John Meenan

Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease

Background : Azathioprine therapy is discontinued in one‐third of patients with inflammatory bowel disease because of toxicity or a lack of clinical response. Patients with thiopurine methyltransferase (TPMT) deficiency are intolerant to azathioprine, whilst carriers are at increased risk of side‐effects.

Altered expression of alpha 4 beta 7, a gut homing integrin, by circulating and mucosal T cells in colonic mucosal inflammation.

BACKGROUND AND AIMS: Expression of alpha 4 beta 7 on memory T lymphocytes identifies a cell population that preferentially migrates to the gut. Detection of alpha 4 beta 7 on circulating lymphocytes may permit the identification of specific subsets trafficking between the circulation and the gut in inflammatory bowel diseases. PATIENTS: Samples and clinical details were taken from patients with Crohns disease (CD), ulcerative colitis (UC), diverticulitis/ infectious colitis, and healthy controls. METHODS: Peripheral blood and lamina propria mononuclear cells were isolated. Cells were labelled with CD3, CD4, CD25, CD45RO or alpha 4 beta 7. RESULTS: Median levels of circulating total memory T cells (CD4+CD45RO+) were increased in CD (p < 0.01) and UC (p < 0.05). However, the proportion of systemic gut homing T cells (CD4+CD45RO+ alpha 4 beta 7+) was decreased in CD (p < 0.05), UC (p < 0.002), and inflammatory controls (p < 0.05). Levels of activated gut homing T cells (CD4+CD25+ alpha 4 beta 7+) were increased in CD (p < 0.01) and UC (p < 0.05). For both CD4+CD45RO+ and CD4+CD25+ cells, the proportion of lymphocytes coexpressing alpha 4 beta 7 was decreased compared with controls. In small and large intestine lamina propria, expression of alpha 4 beta 7+ on CD3+ cells was extensive, although it was decreased in CD (p < 0.03), UC (p < 0.05), and inflammatory controls (p < 0.05). CONCLUSIONS: Circulating and mucosal gut homing lymphocyte populations are changed in patients with colonic inflammation. This may arise due to a dilution effect from recruited naive T cells, or from integrin down regulation. Changes in general CD4+ lymphocyte populations mask more subtle variations in those cells with gut homing potential.

Ferric trimaltol corrects iron deficiency anaemia in patients intolerant of iron

Oral iron supplements, which are usually in the form of ferrous (Fe2+) salts, are toxic to the gastrointestinal mucosa, and so intolerance is common, resulting in poor compliance and failure of treatment. The sugar derivative maltol strongly chelates iron, rendering it available for absorption and stabilized in the less toxic ferric (Fe3+) form.

Dieulafoy's disease : endosonographic detection and endosonography-guided treatment

Abstract Background: To investigate whether endosonography can help in the detection and treatment of Dieulafoys disease, we examined eight patients with suspicion of Dieulafoys disease. Methods: Between December 1992 and April 1995, eight patients were referred because of suspicion of Dieulafoys disease. Seven presented with upper gastrointestinal bleeding and one with a tiny ulcer. In all eight patients the stomach was examined with an Olympus GF-UM20 echoendoscope. The stomach was filled with 200 to 400 ml of water after which the body, fundus, and cardia were carefully visualized. Results: In all eight patients a clearly visible, relatively large caliber (2 to 3 mm) vessel was seen to penetrate the muscularis propria and could be followed running through the submucosa for 2 to 4 cm. Subsequently four patients received sclerotherapy, three under endosonographic guidance. Follow-up of all patients (median 10 months), showed recurrent bleeding in two patients, 3 and 5 months after sclerotherapy. One was then diagnosed with a duodenal ulcer and one with recurrent bleeding from the Dieulafoys lesion. Conclusions: Endosonography is useful in the detection of Dieulafoys disease in patients with unexplained upper gastrointestinal bleeding. Sclerotherapy can be performed during the same procedure, with endosonography-guided injection of the sclerosing agent near the abnormal vessel. (Gastrointest Endosc 1996;44:437-42.)

Efficacy and safety of endoscopic dilation of esophageal strictures in epidermolysis bullosa

BACKGROUND Epidermolysis bullosa is a rare genetically determined disorder of the stratified squamous epithelium. Patients with the most severe forms develop scarring of the esophagus after ingestion of food. This results in dysphagia, which severely compromises the ability to eat. Maintenance of adequate nutritional intake is a central aim, but the most appropriate method is unknown. METHODS The results of endoscopic through-the-scope balloon dilation under propofol anesthesia in 53 patients with epidermolysis bullosa and esophageal strictures are reported. RESULTS Seventy-five percent of patients had a single stricture (range 1 to 6 strictures), most often in the proximal esophagus (median 20 cm from incisors). A total of 182 dilations were performed (median two per patient) over a median follow-up period of 3.5 years. For all but 3 patients, there was an improvement in the dysphagia score. There was a mean increase in weight after the procedure of 2.9 kg: 95% CI[2.0, 3.8]; p<0.001, over a median 29 days. There was no significant post-procedure morbidity. CONCLUSIONS Endoscopic balloon dilation is a safe and effective treatment for the esophageal strictures of epidermolysis bullosa. In the majority of patients, dilation relieves dysphagia and improves nutritional status.

The substitution of endoscopic ultrasound for endoscopic retrograde cholangio-pancreatography: implications for service development and training.

Objectives Choledocholithiasis and other benign conditions of the biliary tree are difficult to define clinically. Endoscopic retrograde cholangio-pancreatography (ERCP) is increasingly being replaced as the investigation of choice by other imaging modalities. The aim of this study was to measure the impact of substituting endoscopic ultrasound (EUS) for ERCP in terms of case throughput and the proportion of therapeutic ERCPs performed. Methods Over a 12-month period, cases with a low/medium likelihood for biliary pathology were triaged to EUS rather than ERCP. Data were collected on the proportion of ERCPs performed with diagnostic or therapeutic intent and compared with data from the preceding 12-month period. Results In the 12 months to April 2001, 518 cases were referred for ERCP; 140 underwent EUS and 378 underwent ERCP. The proportions of diagnostic and therapeutic ERCP were 14% and 86%, respectively. Benign biliary disease represented 33% of all referrals for EUS, and calculi were identified in 6% of these cases. During the preceding year, 637 ERCPs were performed. The proportion of diagnostic (33%) and therapeutic (67%) cases differed from the index year (P < 0.001). Conclusions The substitution of EUS for ERCP results in significant quantitative and qualitative change to ERCP practice, which has direct consequences for training and service development.

Endosonographic staging of lower intestinal malignancy

The use of EUS in the assessment of rectal pathology is well established. The accurate staging of lower intestinal tumours predicts prognosis and guides the planning of individual patient treatment. Increased experience and the development of high resolution three-dimensional EUS has lead to the greater accuracy of rectal staging with EUS of rectal tumours now considered the gold standard showing T stage accuracy that ranges from 75% to 95%, with N stage accuracy ranging from 65% to 80%. The use of EUS in the staging of colonic pathology, however, is not so well established though advances in miniprobe EUS has improved the assessment of colonic tumours. EUS is also of benefit in the assessment of anal pathology though here, accurate correlation with histology has not been firmly established.

Dedicated Barrett's surveillance sessions managed by trained endoscopists improve dysplasia detection rate

Background and study aim Barretts esophagus (BE)-associated dysplasia is an important marker for risk of progression to esophageal adenocarcinoma (EAC) and an indication for endoscopic therapy. However, BE surveillance technique is variable. The aim of this study was to assess the effect of dedicated BE surveillance lists on dysplasia detection rate (DDR). Patients and methods This was a prospective study of patients undergoing BE surveillance at two hospitals - community (UHL) and upper gastrointestinal center (GSTT). Four endoscopists (Group A) were trained in Prague classification, Seattle protocol biopsy technique, and lesion detection prior to performing BE surveillance endoscopies at both sites, with dedicated time slots or lists. The DDR was then compared with historical data from 47 different endoscopists at GSTT and 24 at UHL (Group B) who had undertaken Barretts surveillance over the preceding 5-year period. Results A total of 729 patients with BE underwent surveillance endoscopy between 2007 and 2012. There was no significant difference in patient age, sex, or length of BE between the two groups. There was a significant difference in detection rate of confirmed indefinite or low grade dysplasia and high grade dysplasia (HGD)/EAC between the two groups: 18 % (26 /142) Group A vs. 8 % (45/587) in Group B (P  < 0.001). Documentation of Prague criteria and adherence to the Seattle protocol was significantly higher in Group A. Conclusion This study demonstrated that a group of trained endoscopists undertaking Barretts surveillance on dedicated lists had significantly higher DDR than a nonspecialist cohort. These findings support the introduction of dedicated Barretts surveillance lists.

Use of buffered formaldehyde in the enzymatic digestion of inflamed mucosa.

Mucosal inflammation is associated with altered expression of cell membrane molecules. Disaggregation of tissue for flow cytometry may introduce artefactual changes. In an attempt to prevent the induction of artefacts, cells were fixed prior to isolation. The addition of 0.1% buffered formaldehyde to the collagenase/dispase digestion of mucosal biopsy specimens from patients with inflammatory bowel disease enhances detection of CD3, CD11b, CD16, CD63, and CD14. No significant effect was noted for CD19, CD67 or CD45. The expression of CD3, CD11b and CD45 correlated with the degree of endoscopic inflammation. Dilute buffered formaldehyde may be a useful adjunct to the enzymatic isolation of cells from mucosal specimens, by protecting surface antigens from digestion or alterations in expression.

PWE-154 Endoscopic Ultrasound (EUS) Is Superior to CT/MRI in The Detection of Pancreatic Neuro-Endocrine Tumours (PNETS) As A Baseline Assessment of Patients with Multiple Endocrine Neoplasia Type I (MEN1)

Introduction Early identification of pNETs is a key element to reducing morbidity and mortality in MEN1 patients. Prognosis is associated with tumour size and many pNETs are small subcentimetre lesions and only become symptomatic when the tumour is large. Conventional radiology is suboptimal in detecting such lesions, thus missing the window to remove them at an earlier stage. We compared: (a) linearEUS detection of pNETs in patients with confirmed MEN1 vs triple-phase contrast-enhanced CT/MRI pancreas and (b) incremental benefit of EUS to cross-sectional imaging for detection of small pNETs and quantity of pNETs in this cohort Methods Between Jan 2008- Oct 2015, a total of 20 patients with clinically confirmed MEN1 underwent baseline assessment with EUS, CT/MRI and biochemical screening. Data were retrospectively retrieved from the hospital electronic records database. Statistical analysis was performed using SPSS v20 on the size and number of pNET detection by EUS and CT/MRI using the Wilcoxon Signed Rank Test and McNemar Chi-square Results A total of 28 EUS procedures and an equal number of cross sectional imaging (CT/MRI) were performed. pNETs were identified in 95% of all 20 MEN1 cases. Overall median pNET size was 7.1 mm on EUS and 14.5 mm on CT/MRI (p = 0.007). Median value for smallest pNETs detected by EUS was 4.6 mm and 12.7 mm on CT/MRI (p = 0.001). EUS detected more pancreatic lesions/pNETs compared to CT/MRI (p < 0.001) in 25 of the 28 procedures (89.3% more). The remaining 3 procedures showed equal numbers of pNETs detection by both modalities. The interquartile range (IQR) for smallest pNET detected by EUS was 3.0–5.0 mm while IQR for CT/MRI lies between 8.3 mm-14.8mm. EUS detected all 100% cases of pNETs in our series of MEN1 compared to CT/MRI imaging alone which detected 57.9% cases (p = 0.008). 14 of 20 patients had FNA performed with a positive yield of 85.7%. In 50% of patients, pNET measured ≤10 mm. Conclusions In MEN1 patients, CT/MRI underestimated the presence of pNETs in approximately half of all cases compared to EUS and was not able to identify small pNETs (< 8 mm) in all but one case. Conclusion EUS offers higher sensitivity than cross sectional imaging (CT/MRI) in terms of detecting the number of positive pNET cases as well as a greater number of pancreatic lesions especially subcentimetre ones. EUS should be considered a standard tool in the algorithm for MEN1 workup, instead of an adjunct reserved for diagnostic dilemmas Disclosure of Interest None Declared