Kevin A. Waschke

Tumor necrosis factor receptor gene polymorphisms in Crohn's disease: association with clinical phenotypes.

OBJECTIVES:Crohns disease (CD) is a chronic multifactorial disorder with diverse clinical features that are influenced by a heterogeneous set of genetic factors. TNF-α/TNF receptor interactions play a pivotal role in the pathogenesis of the inflammatory response. Our purpose was to determine whether single nucleotide polymorphisms (SNPs) in the TNF receptors confer susceptibility to Crohns disease and whether they are associated with clinical phenotype.METHODS:A cohort of 205 consecutively identified and unrelated patients with CD and 106 controls were recruited. Subjects were genotyped for polymorphisms in TNFRSF1A (position +36, −609), TNFRSF1B (+196, +1466), along with the three common CARD15 variants and phenotyped for disease behavior. Genotypic and allelic frequencies were compared between CD and controls and a logistic regression model was constructed to determine independent associations with specific clinical phenotypes.RESULTS:Only the TNFRSF1A +36 and TNFRSF1B +196 SNPs were associated with CD (p = 0.0019 and 0.034, respectively). The TNFRSF1A +36 mutation was negatively associated with stricturing disease phenotype (OR = 0.384; CI = 0.166–0.887). In contrast, the TNFRSF1B +196 was negatively associated with colitis (OR = 0.410; CI = 0.191–0.880). These associations were independent of CARD15 mutation status. Finally, TNFRSF1B +196 was negatively associated with surgery in CARD15 negative patients.CONCLUSIONS:These data constitute the first report of an association of TNFRSF1A and TNFRSF1B polymorphisms with CD in a Caucasian population and address the role of TNFR mutations in determining clinical heterogeneity in CD.

Meta‐analysis: rectal indomethacin for the prevention of post‐ERCP pancreatitis

Despite initial evidence in the literature, nonsteroidal anti‐inflammatory drugs (NSAIDs) have not been widely used to prevent post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).

The mechanisms of prednisone inhibition of inflammation in Crohn's disease involve changes in intestinal permeability, mucosal TNFalpha production and nuclear factor kappa B expression.

Background : The clinical course of Crohns disease after the induction of remission with medical therapy is characterized by unpredictable relapse.

Randomized controlled trial comparing outcomes of video capsule endoscopy with push enteroscopy in obscure gastrointestinal bleeding

BACKGROUND Optimal management of obscure gastrointestinal bleeding (OGIB) remains unclear. OBJECTIVE To evaluate diagnostic yields and downstream clinical outcomes comparing video capsule endoscopy (VCE) with push enteroscopy (PE). METHODS Patients with OGIB and negative esophagogastroduodenoscopies and colonoscopies were randomly assigned to VCE or PE and followed for 12 months. End points included diagnostic yield, acute or chronic bleeding, health resource utilization and crossovers. RESULTS Data from 79 patients were analyzed (VCE n=40; PE n=39; 82.3% overt OGIB). VCE had greater diagnostic yield (72.5% versus 48.7%; P<0.05), especially in the distal small bowel (58% versus 13%; P<0.01). More VCE-identified lesions were rated possible or certain causes of bleeding (79.3% versus 35.0%; P<0.05). During follow-up, there were no differences in the rates of ongoing bleeding (acute [40.0% versus 38.5%; P not significant], chronic [32.5% versus 45.6%; P not significant]), nor in health resource utilization. Fewer VCE-first patients crossed over due to ongoing bleeding (22.5% versus 48.7%; P<0.05). CONCLUSIONS A VCE-first approach had a significant diagnostic advantage over PE-first in patients with OGIB, especially with regard to detecting small bowel lesions, affecting clinical certainty and subsequent further small bowel investigations, with no subsequent differences in bleeding or resource utilization outcomes in follow-up. These findings question the clinical relevance of many of the discovered endoscopic lesions or the ability to treat most of these effectively over time. Improved prognostication of both patient characteristics and endoscopic lesion appearance with regard to bleeding behaviour, coupled with the impact of therapeutic deep enteroscopy, is now required using adapted, high-quality study methodologies.

The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

PURPOSE Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). METHODS AND MATERIALS Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. RESULTS At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). CONCLUSIONS This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.

Minimally invasive management of pancreatic disease

1 Department of Surgery, University of Washington, Seattle, WA, USA 2 Department of Surgery, University of Louisville, Louisville, KY, USA 3 Department of Gastroenterology, McGill University, Montreal, Quebec, Canada 4 Department of Surgery, The Beth Israel Deaconess Medical Center, Boston, MA, USA 5 Department of Surgery, The George Washington University Medical Center, 2150 Pennsylvania Avenue NW, Suite 6B, Washington, DC, 20037, USA

Current status of core and advanced adult gastrointestinal endoscopy training in Canada: Survey of existing accredited programs.

OBJECTIVE To determine the current status of core and advanced adult gastroenterology training in Canada. METHODS A survey consisting of 20 questions pertaining to core and advanced endoscopy training was circulated to 14 accredited adult gastroenterology residency program directors. For continuous variables, median and range were analyzed; for categorical variables, percentage and associated 95% CIs were analyzed. RESULTS All 14 programs responded to the survey. The median number of core trainees was six (range four to 16). The median (range) procedural volumes for gastroscopy, colonoscopy, percutaneous endoscopic gastrostomy and sigmoidoscopy, respectively, were 400 (150 to 1000), 325 (200 to 1500), 15 (zero to 250) and 60 (25 to 300). Eleven of 13 (84.6%) programs used endoscopy simulators in their curriculum. Eight of 14 programs (57%) provided a structured advanced endoscopy training fellowship. The majority (88%) offered training of combined endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography. The median number of positions offered yearly for advanced endoscopy fellowship was one (range one to three). The median (range) procedural volumes for ERCP, endoscopic ultrasonography and endoscopic mucosal resection, respectively, were 325 (200 to 750), 250 (80 to 400) and 20 (10 to 63). None of the current programs offered training in endoscopic submucosal dissection or natural orifice transluminal endoscopic surgery. CONCLUSION Most accredited adult Canadian gastroenterology programs met the minimal procedural requirements recommended by the Canadian Association of Gastroenterology during core training. However, a more heterogeneous experience has been observed for advanced training. Additional studies would be required to validate and standardize evaluation tools used during gastroenterology curricula.

A case of acute loss of vision as the presenting symptom of Crohn's disease

Background An adolescent boy aged 17 years presented with sudden onset of visual impairment, which was rapidly diagnosed as bilateral anterior uveitis by an ophthalmologist. A systemic review noted episodes of nonbloody diarrhea, weight loss of 3 kg and a diminished appetite during the previous 10 months. The patients family history revealed an older brother with Crohns disease.Investigations Visual acuity test, slit-lamp examination, ophthalmologic fundoscopy and endoscopic evaluation of the upper and lower gastrointestinal tract with biopsy.Diagnosis Multifocal Crohns disease, involving the terminal ileum and cecum, in addition to the stomach and duodenum.Management Treatment with topical corticosteroids, in the form of ophthalmic drops and oral budesonide ileal-release capsules. Once remission was achieved, it was maintained with mercaptopurine.

Self-Expanding Metal Stents Confer a Survival Advantage in the Palliation of Distal Malignant Biliary Obstruction

Self-Expanding Metal Stents Confer a Survival Advantage in the Palliation of Distal Malignant Biliary Obstruction Kevin Waschke, Eduardo da Silveira, Youssef Toubouti, Elham Rahme, Alan Barkun Background: Plastic and self-expanding metal stents are used to palliate malignant biliary obstruction, yet can be complicated by occlusion. A previous set of meta-analyses by our group showed that no plastic stent design is superior and that adjuvant therapy does not improve stent patency or prolong patient survival. Objectives: To determine the effect of metal stent technologies compared with plastic stent insertion on duration of stent patency and patient survival in malignant biliary obstruction. Methods: Relevant English RCTs (1980-2004) were assessed by 2 reviewers for methodological quality using a validity assessment score created for this analysis. Data were abstracted regarding patient characteristics of stent insertion (ERCP vs. percutaneous) for distal malignant biliary obstruction, excluding hepatic metastases. Only trials with sufficient statistical information were included. The main outcomes were median stent occlusion and median patient survival. The difference of log-transformed median stent patency or survival ratio of the treatment stent vs. control was calculated for each study. Data were pooled using a random effect model and then re-transformed to the original scale to provide pooled estimates and 95% CI. Sensitivity analysis was done. SAS software (v 8.2) was used for statistical analysis. Results: A meta-analysis of 3 trials with 184 patients treated with plastic vs. self-expanding metal stent insertion showed a significant benefit for metal stents in terms of median patency (ratio 0.3, 95% CI 0.131 to 0.599 p Z 0.001). A survival advantage was also noted that favored metal stents (0.69, p Z 0.03, 95% CI 0.486 to 0.968). Conclusions: The use of metal stents results in a prolonged median patency when compared with plastic, which confirms results of individual trials. The use of SEMS was shown in this meta-analysis to provide a survival advantage when compared to plastic stents–this has never been shown in individual trials, probably due to insufficient statistical power but bears significant clinical implications. Additional high quality clinical data are required to assess this important finding. T1324 Case Finding for Celiac Disease Using Zoom Endoscopy Rawya Badreldin, Paul Barrett, John Mansfield, Yan Yiannakou Introduction: The detection of coeliac disease is often difficult as 20-50% of adult coeliac disease (CD) fails to present with malabsorptive symptoms and up to 5% have negative serology. Although coeliac disease fulfils the criteria for mass screening, the best epidemiological approach at present, is a case finding one. Using a zoom endoscope, a patients’ presentation for an endoscopy for any indication provides an opportunity to screen for villous atrophy. The role of zoom endoscopy in coeliac disease has been evaluated in only a few small studies. Aims: 1-To establish the efficacy of zoom endoscopy in detecting villous atrophy villous atrophy in a large case finding series. 2-Compare the detection of villous atrophy using conventional video and magnification endoscopy. Methods: 951 patients were prospectively recruited over a 22 month period. Patients with known coeliac disease were excluded. All endoscopies were performed by one endoscopist using the Olympus Q240Z endoscope. The duodenum was first examined for loss of folds, scalloping and a mosaic pattern. Then on full magnification of 115 normal, a score of Z1 to Z4 was allocated, with Z1 being normal villi and Z4 a flat mucosa. Results: Two patients were excluded; one with childhood coeliac disease and the other with duodenal Crohn’s disease. Of the patients referred, 147 had symptoms consistent with coeliac disease and 802 had non-suggestive symptoms. Twenty-three new cases of coeliac disease were found giving a prevalence rate of 2.42%. Seven of these patients had non-suggestive symptoms giving a prevalence rate of unsuspected CD of 0.74% in this population. Zoom endoscopy has a sensitivity of 95.65% and a specificity of 97.08% in detecting villous atrophy and a negative and positive predictive value of 99.88% and 44.89% respectively. Conclusions: Zoom endoscopy can be utilized successfully as a case finding tool for coeliac disease in patients presenting for endoscopy and is particularly useful when the diagnosis had not been considered.

Advances and challenges in endoscopic training

One of the challenges of the current era is ensuring that endoscopic training is accomplished effectively in the face of multiple competing demands. As health care delivery evolves, with rising patient complexity and increasing productivity requirements, there is mounting pressure on the time available for training in the clinical setting. The practice of endoscopy itself continues to expand to include increasingly complex procedures (eg, therapeutic endoscopic ultrasound, endoscopic submucosal dissection, and peroral endoscopic myotomy) that require dedicated endoscopy training. The rapid pace of progress in the field of endoscopy means that the demand for endoscopy training is not limited to the formal period of training, but instead spans the spectrum to include physicians already in practice. In light of recent advances in our understanding of endoscopy training, this review will serve to highlight the current state of affairs with respect to endoscopic training and how we can consider approaching these challenges.