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N Malats

Publications and source records attributed to N Malats.

49 records · Page 3Linked to original sources
PubMed1995

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↗
PubMed1995

Disagreement between hospital medical records and a structured patient interview on the type and date of the first symptom in cancers of the digestive tract.

Medical records have often been found to be less reliable than interviews to patients when data on the initial signs and symptoms of cancer, and the out-of-hospital diagnostic process are sought; in spite of this, a large body of research on "diagnostic delay" in cancer is based on clinical records. As part of a study on delay in neoplasms of the digestive tract we analyzed the agreement on the type and date of the initial symptom between hospital records and a structured personal interview. Records were abstracted for a random sample (N = 60) of 183 patients interviewed. Concordance on the date of the first symptom was deemed to exist if the difference was +/- 30 days. The Kappa index (kappa) and the overall proportion of agreement (with its corresponding 95% confidence interval) were used. Medical records and structured personal interviews were concordant on the type of the first neoplastic symptom in only 61% of cases (kappa = 0.50): 67% in esophagus cancer (kappa = 0.49), 60% in stomach cancer (kappa = 0.52), and 61% in colorectal cancer (kappa = 0.50). Records underestimated the occurrence of anorexia as first symptom and overestimated weight loss and dysphagia. Only 56% of cases were date-concordant, the agreement being lower in colorectal cancer (46%) than in esophageal (67%) and stomach cancer (75%). Records indicated the first symptom to have occurred at a later date than interviews in 33% of cases; overall, a study based on hospital records would have underestimated the symptom to diagnosis interval by 2.2 months per patient. Only 40% of cases were totally (symptom and date) concordant. Marked discrepancies may exist between the information contained in medical records and what patients report during a structured interview. The quality of medical records data on the duration and nature of cancer symptoms should be assessed before its use in etiologic and evaluative research.

Aged↗
PubMed1994

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↗
PubMed1994

Cancer survival and the duration of symptoms. An analysis of possible forms of the risk function. ISDS II Project Investigators.

The time interval between onset of symptoms and the diagnosis of cancer [symptom to diagnosis interval (SDI), or duration of symptoms] is a highly complex variable reflecting patient behaviour, the clinical course, the functioning of the health system and tumour biology. In order to assess possible forms of the risk function of SDI upon cancer survival whilst taking into account the effects of age, sex, tumour site and stage at diagnosis, 1887 symptomatic cases of lung, breast, stomach, colon, rectal, bladder cancer and lymphomas registered in the Tumour Registry of the Hospital del Mar (Barcelona) were analysed by means of survival curves and Cox proportional hazards regression. Subjects (mean age 64 years) were followed for a median length of 15 months after diagnosis (follow-up rate 93.5%). SDI showed a weak relationship with tumour stage at diagnosis and with survival: out of the seven sites studied, only in breast cancer was tumour extension at diagnosis significantly influenced by duration of symptoms, and only lung and rectal cancers showed a detectable form of the risk function of SDI upon survival; neither was linear, and for rectal cancer the relationship was complexly related with tumour stage. Hence, results show that forms of the risk function of duration of symptoms on cancer survival are specific to tumour sites, and that the interval should not be represented as a linear, continuous term. Studies analysing more complex sets of factors, processes and forms of the SDI function are needed.

Age Distribution↗
PubMed1992

Myelodysplastic syndromes and malignant solid tumors: analysis of 21 cases.

We studied the association between myelodysplastic syndromes (MDS) and malignancies in a cohort of 155 patients with MDS, 21 of whom presented malignant solid tumors. Myelodysplasia was present after the diagnosis of cancer in eight patients (interval between the diagnosis of both conditions 18 months, median survival 49.5 months), simultaneously with diagnosis in 11 (median survival 8 months), and before malignancy in two patients (interval between the diagnosis of both conditions 47 and 7 months). One patient was given chemotherapy for lung cancer, and three patients received radiotherapy for adenocarcinoma of the kidney and cancer of the prostate. At the time of diagnosis of MDS, nine patients already presented metastatic spread. Fourteen patients died, ten as a result of tumor-related complications and four because of transformation to acute nonlymphocytic leukemia. The analysis of the incidence of malignancy in patients with MDS was statistically significant for males, and the relative risk was significant in both sexes. The results of this study show that MDS patients present a higher incidence of malignant tumors than the general population, that MDS may be of real paraneoplastic significance, and that the occurrence of MDS in cancer patients may be considered to be related to the malignancy rather than an independent phenomenon.

Adenocarcinoma↗
PubMed1991

Influence of "diagnostic delay" upon cancer survival: an analysis of five tumour sites.

STUDY OBJECTIVE: The aim was to assess the relationship between survival, tumour stage, and the interval from first symptom to diagnosis (SDI, or duration of symptoms). DESIGN: This was a retrospective follow up study of a cohort of patients registered in the tumour registry of the Hospital del Mar (Barcelona). SETTING: Hospital based tumour registry, with patients derived mainly from the City of Barcelona. PARTICIPANTS: 1247 cases of lung, breast, stomach, colon, or rectal cancer were analysed using survival curves and Cox proportional hazards regression. Subjects (mean age 63.6 years) were followed for a median length of 12.9 months after diagnosis. At the time of diagnosis one fourth of patients had disseminated disease. MEASUREMENTS AND MAIN RESULTS: Based on clinical records, a physician registered the onset time of the first symptom attributable to cancer (from which the SDI is computed), as well as the tumour stage at diagnosis. Other measurements followed standard tumour registry procedures. Overall, the crude mean SDI was 5.15 months (SD 8.03, median 2.03); only 24.5% of cases had an SDI less than a month. Crude mean SDIs by anatomical site were as follows: lung cancer 3.07 months; breast 7.44; stomach 5.34; colon 5.74; rectum 5.03. Tumour extension did not appear to be significantly influenced by SDI, only breast cancer showing a distinct pattern of increased extension with increasing SDI. As expected, the probability of survival decreased monotonically with increasing stage in all sites. Tumour site was also a significant predictor of survival, which at one year ranged from 93% for breast cancer to 28% for lung cancer. However, a longer SDI tended sometimes to be associated with a better chance of survival, a fact that was most apparent in colon cancer. All Cox proportional hazards models showed a consistent picture: SDI was not a significant predictor of survival (age and sex adjusted hazard ratios ranging from 0.97 to 1.01), neither was sex; age did predict survival, and so did site and stage. CONCLUSIONS: The results provide further evidence of a very weak relationship between SDI and tumour stage at diagnosis (except for breast cancer), and between SDI and survival, thus emphasising some limitations within which early clinical detection operates. They also suggest that in addition to reflecting patient and physician behaviour, as well as the functioning of the health system, SDI may be influenced by the biological behaviour of the tumour.

Adult↗
PubMedDate not supplied

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↗
PubMedDate not supplied

[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↗
PubMedDate not supplied

[The symptom-diagnosis interval: a possible approximation to the natural history of neoplasms].

In order to assess the influence that age, sex, site of the primary tumor (SPT), the extension and histology may have on the interval first symptom-diagnosis (ISD), 1.149 cases of lung, breast, stomach, colon and rectum cancer registered in the Tumor Registry of the Hospital del Mar (Barcelona) were analyzed. Overall, mean ISD was 5.7 months. 12.7% of women and 5.5% of men (p less than 0.0001) had an ISD greater than one year. Age does not appear to influence ISD in this population (r = 0.014). Among women, the ISD for each SPT was as follows: breast cancer, 9.1 months; rectal cancer, 6.5; stomach, 4.9; colon, 4.7; lung, 2.7. Men's ISD were: rectum, 6.2; stomach, 5.9; colon, 5.7; lung 3.2. Age, sex, SPT, the extension and histology jointly explain only 18% of the ISD variability (multiple r = 0.42 p less than 0.0001). SPT and histology appear to be the strongest predictors, both remaining statistically significant when adjusting for the other four factors. While only breast cancer clearly showed a positive association between ISD and tumor extension, an unexpected inverse relationship was observed in rectal cancer. In some tumors, the ISD may just be an indicator for the rate of tumor growth. ISD data registered in a Tumor Registry can contribute to the study of a part of the natural history of neoplasms. Such analyses are also relevant for studies of secondary prevention and screening programs, access to and quality of care, and psychosocial predictors of the care seeking process.

Adult↗