Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC)

Alcohol consumption may be associated with risk of colorectal cancer (CRC), but the epidemiological evidence for an association with specific anatomical subsites, types of alcoholic beverages and current vs. lifetime alcohol intake is inconsistent. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 478,732 study subjects free of cancer at enrolment between 1992 and 2000 were followed up for an average of 6.2 years, during which 1,833 CRC cases were observed. Detailed information on consumption of alcoholic beverages at baseline (all cases) and during lifetime (1,447 CRC cases, 69% of the cohort) was collected from questionnaires. Cox proportional hazard models were used to examine the alcohol-CRC association. After adjustment for potential confounding factors, lifetime alcohol intake was significantly positively associated to CRC risk (hazard ratio, HR=1.08, 95%CI=1.04-1.12 for 15 g/day increase), with higher cancer risks observed in the rectum (HR=1.12, 95%CI=1.06-1.18) than distal colon (HR=1.08, 95%CI=1.01-1.16), and proximal colon (HR=1.02, 95%CI=0.92-1.12). Similar results were observed for baseline alcohol intake. When assessed by alcoholic beverages at baseline, the CRC risk for beer (HR=1.38, 95%CI=1.08-1.77 for 20-39.9 vs. 0.1-2.9 g/day) was higher than wine (HR=1.21, 95%CI=1.02-1.44), although the two risk estimates were not significantly different from each other. Higher HRs for baseline alcohol were observed for low levels of folate intake (1.13, 95%CI=1.06-1.20 for 15 g/day increase) compared to high folate intake (1.03, 95%CI=0.98-1.09). In this large European cohort, both lifetime and baseline alcohol consumption increase colon and rectum cancer risk, with more apparent risk increases for alcohol intakes greater than 30 g/day.     

Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk; results from the European prospective investigation into cancer and nutrition

We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, to examine the associations between prediagnostic serum concentrations of C-peptide, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-2, and endometrial cancer risk. Among pre- and post-menopausal women, who were not currently using exogenous hormones, 286 women developed incident endometrial cancer during an average 5.1 years follow-up. Using risk set sampling, 555 matched control subjects were selected. In conditional logistic regression models adjusted for matching factors only, endometrial cancer risk increased with increasing serum levels of C-peptide (relative risks (RR) for the top vs. bottom quartile = 2.13 [95% confidence interval (CI) 1.33-3.41], p(trend) = 0.001, and decreasing serum levels of IGFBP-2 (RR for the top vs. bottom quartile = 0.56 [95% CI 0.35-0.90], p(trend) = 0.03, but was not significantly associated with IGFBP-1 levels (RR for the top vs. bottom quartile = 0.76 [95% CI 0.47-1.21], p(trend) = 0.25). In BMI-adjusted models, only the C-peptide association remained marginally statistically significant (RR for the top vs. bottom quartile = 1.56 [95% CI 0.94-2.57], p(trend) = 0.05 for C-peptide; 0.84 [95% CI 0.50-1.40], p(trend) = 0.74 for IGFBP-2; and 1.08 [95% CI 0.65-1.78], p(trend) = 0.86 for IGFBP-1 levels). These associations were stronger among nonfasting women (< or =< or =6 hr since last meal; 63% of subjects) but were not evident among fasting women, although the interactions were not statistically significant. The C-peptide-risk association was substantially attenuated after adjustment for free estradiol in postmenopausal women (RR for the top vs. bottom quartile = 1.28 [95% CI 0.67-2.45], p(trend) = 0.42. Our results provide modest support to the hypothesis that hyperinsulinaemia is a risk factor for endometrial cancer.     

Lung transplantation in children following treatment for malignancy.

BACKGROUND: End-stage lung disease is a rare complication of treatment for hematologic and solid tumors in children. When present, it is generally progressive, resulting in the patient being cured of cancer only to die of respiratory failure. Lung transplantation is believed by some to be of overly high risk in this population because of the pre-existing malignancy as well as the presumed compromised immune status. METHODS: Six children (Group 1), aged 5 to 17 years (mean 12.4 years), underwent lung transplantation at our institution because of either pulmonary fibrosis or bronchiolitis obliterans following treatment for acute leukemia (n = 5) or medulloblastoma (n = 1). All patients received chemotherapy, radiation and bone marrow transplantation in the course of treatment for their malignancies. The average forced expiratory volume in 1 second (FEV(1)) was 16% of the predicted value and forced vital capacity (FVC) was 28% of predicted. These results were compared with a similar group of 13 patients undergoing lung transplantation at our institution during the same time interval (Group 2). RESULTS: There were 2 deaths in Group 1, 1 early and 1 late, for an overall survival of 67% at a mean follow-up of 4.02 years. There were no early and 7 late deaths in Group 2 for an overall survival of 46% at a mean follow-up of 4.8 years. The acute rejection rate in the first post-transplant year was 0.2 episode/patient in Group 1 and 1.8 episode/patient in Group 2 (p <0.01). No patient in Group 1 has developed post-transplant lymphoproliferative disease or a relapse of their primary malignancy. Two patients in Group 1 developed unusual infections-Aspergillus and Mycobacterium chelonae. No such infections occurred in Group 2. CONCLUSIONS: Although this represents a small series, we believe that patients with respiratory failure following treatment of a prior malignancy are suitable candidates for lung transplantation. Although they may have some relative protection from acute rejection episodes by virtue of an already compromised immunologic status while receiving standard immunosuppression, an increased propensity for opportunistic infection may exist.     

Value of symptoms to predict tilt testing outcome in patients with clinical suspicion of vasovagal syncope

Studies to assess the value of clinical symptoms to predict the head-up tilt test (HUT) outcome in patients with suspicion of vasovagal syncope have shown controversial results. We undertook this study to compare the frequency of symptoms between subjects with and without history of syncope, its association with syncopal spells in those with a history of syncope and positive or negative HUT, and to identify clinical predictors of HUT outcome. Sixty seven subjects with a history of unexplained syncope and 26 subjects without a history of syncope were interviewed using a structured questionnaire before undergoing HUT, which was performed first in a passive phase and, if negative, was repeated with pharmacological challenge using 5 mg of sublingual isosorbide. Questionnaire included the 16 symptoms most frequently reported in previous studies. Only five symptoms were reported more frequently by subjects with history of syncope in comparison with subjects without it: visual blurring, dysesthesia, sighing dyspnea, tremor in fingers, and diaphoresis. Comparison of symptom frequency between patients with history of syncope and positive or negative HUT revealed that only two were significantly different: nausea and hot flashes. However, a detailed analysis of the data indicates that only hot flashes occurring just before the syncope were more common in those with a positive HUT. Although some symptoms were found more frequently in patients with a history of syncope than in those without it, the use of a structured questionnaire in the group of patients failed to predict the outcome of the HUT.     

Return to work after a non-work related sick spell: the role of age, sex, economic activity and autonomous community

BACKGROUND: To describe the duration of non-work related sickness absences incidents according to age, sex, economic activity and Autonomous Community. METHODS: The sample of non-work related sick spells included 76,598 incident cases started in 2002 among workers cover by the general regime of the Social Security system, and managed by an insurance company. The median and intercuartils range were estimated by sex, age, economic activities and Autonomous Comunnity. Probability ratio of continuing out of work (PRCOW) were compared among Autonomous Comunities, after adjusting by sexo, age and economic activities, taking Navarra as reference, using a log-logistic regression model with a gamma distribution. RESULTS: The 25% of cases there were returned to work at 40 day, the 50% at 90 day; and the 75% at 26 degrees day. Extremadura (PCOW=2,7; IC95%: 2,4-3,1) and Galicia (2,6; 2,4-2,9) showed the highest differences with Navarra. There were also statistically significant differences among economic activities after adjusting by age and sex. CONCLUSIONS: Return to work after a non-work related sick spell is a complex process, which is influenced by age, sex, economic activities and autonomous community.     

Prevalence and clinical significance of cardiac arrhythmia in Anderson-Fabry disease

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme alpha-galactosidase A. More than 60% of patients with AFD have evidence for cardiac involvement; the prevalence and clinical significance of arrhythmia in AFD are unknown. Seventy-eight consecutive patients (mean age 43.5 +/- 15.0 years, range 13.0 to 83.0; 43 men) with AFD were studied for 1.9 years (range 0.25 to 10). All patients underwent clinical evaluation, 12-lead electrocardiography, and echocardiography. Sixty patients (76.9%) underwent 24-hour ambulatory electrocardiographic monitoring. Persistent atrial fibrillation (AF) was present in 3 of 78 patients (3.9%); 8 (13.3%) had paroxysmal AF, and 5 (8.3%) had nonsustained ventricular tachycardia (VT). Patients with nonsustained VT were all men, with a maximal left ventricular (LV) wall thickness >20 mm. Age (p <0.001), left atrial diameter (p = 0.001), maximal LV wall thickness (p = 0.003), LV mass index (p = 0.009), and angina (p = 0.02) were univariate predictors of AF or paroxysmal AF. Using these predictors in a stepwise logistic regression analysis model, age was the only independent predictor of AF or paroxysmal AF (odds ratio 1.2, 95% confidence interval 1.1 to 1.3, p = 0.001). During follow-up, there was 1 sudden cardiac death, 4 patients received pacemakers for bradyarrhythmia, and 1 received a biventricular pacemaker and an internal cardioverter defibrillator. In conclusion, arrhythmias are common in older patients with AFD. The high incidence of pacemaker implantation and sudden cardiac death suggests that arrhythmia has a significant impact on the natural history of AFD.     

The Size 1 ProSeal™ laryngeal mask airway in infants: a randomized,noncrossover study with the Classic™ laryngeal mask airway

Background: In recent years, numerous scientific publications have endorsed the superiority of the ProSeal? laryngeal mask airway (PLMA) over the Classic? laryngeal mask airway (cLMA) in adults, children, and infants. The PLMA forms a better seal for both the respiratory and gastrointestinal tracts, provides easier access to the gastrointestinal tract, and exerts lower mucosal pressures for a given seal pressure. This study aims to determine whether this superiority can also be observed for the size 1 PLMA used in anesthetized neonates and infants with positive pressure ventilation. Methods: Sixty consecutive neonates and infants undergoing elective surgical procedures were randomized to airway management with the size 1 PLMA or cLMA. For all patients, we recorded ease of insertion, effective airway time, number of placement attempts, oropharyngeal leak pressure, fiberoptic position, audible leaks, mask displacement, number of reinsertions during maintenance, gastric insufflation, and frequency of blood stain. Results: Ease of insertion, successful insertion in <3 attempts, fiberoptic position of the airway tube, and frequency of blood stain were similar in both groups. Effective airway time was lower for the PLMA group (30.5 vs 35.6 s). Oropharyngeal leak pressure was higher with the PLMA (32.9 vs 22.2 cm H₂O, P < 0.001) and gastric insufflation less common (0% vs 6%, P = 0.492). There were fewer mask displacements during maintenance of anesthesia with the PLMA (0% vs 26.7%, P < 0.001). Mask reinsertion was not necessary during maintenance of anesthesia with the PLMA, although it was necessary in 14 cases in the cLMA group (0% vs 46%, P < 0.001). Audible leaks were less common with the PLMA (0% vs 46%, P < 0.001). Conclusions: We conclude that the size 1 PLMA is a stable, safe, and efficacious airway control device during neonatal and infant anesthesia, allowing higher peak airway pressure during positive pressure ventilation, with fewer mask displacements and gastric insufflations than the cLMA.     

Biomarkers of oxidative stress and risk of developing colorectal cancer: a cohort-nested case-control study in the European Prospective Investigation Into Cancer and Nutrition

Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRR(adj)) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR(adj) = 1.89, 95% CI: 1.06, 3.36) and distal (IRR(adj) = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR(adj) = 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRR(adj) = 2.28, 95% CI: 1.78, 2.94; P-heterogeneity < 0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors.