Alessandro Repici

European evidence based consensus for endoscopy in inflammatory bowel disease

Endoscopy plays an essential role in the diagnosis, management, prognosis, and surveillance of inflammatory bowel disease (IBD), but surprisingly there are few available guidelines.1,2 This prompted the ECCO Guidelines Committee (GuiCom) members to promote a Consensus on the appropriate indication and application of different endoscopic modalities in IBD. Since the development of guidelines is an expensive and time-consuming process, this Consensus may help to avoid duplication of effort in the future. It may also identify issues where the evidence is lacking and controlled studies are awaited. The strategy to reach the Consensus involved five steps: 1. Two members of the GuiCom (VA and RE) identified four main topics: a) Diagnosis and follow-up; b) Score of endoscopic activity; c) Small bowel endoscopy; and d) Surveillance. During 2012 a call for participants to the Guideline was made to ECCO members. In addition, expert endoscopists recognised for their active research in the field were invited. Participants were selected by the Guicom and four working groups were created. Each working group had a chair (VA, MD, MT, and RE), two ECCO members including young members (Y-ECCO) and one experienced endoscopist. For the development of the guideline, relevant questions on separate topics were devised by the chairmen and their working parties. The questions were focused on current practice and areas of controversy. Participants of the Consensus process were asked to answer the questions based on evidence from the literature as well as their experience (Delphi procedure)3; 2. The working parties working in parallel performed a systematic literature search of their topic with the appropriate key words using Medline/Pubmed and the Cochrane database, as well as other relevant sources; 3. Provisional guideline statements on their topic were then written by the chairmen. These were circulated and commented on first by working party members and …

Inflammation and Coagulation in Inflammatory Bowel Disease: The Clot Thickens

Inflammation and coagulation play crucial roles in the pathogenesis of multiple chronic inflammatory disorders. Growing evidence highlights a tight mutual network in which inflammation, coagulation, and fibrinolysis play closely related roles. Crohns disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD), are chronic inflammatory conditions, characterized by a hypercoagulable state and prothrombotic conditions, and accompanied by abnormalities in coagulation. From a pathophysiological point of view, cells and molecules classically implicated in the physiological process of coagulation have now been shown to behave abnormally in IBD and possibly to also play an active role in disease pathogenesis and/or disease progression. This paper reviews studies performed on the coagulation profile and risk factors for thrombosis in IBD. In particular, an overview is provided of the epidemiology, clinical features, and etiology of thromboembolic complications in IBD. Furthermore, we review hemostatic abnormalities in IBD, as well as the cell types involved in such processes. Finally, we highlight the coagulation system as a dynamic participant in the multifaceted process of chronic intestinal inflammation. Overall, an overview is provided that the coagulation system represents an important, though previously underestimated, component of IBD pathogenesis, and may be a possible target for therapeutic intervention.

Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

UNLABELLED This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength of recommendations and the quality of evidence. MAIN RECOMMENDATIONS 1 ESGE recommends endoscopic en bloc resection for superficial esophageal squamous cell cancers (SCCs), excluding those with obvious submucosal involvement (strong recommendation, moderate quality evidence). Endoscopic mucosal resection (EMR) may be considered in such lesions when they are smaller than 10 mm if en bloc resection can be assured. However, ESGE recommends endoscopic submucosal dissection (ESD) as the first option, mainly to provide an en bloc resection with accurate pathology staging and to avoid missing important histological features (strong recommendation, moderate quality evidence). 2 ESGE recommends endoscopic resection with a curative intent for visible lesions in Barretts esophagus (strong recommendation, moderate quality evidence). ESD has not been shown to be superior to EMR for excision of mucosal cancer, and for that reason EMR should be preferred. ESD may be considered in selected cases, such as lesions larger than 15 mm, poorly lifting tumors, and lesions at risk for submucosal invasion (strong recommendation, moderate quality evidence). 3 ESGE recommends endoscopic resection for the treatment of gastric superficial neoplastic lesions that possess a very low risk of lymph node metastasis (strong recommendation, high quality evidence). EMR is an acceptable option for lesions smaller than 10 - 15 mm with a very low probability of advanced histology (Paris 0-IIa). However, ESGE recommends ESD as treatment of choice for most gastric superficial neoplastic lesions (strong recommendation, moderate quality evidence). 4 ESGE states that the majority of colonic and rectal superficial lesions can be effectively removed in a curative way by standard polypectomy and/or by EMR (strong recommendation, moderate quality evidence). ESD can be considered for removal of colonic and rectal lesions with high suspicion of limited submucosal invasion that is based on two main criteria of depressed morphology and irregular or nongranular surface pattern, particularly if the lesions are larger than 20 mm; or ESD can be considered for colorectal lesions that otherwise cannot be optimally and radically removed by snare-based techniques (strong recommendation, moderate quality evidence).

EMR of large sessile colorectal polyps

BACKGROUND EMR optimizes histopathologic assessment of resected lesions. This study evaluated the outcome of EMR of large sessile colorectal polyps in terms of complications and recurrence. METHODS An uncontrolled prospective study was conducted of a cohort of 136 patients with sessile colorectal polyps referred for EMR. After submucosal injection, EMR was performed piecemeal by either snare polypectomy alone or with cap aspiration. RESULTS In 136 patients, a total of 139 sessile polyps were resected, 86 of which were in the right colon. Median polyps diameter was 20 mm in the right colon and 30 mm in the other colonic segments. Intraprocedure bleeding occurred after 15 polypectomies (10.8%) and was controlled endoscopically in all cases; there was no delayed bleeding. Post-polypectomy syndrome occurred in 5 patients (3.7%). There was no perforation. Invasive carcinoma was found in 17 sessile colorectal polyps, and surgery was performed in 10 of 17 cases. Follow-up colonoscopy in 93 patients without invasive carcinoma (96 polyps), over a median of 12.3 months, disclosed local recurrence of 21 adenomatous polyps (21.9%). Colonoscopic follow-up in 5 of the 7 patients, who had sessile colorectal polyps with invasive carcinoma and did not undergo surgery, disclosed no local recurrence. CONCLUSIONS EMR, including EMR with cap aspiration, is effective and safe for removal of sessile colorectal polyps throughout the colon.

Temporary placement of an expandable polyester silicone-covered stent for treatment of refractory benign esophageal strictures

BACKGROUND Benign, refractory esophageal strictures are an important therapeutic challenge. Metal stents occasionally have been used, but results have been disappointing. The present study assessed the safety and the efficacy of temporary placement of the new expandable polyester silicone-covered stent for management of problematic esophageal strictures. METHODS Fifteen patients with benign esophageal strictures were treated by temporary (6 weeks) placement of an expandable polyester silicone-covered stent. All patients had previously been treated, unsuccessfully, by repetitive endoscopic dilation. RESULTS Stent placement was successful in all patients. There was no procedure-related complication. Dilation with over-the-guidewire polyvinyl dilators was required before stent placement. With the stent in situ, dysphagia completely resolved in all patients. Six weeks after placement, one stent was found to have migrated into the stomach. In the remaining patients, the stent was easily removed with a foreign body forceps. The pretreatment dysphagia score was 3 (range 2-4); the post-treatment score was 1 (range 0-1) (p < 0.0005). Long-term resolution (mean follow-up 22.7 [2.6] months) of the stricture was achieved in 12 patients (80%). The treatment failed in 3 patients, all of whom continue to require periodic dilation. CONCLUSIONS In patients with benign esophageal strictures refractory to conventional dilation, temporary placement of a removable expandable polyester silicone-covered stent may lead to long-term relief of dysphagia with minimal morbidity.

A multicentre randomised study of intrasphincteric botulinum toxin in patients with oesophageal achalasia

BACKGROUND Intrasphincteric injection of botulinum toxin (Botx) has been proposed as treatment for oesophageal achalasia. However, the predictors of response and optimal dose remain unclear. AIMS To compare the effect of different doses of Botx and to identify predictors of response. PATIENTS/METHODS A total of 118 achalasic patients were randomised to receive one of three doses of Botx in a single injection: 50 U (n=40), 100 U (n=38), and 200 U (n=40). Of those who received 100 U, responsive patients were reinjected with an identical dose after 30 days. Clinical and manometric assessments were performed at baseline, 30 days after the initial injection of botulinum toxin, and at the end of follow up (mean 12 months; range 7–24 months). RESULTS Thirty days after the initial injection, 82% of patients were considered responders without a clear dose related effect. At the end of follow up however, relapse of symptoms was evident in 19% of patients who received two injections of 100 U compared with 47% and 43% in the 50 U and 200 U groups, respectively. Using Kaplan-Meier analysis, patients in the 100×2 U group were more likely to remain in remission at any time (p<0.04), with 68% (95% CI 59–83) still in remission at 24 months. In a multiple adjusted model, response to Botx was independently predicted by the occurrence of vigorous achalasia (odds ratio 3.3) and the 100×2 U regimen (odds ratio 3.2). CONCLUSIONS Two injections of 100 U of Botx 30 days apart appeared to be the most effective therapeutic schedule. The presence of vigorous achalasia was the principal determinant of the response to Botx.

A Randomized Prospective Comparison of Self-Expandable Plastic Stents and Partially Covered Self-Expandable Metal Stents in the Palliation of Malignant Esophageal Dysphagia

OBJECTIVES:Self-expanding metal stents (SEMS) provide effective palliation in patients with malignant dysphagia, although severe complications and mortality may result. We performed a prospective controlled trial to compare a new self-expanding polyester mesh stent (Polyflex) with SEMS (Ultraflex).METHODS:One hundred one patients with unresectable esophageal carcinoma were randomized to placement of a Polyflex (N = 47) or a partially covered Ultraflex (N = 54) stent. Patients with esophagogastric junction (EGJ) malignancy were excluded.RESULTS:Placement was successful in 46 (98%) patients with the Polyflex and 54 (100%) patients with the Ultraflex stent. In one patient, the Polyflex stent could not be placed. After 1 wk, dysphagia was improved by at least 1 grade in 100% of the Polyflex group and in 94% of the Ultraflex group. Major complications were observed in 48% of the Polyflex group and 33% of the Ultraflex group. Intraprocedural perforation occurred in 1 Polyflex and 1 Ultraflex patient. Two Polyflex patients had postprocedural hemorrhage. Twenty (44%) patients with a Polyflex stent and 18 (33%) with an Ultraflex stent had recurrent dysphagia because of tumor overgrowth, stent migration, hyperplastic granulomatous reaction, or food bolus impaction. Multivariate analysis showed a significantly higher complication rate with Polyflex than with Ultraflex stents (odds ratio 2.3, 95% CI 1.2–4.4). However, median survival was 134 days with Polyflex and 122 days with Ultraflex stents (P = NS).CONCLUSIONS:No difference was seen in palliation of dysphagia between the two stents. Significantly more complications, especially late stent migration, were observed in the Polyflex group.

New Design Esophageal Stents for the Palliation of Dysphagia From Esophageal or Gastric Cardia Cancer: A Randomized Trial

BACKGROUND & AIM:Stents are often used for the palliation of inoperable esophageal or gastric cardia cancer. One of the drawbacks of the currently used stents is the high percentage of recurrent dysphagia due to stent migration and tissue growth. New stents have been designed to overcome this unwanted sequela of stent placement. In the present study, we investigated whether results of stent placement could be improved with newer stent designs.METHODS:Between June 2004 and May 2006, 125 patients with dysphagia from inoperable carcinoma of the esophagus or gastric cardia were randomized to placement of an Ultraflex stent (N = 42), Polyflex stent (N = 41), or Niti-S stent (N = 42). Patients were followed by scheduled telephone calls at 14 days after treatment, and then monthly for 6 months or until death. Technical and functional outcome, complications, recurrent dysphagia, and survival were analyzed with, χ2 tests, Kaplan-Meier curves, and log-rank tests.RESULTS:Stent placement was technically successful in all patients with an Ultraflex stent, in 34/41 (83%) patients with a Polyflex stent, and in 40/42 (95%) patients treated with a Niti-S stent (P = 0.008). Dysphagia score improved from a median of 3 (liquids only) to 1 (ability to eat some solid food) in all patients. There were no differences in complications among the three stent types. Recurrent dysphagia, caused by tissue in- or overgrowth, migration, or food obstruction, was significantly different between patients with an Ultraflex stent and patients with a Polyflex stent or Niti-S stent (22 [52%] vs 15 [37%] vs 13 [31%], P = 0.03). Stent migration occurred more frequently with Polyflex stents, whereas tissue in- or overgrowth was more frequently seen with Ultraflex stents, and to a lesser degree, Niti-S stents. No differences were found in survival (median survival: Ultraflex stent 132 days vs Polyflex stent 102 days vs Niti-S stent 159 days) among the three stent types.CONCLUSIONS:All three stents are safe and offer adequate palliation of dysphagia from esophageal or gastric cardia cancer. Nonetheless, Polyflex stents seem the least preferable in this patient group, as placement of this device is technically demanding and associated with a high rate of stent migrations.

Prospective comparison of computed tomography enterography and magnetic resonance enterography for assessment of disease activity and complications in ileocolonic Crohn's disease

Background: Studies comparing magnetic resonance enterography (MRE) and computerized tomography enterography (CTE) for Crohns disease (CD) are scarce. Methods: The aim of this study was to prospectively compare the sensitivity, specificity, and accuracy of abdominal MRE and CTE to assess disease activity and complications (fistulas, strictures) in ileocolonic CD. A total of 44 patients (23 male; 21 female; mean age 44) with ileocolonic CD underwent both MR and CT in a short time interval (mean 5 days). A 16‐slice CT with intravenous contrast and an MRI with oral and paramagnetic intravenous contrast were performed. Ileocolonoscopy was used as the reference standard. Sensitivity values of CT and MR for detection of extraenteric signs of disease were compared with the McNemar test, with results of imaging studies, surgery, and physical examination as reference standards. Results: No significant differences in sensitivity, specificity, and accuracy were observed between MRE and CTE regarding the following parameters at the patient level: localization of CD (P = 1.0), bowel wall thickening (P = 1.0), bowel wall enhancement (P = 1.0), enteroenteric fistulas (P = 0.08), detection of abdominal nodes (P = 1.0), and perivisceral fat enhancement (P = 0.31). MR was significantly superior compared to CT in detecting strictures (P = 0.04). Per segment analysis showed that MRE was significantly superior to CTE in detecting ileal wall enhancement (P = 0.02). Conclusions: MR and CT are equally accurate to assess disease activity and bowel damage in CD. MR may be superior to CT in detecting intestinal strictures and ileal wall enhancement. MR may represent an alternative technique to CT in assessing ileocolonic CD. (Inflamm Bowel Dis 2010)

Effect of a retrograde-viewing device on adenoma detection rate during colonoscopy: the TERRACE study

BACKGROUND Although colonoscopy is currently the optimal method for detecting colorectal polyps, some are missed. The Third Eye Retroscope provides an additional retrograde view that may detect polyps behind folds. OBJECTIVE To determine whether the addition of the Third Eye Retroscope to colonoscopy improves the adenoma detection rate. DESIGN Prospective, multicenter, randomized, controlled trial. SETTING Nine European and U.S. centers. PATIENTS Of 448 enrolled subjects, 395 had data for 2 procedures. INTERVENTIONS Subjects underwent same-day tandem examinations with standard colonoscopy (SC) and Third Eye colonoscopy (TEC). Subjects were randomized to SC followed by TEC or TEC followed by SC. MAIN OUTCOME MEASUREMENTS Detection rates for all polyps and adenomas with each method. RESULTS In the per-protocol population, 173 subjects underwent SC and then TEC, and TEC yielded 78 additional polyps (48.8%), including 49 adenomas (45.8%). In 176 subjects undergoing TEC and then SC, SC yielded 31 additional polyps (19.0%), including 26 adenomas (22.6%). Net additional detection rates with TEC were 29.8% for polyps and 23.2% for adenomas. The relative risk of missing with SC compared with TEC was 2.56 for polyps (P < .001) and 1.92 for adenomas (P = .029). Mean withdrawal times for SC and TEC were 7.58 and 9.52 minutes, respectively (P < .001). The median difference in withdrawal times was 1 minute (P < .001). The mean total procedure times for SC and TEC were 16.97 and 20.87 minutes, respectively (P < .001). LIMITATIONS Despite randomization and a large cohort, there was disparity in polyp prevalence between the 2 groups of subjects. CONCLUSION The Third Eye Retroscope increases adenoma detection rate by visualizing areas behind folds. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01044732.).