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Prognostic Implications of Portal Venous Circulating Tumor Cells in Resectable Pancreatic Cancer.

ABSTRACT: Circulating tumor cells (CTCs) are a promising prognostic biomarker for cancers. However, the paucity of CTCs in peripheral blood in early-stage cancer is a major challenge. Our study aimed to investigate whether portal venous CTCs can be a biomarker for early recurrence and poor prognosis in pancreatic cancer. Patients who underwent upfront curative surgery for resectable pancreatic cancer were consecutively enrolled in this prospective study. Intraoperatively, 7.5 mL of portal and peripheral blood was collected, and CTC detection and identification were performed using immunofluorescence staining. Peripheral blood CTC sampling was performed in 33 patients, of which portal vein CTC sampling was performed in 28. The median portal venous CTCs (2.5, interquartile ranges (IQR) 1-7.75) were significantly higher than the median peripheral venous CTCs (1, IQR 0-2, p < 0.001). Higher stage and regional lymph node metastasis were related with a larger number of CTCs (≥3) in portal venous blood. Patients with low portal venous CTCs (≤2) showed better overall (p = 0.002) and recurrence-free (p = 0.007) survival than those with high portal venous CTCs (≥3). If validated, portal CTCs can be used as a prognostic biomarker in patients with resectable pancreatic cancer.

SUBMITTER: Choi YH

PROVIDER: S-EPMC9219704 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Prognostic Implications of Portal Venous Circulating Tumor Cells in Resectable Pancreatic Cancer.

Choi Young Hoon YH Hong Tae Ho TH Yoon Seung Bae SB Lee In Seok IS Lee Myung Ah MA Choi Ho Joong HJ Choi Moon Hyung MH Jung Eun Sun ES

Biomedicines 20220531 6

Circulating tumor cells (CTCs) are a promising prognostic biomarker for cancers. However, the paucity of CTCs in peripheral blood in early-stage cancer is a major challenge. Our study aimed to investigate whether portal venous CTCs can be a biomarker for early recurrence and poor prognosis in pancreatic cancer. Patients who underwent upfront curative surgery for resectable pancreatic cancer were consecutively enrolled in this prospective study. Intraoperatively, 7.5 mL of portal and peripheral b ...[more]

PMID: 35740311

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Project description:Circulating tumor cells (CTCs) are useful biomarkers of many solid tumors, but are infrequently detected in early stage pancreatic ductal adenocarcinomas (PDACs). The first drainage of pancreatic venous blood flow come to portal vein and pass through the liver, and they finally go out for peripheral blood. We thought that comparing CTCs from portal vein and peripheral blood could enable us to understand the clinical meaning of CTCs from each different site in PDACs. Therefore, we aimed to determine 1) whether CTCs could be reliably identified in early stages (operable) of PDACs, 2) if there are any differences in the detected number of CTC in portal vein blood and peripheral blood, and 3) whether CTCs can be sensitive biomarkers for the prognosis of resectable PDAC patients. Newly diagnosed PDAC patients who underwent operation with curative intention between 2013 and 2015 were prospectively enrolled. Blood draws from portal and peripheral vein ran through the microfabricated porous filter, and anti-epithelial cell adhesion molecule (EpCAM) and anti-Plectin-1 antibodies were used for CTC identification. Baseline clinical characteristics, tumor characteristics, treatment, and clinical outcomes were assessed. The clinical stages of the 32 enrolled patients were as follows: IA/IB 1 (3.1%); IIA 9 (28.1%); IIB 17 (53.1%); III 5 (15.6%). Twenty-seven patients (84.4%) received R0 resection, while five patients (15.6%) received R1 resection. EpCAM+ CTCs were detected in 20 portal blood (62.5%) and 22 peripheral blood (68.8%). Plectin-1+ CTCs were identified in 14 portal blood (43.8%) and 16 peripheral blood (50%). Plectin-1-expressing CTCs were picked from CTC platform (microfabricated porous filter) and we could find out all KRAS mutation. Patients with detectable EpCAM+ CTC less than one in peripheral blood showed longer overall survival (OS) compared to patients with detectable CTCs more than one (35.5 months vs. 16.0 months). EpCAM and Plectin-1 successfully identified CTCs at the early stage of PDACs. Also, the number of CTCs could be a prognostic marker for survival in resectable PDACs.

Project description:Background & aimsTumor cells circulate in low numbers in peripheral blood; their detection is used predominantly in metastatic disease. We evaluated the feasibility and safety of sampling portal venous blood via endoscopic ultrasound (EUS) to count portal venous circulating tumor cells (CTCs), compared with paired peripheral CTCs, in patients with pancreaticobiliary cancers (PBCs).MethodsIn a single-center cohort study, we evaluated 18 patients with suspected PBCs. Under EUS guidance, a 19-gauge EUS fine needle was advanced transhepatically into the portal vein and as many as four 7.5-mL aliquots of blood were aspirated. Paired peripheral blood samples were obtained. Epithelial-derived CTCs were sorted magnetically based on expression of epithelial cell adhesion molecules; only those with a proper morphology and found to be CD45 negative and positive for cytokeratins 8, 18, and/or 19 and 4',6-diamidino-2-phenylindole were considered to be CTCs. For 5 samples, CTCs also were isolated by flow cytometry and based on CD45 depletion. ImageStream was used to determine the relative protein levels of P16, SMAD4, and P53. DNA was extracted from CTCs for sequencing of select KRAS codons.ResultsThere were no complications from portal vein blood acquisition. We detected CTCs in portal vein samples from all 18 patients (100%) vs peripheral blood samples from only 4 patients (22.2%). Patients with confirmed PBCs had a mean of 118.4 ± 36.8 CTCs/7.5 mL portal vein blood, compared with a mean of 0.8 ± 0.4 CTCs/7.5 mL peripheral blood (P < .01). The 9 patients with nonmetastatic, resectable, or borderline-resectable PBCs had a mean of 83.2 CTCs/7.5 mL portal vein blood (median, 62.0 CTCs/7.5 mL portal vein blood). In a selected patient, portal vein CTCs were found to carry the same mutations as those detected in a metastatic lymph node and expressed similar levels of P16, SMAD4, and P53 proteins.ConclusionsIt is feasible and safe to collect portal venous blood from patients undergoing EUS. We identified CTCs in all portal vein blood samples from patients with PBCs, but less than 25% of peripheral blood samples. Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue. This technique might be used to study the pathogenesis and progression of PBCs, as well as a diagnostic or prognostic tool to stratify risk of cancer recurrence or developing metastases.

Project description:BackgroundNeo-adjuvant chemotherapy (NAC) represents one of the current research hotspots in the field of pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to evaluate the prognostic value of NAC in patients with borderline resectable pancreatic cancer (BRPC) followed by pancreatectomy with portal vein (PV) resection and reconstruction with venous allograft (VAG).MethodsMedical records of patients with BPRC who underwent pancreatectomy with concomitant PV resection and reconstruction with VAG between April 2013 and March 2021 were analyzed retrospectively. Outcomes of patients with and without NAC (NAC, Group 1 vs. non-NAC, Group 2) were compared with focus on R0 resection rates, morbidity, and survival.ResultsOf the 77 patients with pancreatectomy, PV resection and reconstruction with VAG were identified. Overall survival (OS) rates of 0.5-, 1-, and 2-year were 80.5%, 59.7%, and 31.2%, respectively (median survival time, MST, 14 months). Of these, 24 patients (Group 1) underwent operation following received NAC, and the remaining 53 patients did not (Group 2). The R0 resection rate of vascular margin was 100% vs. 84.9% (p = 0.04), respectively. Morbidity of post-operative pancreatic fistula (POPF) was 0% vs. 17.8% (p = 0.07), respectively. The OS of 0.5-, 1- and 2-year and MST of 2 groups were 83.3%, 66.7%, 41.7%, 16 months, and 79.2%, 55.6%, 26.4%, 13 months, respectively. Multivariate analysis revealed that carbohydrate antigen 19-9 (CA19-9) serum level and postoperative chemotherapy were independent prognostic factors in patients with BRPC after surgery.ConclusionNAC might improve the R0 resection rate and POPF in patients with BRPC who underwent pancreatectomy with concomitant PV resection and reconstruction with VAG. Survival benefit exists in patients with BRPC who received NAC before pancreatectomy. Postoperative chemotherapy also had a favorable effect on OS of BRPC patients. Elevated CA 19-9 serum level is associated with poor prognosis, even after NAC-combining operation.

Dataset Information

Prognostic Implications of Portal Venous Circulating Tumor Cells in Resectable Pancreatic Cancer.

Publications

Prognostic Implications of Portal Venous Circulating Tumor Cells in Resectable Pancreatic Cancer.

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