX and to compare the efficacy of them according to LNRs and N stages to evaluate the clinical impact of using LNRs compared with using N staging. Methods Patients undergoing D2 gastrectomy with adequate lymph node dissection and adjuvant chemotherapy for stage II/III gastric cancer between Mar 2011 and Dec 2016 were analysed. Of the 477 patients enrolled, 331 received S-1 and 146 received XELOX. LNR groups were segregated as 0, 0–0.1, 0.1–0.25, and > 0.25 (LNR0, 1, 2, and 3, respectively). Propensity score matching (PSM) was used to minimise potential selection bias and compare DFS and OS stratified by LNRs and N stages in the two treatment groups. Results After PSM, the sample size of each group was 110 patients, and variables were well balanced. All patients had more than 15 examined lymph nodes (median 51, range 16~124). In multivariate analysis, LNR (> 0.25) and N stage (N3) showed independent prognostic value in OS and DFS, but LNR (> 0.25) showed better prognostic value. In subgroup analysis, the LNR3 group showed better 5-year DFS (20% vs 54%; HR 0.29; p = 0.004) and 5-year OS (26% vs 67%; HR 0.28; p = 0.020) in the XELOX group. The N3 group showed better 5-year DFS (38% vs 66%; HR 0.40; p = 0.004) and 5-year OS (47% vs 71%; HR 0.45; p = 0.019) in the XELOX group. Stage IIIC showed better 5-year DFS (22% vs 57%; HR 0.32; p = 0.004) and 5-year OS (27% vs 68%; HR 0.32; p = 0.009) in the XELOX group. The LNR3 group within N3 patients showed better 5-year DFS (21% vs 55%; HR 0.31; p = 0.004) and 5-year OS (27% vs 68%; HR 0.34; p = 0.018) in the XELOX group. Conclusions LNR showed better prognostic value than N staging. LNR3, N3 and stage IIIC groups showed the superior efficacy of XELOX to that of S-1. And the LNR3 group within N3 patients showed more survival benefit from XELOX. LNR > 0.25, N3 stage and stage IIIC were the discriminant factors for selecting XELOX over S-1. Trial registration Not applicable (retrospective study).

Abstract Background KLASS (the Korean Laparoendoscopic Gastrointestinal Surgery Study) is a time-honored study group that has established laparoscopic surgery for gastrointestinal disease in Korea and has performed some important studies for the rationale of laparoscopic gastrointestinal surgery. A multi-center RCT (randomized controlled trial) to compare the quality of life (QOL) of patients undergoing totally laparoscopic distal gastrectomy (TLDG) and laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer, named as KLASS 07, has been currently prepared in Korea. Methods Patients diagnosed as gastric cancer, with clinical stage IA (T1N0M0) or IB (T1N1M0 / T2N0M0) according to the 7th edition of the Americal Joint Committee on Cancer System, were randomized to receive either TLDG or LADG. For surgical quality control, the surgeons participating in this trial had to have performed at least 50 gastrectomies and at least 30 gastrectomies annually (regardless of open or laparoscopic surgery for gastric cancer). The patients who are allocated to TLDG group undergo intracorporeal anastomosis and those who are assigned to LADG undergo extracorporeal anastomosis for gastrointestinal reconstruction. Discussion Thirty-one surgeons from 26 institutions were engaged in this trial. The primary endpoint is 30-day morbidity, and secondary endpoint is QOL assessed by the questionnaire score. The KLASS 07 trial is the first multi-center RCT to investigate whether there are significant and quantifiable differences between the QOL of TLDG and LADG. The findings from this trial are expected to be the critical clues for designing the detailed procedures during laparoscopic surgery for gastric cancer. Trial registration The protocol of KLASS 07 (CKLASS 01) was registered in http://register.clinicaltrials.gov as NCT03393182 (Date of registration: January 2nd, 2018.).

Abstract Background The CD133 transmembrane protein is a well-recognized stem cell marker that has been used to isolate putative cancer stem cell populations from gastric cancers (GCs). However, the molecular features or biomarkers underlying CD133 are largely unknown in GCs. Methods We performed gene expression profiling of CD133+ and CD133- cells sorted by flow cytometry from three GC cell lines to identify the CD133 expression signatures of GC. The CD133 expression signatures were investigated across publicly available expression profiles of multiple tumor types including GC and also for their relationship with patient survival. Results The CD133 signature genes defined as 177 upregulated genes and 129 downregulated genes in CD133+ cells compared to CD133- cells were enriched with genes involving the cell cycle and cytoskeleton, implying that cancer stem cells with unlimited self-renewal play cancer-initiating roles. The CD133 expression signatures in GC expression profiles were positively correlated with those of brain tumors expressing CD133 and human embryonic stem cells, emphasizing the transcriptional similarities across stem cell-related expression signatures. We also found that these stem cell expression signatures were inversely correlated with those representing tumor infiltrating immune and stromal cells. Additionally, high CD133 expression signatures were found in intestinal subtypes and low tumor stage GCs as well as in those with microsatellite instabilities and high mutation burdens. As examined across 20 additional tumor types, both the expression signatures representing CD133 and stromal cells were unfavorable prognostic features; however, their impact were variable across tumor types. Conclusions The transcriptional activities of CD133 and those of stromal cells representing the activity of stem cells and level of epithelial-to-mesenchymal transition, respectively, may be inversely correlated with each other across multiple tumor types including GC. This relationship may be a confounding factor and should therefore be considered when evaluating the clinical relevance of stem cell-related markers.

Abstract Background Dickkopf-1 (DKK1) is a Wnt/ß-catenin pathway antagonist related to gastric cancer (GC) carcinogenesis. However, the prognostic role of combined DKK1 and ß-catenin expression in advanced GC (AGC) is not clear. Methods In total, 158 patients with AGC who underwent gastric resection were enrolled in this study. DKK1 and ß-catenin expression was evaluated in whole tumor sections by immunohistochemistry. Results DKK1 expression was high in 73 (46.2%) patients, while ß-catenin expression was positive in 51 (32.3%) patients. The expression of DKK1 was positively correlated with that of ß-catenin (P