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Arterial resection during pancreatectomy for pancreatic ductal adenocarcinoma with arterial invasion: A single-center experience with 109 patients.

ABSTRACT: Pancreatectomy for pancreatic cancer with arterial invasion is controversial and performed infrequently. As its indication evolves and neoadjuvant chemotherapy also evolves, it is meaningful to identify short- and long-term outcomes of pancreatectomy with arterial resection (AR). This study aimed to retrospectively analyze the clinical outcomes of pancreatectomy with AR for pancreatic ductal adenocarcinoma.Patients with pancreatic ductal adenocarcinoma treated with pancreatectomy with AR at our institute between January 2000 and April 2017 were retrospectively reviewed. Operative outcome and survival were compared according to the presence of neoadjuvant chemotherapy.This study included 109 patients (38 underwent surgery after neoadjuvant chemotherapy, 71 underwent upfront surgery). The median hospital stay was 17 (interquartile range, 12-26.5) days. Clinically relevant postoperative pancreatic fistula (grade B or C) occurred in 14 patients (12.8%). The major morbidity (?grade III) and mortality rates were 26.6% and 0.9%, respectively. R0 resection was achieved in 80 patients (73.4%). Microscopic actual tumor invasion into the arterial wall was identified in 25 patients (22.9%). The median overall survival (OS) of all patients was 18.4 months. The neoadjuvant chemotherapy group showed better OS than the upfront surgery group, without statistical significance (25.3 vs 16.2 months, P?=?.06). Progression-free survival was better in patients with neoadjuvant chemotherapy (13.2 vs 7.1 months, P?=?.01). Patients with partial response to neoadjuvant chemotherapy showed better OS than those with stable disease (33.7 vs 17.5 months, P?=?.04).Pancreatectomy with AR for advanced pancreatic cancer showed acceptable procedure-related morbidity and mortality. A survival benefit of neoadjuvant chemotherapy was identified, compared to upfront surgery.

SUBMITTER: Kwon J

PROVIDER: S-EPMC7489745 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Arterial resection during pancreatectomy for pancreatic ductal adenocarcinoma with arterial invasion: A single-center experience with 109 patients.

Kwon Jaewoo J Shin Sang Hyun SH Yoo Daegwang D Hong Sarang S Lee Jong Woo JW Youn Woo Young WY Hwang Kyungyeon K Lee Seung Jae SJ Park Guisuk G Park Yejong Y Lee Woohyung W Song Ki Byung KB Lee Jae Hoon JH Hwang Dae Wook DW Kim Song Cheol SC

Medicine 20200901 37

Pancreatectomy for pancreatic cancer with arterial invasion is controversial and performed infrequently. As its indication evolves and neoadjuvant chemotherapy also evolves, it is meaningful to identify short- and long-term outcomes of pancreatectomy with arterial resection (AR). This study aimed to retrospectively analyze the clinical outcomes of pancreatectomy with AR for pancreatic ductal adenocarcinoma.Patients with pancreatic ductal adenocarcinoma treated with pancreatectomy with AR at our ...[more]

PMID: 32925757

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Project description:A disintegrin and a metalloprotease (ADAM)-9 is a metzincin cell-surface protease with strongly elevated expression in solid tumors, including pancreatic ductal adenocarcinoma (PDAC). In this study, we performed immunohistochemistry (IHC) of a tissue microarray (TMA) to examine the expression of ADAM9 in a cohort of >100 clinically annotated PDAC cases. We report that ADAM9 is prominently expressed by PDAC tumor cells, and increased ADAM9 expression levels correlate with poor tumor grading (P = 0.027) and the presence of vasculature invasion (P = 0.017). We employed gene expression silencing to generate a loss-of-function system for ADAM9 in two established PDAC cell lines. In vitro analysis showed that loss of ADAM9 does not impede cellular proliferation and invasiveness in basement membrane. However, ADAM9 plays a crucial role in mediating cell migration and adhesion to extracellular matrix substrates such as fibronectin, tenascin, and vitronectin. This effect appears to depend on its catalytic activity. In addition, ADAM9 facilitates anchorage-independent growth. In AsPC1 cells, but not in MiaPaCa-2 cells, we noted a pronounced yet heterogeneous impact of ADAM9 on the abundance of various integrins, a process that we characterized as post-translational regulation. Sprout formation of human umbilical vein endothelial cells (HUVECs) is promoted by ADAM9, as examined by transfer of cancer cell conditioned medium; this finding further supports a pro-angiogenic role of ADAM9 expressed by PDAC cancer cells. Immunoblotting analysis of cancer cell conditioned medium highlighted that ADAM9 regulates the levels of angiogenic factors, including shed heparin-binding EGF-like growth factor (HB-EGF). Finally, we carried out orthotopic seeding of either wild-type AsPC-1 cells or AsPC-1 cells with silenced ADAM9 expression into murine pancreas. In this in vivo setting, ADAM9 was also found to foster angiogenesis without an impact on tumor cell proliferation. In summary, our results characterize ADAM9 as an important regulator in PDAC tumor biology with a strong pro-angiogenic impact.

Project description:Background: Total pancreatectomy (TP) seems to be experiencing a renaissance in recent years. In this study, we aimed to determine the long-term survival of pancreatic ductal adenocarcinoma (PDAC) patients who underwent TP by comparing with pancreaticoduodenectomy (PD), and formulate a nomogram to predict overall survival (OS) for PDAC individuals following TP. Methods: Patients who were diagnosed with PDAC and received PD (n = 5,619) or TP (n = 1,248) between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. OS and cancer-specific survival (CSS) of the PD and TP groups were compared using Kaplan-Meier method and log-rank test. Furthermore, Patients receiving TP were randomly divided into the training and validation cohorts. Univariate and multivariate Cox regression were applied to identify the independent factors affecting OS to construct the nomogram. The performance of the nomogram was measured according to concordance index (C-index), calibration plots, and decision curve analysis (DCA). Results: There were no significant differences in OS and CSS between TP and PD groups. Age, differentiation, AJCC T stage, radiotherapy, chemotherapy, and lymph node ratio (LNR) were identified as independent prognostic indicators to construct the nomogram. The C-indexes were 0.67 and 0.69 in the training and validation cohorts, while 0.59 and 0.60 of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. The calibration curves showed good uniformity between the nomogram prediction and actual observation. DCA curves indicated the nomogram was preferable to the AJCC staging system in terms of the clinical utility. A new risk stratification system was constructed which could distinguish patients with different survival risks. Conclusions: For PDAC patients following TP, the OS and CSS are similar to those who following PD. We developed a practical nomogram to predict the prognosis of PDAC patients treated with TP, which showed superiority over the conventional AJCC staging system.

Dataset Information

Arterial resection during pancreatectomy for pancreatic ductal adenocarcinoma with arterial invasion: A single-center experience with 109 patients.

Publications

Arterial resection during pancreatectomy for pancreatic ductal adenocarcinoma with arterial invasion: A single-center experience with 109 patients.

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