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Max C Schmidt - One of the best experts on this subject based on the ideXlab platform.
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pancreatic cyst fluid vascular endothelial growth factor a and carcinoembryonic antigen a highly accurate test for the diagnosis of serous Cystic Neoplasm
Journal of The American College of Surgeons, 2017Co-Authors: Rosalie A Carr, Michele T Yipschneider, Scott C Dolejs, Bradley A Hancock, Huangbing Wu, Milan Radovich, Max C SchmidtAbstract:Background Accurate differentiation of pancreatic Cystic lesions is important for early detection and prevention of pancreatic cancer, as well as avoidance of unnecessary surgical intervention. Serous Cystic Neoplasms (SCNs) have no malignant potential, but can mimic the following premalignant mucinous Cystic lesions: mucinous Cystic Neoplasm and intraductal papillary mucinous Neoplasm (IPMN). We recently identified vascular endothelial growth factor (VEGF)-A as a novel pancreatic fluid biomarker for SCN. We hypothesize that combining cyst fluid CEA with VEGF-A will improve the diagnostic accuracy of VEGF-A. Methods Pancreatic cyst/duct fluid was collected from consenting patients undergoing surgical cyst resection with corresponding pathologic diagnoses. Pancreatic fluid VEGF-A and CEA levels were detected by ELISA. Results One hundred and forty-nine patients with pancreatic Cystic lesions met inclusion criteria. Pathologic diagnoses included pseudocyst (n = 14), SCN (n = 26), mucinous Cystic Neoplasm (n = 40), low-/moderate-grade IPMN (n = 34), high-grade IPMN (n = 20), invasive IPMN (n = 10), and solid pseudopapillary Neoplasm (n = 5). Vascular endothelial growth factor A was significantly elevated in SCN cyst fluid compared with all other diagnoses (p 5,000 pg/mL, VEGF-A alone has 100% sensitivity and 83.7% specificity to distinguish SCNs from other Cystic lesions. With a threshold of ≤10 ng/mL, CEA alone identifies SCN with 95.5% sensitivity and 81.5% specificity. Sensitivity and specificity of the VEGF-A/CEA combination are 95.5% and 100%, respectively. The c-statistic increased from 0.98 to 0.99 in the receiver operating characteristic analysis when CEA was added to VEGF-A alone. Conclusions Although VEGF-A alone is a highly accurate test for SCN, the combination of VEGF-A with CEA approaches the gold standard for pathologic diagnosis, importantly avoiding false positives. Patients with a positive test indicating benign SCN can be spared a high-risk surgical pancreatic resection.
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vascular endothelial growth factor a novel and highly accurate pancreatic fluid biomarker for serous pancreatic cysts
Journal of The American College of Surgeons, 2014Co-Authors: Michele T Yipschneider, Huangbing Wu, Milan Radovich, Ryan P Dumas, Brad Hancock, Narasimhan P Agaram, Max C SchmidtAbstract:Background Mucinous pancreatic cysts (intraductal papillary mucinous Neoplasm and mucinous Cystic Neoplasm) have the potential to progress to invasive pancreatic adenocarcinoma, presenting an opportunity for early detection, prevention, and cure. Serous Cystic Neoplasms (SCN) have no malignant potential, but can mimic mucinous pancreatic cysts on imaging. Therefore, identification of biomarkers that can distinguish between Cystic lesions is critically important. We hypothesize that vascular endothelial growth factor (VEGF)-A levels in pancreatic fluid correlate with pathologic diagnosis. Study Design Pancreatic cyst/duct fluid samples were prospectively collected from patients undergoing pancreatic resection and correlated with surgical pathology. VEGF levels were detected by ELISA. VEGF-A and VEGF receptor 2 expression in pancreatic tissue was localized by immunohistochemistry. Genetic alterations of the von Hippel-Lindau gene were determined by targeted next-generation sequencing. Results Eighty-seven patients met inclusion criteria for enrollment. Final pathologic diagnoses included pseudocyst (n = 9), SCN (n = 17), mucinous Cystic Neoplasm (n = 24), low/moderate grade intraductal papillary mucinous Neoplasm (n = 16), high-grade/invasive intraductal papillary mucinous Neoplasm (n = 10), and pancreatic ductal adenocarcinoma (n = 11). VEGF-A was significantly upregulated in SCN cyst fluid compared with all other diagnoses (p Conclusions This is the first report of a cyst fluid protein biomarker that can positively identify SCN. The ability to distinguish SCN from premalignant/malignant pancreatic cysts can spare the cost and risk of surveillance and surgical intervention in select patients.
Seungmo Hong - One of the best experts on this subject based on the ideXlab platform.
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coexisting mucinous Cystic Neoplasm of the pancreas and type 1 autoimmune pancreatitis
Journal of pathology and translational medicine, 2019Co-Authors: Tae Jun Song, Seungmo HongAbstract:: Type 1 autoimmune pancreatitis (AIP1) is an IgG4-related systemic disease that mimics tumors. We report a rare case of AIP1 accompanied by mucinous Cystic Neoplasm (MCN). A pancreatic lesion was incidentally detected in a woman in her 60s. After 6 years of follow-up, the lesion abruptly increased in size. Computed tomography showed a 3.5 cm unilocular cyst in the tail of the pancreas and distal pancreatectomy was performed. On microscopic examination, the cyst was lined by mucinous and non-mucinous epithelial cells with mild cytologic atypia. The surrounding stroma comprised ovarian-type spindle cells with progesterone receptor positivity. The periCystic pancreas exhibited multifocal lymphoid follicles, lymphoplasmacytic infiltrations, obliterative phlebitis, and storiform fibrosis. IgG4-positive plasma cell infiltration (215 cells high-power field) and the IgG4/IgG ratio (57%) were increased. Cases of MCN coexisting with AIP1 are extremely rare; only two such cases have been reported in the English-language literature. This third case featured low-grade MCN with AIP1.
Brian C Lewis - One of the best experts on this subject based on the ideXlab platform.
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abstract a08 activation of wnt β catenin in acinar cells accelerates kras induced pdac while activation of wnt signaling pathways in stroma induces mucinous Cystic Neoplasm
Cancer Research, 2015Co-Authors: Makoto Sano, David R Driscoll, David S Klimstra, Wilfredo E Dejesusmonge, Brian C LewisAbstract:Pancreatic ductal adenocarcinoma (PDAC) commonly develops following activating mutations in the KRAS oncogene. Activation of the Wnt signaling pathway is also commonly observed in PDAC, yet whether Wnt ligand induced signaling promotes pancreatic tumorigenesis in vivo remains unclear. To ascertain the impact of postnatal activation of the Wnt signaling pathways in PDAC development, we combined the elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras G12D , Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin S37A and Wnt1 stimulated the progression of premalignant PanIN and PDAC development. Mice injected with RCAS-β-catenin S37A and Wnt1 had reduced survival relative to RCAS-GFP controls (log-rank test; p S37A nor RCAS-GFP, developed mucinous Cystic Neoplasm (MCN). These lesions displayed stereotypical ovarian-like stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR), but they lacked the typical mucinous epithelium observed in human MCN. Analysis of tissue specimens confirmed of activation of both the Wnt/β-catenin and PCP signaling pathways in the stroma, but not the epithelium of MCN lesions. Analysis of human MCN cases identified activation of these Wnt signaling pathways in the ovarian-like stroma, but not the cyst epithelium. Together, these data suggest that the Wnt/β-catenin signaling pathway in acinar cells stimulates Kras-induced PDAC development, while activation of Wnt signaling pathways in the stroma stimulates the development of the ovarian-like stroma and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David R. Driscoll, Wilfredo E. DeJesus-Monge, David S. Klimstra, Brian C. Lewis. Activation of Wnt/β-catenin in acinar cells accelerates Kras-induced PDAC, while activation of Wnt signaling pathways in stroma induces mucinous Cystic Neoplasm. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A08.
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abstract a75 overexpression of wnt1 induces ovarian type stroma that resemble human pancreatic mucinous Cystic Neoplasm mcn
Cancer Research, 2012Co-Authors: Makoto Sano, David R Driscoll, David S Klimstra, Wilfredo E Dejesusmonge, Victoria Appleman, Brian Quattrochi, Brian C LewisAbstract:Pancreatic mucinous Cystic Neoplasm (MCN), a Cystic tumor of the pancreas with a predominant female gender bias, occurs primarily in the body and tail of the pancreas and is characterized by the presence of a mucinous epithelium and ovarian-type stroma. To determine the involvement of Wnt ligand-induced signaling in pancreatic tumorigenesis, we combined the established LSL-KrasG12D, Ptf1a-cre model with the elastase-tva transgenic mouse to facilitate the delivery of avian leukosis virus-based RCASWnt1 viruses to the pancreatic epithelium. We found that female mice injected with RCAS-Wnt1, but not RCAS-GFP, commonly developed unilocular or multilocular cysts, sometimes including hemorrhagic contents (so called chocolate cyst), in the pancreas body and tail. The Cystic lesions were composed of the characteristic ovarian-type stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR) expression; however, they lacked the typical mucinous epithelium. Interestingly, activation of Wnt/β-catenin and PCP signaling pathways – as determined by nuclear β-catenin, p-JNK and p-Rock2 positivity – was detected in the stroma, but not the cyst epithelium. Analysis of human MCN cases identified activation of both the Wnt/β-catenin and PCP signaling pathways in the ovarian-type stroma, but not the cyst epithelium, consistent with our findings in the mouse model. Together, these data suggest that activation of the canonical and non-canonical Wnt signaling pathways stimulates the development of the ovarian-type stroma observed in pancreatic MCN and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David Driscoll, David S. Klimstra, Wilfredo DeJesus-Monge, Victoria Appleman, Brian Quattrochi, Brian C. Lewis. Overexpression of Wnt1 induces ovarian-type stroma that resemble human pancreatic mucinous Cystic Neoplasm (MCN). [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A75.
Huangbing Wu - One of the best experts on this subject based on the ideXlab platform.
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pancreatic cyst fluid vascular endothelial growth factor a and carcinoembryonic antigen a highly accurate test for the diagnosis of serous Cystic Neoplasm
Journal of The American College of Surgeons, 2017Co-Authors: Rosalie A Carr, Michele T Yipschneider, Scott C Dolejs, Bradley A Hancock, Huangbing Wu, Milan Radovich, Max C SchmidtAbstract:Background Accurate differentiation of pancreatic Cystic lesions is important for early detection and prevention of pancreatic cancer, as well as avoidance of unnecessary surgical intervention. Serous Cystic Neoplasms (SCNs) have no malignant potential, but can mimic the following premalignant mucinous Cystic lesions: mucinous Cystic Neoplasm and intraductal papillary mucinous Neoplasm (IPMN). We recently identified vascular endothelial growth factor (VEGF)-A as a novel pancreatic fluid biomarker for SCN. We hypothesize that combining cyst fluid CEA with VEGF-A will improve the diagnostic accuracy of VEGF-A. Methods Pancreatic cyst/duct fluid was collected from consenting patients undergoing surgical cyst resection with corresponding pathologic diagnoses. Pancreatic fluid VEGF-A and CEA levels were detected by ELISA. Results One hundred and forty-nine patients with pancreatic Cystic lesions met inclusion criteria. Pathologic diagnoses included pseudocyst (n = 14), SCN (n = 26), mucinous Cystic Neoplasm (n = 40), low-/moderate-grade IPMN (n = 34), high-grade IPMN (n = 20), invasive IPMN (n = 10), and solid pseudopapillary Neoplasm (n = 5). Vascular endothelial growth factor A was significantly elevated in SCN cyst fluid compared with all other diagnoses (p 5,000 pg/mL, VEGF-A alone has 100% sensitivity and 83.7% specificity to distinguish SCNs from other Cystic lesions. With a threshold of ≤10 ng/mL, CEA alone identifies SCN with 95.5% sensitivity and 81.5% specificity. Sensitivity and specificity of the VEGF-A/CEA combination are 95.5% and 100%, respectively. The c-statistic increased from 0.98 to 0.99 in the receiver operating characteristic analysis when CEA was added to VEGF-A alone. Conclusions Although VEGF-A alone is a highly accurate test for SCN, the combination of VEGF-A with CEA approaches the gold standard for pathologic diagnosis, importantly avoiding false positives. Patients with a positive test indicating benign SCN can be spared a high-risk surgical pancreatic resection.
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vascular endothelial growth factor a novel and highly accurate pancreatic fluid biomarker for serous pancreatic cysts
Journal of The American College of Surgeons, 2014Co-Authors: Michele T Yipschneider, Huangbing Wu, Milan Radovich, Ryan P Dumas, Brad Hancock, Narasimhan P Agaram, Max C SchmidtAbstract:Background Mucinous pancreatic cysts (intraductal papillary mucinous Neoplasm and mucinous Cystic Neoplasm) have the potential to progress to invasive pancreatic adenocarcinoma, presenting an opportunity for early detection, prevention, and cure. Serous Cystic Neoplasms (SCN) have no malignant potential, but can mimic mucinous pancreatic cysts on imaging. Therefore, identification of biomarkers that can distinguish between Cystic lesions is critically important. We hypothesize that vascular endothelial growth factor (VEGF)-A levels in pancreatic fluid correlate with pathologic diagnosis. Study Design Pancreatic cyst/duct fluid samples were prospectively collected from patients undergoing pancreatic resection and correlated with surgical pathology. VEGF levels were detected by ELISA. VEGF-A and VEGF receptor 2 expression in pancreatic tissue was localized by immunohistochemistry. Genetic alterations of the von Hippel-Lindau gene were determined by targeted next-generation sequencing. Results Eighty-seven patients met inclusion criteria for enrollment. Final pathologic diagnoses included pseudocyst (n = 9), SCN (n = 17), mucinous Cystic Neoplasm (n = 24), low/moderate grade intraductal papillary mucinous Neoplasm (n = 16), high-grade/invasive intraductal papillary mucinous Neoplasm (n = 10), and pancreatic ductal adenocarcinoma (n = 11). VEGF-A was significantly upregulated in SCN cyst fluid compared with all other diagnoses (p Conclusions This is the first report of a cyst fluid protein biomarker that can positively identify SCN. The ability to distinguish SCN from premalignant/malignant pancreatic cysts can spare the cost and risk of surveillance and surgical intervention in select patients.
Naoto Gotohda - One of the best experts on this subject based on the ideXlab platform.
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prediction of the probability of malignancy in mucinous Cystic Neoplasm of the pancreas with ovarian type stroma a nationwide multicenter study in japan
Pancreas, 2020Co-Authors: Takao Ohtsuka, Masafumi Nakamura, Susumu Hijioka, Yasuhiro Shimizu, Michiaki Unno, Minoru Tanabe, Yuichi Nagakawa, Kyoichi Takaori, Seiko Hirono, Naoto GotohdaAbstract:OBJECTIVE: The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous Cystic Neoplasm (MCN) of the pancreas with ovarian-type stroma. METHODS: A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed. RESULTS: A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22. CONCLUSIONS: The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.
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a case of mucinous Cystic Neoplasm of the liver a case report
Surgical Case Reports, 2015Co-Authors: Yusuke Nakayama, Yuichiro Kato, Satoshi Okubo, Daigoro Takahashi, Rei Okada, Yasunori Nishida, Kazuhiko Kitaguchi, Naoto Gotohda, Shinichiro Takahashi, Masaru KonishiAbstract:A 71-year-old woman was referred to our institution for further investigation of epigastric pain. The patient had been detected to have a multilocular cyst in the medial segment of the liver measuring 69 mm in diameter at another hospital 2 years ago, and the diameter of the cyst had increased to 90 mm. Although the cyst had gradually increased in size, there was no evidence of mural nodules. As we were concerned about the malignant potential of the lesion, a left hepatic segmentectomy was performed. Pathologically, the cyst was lined by columnar and cuboidal epithelium with low-grade atypia. The epithelium covered an ovarian-like stroma, and the diagnosis was mucinous Cystic Neoplasm of the liver (MCN-L) with low-grade intraepithelial neoplasia. MCN-L is a rare disease and its characteristics are still poorly understood. MCN-L occurs at a lower frequency as compared to the counterpart of MCN of the pancreas, further investigations are necessary to clarify the biological malignancy of MCN-L.
