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Miquel Porta - One of the best experts on this subject based on the ideXlab platform.
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Relationships of hepatic and Pancreatic biomarkers with the cholestatic syndrome and tumor stage in Pancreatic Cancer.
Biomarkers : biochemical indicators of exposure response and susceptibility to chemicals, 2012Co-Authors: Miquel Porta, Núria Malats, Luisa Guarner, José Pumarega, Ricard Solà, Francisco X. RealAbstract:We analyzed relationships of hepatic and Pancreatic biomarkers with the cholestatic syndrome and tumor stage in Exocrine Pancreatic Cancer (N = 183). Information on laboratory tests and on signs and symptoms was obtained from medical records and patient interviews. Bilirubin, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT) and alkaline phosphatase were lower in tumor stage IV. The association was due to the relationship between cholestatic syndrome and earlier presentation of patients. There was no association between hepatic biomarkers and stage when adjusting by cholestatic syndrome. Relationships of hepatic and Pancreatic biomarkers with Pancreatic symptoms and tumor stage must be controlled in “-omics” and other studies using biomarkers.
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How useful is it clinically to analyse the K-ras mutational status for the diagnosis of Exocrine Pancreatic Cancer? A systematic review and meta-analysis.
European journal of clinical investigation, 2011Co-Authors: Lucy A. Parker, Tomás Undabeytia López, Blanca Lumbreras, Ildefonso Hernández-aguado, Miquel PortaAbstract:Eur J Clin Invest 2011; 41 (7): 793–805 Abstract Background More clinically meaningful diagnostic tests are needed in Exocrine Pancreatic Cancer (EPC). K-ras mutations are the most frequently acquired genetic alteration in EPC. We analysed the diagnostic utility of detecting K-ras mutations through a systematic analysis of the literature. Methods We searched PubMed using suitable medical subject headings and text words. Original research articles that evaluated the diagnostic accuracy of detecting K-ras mutations for diagnosis of EPC were selected. Two investigators independently extracted data from each study regarding the methodology used, the methodological quality of the study, the diagnostic accuracy reported and the authors’ conclusions about clinical applicability of the test. Combined estimates for the sensitivity and specificity of K-ras were determined using bivariate meta-analysis; heterogeneity was explored using meta-regression. Results We assessed 34 studies from 30 published articles. The research reports were prone to numerous methodological biases and often lacked vital information for assessing external validity. The sensitivity of detecting K-ras status ranged from 0% through 100%, and the specificity from 58% through 100%. Diagnostic accuracy was highest when cytohistological samples were used: sensitivity and specificity were 76·5% (66·7–84·2) and 91·8% (87·6–94·1), respectively. Studies conducted in a clinically relevant population observed lower accuracy than case–control designs (68·4% vs. 82·7%). Conclusions Because of the numerous methodological limitations of studies, the utility of analysing K-ras mutations for the diagnosis of EPC remains unknown. Flaws in diagnostic biomarkers with well-established biological properties, as K-ras, become even more relevant when the promises of ‘personalized medicine’ are pondered.
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Clinical validity of detecting K-ras mutations for the diagnosis of Exocrine Pancreatic Cancer: a prospective study in a clinically-relevant spectrum of patients.
European journal of epidemiology, 2011Co-Authors: Lucy A. Parker, Alfredo Carrato, Miquel Porta, Luisa Guarner, Juli Rifà, Josep M. Corominas, Tomás Undabeytia López, Blanca Lumbreras, Ildefonso Hernández-aguado, Esteve FernándezAbstract:The diagnostic utility of detecting K-ras mutations for the diagnosis of Exocrine Pancreatic Cancer (EPC) has not been properly studied, and few reports have analysed a clinically relevant spectrum of patients. The objective was to evaluate the clinical validity of detecting K-ras mutations in the diagnosis of EPC in a large sample of clinically relevant patients. We prospectively identified 374 patients in whom one of the following diagnoses was suspected at hospital admission: EPC, chronic pancreatitis, Pancreatic cysts, and Cancer of the extrahepatic biliary system. Mutations in the K-ras oncogene were analysed by PCR and artificial RFLP in 212 patients. The sensitivity and specificity of the K-ras mutational status for the diagnosis of EPC were 77.7% (95% CI: 69.2–84.8) and 78.0% (68.1–86.0), respectively. The diagnostic accuracy was hardly modified by sex and age. In patients with either mutated K-ras or CEA > 5 ng/ml, the sensitivity and specificity were 81.0% (72.9–87.6) and 62.6% (72.9–87.6), respectively. In patients with mutated K-ras and CEA > 5 ng/ml the sensitivity was markedly reduced. In comparisons with a variety of non-EPC patient groups sensitivity and specificity were both always greater than 75%. In this clinically relevant sample of patients the sensitivity and specificity of K-ras mutations were not sufficiently high for independent diagnostic use. However, it seems premature to rule out the utility of K-ras analysis in conjunction with other genetic and ‘omics’ technologies.
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Clinical validity of detecting K- mutations for the diagnosis of Exocrine Pancreatic Cancer: a prospective study in a clinically-relevant spectrum of patients
European Journal of Epidemiology, 2011Co-Authors: Lucy A. Parker, Alfredo Carrato, Miquel Porta, Luisa Guarner, Juli Rifà, Josep M. Corominas, Blanca Lumbreras, Tomàs López, Ildefonso Hernández-aguado, Esteve FernándezAbstract:The diagnostic utility of detecting K- mutations for the diagnosis of Exocrine Pancreatic Cancer (EPC) has not been properly studied, and few reports have analysed a clinically relevant spectrum of patients. The objective was to evaluate the clinical validity of detecting K- mutations in the diagnosis of EPC in a large sample of clinically relevant patients. We prospectively identified 374 patients in whom one of the following diagnoses was suspected at hospital admission: EPC, chronic pancreatitis, Pancreatic cysts, and Cancer of the extrahepatic biliary system. Mutations in the K- oncogene were analysed by PCR and artificial RFLP in 212 patients. The sensitivity and specificity of the K- mutational status for the diagnosis of EPC were 77.7% (95% CI: 69.2-84.8) and 78.0% (68.1-86.0), respectively. The diagnostic accuracy was hardly modified by sex and age. In patients with either mutated K- or CEA > 5 ng/ml, the sensitivity and specificity were 81.0% (72.9-87.6) and 62.6% (72.9-87.6), respectively. In patients with mutated K- and CEA > 5 ng/ml the sensitivity was markedly reduced. In comparisons with a variety of non-EPC patient groups sensitivity and specificity were both always greater than 75%. In this clinically relevant sample of patients the sensitivity and specificity of K- mutations were not sufficiently high for independent diagnostic use. However, it seems premature to rule out the utility of K- analysis in conjunction with other genetic and 'omics' technologies.
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Relationships between occupational history and serum concentrations of organochlorine compounds in Exocrine Pancreatic Cancer
Occupational and environmental medicine, 2010Co-Authors: Magda Bosch De Basea, Juan Alguacil, Miquel Porta, Elisa Puigdomènech, Magda Gasull, Jose Antonio Garrido, Tomás Undabeytia LópezAbstract:Background Previous studies investigating associations between occupational history and risk of Exocrine Pancreatic Cancer (EPC) did not use biomarkers of exposure. The only two studies that measured internal concentrations of organochlorine compounds (OCs) in EPC did not analyse their relationship with occupation. Objective To analyse the relationship between occupational history and blood concentrations of seven OCs in patients with EPC. Methods Incident cases of EPC were prospectively identified, and during hospital admission were interviewed face-to-face on occupational history and life-style factors (n=135). Occupations were coded according to the International Standard of Occupations 1988. Some occupational exposures were also assessed with the Finnish job-exposure matrix (Finjem). Serum concentrations of OCs were analysed by high-resolution gas chromatography with electron-capture detection. Results Craftsmen and related trades workers had significantly higher concentrations of polychlorinated biphenyl (PCB) congeners 138, 153 and 180. Years worked in agriculture did not influence concentrations of p,p9-DDT, p,p9-DDE, hexachlorobenzene or β-hexachlorocyclohexane. Subjects who ever worked in agriculture had lower concentrations of PCBs (all p Conclusions Certain occupations were associated with higher concentrations of PCBs, suggesting that these compounds may account for some increased risks found in previous studies. The lack of association between work in agriculture and concentrations of OC pesticides is consistent with occupation playing a lesser role than diet in influencing OC concentrations. Occupational studies on the relationships among exposure to industrial agents and EPC risk may need to consider adjusting for exposure to PCBs.
Núria Malats - One of the best experts on this subject based on the ideXlab platform.
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Relationships of hepatic and Pancreatic biomarkers with the cholestatic syndrome and tumor stage in Pancreatic Cancer.
Biomarkers : biochemical indicators of exposure response and susceptibility to chemicals, 2012Co-Authors: Miquel Porta, Núria Malats, Luisa Guarner, José Pumarega, Ricard Solà, Francisco X. RealAbstract:We analyzed relationships of hepatic and Pancreatic biomarkers with the cholestatic syndrome and tumor stage in Exocrine Pancreatic Cancer (N = 183). Information on laboratory tests and on signs and symptoms was obtained from medical records and patient interviews. Bilirubin, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT) and alkaline phosphatase were lower in tumor stage IV. The association was due to the relationship between cholestatic syndrome and earlier presentation of patients. There was no association between hepatic biomarkers and stage when adjusting by cholestatic syndrome. Relationships of hepatic and Pancreatic biomarkers with Pancreatic symptoms and tumor stage must be controlled in “-omics” and other studies using biomarkers.
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The relative influence of diet and serum concentrations of organochlorine compounds on K-ras mutations in Exocrine Pancreatic Cancer.
Chemosphere, 2010Co-Authors: Magda Gasull, Jesús Vioque, Miquel Porta, Joan O. Grimalt, Elisa Puigdomènech, Eva Morales, José Pumarega, Magda Bosch De Basea, Núria MalatsAbstract:Abstract Background In Exocrine Pancreatic Cancer (EPC) mechanistic relationships may exist among some organochlorine compounds (OCs) and mutations in the K- ras oncogene, as well as among the latter and dietary factors. Objective To analyze (1) the relationship between food intake and serum concentrations of OCs in EPC patients and (2) the relative influence of food and OCs on the frequency of K- ras mutations in EPC. Patients and methods Incident cases of EPC were prospectively identified, and interviewed face-to-face during hospital admission ( N = 135 patients with data on OCs and diet, and N = 97 with additional information on K- ras status). OCs were measured by high-resolution gas chromatography with electron-capture detection. Results Consumption of milk and other dairy products was positively associated with concentrations of p,p′-DDT, PCB 138 and PCB 153 (log-transformed β s = 0.652, 0.588 and 0.317, respectively; all p ras . By contrast, after adjusting by consumption of dairy products, patients with the highest concentrations of p,p′-DDT and some PCBs remained more likely to have a K- ras -mutated EPC than patients with lower concentrations (OR for upper tertile of PCB 138 = 5.5, 95% CI: 1.3–23.4). Conclusions Dairy products were a source of OCs. The association between dairy products and K- ras mutations was not independent of OCs. By contrast, the association between OCs and K- ras was not confounded by dairy products. OCs may be more likely to contribute to the occurrence of K- ras mutations than nutrients contained in dairy products.
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the influence of lipid and lifestyle factors upon correlations between highly prevalent organochlorine compounds in patients with Exocrine Pancreatic Cancer
Environment International, 2007Co-Authors: Miquel Porta, Núria Malats, Laura Ruiz, Manuel Jariod, Joan O. Grimalt, Esther Marco, Tomás Undabeytia López, Elisa Puigdomènech, Ekhine ZumetaAbstract:We aimed to analyse the influence of cholesterol and triglycerides, and of tobacco, coffee and alcohol consumption upon correlations between serum concentrations of organochlorine compounds (OCs) in patients with Exocrine Pancreatic Cancer (EPC). Incident cases of EPC diagnosed in eastern Spain were prospectively identified (N=144). OCs were analysed by high-resolution gas chromatography with electron-capture detection. A strong correlation was observed between hexachlorobenzene (HCB) and beta-hexachlorocyclohexane (beta-HCH) (Spearman's rho=0.758). beta-HCH showed rho>0.4 with p,p'-DDT, p,p'-DDE, PCB138 and PCB153 (all p<0.001). Some correlations among compounds were slightly affected by tobacco, coffee or alcohol consumption. We observed a striking diversity of correlation patterns by strata of cholesterol and triglycerides. Most correlations were higher in the lowest category of triglycerides than in the lowest category of cholesterol. Most coefficients above 0.7 were seen in the lowest category of triglycerides (e.g., OC pairs p,p'-DDT and HCB, p,p'-DDT and beta-HCH, p,p'-DDE and beta-HCH, or HCB and beta-HCH). Correlations among OCs may be stronger when concentrations of triglycerides are low than when they are high. This is compatible with a dilution in the early phases of Cancer and with a concentration effect as triglycerides become lower in the advanced phases of the disease.
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Food and nutrient intakes and K-ras mutations in Exocrine Pancreatic Cancer
Journal of epidemiology and community health, 2007Co-Authors: Eva Morales, Jesús Vioque, Miquel Porta, Núria Malats, Tomás Undabeytia López, Marta Crous-bou, Michelle A. Mendez, José Pumarega, Joy Ngo, Juli RifàAbstract:Background: No studies have investigated the relation between K- ras mutations and dietary factors in Exocrine Pancreatic Cancer (EPC), and fewer than 10 studies have done so in other neoplasms. Patients and Methods: Incident cases of EPC were prospectively identified, and interviewed face-to-face during hospital admission. Food and nutrient intakes were measured with a food frequency questionnaire. Logistic regression was used to compare EPC cases (n = 107) with and without K- ras mutations (case-case study). Results: K- ras mutations were more common among daily consumers of milk and other dairy products than among non-daily consumers: the odds ratio adjusted by total energy, age, sex, smoking, alcohol and coffee consumption (ORa) was 5.1 (95% CI 1.1 to 24.5, p = 0.040). For all dairy products, including butter, the ORa for the medium and upper tertiles of intake were 5.4 and 11.6, respectively (p for trend = 0.023). The ORa for regular coffee drinkers further adjusted by dairy consumption was 4.7 (95% CI 1.1 to 20.7, p = 0.043). K- ras mutated cases reported a lower intake of vitamin E (ORa = 0.2, p for trend = 0.036), polyunsaturated fats and omega 3 fatty acids (ORa = 0.2; p for trend Conclusions: Results support the hypothesis that in EPC exposure to specific dietary components or contaminants may influence the occurrence or persistence of K- ras mutations.
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The influence of lipid and lifestyle factors upon correlations between highly prevalent organochlorine compounds in patients with Exocrine Pancreatic Cancer.
Environment international, 2007Co-Authors: Miquel Porta, Núria Malats, Laura Ruiz, Manuel Jariod, Joan O. Grimalt, Esther Marco, Tomás Undabeytia López, Elisa Puigdomènech, Ekhine ZumetaAbstract:We aimed to analyse the influence of cholesterol and triglycerides, and of tobacco, coffee and alcohol consumption upon correlations between serum concentrations of organochlorine compounds (OCs) in patients with Exocrine Pancreatic Cancer (EPC). Incident cases of EPC diagnosed in eastern Spain were prospectively identified (N=144). OCs were analysed by high-resolution gas chromatography with electron-capture detection. A strong correlation was observed between hexachlorobenzene (HCB) and beta-hexachlorocyclohexane (beta-HCH) (Spearman's rho=0.758). beta-HCH showed rho>0.4 with p,p'-DDT, p,p'-DDE, PCB138 and PCB153 (all p
Alfredo Carrato - One of the best experts on this subject based on the ideXlab platform.
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Clinical validity of detecting K- mutations for the diagnosis of Exocrine Pancreatic Cancer: a prospective study in a clinically-relevant spectrum of patients
European Journal of Epidemiology, 2011Co-Authors: Lucy A. Parker, Alfredo Carrato, Miquel Porta, Luisa Guarner, Juli Rifà, Josep M. Corominas, Blanca Lumbreras, Tomàs López, Ildefonso Hernández-aguado, Esteve FernándezAbstract:The diagnostic utility of detecting K- mutations for the diagnosis of Exocrine Pancreatic Cancer (EPC) has not been properly studied, and few reports have analysed a clinically relevant spectrum of patients. The objective was to evaluate the clinical validity of detecting K- mutations in the diagnosis of EPC in a large sample of clinically relevant patients. We prospectively identified 374 patients in whom one of the following diagnoses was suspected at hospital admission: EPC, chronic pancreatitis, Pancreatic cysts, and Cancer of the extrahepatic biliary system. Mutations in the K- oncogene were analysed by PCR and artificial RFLP in 212 patients. The sensitivity and specificity of the K- mutational status for the diagnosis of EPC were 77.7% (95% CI: 69.2-84.8) and 78.0% (68.1-86.0), respectively. The diagnostic accuracy was hardly modified by sex and age. In patients with either mutated K- or CEA > 5 ng/ml, the sensitivity and specificity were 81.0% (72.9-87.6) and 62.6% (72.9-87.6), respectively. In patients with mutated K- and CEA > 5 ng/ml the sensitivity was markedly reduced. In comparisons with a variety of non-EPC patient groups sensitivity and specificity were both always greater than 75%. In this clinically relevant sample of patients the sensitivity and specificity of K- mutations were not sufficiently high for independent diagnostic use. However, it seems premature to rule out the utility of K- analysis in conjunction with other genetic and 'omics' technologies.
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Clinical validity of detecting K-ras mutations for the diagnosis of Exocrine Pancreatic Cancer: a prospective study in a clinically-relevant spectrum of patients.
European journal of epidemiology, 2011Co-Authors: Lucy A. Parker, Alfredo Carrato, Miquel Porta, Luisa Guarner, Juli Rifà, Josep M. Corominas, Tomás Undabeytia López, Blanca Lumbreras, Ildefonso Hernández-aguado, Esteve FernándezAbstract:The diagnostic utility of detecting K-ras mutations for the diagnosis of Exocrine Pancreatic Cancer (EPC) has not been properly studied, and few reports have analysed a clinically relevant spectrum of patients. The objective was to evaluate the clinical validity of detecting K-ras mutations in the diagnosis of EPC in a large sample of clinically relevant patients. We prospectively identified 374 patients in whom one of the following diagnoses was suspected at hospital admission: EPC, chronic pancreatitis, Pancreatic cysts, and Cancer of the extrahepatic biliary system. Mutations in the K-ras oncogene were analysed by PCR and artificial RFLP in 212 patients. The sensitivity and specificity of the K-ras mutational status for the diagnosis of EPC were 77.7% (95% CI: 69.2–84.8) and 78.0% (68.1–86.0), respectively. The diagnostic accuracy was hardly modified by sex and age. In patients with either mutated K-ras or CEA > 5 ng/ml, the sensitivity and specificity were 81.0% (72.9–87.6) and 62.6% (72.9–87.6), respectively. In patients with mutated K-ras and CEA > 5 ng/ml the sensitivity was markedly reduced. In comparisons with a variety of non-EPC patient groups sensitivity and specificity were both always greater than 75%. In this clinically relevant sample of patients the sensitivity and specificity of K-ras mutations were not sufficiently high for independent diagnostic use. However, it seems premature to rule out the utility of K-ras analysis in conjunction with other genetic and ‘omics’ technologies.
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Occupational exposures and risk of Pancreatic Cancer
European Journal of Epidemiology, 2010Co-Authors: Miguel Santibañez, Jesús Vioque, Juan Alguacil, Manuela García Hera, Eduardo Moreno-osset, Alfredo Carrato, Miquel Porta, Timo KauppinenAbstract:The objective was to analyze the relationship between occupation (and specific occupational exposures) and risk of Exocrine Pancreatic Cancer (EPC). We conducted a multicenter hospital-based case-control study in Eastern Spain. We included 161 incident cases of EPC (59.6% men, 94 with histological confirmation, of whom 80% had ductal adenocarcinoma). Cases were frequency-matched with 455 controls by sex, age and province of residence. Information was elicited using structured questionnaires. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. Occupational exposure to a selection of carcinogenic substances was assessed with the Finnish Job-Exposure Matrix (FINJEM). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multiple logistic regression, adjusting for sex, age, province, education, alcohol and smoking. A higher risk of EPC was associated with having worked as 'Miners, shotfirers, stone cutters and carvers', 'Machinery mechanics and fitters', 'Building trades workers' and 'Motor vehicle drivers' in men, 'Office Clerks' in women, and 'Waiters' in both sexes. Cases with ductal adenocarcinomas were more likely to have been exposed to chlorinated hydrocarbon solvents (OR = 4.1, 95% CI: 1.1-15.2, -trend = 0.04). We also observed significant associations with exposure to 'synthetic polymer dust exposure' and 'ionizing radiation'. Suggestive increases in risk were observed for 'pesticides', 'diesel and gasoline engine exhaust', and 'hydrocarbon solvents'. Results support the hypothesis that occupational exposure to chlorinated hydrocarbon solvents is associated with Exocrine Pancreatic Cancer.
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Lifetime history of tobacco consumption and K-ras mutations in Exocrine Pancreatic Cancer.
Pancreas, 2007Co-Authors: Marta Crous-bou, Juan Alguacil, Miquel Porta, Núria Malats, Manuel Jariod, Josep M. Corominas, Tomás Undabeytia López, Eva Morales, Esteve Fernández, Alfredo CarratoAbstract:OBJECTIVES We analyzed the relation between mutations in codon 12 of the K-ras oncogene and lifetime consumption of tobacco in patients with Exocrine Pancreatic Cancer (EPC). METHODS Incident cases of EPC were prospectively identified and interviewed during hospital admission about smoking and other factors. Exact logistic regression was used to compare EPC cases (N = 107) with and without K-ras mutations (case-case study). RESULTS Mutated cases were nonsignificantly less likely to have been smokers than wild-type cases: the odds ratio adjusted by age and sex was 0.54 (95% confidence interval, 0.10-2.69; P = 0.613). With respect to never smokers, adjusted odds ratios for former and current smokers were 0.79 and 0.36, respectively (P = 0.193). Pack-years smoked, years of smoking, and cigarettes smoked per year also tended to be higher in nonmutated than in mutated cases. Neither age at onset of smoking nor the time between quitting and diagnosis were associated with K-ras. CONCLUSIONS Tobacco does not play a major part in the acquisition of K-ras mutations in the Pancreatic epithelium. Although both smoking and K-ras mutations have important roles in the etiopathogenesis of EPC, the 2 processes may act independently.
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Molecular biology of Exocrine Pancreatic Cancer
Clinical and Translational Oncology, 2006Co-Authors: José Luis Soto, Víctor Manuel Barbera, Miguel Saceda, Alfredo CarratoAbstract:Exocrine Pancreatic Cancer is one of the neoplasias with a worse prognosis, with conventional treatments having little impact on disease outcome. Research and genomic high-throughput technology is continuously expanding our knowledge of pancreas Cancer biology. Characterization of genetic and epigenetic alterations in Pancreatic tumors has allowed a better understanding of the progression model of the disease at the molecular level. The development of new therapeutic approaches with target-oriented agents is been tested in the preclinical and clinical settings. This review updates the current available data on Pancreatic Cancer molecular biology.
Luisa Guarner - One of the best experts on this subject based on the ideXlab platform.
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Relationships of hepatic and Pancreatic biomarkers with the cholestatic syndrome and tumor stage in Pancreatic Cancer.
Biomarkers : biochemical indicators of exposure response and susceptibility to chemicals, 2012Co-Authors: Miquel Porta, Núria Malats, Luisa Guarner, José Pumarega, Ricard Solà, Francisco X. RealAbstract:We analyzed relationships of hepatic and Pancreatic biomarkers with the cholestatic syndrome and tumor stage in Exocrine Pancreatic Cancer (N = 183). Information on laboratory tests and on signs and symptoms was obtained from medical records and patient interviews. Bilirubin, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT) and alkaline phosphatase were lower in tumor stage IV. The association was due to the relationship between cholestatic syndrome and earlier presentation of patients. There was no association between hepatic biomarkers and stage when adjusting by cholestatic syndrome. Relationships of hepatic and Pancreatic biomarkers with Pancreatic symptoms and tumor stage must be controlled in “-omics” and other studies using biomarkers.
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Clinical validity of detecting K-ras mutations for the diagnosis of Exocrine Pancreatic Cancer: a prospective study in a clinically-relevant spectrum of patients.
European journal of epidemiology, 2011Co-Authors: Lucy A. Parker, Alfredo Carrato, Miquel Porta, Luisa Guarner, Juli Rifà, Josep M. Corominas, Tomás Undabeytia López, Blanca Lumbreras, Ildefonso Hernández-aguado, Esteve FernándezAbstract:The diagnostic utility of detecting K-ras mutations for the diagnosis of Exocrine Pancreatic Cancer (EPC) has not been properly studied, and few reports have analysed a clinically relevant spectrum of patients. The objective was to evaluate the clinical validity of detecting K-ras mutations in the diagnosis of EPC in a large sample of clinically relevant patients. We prospectively identified 374 patients in whom one of the following diagnoses was suspected at hospital admission: EPC, chronic pancreatitis, Pancreatic cysts, and Cancer of the extrahepatic biliary system. Mutations in the K-ras oncogene were analysed by PCR and artificial RFLP in 212 patients. The sensitivity and specificity of the K-ras mutational status for the diagnosis of EPC were 77.7% (95% CI: 69.2–84.8) and 78.0% (68.1–86.0), respectively. The diagnostic accuracy was hardly modified by sex and age. In patients with either mutated K-ras or CEA > 5 ng/ml, the sensitivity and specificity were 81.0% (72.9–87.6) and 62.6% (72.9–87.6), respectively. In patients with mutated K-ras and CEA > 5 ng/ml the sensitivity was markedly reduced. In comparisons with a variety of non-EPC patient groups sensitivity and specificity were both always greater than 75%. In this clinically relevant sample of patients the sensitivity and specificity of K-ras mutations were not sufficiently high for independent diagnostic use. However, it seems premature to rule out the utility of K-ras analysis in conjunction with other genetic and ‘omics’ technologies.
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Clinical validity of detecting K- mutations for the diagnosis of Exocrine Pancreatic Cancer: a prospective study in a clinically-relevant spectrum of patients
European Journal of Epidemiology, 2011Co-Authors: Lucy A. Parker, Alfredo Carrato, Miquel Porta, Luisa Guarner, Juli Rifà, Josep M. Corominas, Blanca Lumbreras, Tomàs López, Ildefonso Hernández-aguado, Esteve FernándezAbstract:The diagnostic utility of detecting K- mutations for the diagnosis of Exocrine Pancreatic Cancer (EPC) has not been properly studied, and few reports have analysed a clinically relevant spectrum of patients. The objective was to evaluate the clinical validity of detecting K- mutations in the diagnosis of EPC in a large sample of clinically relevant patients. We prospectively identified 374 patients in whom one of the following diagnoses was suspected at hospital admission: EPC, chronic pancreatitis, Pancreatic cysts, and Cancer of the extrahepatic biliary system. Mutations in the K- oncogene were analysed by PCR and artificial RFLP in 212 patients. The sensitivity and specificity of the K- mutational status for the diagnosis of EPC were 77.7% (95% CI: 69.2-84.8) and 78.0% (68.1-86.0), respectively. The diagnostic accuracy was hardly modified by sex and age. In patients with either mutated K- or CEA > 5 ng/ml, the sensitivity and specificity were 81.0% (72.9-87.6) and 62.6% (72.9-87.6), respectively. In patients with mutated K- and CEA > 5 ng/ml the sensitivity was markedly reduced. In comparisons with a variety of non-EPC patient groups sensitivity and specificity were both always greater than 75%. In this clinically relevant sample of patients the sensitivity and specificity of K- mutations were not sufficiently high for independent diagnostic use. However, it seems premature to rule out the utility of K- analysis in conjunction with other genetic and 'omics' technologies.
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Exocrine Pancreatic Cancer: Symptoms at presentation and their relation to tumour site and stage
Clinical and Translational Oncology, 2005Co-Authors: Miquel Porta, Alfredo Carrato, Xavier Fabregat, Núria Malats, Luisa Guarner, Ana Miguel, Laura Ruiz, Manuel Jariod, Sergi Costafreda, Susana CollAbstract:Introduction . The need to detect Pancreatic Cancer at earlier stages is undisputed. We recorded the signs and symptoms of patients presenting with Exocrine Pancreatic Cancer and evaluated their association with clinical characteristics such as tumour site and disease stage. Patients and methods . All patients (n=185) with Exocrine Pancreatic Cancer newly diagnosed at five general hospitals in Eastern Spain were prospectively recruited over 3 years. Symptoms were elicited through personal interviews and signs were recorded by the attending physician on admission. Results . At diagnosis, one third of tumours of the pancreas head were in stage I and another third in stage IV. None of the tumours of the body and tail were in stage I, and over 80% were in stage IV (p
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Exocrine Pancreatic Cancer: symptoms at presentation and their relation to tumour site and stage
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexic, 2005Co-Authors: Miquel Porta, Alfredo Carrato, Xavier Fabregat, Núria Malats, Luisa Guarner, Ana Miguel, Laura Ruiz, Manuel Jariod, Sergi Costafreda, Susana CollAbstract:Introduction. The need to detect Pancreatic Cancer at earlier stages is undisputed. We recorded the signs and symptoms of patients presenting with Exocrine Pancreatic Cancer and evaluated their association with clinical characteristics such as tumour site and disease stage.
Åke Andrén-sandberg - One of the best experts on this subject based on the ideXlab platform.
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Other risk factors for Pancreatic Cancer: Hormonal aspects
Annals of Oncology, 1999Co-Authors: Åke Andrén-sandberg, D Hoem, Pia Lena BäckmanAbstract:Exocrine Pancreatic Cancer is significantly more common in younger men than in younger women. The male-to-female sex ratio is, in most countries, between 1.25 and 1.75 to 1, but decreases with increasing age. Moreover, prior oophorectomy appeared in one study to be significantly more common in women with Pancreatic Cancer than in controls. This has raised interest in sex hormones in the development in Pancreatic Cancer. It has been questioned if there are estrogen receptors in ductal Pancreatic Cancer, but there are no doubt estrogen receptors and estrogen-binding protein in human healthy pancreas. It is also well proven that it is possible to influence experimental Pancreatic Cancer with estrogens. However, in clinical studies tamoxifen has repeatedly been shown to be without significant effects. On the other hand, there are also androgen receptors in Pancreatic Cancer and testosterone has been shown to strongly promote growth in experimental Pancreatic Cancers. It is therefore of considerable interest that an antiandrogen recently was shown to significantly prolong life in patients with unresectable Pancreatic carcinoma. However, in patients with advanced Pancreatic carcinoma the S-testosterone is low, far lower than what could be expected due to weight-loss and malnourishment alone. Pancreatic Cancer has etiologically been connected to diet, for example the intake of fat. Cholecystokinin receptors have been found on human Pancreatic Cancer, possible to stimulate in vitro by cholecystokinin (CCK). Studies with CCK-receptor binding, hybridization with radiolabeled complementary DNA (cDNA) probes, or reverse-transcription polymerase chain reaction have shown that CCK-A receptors also are present in rat Pancreatic putative preneoplastic lesions and Cancer tissue, rat Pancreatic-Cancer cell lines, Pancreatic carcinomas in transgenic mice, hamster Pancreatic Cancer, and human Pancreatic Cancer cell lines and tumors. Also, CCK-B receptors have been found in some human Pancreatic Cancers. There are a vast number of experiments done on CCK-stimulation of Pancreatic Cancer. They indicate that CCK may have a promotional effect on Exocrine Pancreatic Cancer, but it is not probable that hyperstimulation with CCK alone induce Pancreatic Cancer. At present, however, despite a lot of evidence for a hormone-dependence of Pancreatic Cancer there are no data confirming a role for estrogens, androgens, CCK or their antagonists in clinical treatment of Exocrine Pancreatic Cancer.
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Pattern of Recurrence After Pancreaticoduodenectomy for Exocrine Pancreatic Cancer: Correlation with Survival
Pancreatoduodenectomy, 1997Co-Authors: Åke Andrén-sandberg, Ingemar IhseAbstract:The results of radical surgery for Pancreatic Cancer depend, like all other Cancer surgery, on the technique used and the biology of the disease. We have analyzed the site and time of recurrence after Pancreaticoduodenectomy for Exocrine Pancreatic Cancer in 99 patients who died more than 6 months postoperatively. All patients had recurrent disease; 87 had local recurrence in the Pancreatic bed and 93 had liver metasases. Local recurrence without liver metastases was found in 6 patients, and 12 had liver metastases but no local recurrence. Both the time from operation to clinically evident recurrence and the postoperative survival time were significantly longer for patients with local recurrence only. None of those with small tumors (≤2 cm) had liver metastases only and none of them was in stage I. Although not statistically significant, there was a tendency (4 in 5) for smaller, well-differentiated tumors without spread outside the pancreas to be associated with local recurrence without liver metastases. We conclude that, in retrospect, the surgical procedures used were inappropriate and inadequate. To cure these patients, a more radical operation or effective adjuvant treatment is needed.
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Tumour marker CA 50 levels compared to signs and symptoms in the diagnosis of Pancreatic Cancer
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 1997Co-Authors: Birger Plsson, Parvesh Masson, Åke Andrén-sandbergAbstract:The diagnostic merits of CA 50 and of symptoms indicating Pancreatic Cancer (pain, jaundice, weight loss, malabsorption) were compared prospectively in 512 consecutive patients. Among the final diagnoses were: Exocrine Pancreatic Cancer, 175; periampullary Cancer, 44; other gastrointestinal Cancer, 45; and chronic pancreatitis, 64 cases. The suspected diagnoses based on symptoms and signs were correct in 80% of the patients with Exocrine Pancreatic Cancer, in 78% with periampullary, in 76% with other gastrointestinal Cancer and in 90% with chronic pancreatitis. CA 50 was pathological in 96% of the cases with Exocrine Pancreatic Cancer, in 70% with periampullary, in 78% with other gastrointestinal malignancies and in 36% with chronic pancreatitis. The sensitivity was 96%, specificity 48%, positive prediction 49% and negative prediction 96%, depending on cut-off level. The single CA 50 value was comparable to symptoms and signs regarding sensitivity and negative prediction. In 28 of 42 cases incorrectly clinically classified, CA 50 alone indicated a benign or malignant diagnosis. If both the modalities 'signs and symptoms' and CA 50 were combined, the sensitivity was 91%, the specificity 92%, the positive prediction 86% and the negative prediction 95%. The initial CA 50 value can help to indicate in which patients a Pancreatic malignancy should be suspected.
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Prospective Evaluation of Pain in Exocrine Pancreatic Cancer
Digestion, 1997Co-Authors: Anna-lena Grahm, Åke Andrén-sandbergAbstract:Background: Although pain is the most feared part of the terminal life of many patients with Cancer, the intensity and the quality of the pain is all too often only scantly describe
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Total Pancreatectomy for Cancer of the Pancreas: Is It Appropriate?
World journal of surgery, 1996Co-Authors: Ingemar Ihse, Harald Anderson, Åke Andrén-sandbergAbstract:During the late 1960s total pancreatectomy was advocated on theoretic grounds as an operation superior to subtotal (Whipple) resection in patients with Pancreatic Cancer. There are, however, no prospective randomized studies and only few institutional comparisons between the two operations. The aim of the present paper was to report the clinical outcome of total and subtotal pancreatectomy, respectively, in a consecutive series of patients with Exocrine Pancreatic Cancer. The short- and long-term results of 89 consecutive patients who underwent total pancreatectomy (1959-1984) for Pancreatic Cancer were retrospectively compared with a similar group of 36 patients who had a subtotal pancreatectomy (1985-1992) for the same diagnosis. The clinical characteristics were on the whole similar in the two groups. Postoperative mortality and morbidity, the amount of intraoperative bleeding, operation time, reoperation rate, postoperative days in the intensive care unit, and duration of hospital stay were statistically significantly increased after total pancreatectomy. The 5-year survival rate was lower after total pancreatectomy when hospital deaths were included in the analysis. At multivariate analysis total pancreatectomy adversely influenced long-term survival compared to subtotal resection, as did positive lymph nodes and poor histologic differentiation. Better early and long-term results were found after subtotal than after total pancreatectomy in patients with Exocrine Pancreatic Cancer. Although the two operations were done during different time periods, we believe the results suggest that total pancreatectomy cannot be recommended as a routine treatment for this patient group.