经结直肠内镜黏膜下剥离术后腔内灌洗脱落肿瘤细胞的体外分析。

In vitro analysis of exfoliated tumor cells in intraluminal lavage samples after colorectal endoscopic submucosal dissection.

机构信息

Department of Surgery, Nara Medical University, Nara, Japan.

Division of Endoscopy, Nara Medical University, Nara, Japan.

出版信息

Int J Colorectal Dis. 2022 Jan;37(1):161-170. doi: 10.1007/s00384-021-04037-y. Epub 2021 Oct 2.

DOI:10.1007/s00384-021-04037-y

PMID:34599685

Abstract

PURPOSE

Colorectal endoscopic submucosal dissection (ESD) produces exfoliated tumor cells that occasionally cause local recurrence. However, the biological characteristics of these tumor cells have not been clarified. The aim of this study was to clarify the genetic background and viability of exfoliated tumor cells in colorectal ESDs, as well as possible method for their elimination.

METHODS

Post-ESD intraluminal lavage samples from 19 patients who underwent colorectal ESDs were collected. In four patients with adenocarcinoma, gene mutations in the primary tumors and exfoliated cells in lavage samples were analyzed using a next-generation sequencer (NGS). In 15 patients with adenoma or adenocarcinoma, the viability of exfoliated cells and the cell-killing effect of povidone-iodine on exfoliated cells were evaluated.

RESULTS

The analysis using a NGS demonstrated that tumors targeted for ESD had already acquired mutations in many genes involved in cell proliferation, angiogenesis, and invasions. Furthermore, gene mutations between the exfoliated tumor cells and tumors resected by ESDs showed a 92 to 100% concordance. The median viable cell counts and the median viability of exfoliated cells in intraluminal lavage samples after ESDs were 4.9 × 10 cells/mL and 24%, respectively. The viability of the exfoliated cells did not decrease even 12 h after ESD. However, contact with 2.0% povidone-iodine solution reduced both viable cell counts and viability, significantly.

CONCLUSION

A large number of tumor cells exfoliated during colorectal ESDs had acquired survival-favorable gene mutations and could survive for some time. Therefore, a lavage using a solution of 2.0% povidone-iodine may be effective against such cells.

TRIAL REGISTRATION

The prospective study registered 1317, and the retrospective study registered 2729. The prospective study approved on June 20, 2016, and the retrospective study approved on October 6, 2020.

摘要

目的

结直肠内镜黏膜下剥离术（ESD）产生的脱落肿瘤细胞偶尔会导致局部复发。然而，这些肿瘤细胞的生物学特性尚未阐明。本研究旨在阐明结直肠 ESD 中脱落肿瘤细胞的遗传背景和活力，以及消除这些细胞的可能方法。

方法

收集了 19 例接受结直肠 ESD 的患者术后腔内冲洗样本。在 4 例腺癌患者中，使用下一代测序仪（NGS）分析原发肿瘤和冲洗样本中脱落细胞的基因突变。在 15 例腺瘤或腺癌患者中，评估了脱落细胞的活力和聚维酮碘对脱落细胞的杀伤作用。

结果

NGS 分析表明，接受 ESD 治疗的肿瘤已经获得了许多参与细胞增殖、血管生成和侵袭的基因的突变。此外，ESD 切除的肿瘤与脱落肿瘤细胞之间的基因突变具有 92%至 100%的一致性。ESD 后腔内冲洗样本中脱落肿瘤细胞的中位活细胞数和中位活力分别为 4.9×10个细胞/ml 和 24%。即使在 ESD 后 12 小时，脱落细胞的活力也没有下降。然而，接触 2.0%的聚维酮碘溶液可显著降低活细胞计数和活力。