Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study.

BACKGROUND: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear. OBJECTIVE: To examine whether coffee consumption is associated with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: 10 European countries. PARTICIPANTS: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition). MEASUREMENTS: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800). RESULTS: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; γ-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels. LIMITATIONS: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once. CONCLUSION: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country. PRIMARY FUNDING SOURCE: European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.

Exploring the nature of prediagnostic blood transcriptome markers of chronic lymphocytic leukemia by assessing their overlap with the transcriptome at the clinical stage.

BACKGROUND: We recently identified 700 genes whose expression levels were predictive of chronic lymphocytic leukemia (CLL) in a genome-wide gene expression analysis of prediagnostic blood from future cases and matched controls. We hypothesized that a large fraction of these markers were likely related to early disease manifestations. Here we aim to gain a better understanding of the natural history of the identified markers by comparing results from our prediagnostic analysis, the only prediagnostic analysis to date, to results obtained from a meta-analysis of a series of publically available transcriptomics profiles obtained in incident CLL cases and controls. RESULTS: We observed considerable overlap between the results from our prediagnostic study and the clinical CLL signals (p-value for overlap Bonferroni significant markers 0.01; p-value for overlap nominal significant markers < 2.20e-16). We observed similar patterns with time to diagnosis and similar functional annotations for the markers that were identified in both settings compared to the markers that were only identified in the prediagnostic study. These results suggest that both gene sets operate in similar pathways. CONCLUSION: An overlap exists between expression levels of genes predictive of CLL identified in prediagnostic blood and expression levels of genes associated to CLL at the clinical stage. Our analysis provides insight in a set of genes for which expression levels can be used to follow the time-course of the disease; providing an opportunity to study CLL progression in more detail in future studies.

Growth rate of small pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: results from an endoscopic ultrasound based cohort study.

Background and aims In multiple endocrine neoplasia type 1 (MEN1), endoscopic ultrasound (EUS) is used for identification and follow-up of pancreatic neuroendocrine tumors (PNETs). The role of EUS in surveillance of small ( < 20 mm) PNETs is unclear, mostly because the natural course of these lesions is largely unknown. We aimed to determine annual growth and incidence rate of small PNETs in patients with MEN1 using EUS-based surveillance. Patients and methods Linear array EUS procedures in patients with MEN1 between 2002 and 2015 were identified. Number, size, and location of PNETs were recorded. Annual growth of PNETs < 20 mm identified at the initial EUS ("prevalent" PNETs) and during follow-up ("incident" PNETs) was calculated using mixed model linear regression analysis. Results A total of 54 patients were identified and 38 patients were included. In all, 226 PNETs were identified (median size 5.0 mm, interquartile range 3.7 - 7.5) of which 124 (55 %) were prevalent and 102 (45 %) were incident PNETs. Annual incidence rate was 0.79 PNETs/year (95 % confidence interval [CI] 0.73 to 0.87). Overall growth rate was 0.10 mm/year (95 %CI 0.02 to 0.19; P = 0.01); PNETs < 10 mm (n = 198) did not grow (P = 0.23), whereas PNETs ≥ 10 mm (n = 28) grew 0.44 mm/year (95 %CI 0.10 to 0.78; P = 0.01). Prevalent PNETs grew 0.21 mm/year (95 %CI 0.10 - 0.32; P < 0.001), whereas incident PNETs did not grow (P = 0.26). Conclusions The annual growth rate of small, solid PNETs in patients with MEN1 is lower than previously thought. Surveillance intervals could probably be prolonged without compromising safety.

Variation in palliative care of esophageal cancer in clinical practice: factors associated with treatment decisions.

Various treatments are available for the palliation of esophageal cancer, but the optimal therapeutic approach is unclear. This study aimed to assess the palliative treatment modalities used in patients with inoperable esophageal cancer and to identify factors associated with treatment decisions. A population-based, retrospective cohort study was conducted using data from the nationwide Netherlands Cancer Registry and medical records of seven participating hospitals. Patients diagnosed with stage III-IV inoperable esophageal or gastric cardia cancer in the central part of the Netherlands between 2001 and 2010 were included. Logistic regression analyses were performed to identify determinants of treatment choices. In total, 736 patients were initially treated with best supportive care (21%), stent placement (19%), chemotherapy (18%), external beam radiotherapy (EBRT) (16%), brachytherapy (6%), a combination of EBRT and brachytherapy (6%), a combination of chemotherapy and EBRT (5%) or another treatment (9%). The palliative approach varied for disease stage (P < 0.01) and hospital of diagnosis (P < 0.01). Independent factors affecting treatment decisions were age, degree of dysphagia, tumor histology, tumor localization, disease stage, and hospital of diagnosis. For example, patients diagnosed in one hospital were less likely to be treated with EBRT than with stent placement compared to patients in another hospital (odds ratio 0.20, 95% confidence interval 0.07-0.59). In conclusion, the initial palliative approach of patients with inoperable esophageal cancer varies widely and is not only associated with patient- and disease-related factors, but also with hospital of diagnosis. These findings suggest a lack of therapeutic guidance and highlight the need for more evidence on palliative care strategies for esophageal cancer.

Cost Efficacy of Metal Stents for Palliation of Extrahepatic Bile Duct Obstruction in a Randomized Controlled Trial.

BACKGROUND & AIMS: Endoscopic stents are placed for palliation of extrahepatic bile duct obstruction. Although self-expandable metal stents (SEMS) remain patent longer than plastic stents, they are more expensive. We aimed to evaluate which type of stent (plastic, uncovered SEMS [uSEMS], or partially covered SEMS [pcSEMS]) is the most effective and we assessed costs. METHODS: We performed a multicenter randomized trial in 219 patients at 18 hospitals in The Netherlands from February 2008 through February 2013. Patients were assigned randomly for placement of a plastic stent (n = 73), uSEMS (n = 75), or pcSEMS (n = 71) during endoscopic retrograde cholangiopancreatography. Patients were followed up for up to 1 year. Researchers were not blinded to groups. The main study end points included functional stent time and costs. RESULTS: The mean functional stent times were 172 days for plastic stents, 288 days for uSEMS, and 299 days for pcSEMS (P < .005 for uSEMS and pcSEMS vs plastic). The initial placement of plastic stents (€1042 or $1106) cost significantly less than placement of SEMS (€1973 or $2094) (P = .001). However, the total cost per patient at the end of the follow-up period did not differ significantly between plastic stents (€7320 or $7770) and SEMS (€6932 or $7356) (P = .61). Furthermore, in patients with short survival times (≤3 mo) or metastatic disease, the total cost per patient did not differ between plastic stents and SEMS. No differences in costs were found between pcSEMS and uSEMS. CONCLUSIONS: Although placement of SEMS (uncovered or partially covered) for palliation of extrahepatic bile duct obstruction initially is more expensive than placement of plastic stents, SEMS have longer functional time. The total costs after 1 year do not differ significantly with stent type. Dutch Clinical Trial Registration no: NTR1361.

Exposure to Ambient Air Pollution and the Risk of Inflammatory Bowel Disease: A European Nested Case-Control Study.

BACKGROUND: Industrialization has been linked to the etiology of inflammatory bowel disease (IBD). AIM: We investigated the association between air pollution exposure and IBD. METHODS: The European Prospective Investigation into Cancer and Nutrition cohort was used to identify cases with Crohn's disease (CD) (n = 38) and ulcerative colitis (UC) (n = 104) and controls (n = 568) from Denmark, France, the Netherlands, and the UK, matched for center, gender, age, and date of recruitment. Air pollution data were obtained from the European Study of Cohorts for Air Pollution Effects. Residential exposure was assessed with land-use regression models for particulate matter with diameters of <10 µm (PM10), <2.5 µm (PM2.5), and between 2.5 and 10 µm (PMcoarse), soot (PM2.5 absorbance), nitrogen oxides, and two traffic indicators. Conditional logistic regression analyses were performed to calculate odds ratios (ORs) with 95 % confidence intervals (CIs). RESULTS: Although air pollution was not significantly associated with CD or UC separately, the associations were mostly similar. Individuals with IBD were less likely to have higher exposure levels of PM2.5 and PM10, with ORs of 0.24 (95 % CI 0.07-0.81) per 5 µg/m(3) and 0.25 (95 % CI 0.08-0.78) per 10 µg/m(3), respectively. There was an inverse but nonsignificant association for PMcoarse. A higher nearby traffic load was positively associated with IBD [OR 1.60 (95 % CI 1.04-2.46) per 4,000,000 motor vehicles × m per day]. Other air pollutants were positively but not significantly associated with IBD. CONCLUSION: Exposure to air pollution was not found to be consistently associated with IBD.

Subtypes of fruit and vegetables, variety in consumption and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of 13 years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95% CI 0.75-1.01, p for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than 10 years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but appears unlikely.

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.

No decrease in the rate of early or missed colorectal cancers after colonoscopy with polypectomy over a 10-year period: a population-based analysis.

BACKGROUND & AIMS: It is not clear whether the incidence of missed or early colorectal cancers (CRCs) has decreased over time. We compared the rates of missed or early CRC after polypectomy between 1996 and 2006, and aimed to identify risk factors for these. METHODS: We performed a population-based, case-control study linking data from the Dutch Pathology Registry with data from The Netherlands Cancer Registry. Of all patients with an incident CRC in 1996 and 2006, we identified whether colonic histology specimens were available in the preceding 3 years. Patients with early or missed CRC were defined as those with previous colonic histology in the 6 to 36 months preceding CRC diagnosis. We performed multivariate logistic regression analysis to identify factors associated with missed or early CRCs. RESULTS: CRC was diagnosed in 6941 patients in 1996 and in 10,963 patients in 2006. The proportion of patients with early or missed CRC was 1.7% of all CRC patients in 1996 and 2.3% in 2006 (P = .012). Early or missed CRCs had a lower tumor, nodal, and metastasis stage than regularly diagnosed CRCs (P < .001), but rate of survival, adjusted for TNM stage, did not differ. CRCs of the right colon and transverse colon and splenic flexure were associated with a missed or early CRC (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.80-3.05; and OR, 2.14; 95% CI, 1.49-3.08, respectively), as was male sex (OR, 1.31; 95% CI, 1.06-1.62). CONCLUSIONS: Based on an analysis of the Dutch population, there has been no decrease in the occurrence of missed or early CRCs over a 10-year period. Location in the right side of the colon was an independent risk factor for missed or early CRCs.

Risk of neoplastic progression in Barrett's esophagus diagnosed as indefinite for dysplasia: a nationwide cohort study.

BACKGROUND AND STUDY AIMS: A histological diagnosis of "indefinite for dysplasia" (IND) in Barrett's esophagus is used when a diagnosis of genuine dysplasia is equivocal. The aim of the present study was to assess the risk of progression to high grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) after a diagnosis of IND in a nationwide cohort of patients with Barrett's esophagus. PATIENTS AND METHODS: Patients with a first diagnosis of IND in Barrett's esophagus between 2002 and 2011 were selected from a nationwide registry of histopathology diagnoses in The Netherlands. Patients were followed up until treatment for HGD, detection of EAC, or date of last endoscopy contact with biopsy sampling. RESULTS: In total, 1258 patients met the inclusion criteria, of whom 842 (66.9 %) underwent endoscopic follow-up. Patients were followed for a total of 2585 person-years (mean ± SD 3.01 ±â€Š2.6). Median duration until first follow-up endoscopy was 1.2 years (interquartile range 0.3 - 1.8 years). The progression rate from IND to the combined end point of HGD or EAC was 2.0 (95 % confidence interval [CI] 1.5 - 2.6) per 100 person-years and progression to EAC was 1.2 (95 %CI 0.8 - 1.6). After excluding cases with HGD or EAC within 1 year after IND diagnosis (n = 16), the progression rates were 1.4 (95 %CI 1.0 - 1.9) and 0.8 (95 %CI 0.5 - 1.2) per 100 person-years for HGD or EAC and EAC, respectively. CONCLUSION: In this large, population-based, cohort of patients with Barrett's esophagus, the incidence rate of HGD or EAC following a diagnosis of IND was 1.4 per 100 person-years. The results demonstrate the need for additional studies to select the subgroup of IND patients with an increased risk of neoplastic progression.

Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99% confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046).

Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy: results from the COIN study.

OBJECTIVE: The introduction of anti tumour necrosis factor-α (anti-TNFα) therapy might impact healthcare expenditures, but there are limited data regarding the costs of inflammatory bowel diseases (IBD) following the introduction of these drugs. We aimed to assess the healthcare costs and productivity losses in a large cohort of IBD patients. DESIGN: Crohn's disease (CD) and ulcerative colitis (UC) patients from seven university hospitals and seven general hospitals were invited to fill-out a web-based questionnaire. Cost items were derived from a 3 month follow-up questionnaire and categorised in outpatient clinic, diagnostics, medication, surgery and hospitalisation. Productivity losses included sick leave of paid and unpaid work. Costs were expressed as mean 3-month costs per patients with a 95% CI obtained using non-parametric bootstrapping. RESULTS: A total of 1315 CD patients and 937 UC patients were included. Healthcare costs were almost three times higher in CD as compared with UC, €1625 (95% CI €1476 to €1775) versus €595 (95% CI €505 to €685), respectively (p<0.01). Anti-TNFα use was the main costs driver, accounting for 64% and 31% of the total cost in CD and UC. Hospitalisation and surgery together accounted for 19% and <1% of the healthcare costs in CD and 23% and 1% in UC, respectively. Productivity losses accounted for 16% and 39% of the total costs in CD and UC. CONCLUSIONS: We showed that healthcare costs are mainly driven by medication costs, most importantly by anti-TNFα therapy. Hospitalisation and surgery accounted only for a minor part of the healthcare costs.

Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (α- and ß-carotene, canthaxanthin, ß-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (α-, ß- and γ- and δ-tocopherol) and dietary consumption of ß-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary ß-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties.

Surveillance of Barrett's esophagus and mortality from esophageal adenocarcinoma: a population-based cohort study.

OBJECTIVES: Barrett's esophagus (BE) is associated with an increased risk of developing esophageal adenocarcinoma (EAC). Patients with a known diagnosis of BE are usually advised to participate in an endoscopic surveillance program, but its clinical value is unproven. Our objective was to compare patients participating in a surveillance program for BE before EAC diagnosis with those not participating in such a program, and to determine predictive factors for mortality from EAC. METHODS: All patients diagnosed with EAC between 1999 and 2009 were identified in the nationwide Netherlands Cancer Registry. These data were linked to Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief, the Dutch Pathology Registry. Prior surveillance was evaluated, and multivariable Cox proportional hazards regression analysis was performed to identify predictors for all-cause mortality at 2-year and 5-year follow-up. RESULTS: In total, 9,780 EAC patients were included. Of these, 791 (8%) patients were known with a prior diagnosis of BE, of which 452 (57%) patients participated in an adequate endoscopic surveillance program, 120 (15%) patients in an inadequate program, and 219 (28%) patients had a prior BE diagnosis without participating. Two-year (and five-year) mortality rates were lower in patients undergoing adequate surveillance (adjusted hazard ratio (HR)=0.79, 95% confidence interval (CI)=0.64-0.92) when compared with patients with a prior BE diagnosis who were not participating. Other factors associated with lower mortality from EAC were lower tumor stage (stage I vs. IV, HR=0.19, 95% CI=0.16-0.23) and combining surgery with neoadjuvant chemo/radiotherapy (HR=0.66, 95% CI=0.58-0.76). CONCLUSIONS: Participation in a surveillance program for BE, but only if adequately performed, reduces mortality from EAC. Nevertheless, it remains to be determined whether such a program is cost-effective, as more than 90% of all EAC patients were not known to have BE before diagnosis.

Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: systematic review and meta-analysis.

BACKGROUND AND STUDY AIMS: Local recurrence has been observed after endoscopic mucosal resection (EMR) of nonpedunculated colorectal lesions. The indications for follow-up colonoscopy and the optimal time interval are currently unclear. The aims of this systematic review were to assess the frequency of local recurrence after EMR, to identify risk factors for recurrence, and to provide follow-up recommendations. METHODS: A literature search was performed in PubMed, EMBASE, and the Cochrane Library. EMR was defined as endoscopic snare resection after submucosal fluid injection for removal of nonpedunculated adenomas and early carcinomas. Local recurrence was subdivided into early recurrence (detected at the first follow-up colonoscopy) and late recurrence (detected after ≥ 1 previous normal colonoscopy). A random effects meta-analysis was performed to calculate the pooled estimate of risk of recurrence. RESULTS: A total of 33 studies were included. The mean recurrence risk after EMR was 15 % (95 % confidence interval [CI] 12 % - 19 %). Recurrence risk was higher after piecemeal resection (20 %; 95 %CI 16 % - 25 %) than after en bloc resection (3 %; 95 %CI 2 % - 5 %; P < 0.0001). In 15 studies that differentiated between early and late recurrences, 152/173 recurrences (88 %) occurred early. In four studies with follow-up at 3, 6, and ≥ 12 months, 19/25 (76 %) recurrences were detected at 3 months, increasing to 24 (96 %) at 6 months. In multivariable analysis, only piecemeal resection was associated with recurrence (3 of 3 studies). CONCLUSION: Local recurrence after EMR of nonpedunculated colorectal lesions occurs in 3 % of en bloc resections and 20 % of piecemeal resections. Piecemeal resection was the only independent risk factor for recurrence. As more than 90 % of recurrences are detected at 6 months after EMR, we propose that 6 months is the optimal initial follow-up interval.

Plasma alkylresorcinol concentrations, biomarkers of whole-grain wheat and rye intake, in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41 nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23 nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye.

Fruit and vegetable intake and cause-specific mortality in the EPIC study.

Consumption of fruits and vegetables is associated with a lower overall mortality. The aim of this study was to identify causes of death through which this association is established. More than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition study were included, of which 25,682 were reported deceased after 13 years of follow-up. Information on lifestyle, diet and vital status was collected through questionnaires and population registries. Hazard ratios (HR) with 95% confidence intervals (95% CI) for death from specific causes were calculated from Cox regression models, adjusted for potential confounders. Participants reporting consumption of more than 569 g/day of fruits and vegetables had lower risks of death from diseases of the circulatory (HR for upper fourth 0.85, 95% CI 0.77-0.93), respiratory (HR for upper fourth 0.73, 95% CI 0.59-0.91) and digestive system (HR for upper fourth 0.60, 95% CI 0.46-0.79) when compared with participants consuming less than 249 g/day. In contrast, a positive association with death from diseases of the nervous system was observed. Inverse associations were generally observed for vegetable, but not for fruit consumption. Associations were more pronounced for raw vegetable consumption, when compared with cooked vegetable consumption. Raw vegetable consumption was additionally inversely associated with death from neoplasms and mental and behavioral disorders. The lower risk of death associated with a higher consumption of fruits and vegetables may be derived from inverse associations with diseases of the circulatory, respiratory and digestive system, and may depend on the preparation of vegetables and lifestyle factors.

Fruit and vegetable consumption and mortality: European prospective investigation into cancer and nutrition.

In this study, the relation between fruit and vegetable consumption and mortality was investigated within the European Prospective Investigation Into Cancer and Nutrition. Survival analyses were performed, including 451,151 participants from 10 European countries, recruited between 1992 and 2000 and followed until 2010. Hazard ratios, rate advancement periods, and preventable proportions to respectively compare risk of death between quartiles of consumption, to estimate the period by which the risk of death was postponed among high consumers, and to estimate proportions of deaths that could be prevented if all participants would shift their consumption 1 quartile upward. Consumption of fruits and vegetables was inversely associated with all-cause mortality (for the highest quartile, hazard ratio = 0.90, 95% confidence interval (CI): 0.86, 0.94), with a rate advancement period of 1.12 years (95% CI: 0.70, 1.54), and with a preventable proportion of 2.95%. This association was driven mainly by cardiovascular disease mortality (for the highest quartile, hazard ratio = 0.85, 95% CI: 0.77, 0.93). Stronger inverse associations were observed for participants with high alcohol consumption or high body mass index and suggested in smokers. Inverse associations were stronger for raw than for cooked vegetable consumption. These results support the evidence that fruit and vegetable consumption is associated with a lower risk of death.

Endoscopic corticosteroid injections do not reduce dysphagia after endoscopic dilation therapy in patients with benign esophagogastric anastomotic strictures.

BACKGROUND & AIMS: Benign anastomotic strictures are often difficult to treat. We assessed the efficacy of adding corticosteroid injections to endoscopic dilation therapy with Savary bougienage. METHODS: In a multicenter, double-blind trial, 60 patients (mean age, 63 ± 9 years; 78% male) with an untreated cervical anastomotic stricture after esophagectomy with gastric tube reconstruction and dysphagia for at least solid food were randomly assigned to groups given 4 quadrant injections of 0.5 mL triamcinolone (40 mg/mL, n = 29) or saline (controls, n = 31) into the stricture, followed by Savary dilation to 16 mm. Dysphagia, complications, and quality of life were assessed after 1 and 2 weeks and 1, 3, and 6 months. The primary end point was a dysphagia-free period of 6 months. RESULTS: In the corticosteroid group, 45% of the patients remained dysphagia-free for 6 months, compared with 36% of controls (relative risk, 1.26; 95% confidence interval, 0.68-2.36; P = .46). Median time to repeat dilation was 108 days (range, 15-180 days) in the corticosteroid group vs 42 days (range, 17-180 days) for controls (P = .11). A median number of 2 dilations (range, 1-7) was performed in the corticosteroid group vs 3 dilations (range, 1-9) in controls (relative risk, 0.76; 95% confidence interval, 0.42-1.38; P = .36). Two major intervention-related complications occurred, 1 submucosal laceration in the corticosteroid group and 1 hemorrhage in the control group. Four patients in the corticosteroid group, but none of the controls, developed Candida esophagitis (P = .03). CONCLUSIONS: Corticosteroid injections do not provide a statistically significant decrease in frequency of repeat dilations or prolongation of the dysphagia-free period in patients with benign anastomotic esophagogastric strictures. Dutch Trial Registration Number 2236.

Meat consumption and mortality--results from the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. RESULTS: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. CONCLUSIONS: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.