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- Ahola, Reea P., et al.
(författare)
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Margin clearance greater than 1 mm in nodal-positive pancreatic adenocarcinoma patients : multicentre retrospective analysis
- 2024
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Ingår i: BJS Open. - : Oxford University Press. - 2474-9842. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: The introduction of the 1 mm cut-off for resection margin according to the Leeds Pathology Protocol has transformed the concept of surgical radicality. Its impact on nodal-positive resected pancreatic ductal adenocarcinoma patients is unclear. The aim of this study was to analyse the effect of margin clearance on survival among resected, nodal-positive pancreatic ductal adenocarcinoma patients whose specimens were analysed according to the Leeds Pathology Protocol.Methods: Data were collected retrospectively from multicentre clinical databases. Resected patients with nodal involvement were included. Overall survival and disease-free survival were analysed according to minimum reported margin clearances of 0, 0.5, 1, and 2 mm. The results are reported separately for patients who had not undergone venous resection and for patients for whom data were available regarding the superior mesenteric vein-facing margin or the vein specimen. The eighth edition of TNM classification by the AJCC was used.Results: The study comprised 290 stage IIB patients and 215 stage III patients without venous resection. The superior mesenteric vein margin analysis comprised 127 stage IIB patients and 198 stage III patients. The different resection margin distances were not associated with overall survival and disease-free survival among patients without venous resection (P > 0.050). Receiving adjuvant therapy was associated with longer overall survival among stage IIB patients (P = 0.034) and stage III patients (P = 0.003) and with longer disease-free survival among stage III patients (P < 0.001).Conclusions: In this study, a margin clearance greater than 1 mm showed no clear effect on overall survival in pancreatic ductal adenocarcinoma patients with nodal involvement, whereas adjuvant therapy was confirmed to be essential to ensure longer overall survival.
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| 2. |
- Ai, Jiaoyu, et al.
(författare)
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Bcl3 Couples Cancer Stem Cell Enrichment With Pancreatic Cancer Molecular Subtypes
- 2021
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 161:1, s. 318-332
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The existence of different subtypes of pancreatic ductal adenocarcinoma (PDAC) and their correlation with patient outcome have shifted the emphasis on patient classification for better decision-making algorithms and personalized therapy. The contribution of mechanisms regulating the cancer stem cell (CSC) population in different subtypes remains unknown.Methods: Using RNA-seq, we identified B-cell CLL/lymphoma 3 (BCL3), an atypical nf-κb signaling member, as differing in pancreatic CSCs. To determine the biological consequences of BCL3 silencing in vivo and in vitro, we generated bcl3-deficient preclinical mouse models as well as murine cell lines and correlated our findings with human cell lines, PDX models, and 2 independent patient cohorts. We assessed the correlation of bcl3 expression pattern with clinical parameters and subtypes.Results: Bcl3 was significantly down-regulated in human CSCs. Recapitulating this phenotype in preclinical mouse models of PDAC via BCL3 genetic knockout enhanced tumor burden, metastasis, epithelial to mesenchymal transition, and reduced overall survival. Fluorescence-activated cell sorting analyses, together with oxygen consumption, sphere formation, and tumorigenicity assays, all indicated that BCL3 loss resulted in CSC compartment expansion promoting cellular dedifferentiation. Overexpression of BCL3 in human PDXs diminished tumor growth by significantly reducing the CSC population and promoting differentiation. Human PDACs with low BCL3 expression correlated with increased metastasis, and BCL3-negative tumors correlated with lower survival and nonclassical subtypes.Conclusions: We demonstrate that bcl3 impacts pancreatic carcinogenesis by restraining CSC expansion and by curtailing an aggressive and metastatic tumor burden in PDAC across species. Levels of BCL3 expression are a useful stratification marker for predicting subtype characterization in PDAC, thereby allowing for personalized therapeutic approaches.
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