scholarly journals Prognostic Evaluation of Vimentin Expression in Correlation with Ki67 and CD44 in Surgically Resected Pancreatic Ductal Adenocarcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Despoina Myoteri ◽  
Dionysios Dellaportas ◽  
Panagis M. Lykoudis ◽  
Alexandros Apostolopoulos ◽  
Athanasios Marinis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Surgical Resection ◽  
Prognostic Significance ◽  
Ductal Adenocarcinoma ◽  
Vimentin Expression ◽  
Term Survival ◽  
Therapeutic Modalities ◽  
Kaplan Meier ◽  
Surgical Resection Margin

Purpose. Radical surgical resection with adjuvant chemotherapy or chemo-radiotherapy is the most effective treatment for pancreatic ductal adenocarcinoma (PDAC). However, relatively few studies investigate the prognostic significance of biological markers in PDAC. This study aims to look into the expressions of vimentin, Ki67, and CD44 in PDAC surgical specimens and their potential prognostic implications in survival. Method. The study was designed as retrospective, and vimentin, Ki67, and CD44 expressions were evaluated by immunohistochemistry in 53 pancreatic ductal adenocarcinoma cases. Overall survival was assessed by the Kaplan–Meier method. Results. Patients’ median age was 68 years. The median survival was 18 months. The tumors were T3-4 in 40/53 (75.5%), and metastases in lymph nodes were found in 42 out of 53 (79.2%) cases. On multivariate analysis, the size of primary tumor (p<0.001), the surgical resection margin status (p=0.042), and vimentin expression (p=0.011) were independently correlated with overall survival. Conclusions. Long-term survival after resection of PDAC is still about 15%. Vimentin expression is a potential independent adverse prognostic molecular marker and should be included in histopathological reports. Also, CD44 expression correlates with high Ki67, vimentin positivity, and N stage and may represent a potential target of novel therapeutic modalities in pancreatic adenocarcinoma patients.

Clinical Characteristics and Overall Survival in Patients with Anaplastic Pancreatic Cancer

2014 ◽  
Vol 80 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Clancy J. Clark ◽  
Janani S. Arun ◽  
Rondell P. Graham ◽  
Lizhi Zhang ◽  
Michael Farnell ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Stage ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Poor Overall Survival ◽  
Perioperative Morbidity ◽  
Log Rank Test ◽  
Kaplan Meier

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.

scholarly journals Additive Value of Preoperative Sarcopenia and Lymphopenia for Prognosis Prediction in Localized Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Christelle d’Engremont ◽  
Julienne Grillot ◽  
Julie Raillat ◽  
Dewi Vernerey ◽  
Lucine Vuitton ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Surgical Resection ◽  
Lymphocyte Count ◽  
Prognostic Score ◽  
Preoperative Evaluation ◽  
High Risk Group ◽  
University Hospital ◽  
Ductal Adenocarcinoma ◽  
Term Survival

BackgroundSurgical resection with adjuvant chemotherapy is the only treatment that can provide long term survival in localized pancreatic ductal adenocarcinoma (LPDAC). Notwithstanding, recurrence occurs in the vast majority of patients and a better stratification of preoperative therapies is required. This study aimed to investigate preoperative immunological and nutritional factors to predict relapse-free survival (RFS) in patients with LPDAC.MethodsAnalyses were derived from all consecutive LPDAC patients treated with surgical resection at Besancon University Hospital, France, between January 2006 and December 2014 (n=146). Biological and nutritional parameters were recorded before and after surgery. The association of 24 baseline parameters with RFS was evaluated using univariate and multivariate Cox analyses. Based on the final model, a prognostic score was developed.ResultsLymphocyte count and body composition were available for 94 patients. In multivariate analysis, preoperative lymphopenia and sarcopenia (or a low muscle mass) were identified as independent prognostic factors for RFS. The score determined three groups with a median RFS of 5.6 months (95% confidence interval [CI] = 4.3 to 9.6 months) for high-risk group, corresponding to patients with lymphopenia; 11.5 months (95%CI = 9.8 to 13.9 months), and 21.2 months (95%CI = 9.9 to 55.3 months), for intermediate-(patient with sarcopenia without lymphopenia), and low-risk groups (no risk factor), respectively (p &lt;0.001). Preoperative sarcopenia predicts the occurrence of postoperative lymphopenia in patients with a preoperative lymphocyte count above 1,000/mm3 (p = 0.0029).ConclusionsPreoperative lymphopenia and sarcopenia are pejorative prognostic factors in LPDAC and should be considered in the preoperative evaluation to stratify death risk in patients with LPDAC.

scholarly journals Pancreatic Ductal Adenocarcinoma at CT: A Combined Nomogram Model to Preoperatively Predict Cancer Stage and Survival Outcome

2021 ◽  
Vol 11 ◽  
Author(s):  
Chunyuan Cen ◽  
Liying Liu ◽  
Xin Li ◽  
Ailan Wu ◽  
Huan Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Characteristics ◽  
Validation Cohort ◽  
Stage I ◽  
Ductal Adenocarcinoma ◽  
Training Cohort ◽  
Calibration Curves ◽  
Kaplan Meier ◽  
Radiomics Signature

ObjectivesTo construct a nomogram model that combines clinical characteristics and radiomics signatures to preoperatively discriminate pancreatic ductal adenocarcinoma (PDAC) in stage I-II and III-IV and predict overall survival.MethodsA total of 135 patients with histopathologically confirmed PDAC who underwent contrast-enhanced CT were included. A total of 384 radiomics features were extracted from arterial phase (AP) or portal venous phase (PVP) images. Four steps were used for feature selection, and multivariable logistic regression analysis were used to build radiomics signatures and combined nomogram model. Performance of the proposed model was assessed by using receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Kaplan-Meier analysis was applied to analyze overall survival in the stage I-II and III-IV PDAC groups.ResultsThe AP+PVP radiomics signature showed the best performance among the three radiomics signatures [training cohort: area under the curve (AUC) = 0.919; validation cohort: AUC = 0.831]. The combined nomogram model integrating AP+PVP radiomics signature with clinical characteristics (tumor location, carcinoembryonic antigen level, and tumor maximum diameter) demonstrated the best discrimination performance (training cohort: AUC = 0.940; validation cohort: AUC = 0.912). Calibration curves and DCA verified the clinical usefulness of the combined nomogram model. Kaplan-Meier analysis showed that overall survival of patients in the predicted stage I-II PDAC group was longer than patients in stage III-IV PDAC group (p&lt;0.0001).ConclusionsWe propose a combined model with excellent performance for the preoperative, individualized, noninvasive discrimination of stage I-II and III-IV PDAC and prediction of overall survival.

Gasdermin C as a potential prognostic biomarker and its correlation with immune infiltration in pancreatic ductal adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16256-e16256
Author(s):  
Xianghou Xia ◽  
Yang Yu ◽  
Hongjian Yang ◽  
Dehong Zou ◽  
Canming Wang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Prognostic Value ◽  
Immune Cell ◽  
Prognostic Significance ◽  
High Expression ◽  
Ductal Adenocarcinoma ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

e16256 Background: Although pyroptosis is critical for macrophages against pathogen infection, its role in cancer cells remains elusive. GSDMC is a pyroptosis executioner newly identified in cancer cells and have been shown to facilitate inflammatory tumor death. However, the expression of GSDMC in Pancreatic Ductal Adenocarcinoma (PDAC), its prognostic significance and possible impact on reshaping tumor immune microenviroment in PDAC is still unknown. Methods: We investigated the expression level of GSDMC using TNM plotter with TCGA and GTEx databases, the prognostic value of GSDMC in PDAC using Kaplan-Meier plotter with TCGA, GTEx and TCGA databases. The correlations between GSDMC and immune infiltration in PDAC were calculated using TIMER2.0 and TIDE with TCGA database. We further validated the prognostic value of GSDMC with immunohistochemistry(IHC) staining on a tissue microarray of 172 cases of PDAC patients receiving treatment in our institution. Correlations between expression of GSDMC and tumor infiltration lymphacytes(TILs) cells were also analyzed on tissue samples of those 172 PDAC patients. Results: TNM plotter analysis shows that the expression of GSDMC in PDAC tumor tissue is 10.49 folds higher than it is in pancreatic normal tissues (p = 8.86*e-56). Results from Kaplan-Meier plotter analysis shows high expression of GSDMC is significantly correlated with poorer overall survival(OS), HR = 1.8(1.19−2.71) logrank P = 0.004 and shorter relapse free survival (RFS), HR = 4.6(1.94−10.88), Logrank P = 0.00014 in PDAC. Analysis with TIMER2.0 and TIDE platform shows that expression of GSDMC is positively correlated with immunosuppressive cells, Cancer Associated Fiberblast (CAF) and Meyloid Derived Tumor Suprresso Cells(MDTSC). IHC staining analysis results is also consistent with aformentioned bioinformatic analysis, showing that high GSDMC expression correlated with shorter OS and reduced Tils infiltration. Conclusions: Our findings suggest that high expression of GSDMC is related to poor prognosis and compromised immune cell infiltration in PDAC. GSDMC holds promise for serving as a valuable prognostic marker and therapeutic target in PDAC.

The pattern of mucin 5AC (MUC5AC) expression using immunohistochemistry and its prognostic significance in patients with pancreatic ductal adenocarcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16756-e16756
Author(s):  
Ashish Manne ◽  
Wadad Mneimneh ◽  
Osama Elkadi ◽  
Daisy E Escobar ◽  
James Coley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
Statistical Analysis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Significance ◽  
Stage Iv ◽  
Ductal Adenocarcinoma ◽  
Ampullary Adenocarcinoma ◽  
Stage Iv Disease ◽  
The University

e16756 Background: Mucin-5AC (MUC5AC) is a secreted form of mucin. Its expression correlates with poor outcome in uterine, ampullary adenocarcinoma and cholangiocarcinoma. Its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) is not well established. Here, we explored the pattern of MUC5AC expression using immunohistochemistry (IHC) and its prognostic significance in patients with PDAC. Methods: This is a retrospective study conducted at the University of South Alabama/Mitchell Cancer Institute. Between 2015-2019, 218 patients with PDAC were identified. Among this cohort, only 45 patients had tissue available for MUC5AC IHC staining. Two pathologists in- dependently scored the expression of MUC5AC. Staining percentage was estimated in 10% increments. Unpaired t test and log-rank Wilcoxon tests were used for statistical analysis. Results: In our cohort, the median age was 65 years (42-85). Males represented 55%. Caucasians, African Americans and other ethnicities (e.g. Asians) represented 71%, 25% and 4% respectively. Twenty patients (44%) had metastatic stage IV disease and 25 patients (56%) had non-metastatic disease. Positive cytoplasmic and apical MUC5AC expression by IHC was seen in 82% and 80% of patients respectively. The median apical MUC5AC expression was higher in metastatic patients compared to non-metastatic patients (67.5 % vs 30%, p = 0.0187 ) while there was no difference in the median cytoplasmic MUC5AC expression between metastatic and non-metastatic patients (13.7 % vs 12.5%, p = 0.3328). In non-metastatic patients, compared to patients with positive apical MUC5AC expression, no expression (0%) was associated with worse overall survival (OS) (43 vs 13 m, p = 0.0322). In metastatic PDAC, there was no difference in OS between patients with positive or no apical MUC5AC expression (18 vs 21 m, p = 0.781). Compared to patients with positive cytoplasmic MUC5AC expression, patients with no cytoplasmic MUC5AC expression (0%) had no difference in OS in both non-metastatic (40 vs 32 m, p = 0.986) and metastatic (36 vs 12.5 m, p = 0.487) patients. Conclusions: MUC5AC expression assessment using IHC is feasible in patients with PDAC. In our cohort, apical, but not cytoplasmic, MUC5AC expression was different between metastatic and non-metatstaic patients and showed prognostic significance in non-metastatic patients. To our knowledge, this is the first study to show prognostic significance of MUC5AC expression in patients with PDAC using IHC.

scholarly journals P-P42 Neo-adjuvant Chemoradiation for Borderline Resectable Pancreatic Adenocarcinoma: A UK Tertiary Surgical Oncology Centre Series

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Marina Likos-Corbett ◽  
Pranav Patel ◽  
Rachna Goburdhun ◽  
Satvinder Mudan ◽  
Amir Khan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Positive Surgical Margin ◽  
Resection Rate ◽  
Adjuvant Chemoradiation ◽  
Borderline Resectable ◽  
Term Survival

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is associated with a historically poor long-term survival of 5-10%, despite surgical resection. Borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) is reported as potentially resectable disease with a degree of vascular involvement, increasing the risk of a positive surgical margin. This cohort of patients have the worst survival despite curative resection and adjuvant chemotherapy. Emerging evidence suggests that neo-adjuvant chemoradiation (NCR) improves R0 resection rates in BR-PDAC patients. We evaluated the R0 resection rate, disease free survival (DFS) and overall survival (OS) in our patients, who had undergone NCR for BR-PDAC at our institution. Methods Data was collected retrospectively for all patients undergoing NCR for BR-PDAC between Jan 2010 to Mar 2020 for this study. Surgical management was ratified by clinical assessment and cross-sectional imaging in a pancreatic multidisciplinary team meeting (MDM). Patients underwent NCR by a number of standardised regimens. Patients with proven regressive or stable disease on imaging underwent a pancreatic resection. All BR-PDAC patients underwent resection in the form of classical Whipple’s or pylorus preserving pancreaticoduodenectomy (PPPD) depending on intra-operative findings. Patient morbidity, R0 resection rate, histological parameters, DFS and OS were evaluated. Results 29 patients were included in the study (16 men and 13 women), with a median age of 65 years (range, 46-74 years). 17 patients received FOLFIRINOX and 12 patients received gemcitabine (GEM) based NCR regimens. All patients received chemoradiation at the end of chemotherapy (range 45-56Gy). 75% had an R0 resection, with a greater proportion in the FOLFIRINOX group. Whole cohort median DFS was 35 months, survival was superior in the FOLFIRINOX group (42 months). Median OS was 30 months for the whole group, with a greater median OS in the FOLFIRINOX versus the GEM cohort (42 versus 29 months). Conclusions We present a single centre retrospective study utilising NCR for BR-PDAC, we reiterate the strong association of an R0 resection with superior patient overall survival following surgery in this cohort. We show that in patients with BR-PDAC, NCR results in superior R0 resection rates with an associated increase in patient survival. Our results show that survival advantage is greatest in BR-PDAC patients who received neo-adjuvant FOLFIRINOX.  Our findings affirm the advantage of NCR prior to surgery, particularly FOLFIRINOX based treatment, in this cohort of patients.

scholarly journals High GFPT1 expression predicts unfavorable outcomes in patients with resectable pancreatic ductal adenocarcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yitao Gong ◽  
Yunzhen Qian ◽  
Guopei Luo ◽  
Yu Liu ◽  
Ruijie Wang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Cox Regression ◽  
Prognostic Significance ◽  
High Rate ◽  
Ductal Adenocarcinoma ◽  
Poor Overall Survival ◽  
Logistic Regression Models ◽  
Kaplan Meier ◽  
Hexosamine Biosynthesis ◽  
Public Datasets

Abstract Background Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which plays a pivotal role in the progression of pancreatic ductal adenocarcinoma (PDAC). Therefore, we investigated the prognostic significance of GFPT1 expression in patients with resectable PDAC. Methods We analyzed public datasets to compare GFPT1 expression in tumor tissues and normal/adjacent pancreatic tissues. We measured the relative GFPT1 expression of 134 resected PDAC specimens in our institution, using real-time polymerase chain reaction (PCR). Survival was compared between high and low GFPT1 expression groups using Kaplan-Meier curves and log-rank tests. Multivariate analyses were estimated using Cox regression and logistic regression models. Results GFPT1 is generally upregulated in PDAC tissues, according to the analysis of public datasets. The data from our institution shows that high GFPT1 expression was correlated with a high rate of lymph node (LN) metastasis (p = 0.038) and was an independent risk factor for LN metastasis (odds ratio (OR) = 3.14, 95% confidence interval (CI) = 1.42 to 6.90, P = 0.005). High GFPT1 expression was significantly associated with poor overall survival (OS; P = 0.019) in patients with resected PDAC. The multivariable-adjusted hazard ratio (HR) for mortality when comparing patients with high and low GFPT1 expression was 2.54 (95% CI = 1.35 to 4.79, P = 0.004). Conclusions GFPT1 is generally upregulated in PDAC tissue and is associated with a high risk of LN metastasis and an unfavorable outcome in patients with resectable PDAC, suggesting its crucial role in PDAC progression.

scholarly journals Prognostic Significance of EIF4G1 in Patients with Pancreatic Ductal Adenocarcinoma

2019 ◽  
Author(s):  
Tae Sik Goh ◽  
Mihyang Ha ◽  
Jung Sub Lee ◽  
Dae Cheon Jeong ◽  
Eun Sang Jung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Survival Analysis ◽  
Survival Rate ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Biomarker ◽  
Prognostic Significance ◽  
Ductal Adenocarcinoma ◽  
Operating Characteristics ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Background: The advances of genomics have greatly improved the survival rate cancer patients. However, due to genetic heterogeneity, pancreatic ductal adenocarcinoma (PDAC) is still difficult to diagnose early and the survival rate is extremely low. Therefore, we identified biomarkers that predict the prognosis of PDAC patients by using independent cohort data. Methods: To develop a novel prognostic biomarker, we used gene expression and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). In Kaplan-Meier survival curve using median values of genes as cut off, the only statistically significant gene in the three cohorts was EIF4G1. We analyzed prognostic significance of EIF4G1 using the time-dependent area under the curve (AUC) of the Uno's C-index, the AUC value of the receiver operating characteristics (ROC) at 3 years, and multivariate cox analysis. Also, we compare EIF4G1 levels between tumor and matched non-tumor. Results: EIF4G1 is the only prognostic gene patients with PDAC which was selected by Kaplan-Meier survival analysis. Kaplan-Meier survival analysis showed that high expression of EIF4G1 was associated with poor prognosis of PDAC with good discriminative ability in 3 independent cohorts. Risk stratifying ability of EIF4G1 was demonstrated by analyzing C-indices and AUC values. Multivariate cox regression analysis confirmed its prognostic significance. EIF4G1 expression was significantly higher in the PDAC tissues than in the matched normal tissues. Conclusions: Herein, the novel prognostic biomarker EIF4G1 could be used as prognostic maker for PDAC and determining suitable treatment options.

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