Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort.

BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB. CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk.

Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (α- and ß-carotene, lycopene, ß-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), α- and γ-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma ß-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and α-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For α- and ß-carotene, lutein, sum of carotenoids and γ-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of ß-carotene, zeaxanthin and α-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted.

Prediagnostic immunoglobulin E levels and risk of chronic lymphocytic leukemia, other lymphomas and multiple myeloma-results of the European Prospective Investigation into Cancer and Nutrition.

Previous epidemiological studies suggest an inverse association between allergies, marked by elevated immunoglobulin (Ig) E levels, and non-Hodgkin lymphoma (NHL) risk. The evidence, however, is inconsistent and prospective data are sparse. We examined the association between prediagnostic total (low: <20; intermediate: 20-100; high >100 kU/l) and specific IgE (negative: <0.35; positive ≥0.35 kU/I) concentrations against inhalant antigens and lymphoma risk in a study nested within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 1021 incident cases and matched controls of NHL, multiple myeloma (MM) and Hodgkin lymphoma with a mean follow-up time of 7 years were investigated. Multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CI) were calculated by conditional logistic regression. Specific IgE was not associated with the risk of MM, B-cell NHL and B-cell NHL subtypes. In contrast, total IgE levels were inversely associated with the risk of MM [high level: OR = 0.40 (95% CI = 0.21-0.79)] and B-cell NHL [intermediate level: OR = 0.68 (95% CI = 0.53-0.88); high level: OR = 0.62 (95% CI = 0.44-0.86)], largely on the basis of a strong inverse association with chronic lymphocytic leukemia [CLL; intermediate level: OR = 0.49 (95% CI = 0.30-0.80); high level: OR = 0.13 (95% CI = 0.05-0.35)] risk. The inverse relationship for CLL remained significant for those diagnosed 5 years after baseline. The findings of this large prospective study demonstrated significantly lower prediagnostic total IgE levels among CLL and MM cases compared with matched controls. This corresponds to the clinical immunodeficiency state often observed in CLL patients prior to diagnosis. No support for an inverse association between prediagnostic levels of specific IgE and NHL risk was found.

Visceral adipose tissue: the link with esophageal adenocarcinoma.

OBJECTIVE: There is strong evidence for an association between obesity and esophageal adenocarcinoma (EAC). This study investigated the association between directly measured visceral adipose tissue and the risk of EAC. METHODS: In a case-control setting, we measured visceral adipose tissue in patients with EAC and healthy controls. Visceral adipose tissue was determined by abdominal CT. Exclusion criteria were uninterpretable CT scans and severe comorbidity. Controls were healthy volunteers undergoing screening CT colonography. Cross-sectional areas of visceral and subcutaneous adipose tissues were measured in cm(2) at L3/L4. Values of adipose tissue of EAC patients were extrapolated to stage 0 and compared to controls. The association between visceral adipose tissue and EAC was calculated with least-squares regression, adjusted for age, sex and TNM stage. RESULTS: We included 175 EAC patients and 251 controls. While body mass index was similar in EAC patients (26.1 kg/m(2)) and controls (26.2 kg/m(2)), visceral adipose tissue was significantly higher in EAC patients at stage 0 than in controls (276 vs. 231 cm(2); p = 0.015). Regarding subcutaneous adipose tissue, there was no difference. CONCLUSIONS: Patients with EAC have significantly higher visceral adipose tissue than healthy controls. Visceral adipose tissue is a risk factor in the development of EAC and seems to be more important than obesity alone.

Meat and fish consumption and risk of pancreatic cancer: results from the European Prospective Investigation into Cancer and Nutrition.

Pancreatic cancer is the fourth most common cause of cancer death worldwide with large geographical variation, which implies the contribution of diet and lifestyle in its etiology. We examined the association of meat and fish consumption with risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 477,202 EPIC participants from 10 European countries recruited between 1992 and 2000 were included in our analysis. Until 2008, 865 nonendocrine pancreatic cancer cases have been observed. Calibrated relative risks (RRs) and 95% confidence intervals (CIs) were computed using multivariable-adjusted Cox hazard regression models. The consumption of red meat (RR per 50 g increase per day = 1.03, 95% CI = 0.93-1.14) and processed meat (RR per 50 g increase per day = 0.93, 95% CI = 0.71-1.23) were not associated with an increased pancreatic cancer risk. Poultry consumption tended to be associated with an increased pancreatic cancer risk (RR per 50 g increase per day = 1.72, 95% CI = 1.04-2.84); however, there was no association with fish consumption (RR per 50 g increase per day = 1.22, 95% CI = 0.92-1.62). Our results do not support the conclusion of the World Cancer Research Fund that red or processed meat consumption may possibly increase the risk of pancreatic cancer. The positive association of poultry consumption with pancreatic cancer might be a chance finding as it contradicts most previous findings.

Intake of coffee, decaffeinated coffee, or tea does not affect risk for pancreatic cancer: results from the European Prospective Investigation into Nutrition and Cancer Study.

BACKGROUND & AIMS: Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer. METHODS: This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression. RESULTS: During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee (HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer (HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer (HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers. CONCLUSIONS: Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer.

Dietary intake of heme iron and risk of gastric cancer in the European prospective investigation into cancer and nutrition study.

Even though recent studies suggest that a high intake of heme iron is associated with several types of cancer, epidemiological studies in relation to gastric cancer (GC) are lacking. Our previous results show a positive association between red and processed meat and non cardia gastric cancer, especially in Helicobacter pylori infected subjects. The aim of the study is to investigate the association between heme iron intake and GC risk in the European prospective investigation into cancer and nutrition (EURGAST-EPIC). Dietary intake was assessed by validated center-specific questionnaires. Heme iron was calculated as a type-specific percentage of the total iron content in meat intake, derived from the literature. Antibodies of H. pylori infection and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control study within the cohort. The study included 481,419 individuals and 444 incident cases of GC that occurred during an average of 8.7 years of followup. We observed a statistically significant association between heme iron intake and GC risk (HR 1.13 95% CI: 1.01-1.26 for a doubling of intake) adjusted by sex, age, BMI, education level, tobacco smoking and energy intake. The positive association between heme iron and the risk of GC was statistically significant in subjects with plasma vitamin C <39 mmol/l only (log2 HR 1.54 95% CI (1.01-2.35). We found a positive association between heme iron intake and gastric cancer risk.

The association of circulating adiponectin levels with pancreatic cancer risk: a study within the prospective EPIC cohort.

Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a case-control study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.23-0.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.67-3.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development.

Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study.

A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 35-70 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical-trapping antioxidant parameter (TRAP), measuring reducing and chain-breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.46-0.95) and TRAP (adjusted HR 0.61; 95%CI (0.43-0.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.22-0.76) p for trend <0.001 for FRAP; adjusted HR 0.52; 95%CI (0.28-0.97) p for trend <0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.21-0.75) p < 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC.

Menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in a cohort of women from the European Prospective Investigation Into Cancer and Nutrition.

The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35-70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; P(trend) = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women.

Surgical gastrojejunostomy or endoscopic stent placement for the palliation of malignant gastric outlet obstruction (SUSTENT study): a multicenter randomized trial.

BACKGROUND: Both gastrojejunostomy (GJJ) and stent placement are commonly used palliative treatments of obstructive symptoms caused by malignant gastric outlet obstruction (GOO). OBJECTIVE: Compare GJJ and stent placement. DESIGN: Multicenter, randomized trial. SETTING: Twenty-one centers in The Netherlands. PATIENTS: Patients with GOO. INTERVENTIONS: GJJ and stent placement. MAIN OUTCOME MEASUREMENTS: Outcomes were medical effects, quality of life, and costs. Analysis was by intent to treat. RESULTS: Eighteen patients were randomized to GJJ and 21 to stent placement. Food intake improved more rapidly after stent placement than after GJJ (GOO Scoring System score > or = 2: median 5 vs 8 days, respectively; P < .01) but long-term relief was better after GJJ, with more patients living more days with a GOO Scoring System score of 2 or more than after stent placement (72 vs 50 days, respectively; P = .05). More major complications (stent: 6 in 4 patients vs GJJ: 0; P = .02), recurrent obstructive symptoms (stent: 8 in 5 patients vs GJJ: 1 in 1 patient; P = .02), and reinterventions (stent: 10 in 7 patients vs GJJ: 2 in 2 patients; P < .01) were observed after stent placement compared with GJJ. When stent obstruction was not regarded as a major complication, no differences in complications were found (P = .4). There were also no differences in median survival (stent: 56 days vs GJJ: 78 days) and quality of life. Mean total costs of GJJ were higher compared with stent placement ($16,535 vs $11,720, respectively; P = .049 [comparing medians]). Because of the small study population, only initial hospital costs would have been statistically significant if the Bonferroni correction for multiple testing had been applied. LIMITATIONS: Relatively small patient population. CONCLUSIONS: Despite slow initial symptom improvement, GJJ was associated with better long-term results and is therefore the treatment of choice in patients with a life expectancy of 2 months or longer. Because stent placement was associated with better short-term outcomes, this treatment is preferable for patients expected to live less than 2 months. ( CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN 06702358.).

Use of a colonoscope for distal duodenal stent placement in patients with malignant obstruction.

BACKGROUND: Stent placement in the distal duodenum or proximal jejunum with a therapeutic gastroscope can be difficult, because of the reach of the endoscope, loop formation in the stomach, and flexibility of the gastroscope. The use of a colonoscope may overcome these problems. OBJECTIVE: To report our experience with distal duodenal stent placement in 16 patients using a colonoscope. METHODS: Multicenter, retrospective series of patients with a malignant obstruction at the level of the distal duodenum and proximal jejunum and treated by stent placement using a colonoscope. Main outcome measurements are technical success, ability to eat, complications, and survival. RESULTS: Stent placement was technically feasible in 93% (15/16) of patients. Food intake improved from a median gastric outlet obstruction scoring system (GOOSS) score of 1 (no oral intake) to 3 (soft solids) (p = 0.001). Severe complications were not observed. One patient had persistent obstructive symptoms presumably due to motility problems. Recurrent obstructive symptoms were caused by tissue/tumor ingrowth through the stent mesh [n = 6 (38%)] and stent occlusion by debris [n = 1 (6%)]. Reinterventions included additional stent placement [n = 5 (31%)], gastrojejunostomy [n = 2 (12%)], and endoscopic stent cleansing [n = 1 (6%)]. Median survival was 153 days. CONCLUSION: Duodenal stent placement can effectively and safely be performed using a colonoscope in patients with an obstruction at the level of the distal duodenum or proximal jejunum. A colonoscope has the advantage that it is long enough and offers good endoscopic stiffness, which avoids looping in the stomach.

ERCP as an outpatient treatment: a review.

BACKGROUND: ERCP on an outpatient basis could be as safe as on an inpatient basis and may also reduce medical costs. OBJECTIVE: To review the available literature to determine the safety of an ERCP performed on an outpatient basis. DESIGN: A review of the published literature was performed by searching PubMed, the Cochrane Library, EMBASE, and the Web of Science. PATIENTS: Patients who were undergoing an ERCP. INTERVENTIONS: An ERCP on an inpatient or outpatient basis. MAIN OUTCOME MEASUREMENTS: Patient and treatment characteristics, complications, and prolonged hospital admissions and readmissions. RESULTS: Eleven studies were included in this review, of which 5 were comparative studies, 5 were prospective studies, and 1 was a retrospective study. In these series, a total of 2483 patients underwent an ERCP on an outpatient basis and 2320 patients were admitted overnight after an ERCP. Complications were seen in 184 of 2483 outpatients (7%), of which 72% of complications (107/149) presented within 2 to 6 hours, 10% (15/149) within 6 to 24 hours, and 18% (27/149) more than 24 hours after the ERCP. Three percent of the inpatients (82/2320) developed a complication, of which 95% of complications (78/82) presented within 24 hours and 5% (4/82) presented more than 24 hours after the ERCP. A prolonged hospital stay after an ERCP was indicated in 6% of the designated outpatients (148/2483), whereas 3% of outpatients (74/2149) and <1% of inpatients (4/2320) were readmitted after discharge. LIMITATIONS: Limited data available. CONCLUSIONS: This review shows that, with a selective policy, an ERCP on an outpatient basis seems as safe as when performed on an inpatient basis.

Stent versus gastrojejunostomy for the palliation of gastric outlet obstruction: a systematic review.

BACKGROUND: Gastrojejunostomy (GJJ) is the most commonly used palliative treatment modality for malignant gastric outlet obstruction. Recently, stent placement has been introduced as an alternative treatment. We reviewed the available literature on stent placement and GJJ for gastric outlet obstruction, with regard to medical effects and costs. METHODS: A systematic review of the literature was performed by searching PubMed for the period January 1996 and January 2006. A total of 44 publications on GJJ and stents was identified and reported results on medical effects and costs were pooled and evaluated. Results from randomized and comparative studies were used for calculating odds ratios (OR) to compare differences between the two treatment modalities. RESULTS: In 2 randomized trials, stent placement was compared with GJJ (with 27 and 18 patients in each trial). In 6 comparative studies, stent placement was compared with GJJ. Thirty-six series evaluated either stent placement or GJJ. A total of 1046 patients received a duodenal stent and 297 patients underwent GJJ. No differences between stent placement and gastrojejunostomy were found in technical success (96% vs. 100%), early and late major complications 7% vs. 6% and 18% vs. 17%, respectively) and persisting symptoms (8% vs. 9%). Initial clinical success was higher after stent placement (89% vs. 72%). Minor complications were less frequently seen after stent placement in the patient series (9% vs. 33%), however the pooled analysis showed no differences (OR: 0.75, p = 0.8). Recurrent obstructive symptoms were more common after stent placement (18% vs. 1%). Hospital stay was prolonged after GJJ compared to stent placement (13 days vs. 7 days). The mean survival was 105 days after stent placement and 164 days after GJJ. CONCLUSION: These results suggest that stent placement may be associated with more favorable results in patients with a relatively short life expectancy, while GJJ is preferable in patients with a more prolonged prognosis. The paucity of evidence from large randomized trials may however have influenced the results and therefore a trial of sufficient size is needed to determine which palliative treatment modality is optimal in (sub)groups of patients with malignant gastric outlet obstruction.

The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: a case-control study within the prospective EPIC Cohort.

BACKGROUND: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. METHODS: Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). RESULTS: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P(interaction) = 0.002). CONCLUSIONS AND IMPACT: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations.

Predictors of survival in patients with malignant gastric outlet obstruction: a patient-oriented decision approach for palliative treatment.

BACKGROUND: Gastrojejunostomy and stentplacement are the most commonly used treatments for malignant gastric outlet obstruction (GOO). The preference for either treatment largely depends on the expected survival. Our objective was to investigate predictors of survival in patients with malignant GOO and to develop a model that could aid in the decision for either gastrojejunostomy or stentplacement. METHODS: Prognostic factors for survival were collected from a literature search and evaluated in our patient population, which included 95 retrospectively and 56 prospectively followed cases. All 151 patients were treated with gastrojejunostomy or stentplacement. RESULTS: A higher WHO performance score was the only significant prognostic factor for survival in our multivariable analysis (HR 2.2 95%CI 1.7-2.9), whereas treatment for obstructive jaundice, gender, age, metastases, weight loss, level of obstruction and pancreatic cancer were not. A prognostic model that includes the WHO score was able to distinguish patients with a poor survival (WHO score 3-4, median survival: 31 days) from those with a relatively intermediate or good survival (WHO score 2, median survival: 69 and WHO score 0-1, median survival: 139 days, respectively). CONCLUSIONS: Only the WHO score is a significant predictor of survival in patients with malignant GOO. A simple prognostic model is able to guide the palliative treatment decision for either gastrojejunostomy (WHO score 0-1) or stentplacement (WHO 3-4) in patients with malignant GOO.

Barrett's esophagus in children: does it need more attention?

BACKGROUND: Few studies have reported on Barrett's esophagus (BE) in children. Moreover, information on the age at diagnosis and the duration between reflux-symptoms and diagnosis is lacking. METHODS: A review of the literature was performed in PubMed, EMBASE and the Cochrane database. RESULTS: Fourteen articles were included, of which 4 cohort studies and 10 studies investigating patients already diagnosed with BE. The cohort studies showed 37 patients diagnosed with BE (0.3-4.8%), mean age 12.4 years. Time between onset of reflux-symptoms and BE was 2.8 years. All 14 studies together showed 176 patients with BE (mean age 9.5 years). Time between onset of reflux-symptoms and BE was 5.3 years. During endoscopic follow-up of 45 patients, 26 still had BE, 17 no longer had evidence of BE, and two had developed esophageal-adenocarcinoma. CONCLUSION: This review shows that BE and esophageal-adenocarcinoma occur in children. However, criteria used to define BE by the included studies were not comparable to the current criteria and data on GERD symptoms may have been inaccurate. Therefore, we recommend performing a long-term prospective study on the relationship between (duration of) GERD and the development of BE in children in order to define screening guidelines.

A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.

Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (± 1 year), date (± 1 year) and time (± 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate ≤ 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI=0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR=1.17, 95% CI=1.00-1.38) but not in women (OR=0.91, 95% CI=0.78-1.07; p for heterogeneity <0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.