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.
| Original language | English |
|---|---|
| Pages (from-to) | 767-774 |
| Number of pages | 8 |
| Journal | Surgery (United States) |
| Volume | 165 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2019 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Surgery
Cite this
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.
In: Surgery (United States), Vol. 165, No. 4, 01.04.2019, p. 767-774.Research output: Contribution to journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=85057136633&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057136633&partnerID=8YFLogxK
U2 - 10.1016/j.surg.2018.10.025
DO - 10.1016/j.surg.2018.10.025
M3 - Article
C2 - 30497813
AN - SCOPUS:85057136633
VL - 165
SP - 767
EP - 774
JO - Surgery
JF - Surgery
SN - 0039-6060
IS - 4
ER -