Clinical validity of detecting K-ras mutations for the diagnosis of exocrine pancreatic cancer: a prospective study in a clinically-relevant spectrum of patients.

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.

Risk assessment model for first-cycle chemotherapy-induced neutropenia in patients with solid tumours.

Chemotherapy-induced neutropenia, the major dose-limiting toxicity of chemotherapy, is directly associated with concomitant morbidity, mortality and health-care costs. The use of prophylactic granulocyte colony-stimulating factors may reduce the incidence and duration of chemotherapy-induced neutropenia, and is recommended in high-risk patients. The objective of this study was to develop a model to predict first-cycle chemotherapy-induced neutropenia (defined as neutropenia grade>or=3, with or without body temperature>or=38 degrees C) in patients with solid tumours.

A regiospecific synthesis of both positional isomers of 4,6-disubstituted 2-dicyanomethylene-1, 2-dihydropyridin-3-carbonitriles.

A protocol allowing the regiospecific synthesis of both positional isomers of 4,6-disubstituted 2-dicyanomethylene-1,2-dihydropyridin-3-carbonitriles, precursors of 1,6-naphthyridines, is presented. Thus, treatment of enaminoketones with the propanedinitrile dimer yields one regioisomer while the treatment of the corresponding (3-chloro-allylidene)-dimethylammonium perchlorates (easily obtained from enaminoketones and POCl(3)), in which the nature of the reactive centers is inverted with respect to the enaminoketone, yields the other regioisomer.

In pancreatic ductal adenocarcinoma blood concentrations of some organochlorine compounds and coffee intake are independently associated with KRAS mutations.

While KRAS activation is a fundamental initiating event in the aetiopathogenesis of pancreatic ductal adenocarcinoma (PDA), environmental factors influencing the occurrence and persistence of KRAS mutations remain largely unknown. The objective was to test the hypothesis that in PDA there are aetiopathogenic relationships among concentrations of some organochlorine compounds (OCs) and the mutational status of the KRAS oncogene, as well as among the latter and coffee intake. Incident cases of PDA were interviewed and had blood drawn at hospital admission (N = 103).

Lifetime history of alcohol consumption and K-ras mutations in pancreatic ductal adenocarcinoma.

Background: In pancreatic ductal adenocarcinoma (PDA), evidence on the etiopathogenic role of alcohol consumption in the occurrence of K-ras mutations is scant, and the role of alcohol in pancreatic carcinogenesis is not well established. We analyzed the relation between lifetime consumption of alcohol and mutations in codon 12 of the K-ras oncogene in patients with PDA.

Methods: Incident cases of PDA were prospectively identified and interviewed face-to-face during hospital admission about lifetime alcohol consumption and other lifestyle factors.

Non-pegylated liposomal doxorubicin combined with gemcitabine as first-line treatment for metastatic or locally advanced breast cancer. Final results of a phase I/II trial.

Doxorubicin and gemcitabine are active as single agents in breast cancer, have different mechanisms of action, and mainly have non-overlapping side effects. Dose-dependent doxorubicin-related cardiac toxicity is the principal limitation in the metastatic setting. This open, multicenter, single-arm phase I/II study assessed the safety and activity of gemcitabine in combination with non-pegylated liposomal doxorubicin (Myocet), a more cardiac-friendly anthracycline, in the first-line treatment of patients with advanced breast cancer.

CYP1B1 polymorphisms and k-ras mutations in patients with pancreatic ductal adenocarcinoma.

The frequency of CYP1B1 polymorphisms in pancreatic cancer has never been reported. There is also no evidence on the relationship between CYP1B1 variants and mutations in ras genes (K-, H- or N-ras) in any human neoplasm. We analyzed the following CYP1B1 polymorphisms in 129 incident cases of pancreatic ductal adenocarcinoma (PDA): the m1 allele (Val to Leu at codon 432) and the m2 allele (Asn to Ser at codon 453).

A single-nucleotide polymorphism in the aromatase gene is associated with the efficacy of the aromatase inhibitor letrozole in advanced breast carcinoma.

Purpose: To evaluate the efficacy of treatment with the aromatase inhibitor letrozole in breast cancer patients segregated with respect to DNA polymorphisms of the aromatase gene CYP19.

Patients And Methods: Postmenopausal patients (n = 67) with hormone receptor-positive metastatic breast cancer were treated with the aromatase inhibitor letrozole. PCR allelic discrimination was used to examine three single-nucleotide polymorphisms (SNP) in DNA obtained from breast carcinoma tissue.

R-CHOP-14 in patients with diffuse large B-cell lymphoma younger than 70 years: a multicentre, prospective study.

Several studies have shown that adding rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or reducing the interval between chemotherapy cycles from 3 weeks to 2 weeks improves survival in patients with diffuse large B-cell lymphoma (DLBCL). These studies prompted our group (GOTEL) to evaluate prospectively in a pilot study the feasibility and efficacy of R-CHOP-14 in patients with DLBCL. Patients (<70 years) with stage II bulky or stage III or IV DLBCL and no significant comorbidities were included in the study.

Food and nutrient intakes and K-ras mutations in exocrine pancreatic cancer.

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.

Biweekly gemcitabine plus vinorelbine in first-line metastatic breast cancer: efficacy and correlation with HER2 extracellular domain.

Purpose. To assess the toxicity and efficacy of biweekly gemcitabine plus vinorelbine in first-line advanced breast cancer, and to establish whether circulating HER2 ECD levels correlate with the efficacy of the combination. Patients and methods.

Phase II multicentre study of temozolomide in combination with interferon alpha-2b in metastatic malignant melanoma.

Objective: Temozolomide is a novel oral alkylating agent, active against metastatic melanoma. Combinations of chemotherapy and biological response modifiers have been associated with increased antitumour activity. A multicentre phase II study was performed to assess the activity and toxicity of temozolomide in combination with interferon alpha-2b.

Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

Background: The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma.

Patients And Methods: Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design.

Toxic epidermal necrolysis in patients receiving anticonvulsants and cranial irradiation: a risk to consider.

Toxic epidermal necrolysis (TEN) is an infrequent disease but with a high mortality rate. It is a mucocutaneous reaction resulting from hypersensitivity to a variety of agents including most anticonvulsants. Many patients with primary or metastatic intracranial tumours receive anticonvulsants for seizure prophylaxis despite their efficacy not having been clearly demonstrated.

Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Comparison with the main clinical and pathological prognostic factors.

CEA, CA 125, SCC, CYFRA 21-1 and NSE were prospectively studied in 211 patients with non-small cell lung cancer and compared with clinical parameters (age, sex, Karnofsky Index, symptoms and smoking status), histopathological parameters (stage, histology, tumor size and nodal involvement), biological parameters (LDH and albumin) and the therapy used (surgery, chemotherapy or radiotherapy). Tumor marker sensitivity was CYFRA 21-1: 76%, CA 125: 55%, CEA: 52%, SCC: 33% and NSE: 22%. One of the tumor markers was abnormally high in 87% of the patients with locoregional disease and in 100% of the patients with metastases.

Quality of life for oncology patients during the terminal period. Validation of the HRCA-QL index.

Aim: The evolution of performance status, disability, and quality of life (QL) according to the Hebrew Rehabilitation Center for Aged QL (HRCA-QL) index for cancer patients through their terminal period is described. The assessment of HRCA-QL validity and reliability is also described.

Design: A total of 200 cancer patients were followed up from the onset of their "terminal phase" until they died.

Generalizing molecular results arising from incomplete biological samples: expected bias and unexpected findings.

Purpose: In molecular epidemiology, obtaining biological samples for all subjects targeted for study is frequently hampered by ethical, clinical, and logistic factors. The extent to which the incompleteness of biological samples could cause bias is rarely analyzed in depth. Here we report some expected bias and some unexpected findings during a study on mutations in the K-ras gene in exocrine pancreatic cancer (EPC).

Occupation and pancreatic cancer in Spain: a case-control study based on job titles. PANKRAS II Study Group.

Background: Occupational exposures may increase the risk of exocrine pancreatic cancer. This study aimed to identify occupations that in Spain may be associated with such risk.

Methods: Incident cases of pancreatic cancer and hospital controls were prospectively identified and interviewed during their hospital stay.

Validity of the hospital discharge diagnosis in epidemiologic studies of biliopancreatic pathology. PANKRAS II Study Group.

Background: The aim was to analyse the magnitude, direction and predictors of change in the main hospital discharge diagnosis (HDD) after a clinical expert review, among patients included in a multicentre molecular epidemiologic study of biliopancreatic diseases.

Methods: A total of 602 patients with a suspicion diagnosis of pancreas cancer (PC), cancer of the extrahepatic biliary system (CEBS) or benign biliopancreatic pathologies (BPP) were prospectively recruited at five general hospitals. A structured form was used to collect information from medical records.

Terminal cancer. duration and prediction of survival time.

The duration of the terminal period of cancer allows us to determine its prevalence, which is necessary to plan palliative care services. Clinical prediction of survival influences access to palliative care and the healthcare approach to be adopted. The objective of this study was to determine the duration of the terminal period, the prognostic ability of healthcare professionals to predict this terminal period and the factors that can improve the prognostic accuracy.

Risk of pancreatic cancer and occupational exposures in Spain. PANKRAS II Study Group.

The objective of the study was to analyse the relationship between occupational exposures and risk of pancreatic cancer. Incident cases of pancreatic cancer and hospital controls were prospectively identified and interviewed during the hospital stay. Occupational history was obtained by direct interview with the patient, and was available for 164 (89%) of 185 pancreatic cancer cases, and 238 (90%) of 264 controls.

Association between coffee drinking and K-ras mutations in exocrine pancreatic cancer. PANKRAS II Study Group.

Study Objective: To analyse the relation between coffee consumption and mutations in the K-ras gene in exocrine pancreatic cancer.

Design: Case-case study. Consumption of coffee among cases with the activating mutation in the K-ras gene was compared with that of cases without the mutation.