Richard J. Robinson

Meta-analysis: cancer risk of low-grade dysplasia in chronic ulcerative colitis.

The cancer risk of low‐grade dysplasia (LGD) in chronic ulcerative colitis is variable and its management remain contentious.

Meta analysis: Cancer risk in Barrett's oesophagus.

Background  Risk of cancer in Barrett’s oesophagus is reported to vary between studies and also between countries, where the studies were conducted as per several systematic reviews. Cancer incidence has implications on surveillance strategies.

Osteoporosis and determinants of bone density in patients with Crohn's disease

Low bone mineral density (BMD) is common inpatients with Crohns disease; however, the pathogenesisof bone loss and risk factors for osteoporosis are notestablished. Our aim was to evaluate the clinical, dietary, and nutritional determinants of BMD inCrohns disease. A cross-sectional analysis of 117patients with Crohns disease was undertaken. Allpatients underwent a clinical and dietary evaluation including assessment of nutritional state andlife-style. BMD was measured at the hip and lumbar spineby dual-energy x-ray absorptiometry; and z scoresobtained by comparison with age- and sex-matched normal values for the healthy UK population.Multiple regression analysis was used to assessassociations between BMD and potential risk factors,allowing for possible confounding variables. Thirteen(11%) patients had osteoporosis (z score<–2), with osteopenia (z score <–1,>–2) in a further 34 (29%). Patients withjejunal disease had significantly lower BMD at the spine(P = 0.03) and femoral neck (P = 0.02) than those with disease atother sites. Mean BMD was significantly lower at the hipof patients with previous bowel resection (diff in means= 0.53, 95% CI-0.97, –0.08, P = 0.02), but type of surgery was not significant. Active disease,menstrual history, diet, level of physical activity, andsmoking were not associated with low bone mass. At thelumbar spine, body weight (P < 0.0001), male sex (P < 0.0001), and currentprednisolone use (P < 0.02) were independentlypredictive of low bone mass. Body weight (P <0.0001), male sex (P < 0.0001), and cumulativesteroid dose (P = 0.02) were predictive at the femoralneck. The major determinants of BMD in Crohns diseaseare body weight, current steroid use, and cumulativesteroid dose. Men with Crohns disease are at greatest risk of osteoporosis, with jejunal involvementand previous bowel resection also contributing to thelow bone mineral density.

Effect of a low-impact exercise program on bone mineral density in Crohn's disease: A randomized controlled trial

BACKGROUND & AIMS Physical exercise increases bone mineral density (BMD) in healthy young adults and slows the rate of bone loss in later life. The aim of this randomized controlled trial was to investigate the effect of exercise on BMD in patients with Crohns disease. METHODS A total of 117 patients with Crohns disease were randomized to a control group or a low-impact exercise program of increasing intensity. BMD (g/cm2) was measured at baseline and 12 months at the hip and spine (L2-L4) by dual energy x-ray absorptiometry. RESULTS Nonsignificant gains in BMD occurred at the hip and spine in the exercise group compared with controls (P > 0.05). In fully compliant patients, BMD increased by 3.54% (7.95%) at the femoral neck, 2.97% (7.7%) at the spine, 4.1% (10.26%) at Wards triangle, and 7.77% (8.2%) at the greater trochanter. Compared with controls, gain in BMD at the greater trochanter was statistically significant (difference in means, 4.67; 95% confidence interval, 0.86-8.48; P = 0.02). Increases in BMD were significantly related to the number of exercise sessions completed (femoral neck; r = 0.28; 95% confidence interval, 0.10-0.45; P = 0.04). CONCLUSIONS Progressive low-impact exercise is a potentially effective method of increasing BMD in Crohns disease. If sustained, the increases in BMD may reduce the risk of osteoporotic fracture.

Screening for osteoporosis in Crohn's disease. A detailed evaluation of calcaneal ultrasound

Objectives To compare calcaneal broadband ultrasonic attenuation (BUA) and velocity of sound (VOS) in patients with Crohns disease with an age-matched control population. The validity of BUA as a screening tool for osteoporosis was evaluated and the relationship between BUA and previous fracture studied. Design Cross-sectional study. Background Since patients with Crohns disease are at risk of osteoporosis and premature fracture, routine assessment of bone mineral density (BMD) is recommended. Quantitative ultrasound of the calcaneum is an inexpensive and radiation-free means of assessing bone density which also provides information on bone microstructure. Methods BUA (dB/MHz) and VOS (m/s) were measured at the calcaneum (CUBAclinical, McCue Ultrasonics, Winchester, UK) and compared with bone mineral density at the hip and lumbar spine measured by dual-energy X-ray absorptiometry (DEXA); 100 patients (42 men) with Crohns disease and 52 age-matched healthy controls (23 men) were studied. Results BUA was significantly reduced in patients with Crohns disease compared with age-matched controls [76.53 dB/MHz (±17.3) vs 87.29 dB/MHz (±17.9), difference in means = 10.76, 95% CI −16.67, −4.85, P= 0.0004] and was significantly associated with BMD at the spine (r=0.49, 95% CI 0.32, 0.63, P < 0.0001) and femoral neck (r=0.54, 95% CI 0.38, 0.67, P< 0.0001). In the diagnosis of osteoporosis (t score < −2.5) BUA had a sensitivity of 66.7% at the femoral neck, with a specificity of 85.6%; sensitivity of BUA at the spine was 75% with specificity 89%. Conclusion Patients with Crohns disease have reduced BUA compared with an age-matched control population. Calcaneal BUA is significantly associated with BMD at the hip and spine but the correlation is insufficient to recommend ultrasound as a screening tool for DEXA.

Is transcutaneous electrical nerve stimulation an effective analgesia during colonoscopy

OBJECTIVES To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) as analgesia during colonoscopy. DESIGN In a randomised controlled trial, patients undergoing diagnostic colonoscopy were assigned to one of three groups: standard medication only (midazolam); active TENS plus standard medication; or non-functioning TENS and standard medication. Efficacy of TENS was determined using numerical rating scores for pain and the post-procedural evaluation questionnaire. SETTING Patients undergoing diagnostic colonoscopy in a teaching hospital. MAIN OUTCOME There was no statistically significant differences between the three groups. However in the active TENS group there was a greater variation in “physical discomfort” and “psychological distress”, suggesting TENS may be effective in subgroup of patients.

Aspirin, NSAIDS, Calcium-channel blockers and statins in the aetiology of pancreatic cancer: preliminary results from a case-control study in two centres in the UK

Introduction There are plausible mechanisms that carcinogenesis may be altered by: aspirin, NSAIDs, calcium-channel blockers and statins, through both inhibition of cyclo-oxygenase enzymes and the production of mediators of the cell cycle. The current epidemiological data in this area is either limited, reports conflicting results or does not consider important confounders. The aim of this study was to investigate whether there is a negative association between these medications and the development of pancreatic cancer in a case-control study in the UK. Methods Clinical management databases were used to identify patients diagnosed with pancreatic cancer managed in Norfolk (years 2004–2006) and Leicestershire (2007). The use of these medications, prior to diagnosis, was recorded from a detailed review of the medical records. The control group were 251 dermatology patients of similar ages treated for basal cell carcinoma. ORs with 95% CI, for the development of pancreatic cancer for each medication, were estimated using unconditional logistic regression and adjusted for gender, age at diagnosis, cigarette smoking and type II diabetes. Results A total of 206 cases of adenocarcinoma of the pancreas (median age=71 years, range 49–99 years, 52% women, a median survival of 3.5 months) and 251 controls were identified. Aspirin use was negatively associated with the development of pancreatic cancer (OR=0.49, 95% CI 0.29 to 0.84, p=0.01). There were no associations with either NSAIDs (OR=0.98, CI 0.50 to 1.91, p=0.95), statins (OR=0.64, CI 0.38 to 1.11, p=0.11) or calcium-channel blockers (OR=0.78, 95% CI 0.43 to 1.39, p=0.40). Conclusion The data support a protective role for aspirin, but not currently for the remaining medications in the aetiology of pancreatic cancer. The work is continuing to identify more cases and controls that may confirm our preliminary results for aspirin9s negative association and also show an effect for statins. Before aspirin can be recommended as a chemo-preventive agent, further population-based studies are required to confirm the association and provide detailed information on the dose of aspirin needed and its duration of use.

Production and evaluation of guidelines for the management of inflammatory bowel disease: the Leicester experience

Consensus guidelines for the management of patients with inflammatory bowel disease were produced by gastroenterologists, gastrointestinal surgeons and a cross-section of general practitioners (GPs) from Leicestershire in order to develop a seamless pattern of care with a common approach to diagnosis and treatment. It was hoped that the guidelines would encourage a movement towards care in the community for many patients with stable disease and so speed up new consultation rates. The study then assessed the impact of these guidelines on the referral letters of GPs to hospital consultants, the prediction of disease and adherence to them on re-referring patients after discharge. The guidelines were distributed to all 487 GPs in the Leicester Health Authority area and the gastroenterology teams within the hospitals. The value of the guidelines was assessed by an audit of referral letters, the length of time from referral letter to out-patient appointment, both before and after the launch of the guidelines, adherence to the guidelines on re-referral, and monitoring the outcome of the discharged patients. Whilst the guidelines may have helped GPs to manage stable patients in the community, the content of referral letters and the diagnostic abilities of GPs were not seen to improve since the launch of the guidelines. However, only 5% of stable patients who were discharged from one clinic were re-referred for inflammatory bowel disease.

The short-term effects of Eudragit-L-coated prednisolone metasulphobenzoate (Predocol) on bone formation and bone mineral density in acute ulcerative colitis.

Background The aetiology of bone loss in ulcerative colitis is multifactorial, but corticosteroid treatment is an important risk factor. A novel formulation of Eudragit-L-coated prednisolone metasulphobenzoate (Predocol) has been developed, in order to deliver high mucosal levels of prednisolone within the colon but with little systemic absorption. The aim of this study was to investigate its efficacy, and short-term effects on bone formation and bone mineral density. Methods In a 12-week longitudinal study 13 patients with active colitis were treated with a reducing dose of Predocol. Disease activity scores were recorded and the bone formation marker osteocalcin was measured before, during and after treatment, with hip and spine bone mineral density assessed at baseline and after treatment. Results Eleven of the 13 patients completed the study. Compared with baseline, disease activity scores improved significantly after 4 weeks [difference in means, 6.9; 95% confidence interval (CI), 5.2, 8.7; P < 0.0001] and 12 weeks (difference in means, 5.7; 95% CI, 3.3, 8.2; P < 0.0001) of treatment. Osteocalcin did not fall compared with baseline [16.91 mg/l (95% CI, 12.70, 21.12)], after 4 weeks [13.67 mg/l (95% CI, 8.72, 18.60)] (difference in means, 3.25; 95% CI, 2.37, 8.87; P = 0.23) or 12 weeks [23.91 mg/l (95% CI, 16.10, 31.74)] (difference in means, 13.23; 95% CI, 2.45, 16.48; P = 0.13) of treatment. Similarly, bone mineral density at the hip [0.99 g/cm2 (95% CI, 0.90, 1.09)] did not change after 12 weeks of treatment [1.00 g/cm2 (95% CI, 0.89, 1.11)] (difference in means, 0.01; 95% CI, 0.25, 0.34; P = 0.74). Spine bone mineral density did not fall from pre-treatment levels [1.20 g/cm2 (95% CI, 1.11, 1.30)] after 12 weeks [1.19 g/cm2 (95% CI, 1.10, 1.29)] (difference in means, 0.01; 95% CI, 0.004, 0.01; P = 0.26). Conclusions These results confirm that Predocol is effective treatment for acute ulcerative colitis and short courses of the steroid have no adverse effects on bone formation and bone mineral density. The encouraging results from this study suggest that Predocol may be a significant advance in preventing corticosteroid induced bone loss in ulcerative colitis.

PTU-090 Type 2 diabetes as a positive risk factor in the aetiology of cholangiocarcinoma: a case-control study in two UK centres

Introduction The incidence of cholangiocarcinoma has increased worldwide with the mortality still remaining high. The aetiology in Western populations is largely unknown, but diabetes may be involved by influencing the neoplastic process via hyperinsulinaemia and the stimulation of the IGF-1 axis. As there are few population based studies looking at this, the aim of this study was to investigate if there is a positive association between type 2 diabetes and the development of cholangiocarcinoma in two centres in the UK. As oral hypoglycaemics may have anti-cancer properties, these drugs were considered when assessing the effect of diabetes. Methods Cases of cholangiocarcinoma were identified in Norwich (years 2004–2010) and Leicester (year 2007) from multi-disciplinary team meeting clinical databases. Inclusion required diagnostic evidence from CT scans and/or histology. Controls were patients, of similar ages and gender, with basal cell carcinomas treated in the dermatology departments at each hospital. The case notes of all subjects were reviewed to obtain confirmatory clinical information on cholangiocarcinoma and type 2 diabetes. Data were analysed using unconditional logistic regression to calculate ORs with 95% CIs, adjusted for age at diagnosis and gender. Results A total of 80 cases of cholangiocarcinoma (median age at diagnosis = 76 yrs, range 41–96 years, 51% men) and 411 controls were identified. All patients had radiological evidence of cancer, with 86% involving the extrahepatic biliary system. The median survival of cases was 158 days (range 2–1092 days). There was a statistically significant increase in the odds of developing cholangiocarcinoma for those with type 2 diabetes (OR=3.00, 95% CI 1.44 to 6.25), but not for type 1 (OR=1.62, 95% CI 0.165 to 16.08). When the effect of type 2 diabetes was adjusted for use of oral hypoglycaemics, the associations were maintained (metformin OR=3.60, 95% CI 1.26 to 10.25 and sulphonylureas, OR=6.31, 95% CI 2.31 to 17.18). Conclusion This epidemiological data supports the biological evidence for type 2 diabetes promoting the development of cholangiocarcinoma. Type 2 diabetes should be considered as a potential risk factor for cholangiocarcinoma in future aetiological studies. Competing interests None declared.