المؤلفون: Juri Ikemoto, Ryota Kawamura, Shinya Nakamura, Keiji Hanada, Masahiro Serikawa, Tsuyoshi Sekitou, Keisuke Kurihara, Tetsuro Hirano, Tomofumi Tsuboi, Takeshi Mori, Kazuaki Chayama, Yasutaka Ishii

المصدر: Pancreas

مصطلحات موضوعية: Male, Vascular Endothelial Growth Factor A, Pathology, Endocrinology, Diabetes and Metabolism, pancreatic duct cancer, FDG-Positron Emission Tomography, 0302 clinical medicine, Endocrinology, SUVmax - maximal standardized uptake volume, pancreas, Child, FDG-PET, PNEN - pancreatic neuroendocrine neoplasm, Glucose Transporter Type 1, JPS - Japan Pancreas Society, medicine.diagnostic_test, Middle Aged, solid pseudopapillary neoplasm, VEGF - vascular endothelial growth factor, medicine.anatomical_structure, Positron emission tomography, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Hypoxia-Inducible Factor 1, Pancreas, medicine.drug, Adult, tumor, medicine.medical_specialty, Adolescent, CT - contrast computed tomography, PDC - pancreatic duct cancer, SPN - solid pseudopapillary neoplasm, Young Adult, GLUT1 - glucose transporter protein type 1, 03 medical and health sciences, Fluorodeoxyglucose F18, Internal Medicine, medicine, Carcinoma, Humans, Aged, Pancreatic duct, Fluorodeoxyglucose, Hepatology, business.industry, Cancer, Original Articles, FDG-PET - fluorodeoxyglucose positron emission tomography, medicine.disease, Carcinoma, Papillary, HIF - hypoxia-inducible factor, Pancreatic Neoplasms, Pancreatic Neuroendocrine Neoplasm, Positron-Emission Tomography, Radiopharmaceuticals, pancreatic neuroendocrine neoplasm, business

الوصف: Objectives This study aimed to investigate the utility of fluorodeoxyglucose (FDG) positron emission tomography for solid pseudopapillary neoplasm (SPN) diagnosis. Methods The subjects included 53 cases of SPN. We compared the maximal standardized uptake volume (SUVmax) with those of 25 cases of pancreatic duct cancer and 18 cases of pancreatic neuroendocrine neoplasm. In addition, immunopathological testing for SPN with regard to FDG uptake was undertaken. Results An increase in SUVmax was observed in all tumors with increased tumor diameter. Among tumors of 20 mm or smaller, the SUVmax of SPN was significantly higher than those of pancreatic duct cancer and pancreatic neuroendocrine neoplasm. The results of a pathological study of FDG uptake in SPN revealed increased glucose transporter protein type 1 expression with tumor enlargement. Furthermore, increased hypoxia-inducible factor-1 and vascular endothelial growth factor expression under hypoxic conditions were observed in the areas of necrosis. Conclusions In cases in which high FDG uptake is observed in small pancreatic tumors, FDG positron emission tomography is potentially useful for SPN differentiation. The factors involved in FDG uptake in SPN include cell density and glucose transporter protein expression, as well as hypoxia-inducible factor and vascular endothelia growth factor expression in the hypoxic environment of necrotic areas.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4836cd159bb4e4692bdf47d627d8d59Test
https://doi.org/10.1097/mpa.0000000000001424Test

المؤلفون: Michael P. Kim, Asif Rashid, Gauri R. Varadhachary, Ignacio I. Wistuba, Robert A. Wolff, Minhua Wang, Anirban Maitra, Jeffrey E. Lee, Matthew H.G. Katz, Huamin Wang, Jeannelyn S. Estrella

المصدر: Pancreas

مصطلحات موضوعية: Adult, Male, Oncology, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Vimentin, Article, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Internal Medicine, medicine, Carcinoma, Humans, Epithelial–mesenchymal transition, Neoadjuvant therapy, Aged, Aged, 80 and over, Hepatology, biology, business.industry, Hazard ratio, Zinc Finger E-box-Binding Homeobox 1, Middle Aged, Cadherins, medicine.disease, Neoadjuvant Therapy, Pancreatic Neoplasms, 030220 oncology & carcinogenesis, Pancreatectomy, biology.protein, Adenocarcinoma, Female, 030211 gastroenterology & hepatology, business, Biomarkers, Carcinoma, Pancreatic Ductal

الوصف: Objectives Epithelial-mesenchymal transition (EMT) plays an important role in the progression, metastasis, and chemoresistance of pancreatic duct adenocarcinoma (PDAC); however, the expression of EMT markers and their clinical significance in PDAC patients who received neoadjuvant therapy (NAT) are unclear. Methods We examined the expression of EMT markers, including Zeb-1 (zinc finger E-box-binding homeobox 1), E-cadherin, and vimentin by immunohistochemistry in 120 PDAC patients who received NAT and pancreatectomy from 1999 to 2007. The results were correlated with clinicopathologic parameters and survival. Results Among 120 cases, 45 (37.5%) and 14 (11.7%) were positive for Zeb-1 and vimentin, respectively, and 25 (20.8%) were E-cadherin-low. The median overall survival and disease-free survival were 35.3 (standard deviation [SD], 2.8) and 15.9 (SD, 3.6) months, respectively, in vimentin-negative group compared with 16.1 (SD, 1.1) (P = 0.03) and 7.0 (SD, 1.1) months (P = 0.02) in the vimentin-positive group. In multivariate analysis, vimentin expression was an independent predictor of shorter disease-free survival (hazard ratio, 2.50; 95% confidence interval, 1.31-4.78; P = 0.016) and overall survival (hazard ratio, 2.55; 95% confidence interval, 1.33-4.89; P = 0.01). Conclusions Epithelial-mesenchymal transition markers are frequently expressed in treated PDAC. Vimentin expression is a prognostic biomarker for survival in PDAC patients who received NAT.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dba4ba1868952a6cbf35c705bd604ca9Test
https://doi.org/10.1097/mpa.0000000000001432Test

المؤلفون: Simon Gronowitz, Oliver Strobel, Magnus Neumüller, Ulf Hinz, Mattias Bergqvist, Sophie Dobiasch, Klaus Felix, Frank Bergmann, Thilo Hackert

المصدر: Pancreas. 47:72-79

مصطلحات موضوعية: Adult, 0301 basic medicine, Oncology, medicine.medical_specialty, Thymidine kinase activity, Pancreatic ductal adenocarcinoma, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Kaplan-Meier Estimate, Thymidine Kinase, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Predictive Value of Tests, Internal medicine, Pancreatic cancer, Outcome Assessment, Health Care, Biomarkers, Tumor, Internal Medicine, medicine, Carcinoma, Humans, Thymidine kinase 1, Neoadjuvant therapy, Aged, Monitoring, Physiologic, Predictive biomarker, Hepatology, business.industry, Middle Aged, Prognosis, medicine.disease, Neoadjuvant Therapy, digestive system diseases, Pancreatic Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, Predictive value of tests, Preoperative Period, business, Carcinoma, Pancreatic Ductal

الوصف: The aim of the study was to investigate serum thymidine kinase 1 (S-TK) activity as a diagnostic and prognostic marker for patients with pancreatic ductal adenocarcinoma (PDAC).Using the sensitive TK activity assay DiviTum, preoperative serum samples from 404 PDAC, 28 chronic pancreatitis, and 25 autoimmune pancreatitis patients and 83 healthy volunteers were analyzed. The preoperative S-TK activities of 54 PDAC patients who received neoadjuvant therapy (nTx) were also compared with those of 258 PDAC patients who did not receive nTx.The preoperative S-TK activities of PDAC patients were significantly higher and discriminatory from autoimmune and chronic pancreatitis patients and control groups. The S-TK activity in PDAC patients was associated with overall survival. Patients with S-TK activity of less than 80 Du (DiviTum units)/L demonstrated median survival of 20.3 months with an estimated 18.0% 5-year survival rate; for S-TK activity of 80 Du/L or greater, median survival was 15.1 months with a 6.8% 5-year survival rate. For early-stage PDAC, these differences were even more pronounced. The S-TK activity in the nTx group was significantly higher than that in the group not receiving nTx.Pancreatic ductal adenocarcinomas reveal a significant increase in S-TK activity, which is associated with overall survival, especially in early tumor stages. Serum thymidine kinase 1 activity may be a useful parameter for monitoring nTx efficacy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0ac6b9a320cf964e94012753d6e396dTest
https://doi.org/10.1097/mpa.0000000000000966Test

المؤلفون: Yan Chen, Yu-Ling Wang, Quan-Cai Cai, Hai-Tao Chen, Yong-Zhen Zhang, Xiao-Hua Man, Ming Yang, Zhao-Shen Li, Jianming Zheng

المصدر: Pancreas. 46:323-334

مصطلحات موضوعية: Adult, Male, musculoskeletal diseases, 0301 basic medicine, Oncology, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Kaplan-Meier Estimate, Logistic regression, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Predictive Value of Tests, Internal medicine, Pancreatic cancer, Biomarkers, Tumor, Internal Medicine, Carcinoma, medicine, Humans, Chitinase-3-Like Protein 1, Survival analysis, Aged, Neoplasm Staging, Aged, 80 and over, Hepatology, Proportional hazards model, business.industry, Hazard ratio, Odds ratio, Middle Aged, Prognosis, medicine.disease, Immunohistochemistry, Pancreatic Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, Predictive value of tests, Multivariate Analysis, Female, business, Carcinoma, Pancreatic Ductal

الوصف: OBJECTIVES The aim of this study was to determine the prognostic value of YKL-40 expression in patients undergoing curative resection of pancreatic cancer. METHODS This cohort study included 234 consecutive patients with pancreatic ductal adenocarcinoma who underwent curative resection. Surgical specimens were immunohistochemically assessed for YKL-40 expression. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of YKL-40 expression. A multivariate logistic regression model was performed to examine the correlation between YKL-40 expression and tumor stage. RESULTS Of the 234 patients, YKL-40 overexpression was detected in 149 (63.7%) patients. Survival curves showed that patients with YKL-40 overexpression had significantly shorter survival time than those with low YKL-40 expression (P < 0.001). Cox regression analysis indicated that YKL-40 expression was an independent prognostic factor for both overall survival (hazard ratio, 3.82; 95% confidence interval [CI], 2.38-6.13) and progression-free survival (hazard ratio, 3.73; 95% CI, 2.33-5.99). Multivariate logistic regression analysis demonstrated that YKL-40 overexpression was an independent predictor for advanced tumor stage (odds ratio 4.15; 95% CI, 1.35-12.71). CONCLUSIONS YKL-40 overexpression predicts poor prognosis and advanced tumor stage in patients undergoing curative resection of pancreatic cancer. Application of adjuvant treatment targeting the YKL-40 pathway may improve prognosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a064bfca20b47d111c6abe833dcda7b2Test
https://doi.org/10.1097/mpa.0000000000000751Test

المؤلفون: Jian Fei, Wei An, Ping Li, Qiwen Ben, Zhao-Shen Li, Jianming Zheng, Yaozong Yuan

المصدر: Pancreas. 43:744-749

مصطلحات موضوعية: Adult, Male, Oncology, medicine.medical_specialty, Angiogenesis, Endocrinology, Diabetes and Metabolism, Kaplan-Meier Estimate, Adenocarcinoma, Neovascularization, Young Adult, Endocrinology, Internal medicine, Neuropilin 1, Internal Medicine, medicine, Carcinoma, Humans, Lymph node, Aged, Neoplasm Staging, Aged, 80 and over, Neovascularization, Pathologic, Hepatology, business.industry, Hazard ratio, Middle Aged, medicine.disease, Immunohistochemistry, Neuropilin-1, Pancreatic Neoplasms, Platelet Endothelial Cell Adhesion Molecule-1, medicine.anatomical_structure, Lymphatic Metastasis, Multivariate Analysis, T-stage, Female, medicine.symptom, business, Carcinoma, Pancreatic Ductal

الوصف: Objectives Neuropilin 1 (NRP-1) appears to promote angiogenesis by acting as a coreceptor with vascular endothelial growth factor receptor. We correlated NRP-1 expression with microvessel density (MVD) and overall survival (OS) in human pancreatic ductal adenocarcinomas (PDACs). Methods Neuropilin 1 expression was graded semiquantitatively using immunohistochemistry in patients with resected PDAC. Moreover, MVD was determined with an anti-CD31 antibody staining. Expression of NRP-1 was correlated with MVD and clinicopathologic features in patients with PDAC. Overall survival effects of NRP-1 expression were evaluated by multivariate Cox regression and Kaplan-Meier analyses. Results High NRP-1 expression was associated with advanced Union for International Cancer Control stage (P = 0.046), T stage (P = 0.031), and lymph node invasion (P = 0.045). Microvessel density was significantly higher in the tumors with high NRP-1 expression than that in the tumors with low NRP-1 expression (mean, 13.9 [SD, 9.1] vs 10.2 [SD, 7.2] per high-power field; P = 0.001). The multivariate Cox regression analysis demonstrated that high NRP-1 expression was independently associated with reduced OS (hazard ratio, 2.10; 95% confidence interval, 1.19-3.70). Conclusions Neuropilin 1 is highly expressed in PDACs, and high expression of NRP-1 is significantly correlated with angiogenesis, advanced tumor-node-metastasis stage, p T stage, node invasion, and poor postoperative OS.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8a752f3df3d5f1ec6c39fa183371d905Test
https://doi.org/10.1097/mpa.0000000000000117Test

المؤلفون: Yang K. Chen, Daniel Langer, Joel S. Bentz, Jackie Papkoff, S. Russell Nash, Raj J. Shah, Wenhui Liu, Nida S. Awadallah, Kenneth R. Shroyer, Kathleen C. Torkko

المصدر: Pancreas. 36:200-206

مصطلحات موضوعية: Adult, Male, Pathology, medicine.medical_specialty, Tissue Fixation, Pancreatic ductal adenocarcinoma, Endocrinology, Diabetes and Metabolism, Biopsy, Fine-Needle, Pilot Projects, Malignancy, Endosonography, Immunoenzyme Techniques, Endocrinology, Predictive Value of Tests, Pancreatic cancer, Biomarkers, Tumor, Internal Medicine, Carcinoma, medicine, Humans, Pancreas, P53 expression, Aged, Neoplasm Staging, Hepatology, Immunoperoxidase, business.industry, Reproducibility of Results, Cancer, Middle Aged, V-Set Domain-Containing T-Cell Activation Inhibitor 1, medicine.disease, digestive system diseases, Pancreatic Neoplasms, B7-1 Antigen, Biomarker (medicine), Female, Tumor Suppressor Protein p53, business, Carcinoma, Pancreatic Ductal

الوصف: Objectives: This study compared p53 expression with B7-H4, a novel cancer biomarker, in pancreatic ductal adenocarcinoma (PDA) resection specimens and in a pilot series of endoscopic ultrasound-guided fine-needle aspirations (EUS-FNAs). Methods: B7-H4 and p53 expression were evaluated by immunoperoxidase methods in 36 PDA and 15 EUS-FNA specimens and were scored for intensity and proportion of positive cells; cases were then assigned a final sum score. Results: B7-H4 was detected in 33 (92%) of 36 PDA sections, 8 (89%) of 9 cytologically positive EUS-FNAs, and 1 (20%) of 5 cytologically negative EUS-FNAs. p53 was detected in 30 (83%) of 36 PDA sections, 4 (44%) of 9 cytologically positive EUS-FNAs, and 1 (20%) of 5 cytologically negative cases. One EUS-FNA case that was cytologically atypical but not diagnostic of malignancy expressed B7-H4 and p53. Some benign tissue components (intercalated cells/ducts, main pancreatic ducts, and acinar cells) were also positive for B7-H4 and/or p53. Overall expression of B7-H4 in benign tissues, however, was relatively low compared with that seen in most carcinoma cases. Conclusions: B7-H4 was expressed more often in PDA than was p53. Despite potentially problematic expression in benign/normal cells, the 2 markers target different cellular components and demonstrate potential diagnostic use for detection of PDA in resected and EUS-FNA specimens.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f46a1cefdbe4d44ea1eaf01397a8aeaTest
https://doi.org/10.1097/mpa.0b013e318150e4e0Test

المؤلفون: Akihiko Kidani, Yoshitsugu Tajima, Takeshi Nishi, Yasunari Kawabata

المصدر: Pancreas. 44(6)

مصطلحات موضوعية: Oncology, Male, Time Factors, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Kaplan-Meier Estimate, Endocrinology, Risk Factors, Medicine, Excision repair cross-complementing, Aged, 80 and over, Hazard ratio, Middle Aged, Pancreaticoduodenectomy, Immunohistochemistry, DNA-Binding Proteins, Treatment Outcome, Chemotherapy, Adjuvant, Disease Progression, Female, Adjuvant, Adult, medicine.medical_specialty, Ampulla of Vater, Common Bile Duct Neoplasms, Disease-Free Survival, Equilibrative Nucleoside Transporter 1, Internal medicine, Internal Medicine, Dihydropyrimidine dehydrogenase, Biomarkers, Tumor, Humans, Dihydrouracil Dehydrogenase (NADP), Aged, Proportional Hazards Models, Retrospective Studies, Chi-Square Distribution, Hepatology, business.industry, Proportional hazards model, Patient Selection, Carcinoma, Endonucleases, Molecular biology, Confidence interval, Multivariate Analysis, ERCC1, Neoplasm Recurrence, Local, business

الوصف: OBJECTIVES The purpose of this study was to characterize the intratumoral expression profiles of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), and human equilibrative nucleotide transporter 1 (hENT1) in ampullary carcinomas (ACs) to evaluate their prognostic values and better tailor adjuvant chemotherapy for individual patients with AC after surgery. METHODS This study included 49 patients with AC who underwent a curative pancreaticoduodenectomy. Various clinicopathological factors, including ERCC1, DPD, and hENT1, were analyzed in relation to postoperative disease recurrence and the patients' survival. RESULTS The median recurrence-free survival and overall survival were 24.5 months and 32.4 months, respectively. Multivariate Cox regression analysis of recurrence-free survival identified a DPD expression (hazard ratio [HR], 8.18; 95% confidence interval [CI], 2.00-34.8; P = 0.003) and combined ERCC1/DPD expression (HR, 134.8; 95% CI, 11.8-1920; P < 0.001) as independent predictors of disease recurrence. Multivariate Cox regression analysis of overall survival also identified a DPD expression (HR, 8.48; 95% CI, 1.71-46.3; P = 0.008) and combined ERCC1/ DPD expression (HR, 135.6; 95% CI, 11.8-1940; P < 0.001) as independent predictors of survival. CONCLUSIONS The DPD and ERCC1 expression profile could potentially serve as a useful prognostic biomarker and therapeutic target for surgically resected patients with AC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71afe4a804b94caeef5b51b361946b03Test
https://pubmed.ncbi.nlm.nih.gov/25906447Test

المؤلفون: Christopher J. Jackson, Christopher J. Scarlett, Ross C. Smith, Aiqun Xue, Barry J. Allen

المصدر: Pancreas. 36(2)

مصطلحات موضوعية: Male, Time Factors, Endocrinology, Diabetes and Metabolism, Kaplan-Meier Estimate, Endocrinology, Epidermal growth factor receptor, Receptor, Regulation of gene expression, Aged, 80 and over, biology, Reverse Transcriptase Polymerase Chain Reaction, Middle Aged, Up-Regulation, ErbB Receptors, Gene Expression Regulation, Neoplastic, Insulin-Like Growth Factor Binding Proteins, Treatment Outcome, Intercellular Signaling Peptides and Proteins, Female, medicine.drug, Carcinoma, Pancreatic Ductal, Adult, Receptors, Cell Surface, Receptors, Urokinase Plasminogen Activator, Downregulation and upregulation, Somatomedins, Cystadenoma, Mucinous, Plasminogen Activator Inhibitor 1, Internal Medicine, Carcinoma, medicine, Plasminogen Activator Inhibitor 2, Humans, RNA, Messenger, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Urokinase, Messenger RNA, Hepatology, business.industry, Receptors, Somatomedin, medicine.disease, Urokinase-Type Plasminogen Activator, Pancreatic Neoplasms, Logistic Models, ROC Curve, Cancer research, biology.protein, business, Plasminogen activator

الوصف: To determine the diagnostic and prognostic significance of growth factors and the urokinase-type plasminogen activator (uPA) system in pancreatic ductal adenocarcinoma (PDAC) using a multigene assay.Messenger RNA (mRNA) expression of 15 genes from epidermal growth factor receptor, insulin-like growth factor (IGF), and uPA families were measured in 46 PDAC tissue samples using quantitative real-time reverse transcription-polymerase chain reaction. These results were compared with those of the uninvolved adjacent (AP) tissue and benign mucinous cystadenomas (BMC). The mRNA expression was evaluated using logistic regression and receiver operating characteristic area under the curve (ROC AUC) analyses. Their relationship with prognosis was tested by Cox regression multivariate analysis.All genes were overexpressed in most of the PDAC tissue. When compared with AP tissue, the median expression values for IGF-binding protein 3 (IGFBP-3) and uPA receptor (uPAR) was 9.8- and 9.6-fold, respectively. Expression levels of uPA, uPAR, IGF-I, and IGFBP-3 mRNA were significantly greater in PDAC than in BMC. The IGFBP-3 mRNA expression demonstrated greatest ROC AUC values for PDAC versus AP tissue (ROC AUC, 0.745; 95% confidence interval [CI], 0.65-0.86); whereas ROC AUC values were greatest for uPAR when PDAC was compared with BMC (ROC AUC, 0.846; 95% CI, 0.76-0.94). The combination of uPA, uPAR, and IGF-I significantly improved discriminatory power (ROC AUC, 0.965; 95% CI, 0.93-1.00). The IGFBP-3, uPA, plasminogen activator inhibitor-2, and International Union Against Cancer stage had a significant influence on survival, but the effect of IGFBP-3 was lost after multivariate stepwise analysis.These results indicate that there is an influence of IGF system in tumor progression from BMC to PDAC, whereas the uPA/uPAR system has the greater influence on survival in PDAC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b9b1677bd7c06ba45e374cb5dd59d94Test
https://pubmed.ncbi.nlm.nih.gov/18376307Test