An observational study to justify and plan a future phase III randomized controlled trial of metformin in improving overall survival in patients with inoperable pancreatic cancer without liver metastases.

PURPOSE: Metformin has plausible direct and indirect anti-cancer properties against pancreatic adenocarcinoma cells. However, metformin may only be efficacious in patients with inoperable pancreatic ductal adenocarcinoma (PDAC) without liver metastases. Absorption may be decreased by gastrointestinal symptoms and proton pump inhibitors (PPIs). We aimed to justify and inform a future phase III trial of metformin versus placebo on survival in inoperable PDAC by documenting prevalence of patients meeting eligibility criteria, gastrointestinal symptoms and PPI use. METHODS: Patient notes with PDAC were reviewed at a large teaching hospital over 2 years. Study variables were obtained from multiple sources of information. RESULTS: 141 participants were identified (51.8% female), of which 37.6% were not prescribed metformin at diagnosis and had no radiological hepatic metastases. Characteristics were similar between non-metformin and metformin users. In eligible patients, 65.2% reported nausea and vomiting and 46.2% were prescribed PPIs. CONCLUSION: Approximately, a third of all patients with inoperable PDAC are eligible for a future trial of metformin, allowing an estimate of the number of hospitals required for recruitment. Nausea and vomiting are common and should be managed effectively to prevent trial dropouts. PPI use is frequent and their influence on metformin's pharmacodynamic actions needs to be clarified.

Adherence to a Mediterranean diet is associated with a lower risk of later-onset Crohn's disease: results from two large prospective cohort studies.

OBJECTIVE: To examine the relationship between Mediterranean diet and risk of later-onset Crohn's disease (CD) or ulcerative colitis (UC). DESIGN: We conducted a prospective cohort study of 83 147 participants (age range: 45-79 years) enrolled in the Cohort of Swedish Men and Swedish Mammography Cohort. A validated food frequency questionnaire was used to calculate an adherence score to a modified Mediterranean diet (mMED) at baseline in 1997. Incident diagnoses of CD and UC were ascertained from the Swedish Patient Register. We used Cox proportional hazards modelling to calculate HRs and 95% CI. RESULTS: Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC with an average follow-up of 17 years. Higher mMED score was associated with a lower risk of CD (Ptrend=0.03) but not UC (Ptrend=0.61). Compared with participants in the lowest category of mMED score (0-2), there was a statistically significant lower risk of CD (HR=0.42, 95% CI 0.22 to 0.80) but not UC (HR=1.08, 95% CI 0.74 to 1.58). These associations were not modified by age, sex, education level, body mass index or smoking (all Pinteraction >0.30). The prevalence of poor adherence to a Mediterranean diet (mMED score=0-2) was 27% in our cohorts, conferring a population attributable risk of 12% for later-onset CD. CONCLUSION: In two prospective studies, greater adherence to a Mediterranean diet was associated with a significantly lower risk of later-onset CD.

Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012: a matched case-control study.

BACKGROUND: Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking. OBJECTIVE: To assess the association between oral antibiotic use and CRC risk. DESIGN: A matched case-control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012. RESULTS: 28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (ptrend <0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (ptrend=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, pinteraction<0.001; proximal colon versus distal colon, pinteraction=0.019). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)). CONCLUSION: Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.

Bridging clinic: The initial medical management of patients with newly diagnosed pancreatic cancer.

Pancreatic cancer is the 11th most common cancer in the UK and has the worst prognosis of any tumour with minimal improvements in survival over recent decades. As most patients are either ineligible for surgery or may decline chemotherapy, the emphasis is on control of symptoms and management of complications such as poor nutritional status. The time period between informing the patient of their diagnosis and commencing cancer treatments presents a valuable opportunity to proactively identify and treat symptoms to optimise patients' overall well-being. The 'bridging clinic', delivered by a range of healthcare professionals from gastroenterologists to nurse practitioners, can provide this interface where patients are first informed of their diagnosis and second supportive therapies offered. In this article, we provide a structure for instituting such supportive therapies at the bridging clinic. The components of the clinic are summarised using the mnemonic INDASH (Information/Nutrition/Diabetes and Depression/Analgesia/Stenting/Hereditary) and each is discussed in detail below.

The association between preoperative cardiopulmonary exercise-test variables and short-term morbidity after esophagectomy: A hospital-based cohort study.

BACKGROUND: Postoperative complications after esophagectomy are thought to be associated with reduced fitness. This observational study explored the associations between aerobic fitness, as determined objectively by preoperative cardiopulmonary exercise testing (CPEX), and 30-day morbidity after esophagectomy. METHODS: We retrospectively identified 254 consecutive patients who underwent esophagectomy at a single academic teaching hospital between September 2011 and March 2017. Postoperative complication data were measured using the Esophageal Complications Consensus Group definitions and graded using the Clavien-Dindo classification system of severity (blinded to cardiopulmonary exercise testing values). Associations between preoperative cardiopulmonary exercise testing variables and postoperative outcomes were estimated using logistic regression. RESULTS: A total of 206 patients (77% male) were included in the analyses, with a mean age of 67 years (SD 9). The mean values for the maximal oxygen consumed at the peak of exercise (VO2peak) and the anaerobic threshold were 21.1 mL/kg/min (SD 4.5) and 12.4 mL/kg/min (SD 2.8), respectively. The vast majority of patients (98.5%) had malignant disease-predominantly adenocarcinoma (84.5%), for which most received neoadjuvant chemotherapy (79%) and underwent minimally invasive Ivor Lewis esophagectomy (53%). Complications at postoperative day 30 occurred in 111 patients (54%), the majority of which were cardiopulmonary (72%). No associations were found between preoperative cardiopulmonary exercise testing variables and morbidity for either VO2peak (OR 1.00, 95% CI 0.94-1.07) or anaerobic threshold (OR 0.98, 95% CI 0.89-1.09). CONCLUSION: Preoperative cardiopulmonary exercise testing variables were not associated with 30-day complications after esophagectomy. The findings do not support the use of cardiopulmonary exercise testing as an isolated preoperative screening tool to predict short-term morbidity after esophagectomy. This modestly sized observational work highlights the need for larger studies examining associations between preoperative cardiopulmonary exercise testing and outcomes after esophagectomy to look for consistency in our findings.

No Association Between Consumption of Sweetened Beverages and Risk of Later-Onset Crohn's Disease or Ulcerative Colitis.

BACKGROUND & AIMS: Consumption of sweetened beverages has been associated with inflammation based on measurements of C-reactive protein and tumor necrosis factor, as well as immune-mediated disorders including rheumatoid arthritis. We investigated associations with Crohn's disease (CD) or ulcerative colitis (UC). METHODS: We conducted a prospective cohort study of 83,042 participants (age, 44-83 y) enrolled in the Cohort of Swedish Men or the Swedish Mammography Study. Dietary and lifestyle data were collected using a validated food frequency questionnaire at baseline in 1997. Diagnoses of CD and UC were ascertained from the Swedish Patient Register. We used Cox proportional hazards modeling to calculate hazard ratios and 95% CIs. RESULTS: Through December of 2014, we confirmed 143 incident cases of CD (incidence rate, 11 cases/100,000 person-years) and 349 incident cases of UC (incidence rate, 28 cases/100,000 person-years) over 1,264,345 person-years of follow-up evaluation. Consumption of sweetened beverages was not associated with increased risk of CD (Ptrend = .34) or UC (Ptrend = .40). Compared with participants who reported no consumption of sweetened beverages, the multivariable-adjusted hazard ratios for 1 or more servings per day were 1.02 for CD (95% CI, 0.60-1.73) and 1.14 for UC (95% CI, 0.83-1.57). The association between consumption of sugar-sweetened beverages and risk of CD or UC were not modified by age, sex (cohort), body mass index, or smoking (all Pinteraction ≥ .12). CONCLUSIONS: In analyses of data from 2 large prospective cohort studies from Sweden, we observed no evidence for associations between consumption of sweetened beverages and later risk of CD or UC.

Dietary Fiber and the Risk of Pancreatic Cancer.

OBJECTIVES: High dietary fiber may protect against pancreatic ductal adenocarcinoma (PDAC). We investigated associations between fiber intake and the risk of PDAC using for the first time 7-day food diaries. METHODS: Participants in the European Prospective Investigation Into Cancer-Norfolk completed the 7-day food diaries at recruitment. The cohort was followed up for 17 years to identify those who developed PDAC. Participants were divided into quintiles of fiber intake, and hazard ratios (HR) were estimated with their 95% confidence intervals (CIs). Fiber was tested for effect modification of high red and processed meat intake and smoking and the risk of PDAC. RESULTS: No significant associations for any quintiles of intake (HR Q5 vs Q1, 1.08; 95% CI, 0.56-2.08) were detected with no trend across quintiles. A high-fiber diet modified positive associations between red and processed meats with the development of PDAC (HR trends, 0.89 [95% CI, 0.47-1.69] and 1.02 [95% CI, 0.55-1.88], respectively) but not those with lower fiber intake. Fiber intake did not modify the risk of PDAC in past and current smokers. CONCLUSION: The findings do not suggest that fiber protects against PDAC, although it may decrease potential deleterious effects of meats.

Metformin as an Adjunctive Therapy for Pancreatic Cancer: A Review of the Literature on Its Potential Therapeutic Use.

Pancreatic ductal adenocarcinoma has the worst prognosis of any cancer. New adjuvant chemotherapies are urgently required, which are well tolerated by patients with unresectable cancers. This paper reviews the existing proof of concept data, namely laboratory, pharmacoepidemiological, experimental medicine and clinical trial evidence for investigating metformin in patients with pancreatic ductal adenocarcinoma. Laboratory evidence shows metformin inhibits mitochondrial ATP synthesis which directly and indirectly inhibits carcinogenesis. Drug-drug interactions of metformin with proton pump inhibitors and histamine H2-receptor antagonists may be of clinical relevance and pertinent to future research of metformin in pancreatic ductal adenocarcinoma. To date, most cohort studies have demonstrated a positive association with metformin on survival in pancreatic ductal adenocarcinoma, although there are many methodological limitations with such study designs. From experimental medicine studies, there are sparse data in humans. The current trials of metformin have methodological limitations. Two small randomized controlled trials (RCTs) reported null findings, but there were potential inequalities in cancer staging between groups and poor compliance with the intervention. Proof of concept data, predominantly from laboratory work, supports assessing metformin as an adjunct for pancreatic ductal adenocarcinoma in RCTs. Ideally, more experimental medicine studies are needed for proof of concept. However, many feasibility criteria need to be answered before such trials can progress.

Dietary oleic acid is inversely associated with pancreatic cancer - Data from food diaries in a cohort study.

BACKGROUND: Dietary oleic acid may prevent pancreatic ductal adenocarcinoma (PDA) by reducing hyperinsulinaemia which can otherwise promote DNA damage and tumour growth. Results from previous epidemiological studies investigating oleic acid are inconsistent. This study aims to clarify the relationship between dietary oleic acid intake and the risk of developing PDA using nutritional information from food diaries plus published serum biomarker data from HbA1c. METHODS: 23,658 participants, aged 40-74 years, were recruited into EPIC-Norfolk and completed 7-day food diaries which recorded; foods, brands and portion sizes to calculate nutrient intakes. Serum HbA1c was measured at recruitment in 11,147 participants (48.7% of cohort). Hazard ratios (HRs) for quintiles of dietary oleic acid intake and serum HbA1c were estimated using Cox regression. Additional analyses were made according to whether body mass index (BMI) was greater or less than 25 kg/m2 as this influences hyperinsulinaemia. RESULTS: 88 participants (55% women) developed PDA after a mean follow-up of 8.4 years (SD = 3.9) (mean age at diagnosis = 72.6 years, SD = 8.8). A decreased risk of PDA was associated with increased dietary oleic acid intake (highest vs lowest quintile, HR = 0.29, 95% CI = 0.10-0.81, P trend across quintiles = 0.011), with statistical significance maintained when BMI>25 kg/m2 but not if BMI<25 kg/m2. An elevated serum HbA1c was associated with increased risk of disease (highest vs lowest quintiles, HR = 6.32, 95% CI = 1.38-28.89, P for trend = 0.004). CONCLUSIONS: The data supports a protective role of oleic acid against development of PDA in those with higher BMIs possibly through influencing hyperinsulinaemia. Oleic acid intake should be accurately measured in future aetiological studies.

Dietary antioxidant intake and the risk of developing Barrett's oesophagus and oesophageal adenocarcinoma.

BACKGROUND: We investigated in a cohort study, for the first time using 7-day food diaries (7-DFDs), for age-dependent inverse associations with antioxidants, which have anti-carcinogenic properties, and development of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). METHODS: A total of 24,068 well individuals completed 7-DFDs and donated blood. Vitamins C and E, carotenes, zinc and selenium intakes, and plasma vitamin C were measured. Participants were monitored for 15 years for BO and OAC. Hazard ratios (HRs) were estimated for: quintiles of intake and in participants younger and >=65 years at recruitment, the midpoint of BO peak prevalence. RESULTS: A total of 197 participants developed BO and 74 OAC. There were no significant associations between antioxidants and BO or OAC in the whole cohort or if >65 years at recruitment. In participants <65 years, for BO, there was an inverse trend across plasma vitamin C quintiles (trend HR = 0.82; 95% CI = 0.71-0.96, P = 0.01), OAC for plasma vitamin C (trend HR = 0.58; 95% CI = 0.37-0.92, P = 0.02) and for dietary vitamins C and E (trend HR = 0.71 95% CI = 0.51-0.99, P = 0.04 and trend HR = 0.70; 95% CI = 0.51-0.96; P = 0.03). CONCLUSIONS: Data supports a role for dietary antioxidants prevent BO and OAC, perhaps at the earlier stages of carcinogenesis.

The role of diet in the aetiopathogenesis of inflammatory bowel disease.

Crohn's disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the complex interaction between diet, host genetics, the gut microbiota and immune function in the pathogenesis of IBD. In this Review, we discuss the recent epidemiological, gene-environment interaction, microbiome and animal studies that have explored the relationship between diet and the risk of IBD. In addition, we highlight the limitations of these prior studies, in part by explaining their contradictory findings, and review future directions.

Prediagnostic Serum Vitamin D Levels and the Risk of Crohn's Disease and Ulcerative Colitis in European Populations: A Nested Case-Control Study.

Background: A low vitamin D status has been put forward as a potential risk factor for the development of inflammatory bowel disease (IBD). This study investigated the association between prediagnostic circulating vitamin D concentrations and dietary intakes of vitamin D, and the risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods: Among 359,728 participants of the European Prospective Investigation into Cancer and Nutrition cohort, individuals who developed CD or UC after enrollment were identified. Each case was matched with2 controls by center, gender, age, date of recruitment, and follow-up time. At cohort entry, blood samples were collected and dietary vitamin D intakes were obtained from validated food frequency questionnaires. Serum 25-hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry. Conditional logistic regression was performed to determine the odds of CD and UC. Results: Seventy-two participants developed CD and 169 participants developed UC after a median follow-up of 4.7 and 4.1 years, respectively. Compared with the lowest quartile, no associations with the 3 higher quartiles of vitamin D concentrations were observed for CD (p trend = 0.34) or UC (p trend = 0.66). Similarly, no associations were detected when serum vitamin D levels were analyzed as a continuous variable. Dietary vitamin D intakes were not associated with CD (p trend = 0.39) or UC (p trend = 0.83). Conclusions: Vitamin D status was not associated with the development of CD or UC. This does not suggest a major role for vitamin D deficiency in the etiology of IBD, although larger studies are needed to confirm these findings.

The association between physical activity and the risk of symptomatic Barrett's oesophagus: a UK prospective cohort study.

BACKGROUND: Physical activity affects the functioning of the gastrointestinal system through both local and systemic effects and may play an important role in the aetiology of gastroesophageal reflux disease, Barrett's oesophagus and oesophageal adenocarcinoma. We investigated, for the first time in a large prospective cohort study, associations between recreational and occupational levels of physical activity and the incidence of Barrett's oesophagus. PARTICIPANTS AND METHODS: The European Prospective Investigation of Cancer-Norfolk recruited 30 445 men and women between 1993 and 1997. Occupational and recreational levels of physical activity were measured using a baseline questionnaire. The cohort was followed up until 2015 to identify symptomatic cases of Barrett's oesophagus. Cox proportional hazard regression estimated hazard ratios (HR) for physical activity and the development of disease. RESULTS: Two hundred and three participants developed Barrett's oesophagus (mean age: 70.6 years) the majority of whom were men (70.9%). There was an inverse association between standing occupations and disease risk [HR: 0.50, 95% confidence interval (CI): 0.31-0.82, P=0.006] when compared with sedentary jobs. Heavy manual occupations were positively associated with disease risk (HR: 1.66, 95% CI: 0.91-3.00), but conventional statistical significance was not reached (P=0.09). No associations were found between recreational activity and the risk of Barrett's oesophagus (HR: 1.34, 95% CI: 0.72-2.50, P=0.35, highest vs. lowest levels of activity). CONCLUSION: Our study suggests that occupational levels of physical activity may be associated with the risk Barrett's oesophagus. However, further work is required to confirm and describe specific occupations that may be protective.

Dietary Polyphenols in the Aetiology of Crohn's Disease and Ulcerative Colitis-A Multicenter European Prospective Cohort Study (EPIC).

BACKGROUND: Oxidative stress may be involved in the aetiology of inflammatory bowel disease and whether dietary polyphenols, which possess antioxidants properties, prevent its development is unknown. METHODS: A total of 401,326 men and women aged 20 to 80 years from 8 countries were recruited between 1991 and 1998 and at baseline completed validated food frequency questionnaires. Dietary polyphenol intake was measured using Phenol-Explorer, a database with information on the content of 502 polyphenols. Incident cases of Crohn's diseases (CD) and ulcerative colitis (UC) were identified during the follow-up period of up to December 2010. A nested case-control study using conditional logistic regression estimated the odds ratios (ORs), and 95% confidence intervals, for polyphenol intake (categories based on quartiles) and developing CD or UC. RESULTS: In total, 110 CD (73% women) and 244 UC (57% women) cases were identified and matched to 440 and 976 controls, respectively. Total polyphenol intake was not associated with CD (P trend = 0.17) or UC (P trend = 0.16). For flavones and CD, there were reduced odds for all quartiles, which were statistically significant for the third (OR3rd versus 1st quartile = 0.33; 95% confidence interval, 0.15-0.69) and there was an inverse trend across quartiles (P = 0.03). Similarly, for resveratrol, there was an inverse association with CD (OR4th versus 1st quartile = 0.40; 95% confidence interval, 0.20-0.82) with an inverse trend across quartiles (P = 0.02). No significant associations between subtypes of polyphenols and UC were found. Effect modification by smoking in CD was documented with borderline statistical significance. CONCLUSIONS: The data supports a potential role of flavones and resveratrol in the risk of developing CD; future aetiological studies should investigate these dietary components and further examine the potential for residual confounding.

Higher Meat Intake Is Positively Associated With Higher Risk of Developing Pancreatic Cancer in an Age-Dependent Manner and Are Modified by Plasma Antioxidants: A Prospective Cohort Study (EPIC-Norfolk) Using Data From Food Diaries.

OBJECTIVE: Carcinogens in meat may be involved in pancreatic carcinogenesis. Meat intake was investigated using 7-day food diaries and according to factors potentially influencing carcinogenesis: age, cooking method, and antioxidants. METHODS: Twenty-three thousand one hundred thirty-three participants in the European Prospective Investigation of Cancer-Norfolk cohort study completed 7-day food diaries and were followed up. Meat intakes were compared with controls and hazard ratios (HRs) calculated. RESULTS: Eighty-six participants developed pancreatic cancer. If younger than 60 years at recruitment, all quintiles of red meat (Q1 vs Q5; HR, 4.62; 95% confidence interval [CI], 0.96-22.30; P = 0.06) and processed meat (Q1 vs Q5; HR, 3.73; 95% CI, 0.95-14.66; P = 0.06) were nonsignificantly positively associated, with significant trends across quintiles (HRtrend, 1.33; 95% CI, 1.01-1.77 and HRtrend, 1.37; 95% CI, 1.04-1.82, respectively). Red meat's effect was attenuated by higher, but not lower, plasma vitamin C (HR, 1.06; 95% CI, 0.69-1.63 vs HR, 1.84; 95% CI, 1.09-3.14) and for processed meat (HR, 1.07; 95% CI, 0.71-1.63 vs HR, 1.80; 95% CI, 1.10-2.96). A nonstatistically significant risk was observed for high-temperature cooking methods in younger people (HR, 4.68; 95% CI, 0.63-34.70; P = 0.13). CONCLUSIONS: Red and processed meats may be involved in pancreatic carcinogenesis.

Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments.

Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients' quality of life and survival.

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.

Dairy Products, Dietary Calcium, and Risk of Inflammatory Bowel Disease: Results From a European Prospective Cohort Investigation.

BACKGROUND: Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this relationship are limited. We investigated the association between prediagnostic intake of these foods and dietary calcium, and the subsequent development of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: In total, 401,326 participants were enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. At recruitment, consumption of total and specific dairy products (milk, yogurt, and cheese) and dietary calcium was measured using validated food frequency questionnaires. Cases developing incident CD (n = 110) or UC (n = 244) during follow-up were matched with 4 controls. Conditional logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for total energy intake and smoking. RESULTS: Compared with the lowest quartile, the ORs for the highest quartile of total dairy products and dietary calcium intake were 0.61 (95% CI, 0.32-1.19, p trend = 0.19) and 0.63 (95% CI, 0.28-1.42, p trend = 0.23) for CD, and 0.80 (95% CI, 0.50-1.30, p trend = 0.40) and 0.81 (95% CI, 0.49-1.34, p trend = 0.60) for UC, respectively. Compared with nonconsumers, individuals consuming milk had significantly reduced odds of CD (OR 0.30, 95% CI, 0.13-0.65) and nonsignificantly reduced odds of UC (OR 0.85, 95% CI, 0.49-1.47). CONCLUSIONS: Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established. Further studies are warranted to confirm this possible protective effect.

Association Between Statin Use After Diagnosis of Esophageal Cancer and Survival: A Population-Based Cohort Study.

BACKGROUND & AIMS: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), commonly prescribed in the primary and secondary prevention of cardiovascular disease, promote apoptosis and limit proliferation of esophageal cancer cell lines. We investigated whether statin use after a diagnosis of esophageal cancer is associated with reduced esophageal cancer-specific and all-cause mortality. METHODS: We identified a cohort of 4445 men and women in the United Kingdom diagnosed with esophageal cancer from January 2000 through November 2009 using the General Practice Research Database. The National Cancer Registry and Office of National Statistics datasets established the histologic subtype and cancer-specific mortality, respectively. Cox proportional hazard regression analysis with time-dependent exposures estimated the association between statin use after diagnosis and esophageal cancer-specific and all-cause mortality. RESULTS: The median survival time of the entire cohort was 9.2 months (interquartile range [IQR], 3.7-23.2 mo). Among subjects who used statins after a diagnosis of esophageal cancer, the median survival time was 14.9 months (IQR, 7.1-52.3 mo) compared with 8.1 months for nonusers (IQR, 3.3-20 mo). In the entire cohort, statin use after diagnosis was associated with a decreased risk of esophageal cancer-specific mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.44-0.86) and all-cause mortality (HR, 0.67; 95% CI, 0.58-0.77). In patients with esophageal adenocarcinoma, statin use after diagnosis was associated with a decreased risk of esophageal cancer-specific mortality (HR, 0.61; 95% CI 0.38-0.96) and all-cause mortality (HR, 0.63; 95% 0.43-0.92). This effect was not observed in patients with esophageal squamous cell carcinoma. There was no evidence for effect modification of these associations with statin use before the cancer diagnosis. CONCLUSIONS: In a large population-based cohort, statin use after a diagnosis of esophageal adenocarcinoma, but not esophageal squamous cell carcinoma, was associated with reduced esophageal cancer-specific and all-cause mortality.