Genetic assessment of recurrent pancreatic high-risk lesions in the remnant pancreas

Metachronous multifocal lesion or local recurrence?

Yoshitaka Gotoh, Ohtsuka Takao, So Nakamura, Koji Shindo, Kenoki Ouchida, Yoshihiro Miyasaka, Yasuhisa Mori, Naoki Mochidome, Yoshinao Oda, Masafumi Nakamura

研究成果: ジャーナルへの寄稿記事

抄録

Background: It is difficult to determine whether a second high-risk lesion, including pancreatic ductal adenocarcinoma or high-grade pancreatic intraepithelial neoplasm, is a metachronous multifocal lesion or represents local recurrence after resection of the first high-risk lesion. This study attempts to clarify the characteristics of second high-risk lesions in the remnant pancreas using genetic analyses. Methods: Clinicopathologic data were collected from 12 patients who underwent pancreatectomy for a second high-risk lesion in the remnant pancreas. We performed mutational and immunohistochemical analyses of 4 major genes—KRAS, TP53, CDKN2A, and SMAD4—associated with pancreatic ductal adenocarcinoma progression, as well as targeted next-generation sequencing. Results: Mutations in the four genes in the second high-risk lesion were consistent with the first lesion in four patients but were inconsistent in the remaining eight patients, and thus we considered that the latter eight patients likely had metachronous multifocal high-risk lesions and the other four patients had local recurrence. The estimated cumulative recurrence rate after resection of the second high-risk lesion was greater in the local recurrence group compared with the metachronous multifocal group, and the estimated cumulative disease-specific survival rate was greater in the metachronous multifocal group. Targeted next-generation sequencing demonstrated that the second lesions in the metachronous multifocal high-risk lesion group showed differences in founder mutations compared with the first lesion. In the local recurrence group, the founder mutations in the second lesion were common with those in the first lesion. Conclusion: Genetic assessment might help discriminate metachronous multifocal high-risk lesions from local recurrence.

元の言語英語
ページ(範囲)767-774
ページ数8
ジャーナルSurgery (United States)
165
発行部数4
DOI
出版物ステータス出版済み - 4 1 2019

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Pancreas
Recurrence
Mutation
Adenocarcinoma
Pancreatectomy
Carcinoma in Situ
Pancreatic Neoplasms
Survival Rate
Genes

All Science Journal Classification (ASJC) codes

  • Surgery

これを引用

Genetic assessment of recurrent pancreatic high-risk lesions in the remnant pancreas : Metachronous multifocal lesion or local recurrence? / Gotoh, Yoshitaka; Takao, Ohtsuka; Nakamura, So; Shindo, Koji; Ouchida, Kenoki; Miyasaka, Yoshihiro; Mori, Yasuhisa; Mochidome, Naoki; Oda, Yoshinao; Nakamura, Masafumi.

:: Surgery (United States), 巻 165, 番号 4, 01.04.2019, p. 767-774.

研究成果: ジャーナルへの寄稿記事

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title = "Genetic assessment of recurrent pancreatic high-risk lesions in the remnant pancreas: Metachronous multifocal lesion or local recurrence?",
abstract = "Background: It is difficult to determine whether a second high-risk lesion, including pancreatic ductal adenocarcinoma or high-grade pancreatic intraepithelial neoplasm, is a metachronous multifocal lesion or represents local recurrence after resection of the first high-risk lesion. This study attempts to clarify the characteristics of second high-risk lesions in the remnant pancreas using genetic analyses. Methods: Clinicopathologic data were collected from 12 patients who underwent pancreatectomy for a second high-risk lesion in the remnant pancreas. We performed mutational and immunohistochemical analyses of 4 major genes—KRAS, TP53, CDKN2A, and SMAD4—associated with pancreatic ductal adenocarcinoma progression, as well as targeted next-generation sequencing. Results: Mutations in the four genes in the second high-risk lesion were consistent with the first lesion in four patients but were inconsistent in the remaining eight patients, and thus we considered that the latter eight patients likely had metachronous multifocal high-risk lesions and the other four patients had local recurrence. The estimated cumulative recurrence rate after resection of the second high-risk lesion was greater in the local recurrence group compared with the metachronous multifocal group, and the estimated cumulative disease-specific survival rate was greater in the metachronous multifocal group. Targeted next-generation sequencing demonstrated that the second lesions in the metachronous multifocal high-risk lesion group showed differences in founder mutations compared with the first lesion. In the local recurrence group, the founder mutations in the second lesion were common with those in the first lesion. Conclusion: Genetic assessment might help discriminate metachronous multifocal high-risk lesions from local recurrence.",
author = "Yoshitaka Gotoh and Ohtsuka Takao and So Nakamura and Koji Shindo and Kenoki Ouchida and Yoshihiro Miyasaka and Yasuhisa Mori and Naoki Mochidome and Yoshinao Oda and Masafumi Nakamura",
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T1 - Genetic assessment of recurrent pancreatic high-risk lesions in the remnant pancreas

T2 - Metachronous multifocal lesion or local recurrence?

AU - Gotoh, Yoshitaka

AU - Takao, Ohtsuka

AU - Nakamura, So

AU - Shindo, Koji

AU - Ouchida, Kenoki

AU - Miyasaka, Yoshihiro

AU - Mori, Yasuhisa

AU - Mochidome, Naoki

AU - Oda, Yoshinao

AU - Nakamura, Masafumi

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Background: It is difficult to determine whether a second high-risk lesion, including pancreatic ductal adenocarcinoma or high-grade pancreatic intraepithelial neoplasm, is a metachronous multifocal lesion or represents local recurrence after resection of the first high-risk lesion. This study attempts to clarify the characteristics of second high-risk lesions in the remnant pancreas using genetic analyses. Methods: Clinicopathologic data were collected from 12 patients who underwent pancreatectomy for a second high-risk lesion in the remnant pancreas. We performed mutational and immunohistochemical analyses of 4 major genes—KRAS, TP53, CDKN2A, and SMAD4—associated with pancreatic ductal adenocarcinoma progression, as well as targeted next-generation sequencing. Results: Mutations in the four genes in the second high-risk lesion were consistent with the first lesion in four patients but were inconsistent in the remaining eight patients, and thus we considered that the latter eight patients likely had metachronous multifocal high-risk lesions and the other four patients had local recurrence. The estimated cumulative recurrence rate after resection of the second high-risk lesion was greater in the local recurrence group compared with the metachronous multifocal group, and the estimated cumulative disease-specific survival rate was greater in the metachronous multifocal group. Targeted next-generation sequencing demonstrated that the second lesions in the metachronous multifocal high-risk lesion group showed differences in founder mutations compared with the first lesion. In the local recurrence group, the founder mutations in the second lesion were common with those in the first lesion. Conclusion: Genetic assessment might help discriminate metachronous multifocal high-risk lesions from local recurrence.

AB - Background: It is difficult to determine whether a second high-risk lesion, including pancreatic ductal adenocarcinoma or high-grade pancreatic intraepithelial neoplasm, is a metachronous multifocal lesion or represents local recurrence after resection of the first high-risk lesion. This study attempts to clarify the characteristics of second high-risk lesions in the remnant pancreas using genetic analyses. Methods: Clinicopathologic data were collected from 12 patients who underwent pancreatectomy for a second high-risk lesion in the remnant pancreas. We performed mutational and immunohistochemical analyses of 4 major genes—KRAS, TP53, CDKN2A, and SMAD4—associated with pancreatic ductal adenocarcinoma progression, as well as targeted next-generation sequencing. Results: Mutations in the four genes in the second high-risk lesion were consistent with the first lesion in four patients but were inconsistent in the remaining eight patients, and thus we considered that the latter eight patients likely had metachronous multifocal high-risk lesions and the other four patients had local recurrence. The estimated cumulative recurrence rate after resection of the second high-risk lesion was greater in the local recurrence group compared with the metachronous multifocal group, and the estimated cumulative disease-specific survival rate was greater in the metachronous multifocal group. Targeted next-generation sequencing demonstrated that the second lesions in the metachronous multifocal high-risk lesion group showed differences in founder mutations compared with the first lesion. In the local recurrence group, the founder mutations in the second lesion were common with those in the first lesion. Conclusion: Genetic assessment might help discriminate metachronous multifocal high-risk lesions from local recurrence.

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DO - 10.1016/j.surg.2018.10.025

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SP - 767

EP - 774

JO - Surgery

JF - Surgery

SN - 0039-6060

IS - 4

ER -