Explore the vast range of titles available.

Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer. Identifying patients that will respond to a particular therapy remains a key challenge in precision oncology. Here, in gastric cancer, the authors show that circulating tumour DNA can predict recurrence, provided that the signal from white blood cells is filtered out.

INTRODUCTION:The early detection of gastric neoplasms (GNs) leads to favorable treatment outcomes. The latest endoscopic system, EVIS X1, includes third-generation narrow-band imaging (3G-NBI), texture and color enhancement imaging (TXI), and high-definition white-light imaging (WLI). Therefore, this randomized phase II trial aimed to identify the most promising imaging modality for GN detection using 3G-NBI and TXI.METHODS:Patients with scheduled surveillance endoscopy after a history of esophageal cancer or GN or preoperative endoscopy for known esophageal cancer or GN were randomly assigned to the 3G-NBI, TXI, or WLI groups. Endoscopic observations were performed to detect new GN lesions, and all suspected lesions were biopsied. The primary endpoint was the GN detection rate during primary observation. Secondary endpoints were the rate of missed GNs, early gastric cancer detection rate, and positive predictive value for a GN diagnosis. The decision rule had a higher GN detection rate between 3G-NBI and TXI, outperforming WLI by >1.0%.RESULTS:Finally, 901 patients were enrolled and assigned to the 3G-NBI, TXI, and WLI groups (300, 300, and 301 patients, respectively). GN detection rates in the 3G-NBI, TXI, and WLI groups were 7.3, 5.0, and 5.6%, respectively. The rates of missed GNs were 1.0, 0.7, and 1.0%, the detection rates of early gastric cancer were 5.7, 4.0, and 5.6%, and the positive predictive values for the diagnosis of GN were 36.5, 21.3, and 36.8% in the 3G-NBI, TXI, and WLI groups, respectively.DISCUSSION:Compared with TXI and WLI, 3G-NBI is a more promising modality for GN detection.

ObjectiveTo develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy.DesignThis was a nationwide multicentre cross-sectional study. Individuals aged 40–80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti-Helicobacter pylori IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled.ResultsThe novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, H. pylori infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12–16) or high-risk (17–25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001).ConclusionsThe developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

ObjectiveEarly detection of gastric cancer has been the topic of major efforts in high prevalence areas. Whether advanced imaging methods, such as second-generation narrow band imaging (2G-NBI) can improve early detection, is unknown.DesignThis open-label, randomised, controlled tandem trial was conducted in 13 hospitals. Patients at increased risk for gastric cancer were randomly assigned to primary white light imaging (WLI) followed by secondary 2G-NBI (WLI group: n=2258) and primary 2G-NBI followed by secondary WLI (2G-NBI group: n=2265) performed by the same examiner. Suspected early gastric cancer (EGC) lesions in both groups were biopsied. Primary endpoint was the rate of EGC patients in the primary examination. The main secondary endpoint was the positive predictive value (PPV) for EGC in suspicious lesions detected (primary examination).ResultsEGCs were found in 44 (1.9%) and 53 (2.3%; p=0.412) patients in the WLI and 2G-NBI groups, respectively, during primary EGD. In a post hoc analysis, the overall rate of lesions detected at the second examination was 25% (n=36/145), with no significant differences between groups. PPV for EGC in suspicious lesions was 13.5% and 20.9% in the WLI (50/371 target lesions) and 2G-NBI groups (59/282 target lesions), respectively (p=0.015).ConclusionThe overall sensitivity of primary endoscopy for the detection of EGC in high-risk patients was only 75% and should be improved. 2G-NBI did not increase EGC detection rate over conventional WLI. The impact of a slightly better PPV of 2G-NBI has to be evaluated further.Trial registration numberUMIN000014503.

Data on the evolution of gastric precancerous lesions (GPL), especially in countries of a Low gastric cancer incidence area are limited. Our objective was to study a long-term evolution of GPL in France. All the patients diagnosed with GPL (atrophic gastritis, intestinal metaplasia [IM], and dysplasia) between 2000 and 2015 and fulfilling criteria for evolution assessment (at least 2 endoscopies, minimal follow-up of 6 months, and at least 2 biopsies obtained from the antrum and corpus) were included. Clinical and endoscopic data were analyzed, and histological samples were reviewed by an expert pathologist with evaluation of the Operative Link on Gastric Intestinal Metaplasia Assessment stage and type of IM. From the 507 patients with GPL, 79 fulfilled the strict criteria. During a mean follow-up of 66 months, during which the patients had a mean number of 4 endoscopies (min-max: 2-21) with 9 biopsies/endoscopy, a stability was observed in 70% of patients. Progression occurred in 14% of patients, within a mean delay of 62.1 months (min-max: 17-99). Progression of the lesions was significantly higher in patients with incomplete type of IM (relative risk of progression for incomplete IM: 11.5; 95% confidence interval 2.5-53.1). Regression of IM occurred in 16% of the patients, after a mean delay of 90 months. This study shows that the patients with antrum-limited IM, especially of incomplete type, are at the highest risk of developing gastric cancer. In most patients, however, the lesions remain stable, which highlights the need for additional markers to better target the patients at risk of progression.

Background With the goal of discovering non-invasive biomarkers for early diagnosis of GC, we conducted a case-control study utilising urine samples from individuals with predominantly early GC vs. healthy control (HC). Methods Among urine samples from 372 patients, age- and sex-matched 282 patients were randomly divided into three groups: 18 patients in a discovery cohort; 176 patients in a training cohort and 88 patients in a validation cohort. Results Among urinary proteins identified in the comprehensive quantitative proteomics analysis, urinary levels of TFF1 (uTFF1) and ADAM12 (uADAM12) were significantly independent diagnostic biomarkers for GC, in addition to Helicobacter pylori status. A urinary biomarker panel combining uTFF1, uADAM12 and H. pylori significantly distinguished between HC and GC patients in both training and validation cohorts. On the analysis for sex-specific biomarkers, this combination panel demonstrated a good AUC of 0.858 for male GC, whereas another combination panel of uTFF1, uBARD1 and H. pylori also provided a good AUC of 0.893 for female GC. Notably, each panel could distinguish even stage I GC patients from HC patients (AUC = 0.850 for males; AUC = 0.845 for females). Conclusions Novel urinary protein biomarker panels represent promising non-invasive biomarkers for GC, including early-stage disease.

Bemarituzumab is an afucosylated monoclonal antibody against FGFR2b (a FGF receptor) with demonstrated monotherapy clinical activity in patients with late-line gastric cancer whose tumors overexpress FGFR2b (NCT02318329). We describe the rationale and design of the FIGHT trial (NCT03343301), a global, randomized, double-blind, placebo-controlled Phase III study evaluating the role of bemarituzumab in patients with previously untreated, FGFR2b-overexpressing advanced gastroesophageal cancer. Patients are randomized in a blinded fashion to the combination of mFOLFOX6 and bemarituzumab or mFOLFOX6 and placebo. Eligible patients are selected based on the presence of either FGFR2b protein overexpression determined by immunohistochemistry or gene amplification determined by circulating tumor DNA. The primary end point is overall survival, and secondary end points include progression-free survival, objective response rate and safety.

Objective Patients with gastric atrophy and intestinal metaplasia (IM) were at risk for gastric cancer, necessitating an accurate risk assessment. We aimed to establish and validate a diagnostic approach for gastric biopsy specimens using deep learning and OLGA/OLGIM for individual gastric cancer risk classification. Methods In this study, we prospectively enrolled 545 patients suspected of atrophic gastritis during endoscopy from 13 tertiary hospitals between December 22, 2017, to September 25, 2020, with a total of 2725 whole-slide images (WSIs). Patients were randomly divided into a training set ( n  = 349), an internal validation set ( n  = 87), and an external validation set ( n  = 109). Sixty patients from the external validation set were randomly selected and divided into two groups for an observer study, one with the assistance of algorithm results and the other without. We proposed a semi-supervised deep learning algorithm to diagnose and grade IM and atrophy, and we compared it with the assessments of 10 pathologists. The model’s performance was evaluated based on the area under the curve (AUC), sensitivity, specificity, and weighted kappa value. Results The algorithm, named GasMIL, was established and demonstrated encouraging performance in diagnosing IM (AUC 0.884, 95% CI 0.862–0.902) and atrophy (AUC 0.877, 95% CI 0.855–0.897) in the external test set. In the observer study, GasMIL achieved an 80% sensitivity, 85% specificity, a weighted kappa value of 0.61, and an AUC of 0.953, surpassing the performance of all ten pathologists in diagnosing atrophy. Among the 10 pathologists, GasMIL’s AUC ranked second in OLGA (0.729, 95% CI 0.625–0.833) and fifth in OLGIM (0.792, 95% CI 0.688–0.896). With the assistance of GasMIL, pathologists demonstrated improved AUC ( p  = 0.013), sensitivity ( p  = 0.014), and weighted kappa ( p  = 0.016) in diagnosing IM, and improved specificity ( p  = 0.007) in diagnosing atrophy compared to pathologists working alone. Conclusion GasMIL shows the best overall performance in diagnosing IM and atrophy when compared to pathologists, significantly enhancing their diagnostic capabilities.

Objective To clarify the effectiveness of second-look endoscopy (SLE) at preventing bleeding after gastric endoscopic submucosal dissection (ESD). Design A multicentre prospective randomised controlled non-inferiority trial was conducted at five referral institutions across Japan. Patients with a solitary gastric neoplasm were enrolled. Exclusion criteria were previous oesophagogastric surgery or radiation therapy; perforation and the administration of antithrombotics, steroids or non-steroidal anti-inflammatory drugs. Patients were assigned to the SLE group or the non-SLE group by a computer-generated random sequence after ESD and were treated perioperatively with a proton pump inhibitor. SLE was performed one day after ESD. The primary endpoint was post-ESD bleeding, defined as an endoscopically proven haemorrhage. The trial had the power to detect a non-inferiority criterion of 7% between the groups. Results From February 2012 to February 2013, 130 and 132 patients were assigned to the SLE and the non-SLE groups, respectively. All patients were included in the intention-to-treat analysis of the primary endpoint. Post-ESD bleeding occurred in seven patients with (5.4%) SLE and five patients with (3.8%) non-SLE (risk difference −1.6% (95% CI −6.7 to 3.5); pnon-inferiority<0.001), meeting the non-inferiority criterion. All 12 patients with post-ESD bleeding and one patient with a delayed perforation were successfully managed with conservative treatment. Conclusions SLE after gastric ESD is not routinely recommended because it does not contribute to the prevention of post-ESD bleeding for patients with an average bleeding risk. Trial registration number UMIN-CTR000007170.

BackgroundThe tumor location-modified Lauren classification (mLC) has been proposed recently, but its clinical significance remains under debate. This study aimed to elucidate the clinical relevance of mLC and evaluate its superiority to the Lauren classification (LC) for gastric cancer patients with gastrectomy.MethodsThis study retrospectively evaluated 2764 consecutive gastric cancer patients from three comprehensive medical institutions. The patients were categorized into training, inner-validation, and independent validation sets. The relationships between mLC and other clinicopathologic factors were analyzed, and independent prognostic factors were identified. Survival prognostic discriminatory ability and predictive accuracy were compared between mLC and LC using the concordance index (C-index) and Akaike’s information criterion (AIC), and a nomogram based on mLC was constructed to compare its prognostic improvement with the tumor-node metastasis (TNM) staging system.ResultsA significant association between mLC and gender, age, histologic type, T stage, N stage, and M stage was found. The findings showed that mLC, not LC, is an independent prognostic factor, with a smaller AIC and a higher C-index than LC. The nomogram based on mLC showed a better predictive ability than TNM alone.ConclusionsCompared with LC, mLC, which could be considered a more reliable prognostic factor, may improve the prognostic discriminatory ability and predictive accuracy for gastric cancer patients with gastrectomy.