31 results on '"Cyst Fluid chemistry"'
Search Results
2. High Expression of microRNA-371a-3p in Cystic Fluid of Post-Chemotherapy Teratoma with Concurrent Normal Serum Levels in Patients with Non-Seminomatous Testicular Germ Cell Tumours.
- Author
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Dieckmann KP, Hennig F, Anheuser P, Gehrckens R, Viehweger F, Wülfing C, and Belge G
- Subjects
- Adolescent, Adult, Biomarkers, Tumor biosynthesis, Humans, Male, MicroRNAs biosynthesis, Young Adult, Biomarkers, Tumor analysis, Cyst Fluid chemistry, MicroRNAs analysis, Neoplasms, Germ Cell and Embryonal drug therapy, Neoplasms, Second Primary metabolism, Retroperitoneal Neoplasms metabolism, Teratoma metabolism, Testicular Neoplasms drug therapy
- Abstract
Background: MicroRNA-371a-3p (miR-371), the novel serum biomarker of testicular germ cell tumours (GCTs), is produced by undifferentiated subtypes of GCTs but not by teratoma. Cystic teratoma developing from retroperitoneal metastases of GCT subsequent to chemotherapy had been shown to contain high levels of classical serum tumour markers of GCT in the presence of normal marker levels in serum. To date, no information is available regarding the presence of miR-371 in the cystic fluid of residual teratoma after chemotherapy., Methods: Four patients (age 18-26 years) undergoing retroperitoneal lymph node dissection (RPLND) for cystic residual masses resulting from chemotherapy of bulky retroperitoneal GCT had measurements of miR-371 in both serum and cystic fluid aspirated from surgical specimens. Measurement of the miR was performed with quantitative real-time PCR using miR-30b-5p as reference. Results were tabulated and analysed in a descriptive manner., Results: Histologically, all of the surgical specimens involved teratoma only with no evidence of vital undifferentiated GCT tissue. All patients were cured. Prior to RPLND, miR-371 serum levels were not measurable or close to zero in all of the patients. Cystic fluid revealed elevated levels of miR-371 in 3 patients and traces of miR in one., Conclusions: The detection of miR-371 in the cystic fluid of teratoma is somewhat enigmatic since this GCT subtype usually does not express the miR. Two hypotheses may explain the finding: First, miR-371 molecules were released into the cystic fluid by active GCT tissue prior to chemotherapy. High levels were kept after regression of vital GCT tissue because the cystic lumen is without a specific drainage system. Second, teratoma cells lining the interior cyst wall may shed small amounts of miR-371 into the lumen. Because of the lacking drainage system, even small levels may accumulate. The present finding adds to the understanding of the biology of the novel biomarker of GCT., (© 2020 S. Karger AG, Basel.)
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- 2021
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3. Cyst Fluid Biosignature to Predict Intraductal Papillary Mucinous Neoplasms of the Pancreas with High Malignant Potential.
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Maker AV, Hu V, Kadkol SS, Hong L, Brugge W, Winter J, Yeo CJ, Hackert T, Büchler M, Lawlor RT, Salvia R, Scarpa A, Bassi C, and Green S
- Subjects
- Female, Humans, Male, Polymerase Chain Reaction methods, Predictive Value of Tests, Principal Component Analysis, Adenocarcinoma, Mucinous pathology, Biomarkers, Tumor chemistry, Carcinoma, Pancreatic Ductal pathology, Cyst Fluid chemistry, Pancreatic Neoplasms pathology
- Abstract
Background: Current standard-of-care technologies, such as imaging and cyst fluid analysis, are unable to consistently distinguish intraductal papillary mucinous neoplasms (IPMNs) of the pancreas at high risk of pancreatic cancer from low-risk IPMNs. The objective was to create a single-platform assay to identify IPMNs that are at high risk for malignant progression., Study Design: Building on the Verona International Consensus Conference branch duct IPMN biomarker review, additional protein, cytokine, mucin, DNA, and microRNA cyst fluid targets were identified for creation of a quantitative polymerase chain reaction-based assay. This included messenger RNA markers: ERBB2, GNAS, interleukin 1β, KRAS, MUCs1, 2, 4, 5AC, 7, prostaglandin E2R, PTGER2, prostaglandin E synthase 2, prostaglandin E synthase 1, TP63; microRNA targets: miRs 101, 106b, 10a, 142, 155, 17, 18a, 21, 217, 24, 30a, 342, 532, 92a, and 99b; and GNAS and KRAS mutational analysis. A multi-institutional international collaborative contributed IPMN cyst fluid samples to validate this platform. Cyst fluid gene expression levels were normalized, z-transformed, and used in classification and regression analysis by a support vector machine training algorithm., Results: From cyst fluids of 59 IPMN patients, principal component analysis confirmed no institutional bias/clustering. Lasso (least absolute shrinkage and selection operator)-penalized logistic regression with binary classification and 5-fold cross-validation used area under the curve as the evaluation criterion to create the optimal signature to discriminate IPMNs as low risk (low/moderate dysplasia) or high risk (high-grade dysplasia/invasive cancer). The most predictive signature was achieved with interleukin 1β, MUC4, and prostaglandin E synthase 2 to accurately discriminate high-risk cysts from low-risk cysts with an area under the curve of up to 0.86 (p = 0.002)., Conclusions: We have identified a single-platform polymerase chain reaction-based assay of cyst fluid to accurately predict IPMNs with high malignant potential for additional studies., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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4. Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia.
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Singhi AD, McGrath K, Brand RE, Khalid A, Zeh HJ, Chennat JS, Fasanella KE, Papachristou GI, Slivka A, Bartlett DL, Dasyam AK, Hogg M, Lee KK, Marsh JW, Monaco SE, Ohori NP, Pingpank JF, Tsung A, Zureikat AH, Wald AI, and Nikiforova MN
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Pancreatic Ductal diagnosis, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal surgery, Chromogranins genetics, DNA, Neoplasm genetics, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Female, Follow-Up Studies, GTP-Binding Protein alpha Subunits, Gs genetics, Humans, Male, Middle Aged, Mutation, Neoplasm Proteins genetics, Neoplasms, Cystic, Mucinous, and Serous diagnosis, Neoplasms, Cystic, Mucinous, and Serous genetics, Neoplasms, Cystic, Mucinous, and Serous surgery, Pancreatic Cyst genetics, Pancreatic Cyst pathology, Pancreatic Cyst surgery, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Pancreatic Neoplasms surgery, Preoperative Care, Prospective Studies, Proto-Oncogene Proteins p21(ras) genetics, Sensitivity and Specificity, Young Adult, Biomarkers, Tumor genetics, Cyst Fluid chemistry, High-Throughput Nucleotide Sequencing methods, Pancreatic Cyst diagnosis, Pancreatic Neoplasms diagnosis
- Abstract
Objective: DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in KRAS / GNAS are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while TP53 / PIK3CA / PTEN alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing., Design: Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopic ultrasound (EUS)-fine needle aspiration and assessed by targeted next-generation sequencing (NGS). Molecular results were correlated with EUS findings, ancillary studies and follow-up. A separate cohort of 159 PCF specimens was also evaluated for KRAS / GNAS mutations by Sanger sequencing., Results: KRAS/GNAS mutations were identified in 308 (49%) PCs, while alterations in TP53/PIK3CA/PTEN were present in 35 (6%) cases. Based on 102 (17%) patients with surgical follow-up, KRAS/GNAS mutations were detected in 56 (100%) IPMNs and 3 (30%) MCNs, and associated with 89% sensitivity and 100% specificity for a mucinous PC. In comparison, KRAS/GNAS mutations by Sanger sequencing had a 65% sensitivity and 100% specificity. By NGS, the combination of KRAS/GNAS mutations and alterations in TP53/PIK3CA/PTEN had an 89% sensitivity and 100% specificity for advanced neoplasia. Ductal dilatation, a mural nodule and malignant cytopathology had lower sensitivities (42%, 32% and 32%, respectively) and specificities (74%, 94% and 98%, respectively)., Conclusions: In contrast to Sanger sequencing, preoperative NGS of PCF for KRAS / GNAS mutations is highly sensitive for IPMNs and specific for mucinous PCs. In addition, the combination of TP53 / PIK3CA / PTEN alterations is a useful preoperative marker for advanced neoplasia., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2018
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5. Identifying precursor lesions of pancreatic cancer.
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Venkatesan P
- Subjects
- Adenocarcinoma diagnosis, Humans, Mass Spectrometry, Pancreatic Cyst diagnosis, Pancreatic Neoplasms diagnosis, Precancerous Conditions diagnosis, Predictive Value of Tests, Prognosis, Adenocarcinoma chemistry, Biomarkers, Tumor analysis, Cyst Fluid chemistry, Pancreatic Cyst metabolism, Pancreatic Neoplasms chemistry, Precancerous Conditions metabolism
- Published
- 2018
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6. Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts.
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Zikos T, Pham K, Bowen R, Chen AM, Banerjee S, Friedland S, Dua MM, Norton JA, Poultsides GA, Visser BC, and Park WG
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- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor analysis, Biopsy, Fine-Needle, Carcinoembryonic Antigen analysis, Carcinoma, Pancreatic Ductal metabolism, Cystadenocarcinoma diagnosis, Cystadenocarcinoma metabolism, Cystadenocarcinoma, Mucinous diagnosis, Cystadenocarcinoma, Mucinous metabolism, Female, Glucose analysis, Humans, Male, Middle Aged, Neoplasms, Cystic, Mucinous, and Serous metabolism, Pancreatic Cyst metabolism, Pancreatic Neoplasms metabolism, Pancreatic Pseudocyst diagnosis, Pancreatic Pseudocyst metabolism, Prospective Studies, Sensitivity and Specificity, Young Adult, Biomarkers, Tumor metabolism, Carcinoembryonic Antigen metabolism, Carcinoma, Pancreatic Ductal diagnosis, Cyst Fluid chemistry, Glucose metabolism, Neoplasms, Cystic, Mucinous, and Serous diagnosis, Pancreatic Cyst diagnosis, Pancreatic Neoplasms diagnosis
- Abstract
Objectives: Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip., Methods: Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed., Results: Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00)., Conclusions: Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.
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- 2015
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7. Re: proteomic mucin profiling for the identification of cystic precursors of pancreatic cancer.
- Author
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Kleeff J, Kong B, Siveke J, and Esposito I
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- Female, Humans, Male, Biomarkers, Tumor analysis, Cyst Fluid chemistry, Gene Expression Profiling, Mucins analysis, Pancreatic Cyst metabolism, Pancreatic Cyst pathology, Pancreatic Neoplasms pathology, Precancerous Conditions chemistry
- Published
- 2014
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8. Response.
- Author
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Jabbar KS, Verbeke C, Hyltander AG, Sjövall H, Hansson GC, and Sadik R
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- Female, Humans, Male, Biomarkers, Tumor analysis, Cyst Fluid chemistry, Gene Expression Profiling, Mucins analysis, Pancreatic Cyst metabolism, Pancreatic Cyst pathology, Pancreatic Neoplasms pathology, Precancerous Conditions chemistry
- Published
- 2014
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9. Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts.
- Author
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Singhi AD, Nikiforova MN, Fasanella KE, McGrath KM, Pai RK, Ohori NP, Bartholow TL, Brand RE, Chennat JS, Lu X, Papachristou GI, Slivka A, Zeh HJ, Zureikat AH, Lee KK, Tsung A, Mantha GS, and Khalid A
- Subjects
- Adenocarcinoma diagnosis, Adenocarcinoma genetics, Adenocarcinoma, Mucinous diagnosis, Adenocarcinoma, Mucinous genetics, Adult, Aged, Aged, 80 and over, Biopsy, Fine-Needle, Carcinoma, Pancreatic Ductal diagnosis, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Papillary diagnosis, Carcinoma, Papillary genetics, Chromogranins, Cyst Fluid chemistry, Cyst Fluid metabolism, Cystadenoma, Serous diagnosis, Cystadenoma, Serous genetics, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Staging, Pancreatic Cyst metabolism, Pancreatic Neoplasms genetics, Preoperative Care, Prognosis, Proto-Oncogene Proteins p21(ras), Young Adult, Biomarkers, Tumor genetics, GTP-Binding Protein alpha Subunits, Gs genetics, Mutation genetics, Pancreatic Cyst pathology, Pancreatic Neoplasms diagnosis, Proto-Oncogene Proteins genetics, ras Proteins genetics
- Abstract
Purpose: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear., Experimental Design: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst., Results: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92)., Conclusions: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms., (©2014 American Association for Cancer Research.)
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- 2014
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10. Intraductal tubulopapillary neoplasm of the pancreas on fine needle aspiration: case report with differential diagnosis.
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Guan H, Gurda G, Lennon AM, Hruban RH, and Erozan YS
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- Adult, Amylases analysis, Carcinoembryonic Antigen analysis, Carcinoma, Pancreatic Ductal diagnostic imaging, Carcinoma, Pancreatic Ductal genetics, Cyst Fluid chemistry, Diagnosis, Differential, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Female, Humans, Mucin-1 analysis, Pancreatic Cyst diagnostic imaging, Pancreatic Cyst genetics, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms genetics, Point Mutation, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins p21(ras), Rare Diseases, ras Proteins genetics, Biomarkers, Tumor analysis, Carcinoma, Pancreatic Ductal chemistry, Carcinoma, Pancreatic Ductal pathology, Pancreatic Cyst chemistry, Pancreatic Cyst pathology, Pancreatic Neoplasms chemistry, Pancreatic Neoplasms pathology
- Abstract
Intraductal tubulopapillary neoplasm (ITPN) is a rare primary pancreatic neoplasm accounting for less than 1% of all pancreatic exocrine neoplasms and 3% of intraductal neoplasms of the pancreas. Data on this entity are still limited. Here, we report a case of ITPN with cytopathologic and histopathologic findings. A 41-year-old woman with a 2.2 cm cyst in the head of the pancreas for five years was referred to our institution. The endoscopic ultrasound-guided fine-needle aspiration produced cytospins were moderately cellular with a few fragments of markedly atypical epithelium. The neoplastic cells displayed high-grade nuclear atypia with enlarged, eccentric nuclei, anisonucleosis and prominent nucleoli, irregular nuclear membranes, high nucleus to cytoplasmic (N/C) ratios, and a moderate amount of cytoplasm with no intracytoplasmic mucin. Histologically, the lesion was found to be an ITPN with focal high-grade dysplasia. No invasive carcinoma was identified. The neoplastic cells exhibited luminal immunolabeling for MUC-1, but were negative for MUC-2, trypsin, chymotrypsin, and P53. Approximately 5% of the neoplastic cells showed Ki-67 immunoreactivity. ITPN of pancreas may be a source of markedly atypical epithelial cells in pancreatic cystic aspiration. Clinical and radiographic findings, molecular mutational analysis, in combination with cytological features are essential to differentiate it from other disease entities., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2014
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11. Proteomic mucin profiling for the identification of cystic precursors of pancreatic cancer.
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Jabbar KS, Verbeke C, Hyltander AG, Sjövall H, Hansson GC, and Sadik R
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- Adult, Aged, Biomarkers, Tumor blood, Carcinoembryonic Antigen blood, Chromatography, Liquid, Electrophoresis, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Mass Spectrometry, Middle Aged, Mucins genetics, Pancreatic Neoplasms chemistry, Precancerous Conditions pathology, Predictive Value of Tests, Biomarkers, Tumor analysis, Cyst Fluid chemistry, Gene Expression Profiling, Mucins analysis, Pancreatic Cyst metabolism, Pancreatic Cyst pathology, Pancreatic Neoplasms pathology, Precancerous Conditions chemistry
- Abstract
Background: Pancreatic cystic lesions (PCLs) are increasingly frequent radiological incidentalomas, with a considerable proportion representing precursors of pancreatic cancer. Better diagnostic tools are required for patients to benefit from this development., Methods: To evaluate whether cyst fluid mucin expression could predict malignant potential and/or transformation in PCLs, a proteomic method was devised and prospectively evaluated in consecutive patients referred to our tertiary center for endoscopic ultrasound-guided aspiration of cystic lesions from May 2007 through November 2008 (discovery cohort) and from December 2008 through October 2012 (validation cohort). Cytology and cyst fluid carcinoembryonic antigen (CEA; premalignancy > 192 ng/mL, malignancy > 1000 ng/mL) were routinely analyzed, and samples were further processed as follows: one-dimensional gel electrophoresis, excision of high-mass areas, tryptic digestion and nano-liquid chromatography-tandem mass spectrometry, with peptide identification by Mascot software and an in-house mucin database. All diagnostic evaluations were blinded to proteomics results. Histology was required to confirm the presence/absence of malignant transformation. All statistical tests were two-sided., Results: Proteomic mucin profiling proved statistically significantly more accurate (97.5%; 95% confidence interval [CI] = 90.3% to 99.6%) than cytology (71.4%; 95% CI = 59.8% to 80.9%; P < .001) and cyst fluid CEA (78.0%; 95% CI = 65.0% to 87.3%; P < .001) in identifying the 37 (out of 79; 46.8%) lesions with malignant potential (ie, premalignant or malignant tumors). The accuracy of proteomics was nearly identical (96.6% vs 98.0%) between the discovery (n = 29) and validation (n = 50) cohorts. Furthermore, mucin profiling predicted malignant transformation, present in 16 out of 29 (discovery cohort: 9, validation cohort: 20) lesions with available histology, with 89.7% accuracy (95% CI = 71.5% to 97.3%) (for the validation cohort only: 95.0%; 95% CI = 73.1% to 99.7%). This markedly exceeded corresponding results for cytology (51.7%; 95% CI = 32.9% to 70.1%; P = .003) and CEA (57.1%; 95% CI = 34.4% to 77.4%; P = .02)., Conclusions: Proteomic cyst fluid mucin profiling robustly discriminates benign, premalignant, and malignant PCLs. Consequently, it may improve pancreatic cancer prevention and reduce the morbidity burden of unwarranted pancreatic surgery.
- Published
- 2014
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12. Cyst fluid SPINK1 may help to differentiate benign and potentially malignant cystic pancreatic lesions.
- Author
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Räty S, Sand J, Laukkarinen J, Vasama K, Bassi C, Salvia R, and Nordback I
- Subjects
- Adenocarcinoma, Mucinous diagnosis, Adenocarcinoma, Mucinous pathology, Adolescent, Adult, Aged, Aged, 80 and over, Cystadenoma, Serous diagnosis, Female, Humans, Male, Middle Aged, Sensitivity and Specificity, Biomarkers, Tumor analysis, Cyst Fluid chemistry, Pancreatic Cyst diagnosis, Pancreatic Neoplasms diagnosis, Trypsin Inhibitor, Kazal Pancreatic analysis
- Abstract
Objective: Differential diagnosis between benign and potentially malignant cystic pancreatic lesions may be difficult. Previously we have compared cyst fluid serine protease inhibitor Kazal type I (SPINK1) with some traditionally used tumour markers (amylase, CEA, Ca19-9) and found that it may be a new promising maker in the differential diagnosis of cystic pancreatic lesions. In the present study, we focused on cyst fluid SPINK1 levels in benign and potentially malignant cystic pancreatic lesions., Design: Sixty-one patients operated on for cystic pancreatic lesion in Tampere University Hospital, Finland and in Verona University Hospital, Italy, were included. Cyst fluid was aspirated during surgery, stored at -70 °C, and analysed with immunofluorometric assay for SPINK1. The final diagnosis was acute pancreatitis with fluid collection (Acute FC) in 4 patients, chronic pseudocyst (PS) in 17 patients, serous cystadenoma (SCA) in 7 patients, mucinous cystadenoma (MCA) in 21 patients and intraductal papillary-mucinous neoplasm (IPMN) in 12 patients (9 main/mixed duct type and 3 branch duct type)., Results: The acute FC patients had high SPINK1 levels. Among chronic cysts, SPINK1 levels were significantly higher in patients with potentially malignant cysts (main/mixed duct IPMN and MCA) than with benign cysts (side branch IPMN and SCA), (median and range, [480 (13-3602) vs. 18 (0.1-278) μg/L]; p < 0.0001). In the subcohort of 24 patients with <3 cm chronic cyst, cyst fluid SPINK 1 levels were significantly lower in SCA or side branch IPMN (3 [2-116] μg/L) than in main duct IPMN or MCA (638 [66-3602] μg/L; p = 0.018). The best sensitivity and specificity to differentiate any size MCA or main/mixed type IPMN from SCA or side branch IPMN were 85% and 84% (AUC 0.94; cut-off value 118 μg/L). The best sensitivity and specificity to differentiate <3 cm MCA or main duct IPMN from SCA or side branch IPMN were 93% and 89% (AUC 0.98; cut-off value 146 μg/L)., Conclusions: Cyst fluid SPINK1 may be a possible marker in the differential diagnosis of benign and potentially malignant cystic pancreatic lesions., (Copyright © 2013. Published by Elsevier B.V.)
- Published
- 2013
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13. Ovarian cyst fluids are a cache of tumor biomarkers that include calgranulin A and calgranulin B isoforms.
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Skaggs HS, Saunders BA, Miller RW, Goodrich ST, King MS, Kimbler KD, Branscum AJ, Fung ET, DePriest PD, van Nagell JR, Ueland FR, and Baron AT
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- Adult, Aged, Aged, 80 and over, Blotting, Western, Calgranulin A biosynthesis, Calgranulin B biosynthesis, Cyst Fluid chemistry, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Female, Humans, Middle Aged, Ovarian Neoplasms metabolism, Protein Isoforms analysis, Protein Isoforms biosynthesis, Sensitivity and Specificity, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Biomarkers, Tumor analysis, Calgranulin A analysis, Calgranulin B analysis, Ovarian Cysts chemistry, Ovarian Neoplasms diagnosis
- Abstract
SELDI-TOF MS analysis of cyst fluids identified 95 peaks that discriminate malignant, borderline, and benign ovarian tumors. Three prominent peaks, which correspond to calgranulin A (m/z 10847) and two isoforms of calgranulin B (m/z 12717 and 13294), have higher concentrations in borderline and malignant cyst fluids. Together, calgranulin A and B distinguish borderline and malignant tumors from benign tumors with 28.6% and 63.6% sensitivity for early stage disease, respectively, at 95% specificity and with 74.8% accuracy. Ovarian cyst fluids are useful for discovering discriminatory biomarkers, such as calgranulin, which may have utility for detecting, diagnosing, and biochemically classifying ovarian tumors.
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- 2013
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14. Immunoprofile of mucinous non-neoplastic cyst of the pancreas.
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Zhu B and Lin X
- Subjects
- 12E7 Antigen, Adenocarcinoma, Mucinous genetics, Adenocarcinoma, Mucinous pathology, Aged, Amylases genetics, Antigens, CD genetics, Carcinoembryonic Antigen genetics, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal pathology, Cell Adhesion Molecules genetics, Cyst Fluid chemistry, Cystadenoma, Mucinous genetics, Cystadenoma, Mucinous pathology, Diagnosis, Differential, Female, Gene Expression, Homeodomain Proteins genetics, Humans, Immunohistochemistry, Male, Middle Aged, Neprilysin genetics, Pancreatic Cyst genetics, Pancreatic Cyst pathology, Trans-Activators genetics, Adenocarcinoma, Mucinous diagnosis, Biomarkers, Tumor genetics, Carcinoma, Pancreatic Ductal diagnosis, Cystadenoma, Mucinous diagnosis, Pancreatic Cyst diagnosis
- Abstract
Background: A recently described mucinous non-neoplastic cyst (MNNC) of the pancreas is a benign cyst and should be distinguished from mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm (IPMN) due to different management and prognosis. The immunoprofile of MNNC has not been well studied., Design: Twenty-three MNNCs diagnosed on surgical resection were retrieved. Immunohistochemical (IHC) staining was performed on surgically resected specimen. Sixteen IPMN and 15 MCN cases were also retrieved for comparison. Cyst fluid carcinoembryonic antigen and amylase concentrations were retrieved., Result: MNNCs were randomly located in the pancreas and were either unilocular or multilocular cysts that were lined by a single layer of bland columnar or cuboidal mucinous cells and supported by paucicellular stroma. The glandular epithelial cells were diffusely positive for CK7 (100%) and PDX-1 (65%); focally positive for CD10 (superficial, 65%), CD99 (basally, 100%), CDX-2 (17%), and CK20 (4%); and negative for MUC2. Only rare stromal cells in the cyst wall were weakly positive for estrogen receptor or progesterone receptor in only 6% of cases and negative for inhibin. These results were also compared with the immunoprofile of IPMN and MCN., Conclusions: Although MNNC shares some IHC markers with IPMN or MCN, an IHC panel can help distinguish MNNC from IPMN or MCN. The results suggest that MNNC is different from IPMN and MCN.
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- 2013
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15. Diagnosis of congenital cervical cysts using carcinoembryonic antigen levels in cyst fluid.
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Konomi U, Tokashiki R, Yoshida T, Shimizu A, Tsukahara K, and Suzuki M
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- Adolescent, Adult, Aged, Aged, 80 and over, Biopsy, Fine-Needle, Branchioma pathology, Case-Control Studies, Child, Cyst Fluid chemistry, Cysts chemistry, Cysts congenital, Cysts pathology, Female, Head and Neck Neoplasms chemistry, Head and Neck Neoplasms pathology, Humans, Male, Middle Aged, Neck pathology, Biomarkers, Tumor analysis, Branchioma diagnosis, Carcinoembryonic Antigen analysis, Cysts diagnosis, Head and Neck Neoplasms diagnosis
- Abstract
Objective: To investigate whether carcinoembryonic antigen (CEA) levels in the fluid of median or lateral cervical cysts can improve diagnosis., Methods: Cyst fluid CEA levels in 10 cases of median cervical or lateral cervical cysts based on pathological diagnoses (congenital cervical cyst group) were measured. These results were compared with the CEA levels of the control group comprising 10 cases of other head and neck cyst disorders., Results: The CEA levels in nine out of ten cases in the congenital cervical cyst group were ≥10,000ng/mL. The CEA level in the remaining case was 8290ng/mL. In contrast, the CEA levels were low in the control group (>1000ng/mL). The optimal cut-off level between these groups was 8290ng/mL in the receiver operating characteristic curve (p<0.01)., Conclusion: Cyst fluid CEA levels may assist in the diagnosis of median and lateral cervical cysts., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2012
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16. Cyst fluid carcinoembryonic antigen in the investigation of cystic neuroendocrine tumors of the pancreas.
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Croagh D, Forde C, Boulton R, and Mahon B
- Subjects
- Aged, Cystadenocarcinoma diagnosis, Diagnosis, Differential, Endosonography, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neuroendocrine Tumors chemistry, Neuroendocrine Tumors diagnosis, Pancreatic Neoplasms diagnosis, Pancreatic Pseudocyst diagnosis, Retrospective Studies, Tomography, X-Ray Computed, Biomarkers, Tumor analysis, Carcinoembryonic Antigen analysis, Cyst Fluid chemistry, Cystadenocarcinoma chemistry, Pancreatic Neoplasms chemistry, Pancreatic Pseudocyst chemistry
- Published
- 2011
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17. Cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts.
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Cizginer S, Turner BG, Bilge AR, Karaca C, Pitman MB, and Brugge WR
- Subjects
- Aged, Biopsy, Fine-Needle, Boston, Diagnosis, Differential, Endosonography, Female, Humans, Male, Middle Aged, Neoplasms, Cystic, Mucinous, and Serous chemistry, Neoplasms, Cystic, Mucinous, and Serous diagnostic imaging, Neoplasms, Cystic, Mucinous, and Serous pathology, Pancreatic Cyst chemistry, Pancreatic Cyst diagnostic imaging, Pancreatic Cyst pathology, Pancreatic Neoplasms chemistry, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms pathology, Predictive Value of Tests, Prospective Studies, ROC Curve, Radioimmunoassay, Sensitivity and Specificity, Biomarkers, Tumor analysis, Carcinoembryonic Antigen analysis, Cyst Fluid chemistry, Neoplasms, Cystic, Mucinous, and Serous diagnosis, Pancreatic Cyst diagnosis, Pancreatic Neoplasms diagnosis
- Abstract
Objectives: Endoscopic ultrasound (EUS) may offer a diagnostic tool through the combination of imaging and guided fine-needle aspiration of pancreatic cysts. The purpose of this investigation was to determine the most accurate test for differentiating mucinous from nonmucinous cysts., Methods: The results of EUS imaging, cytology, and cyst fluid biochemical markers were prospectively collected and compared in a large single-center study (776 patients) using histology or malignant cytology as the final diagnostic standard in 198 patients., Results: The mean cyst fluid carcinoembryonic antigen (CEA) was greater in mucinous cysts (4703.0 ng/mL) compared with nonmucinous cysts (25.8 ng/mL) (P = 0.008). When using the optimal cutoff value of 109.9 ng/mL, the CEA was more accurate (86%, receiver operating characteristic area = 0.928) than EUS imaging (48%) and cytology (58%) in predicting a mucinous cyst (P < 0.0001). Malignant cysts had a mean cyst fluid CEA value (2558.2 ng/mL) similar to benign cysts (4700.2 ng/mL). Cytology (75%) more accurately diagnosed malignant cysts than EUS (66%) and CEA (62%) (P < 0.05)., Conclusions: Cyst fluid CEA concentration provides a highly accurate test for the diagnosis of a mucinous cyst, but does not distinguish benign from malignant cysts. Cytology is the most accurate test for the diagnosis of a malignant cyst.
- Published
- 2011
- Full Text
- View/download PDF
18. K-ras mutations correlate with atypical cytology and elevated CEA levels in pancreatic cystic neoplasms.
- Author
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Mertz H
- Subjects
- Adenocarcinoma surgery, Aged, Biopsy, Fine-Needle, Cyst Fluid chemistry, Humans, Middle Aged, Mutation, Pancreatic Cyst surgery, Pancreatic Neoplasms surgery, Treatment Outcome, Adenocarcinoma genetics, Biomarkers, Tumor genetics, Carcinoembryonic Antigen blood, Genes, ras, Pancreatic Cyst blood, Pancreatic Cyst genetics, Pancreatic Neoplasms genetics
- Abstract
Introduction: Benign pancreatic cystic neoplasms are important precursors to pancreatic adenocarcinoma, and offer the opportunity to prevent cancer. Conversely, prevention only occurs with surgical resection associated with significant morbidity and mortality, while the natural history of small cystic neoplasms is a slow and uncertain progression to malignancy. Markers that predict progression to malignancy are needed. Cyst fluid DNA analysis including K-ras mutations may predict more aggressive natural history of pancreatic cystic neoplasms., Methods: Sixty patients with pancreatic cysts measuring less than 3 cm without solid component or pancreatic ductal dilation underwent EUS with fine needle aspiration. Nine had surgical resection. Cyst fluid was tested for cytology, CEA levels, and DNA analysis including K-ras mutations, and eight loss of heterozygosity mutations. Mutations were correlated with findings of atypia and CEA levels., Results: Cyst fluid K-ras mutation was found in 30% of patients. Patients with mutated K-ras were more likely to have atypia on cytology or pathology (39 vs. 14%) and higher CEA (median 591 vs. 42) compared to wild-type K-ras. K-ras mutants were more likely to have two or more loss of heterozygosity mutations. Loss of heterozygosity mutations did not correlate with atypia or CEA levels., Conclusions: Cyst fluid K-ras mutation correlates with other markers of aggressive cyst behavior. EUS with cyst DNA analysis may alter management of smaller pancreatic cysts when surgery might otherwise be deferred. Further studies of cyst fluid DNA and long-term outcomes are needed.
- Published
- 2011
- Full Text
- View/download PDF
19. Role of proteomics to differentiate between benign and potentially malignant pancreatic cysts.
- Author
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Cuoghi A, Farina A, Z'graggen K, Dumonceau JM, Tomasi A, Hochstrasser DF, Genevay M, Lescuyer P, and Frossard JL
- Subjects
- Amylases analysis, CA-19-9 Antigen analysis, Carcinoembryonic Antigen analysis, Chromatography, Liquid, Electrophoresis, Polyacrylamide Gel, Granulocyte Colony-Stimulating Factor metabolism, Humans, Immunoassay, Immunoblotting, Immunohistochemistry, Mucins metabolism, Pancreatic Cyst metabolism, Pancreatic Neoplasms metabolism, Tandem Mass Spectrometry, Biomarkers, Tumor analysis, Cyst Fluid chemistry, Pancreatic Cyst diagnosis, Pancreatic Neoplasms diagnosis, Proteomics methods
- Abstract
Pancreatic cystic neoplasms represent 10-15% of primary cystic masses of the pancreas. While pancreatic cysts are detected with an increasing frequency due to the use of advanced imaging modalities in clinical practice, the diagnosis of pancreatic cystic neoplasms remains unsatisfactory because available diagnostic techniques proved not sensitive enough so far. This study was designed to characterize the proteomic pattern of pancreatic cyst fluids obtained from various cystic lesions. Cyst fluids were collected by direct puncture during open surgery to avoid any possible contamination from other tissues. CEA, CA-19-9, and amylase concentrations were measured using specific immunoassays. After immunodepletion and fractionation by SDS-PAGE, proteins were digested and analyzed by LC-MS/MS. Specific histological lesions were found to be associated with distinct protein patterns. Interestingly, some of these proteins have been proposed as biomarkers of pancreatic cancer. Immunoblots allowed for verifying the differential expression in specific cyst fluids of two selected proteins, olfactomedin-4 and mucin-18. Finally, immunohistochemistry was performed to correlate these data with the expression pattern of olfactomedin-4 and mucin-18 in pancreatic cyst tissues. Results from this study indicate that proteomic analysis of cyst fluid could provide reliable candidates for developing new biomarkers for the preoperative management of malignant and premalignant pancreatic cysts.
- Published
- 2011
- Full Text
- View/download PDF
20. Elevated microRNA miR-21 levels in pancreatic cyst fluid are predictive of mucinous precursor lesions of ductal adenocarcinoma.
- Author
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Ryu JK, Matthaei H, Dal Molin M, Hong SM, Canto MI, Schulick RD, Wolfgang C, Goggins MG, Hruban RH, Cope L, and Maitra A
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Pancreatic Cyst diagnosis, Pancreatic Neoplasms diagnostic imaging, Prospective Studies, Ultrasonography, Biomarkers, Tumor analysis, Cyst Fluid chemistry, Cystadenocarcinoma, Mucinous diagnosis, MicroRNAs analysis, Pancreatic Cyst metabolism, Pancreatic Neoplasms diagnosis
- Abstract
Background: Biomarkers for the diagnostic classification of pancreatic cysts are urgently needed. Deregulated microRNA (miRNAs) expression is widespread in pancreatic cancer. We assessed whether aberrant miRNAs in pancreatic cyst fluid could be used as potential biomarkers for cystic precursor lesions of pancreatic cancer., Methods: Cyst fluid specimens were prospectively collected from 40 surgically resected pancreatic cysts, and small RNAs were extracted. The 'mucinous' cohort included 14 intraductal papillary mucinous neoplasms (including 3 with an associated adenocarcinoma) and 10 mucinous cystic neoplasms; the 'nonmucinous' cohort included 11 serous cystadenomas and 5 other benign cysts. Quantitative reverse transcription PCR was performed for five miRNAs (miR-21, miR-155, miR-221, miR-17-3p, miR-191), which were previously reported as overexpressed in pancreatic adenocarcinomas., Results: Significantly higher expression of miR-21, miR-221, and miR-17-3p was observed in the mucinous versus nonmucinous cysts (p < 0.01), with the mean relative fold differences being 7.0-, 7.9-, and 5.4-fold, respectively. Receiver operating characteristic curves demonstrated the highest median area under the curve for miR-21, with a median specificity of 76%, at a sensitivity of 80%., Conclusion: This pilot study demonstrates that profiling miRNAs in pancreatic cyst fluid samples is feasible and can yield potential biomarkers for the classification of cystic lesions of the pancreas. and IAP., (Copyright © 2011 S. Karger AG, Basel.)
- Published
- 2011
- Full Text
- View/download PDF
21. Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms.
- Author
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Haab BB, Porter A, Yue T, Li L, Scheiman J, Anderson MA, Barnes D, Schmidt CM, Feng Z, and Simeone DM
- Subjects
- Biopsy, Fine-Needle, Cystadenocarcinoma chemistry, Cystadenoma, Mucinous chemistry, Cystadenoma, Serous chemistry, Glycosylation, Humans, Image Processing, Computer-Assisted, Logistic Models, Mucin 5AC analysis, Pancreatic Neoplasms chemistry, Pancreatic Pseudocyst chemistry, Pancreatic Pseudocyst diagnosis, Protein Array Analysis, Sensitivity and Specificity, Biomarkers, Tumor analysis, Carcinoembryonic Antigen analysis, Cyst Fluid chemistry, Mucins analysis, Pancreatic Neoplasms diagnosis
- Abstract
Background and Aims: Cystic lesions of the pancreas are increasingly being recognized due to the widespread use of high resolution abdominal imaging. Since certain cyst types are precursors to invasive cancer, this situation presents an opportunity to intervene prior to malignant progression. Effective implementation of that strategy has been hampered by difficulties in clearly distinguishing cystic lesions with no malignant potential from those with malignant potential. Here we explored whether glycosylation variants on specific proteins in cyst fluid samples could serve as biomarkers to aid in this diagnosis., Methods: We used a novel antibody-lectin sandwich microarray method to measure the protein expression and glycosylation of mucin (MUC)1, MUC5AC, MUC16, carcinoembryonic antigen, and other proteins implicated in pancreatic neoplasia in cyst fluid samples. Fifty-three cyst fluid samples were obtained from patients with mucinous cystic neoplasms (n=17), intraductal papillary mucinous neoplasms (n=15), serous cystadenomas (n=12), or pseudocysts (n=9), with confirmation of histologic diagnosis at surgical resection., Results: The detection of a glycan variant on MUC5AC using the lectin wheat-germ agglutinin discriminated mucin-producing cystic tumors (mucinous cystic neoplasms+intraductal papillary mucinous neoplasms) from benign cystic lesions (serous cystadenomas+pseudocysts) with a 78% sensitivity at 80% specificity, and when used in combination with cyst fluid CA 19-9 gave a sensitivity of 87% at 86% specificity. These biomarkers performed better than cyst fluid carcinoembryonic antigen (37%/80% sensitivity/specificity)., Conclusions: These results demonstrate the value of glycan variants for biomarker discovery and suggest that these biomarkers could greatly enhance the accuracy of differentiating pancreatic cystic tumors. Validation studies will be required to determine the clinical value of these markers.
- Published
- 2010
- Full Text
- View/download PDF
22. GSTP1-1 in ovarian cyst fluid and disease outcome of patients with ovarian cancer.
- Author
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Kolwijck E, Zusterzeel PL, Roelofs HM, Hendriks JC, Peters WH, and Massuger LF
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Cyst Fluid chemistry, Cyst Fluid enzymology, Disease-Free Survival, Enzyme-Linked Immunosorbent Assay, Female, Glutathione S-Transferase pi analysis, Humans, Kaplan-Meier Estimate, Middle Aged, Neoplasm Staging, Neoplasms, Glandular and Epithelial mortality, Neoplasms, Glandular and Epithelial pathology, Ovarian Cysts chemistry, Ovarian Cysts pathology, Ovarian Neoplasms mortality, Ovarian Neoplasms pathology, Prognosis, Treatment Outcome, Biomarkers, Tumor analysis, Glutathione S-Transferase pi metabolism, Neoplasms, Glandular and Epithelial enzymology, Ovarian Cysts enzymology, Ovarian Neoplasms enzymology
- Abstract
Detoxification enzymes, especially glutathione S-transferase P1-1 (GSTP1-1), have been implicated in resistance to platinum-based chemotherapy. We studied GSTP1-1 levels in ovarian cyst fluid (oCF), obtained during surgery before chemotherapy, of patients with epithelial ovarian cancer and clinical outcomes were correlated. GSTP1-1 was determined by ELISA in oCF of 56 patients with epithelial ovarian cancer and 109 noncancer controls (21 borderline and 88 benign ovarian tumors). Differences in median GSTP1-1 between clinicopathologic subgroups were studied using Mann-Whitney U and Kruskal Wallis tests. Differences in disease-free (DFS) and overall survival (OS) between groups were analyzed by applying Kaplan-Meyer estimates and log-rank tests. Univariate and multivariate analysis were done using Cox proportional hazard model. Significantly higher levels of GSTP1-1 were found in the oCF of malignant (median, 383; range, 10-32,695 ng/mL) compared with benign (median, 20; range, 0-1,128 ng/mL) ovarian tumors (P < 0.01). Significantly higher GSTP1-1 levels were found in patients with advanced International Federation of Gynaecologists and Obstetricians stage (P = 0.01), high-grade tumors (P = 0.44), and/or high levels of preoperative CA 125 (P = 0.01). Of patients who received chemotherapy (stage, >or=Ic; n = 30), high GSTP1-1 levels were significantly associated with a poor DFS and OS (log-rank P = 0.047 and P = 0.033, respectively). International Federation of Gynaecologists and Obstetricians stage was the only independent predictor for DFS. GSTP1-1 was the only independent predictor for OS.
- Published
- 2009
- Full Text
- View/download PDF
23. The level of carcinoembryonic antigen and the presence of mucin as predictors of cystic pancreatic mucinous neoplasia.
- Author
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Shami VM, Sundaram V, Stelow EB, Conaway M, Moskaluk CA, White GE, Adams RB, Yeaton P, and Kahaleh M
- Subjects
- Aged, Analysis of Variance, Biopsy, Fine-Needle, Carcinoma, Pancreatic Ductal chemistry, Carcinoma, Pancreatic Ductal pathology, Cyst Fluid chemistry, Cyst Fluid cytology, Cystadenocarcinoma, Mucinous chemistry, Cystadenocarcinoma, Mucinous pathology, Endosonography, Female, Humans, Male, Middle Aged, Pancreatic Cyst chemistry, Pancreatic Cyst pathology, Pancreatic Neoplasms chemistry, Pancreatic Neoplasms pathology, Predictive Value of Tests, Prospective Studies, Sensitivity and Specificity, Ultrasonography, Interventional, Virginia, Biomarkers, Tumor analysis, Carcinoembryonic Antigen analysis, Carcinoma, Pancreatic Ductal diagnosis, Cystadenocarcinoma, Mucinous diagnosis, Mucins analysis, Pancreatic Cyst diagnosis, Pancreatic Neoplasms diagnosis
- Abstract
Objectives: Characterization of pancreatic cysts using endoscopic ultrasound-guided fine-needle aspiration includes cytological interpretation and chemical analysis. We prospectively analyzed the contribution of carcinoembryonic antigen (CEA) and cytological identification of extracellular mucin as predictors of mucinous neoplasia and malignancy., Methods: From January 2003 to October 2005, all patients referred to the University of Virginia with cystic lesions of the pancreas underwent endoscopic ultrasound-guided fine-needle aspiration with cytological evaluation and CEA level analysis. Data were collected prospectively and confirmed by resection or tissue biopsy. Univariate and multivariate analyses were performed on the following variables with regard to their ability to predict mucinous neoplasia: age (<55 or >55 years), sex, CEA level (<300 or >300 ng/mL), and cytological appreciation of extracellular mucin (positive or negative). P values less than 0.05 were considered significant., Results: A total of 43 patients were included in this study. There were 19 men and 24 women with a mean age of 63 +/- 14 years. The only complication was pancreatitis secondary to cyst leak in one patient. Multivariate analysis confirmed CEA level greater than 300 ng/mL (P= 0.007) and the identification of mucin (P < 0.001) as significant predictors., Conclusions: With pancreatic cyst fluid analysis, the strongest predictor of mucinous neoplasia is the presence of identifiable mucin, followed by a CEA level greater than 300 ng/mL. The workup of cystic lesions of the pancreas should include chemical analysis for the CEA level and cytological examination with particular attention to extracellular mucin.
- Published
- 2007
- Full Text
- View/download PDF
24. Cyst fluid analysis obtained by EUS-guided FNA in the evaluation of discrete cystic neoplasms of the pancreas: a prospective single-center experience.
- Author
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Linder JD, Geenen JE, and Catalano MF
- Subjects
- Adult, Aged, Amylases analysis, Analysis of Variance, CA-19-9 Antigen analysis, Carcinoembryonic Antigen analysis, Cystadenocarcinoma chemistry, Cystadenoma, Mucinous chemistry, Cystadenoma, Serous chemistry, Female, Humans, Lipase analysis, Male, Middle Aged, Mucins analysis, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms pathology, Pancreatic Pseudocyst diagnostic imaging, Pancreatic Pseudocyst pathology, Prospective Studies, Retrospective Studies, Sensitivity and Specificity, Viscosity, Wisconsin, Biomarkers, Tumor analysis, Biopsy, Fine-Needle methods, Cyst Fluid chemistry, Endosonography, Pancreatic Neoplasms chemistry, Pancreatic Pseudocyst chemistry
- Abstract
Background: Accurate assessment of pancreatic cystic neoplasms is imperative before selecting available treatment options, such as surgical resection, drainage, or conservative therapy. Available modalities, CT and magnetic resonance imaging, have been inconsistent in diagnosis. Reports involving EUS and cyst fluid analysis have been encouraging, including studies of EUS features and/or cyst fluid analysis, which may differentiate pancreatic cystic neoplasms., Objective: To retrospectively determine cyst fluid characteristics that differentiate cystic neoplasms., Design: Patient evaluation included (1) EUS features (reported elsewhere) and (2) cyst fluid analysis (carcinoembryonic antigen [CEA], carbohydrate antigen 19-9 [CA 19-9], amylase and lipase, viscosity [VIS], mucin stain, and cytology). Exclusion criteria included the following: intraductal papillary mucinous tumor lesions, bloody cyst aspirate, neuroendocrine tumors, and patients without surgical histopathology., Setting: Pancreatic Biliary Center, St Luke's Medical Center, Milwaukee, Wisconsin., Patients: A total of 102 patients (60 women, 42 men; age, 23-76 years) presented for evaluation of pancreatic cystic neoplasm; 71 underwent surgical resection., Results: Seventy-one of 102 patients who underwent surgery presented the following histopathologic correlates: 23 pseudocysts (PC), 13 serous cystadenoma (SCyA), 21 mucinous cystadenoma (MCyA), and 14 mucinous cystadenocarcinoma (MCyA-CA). Cyst fluid analysis of these patients showed the following: VIS was lower in PC (mean, 1.3) and SCyA (1.27) when compared with MCyA (1.84) and MCyA-CA (1.9). All mucinous neoplasms had VIS >1.6, whereas only 2 mucinous cystic neoplasms (MCN) had VIS = 1.6 (both PC). The CEA level was significantly higher in MCyA (adenoma [878 ng/mL], carcinoma [27,581 ng/mL]) vs PC (189 ng/mL), and SCyA (121 ng/mL). Amylase levels were higher in PC (7210 U/L) compared with cystic neoplasm (SCyA, 679 U/L; MCyA, 1605 U/L; MCyA-CA, 569 U/L)., Conclusions: Differential diagnosis of pancreatic cystic neoplasm is significantly enhanced by cyst fluid analysis. Elevated CEA (> or =480 ng/mL) and VIS (>1.6) accurately predict MCN from SCyA and PC. Malignant from benign MCN can be differentiated by CEA levels > or =6000 ng/mL.
- Published
- 2006
- Full Text
- View/download PDF
25. The mistletoe and cyst-fluid analysis: a sticky insight.
- Author
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Brugge WR
- Subjects
- Amylases analysis, CA-19-9 Antigen analysis, Carcinoembryonic Antigen analysis, Cystadenocarcinoma chemistry, Cystadenoma, Mucinous chemistry, Cystadenoma, Serous chemistry, Humans, Lipase analysis, Mucins analysis, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms pathology, Pancreatic Pseudocyst diagnostic imaging, Pancreatic Pseudocyst pathology, Viscosity, Biomarkers, Tumor analysis, Biopsy, Fine-Needle methods, Cyst Fluid chemistry, Endosonography, Pancreatic Neoplasms chemistry, Pancreatic Pseudocyst chemistry
- Published
- 2006
- Full Text
- View/download PDF
26. Apocrine cysts of the breast: biomarkers, origin, enlargement, and relation with cancer phenotype.
- Author
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Celis JE, Gromov P, Moreira JM, Cabezón T, Friis E, Vejborg IM, Proess G, Rank F, and Gromova I
- Subjects
- Adult, Aged, Aged, 80 and over, Apocrine Glands metabolism, Breast metabolism, Breast Neoplasms metabolism, Cyst Fluid chemistry, Cysts metabolism, Cytokines metabolism, Female, Humans, Hydroxymethylglutaryl CoA Reductases metabolism, Hydroxyprostaglandin Dehydrogenases metabolism, Middle Aged, Neoplasm Proteins analysis, Neoplasm Proteins chemistry, Neoplasm Staging, Patient Selection, Phenotype, Proteome analysis, Proteome chemistry, Reproducibility of Results, Apocrine Glands pathology, Biomarkers, Tumor analysis, Breast pathology, Breast Neoplasms pathology, Cysts pathology
- Abstract
Up to one-third of women aged 30-50 years have cysts in their breasts and are presumed to be at increased risk of developing breast cancer. Here we present an extensive proteomic and immunohistochemistry (IHC) study of breast apocrine cystic lesions aimed at generating specific biomarkers and elucidating the relationship, if existent, of apocrine cysts with cancer phenotype. To this end we compared the expression profiles of apocrine macrocysts obtained from mastectomies from high risk cancer patients with those of cancerous and non-malignant mammary tissue biopsies collected from the same patients. We identified two biomarkers, 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase, that were expressed specifically by apocrine type I cysts as well as by apocrine metaplastic cells in type II microcysts, terminal ducts, and intraductal papillary lesions. No expression of these markers was observed in non-malignant terminal ductal lobular units, type II flat cysts, stroma cells, or fat tissue as judged by IHC analysis of matched non-malignant tissue samples collected from 93 high risk patients enrolled in our cancer program. IHC analysis of the corresponding 93 primary tumors indicated that most apocrine changes have little intrinsic malignant potential, although some may progress to invasive apocrine cancer. None of the apocrine lesions examined, however, seemed to be a precursor of invasive ductal carcinomas, which accounted for 81% of the tumors analyzed. Our studies also provided some insight into the origin, development, and enlargement of apocrine cysts in mammary tissue. The successful identification of differentially expressed proteins that characterize specific steps in the progression from early benign lesions to apocrine cancer opens a window of opportunity for designing and testing new approaches for pharmacological intervention, not only in a therapeutic setting but also for chemoprevention, to inhibit cyst development as both 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase are currently being targeted for chemoprevention strategies in various malignancies.
- Published
- 2006
- Full Text
- View/download PDF
27. Cyst fluid tumor-associated trypsin inhibitor may be helpful in the differentiation of cystic pancreatic lesions.
- Author
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Räty S, Sand J, Alfthan H, Haglund C, and Nordback I
- Subjects
- Adult, Aged, Aged, 80 and over, Chorionic Gonadotropin analysis, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Biomarkers, Tumor analysis, Cyst Fluid chemistry, Pancreatic Cyst diagnosis, Pancreatic Neoplasms diagnosis, Trypsin Inhibitor, Kazal Pancreatic analysis
- Abstract
In clinical practice it is important to differentiate pseudocysts from cystic pancreatic tumors, especially potentially malignant mucinous cystic tumors. We investigated three new markers-tumor-associated trypsin inhibitor (TATI) and the free alpha and beta subunits of human choriogonadotropin (hCGalpha and hCGbeta, respectively)-in the cyst fluid of patients with cystic pancreatic lesions and compared the concentrations of these markers to those of carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 125, CA 15-3, alpha-fetoprotein, and tissue polypeptide antigen in order to distinguish benign cysts from malignant cysts. Between 1995 and 2001, a total of 34 patients operated on for cystic pancreatic lesions at Tampere University Hospital were included. Cyst fluid was aspirated at operation and stored at -70 C. The histologic diagnosis was pseudocyst in 23 patients, serous cystadenoma (SCA) in four patients, benign mucinous cystadenoma (MCA) in four patients, cystic papillary neoplasm (CPN) in one patient, glucagonoma in one patient, and malignant endocrine islet cell carcinoma (EC) in one patient. Significantly higher concentrations of TATI were found in patients with MCA and EC (2239 +/- 149 microg/L [mean +/- SEM]) than in patients with pseudocyst (55 +/- 29 microg/L; P=0.001) and in patients with SCA (36 +/- 23 microg/L; P=0.01). The patient with CPN and the patient with glucagonoma had relatively low levels of TATI (30.7 and 46.5 microg/L). Mean CEA was higher in patients with MCA compared to those with pseudocysts (19,993 +/- 9418 vs. 53 +/- 20 microg/L, P=0.002) and SCA (0.4 +/- 0.1 microg/L; P=0.02), but in the patient with malignant EC, the patient with CPN, and the patient with glucagonoma, CEA was normal. HCGalpha, hCGbeta, CA 19-9, CA 242, CA 125, CA 15-3, alpha fetoprotein, and tissue polypeptide antigen could not distinguish between MCA vs. pseudocyst or SCA, because both normal and elevated values were seen in all groups. To our knowledge, this is the first time that TATI has been quantitated in the cyst fluid of patients with cystic pancreatic lesions. It appears to be a potential marker in the differential diagnosis of benign from malignant cystic pancreatic lesions.
- Published
- 2004
- Full Text
- View/download PDF
28. Tumor marker levels in post-chemotherapy cystic masses: clinical implications for patients with germ cell tumors.
- Author
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Beck SD, Patel MI, and Sheinfeld J
- Subjects
- Cyst Fluid chemistry, Cysts surgery, Humans, Lymph Node Excision, Male, Retroperitoneal Space, Testicular Diseases diagnosis, Testicular Diseases surgery, Biomarkers, Tumor analysis, Chorionic Gonadotropin analysis, Cysts chemistry, Cysts diagnosis, Germinoma drug therapy, Testicular Neoplasms drug therapy, alpha-Fetoproteins analysis
- Abstract
Purpose: Increased tumor markers after induction chemotherapy for patients with germ cell tumor usually represent systemic disease and consequently second line chemotherapy is instituted, while retroperitoneal lymph node dissection (RPLND) is reserved for patients with marker normalization. We report the concentration of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in the fluid of post-chemotherapy cystic masses to evaluate this as a potential source for serum marker elevation., Materials and Methods: From March 2002 to December 2002, 11 consecutive patients with post-chemotherapy cystic masses underwent RPLND. Following resection, aspirated fluid was analyzed for AFP and HCG. Only 5 post-chemotherapy RPLNDs were performed in patients with increased serum tumor markers, including the 3 patients in our study. Patients with increasing tumor markers and/or multifocal disease with noncystic residual masses after induction chemotherapy underwent salvage chemotherapy despite teratomatous elements in the primary tumor., Results: All 11 patients had teratoma in the orchiectomy specimen and retroperitoneum, including one with malignant transformation. Cystic fluid markers were increased in all patients, 9 of 9 with HCG (range 7.0 to 6,880) and 9 of 11 with AFP (27.5 to 521.2). Two patients with an increased serum AFP before surgery (47.9 and 31.6) had cyst levels of 73.5 and 790.4 respectively. Both serum markers normalized postoperatively. One patient with increased pre-RPLND serum HCG (11.6) had a cyst level of 233. HCG continued to increase postoperatively and the patient died of disease. The remaining 10 patients remain disease free., Conclusion: Fluid from cystic teratoma contains variably elevated levels of HCG and AFP in all patients and appears to be independent of serum marker level or pathology. It is possible that a "slow leak" of fluid from cystic teratoma may explain elevated serum markers in selected patients with teratoma and thus may potentially avoid second line chemotherapy.
- Published
- 2004
- Full Text
- View/download PDF
29. Role of tumor markers in the diagnosis of cystic and intraductal neoplasms.
- Author
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Hammel P
- Subjects
- Antigens, Tumor-Associated, Carbohydrate analysis, CA-19-9 Antigen analysis, Carcinoembryonic Antigen analysis, Cyst Fluid chemistry, Cystadenocarcinoma, Mucinous blood, Cystadenocarcinoma, Mucinous diagnosis, Cystadenoma, Mucinous blood, Cystadenoma, Mucinous diagnosis, Cystadenoma, Serous blood, Cystadenoma, Serous diagnosis, Diagnosis, Differential, Discriminant Analysis, Humans, Mucin-1 analysis, Pancreatic Cyst blood, Pancreatic Neoplasms blood, Papilloma, Intraductal blood, Papilloma, Intraductal diagnosis, Reproducibility of Results, Sensitivity and Specificity, Biomarkers, Tumor analysis, Pancreatic Cyst diagnosis, Pancreatic Neoplasms diagnosis
- Abstract
Despite recent advances in imaging procedures, the correct diagnosis of cystic lesions of the pancreas is lacking in about one third of cases. Cyst fluid analysis can help in the differential diagnosis, particularly in patients with unilocular or paucilocular lesions, thus precluding unjustified resection in patients with benign cystic lesions of the pancreas. Although use of cystic fluid marker analysis is helpful in several situations, it is crucial to carefully evaluate the clinical context with appraisal of patient's demographics, clinical symptoms, and morphologic data. A multidisciplinary approach is advised and should improve the overall diagnostic performance and lead to better management strategies in patients presenting with such tumors of the pancreas.
- Published
- 2002
- Full Text
- View/download PDF
30. Gonadotropin levels in ovarian cyst fluids: a predictor of malignancy?
- Author
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Krämer S, Leeker M, and Jäger W
- Subjects
- Biomarkers, Tumor blood, Cystadenoma, Serous chemistry, Cystadenoma, Serous diagnosis, Female, Follicle Stimulating Hormone blood, Humans, Luteinizing Hormone blood, Menopause, Biomarkers, Tumor analysis, Cyst Fluid chemistry, Follicle Stimulating Hormone analysis, Luteinizing Hormone analysis, Ovarian Cysts chemistry, Ovarian Neoplasms diagnosis
- Abstract
Gonadotropins can stimulate ovarian cancer growth in cell cultures. Corresponding LH/hCG receptors have been demonstrated in ovarian cancer. However, reduction of elevated serum gonadotropins by GnRH analogs in ovarian cancer patients did not lead to growth restriction, which means that serum levels of gonadotropins may not play the most important role in ovarian cancer. We therefore analyzed the LH and FSH concentrations in cyst fluids of ovarian cancer. Patients with preoperatively diagnosed cystic ovarian tumors were eligible for the study. Serum samples of the patients were obtained during surgery, while the fluids within the cysts were aspirated after surgical removal of the tumor. FSH and LH levels in serum and cyst fluids were measured using single antibody EIA (Boehringer Mannheim GmbH, Germany). Cyst fluids and sera of 108 patients were evaluated. While there were no significant differences in the FSH and LH serum concentrations, highly significant differences in the FSH and LH levels in cyst fluids were found. Only cancer cysts contained FSH and LH, while the corresponding concentrations in benign cysts were always below the measuring range of the assays. This clear division between high gonadotropin levels in cysts of serous ovarian cancer and low or absent concentrations in benign ovarian tumors further supports the hypothesis that FSH and LH may play a role in ovarian cancer; however, explanations for this surprising finding are still lacking.
- Published
- 1998
31. [Intracystic biochemical and tumor markers in a case of pseudo-papillary and solid tumor of the pancreas: pay attention to the interpretation].
- Author
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Lévy P, Perniceni T, and Gayet B
- Subjects
- Adult, Biomarkers chemistry, Cystadenoma, Papillary diagnosis, Diagnosis, Differential, Female, Humans, Pancreatic Neoplasms diagnosis, Biomarkers, Tumor analysis, Cyst Fluid chemistry, Cystadenoma, Papillary chemistry, Pancreatic Neoplasms chemistry
- Published
- 1998
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