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J Rifà

Publications and source records attributed to J Rifà.

17 recordsLinked to original sources

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. 52 patients were treated with gemcitabine 2500 mg/m(2) plus vinorelbine 30 mg/m(2), both on day 1 of 14-day cycles, for a maximum of 10 cycles. Baseline serum levels of HER2 ECD were assessed with an ELISA. Results. All patients were evaluable for toxicity, and 50 for efficacy. Overall toxicity was moderate. Grade 3 neutropenia occurred in 35% of patients and grade 4 in 19%. Other grade 3 toxicities were observed in less than 6%. There was one episode of febrile neutropenia, and one death after cycle three. Overall response rate was 52% (95% CI: 38% to 66%), with 2 patients achieving a CR (4%). Response rate did not correlate with HER2 ECD, with 50% of HER2 ECD positive patients responding, vs 48.5% of the HER2 ECD negative. Median overall survival was 24.6 months. Conclusion. Gemcitabine plus vinorelbine, given as an every-two-week schedule, is an active regimen in advanced breast carcinoma. This combination can be an option when anthracyclines and taxanes are not preferred. HER2 ECD has no predictive value in this non-taxane combination.

Adenocarcinoma↗

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. In the island of Mallorca, Spain, we followed 200 cancer patients at the inception of the terminal period. Twenty-one symptoms, quality of life, prognosis and duration of survival were measured. Using a Cox regression model, a predictive survival model was built. Median duration was 59 days; 95% confidence interval (CI)=49-69 days, mean=99 days. The oncologists were accurate in their predictions (+/-1/3 duration) in 25.7% of cases, the nurses in 21.5% of cases and the family physicians in 21.7% of cases. Errors of overestimation occurred 2.86-4.14 times more frequently than underestimation. In the final model, in addition to clinical prognosis (P=0.0094), asthenia (P=0.0257) and the Hebrew Rehabilitation Centre for Aged Quality of Life (HRCA-QL) Index (P=0.0002) were shown to be independent predictors of survival. In this study, the estimated duration of the terminal period was greater than that reported in a series of palliative care programmes, and survival was overestimated. Oncologists could estimate prognosis more accurately if they also take into account asthenia and HRCA-QL Index.

Adult↗

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. A panel of experts revised all diagnostic information and established the main clinicopathological diagnosis (CPD) by consensus. RESULTS: Of the 204 cases with a HDD of PC, 176 (86%) were deemed to have a CPD of PC, eight of CEBS, twelve a neoplasm of different origin, four BPP and four syndromic diagnoses. Thus, 28 cases (14%) were false positives. Of the 129 patients with a HDD of CEBS, 15 (12%) were false positives. Nine of the 396 cases with a HDD of non-PC (2%) had a CPD of PC (false negatives), whilst 14 of 471 patients with a HDD of non-CEBS (3%) were deemed to have CEBS. Overall, sensitivity and specificity of HDD for PC were, respectively, 95 and 93%, and for CEBS, 89 and 97%. Cytohistological confirmation and laparotomy were independent predictors of diagnostic change. CONCLUSIONS: Validity of the HDD was high, but its association with some clinical variables suggests that sole reliance on HDD can significantly bias results, and highlights the need to review all HDDs. Alternatively, only patients at high risk of misdiagnosis could be reviewed: primarily, those lacking a cytohistological diagnosis or a laparotomy. No exclusions appear warranted solely on the basis of age, gender or tumour spread.

Aged↗

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. Occupational history was obtained by direct interview with the patient and was available for 164 (89%) of 185 pancreatic cancer cases and for 238 (90%) of 264 controls. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. RESULTS: A significant increased odds ratio (OR) was observed in men for 'physical, chemistry and engineering science technicians'. Elevated risks were also found for 'metal moulders, sheet-metal workers, structural metal workers, welders and related workers', 'painters and varnishers' and 'machinery mechanics and fitters'. 'Agricultural workers' did not present an increased risk for pancreas cancer in men. In women, however, high OR were observed for 'agricultural workers' and for 'textile and garment workers'. Most associations remained unchanged after considering long duration of the exposure and the period 5-15 years before diagnosis. CONCLUSIONS: Few occupations were at increased risk for pancreatic cancer, and the associations observed are in accordance with previous studies. The increases in risk observed for women in agricultural and textile jobs, and for men in the manufacture of dyes and pigments may deserve further attention.

Acute Disease↗

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. Two industrial hygienists evaluated exposures to 22 suspected carcinogens previously associated with pancreatic cancer. Occupational exposures were also assessed using the Finnish job-exposure matrix (FINJEM). For each type of pesticide group, moderately increased odds ratios (OR) were apparent in the high-intensity category, highest for arsenical pesticides (OR=3.4; 95% CI 0.9-12.0), and 'other pesticides' (OR=3.17; 95% CI 1.1-9.2). ORs for aniline derivatives, and dyes and organic pigments, were also higher for high-intensity exposure, and increased when lagged and restricted to long duration of exposure. ORs above 3 were observed for the following agents evaluated by FINJEM: pesticides, benzo[a]pyrene, lead, volatile sulphur compounds, and sedentary work. Whilst generally negative, results lend moderate support to the hypothesis of an association between exposure to some pesticides and pancreatic cancer. Larger studies could address the potential for these compounds to modify the carcinogenic risk of other environmental exposures. Suggestive increases in risk from aniline derivatives, dyes and organic pigments, and benzo[a]pyrene may also deserve further attention.

Aged↗

Medical conditions in patients with pancreatic and biliary diseases: validity and agreement between data from questionnaires and medical records. PANKRAS II Study Group.

The aims of the study were to assess the agreement between data from personal interviews and medical records on selected medical conditions, to evaluate the validity of each source of information, and to estimate the prevalence of these conditions in pancreatobiliary pathology. Between 1992 and 1995, 602 patients with pancreatobiliary diseases were included in the PANKRAS II Study. Information from interview and medical records was available in 88% of cases. The agreement between both data sources was poor only for cholecystitis and mental disorders. The validity of both sources of information was high or acceptable for all conditions except for cholecystitis. Prevalence of past medical conditions was similar to that reported previously and varied according to diagnosis, gender, age, educational level, and hospital of admission. Research aimed at assessing the prevalence of less common diseases should consider subject- and health-related factors in collecting information.

Adolescent↗

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. SETTING AND PATIENTS: All cases of pancreatic cancer newly diagnosed at five hospitals in Spain during three years were included in the PANKRAS II Study (n = 185, of whom 121 whose tissue was available for molecular analysis are the object of the present report). Over 88% were personally interviewed in hospital. DNA was amplified from paraffin wax embedded tissues, and mutations in codon 12 of K-ras were detected by the artificial RFLP technique. MAIN RESULTS: Mutations were found in tumours from 94 of 121 patients (77.7%). Mutations were more common among regular coffee drinkers than among non-regular coffee drinkers (82.0% v 55.6%, p = 0.018, n = 107). The odds ratio adjusted by age, sex, smoking and alcohol drinking was 5.41 (95% CI 1.64, 17.78). The weekly intake of coffee was significantly higher among patients with a mutated tumour (mean of 14.5 cups/week v 8.8 among patients with a wild type tumour, p < 0.05). With respect to non-regular coffee drinkers, the odds ratio of a mutated tumour adjusted by age, sex, smoking and alcohol drinking was 3.26 for drinkers of 2-7 cups/week, 5.77 for drinkers of 8-14 cups/week and 9.99 for drinkers of > or = 15 cups/week (p < 0.01, test for trend). CONCLUSIONS: Pancreatic cancer cases without activating mutations in the K-ras gene had drank significantly less coffee than cases with a mutation, with a significant dose response relation: the less they drank, the less likely their tumours were to harbour a mutation. In exocrine pancreatic cancer the K-ras gene may be activated less often among non-regular coffee drinkers than among regular drinkers. Caffeine, other coffee compounds or other factors with which coffee drinking is associated may modulate K-ras activation.

Adolescent↗

Ki-ras mutations in exocrine pancreatic cancer: association with clinico-pathological characteristics and with tobacco and alcohol consumption. PANK-ras I Project Investigators.

The aims of this study were (i) to assess the prevalence and spectrum of codon 12 Ki-ras mutations in patients diagnosed with exocrine pancreatic cancer (EPC) in 2 general hospitals between 1980 and 1990, (ii) to analyze the association of this genetic alteration with clinical and pathological characteristics, and (iii) to determine the association of Ki-ras mutations with tobacco and alcohol consumption. DNA was amplified from paraffin-embedded tissue samples and mutations in codon 12 of Ki-ras were detected using the artificial RFLP technique. Cox proportional-hazards regression and unconditional logistic regression were applied. Codon 12 Ki-ras mutations were detected in 30 of 51 cases for which molecular results were available. The amino-acid substitutions were Asp (8), Val (6), and Arg (3). A double mutation, including always a Val, was detected in 5 cases. None of the 4 nonductal pancreatic neoplasms were mutated. The mutation prevalence was 79% in metastases and 54% in primary tumors. The risk of a mutated tumor was 3 times higher in alcohol drinkers than in non-drinkers, and a linear trend was apparent. When age, gender, hospital, and tobacco and alcohol consumption were taken into account, a high risk for mutations was detected in patients who only smoked and in patients who only drank, but less so in patients who both smoked and drank. These results raise novel hypotheses regarding the role of tobacco and alcohol in EPC.

Adult↗

[Changes in the natural history of AIDS in patients from Mallorca and Ibiza: 1986-1992].

BACKGROUND: Longitudinal follow-up studies in patients with human immunodeficiency virus (HIV) infection and AIDS, which are fundamental for the knowledge of variations the natural history of this disease, have generally been carried out by Public Health Departments and in populations in which homosexual males predominate. The aim of the present study was to analyze the changes in the natural history of the patients diagnosed with AIDS in the islands of Mallorca and Ibiza. METHODS: A prospective study of the adult patients diagnosed with AIDS in Mallorca and Ibiza, from 1986 to 1992 was performed. RESULTS: The annual incidence of the cases of AIDS increased throughout the study. The mean age of the patients did not vary, and neither did that in relation to sexes. A progressive decrease was observed in CD4 lymphocytes at the time of diagnosis (from 0.168 x 10(9)/l in 1986 to 0.079 x 10(9)/l in 1992). There was an increase in heterosexual transmission patients with no known risk factors also increased over the period studied. The incidence of extrapulmonary tuberculosis decreased both as the form of presentation and in its global frequency. Pneumonia by Pneumocystis carinii increased mainly as a initial feature. The median survival was 547 days and did not vary significantly throughout the study. CONCLUSIONS: The epidemiologic and clinical study of AIDS in Mallorca and Ibiza, Spain is similar to that observed in other Mediterranean regions. The incidence of extrapulmonary tuberculosis has decreased.

AIDS-Related Opportunistic Infections↗

Ki-ras mutations as a prognostic factor in extrahepatic bile system cancer. PANK-ras I Project Investigators.

PURPOSE: To assess the prevalence and prognostic significance of Ki-ras codon 12 mutations in extrahepatic biliary system cancer (EBSC). PATIENTS AND METHODS: Patients diagnosed with EBSC between 1980 and 1990 (N = 111) were selected from two hospitals. DNA was amplified from paraffin-embedded tissues and mutations in codon 12 of Ki-ras were detected using the artificial restriction fragment-length polymorphism (RFLP) technique. RESULTS: Tissue was available from 68.5% of patients. The prevalence of mutations was 41%. There was no association between mutations and clinical and pathologic characteristics; however, mutations in Ki-ras were associated with survival, with a median survival duration of 7.7 months for patients with wild-type Ki-ras and 1.7 months for patients with mutated tumors (hazards ratio [HR] = 1.67; P = .075). Among patients with stage I to II tumors, the chance of dying of patients with the mutation was 7.8 times higher than that of patients without the mutation (P = .087); the corresponding HR for patients with stage III to IV disease was 2.9 (P = .003). After adjusting for age, tumor site, histology, differentiation, and stage, the HR for Ki-ras mutations was 2.12 (P = .026). CONCLUSION: Ki-ras codon 12 mutations are an independent prognostic indicator in patients with EBSC. Mutation detection may be of help in the management of these patients.

Adenocarcinoma↗

Diagnostic certainty and potential for misclassification in exocrine pancreatic cancer. PANKRAS I Project Investigations.

Whereas over the last decade epidemiologic studies on exocrine pancreatic cancer (EPC) continued to show a remarkable heterogeneity in diagnostic criteria applied to define caseness, the actual magnitude and consequences of misclassification remain largely unexplored. The objectives were: (1) to estimate the degree of certainty with which cases of EPC are diagnosed in the two participating hospitals (to this end a diagnostic certainty classification (DCC) was developed; (2) to test whether characteristics of cases differed by degree of diagnostic certainty; and (3) to assess what influence different definitions of case might have on risk estimates for tobacco and alcohol. All cases with a discharge diagnosis of EPC who attended at the Hospital del Mar between 1980-90 and at the Hospital Son Dureta between 1983-90 were identified through their respective tumor registries, and their clinical records were reviewed. Only 52% of 140 cases were classified in the group with a higher probability of EPC (group H). Diagnostic certainty appeared somewhat greater among women (age-adjusted odds ratio [ORa] 1.60, p = 0.18). Group H showed a higher proportion of cases with an interval from first symptom to diagnosis < or = 1 month (ORa = 2.38, p < 0.05) and the proportion of adenocarcinomas was slightly higher than in less certain cases (group L) (p = 0.051). A radical treatment was exclusively attempted in group H (p < 0.001). DCC cut-off points had a significant effect on the proportion of smokers and of alcohol drinkers, as well as on the percent of cases with pathological (cytohistological) confirmation. The proportion of cases unlikely to be of pancreatic origin in spite of having pathological confirmation was high enough to cause significant misclassification bias. Because past exposure to certain risk factors may differ among cases with different diagnostic certainty, we suggest to initially include in the case group patients who in spite of lacking pathological confirmation have strong clinical evidence supporting the diagnosis of EPC; subsequently, risk estimates should be computed across strata of diagnostic certainty to assess whether heterogeneity exists. In exocrine pancreatic cancer the impact of misclassification of disease status upon etiologic and prognostic estimates deserves at least as much attention as misclassification of exposure.

Adenocarcinoma↗

Blood transfusion has no effect on colorectal cancer survival. A population-based study.

This study was conducted to evaluate the impact on survival of perioperative blood transfusion in a series of 698 colorectal cancer patients undergoing radical surgery. Patients were identified, and follow-up was carried out by the local population-based cancer registry. Data on blood transfusion was obtained by record linkage with the files of the blood banks operating in the area covered by the registry. Prognostic factors were age, Dukes stage and topography of the primary tumour. Relative risk (RR) for Dukes B patients was 1.53 [95% confidence interval (CI) 0.94-2.50] and for Dukes C, 3.57 (95% CI 2.22-5.75) when compared with Dukes A patients. For the left colon, RR was 0.96 (0.61-1.52) and for the rectum 1.87 (1.22-2.86) when compared with the right colon. When adjusting for these factors and excluding operative mortality, RR for transfused patients was 1.16 (95% CI 0.87-1.55). It is concluded that blood transfusion does not adversely affect survival in colorectal cancer patients.

Adult↗

Serum concentrations of organochlorine compounds and K-ras mutations in exocrine pancreatic cancer. PANKRAS II Study Group.

BACKGROUND: Organochlorine compounds such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (p,p'-DDT), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE), and some polychlorinated biphenyls (PCBs) are carcinogenic to animals and possibly also to human beings. Occupational exposure to DDT may increase the risk of pancreas cancer. The high frequency of K-ras mutations in pancreatic cancer remains unexplained. We analysed the relation between serum concentrations of selected organochlorine compounds and mutations in codon 12 of the K-ras gene in patients with exocrine pancreatic cancer. METHODS: Cases were prospectively identified in five hospitals. Mutations in K-ras were analysed by PCR and artificial restriction fragment length polymorphism. Cases of pancreatic cancer with wild-type K-ras (n=17) were frequency matched for age and sex to cases of pancreatic cancer with a K-ras mutation (n=34, case-case study). These 51 cases were further compared with 26 hospital controls (case-control comparison). Serum organochlorine concentrations were measured by high-resolution gas chromatography with electron-capture detection and negative ion chemical ionisation mass spectrometry. FINDINGS: Serum concentrations of p,p'-DDT were significantly higher in pancreatic cancer cases with a K-ras mutation than in cases without a mutation (odds ratio for upper tertile 8.7 [95% CI 1.6-48.5], p for trend=0.005). For p,p'-DDE the corresponding figures were 5.3 (1.1-25.2, p for trend=0.031). These estimates held after adjusting for total lipids, other covariates, and total PCBs. A specific association was observed between a glycine to valine substitution at codon 12 and both p,p'-DDT and p,p'-DDE concentrations (odds ratio 15.9, p=0.044 and odds ratio 24.1, p=0.028; respectively). A similar pattern was shown for the major di-ortho-chlorinated PCBs (congeners 138, 153, and 180), even after adjustment for p,p'-DDE, but without a specific association with spectrum. Concentrations of p,p'-DDT and p,p'-DDE were similar among wild-type cases and controls, but significantly higher for K-ras mutated cases than for controls (p<0.01). INTERPRETATION: Organochlorine compounds such as p,p'-DDT, p,p'-DDE, and some PCBs could play a part in the pathogenesis of exocrine pancreatic cancer through modulation of K-ras activation. The results require replication, but they suggest new roles for organochlorines in the development of several cancers in human beings.

Aged↗

[Agreement between information supplied by the patient and a family member on medical history, consumption of tobacco, alcohol and coffee and diet in cancer of the exocrine pancreas and extrahepatic biliary tract].

OBJECTIVE: No study on mutations in the K-ras oncogene and cancer of the exocrine pancreas or cancer of the biliary system has analyzed the reliability of clinical and epidemiological information. METHODS: Agreement between patient and surrogate on factors potentially related to both tumours was evaluated within a multicentre prospective study. Interviews were personally administered to both patient and surrogate (N = 110 pairs). Agreement was examined via the simple kappa index (k), the weighted kappa index (kw), the percentage of simple agreement, and the percentages of positive and negative agreement. RESULTS: Agreement for medical history was excellent (k between 0.89 and 0.76), as it was for tobacco consumption (k = 0.98). Agreement was moderate for coffee consumption (k = 0.68), frequencies of food groups (kw from 0.66 to 0.38), and consumption of alcoholic drinks (k from 0.66 to 0.32). Surrogates indicated a higher consumption of alcohol than patients. CONCLUSION: Surrogates can be an alternative source of information when patients cannot be interviewed, but information on alcohol consumption should be treated with caution.

Adult↗