GC

Nishi Memorial Award in Gastric Cancer

Correction to: Oncological safety of proximal gastrectomy for T2/T3 proximal gastric cancer The correct name of the corresponding author should be “Takaki Yoshikawa”, and not “Takaki Yoshiaki” as given in the original publication of the article.

Where does signet-ring cell carcinoma come from and where does it go?

Outcomes of endoscopic submucosal dissection for gastric epithelial neoplasm in chronic kidney disease patients: propensity score-matched case–control analysis, methodological and statistical issues

Gastric sub-epithelial tumors: identification of gastrointestinal stromal tumors using CT with a practical scoring method Abstract Objectives To determine CT features that can identify gastrointestinal stromal tumors (GISTs) among gastric sub-epithelial tumors (SETs) and to explore a practical scoring method. Methods Sixty-four patients with gastric SETs (51 GISTs and 13 non-GISTs) from hospital I were included for primary analyses, and 92 (67 GISTs and 25 non-GISTs) from hospital II constituted a validation cohort. Pre-operative CT images were reviewed for imaging features: lesion location, growth pattern, lesion margin, enhancement pattern, dynamic pattern, attenuation at each phasic images and presence of necrosis, superficial ulcer, calcification, and peri-lesion enlarged lymph node (LN). Clinical and CT features were compared between the two groups (GISTs versus non-GISTs) and a GIST-risk scoring method was developed; then, its performance for identifying GISTs was tested in the validation cohort. Results Seven clinical and CT features were significantly suggestive of GISTs rather than non-GISTs: older age (> 49 years), non-cardial location, irregular margin, lower attenuation on unenhanced images (≤ 43 HU), heterogeneous enhancement, necrosis, and absence of enlarged LN (p < 0.05). At validation step, the established scoring method with cut-off score dichotomized into ≥ 4 versus < 4 for identifying GISTs revealed an AUC of 0.97 with an accuracy of 92%, a sensitivity of 100% and a negative predictive value (NPV) of 100%. Conclusions Gastric GISTs have special CT and clinical features that differ from non-GISTs. With a simple and practical scoring method based on the significant features, GISTs can be accurately differentiated from non-GISTs.

Impact of preoperative wait time on survival in patients with clinical stage II/III gastric cancer Abstract Background Preoperative wait time is affected by various factors, and a certain time is needed before surgery. There is a concern that cancer treatment delay can lead to poor survival. The present study aimed to evaluate the impact of preoperative wait time on survival in patients with clinical stage (cStage) II/III gastric cancer. Methods The study included patients with cStage II/III primary gastric cancer undergoing surgery between 2002 and 2012. Preoperative wait time was defined as the time from endoscopy for initial diagnosis to surgery. Patients were divided into the following three groups according to wait time: short wait group (≤ 30 days), intermediate wait group (> 30 and ≤ 60 days), and long wait group (> 60 and ≤ 90 days). Patient characteristics and survival were compared among the groups. Results This study included 467 male (67%) and 229 female (33%) patients, and the median patient age was 67 years. The numbers of cStage II and III patients were 332 (48%) and 364 (52%), respectively. The median wait time was 45 days. The body mass index was lower in the short wait group than in the other groups. A shorter wait time tended to be associated with a more advanced cStage. Although survival was significantly worse in the short wait group than in the long wait group, wait time was not identified as an independent prognostic factor in multivariate analysis. Conclusion Preoperative wait time up to 90 days does not affect survival in patients with cStage II/III gastric cancer.

Genome-wide long non-coding RNAs identified a panel of novel plasma biomarkers for gastric cancer diagnosis Abstract Background Although long non-coding RNAs (lncRNAs) are regarded as useful plasma-based biomarkers for cancer detection, the potential diagnostic value of lncRNAs in gastric cancer (GC) remains unclear. Methods To screen promising lncRNAs biomarkers for GC, we performed genome-wide lncRNA microarray assay between five GC cases plasma and matched healthy controls plasma. The expression of candidate plasma-related lncRNAs were validated in two-phase validation of 446 subjects. The receiver operating characteristic curve was constructed for evaluating diagnostic accuracy. We also determined the origin and stability of plasma lncRNAs, and investigated biological effects of candidate lncRNAs on cellular phenotypes. Results A total of 3878 lncRNAs were expressed differentially in GC plasma, among which the top 10 up-regulated lncRNAs were selected for further validation. A two-stage validation revealed that plasma levels of three lncRNAs (FAM49B-AS, GUSBP11, and CTDHUT) were significantly higher in GC plasma as compared with healthy controls (P < 0.05), and the combined area under curve of these lncRNAs was 0.818 (95% CI 0.772–0.864). Moreover, these lncRNAs were stable and detectable in human plasma, and also enriched in extracellular fluid. The expression levels of all three lncRNAs dropped significantly on day 10 after radical surgery compared with preoperative levels (P < 0.05). Also, lncRNA FAM49B-AS significantly promoted GC cell viability and invasion. Conclusions Plasma lncRNA FAM49B-AS, GUSBP11 and CTDHUT have a strong potential to serve as noninvasive biomarkers for GC diagnosis.

Number of retrieved lymph nodes is an independent prognostic factor after total gastrectomy for patients with stage III gastric cancer: propensity score matching analysis of a multi-institution dataset Abstract Background The prognostic significance of the number of retrieved lymph nodes (RLNs) in gastric cancer remains controversial. Therefore, we designed a multicenter collaborative database to investigate the correlation between the number of RLNs and prognosis of patients with advanced gastric cancer after curative resection. Methods We retrospectively analyzed 1103 patients who underwent gastrectomy for stage II/III gastric cancer between 2010 and 2014. Lymph nodes, which were retrieved by surgeons from surgically resected specimens, were validated by pathologists. A target population and the optimal cutoff were determined using receiver operating characteristic (ROC) curve analysis. After propensity score matching of eight variables, including splenectomy and adjuvant chemotherapy, the prognostic significance of RLNs was evaluated. Results According to ROC curve analysis, the optimum cutoff score for predicting postoperative survival was 40. After matching, the backgrounds of patients in the RLN < 40 and RLN ≥ 40 groups (n = 87 each) became well-balanced. The RLN < 40 group experienced significantly shorter relapse-free and overall survival. The prevalence of peritoneal recurrence was significantly increased in the RLN < 40 group. RLN < 40 was an independent prognostic factor in multivariable analysis, although pathological N status was not. A forest plot revealed that the RLN < 40 group was at greater risk of recurrence in most subgroups. Conclusions RLN < 40 was associated with an adverse prognosis of patients with stage III gastric cancer who underwent total gastrectomy.

Predictive factors for hyperprogressive disease during nivolumab as anti-PD1 treatment in patients with advanced gastric cancer Abstract Background Hyperprogressive disease (HPD) during treatment with anti-programmed death-1/programmed death-ligand 1 monoclonal antibodies has anecdotally been reported in some types of cancers, but is not well-characterized in patients with advanced gastric cancer (AGC). Methods Total 62 AGC patients treated with nivolumab in a single institution from September 2017 to April 2018 were enrolled in this study. Tumor responses were assessed according to Response Evaluation Criteria in Solid Tumors version 1.1, and HPD was defined as ≥ two fold increase in tumor growth rate. Clinicopathological and molecular characteristics associated with HPD were also investigated. Results Thirteen of 62 patients (21%) developed HPD after nivolumab treatment. Overall survival (OS) and progression-free survival (PFS) were significantly shorter in patients with HPD than in patients without HPD (median OS: 2.3 months vs. not reached, P < 0.001; median PFS: 0.7 months vs. 2.4 months, P < 0.001). Liver metastases (77% vs. 41%), Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or 2 (77% vs. 29%), and a large sum of target lesion diameters at baseline (median 104.2 mm vs. 44.9 mm) were significantly associated with HPD. Absolute neutrophil count (ANC) and C-reactive protein (CRP) level significantly increased in the first 4 weeks in only patients with HPD. Conclusions HPD was observed in AGC patients treated with nivolumab and correlated with some clinicopathological characteristics. Elevations in ANC and CRP levels upon treatment might indicate HPD.

Predictive value of MLH1 and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer Abstract Background Microsatellite instability (MSI) and programmed death-ligand 1 (PD-L1) are candidate predictors for the response to immune checkpoint inhibitors, and may predict chemotherapy sensitivity. We investigated the simultaneous expression of mutL homolog 1 (MLH1), a mismatch repair gene, and PD-L1 in gastric cancers. Methods We examined MLH1 and PD-L1 expression in surgical specimens from 285 gastric cancer patients treated with or without preoperative chemotherapy, and assessed the relation between expression results and both histological response and recurrence-free survival (RFS). Results Of 285 patients, 28 (9.8%) and 70 (24.6%) exhibited negative MLH1 and high PD-L1 expression, respectively. Most MLH1-negative tumors (85.7%) showed high MSI, and these tumors exhibited high PD-L1 expression more frequently than MLH1-positive tumors (57.1% vs. 21.0%, P < 0.001). MLH1-negative patients were significantly less likely to respond to preoperative chemotherapy than MLH1-positive patients (16.7% vs. 61.2%, P = 0.005), whereas there was no significant difference between high- and low-PD-L1 expression patients (55.9% vs. 56.6%, P = 0.95). RFS in patients without preoperative chemotherapy was significantly longer in the MLH1-negative group than in the MLH1-positive group (HR 0.30; 95% CI 0.09–0.95; P = 0.030), whereas in patients with preoperative chemotherapy there was no significant difference in RFS between the two groups (HR 0.70; 95% CI 0.30–1.63; P = 0.41). PD-L1 expression was not associated with RFS in patients with or without chemotherapy. Conclusions Loss of MLH1 was associated with chemoresistance and did not prolong survival following neoadjuvant chemotherapy. The strong association between MLH1 and MSI status suggests that immune checkpoint inhibitors may be preferable to conventional chemotherapy for MLH1-negative gastric cancer.