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Peritoneal Lavage Tumor DNA as a Novel Biomarker for Predicting Peritoneal Recurrence in Pancreatic Ductal Adenocarcinoma

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The clinical role of peritoneal lavage cytology (CY) in pancreatic ductal adenocarcinoma (PDAC) remains controversial, partly due to its low sensitivity. This study aimed to develop a new biomarker, defined as peritoneal lavage tumor DNA (ptDNA), using DNAs extracted from peritoneal lavage samples from patients with PDAC.

Methods

Samples were collected intraoperatively from 89 PDAC patients who underwent pancreatectomy between 2012 and 2017. Droplet digital polymerase chain reaction (PCR) was used to measure ptDNA for detection of KRAS mutations. The ptDNA status and clinical characteristics were retrospectively evaluated.

Results

Positive ptDNA was found in 41 patients, including all 9 patients positive for CY (CY+) and 32 patients negative for CY (CY−). The mutant allele frequency was significantly higher in the CY+ patients than in the CY− patients. The disease-free survival (DFS) and overall survival (OS) were significantly poorer in the high-ptDNA group than in the low-ptDNA group (median DFS, 11.0 vs. 18.8 months; p = 0.007; median OS, 28.7 vs not reached; p = 0.001). The survival curves of DFS and OS in the CY+ group were almost equal to those in the CY− and high-ptDNA group. In a multivariable analysis, ptDNA was an independent predictive factor for DFS (p = 0.025) and OS (p = 0.047). The estimated cumulative incidence of peritoneal recurrence was 45.5% in the high-ptDNA group. The ptDNA biomarker had a much higher sensitivity for peritoneal recurrence than CY, whereas CY had higher specificity.

Conclusions

As a promising biomarker, ptDNA may predict poor prognosis and peritoneal recurrence in PDAC, resolving the controversy surrounding CY.

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Acknowledgments

This work was supported by the Aichi Cancer Research Foundation. The authors thank Dr. Akiko Kada, a biostatistician at Nagoya Medical Center, Nagoya, Japan, for her kind advice. They also thank Yoko Nishikawa and Hisae Mizuno for their excellent assistance in this study.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

    Masaya Suenaga MD, PhD, Tsutomu Fujii MD, PhD, FACS, Suguru Yamada MD, PhD, Masamichi Hayashi MD, PhD, Hideki Takami MD, PhD, Yukiko Niwa MD, PhD, Fuminori Sonohara MD, PhD, Dai Shimizu MD, PhD, Mitsuro Kanda MD, PhD, Daisuke Kobayashi MD, PhD, Chie Tanaka MD, PhD, Goro Nakayama MD, PhD, Masahiko Koike MD, PhD, Michitaka Fujiwara MD, PhD & Yasuhiro Kodera MD, PhD

  2. Department of Surgery, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Masaya Suenaga MD, PhD

  3. Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Tsutomu Fujii MD, PhD, FACS

  4. Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Keiko Shinjo MD, PhD & Yutaka Kondo MD, PhD

Authors
  1. Masaya Suenaga MD, PhD
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  2. Tsutomu Fujii MD, PhD, FACS
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  3. Suguru Yamada MD, PhD
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  17. Yasuhiro Kodera MD, PhD
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Corresponding author

Correspondence to Tsutomu Fujii MD, PhD, FACS.

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Suenaga, M., Fujii, T., Yamada, S. et al. Peritoneal Lavage Tumor DNA as a Novel Biomarker for Predicting Peritoneal Recurrence in Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 28, 2277–2286 (2021). https://doi.org/10.1245/s10434-020-08990-w

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  • DOI: https://doi.org/10.1245/s10434-020-08990-w

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