Sentinel node mapping for post-endoscopic resection gastric cancer: multicenter retrospective cohort study in Japan
- 作者列表："Mayanagi, Shuhei","Takahashi, Naoto","Mitsumori, Norio","Arigami, Takaaki","Natsugoe, Shoji","Yaguchi, Yoshihisa","Suda, Takeshi","Kinami, Shinichi","Ohi, Masaki","Kawakubo, Hirofumi","Sato, Yasunori","Takeuchi, Hiroya","Aikou, Takashi","Kitagawa, Yuko","Japanese Society for Sentinel Node Navigation Surgery
Background Standard gastrectomy with systematic lymphadenectomy as an additional surgery after endoscopic resection (ER) causes a deterioration in long-term quality of life. If the sentinel lymph node (SN) basin concept can be applied in post-ER gastric cancer, minimal surgery can be applied without reducing the curability. This retrospective multicenter cohort study aimed to verify the validity of the SN basin concept in post-ER gastric cancer. Patients and methods Individual data of 132 patients who underwent SN mapping after ER were collected from 8 university hospitals in Japan from 2001 to 2016. Tracers were injected endoscopically in the submucosal layer at four sites around the post-ER scar. We compared the SN basin distribution of post-ER gastric cancer with that of 275 patients with non-ER gastric cancer. Results Two cases of SN were unidentified, both involving a single tracer (SN detection rate: 98.5%). Nine cases (6.8%) of lymph node metastasis were found, of which eight had a metastatic lymph node within the SNs and one had a non-SN metastasis within the SN basin. The diagnostic sensitivity of SN mapping for lymph node metastasis was 88.9% in post-ER group and 95.7% in non-ER group ( P = 0.490); the accuracy was 99.2% and 99.6% ( P = 0.539), respectively. Regarding the SN basin, no significant intergroup differences were found regardless of the primary tumor location. Conclusions Our findings clarified the feasibility of SN mapping based on the SN basin concept in patients with gastric cancer who previously underwent ER.
背景标准胃切除术联合系统性淋巴结切除术作为内镜切除术 (ER) 后的一项额外手术，会导致长期生活质量的恶化。如果前哨淋巴结 (SN) 盆地概念可以应用于 ER 术后胃癌，则可以在不降低可治愈性的情况下应用微创手术。这项回顾性多中心队列研究旨在验证 SN 盆地概念在 ER 后胃癌中的有效性。患者和方法收集了 2001年至 2016年日本 8 所大学医院 132 例接受 ER 后 SN 映射的患者的个体资料。在 ER 后瘢痕周围四个部位的粘膜下层内镜下注射示踪剂。我们比较了 ER 后胃癌与 275 例非 ER 胃癌患者的 SN 盆地分布。结果 2 例 SN 不明，均累及单一示踪剂 (SN 检出率: 98.5%)。发现淋巴结转移 9 例 (6.8%)，其中 8 例 SNs 内淋巴结转移，1 例 SN 盆地内无 SN 转移。SN mapping 对淋巴结转移的诊断敏感性在 ER 后组为 88.9%，在非 ER 组为 95.7% (P = 0.490); 准确率分别为 99.2% 和 99.6% (P = 0.539)。关于 SN 盆地，无论原发肿瘤位置如何，均未发现显著的组间差异。结论我们的研究结果阐明了在既往接受过 ER 的胃癌患者中基于 SN 盆地概念进行 SN 映射的可行性。
METHODS::Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.
METHODS::Aim: To identify the methylated-differentially expressed genes (MDEGs) that may serve as diagnostic markers and therapeutic targets in Epstein-Barr virus-associated gastric cancer (EBVaGC) and to explore the methylation-based pathways for elucidating biological mechanisms of EBVaGC. Materials & methods: Gene expression and methylation profiles were downloaded from GEO database. MDEGs were identified by GEO2R. Pathway enrichment analyses were conducted based on DAVID database. Hub genes were identified by Cytoscape, which were further verified by The Cancer Genome Atlas database. Results: A total of 367 hypermethylated, lowly expressed genes were enriched in specific patterns of cell differentiation. 31 hypomethylated, highly expressed genes demonstrated enrichment in regulation of immune system process. After validation using The Cancer Genome Atlas database, seven genes were confirmed to be significantly different hub genes in EBVaGC. Conclusion: EBVaGC-specific MDEGs and pathways can be served as potential biomarkers for precise diagnosis and treatment of EBVaGC and provide novel insights into the mechanisms involved.
METHODS:Gastric adenocarcinoma, like other cancers, is a multifactorial genetic disease, andmetastasis of cancer cells is one of the main features of this illness. The expressionlevels of the CFL1 gene have been modulated in this pathway. Using small interferingRNA (siRNA) in the treatment of gastric cancer is considered a hopeful genetherapeutic approach. The present study reported the level of CFL1 genes betweentumor and margin and healthy tissue of gastric cancer. Also, the features of a cationicnanoparticle with a polymer coating containing polyacrylic acid and polyethylenei-mine that were used in the delivery of CFL1 siRNA, were shown. Then thecytotoxicity, cellular uptake, and gene silencing efficiency of this nanoparticle wereevaluated with CFL1siRNA. Method:In this study, the CFL1 gene expression was measured in 40 gastricadenocarcinoma, marginal and 15 healthy biopsy samples by a real‐time polymerasechain reaction. Physicochemical characteristics, apoptosis, and inhibition of migrationof the delivery of CFL1 siRNA by nanoparticle and lipofectamine were investigated ingastric cancer cells. Result:The CFL1 expression was remarkably increased in gastric cancer tissues incomparison with the marginal samples and normal tissues (p< .05) and the biomarkerindex for CFL1 was obtained as 0.94, then this gene can be probably used as abiomarker for gastric cancer. After treatment of the AGS cell line by CFL1 siRNA, theCFL1 expression level of mRNA and migration in AGS cells were remarkablysuppressed after transfection. Furthermore, the amount of apoptosis increased(p< .05). Conclusion:Our results demonstrated that CFL1 downregulation in AGS cells caninterdict cell migration. Finally, our outcomes propose that CFL1 can function as anoncogenic gene in gastric cancer and would be considered as a potential purpose ofgene therapy for gastric cancer treatment