scholarly journals Identification and validation of heterotypic cell-in-cell structure as an adverse prognostic predictor for young patients of resectable pancreatic ductal adenocarcinoma

2020 ◽  
Author(s):  
Hongyan Huang ◽  
Meifang He ◽  
Yanbin Zhang ◽  
Bo Zhang ◽  
Zubiao Niu ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Cells ◽  
Area Under The Curve ◽  
Tnm Stage ◽  
Ductal Adenocarcinoma ◽  
Clinicopathological Parameters ◽  
Survival Prediction ◽  
Low Grade

OBJECTIVES: A proportion of resectable pancreatic ductal adenocarcinoma (PDAC) patients display poorer survival due to profound local immune suppression. However, a pathological/morphological parameter that could functionally read out immune evasion and predict patient survival has not been defined. This study investigated the feasibility of heterotypic cell-in-cell (CIC) structures for immune cell cannibalism by tumor cells to serve as a parameter for survival prediction in resectable PDAC patients. METHODS: A total of 410 samples from PDAC patients were examined using the methods of "EML" multiplex staining or immunohistochemistry (IHC). Prognostic CIC candidates were initially identified in samples plotted in tissue microarray (n=300), then independently validated in specimens from the First Affiliated Hospital of Sun Yat-Sen University (n=110). The Kaplan - Meier estimator and/or the Cox regression model were used for univariate and multivariate analysis. A nomogram was made using the Regression Modeling Strategies. RESULTS: CICs were prevalent in cancerous (203/235) but not non-malignant tissues (15/147). Among the 4 CIC subtypes identified, 2 heterotypic subtypes with tumor cells internalizing CD45+ lymphocytes (LiT, mOS = 8 vs. 14.5 months, p = 0.008) or CD68+ monocytes (MiT, mOS = 7.5 vs. 15 months, p = 0.001), and overall CICs (oCIC, mOS = 10 vs. 27 months, p = 0.021), but not homotypic CICs (TiT, p = 0.089), were identified in univariate analysis as adverse prognostic factors of overall survival (OS) of PDAC. Notably, through cannibalism of immune cells by tumor cells, heterotypic CICs (L/MiT: LiT plus MiT) could independently predict shorter OS (HR = 1.85, p = 0.008) in multivariate analysis, with a performance comparable or even superior to traditional clinicopathological parameters such as histological grade (HR = 1.78, p = 0.012) and TNM stage (HR=1.64, p = 0.108). This was confirmed in the validation cohort, where L/MiT (HR = 1.71, p = 0.02) and tumor-node-metastasis (TNM) stage (HR = 1.66, p = 0.04) were shown to be independent adverse prognostic factors. Moreover, L/MiT stood out as the most prominent contributor in nomogram models constructed for survival prediction (area under the curve = 0.696 at 14 months), the dropout of which compromised prediction performance (area under the curve = 0.661 at 14 months). Furthermore, stratification analysis indicated that L/MiT tended preferentially to impact young and female patients (HR = 11.61, p < 0.0001, and HR = 9.55, p = 0.0008, respectively) in particular with early-stage and low-grade PDAC (HR = 2.37, p < 0.0001, and HR = 2.19, p < 0.0001, respectively), while TNM stage demonstrated little preference.

scholarly journals The prognostic value of CA19-9, D-dimer and expression of TNFAIP3(A20) protein in pancreatic ductal adenocarcinoma patients

2020 ◽  
Author(s):  
Peng Xu ◽  
Dong Xiao Wang ◽  
Nan Zheng Li ◽  
Jun Jian Qian ◽  
Jie Yao ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lymph Node ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Markers ◽  
Tnm Stage ◽  
Ductal Adenocarcinoma ◽  
Survival Ratio ◽  
Node Metastasis ◽  
Kaplan Meier ◽  
D Dimer

Abstract Background: To explore significance of CA19-9, D-dimer with TNFAIP3 (A20) protein and evaluate its prognostic significance in patients suffering from pancreatic ductal adenocarcinoma (PDAC). Methods: 148 patients suffering from pancreatic ductal adenocarcinoma in Northern Jiangsu People’s Hospital affiliated to Yangzhou University between January 2012 to December 2016 were studied. Cutoff values of prognostic factors were predicted by Receiver operating characteristic curve (ROC curve). Kaplan-Meier method was used to describe survival curve of patients. Univariate and multivariate regression analyses were used to analyze prognostic factors of patients. Results: The recommended cutoff values of the neutrophil-lymphocyte rate (NLR), platelet-lymphocyte rate (PLR), CA19-9 and D-dimer were 2.04 (sensitivity, 0.59; specificity, 0.9; area under the ROC curve (AUC), 0.749; P<0.001), 52.94 (sensitivity, 0.73; specificity, 0.95; AUC, 0.829; P<0.001), 176.66U/ml (sensitivity, 0.7; specificity, 0.9; AUC, 0.794; P<0.001) and 1.18mg/L (sensitivity, 0.82; specificity, 0.9; AUC, 0.845; P<0.001) respectively. The expression of CA19-9 in serum was related with lymph node metastasis (P = 0.010), tumor lymph node metastasis (TNM) stage (P <0.001) and survival ratio (P <0.001). The D-dimer was positively related with differentiation grade (P=0.014), tumor size (P=0.045), TNM stage (P=0.006) and survival ratio (P<0.001). A20 was positively related with differentiation grade (P<0.001), BMI (P<0.001), TNM stage (P=0.024) and survival ratio (P<0.001). The Kaplan-Meier curves showed that the patients with pancreatic ductal adenocarcinoma had a significant difference in the expression of CA19-9 group, expression of D-dimer group and expression of A20 (P<0.05). CA19-9, D-dimer, TNM stage, differentiation grade and A20 were independent prognostic markers for patients sufferingfrom pancreatic ductal adenocarcinoma by univariate and COX multivariate analyses. Conclusions: CA19-9, D-dimer and A20 were independent prognostic markers for pancreatic ductal adenocarcinoma patients.

scholarly journals Prognostic factors following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma

2018 ◽  
Vol 5 (12) ◽  
pp. 3877 ◽  
Author(s):  
Hazem M. Zakaria ◽  
Anwar Mohamed ◽  
Ayman Alsebaey ◽  
Hazem Omar ◽  
Dina ELazab ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Size ◽  
Ductal Adenocarcinoma ◽  
Tumor Diameter ◽  
Advanced Tumor Stage ◽  
Poorly Differentiated ◽  
Risk Factors For Survival

Background: Pancreatic ductal adenocarcinoma (PDAC) had a poor prognosis and surgical resection remains the only potentially curative treatment. The aim of the study was to identify the outcome and risk factors affecting survival after pancreaticoduodenectomy (PD) for PDAC.Methods: The patients who underwent PD for PDAC from 2007 to 2015 were retrospectively studied. Cox regression test for multivariate analysis was used for evaluation of prognostic factors for survival.Results: Ninety-four patients underwent PD for PDAC, 20 patients (21.3%) had major postoperative complications. The perioperative mortality was 4.3%. The 1-, 3-, and 5-years survival rates were 74.5%, 38.7%, 23.4, respectively. In univariate analysis the risk factors for survival were; presence of co-morbidity (P=0.03), high preoperative carbohydrate antigen (CA)19-9 > 400U/ml (P=0.02), advanced tumor stage (P=0.03), large tumor diameter >3cm (P=0.01), poorly differentiated tumor (P= 0.02), involved resection margin (P=0.04), and positive lymph nodes in pathology after surgery (P=0.03). In multivariate analysis the independent risk factors for survival were; high preoperative CA 19-9 (P=0.042), tumor size >3cm (P=0.038), poorly differentiated tumor in histopathology (P=0.045).Conclusions: High tumor marker CA19-9, tumor size, and grade are significant risk factors for poor survival after resection of PDAC and should be taken into account in the selection of patients for surgery to improve the outcome.

Clinical features and outcomes of colloid carcinoma of pancreas compared to pancreatic ductal adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16259-e16259
Author(s):  
Lana Khalil ◽  
Katerina Mary Zakka ◽  
Renjian Jiang ◽  
Mckenna Penely ◽  
Olatunji B. Alese ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Features ◽  
Primary Site ◽  
Stage I ◽  
Stage Ii ◽  
Ductal Adenocarcinoma ◽  
Carcinoma Of Pancreas

e16259 Background: Colloid carcinoma (CC) of the pancreas is a rare histopathological subtype of ductal adenocarcinoma (PDAC), with poorly defined prognostic factors and therapeutic outcomes. The aim of this study is to characterize the clinicopathological features and evaluate the overall survival (OS) and prognostic factors of patients with pancreatic CC using National Cancer Database (NCDB). Methods: Patients diagnosed with CC of the pancreas and PDAC between 2004 and 2016 were identified from the NCDB using ICD-O-3 morphology (8480/3 for CC and 8140/3 for PDAC) and topography codes (C25). Univariate and multivariable analyses were conducted and Kaplan-Meier analysis and Cox proportional hazards models were used to perform OS analysis. Results: A total of 56,846 patients met the inclusion criteria for the final analysis. Of the total population included, 2,430 patients (4.3%) had CC and 54,416 patients (95.7%) had PDAC. For both, CC and PDAC, there was a male preponderance (52.0%, 52.5%), Caucasians (85.1%, 84%), occurrence above the age of 70 (39.2%, 38.2%), and the most common primary site was the head of the pancreas (50.5%, 53%). For CC, the percentage of pathologic stage III colloid pancreas cancer appeared the lowest (3.5%, 85 patients), compared to stage I (16.7%), stage II (37.8%), and stage IV (42.1%). While in PDAC, the percentage of pathologic stage I (5.94%) and stage III (4.44%) patients was lower than stage II (37.21%) and IV (52.41%). CC and PDAC more frequently presented with < 5cm tumor, at academic or research cancer centers, and diagnosed between 2009 and 2013 compared to 2004–2008 ( p< 0.001). For both CC and PDAC, the majority underwent surgical resection (58%, 53%), systemic chemotherapy (57.8%, 63%) and did not receive radiotherapy (78.8%, 77.6%). A positive surgical margin on pathologic evaluation was associated with worse outcomes for CC and PDAC in both univariate and multivariate analysis (HR 1.61; 1.56–1.66; p< 0.001 and HR 1.43; 1.38–1.48, p< 0.001). CC had a better 1-year overall survival (OS) in all stages compared to PDAC (p < 0.001). In multivariate analysis, mucinous carcinoma histology, female sex, diagnosis between 2004 and 2009, well/moderately differentiated histology, chemotherapy, age at diagnosis less than 60, radiation therapy after surgery, and local surgical procedure of primary site and pancreatectomy (p < 0.001) were associated with better OS compared to PDAC. Colloid histology was associated with better 1-year overall survival (OS) in all stages compared to PDAC (p < 0.001). Conclusions: Colloid carcinoma of pancreas is associated with a better overall survival as compared to pancreatic ductal adenocarcinoma. This is the largest study to address the clinical features and outcomes of colloid carcinoma of pancreas.

scholarly journals High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1656 ◽  
Author(s):  
Etienne Buscail ◽  
Catherine Alix-Panabières ◽  
Pascaline Quincy ◽  
Thomas Cauvin ◽  
Alexandre Chauvet ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Neoadjuvant Treatment ◽  
Digital Pcr ◽  
Portal Blood ◽  
Ductal Adenocarcinoma ◽  
Clinical Value ◽  
Liquid Biopsies

Purpose: Expediting the diagnosis of pancreatic ductal adenocarcinoma (PDAC) would benefit care management, especially for the start of treatments requiring histological evidence. This study evaluated the combined diagnostic performance of circulating biomarkers obtained by peripheral and portal blood liquid biopsy in patients with resectable PDAC. Experimental design: Liquid biopsies were performed in a prospective translational clinical trial (PANC-CTC #NCT03032913) including 22 patients with resectable PDAC and 28 noncancer controls from February to November 2017. Circulating tumor cells (CTCs) were detected using the CellSearch® method or after RosetteSep® enrichment combined with CRISPR/Cas9-improved KRAS mutant alleles quantification by droplet digital PCR. CD63 bead-coupled Glypican-1 (GPC1)-positive exosomes were quantified by flow cytometry. Results: Liquid biopsies were positive in 7/22 (32%), 13/22 (59%), and 14/22 (64%) patients with CellSearch® or RosetteSep®-based CTC detection or GPC1-positive exosomes, respectively, in peripheral and/or portal blood. Liquid biopsy performance was improved in portal blood only with CellSearch®, reaching 45% of PDAC identification (5/11) versus 10% (2/22) in peripheral blood. Importantly, combining CTC and GPC1-positive-exosome detection displayed 100% of sensitivity and 80% of specificity, with a negative predictive value of 100%. High levels of GPC1+-exosomes and/or CTC presence were significantly correlated with progression-free survival and with overall survival when CTC clusters were found. Conclusion: This study is the first to evaluate combined CTC and exosome detection to diagnose resectable pancreatic cancers. Liquid biopsy combining several biomarkers could provide a rapid, reliable, noninvasive decision-making tool in early, potentially curable pancreatic cancer. Moreover, the prognostic value could select patients eligible for neoadjuvant treatment before surgery. This exploratory study deserves further validation.

scholarly journals Coagulation Signaling through PAR1 as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 22 (10) ◽  
pp. 5138
Author(s):  
Aditi Kothari ◽  
Matthew J. Flick
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Reciprocal Relationship ◽  
Coagulation System ◽  
Ductal Adenocarcinoma ◽  
Protease Activated Receptors ◽  
Major Mechanism ◽  
Signaling Axis ◽  
Venous Thromboembolic

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with a 5-year survival rate of less than 10% following diagnosis. The aggressive and invasive properties of pancreatic cancer tumors coupled with poor diagnostic options contribute to the high mortality rate since most patients present with late-stage disease. Accordingly, PDAC is linked to the highest rate of cancer-associated venous thromboembolic disease of all solid tumor malignancies. However, in addition to promoting clot formation, recent studies suggest that the coagulation system in PDAC mediates a reciprocal relationship, whereby coagulation proteases and receptors promote PDAC tumor progression and dissemination. Here, upregulation of tissue factor (TF) by tumor cells can drive local generation of the central coagulation protease thrombin that promotes cell signaling activity through protease-activated receptors (PARs) expressed by both tumor cells and multiple stromal cell subsets. Moreover, the TF-thrombin-PAR1 signaling axis appears to be a major mechanism of cancer progression in general and PDAC in particular. Here, we summarize the current literature regarding the role of PAR1 in PDAC and review possibilities for pharmacologically targeting PAR1 as a PDAC therapeutic approach.

scholarly journals Prognostic Nomogram for Patients With Pancreatic Ductal Adenocarcinoma of Pancreatic Head After Pancreaticoduodenectomy

2021 ◽  
Vol 15 ◽  
pp. 117955492110241
Author(s):  
Hongkai Zhuang ◽  
Zixuan Zhou ◽  
Zuyi Ma ◽  
Shanzhou Huang ◽  
Yuanfeng Gong ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Perineural Invasion ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Cox Regression Analysis ◽  
Ajcc Stage

Background: The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) of pancreatic head remains poor, even after potentially curative R0 resection. The aim of this study was to develop an accurate model to predict patients’ prognosis for PDAC of pancreatic head following pancreaticoduodenectomy. Methods: We retrospectively reviewed 112 patients with PDAC of pancreatic head after pancreaticoduodenectomy in Guangdong Provincial People’s Hospital between 2014 and 2018. Results: Five prognostic factors were identified using univariate Cox regression analysis, including age, histologic grade, American Joint Committee on Cancer (AJCC) Stage 8th, total bilirubin (TBIL), CA19-9. Using all subset analysis and multivariate Cox regression analysis, we developed a nomogram consisted of age, AJCC Stage 8th, perineural invasion, TBIL, and CA19-9, which had higher C-indexes for OS (0.73) and RFS (0.69) compared with AJCC Stage 8th alone (OS: 0.66; RFS: 0.67). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve for the nomogram for OS and RFS were significantly higher than other single parameter, which are AJCC Stage 8th, age, perineural invasion, TBIL, and CA19-9. Importantly, our nomogram displayed higher C-index for OS than previous reported models, indicating a better predictive value of our model. Conclusions: A simple and practical nomogram for patient prognosis in PDAC of pancreatic head following pancreaticoduodenectomy was established, which shows satisfactory predictive efficacy and deserves further evaluation in the future.

scholarly journals A Novel Nomogram for Predicting Cancer-Specific Survival in Patients With Spinal Chordoma: A Population-Based Analysis

2021 ◽  
Vol 20 ◽  
pp. 153303382110365
Author(s):  
Zhangheng Huang ◽  
Zhiyi Fan ◽  
Chengliang Zhao ◽  
He Sun
Keyword(s):  
Prognostic Factors ◽  
Area Under The Curve ◽  
Risk Groups ◽  
Population Based ◽  
Disease Stage ◽  
Survival Prediction ◽  
Cancer Specific Survival ◽  
Spinal Chordoma ◽  
Prediction Of Prognosis ◽  
High Degree

Background: Chordoma is a rare malignant bone tumor, and the survival prediction for patients with chordoma is difficult. The objective of this study was to construct and validate a nomogram for predicting cancer-specific survival (CSS) in patients with spinal chordoma. Methods: A total of 316 patients with spinal chordoma were identified from the SEER database between 1998 and 2015. The independent prognostic factors for patients with spinal chordoma were determined by univariate and multivariate Cox analyses. The prognostic nomogram was established for patients with spinal chordoma based on independent prognostic factors. Furthermore, we performed internal and external validations for this nomogram. Results: Primary site, disease stage, histological type, surgery, and age were identified as independent prognostic factors for patients with spinal chordoma. A nomogram for predicting CSS in patients with spinal chordoma was constructed based on the above 5 variables. In the training cohort, the area under the curve for predicting 1-, 3-, and 5-year CSS were 0.821, 0.856, and 0.920, respectively. The corresponding area under the curve in the validation cohort were 0.728, 0.804, and 0.839, respectively. The calibration curves of the nomogram showed a high degree of agreement between the predicted and the actual results, and the decision curve analysis further demonstrated the satisfactory clinical utility of the nomogram. Conclusions: The prognostic nomogram provides a considerably more accurate prediction of prognosis for patients with spinal chordoma. Clinicians can use it to categorize patients into different risk groups and make personalized treatment methods.

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