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

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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 × 105 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.

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Acknowledgements

We thank Mr. Naoto Kondo, Mr. Takanori Washio, and Ms. Emi Kanno (Riken Genesis Co., Ltd., Kawasaki, Japan) for their technical assistance in gene mutation sequencing using next-generation sequencing.

Funding

This study was supported in part by the Japan Society for the Promotion of Science KAKENHI Grant (No. 18K16326 to T. Inoue).

Author information

Authors and Affiliations

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

    Takayuki Nakamoto, Fumikazu Koyama, Hiroyuki Kuge, Shinsaku Obara, Naoya Ikeda, Yosuke Iwasa, Takeshi Takei, Tomomi Sadamitsu, Suzuka Harada, Kosuke Fujimoto, Takashi Inoue & Masayuki Sho

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

    Takayuki Nakamoto & Fumikazu Koyama

  3. Department of Diagnostic Pathology, Nara Medical University, Nara, Japan

    Kinta Hatakeyama & Chiho Ohbayashi

Authors
  1. Takayuki Nakamoto
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  2. Fumikazu Koyama
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  3. Hiroyuki Kuge
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  4. Shinsaku Obara
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  5. Naoya Ikeda
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  6. Yosuke Iwasa
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  7. Takeshi Takei
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  8. Tomomi Sadamitsu
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  9. Suzuka Harada
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  10. Kosuke Fujimoto
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  11. Takashi Inoue
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  12. Kinta Hatakeyama
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  13. Chiho Ohbayashi
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  14. Masayuki Sho
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by Takayuki Nakamoto, Fumikazu Koyama, Hiroyuki Kuge, Shinsaku Obara, Yosuke Iwasa, Takeshi Takei, Tomomi Sadamitsu, Suzuka Harada, Kosuke Fujimoto, Takashi Inoue. Histological examinations were performed by Kinta Hatakeyama and Chiho Ohbayashi. Data analysis and interpretation were performed by Takayuki Nakamoto, Fumikazu Koyama, Hiroyuki Kuge, Shinsaku Obara, Naoya Ikeda, Kinta Hatakeyama, Chiho Ohbayashi, and Masayuki Sho. The first draft of the manuscript was written by Takayuki Nakamoto, Fumikazu Koyama, and Naoya Ikeda, and critical revision of the manuscript was performed by Fumikazu Koyama, Takayuki Nakamoto and Masayuki Sho. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Fumikazu Koyama.

Ethics declarations

Ethics approval

This study was approved by our institutional ethics committee (No. 1317 and 2729). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

Consent to participate

Written informed consent was obtained from all the patients.

Consent for publication

Written informed consent was obtained from all the patients.

Conflict of interest

The authors declare no competing interests.

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Nakamoto, T., Koyama, F., Kuge, H. et al. In vitro analysis of exfoliated tumor cells in intraluminal lavage samples after colorectal endoscopic submucosal dissection. Int J Colorectal Dis 37, 161–170 (2022). https://doi.org/10.1007/s00384-021-04037-y

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  • DOI: https://doi.org/10.1007/s00384-021-04037-y

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