Faculty Bibliography

BACKGROUND:We evaluated whether articles on molecular diagnostic tests interpret appropriately the clinical applicability of their results. METHODS:We selected original-research articles published in 2006 that addressed the diagnostic value of a molecular test. We defined overinterpretation of clinical applicability by means of prespecified rules that evaluated study design, conclusions regarding applicability, presence of statements suggesting the need for further clinical evaluation of the test, and diagnostic accuracy. Two reviewers independently evaluated the articles; consensus was reached after discussion and arbitration by a third reviewer. RESULTS:Of 108 articles included in the study, 82 (76%) used a design that used healthy controls or alternative-diagnosis controls, only 15 (11%) addressed a clinically relevant population similar to that in which the test might be applied in practice, 104 articles (96%) made definitely favorable or promising statements regarding clinical applicability, and 61 (56%) of the articles apparently overinterpreted the clinical applicability of their findings. Articles published in journals with higher impact factors were more likely to overinterpret their results than those with lower impact factors (adjusted odds ratio, 1.71 per impact factor quartile; 95% CI, 1.09-2.69; P = 0.020). Overinterpretation was more common when authors were based in laboratories than in clinical settings (adjusted odds ratio, 18.7; 95% CI, 1.41-249; P = 0.036). CONCLUSIONS:Although expectations are high for new diagnostic tests based on molecular techniques, the majority of published research has involved preclinical phases of research. Overinterpretation of the clinical applicability of findings for new molecular diagnostic tests is common.

INTRODUCTION/BACKGROUND:When studying the effects of organochlorine compounds (OCs) on human health it is common to correct serum concentrations of OC by total lipids (TL). However, the relationship between serum OCs and serum TL is far from established in many diseases, including several cancers. Our aim was to analyze the relationship between serum OC and TL in patients with pancreatic ductal adenocarcinoma (PDA), and to explore several alternatives to perform the OC lipid correction. METHODS:Incident cases of PDA were interviewed and had blood drawn soon around hospital admission (n=144). Serum concentrations of OCs were analysed by high-resolution gas chromatography with electron-capture detection. RESULTS:Most patients with high TL had moderate or low concentrations of OCs. By contrast, the variability of OC values among patients with normal TL was large. Correlations were of a similar magnitude between OC and TL and between OC and total cholesterol; while these correlations were weak (all Spearman's rho<0.3 and R(2)<0.11), no OC were significantly correlated with triglycerides. Although all alternatives to the OC/TL linear ratio were statistically significant for at least one OC, their R(2) was always below 10%. CONCLUSIONS:In patients with severe diseases as PDA, linear correction of OC by TL as commonly performed in epidemiologic studies may be inappropriate. Results contribute to the scant literature on the rationale to correct serum concentrations of OC by lipids. They suggest that it is unwarranted to routinely correct OC by TL, offer ways to assess such need, and present alternatives as no TL correction, correction by total cholesterol only or use of different statistical models.

BACKGROUND:Knowledge is scant on the relationships between pathophysiologic processes common during cancer progression and changes in blood concentrations of organochlorine compounds (OCs). OBJECTIVE:To analyze the influence of tumor stage, cancer symptoms, and time of blood extraction on serum concentrations of OCs in exocrine pancreatic cancer (EPC). METHODS:Subjects were 144 incident cases of EPC prospectively recruited in eastern Spain. Blood was drawn and face-to-face interviews with patients were conducted during hospital admission. Information on signs and symptoms was obtained from medical records and patient interviews. OCs were analyzed by high-resolution gas chromatography with electron-capture detection. General linear models were applied to analyze log-transformed OCs corrected for total lipids. RESULTS:Lower concentrations of six of the seven OCs analyzed (p,p'-DDE, three polychlorinated biphenyls, hexachlorobenzene, and β-hexachlorocyclohexane) were observed in patients with cholestatic syndrome (jaundice, hypocholia, and choluria). The constitutional syndrome increased only p,p'-DDT. The lowering effect of the cholestatic syndrome was stronger than the increasing effect of the constitutional syndrome (fatigue, anorexia, and weight loss), except for p,p'-DDT. When symptoms were considered, stage had only weakly inverse relationships with OC levels. The effects of symptoms on p,p'-DDE, p,p'-DDT, and the three PCBs remained significant after adjusting by the interval from blood extraction to first symptom of EPC, and even when further adjusting by stage. CONCLUSIONS:Restriction or adjustment by stage and timing of blood draw may be insufficient to prevent biases associated with cancer progression. Symptoms may enable investigators to assess disease-induced changes in lipophilic exposure biomarkers.

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. Logistic regression was used to compare PDA cases (N = 107) with mutated and wild-type K-ras tumors (case-case study). RESULTS:Mutated cases were moderate or heavy drinkers more frequently than wild-type cases: the odds ratio adjusted by age, sex, smoking, and history of pancreatitis (ORa) was 3.18 (95% confidence interval: 1.02-9.93; P = 0.046). Total grams of alcohol and years of consumption were higher in mutated than in wild-type cases: the ORa for lifetime alcohol consumption over 507,499 g was 3.35 (95% CI: 0.81-13.88); and for more than 40 years of alcohol consumption it was 4.47 (95% CI: 1.05-19.02). Age at onset of alcohol consumption and years of abstinence were also associated with the presence of K-ras mutations. There were no significant differences in alcohol dependency. CONCLUSIONS:Alcohol consumption is weakly associated with an increased risk of having a K-ras mutated PDA. To confirm or to refute the hypothesis that ethanol, acetaldehyde or other alcohol-related substances might influence the acquisition or persistence of K-ras mutations in the pancreatic epithelium, large and unselected studies are warranted.

BACKGROUND:Little is known about factors affecting participation in population-based biomonitoring studies. We analyzed socioeconomic factors influencing participation in the Barcelona Health Survey (BHS) study on the distribution of serum concentrations of persistent organic pollutants (POPs). METHODS:After completing the BHS personal interview at home participants aged >or=15 years were invited to donate blood. Conducted on a different date and location, the POPs study included additional questions, blood extraction, and a brief physical examination. Factors influencing participation were analyzed by logistic regression. RESULTS:Of 523 BHS participants that we contacted to participate in the study, 231 (44%) participated; they were broadly representative of the city population regarding sex, birth place, body mass index (BMI), employment status and occupational social class. Participants in the POPs study had higher educational level and family income. Controlling for confounders, participation was slightly higher among women than men (odds ratio [OR]=1.38, p=0.02), and lower among the youngest and oldest subjects (p=0.002), with a strong and monotonic trend of increasing participation with increasing educational level (p<0.001) (OR for university level vs. no studies=4.58, 95% CI: 2.3-9.3). CONCLUSIONS:Although participation was somewhat low, participants were similar to the city population regarding sex, BMI, birth place, employment, and occupational social class. Health surveys that integrate environmental biomarkers should invest specific resources to encourage participation of the youngest and oldest individuals, and of those with more disadvantaged socioeconomic position (particularly, citizens with lowest education).

BACKGROUND:Targets set by health care organizations on time intervals between cancer diagnosis and treatment often go unmet. The objective of the study was to analyse the interval from diagnosis to treatment onset, and related factors, in the six most incident cancers in Catalonia (Spain), a developed European region with universal free access to health care. METHODS:Twenty-two hospitals contributed 1023 incident cancer patients (198 lung, 253 colorectal, 95 prostate, 109 urinary bladder, 266 breast, 102 endometrial). Information was gathered from hospital medical records. The dependent variable was the length of the diagnosis to treatment interval (DTI). Independent variables were age, sex, disease stage, hospital level, mode of admission to hospital, and type of physician seen before admission. Multivariate-adjusted odds ratios were calculated by unconditional logistic regression for each cancer site. RESULTS:The median DTI (in days) was 39 for lung cancer, 25 for colorectal, 108 for prostate, 69 for bladder, 35 for breast and 40 for endometrial cancer. In prostate and bladder cancers, over 78% of patients showed a DTI >30 days, while in colorectal the figure was 42%. Disseminated stage (distant metastases) was associated with a lower DTI in all sites. Patients admitted to third-level hospitals and with an elective admission were more likely to have a DTI >30 days. CONCLUSIONS:In Catalonia, a substantial proportion of cancer patients experience treatment delays that may impact negatively on psychological well-being, quality of life, and probably survival as well.