Background: Gastric gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms with heterogeneous malignant behaviour. Adjuvant therapy and routine surveillance are guided by the risk of ...recurrence, which is largely determined by tumour location, mitotic rate, size and intraoperative tumour rupture. Recurrence after surgical resection of very-low-risk and low-risk gastric GISTs is exceedingly rare. Despite this, the National Comprehensive Cancer Network suggest abdominopelvic crosssectional imaging every 3-6 months for 3-5 years then annually, while the European Society for Medical Oncology states that routine follow-up may not be warranted in very-low-risk GIST and the benefit of routine follow-up is not known. Consequently, the aim of this study was to characterize the patterns of recurrence among the low-risk and very-low-risk gastric GISTs and determine the value of surveillance at our centre. Methods: Adult patients with gastric GIST who underwent surgical resection at a single tertiary care centre between 2010 and 2020 were evaluated. Demographics, clinical presentation, radiologic and endoscopic findings, pathological results and surveillance data were collected and analyzed. Results: In total, 139 patients underwent resection of a gastric GIST and were eligible for inclusion. According to the National Institute of Health modified classification system, 8.6% (n = 12) were considered very low risk, 37.4% (n = 52) low risk, 36% (n = 50) intermediate risk and 18% (n = 25) high risk. We observed 1 recurrence in the intermediate-risk group at 4 years (2%) and 2 within the high-risk group at 2 and 3 years (8%), all of which were nonperforated, asymptomatic and detected on routine surveillance imaging. Among the very-low-risk group, 3 were discharged to their family physician for surveillance, and the remaining 77.8% (n = 7) underwent surveillance with cross-sectional abdominal imaging and 33.3% (n = 3) with additional chest imaging, respectively. Among the low-risk group, 10 patients were discharged to their family physician for surveillance, and the remainder 57.1% (n = 24) underwent surveillance with crosssectional abdominal imaging and 30.9% (n = 13) with additional chest imaging, respectively. Nine patients of the low-risk group underwent endoscopic surveillance. Conclusion: After a median of 37.1 and 34.3 months of surveillance within the very-low-risk and low-risk groups, we observed no recurrences and detected no additional malignancies. There were no recurrences of very-lowrisk and low-risk gastric GISTs after surgical resection in this single-site population. While considering cost-effectiveness and in the absence of randomized controlled trials, this evidence may support that routine radiologic and endoscopic surveillance may not be warranted among these subgroups.
Neuroendocrine tumors are derived from neuroendocrine cells which are commonly found in gastrointestinal system. Neuroendocrine cells take the electrical signals from the nervous system, convert them ...into hormonal signals with production of hormones, peptides and amines. As neuroendocrine cells are ubiquitous in our body, but NETs usually locates in the gastrointestinal (55%) or in the bronchopulmonary system (25%). The incidence and prevalence of NETs have been increasing over the years possibly due to increased awareness, and widespread use of endoscopy and imaging studies for various gastrointestinal diseases.
Curcumin (Diferuloylmethane), a polyphenolic compound with antioxidant, anti-inflammatory and anticancer properties, has been found to increase chemotherapeutic agents-induced cytotoxicity in some ...resistant cancer cell lines. This investigation aimed to study the effects of curcumin on efficacy of some common anticancer agents in gastric cancer cells. AGS cells were cultured in RPMI-1640 medium under standard culture conditions (5% CO2 and 95% humidified air at 37°C). Curcumin was used at concentrations of 5, 15, 30 and 50 µM. Cells were treated with a combination of curcumin and paclitaxel (300 nm) or methotrexate (100 µm) or vincristine (5 nm). Cell viability, the percentage of live cells in the whole population, was evaluated by MTT assay after 48 hours. The results showed that cell viability was significantly decreased after incubation of AGS cells with curcumin. Combination with curcumin (15-50 µm) significantly increased cytotoxicity of all three agents (P<0.001). Regarding high anticancer potential and enhancement of chemotherapeutic agent-induced cytotoxicity, the combined use of curcumin with standard chemotherapy of gastric cancer is suggested as a strategy for better management of this fatal cancer.
The variant curation guidelines published in 2015 by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) provided the genetics community with ...a framework to assess variant pathogenicity; however, these rules are not gene specific. Germline pathogenic variants in the CDH1 gene cause hereditary diffuse gastric cancer and lobular breast cancer, a clinically challenging cancer predisposition syndrome that often requires a multidisciplinary team of experts to be properly managed. Given this challenge, the Clinical Genome Resource (ClinGen) Hereditary Cancer Domain prioritized the development of the CDH1 variant curation expert panel (VCEP) to develop and implement rules for CDH1 variant classifications. Here, we describe the CDH1 specifications of the ACMG/AMP guidelines, which were developed and validated after a systematic evaluation of variants obtained from a cohort of clinical laboratory data encompassing ∼827,000 CDH1 sequenced alleles. Comparing previously reported germline variants that were classified using the 2015 ACMG/AMP guidelines to the CDH1 VCEP recommendations resulted in reduced variants of uncertain significance and facilitated resolution of variants with conflicted assertions in ClinVar. The ClinGen CDH1 VCEP recommends the use of these CDH1‐specific guidelines for the assessment and classification of variants identified in this clinically actionable gene.
Germline pathogenic variants in the CDH1 gene cause hereditary diffuse gastric cancer and lobular breast cancer. The ClinGen CDH1 Expert Panel developed and implemented rules for CDH1 variant curation, providing the genetic community with a gene‐specific framework for the classification of variants identified in this clinically actionable gene. Overall, the Expert Panel specifications resulted in reduced variants of uncertain significance and facilitated resolution of variants with conflicted assertions in ClinVar.
This study explored the prognostic impact of tumor-infiltrating lymphocytes (TILs) and investigated whether three histologic subtypes (lymphoepithelioma-like carcinoma, carcinoma with Crohn's ...disease-like lymphoid reaction, and conventional-type adenocarcinoma) could stratify a prognostic subset for patients with Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC).
After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. The evaluation of the percentage of intratumoral (iTu-) and stromal (str-) TILs was carried out, and the cases were also subclassified into three histologic subtypes as noted above.
Among the 120 patients, 73 patients (60.8%) and 60 patients (50.0%) were determined as str-TIL-positive and iTu-TIL-positive, respectively. In a univariate analysis, str-TIL-positivity was significantly associated with longer recurrence-free survival (RFS; P = 0.002) and disease-free survival (DFS; P = 0.008), yet not overall survival (OS; P = 0.145). While iTu-TIL-positivity has a tendency of favorable outcome indicator for DFS and OS, but statistically significant differences were not shown, respectively (RFS, P = 0.058; DFS, P = 0.151; OS, P = 0.191). In a multivariate analysis using a Cox proportional hazard model adjusted for age, pTNM stage, lymphatic invasion, perineural invasion, and venous invasion; histologic subtype, WHO classification, and str-TIL-positivity were independently or tentatively associated with favorable RFS (hazard ratio HR = 12.193, 95% confidence interval 95% CI 1.039–143.055, P = 0.047) or DFS (HR = 4.836, 95% CI 0.917–25.525, P = 0.063).
The histologic subclassification and TILs can be used to predict RFS and DFS for patients with EBVaGC.
N-Nitroso compounds (NOCs) are recognized as important factors that promote gastric cancer development, but the specific effects and potential mechanisms by which NOC exposure promotes gastric cancer ...are still poorly understood. In this study, we explored the effects and potential molecular mechanisms of NOCs on the promotion of gastric cancer using methylnitronitrosoguanidine (MNNG), a classical direct carcinogen of NOC. The results of in vivo and in vitro experiments showed that chronic and low-concentration MNNG exposure significantly promoted the malignant progression of tumors, including cell migration, cell invasion, vasculogenic mimicry (VM) formation, cell spheroid formation, stem cell-like marker expression, and gastric cancer growth and metastasis. Mechanistically, we revealed that demethylase ALKBH5 regulated the level of the N6‑methyladenosine (m6A) modification in the 3′UTR and CDS region of the ZKSCAN3 mRNA to promote ZKSCAN3 expression, mediated the binding of ZKSCAN3 to the VEGFA promoter region to regulate VEGFA transcription, and participated in MNNG-induced gastric cancer cell migration, invasion, VM formation, cell spheroid formation, stem cell-like marker expression and ultimately gastric cancer progression. In addition, our study revealed that ALKBH5-ZKSCAN3-VEGFA signaling was significantly activated during MNNG-induced gastric carcinogenesis, and further studies in gastric cancer patients showed that ALKBH5, ZKSCAN3, and VEGFA expression were upregulated in cancers compared with paired gastric mucosal tissues, that ALKBH5, ZKSCAN3, and VEGFA could serve as important biomarkers for determining patient prognosis, and that the molecular combination showed greater prognostic value. These findings provide a theoretical basis for developing gastric cancer interventions for NOCs and for determining gastric cancer progression.
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•Chronic MNNG exposure promoted the malignant progression of gastric cancer.•MNNG exposure significantly increased ZKSCAN3 mRNA expression.•ZKSCAN3 bound to the promoter regions of VEGFA and activated its transcription.•ALKBH5-m6A-YTHDF2 mechanism regulated ZKSCAN3 expression.•ALKBH5, ZKSCAN3, and VEGFA served as biomarkers for patient’s prognosis.
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