Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) technique and analgesic efficacy in patients with pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN) for the treatment of abdominal pain in pancreatic cancer can be administered in three different ways, depending on the site of needle insertion: central injection (CI), bilateral injection (BI) and celiac ganglia neurolysis (CGN). This meta-analysis aimed to (1) estimate the overall efficacy of the EUS-CPN; (2) compare the efficacy of each of the three techniques; and (3) investigate demographic and disease characteristics as potential predictors of treatment response. METHODS: We searched MEDLINE and EMBASE for studies that reported the proportion of treatment responders to EUS-CPN overall, and according to the technique used. We performed a random effects meta-analysis of proportions, and meta-regression was used to estimate the association between technique and clinical characteristics on treatment response. The safety profile was reviewed through narrative synthesis. RESULTS: Overall response rate to EUS-CPN was 68% (95% CI 61%-74%) at week two and 53% (95% CI 45%-62%) at week four. There was no evidence of a significant difference in the response rates between the three techniques. Demographics and disease characteristics were not associated with treatment response. Serious complications have been reported for BI and CGN but not for CI. Moderate to high risk of bias was observed. DISCUSSION: EUS-CPN is a useful adjunct to opioids in the management of pain. There is no evidence of a difference in the efficacy among the three techniques, however, CI is the only one for which serious complications have not been reported. Future research should focus on the appropriate timing of EUS-CPN (early versus on demand) and randomised comparison to establish the comparative efficacy of each technique.

Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT-ROC feasibility study.

BACKGROUND: Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. METHODS: For this multicentre, double-blind, parallel-group, randomized, placebo-controlled feasibility trial, adults with OAC (including Siewert I-II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. RESULTS: A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low-density lipoprotein cholesterol levels by 3 months (adjusted mean difference -0·83 (95 per cent c.i. -1·4 to -0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow-up. Adverse events were similar between the groups. Quality-of-life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non-randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. CONCLUSION: This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com).

ANTECEDENTES: Las estatinas inhiben las señalizaciones proliferativas en el adenocarcinoma de esófago (oesophageal adenocarcinoma, OAC) y su uso se asocia con mejor supervivencia en estudios observacionales. El presente estudio se llevó a cabo para examinar la viabilidad de evaluar el tratamiento adyuvante con estatinas en pacientes con OAC operable en un ensayo aleatorizado y controlado de fase III. MÉTODOS: En este ensayo de viabilidad controlado por placebo, aleatorizado, de grupos paralelos, doble ciego y multicéntrico, los pacientes adultos con OAC (incluyendo lesiones Siewert I/II) que fueron sometidos a esofaguectomía se asignaron de forma centralizada (1:1) a tratamiento con simvastatina 40 mg o placebo equivalente mediante aleatorización en bloques, estratificados por centro. Los participantes, los clínicos y los investigadores desconocían la asignación del tratamiento. Los pacientes recibieron el tratamiento hasta un año. Los resultados de viabilidad fueron reclutamiento, retención, absorción del fármaco, adherencia, seguridad, calidad de vida, generalización, y supervivencia. RESULTADOS: Un total de 120 pacientes fueron evaluados para elegibilidad en 4 centros, de los cuales 32 (26,7%) fueron aleatorizados, 16 en cada grupo. Siete pacientes abandonaron el ensayo. Los pacientes asignados a tratamiento con simvastatina tenían niveles de colesterol LDL más bajos a los 3 meses (diferencia media ajustada, −0,83 mmol/L, i.c. del 95% −1,4 a −0,22, P = 0,009). La mediana de la adherencia a la medicación fue mayor del 90% entre los 3-12 meses de seguimiento. Los eventos adversos fueron similares entre los grupos. Los datos de calidad de vida estaban completos en el 98,3% de las preguntas del cuestionario. Enfermedad cardiovascular, diabetes y uso de aspirina eran más prevalentes en el grupo no aleatorizado, mientras que la localización del tumor, el estadio y el grado fueron similares entre los grupos. Las estimaciones de supervivencia fueron imprecisas. CONCLUSIÓN: Este RCT apoya la realización e informa de las consideraciones de diseño para un futuro ensayo de fase III de tratamiento adyuvante con estatinas en pacientes con OAC.

Does physical activity protect against the development of gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma? A review of the literature with a meta-analysis.

Physical activity affects the functioning of the gastrointestinal system through both local and systemic effects and may play an important role in reducing the risk of esophageal adenocarcinoma. This review assesses the biological mechanisms and epidemiological evidence for the relationship between physical activity and the development of esophageal adenocarcinoma and its precursor diseases: gastroesophageal reflux disease (GORD) and Barrett's esophagus. A search of PubMed, Medline, Embase, and CINAHL was conducted from their inceptions to 25th March 2017 for analytical studies that examined associations between recreational and/or occupational levels of physical activity and the risk of GORD, Barrett's esophagus, and esophageal adenocarcinoma. Where appropriate, a meta-analysis of effects was undertaken. Seven studies were included (2 cohort, 5 case control). For GORD, there were three case-control studies with 10 200 cases among 78 034 participants, with a pooled estimated OR of 0.67 (95% CI 0.57-0.78) for high versus low levels of recreational physical activity. In Barrett's esophagus, there was a single case-control study, which reported no association, OR 1.19 (95% CI 0.82-1.73). For esophageal adenocarcinoma, there were three studies (two prospective cohort, one case control) with 666 cases among 910 376 participants. The largest cohort study reported an inverse association for high versus low levels of recreational physical activity, RR 0.68, 95% CI 0.48-0.96. The remaining two studies reported no associations with either occupational or combined recreational and occupational activity. Heterogeneity in the measurement of exposure (recreational, occupational, and both) made a pooled estimate for esophageal adenocarcinoma inappropriate. Although limited, there is some evidence that higher levels of recreational physical activity may reduce the risk of both GORD and esophageal adenocarcinoma, but further large cohort studies examining the type, intensity and duration of activities that may be beneficial are needed.

No association of alcohol use and the risk of ulcerative colitis or Crohn's disease: data from a European Prospective cohort study (EPIC).

BACKGROUND/OBJECTIVES: The role of long-term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn's disease (CD) is unclear. For the first time, to prospectively assess the role of pre-disease alcohol consumption on the risk of developing UC or CD. SUBJECTS/METHODS: Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC-IBD), incident UC and CD cases and matched controls where included. At recruitment, participants completed validated food frequency and lifestyle questionnaires. Alcohol consumption was classified as either: non-use, former, light (⩽0.5 and 1 drink per week), below the recommended limits (BRL) (⩽1 and 2 drinks per day), moderate (⩽2.5 and 5 drinks per day), or heavy use (>2.5 and >5 drinks per day) for women and men, respectively; and was expressed as consumption at enrolment and during lifetime. Conditional logistic regression was applied adjusting for smoking and education, taking light users as the reference. RESULTS: Out of 262 451 participants in six countries, 198 UC incident cases/792 controls and 84 CD cases/336 controls were included. At enrolment, 8%/27%/32%/23%/11% UC cases and 7%/29%/40%/19%/5% CD cases were: non-users, light, BRL, moderate and heavy users, respectively. The corresponding figures for lifetime non-use, former, light, BRL, moderate and heavy use were: 3%/5%/23%/44%/19%/6% and 5%/2%/25%/44%/23%/1% for UC and CD cases, respectively. There were no associations between any categories of alcohol consumption and risk of UC or CD in the unadjusted and adjusted odds ratios. CONCLUSION: There was no evidence of associations between alcohol use and the odds of developing either UC or CD.

Diffusion-weighted imaging and magnetic resonance proton spectroscopy following preterm birth.

AIM: To study the associations between magnetic resonance proton spectroscopy (MRS) data and apparent diffusion coefficients (ADC) from the preterm brain with developmental outcome at 18 months corrected age and clinical variables. MATERIALS AND METHODS: A prospective observational cohort study of 67 infants born before 35 weeks gestational age who received both magnetic resonance imaging of the brain between 37 and 44 weeks corrected gestational age and developmental assessment around 18 months corrected age. RESULTS: No relationships were found between ADC values and MRS results or outcome. MRS ratios involving N-acetyl aspartate (NAA) from the posterior white matter were associated with "severe" and "moderate to severe" difficulties, and fine motor scores were significantly lower in participants with a visible lactate doublet in the posterior white matter. The presence of a patent ductus arteriosus (PDA) was the only clinical factor related to NAA ratios. CONCLUSION: Altered NAA levels in the posterior white matter may reflect subtle white matter injury associated with neuro-developmental difficulties, which may be related to a PDA. Further work is needed to assess the longer-term neuro-developmental implications of these findings, and to study the effect of PDAs on developmental outcome in later childhood/adolescence.

Association between high dietary intake of the n-3 polyunsaturated fatty acid docosahexaenoic acid and reduced risk of Crohn's disease.

BACKGROUND: There are plausible mechanisms for how dietary docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, could prevent Crohn's disease (CD). AIM: To conduct a prospective study to investigate the association between increased intake of DHA and risk of CD. METHODS: Overall, 229 702 participants were recruited from nine European centres between 1991 and 1998. At recruitment, dietary intakes of DHA and fatty acids were measured using validated food frequency questionnaires. The cohort was monitored through to June 2004 to identify participants who developed incident CD. In a nested case-control analysis, each case was matched with four controls; odds ratios (ORs) were calculated for quintiles of DHA intake, adjusted for total energy intake, smoking, other dietary fatty acids, dietary vitamin D and body mass index. RESULTS: Seventy-three participants developed incident CD. All higher quintiles of DHA intake were inversely associated with development of CD; the highest quintile had the greatest effect size (OR = 0.07; 95% CI = 0.02-0.81). The OR trend across quintiles of DHA was 0.54 (95% CI = 0.30-0.99, Ptrend  = 0.04). Including BMI in the multivariate analysis, due to its correlation with dietary fat showed similar associations. There were no associations with the other dietary fatty acids studied. CONCLUSION: There were inverse associations, with a biological gradient between increasing dietary docosahexaenoic acid intakes and incident Crohn's disease. Further studies in other populations should measure docosahexaenoic acid to determine if the association is consistent and the hypothesis tested in randomised controlled trials of purely docosahexaenoic acid supplementation.

Aspirin may prevent cholangiocarcinoma: a case-control study from the United kingdom.

BACKGROUND: The proliferation of cholangiocarcinoma cells is suppressed in cell culture by nonsteroidal antiinflammatory drugs (NSAIDs) through the inhibition of cyclo-oxygenase-2 enzyme and also by statins which decrease the production of mediators of the cell cycle. AIMS: To investigate whether there is an inverse association between NSAIDs, including aspirin, and the development of cholangiocarcinoma and, for the first time in a Western population, between statin use and the development of cholangiocarcinoma. METHODS: This epidemiological study had a case-control design in which cases of cholangiocarcinoma diagnosed in Norwich between 2004 and 2010 and in Leicester in 2007 were identified from clinical databases. Controls were patients with basal cell carcinomas treated in the respective dermatology departments. The case notes of all subjects were reviewed to confirm diagnoses and obtain information on medication use. The data were analyzed using unconditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI). RESULTS: In total, 81 cases of cholangiocarcinoma and 275 controls were identified. For all cases there was radiological evidence of cancer and 86 % of the cases involved the extrahepatic biliary system. Aspirin use was inversely associated with the development of cholangiocarcinoma (OR 0.45, 95 % CI 0.22-0.92), but there were no significant associations between the development of cholangiocarcinoma and NSAIDs (OR 0.39; 95 % CI 0.11-1.42) or statins (OR 0.58; 95 % CI 0.28-1.19). CONCLUSIONS: The epidemiological data from this study support the biological evidence for aspirin having a protective effect against the development of cholangiocarcinoma. Aspirin use should be measured in future etiological studies and assessed as a chemoprevention agent in those at high risk of developing this type of cancer.

CT of the neonatal head.

Computed tomography (CT) is used less often than other techniques on neonatal units. However, in the acute setting, CT can be invaluable in diagnosing or excluding potentially life-threatening conditions and guiding initial management in neonates. Common indications for scanning include trauma, suspected non-accidental injury, infection, or an acute hypoxic or metabolic event. The aim of this review is to provide an overview of the normal neonatal head at CT and compare this to the common pathological abnormalities. Several key features of each condition will be highlighted. It is important to note that some pathological conditions can have overlapping features at CT and, therefore, the clinical history and additional investigations are also of key importance in determining the diagnosis.

The differential effects of statins on the risk of developing pancreatic cancer: a case-control study in two centres in the United Kingdom.

INTRODUCTION: There are plausible biological mechanisms for how statins may prevent pancreatic cancer, although the evidence from epidemiological studies in the general population is conflicting. This study aims to clarify whether statins exert their effects in specific sub-groups, namely, gender, smoking status and diabetes. METHODS: A matched case-control study was conducted in patients diagnosed with pancreatic cancer, and a group of dermatology patients of similar ages and gender, diagnosed with basal cell carcinoma. Participants' medical records were reviewed for information on statin use prior to diagnosis. Odds ratios and 95 % CIs for the development of pancreatic cancer were estimated using conditional logistic regression. Subgroup analysis was performed in men, women, smokers and those with type 2 diabetes. RESULTS: Two hundred fifty-two cases (median age 71 years, range 48-73 years, 51 % women) and 504 controls were identified, of which 23 % of cases were regular statin users versus 21 % of controls. In the general study population there was no association between pancreatic cancer and regular statin use (OR 0.82, 95 % CI 0.53-1.23, p = 0.33). However, in male smokers, regular statin use was associated with significantly reduced odds of pancreatic cancer compared to male smokers not prescribed a statin (OR 0.11, 95 % CI 0.01-0.96, p = 0.05). In patients with type 2 diabetes statins use was not associated with reduced odds (OR 0.92, 95 % CI 0.35-2.45, p = 0.80), with no gender effects. CONCLUSIONS: In male smokers, statins may reduce the odds of pancreatic cancer. Statin use should be measured in aetiological studies of pancreatic cancer but analysed in specific sub-groups. Future work should investigate statins as chemopreventative agents in this high risk sub-group.

Diverticular disease in younger patients--is it clinically more complicated and related to obesity?

AIM: The aims of this systematic review were to determine the presentations of diverticular disease in patients under 40 years of age and to assess whether obesity is an important factor. METHOD: The PubMed and EMBASE databases and the Cochrane Library were searched to identify all original articles published between 1990 and 2011 on diverticular disease severity in obese patients (body mass index of ≥ 30 kg/m(2) ) under 40 years of age. RESULTS: Twenty-three clinical case series (two of which were prospective) were identified plus two large aetiological population-based studies. These reported that young patients with diverticular disease were presenting more frequently, that diverticular disease in this age group was less likely to be complicated but that emergency operation rates were higher. The majority (63.1-96.5%) of patients under 40 years of age with diverticular disease were obese. CONCLUSION: The studies suggest that in the young, obese patient with lower abdominal pain, diverticulitis and appendicitis are included in the differential diagnosis. CT and/or laparoscopy should be considered where the diagnosis is in doubt.

Systematic review: potential preventive effects of statins against oesophageal adenocarcinoma.

BACKGROUND: The incidence of oesophageal adenocarcinoma (OAC) has risen dramatically in recent decades, and its prognosis remains extremely poor. There is emerging evidence that statins may prevent OAC. AIM: To systematically review both the experimental and epidemiological evidence to determine whether statins reduce the risk of developing OAC. METHODS: Relevant laboratory and epidemiological studies were identified by systematically searching the PUBMED and EMBASE electronic databases for data on statins and oesophageal cancer (OC). The evidence was assessed according to the nine Bradford Hill criteria (BHC) of causality. Pooled effect sizes (ES) were calculated for the risk of OC with prior statin use. RESULTS: Many of the BHC were supported including: 'plausible biological mechanisms', 'coherence', 'strong associations', 'consistency', 'biological gradient', 'analogy' and 'temporality'. Three experimental studies reported that statins inhibited proliferation, induced apoptosis and may limit metastatic potential in OAC cell lines. Fixed effects meta-analysis of two prospective studies in Barrett's oesophagus cohorts, involving 1382 participants, showed an ES of 0.53 (95% CI = 0.36-0.78, P = 0.001, I(2)  = 0%) for risk of OAC with prior statin use. Meta-analysis of three prospective studies in general population cohorts, involving 35 214 participants, showed an ES of 0.86 (95% CI = 0.78-0.94, P = 0.001, I(2)  = 0%) for risk of OC with prior statin use. The most important criterion, 'experiment', is as yet unfulfilled as to date there are no clinical trials which investigate this hypothesis. CONCLUSION: There is some evidence that statins may protect against the development of OAC, although to be conclusive, data from randomised clinical trials are required.

An MR-compatible neonatal incubator.

OBJECTIVES: To develop a neonatal MR-compatible incubator for transporting babies between a neonatal intensive care unit and an MRI unit that is within the same hospital but geographically separate. METHODS: The system was strapped to a standard MR-compatible patient trolley, which provides space for resuscitation outside the incubator. A constant-temperature exothermic heat pad was used to maintain temperature together with a logging fluoro-optic temperature monitor and alarm system. The system has been designed to accommodate standard knee-sized coils from the major MR manufacturers. The original incubator was constructed from carbon fibre, but this required modification to prevent radiofrequency shading artefacts due to the conducting properties of the carbon fibre. A high-tensile polyester material was used, which combined light weight with high impact strength. The system could be moved onto the patient bed with the coils and infant in place by one technologist. RESULTS: Studies in eight neonatal patients produced high quality 1.5 T MR images with low motion artefacts. The incubator should also be compatible with imaging in 3 T MR systems, although further work is required to establish this. Images were acquired using both rapid and high-resolution sequences, including three-dimensional volumes, proton spectra and diffusion weighting. CONCLUSION: The incubator provides a safe, quiet environment for neonates during transport and imaging, at low cost.

Aspirin in the aetiology of Crohn's disease and ulcerative colitis: a European prospective cohort study.

BACKGROUND: Aspirin has detrimental effects on the gastrointestinal tract mucosa and may play a role in the aetiology of inflammatory bowel disease. AIM: To investigate if the regular use of aspirin is associated with the development of Crohn's disease (CD) and ulcerative colitis (UC) using, for the first time, a prospective cohort study design. METHODS: A total of 135,780 men and women in Europe, aged 30-74years, were recruited into the European Prospective Investigation into Cancer and Nutrition study. Participants completed questionnaires at baseline detailing their regular aspirin use and were then followed up to identify those who developed either incident CD or UC. Each case was matched with four controls and odds ratios (OR) were calculated, adjusting for cigarette smoking. Potential interactions between aspirin and smoking were assessed. RESULTS: A total of 35 participants developed CD and a further 84 were diagnosed with UC. Regular aspirin intake was positively associated with the risk of developing CD (OR=6.14, 95% CI=1.76-21.35). In those who took aspirin and smoked there was no detectable increased risk of CD (OR=0.30, 95% CI=0.03-3.08). No association was found between regular aspirin use and UC (OR=1.29, 95% CI=0.67-2.46). CONCLUSIONS: A strong positive association between regular aspirin use and CD, but not UC, was observed. The data suggest that regular aspirin use should be measured in epidemiological work on CD. If such findings are consistent in other work then aspirin may affect the development of CD in a middle-aged to elderly population.

Evaluation of a computer program ('disect') to consolidate anatomy knowledge: a randomised-controlled trial.

BACKGROUND: The teaching of anatomy to medical undergraduates continues to develop. Medical imaging can accurately demonstrate anatomy. 'disect' is a computer program which manipulates and reconstructs real CT images in 3-D. AIM: To implement and assess a novel computer-based imaging resource. METHODS: Third-year undergraduate medical students at the University of East Anglia were randomised to different methods of delivering the program - either self-directed use or guided use with worksheets. Knowledge of gastro-intestinal anatomy was assessed using a 20-item test. Attitudes to using 'disect' were evaluated using Likert scales. RESULTS: Most students reported the program was easy to use and a valuable resource for learning anatomy. There was no difference in scores between guided use and self-directed use (10.7 marks versus 10.6 marks, p = 0.52). Students who undertook the anatomy special study module, which involved dissection of the digestive system, performed best (12.8 marks versus 9.9 marks, p = 0.005). CONCLUSION: Students can adequately use a computer program to see major anatomical structures derived from CT scans. Students reported that learning anatomy can be aided by the imaging-based resource. Learning anatomy is a multi-modal activity and packages like 'disect' can enhance learning by supplementing current teaching methods.

Is learning anatomy facilitated by computer-aided learning? A review of the literature.

BACKGROUND: There is ongoing debate concerning the best way to teach anatomy. Computer-assisted learning (CAL) is one option for teaching anatomy and these resources are increasingly available. AIMS: To assess the use of such resources in undergraduate medical student anatomy tuition. METHOD: Literature review. RESULTS: Eight quantitative studies were found and these tended to report favourably. Though these educational packages can show improvement in knowledge, the studies tended to cover small areas of anatomy or were assessed in short courses. There were also several assessments of learner's attitudes to CAL which tended to report favourably in terms of educational satisfaction and enjoyment. CONCLUSIONS: There is insufficient evidence to show that these resources have a true place for replacing traditional methods in teaching anatomy. Further research should be conducted to determine how to use these resources in conjunction with current teaching methods or how their use can be integrated into the current anatomy curriculum.