Toenail concentrations of trace elements and occupational history in pancreatic cancer.

BACKGROUND: Some occupations potentially entailing exposure to cadmium, arsenic, lead, selenium, nickel, and chromium have been associated with an increased risk of exocrine pancreatic cancer (EPC), but no studies have assessed whether body concentrations of such compounds differed among subjects occupationally exposed and unexposed. No studies which found that exposure to such metals increased the risk of EPC assessed whether past occupations were the source of exposure. OBJECTIVE: The aim was to analyse the relationship between toenail concentrations of trace elements and occupational history in EPC patients. METHODS: The study included 114 EPC cases personally interviewed on occupational history and lifestyle factors. Occupations were coded according to the International Standard Classification of Occupations 1988. Selected occupational exposures were assessed by two industrial hygienists and with the Finnish job-exposure matrix (Finjem). Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Adjusted geometric means (aGMs) and 95% confidence intervals (95% CI) were calculated. RESULTS: Patients occupationally exposed to aromatic hydrocarbon solvents (AHs) had higher concentrations of cadmium, manganese, lead, iron and vanadium. The aGM of cadmium concentrations for cases exposed to any pesticide was 0.056 µg/g [95% CI: 0.029-0.108], and, for unexposed cases, 0.023 µg/g [0.017-0.031]. Patients occupationally exposed to pesticides had higher concentrations of cadmium and manganese. Higher concentrations of vanadium, lead and arsenic were related to exposure to formaldehyde. Vanadium and lead were also associated with exposure to chlorinated hydrocarbon solvents, and arsenic was related to exposure to polycyclic aromatic hydrocarbons (PAHs). CONCLUSIONS: Patients occupationally exposed to AHs, pesticides, chlorinated hydrocarbon solvents, formaldehyde, volatile sulphur compounds and PAHs had higher concentrations of several metals. These elements may account for some of the occupational risks previously reported for pancreatic cancer.

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. 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.

Relationships between occupational history and serum concentrations of organochlorine compounds in exocrine pancreatic cancer.

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,p'-DDT, p,p'-DDE, hexachlorobenzene or ß-hexachlorocyclohexane. Subjects who ever worked in agriculture had lower concentrations of PCBs (all p < 0.05). Occupational exposure to lead, nickel and low frequency magnetic fields was significantly associated with higher concentrations of PCBs. 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.

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). The calculated frequencies for the m1 Val and m2 Asn alleles were 0.45 and 0.68, respectively. CYP1B1 genotypes were out of Hardy-Weinberg equilibrium; this was largely due to K-ras mutated PDA cases. The Val/Val genotype was over five times more frequent in PDA cases with a K-ras mutation than in wild-type cases (OR = 5.25; P = 0.121). In PDA, polymorphisms in CYP1B1 might be related with K-ras activation pathways.

Timing of blood extraction in epidemiologic and proteomic studies: results and proposals from the PANKRAS II Study.

There are no consensus guidelines or standards for epidemiologic and '-omics' studies using blood biomarkers on how to report the timing of extraction of blood samples. However, disease-induced changes in blood concentrations of exogenous and endogenous compounds may bias studies. The aim of the present report is to describe the timing of blood collection with respect to a variety of relevant clinical events in the PANKRAS II Study, and to suggest ways to display graphically the quantitative information. Subjects were 167 incident cases of exocrine pancreatic cancer prospectively recruited in five teaching hospitals in eastern Spain. Over 80% of patients had blood extracted during the first 6 months since onset of cancer symptoms, and 82% within the first month of admission to a study hospital. Over 80% of cases had blood drawn after an ultrasound, a CT scan or an ERCP, 25% after a laparotomy, and 37% after treatment onset. All three intervals from blood extraction to diagnosis, to treatment onset and to interview had a median of 0 days, and 88% of cases had blood drawn within 2 weeks of diagnosis. Over 72% of cases had concentrations of total lipids in the medium, normal range. Results suggest ways to report intervals involving blood biomarkers and may contribute to develop consensus guidelines and standards on the collection of blood samples in epidemiologic and '-omics' research.

Mixing journal, article, and author citations, and other pitfalls in the bibliographic impact factor

Noticias sobre la desaparición de las revistas biomédicas parecen prematuras. Puestas al día, las revistas científicas tradicionales continúan siendo fuentes altamente valiosas, vehículos de información, debate crítico y conocimiento. Algunos de los análisis muestran un énfasis desproporcionado sobre cuestiones tecnológicas y formales, si los comparamos con la importancia atribuida a los asuntos relacionados con el poder. No todas las revistas deben tener una tirada grande. Hay muchos ejemplos de revistas eficientes y de alta calidad con un magnífico impacto en audiencias relativamente pequeñas, a quienes la revista les resulta crítica desde el punto de vista intelectual, provechosa y agradable para la lectura. ¿Cómo podemos alcanzar un mejor conocimiento de la gama de impactos completa de un artículo? La mezcla entre las tres entidades definidas (revistas, artículos y autores) ha dominado a menudo los juicios de valor. Datos utilizados por el Instituto para la Información Científica presentan puntos flacos en los análisis atentos de sus exámenes. El plazo de dos años para que las citas cuenten con los favores de "movimiento rápido" del factor de impacto bibliográfico, "elementales" disciplinas biomédicas, consideramos que es menos apropiada para los estudios de salud pública. Es cada vez mayor la atención prestada al número de citas recibidas por cada artículo individual. Por lo que es posible realizar progresos dirigidos a asuntos más válidos, precisos, justos y relevantes.

Semiology, proteomics, and the early detection of symptomatic cancer.

"Diagnostic delay," the duration of symptoms or the symptom to diagnosis interval (SDI), are highly complex variables that reflect the behavior of the patient and the attending physician, tumor biology and host-tumor interactions, the functioning of the health care system, and sociocultural norms. In addition to tumor stage, other variables mediate the relationship between duration of symptoms and survival; clinical and epidemiologic procedures to measure them must be improved. Largely at odds with clinical and common wisdom, decades of research have shown that often SDI is not associated with tumor stage and/or with survival from cancer. It would be relevant to increase evidence in support of the notion that, for each type of tumor, there is a positive relationship between the length of the presymptomatic and the symptomatic phases. SDI could then be used to classify tumors according to their likelihood of being detected early when still asymptomatic. Also, tumors could be classified according to the ratio of the median SDI to the median survival (SDI to survival ratio, SSR), which may estimate the relative likelihood for clinical lead-time bias. If adhering to rigorous methodologic standards, proteomic analyses of early-stage cancers might provide new insights into changes that occur in early phases of tumorigenesis. More real examples are needed of uses of pathologic and genomic data to study mechanisms through which SDI influences-or fails to influence-prognosis. The degree of correlation between proteomic patterns and classic semiology constitutes an area of interest in itself; their respective correlations with cancer prognosis should be assessed in properly designed epidemiologic studies.

Mixing journal, article, and author citations, and other pitfalls in the bibliographic impact factor.

News of the death of biomedical journals seem premature. Revamped traditional scientific journals remain highly valued sources and vehicles of information, critical debate, and knowledge. Some analyses seem to place a disproportionate emphasis on technological and formal issues, as compared to the importance ascribed to matters of power. Not all journals must necessarily have a large circulation. There are many examples of efficient, high-quality journals with a great impact on relatively small audiences for whom the journal is thought-provoking, useful, and pleasant to read. How can we achieve a better understanding of an article s spectrum of impacts? A certain mixing of three distinct entities (journals, articles, and authors) has often pervaded judgments. Data used by the Institute for Scientific Information present weaknesses in their accuracy. The two-year limit for citations to count towards the bibliographic impact factor favors "fast-moving", "basic" biomedical disciplines and is less appropriate for public health studies. Increasing attention is given to the specific number of citations received by each individual article. It is possible to make progress towards more valid, accurate, fair, and relevant assessments.