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.

Is remnant pancreatic cancer after pancreatic resection more frequent in early‐stage pancreatic cancer than in advanced‐stage cancer?

“…One possible explanation may be that the remnant pancreatic lesions in the advanced‐stage group included more recurrent lesions than those in the early‐stage group. If a remnant pancreatic lesion is due to recurrence, then the prognosis might be poorer than in the case of multifocal lesions 10 . In contrast, a pooled analysis by Zhou et al in patients who underwent a second pancreatectomy for remnant pancreatic cancer showed the opposite result 18 .…”

“…One is the recurrence of the initial pancreatic cancer, and the other is the metachronous development of a new primary cancer 4 . Several studies that compared genetic mutations between the initial and remnant pancreatic lesions supported the presence of both patterns 8,10,11 . Because of the aggressive nature of pancreatic cancer, approximately 80% of patients who undergo surgery for pancreatic cancer develop recurrence 12,13 .…”

“…Multifocal lesions may develop metachronously after partial pancreatic resection for pancreatic cancer. Gotoh et al divided remnant pancreatic cancer cases into cases with recurrence or multifocal lesions according to mutational and immunohistochemical assessment, and the authors found that the cases with multifocal lesions showed a longer interval between the initial and secondary lesions and a lower cumulative recurrence rate after resection of remnant pancreatic lesions compared with the cases with recurrence 10 …”

Focal Parenchymal Atrophy and Fat Replacement Are Clues for Early Diagnosis of Pancreatic Cancer with Abnormalities of the Main Pancreatic Duct

“…In a prospective study of 30 patients with Stage 0 or IA, 9 patients developed recurrence (8 in the remnant pancreas and 1 in the liver) during the median follow-up period of 54 months. Discrimination of local recurrence from multicentric cancer is difficult in the absence of genetic analysis (Gotoh et al 2019). Mikata et al (2013) reported that SPACE was a feasible method in the diagnosis of pancreatic high-grade PanIN/ CIS.…”

Multifocal lesions in intraductal papillary mucinous neoplasms: Intraoperative pancreatic juice cytology

“…On the other hand, in pathological assessment, most of these patients had lots of micro premalignant lesions such as small IPMNs and pancreatic intraepitehrial neoplasms (PanINs) in the background pancreas, indicating that all the pancreas having IPMNs have a potential to develop multifocal lesions. There are 3 possible types of multifocal lesions in patients with IPMNs, namely multiple branch duct IPMNs (BD-IPMNs) by multicentric development, multiple main duct or mixed type IPMNs (MD-or Mix-IPMNs) by the mechanism of intraductal dissemination of the neoplastic cells [1,2], and the development of pancreatic ductal adenocarcinoma (PDAC) concomitant with IPMNs [3,4]. Pancreatic juice cytology under endoscopic retrograde pancreatography is reported to leads early detection of concomitant PDAC during assessment of IPMNs [5], while it is often difficult to determine the location of malignant lesions when pancreatography and other imaging modalities cannot provide any significant abnormalities.…”