Amir Klein

Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: Definitions, frequency and pharmacological aspects

The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and loss of response to anti-TNF agents in IBD. The outcome of this workshop is presented into two parts. This first section addresses definitions, frequency and pharmacological aspects of anti-TNF therapy failure, including pharmacokinetics of anti-TNF monoclonal antibodies and immune and non-immune mediated clearance of anti-TNF mAbs. The second section concerns the biological roles of TNF and TNF antagonists, including mechanisms of action of anti-TNF agents, and discuss hypothesis regarding their failures and phenomenon of paradoxical inflammation, including the potential role of TNF independent inflammatory pathways.

Non Steroidal Anti-Inflammatory Drugs and Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) are an immune mediated chronic or relapsing disorders of the gastrointestinal (GI) tract. IBD is characterized by a chronic intestinal inflammatory process with various components contributing to the pathogenesis of the disease including environmental factors such as smoking or use of Non Steroidal Anti-Inflammatory Drugs (NSAIDS). NSAIDS are among the most commonly used medications for the treatment of various inflammatory conditions. The main factor limiting NSAIDS use is the concern for the development of gastrointestinal toxicity including mucosal injury. A possible association between the use of NSAIDS and the onset or relapse of IBD has been repeatedly suggested. This article will review the current concepts and evidence of the relationship between IBD and NSAIDS.

Acute, nonvariceal upper gastrointestinal bleeding.

Purpose of reviewAcute, nonvariceal upper gastrointestinal bleeding (UGIB) is a common medical emergency encountered worldwide. Despite medical and technological advances, it remains associated with significant morbidity and mortality. Recent findingsRapid patient assessment and management are paramount. When indicated, upper endoscopy in patients presenting with acute UGIB is effective for both diagnosis of the bleeding site and provision of endoscopic hemostasis. Endoscopic hemostasis significantly reduces rebleeding rates, blood transfusion requirements, length of hospital stay, surgery, and mortality. Furthermore, early upper endoscopy, defined as being performed within 24u200ah of patient presentation, improves patient outcomes. SummaryA structured approach to the patient with acute UGIB that includes early hemodynamic resuscitation and stabilization, preendoscopic risk stratification using validated instruments, pharmacologic and endoscopic intervention, and postendoscopy therapy is important to optimize patient outcome and assure efficient use of medical resources.

Bowel preparation in "real-life" small bowel capsule endoscopy: a two-center experience

Background Video capsule endoscopy (VCE) is an established diagnostic tool for the investigation of small bowel (SB) pathology. Bowel preparation prior to VCE may improve visualization, transit time, and diagnostic yield. We aimed to evaluate the “real-life” experience comparing two different preparation protocols in patients undergoing SB VCE. Methods We performed a retrospective analysis of prospectively collected data from SB VCE procedures, performed in two tertiary care medical centers in Israel. VCE procedures performed at “Sheba Medical Center” used a 2-L polyethylene glycol (PEG) bowel preparation (n=360) while VCEs performed at “Rambam Health Care campus” used a clear liquid diet plus 12-h fast protocol (n=500). A dichotomous preparation scale (adequate, inadequate) was used to classify cleansing quality. Data collection included patient and procedural details. The proportion of VCE procedures with adequate bowel preparation and the overall positive SB findings in the two different bowel preparation protocols were evaluated. Results SB completion rates were higher in the PEG protocol (96% vs. 83%, P<0.001) and SB passage time was significantly faster in the PEG protocol (mean 217±73 vs. 238±77 min, P<0.001). Bowel preparation quality was similar between groups (8% vs. 7% inadequate preparation, P=0.591). Overall positive SB findings were similar between the two groups (57% clear liquid fasting only vs. 51% PEG protocol, P=0.119). Conclusion In this large cohort, a 2-L PEG protocol had similar preparation quality and diagnostic yield compared with clear liquid fasting.

Single-dose intra-procedural ceftriaxone during endoscopic ultrasound fine-needle aspiration of pancreatic cysts is safe and effective: results from a single tertiary center

Background Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) is universally used for the investigation and diagnosis of pancreatic cystic lesions (PCL). Infectious complications following EUS-FNA of PCL are rare. Antibiotic prophylaxis to reduce the risk of infection is recommended; however, there is no consensus on the optimal regimen or route of administration. Potential advantages of a single-dose intravenous (IV) antibiotic over a prolonged oral regimen include simplicity, guaranteed delivery and fewer antibiotic related adverse events, but there are only limited data to support this. We aimed to investigate the safety and efficacy of a single 1 g dose of IV ceftriaxone in preventing infectious complications following EUS-FNA of PCL. Methods A retrospective analysis was conducted of EUS-FNA of PCL procedures performed at our center. We reviewed patient medical records for any presentation to a hospital in our district within 30 days of the procedure. An infectious complication was defined as fever/rigors, or bacteremia, or abdominal pain accompanied by imaging or laboratory results suggestive of infection, within 30 days of the procedure. Data collection included patient demographics, procedural data and outcome. Results EUS-FNA of 204 PCL (mean size 18.0 mm) was performed. Successful fluid aspiration was achieved in 94% of cases. Single-dose IV ceftriaxone was given in 146/204 (72%) cases. Four patients had a complication (pancreatitis n=1, post-procedural pain n=3). No infectious complications and no IV antibiotic-related adverse events were identified. Conclusion A single dose of IV ceftriaxone appears to be a safe, effective and convenient intervention for preventing infectious complications after FNA.

Duodenal and Papillary Adenomas

Abstract Duodenal polyps are uncommon. They can be found in 0.3%–4.6% of patients undergoing upper gastrointestinal endoscopy, and are usually an incidental finding. Adenomas account for approximately 7% of all duodenal polyps. They are most commonly found in the second part of the duodenum, and are usually solitary, flat, sessile lesions. Duodenal adenomas can be classified as papillary adenomas (PAs), when primarily involving the papilla Vateri, or duodenal adenomas (DAs), when there is no involvement of the papilla. These adenomas can be further classified as sporadic papillary adenomas (SPAs) or sporadic duodenal adenomas (SDAs), i.e., those not associated with genetic polyposis syndromes, or as those related to familial adenomatous polyposis (FAP). It is estimated that 40% of duodenal adenomas are sporadic and 60% are related to FAP. Endoscopic resection (ER) of DA and PA is quickly becoming the treatment of choice for noninvasive lesions, even when they are very extensive. Although no systematic comparative data exist, due to the lower risks of morbidity, mortality, and long-term digestive dysfunction, ER is considered preferable to surgery. ER in the duodenum requires a diverse range of endoscopic skills. These include proficiency in advanced endoscopic resection techniques, experience with pancreaticobiliary endoscopy, and the ability to identify and manage complications. These procedures should be performed by experienced endoscopists practicing in tertiary referral centers with access to surgical and interventional radiology support. A structured approach to lesion assessment, the technical aspects of resection, and postresection surveillance is required.

Hemostasis of Acute Nonvariceal Upper Gastrointestinal Bleeding

Peptic ulcers, mucosal erosions, erosive esophagitis, Mallory-Weiss tear, angiodysplasias, gastric antral vascular ectasia, and tumors are common causes of non-variceal upper gastrointestinal bleeding (NVUGIB). Endoscopy is an integral part of the management algorithm for NVUGIB. Endoscopic modalities that have proven to be effective in achieving primary hemostasis and preventing rebleeding include injection therapy, thermal therapies, and mechanical devices, such as clips and bands. The identification of bleeding lesions that are suitable for endoscopic hemostasis, careful selection of specific device(s) for a particular lesion, and operator familiarity and dexterity in handling hemostatic devices are principal determinants for a successful endoscopic outcome.

Endoscopist-directed balanced propofol sedation is safe and effective in patients undergoing outpatient colonoscopy

Background and Aims: Propofol administered in combination with other moderate sedation medications (balanced propofol sedation [BPS]) is an appealing and effective sedation regimen for gastrointestinal (GI) endoscopy procedures. However, product labeling dictates propofol be administered only by anesthesiology personnel. We evaluated the safety of endoscopist-directed as well as anesthesiologist-administered BPS during outpatient colonoscopy. Methods: We performed a retrospective cohort study using prospectively collected endoscopy data where endoscopist-directed BPS is standard practice. Measured patient outcomes included: BPS drug dosages, postcolonoscopy oxygen saturation levels, pulse, and systolic/diastolic blood pressures, need for mask bag ventilation or endotracheal intubation, aborted colonoscopy due to sedation, hospital admission postcolonoscopy, and mortality. Results: From April 1 to November 30, 2013, 1036 patients undergoing outpatient colonoscopy (mean age 56.4 years, 55% males, 32% American Society of Anesthesiologists [ASA] I, 59% ASA II, 9% ASA III) received endoscopist-directed BPS. During the same time period, 40 patients (mean age 66.6 years, 55% males, 33% ASA II, 67% ASA III) received anesthesiologist-administered BPS. Indications for colonoscopy for the endoscopist-directed BPS included 352 (34%) colorectal cancer screening/surveillance, 404 (39%) evaluation of lower GI symptoms, 156 (15%) positive fecal occult blood, and 124 (12%) inflammatory bowel disease. BPS dosages (mean ± standard deviation) per patient were Fentanyl 0.05 mg (fixed dose), midazolam 1.6 mg ± 0.5 mg (range: 1-5 mg), and propofol 104 mg ± 62 mg (range: 10-460 mg). Propofol doses correlated inversely with patient age ( r = −0.35; P P Conclusions: Endoscopist-directed BPS appears safe and effective for low-, intermediate- and high-risk patients undergoing outpatient colonoscopy.

Su1303 Early Histological Findings May Predict the Clinical Phenotype in Crohn's Colitis

Background: The clinical course of Crohns disease (CD) is variable and relevant for treatment selection. Early aggressive treatment may change disease course, but should be balanced with safety considerations. Currently, diagnostic tools for prediction of disease phenotype and complications are lacking. Histomorphometric analysis allows for quantitative measurements of size, shapes and orientation of cells and structures in tissues. In a previous pilot study, we were able to show that morphometric analysis may contribute to the prediction of the clinical phenotype and surgery in patients with Crohns colitis. Aim: To further evaluated and validate the histomorphometric features of early colonic biopsies from patients with Crohns colitis and their relationship to evolving clinical phenotypes. Methods: Colonic biopsies from 100 CD patients classified according to the Montreal classification with at least 5 years post biopsy follow up were analyzed. The results were used to predict post biopsy clinical phenotypes and outcomes. Data analysis was performed using multivariate regression models, discriminant score (DS) computations and Neural Network (NNET). Results: Multivariate analysis differentiated between B1 and B2 phenotypes (sensitivity-81%, specificity-74%, accuracy on cross validation-75%). ROC analysis of the discriminant score (DS) yielded an area under the curve (AUC) of 0.74 (CI 0.6-0.84). A NNET model also differentiated between B1and B2 phenotypes (sensitivity87%, specificity-67% on the testing population). Differentiation between B1 and B3 phenotypes, had a sensitivity of 69% and a specificity of 76% with an accuracy of 70.5% on cross validation. ROC analysis of the DS