Presentation on theme: "Consensus Report the 5 th International Conference on Capsule Endoscopy™ Conference Chairs Blair S. Lewis Roberto de Franchis Gèrard Gay."— Presentation transcript:
Consensus Report the 5 th International Conference on Capsule Endoscopy™ Conference Chairs Blair S. Lewis Roberto de Franchis Gèrard Gay
ICCE 2006 Two clinical congresses in 2006 Boca Raton, Florida, USA March 6-7, 2006 Paris, France June 9-10, 2006 Combined statistics 622 attendees 40 countries represented 146 abstracts presented 89 oral presentations
Consensus Activities Reviewed last year’s data and updated ICCE 2005 Consensus Drafted paper for peer-reviewed publication in Endoscopy this fall Consensus Topics IBD Esophagus Tumors Bleeding Celiac Preps/Prokinetics
Inflammatory Bowel Disease (IBD) Panel Co-Chairmen E. Seidman I. Bjarnason Panel Members: J. Leighton, P. Legnani, M. Gassull, J.F. Columbel, V. Manoury, A. Kornbluth June 2006
IBD Consensus Capsule Endoscopy (CE) for IBD: Higher sensitivity for assessing small bowel mucosal lesions compared to other imaging techniques
Meta-analysis of Prospective Comparative Crohn’s Disease Studies: CE vs. Other Modalities Triester et al Am J Gastroenterol 2006;101: studies, n=223 Established or Suspected nPublished Study Established/Suspected 3 Costamagna 2002 Established 17Heigh 2003 Established/Suspected 19Bloom 2003 Established23Buchman 2003 Established 5Goelder 2003 Established 8Voderholzer 2003 Established/Suspected 21Chong 2003 Suspected35Eliakim 2004 Established/Suspected 47Toth 2004 Established/Suspected 31Dubcenco 2004 Established 19Marmo 2004
: CE vs. SB Radiography : 0.33 [-0.42, 1.09] 0.37 [0.08, 0.66] 0.48 [0.22, 0.73] 0.47 [0.17, 0.77] 0.00 [-0.27, 0.27] 0.61 [0.42, 0.81] 0.54 [0.35, 0.74] 0.53 [0.26, 0.80] 0.34 [0.17, 0.51] StudyIY (random)Incremental Yield (random) 95% CI Costamagna 2002 Bloom 2003 Chong 2003 Heigh 2003 Buchman 2004 Dubcenco 2004 Eliakim 2004 Marmo 2004 Toth 2004 Total ( 95 % CI) 0.42 [0.30, 0.54 ] Total yield: 66% (CE), 24% (SB radio) Test for heterogeneity: P = 0.03, I² = 52.1% Test for overall effect: P < Higher yield SB radiography Higher yield CE Triester et al Am J Gastroenterol 2006;101:
CE vs. Ileoscopy Study IY (fixed) 95% CI Bloom [-0.26, 0.37] Heigh [-0.26, 0.37] Dubcenco [0.09, 0.55] Toth [-0.09, 0.30] Total (95% CI) 0.15 [0.02, 0.27] Total yield: 61% (CE), 46% (Ileoscopy) Test for heterogeneity: P = 0.38, I² = 2.1% Test for overall effect: P = Higher yield Ileoscopy Higher yield CE Triester et al Am J Gastroenterol 2006;101:
Study IY (fixed) 95% CI Heigh [-0.14, 0.50] Voderholzer [-0.42, 0.42] Eliakim [0.38, 0.76] Total (95% CI) 0.38 [0.23, 0.54] Total yield: 75% (CE), 37% (CTE) Test for heterogeneity: P = 0.01, I² = 76.2% Test for overall effect: P < Higher yield CTE Higher yield CE Triester et al. Am J Gastroenterol 2006;101: CE vs. CT Enterography (CTE)
Summary of Incremental Yield (IY) of CE Over Other Modalities Triester et al. Am J Gastroenterol 2006;101: % IY for CE (95% CI) Total yield other modality (%) Total yield CE (%) 42 ( )2466vs. SB Radiography 15 ( )4661vs. Ileoscopy 38 ( )3775vs. CT Enterography 44 ( )751vs. Push Enteroscopy 20 ( )4060vs. Small Bowel MRI
Suspected CD subgroup Study IY (random) [95% CI] Costamagna [-0.85, 0.85] Dubcenco [-0.04, 0.79] Eliakim [0.35, 0.74] Toth [-0.02, 0.37] Chong [-0.11, 0.11] Hara [-0.16, 0.66] Total (95% CI) 0.24 [-0.03, 0.51] Total yield (fixed): 43% (CE), 13% (barium radiography) Test for heterogeneity: P < 0.001, I² = 85.6% Test for overall effect: P = Yield higher in barium radiography Yield higher in capsule endoscopy Study IY (random) [95% CI] Costamagna [-0.21, 1.21] Buchman [-0.20, 0.27] Dubcenco [0.49, 0.90] Marmo [0.23, 0.67] Toth [0.35, 0.87] Chong [0.38, 0.86] Hara [0.34, 0.99] Total (95% CI) 0.51 [0.31, 0.70] Total yield (fixed): 78% (CE), 32% (barium radiography) Test for heterogeneity: P = 0.001, I² = 72.9% Test for overall effect: P < Yield higher in barium radiography Yield higher in capsule endoscopy Established CD subgroup CE vs. Barium Radiography
CE vs. CT Enterography (n=58 pts) CE detects more proximal disease Voderholzer et al. Gut 2005;54: Hara et al. Radiology 2006;238(1): exams
MR Enteroclysis (n=18 pts) Golder et al. Int’l J of Colorectal Disease 2006;21(2): exams
IBD Consensus Capsule endoscopy (CE) vs. other imaging: Limitations The available data are more evidence based for known, non-stricturing CD than for suspected CD. No “gold standard” available for CD. CE is superior to CT enterography & MRI; particularly for proximal - mid small bowel CD. CE demonstrates mucosal lesions missed by other imaging. No single test is available for diagnosing CD.
CE may be useful in the study of indeterminate colitis: 22 pts with colonic IBD underwent CE. 9 (40%) with “colitis” were found to have small bowel lesions. 27 pts with IC underwent CE. 8 (29%) had small bowel lesions. 10 pts with IC underwent CE. 4 (40%) had small bowel lesions. Mow WS, et al. CGH 2004;2:31-40 Mascarenhas-Saraiva M, et al. ICCE 2005 AB 115 Hume G, et al. ICCE 2004 AB 1054 IBD Consensus
31 patients with IC and known serology CE and serology equally sensitive (61%). CE was more sensitive than ASCA or OMP-C in diagnosing small bowel CD. Conclusion: CE was superior to CD-like markers in identifying small bowel disease in IC patients. Lo SK, et al., Gastrointest Endosc 2003;57(5):AB 1889 IBD Consensus
Role of CE in assessing for early post- operative recurrence 32 post-op ileocecal resection CE & ileo-colonoscopy < 6 months Recurrence: 21/32 – sensitivity Ileo-colonoscopy 90% vs. 62% for CE CE identified more proximal disease in 2/3 of cases. CE may be useful as a first line evaluation of post- operative recurrence due to its good tolerability. Bourreille et al Gut 2006;55: IBD Consensus
Role of CE in assessing for early post-operative recurrence 14 patients post-op ileocecal resection x 1 yr CE & small bowel US compared in 13 (1 stricture) Recurrence: 12/13 by colonoscopy US: 13/13 ( 1 false +) CE: 12/13 (all true +) CE represents an alternative minimally-invasive technique for assessing CD recurrence in patients under follow-up of ileo-colonic resection. Biancone et al; Gastroenterology 2006;130(4):Supp S2: AB S1336 IBD Consensus
Capsule endoscopy (CE) for suspected IBD: Useful and safe in patients with suspected Crohn’s disease and negative endoscopic & small bowel imaging Evidence: based mainly on retrospective studies; more prospective data needed. Positive CE findings not well defined (lack of validated scoring index). Has potential to affect patient management. Scoring index may provide diagnostic threshold. IBD Consensus
Capsule Endoscopy: Are All Ulcers Crohn’s? Which image is an ulcer from Crohn’s disease? The answer is all three. However, patient history will define if another cause, such as NSAID damage or radiation enteropathy caused the ulceration. ABC
IBD Consensus Standardized CE scoring index of disease severity to differentiate normal from small bowel inflammatory disorders in development. Correlation of CE index with clinical disease activity scores needed. CE scoring index may not distinguish between various causes of inflammation (NSAIDs, radiation enteropathy).
Scoring Index Parameters Villous Appearance Ulceration Stenosis Scale Normal, edematous Number - single, few, multiple Distribution - localized, patchy, diffuse Longitudinal extent - short, long, whole segment Ulcer size - based on amount of bowel wall circumference involved Stenosis - ulcerated or not, traversed or not
Example of Score Template Global Disease Assessment: Normal, Mild, Moderate/Severe
Suspected Crohn’s Disease Patients with characteristic GI symptoms of CD (at least 1 from “A”), and with at least one of the criteria under “B”, “C” or “D”: Characteristic GI Symptoms (anti-tTG negative) Chronic abdominal pain Chronic diarrhea Significant weight loss Growth failure Extra-intestinal Symptoms Unexplained recurrent fever Arthritis/arthralgias Pyoderma/erythema nodosum Aphthous stomatitis Perianal disease PSC/recurrent cholangitis Inflammatory Markers Iron deficiency anemia Thrombocytosis or leukocytosis Elevated ESR or CRP Hypoalbuminemia Positive IBD serology Fecal markers: lactoferrin, alpha-1 antitrypsin, calprotectin; heme +; leucocyte + Abnormal, Non-diagnostic Imaging
Figure 1. Algorithm for the approach to suspected small bowel Crohn’s Disease (CD). The absence of any mucosal lesions demonstrated by a complete assessment of the small bowel by capsule endoscopy excludes active CD of the small bowel. Patients with symptoms suggestive of obstruction, or known to have a stenosis should either undergo a patency capsule exam or evaluation by CTE or MRE prior to capsule endoscopy. Abbreviations: SB CD=small bowel Crohn’s Disease, CTE=CT enterography, MRE=MR enterography, SBFT=small bowel follow through. Suspected SB CD Positive ileocolonoscopy Negative ileocolonoscopy or unsuccessful Possible or known obstruction No obstruction Patency capsule CTE/MRE (SBFT) Capsule endoscopy Presence of SBCD Treat accordingly ObstructionNo obstruction either/or
Capsule Retention and CD TypeCapsule Retention (%) Patients (n)Author Type Known450Mow Suspected021Herrerias Suspected017Fireman Suspected020Eliakim Suspected520Sant’Anna Known6.730Buchman Known strictures13.038Chiefetz
Capsule Retention in Crohn’s Disease In patients with Established CD, the risk is 5%, despite absence of strictures on SBFT. In cases with Suspected CD: The risk is low with negative SBFT. If no SBFT, in the absence of obstructive symptoms, risk is yet unknown.
Conclusions CE has a higher sensitivity for assessing small bowel mucosal lesions compared to other imaging techniques. CE is helpful diagnosing suspected Crohn’s in the pediatric population. CE is superior to CT enterography & MRI; particularly for proximal - mid small bowel CD. CE may be useful as a first line evaluation of postoperative recurrence of CD. CE can detect small bowel lesions in a significant number of patients with indeterminate colitis and may alter disease management. CE is useful and safe in patients with suspected Crohn’s disease and negative endoscopic & small bowel imaging.
Esophagus Panel Co-Chairmen R. Eliakim G. Eisen Panel Members: J.P. Galmiche, T. Roesch, F. Schnoll-Sussman, J. Herrerias, V.K. Sharma, E. Coron June 2006
Consensus Statement - Esophageal Capsule Endoscopy (ECE) A new approach to esophageal diagnostics Simple and easy Patient-friendly Screening tool for esophageal diseases Encouraging initial clinical data Esophageal Varices Barrett’s Esophagus
Consensus Statement – Varices Eisen G, De Franchis R, Eliakim R, Zaman A, Schwartz J, Faigel D, Rondonotti E, Villa F, Weizman E, Yassin K. Preliminary results of International Multicenter Trial. 32 patients reported. ICCE 2006 AB Esophageal varices (EV) are a serious consequence of portal hypertension (PHT). In patients with cirrhosis, the incidence of EV increases 5% per year and the rate of progression from small to large varices is 5-10%. Increasing size of varices is associated with increased wall tension leading to rupture and bleeding. AASLD/UK guidelines recommend endoscopic screening of patients with cirrhosis for varices and treatment of patients with medium/large varices to prevent bleeding.
Consensus Statement – Varices (continued) Recommended endoscopic screening intervals are 1-3 years, depending on presence/absence of varices and whether patient has compensated/decompensated liver disease. Endoscopic surveillance is performed in patients after obliteration of varices. This patient population could benefit from a non- invasive diagnostic test that does not require sedation. These recommendations/practices represent a potentially large endoscopic burden. Eisen G, De Franchis R, Eliakim R, Zaman A, Schwartz J, Faigel D, Rondonotti E, Villa F, Weizman E, Yassin K. Preliminary results of International Multicenter Trial. 32 patients reported. ICCE 2006 AB 20154
EV Screening Pilot Trial Initial pilot trial – EV screening with ESO Prospective blinded, 3 center study 32 patients – enriched population with surveillance No complications, no retention Japanese endoscopic grading system F0 = none F1 = small F2 = medium F3 = large Modified classification for current trial None/small/medium-large Medium-Large > 25% circumference Eisen G, Eliakim R, Zaman A, Schwartz J,Faigel D, Rondonotti E, Villa F, Weizman E, Yassin K, de Franchis R. Endoscopy 2006:38:1-5
Comparison of PillCam ESO and EGD: Esophageal Varices NPVPPVSpecificitySensitivity Study Design # PatientsReference 57%100% 81%Prospective Blinded 21Study 1 74%94%87% Prospective Blinded 97Study 2 100%96%89%100%Prospective Blinded 32Study 3 1. Lapalus MG. Endoscopy 2006;38: Eisen GM, de Franchis R. Interim Analysis of the Evaluation of PillCam ESO in the Detection of Esophageal Varices AB Eisen G, de Franchis R, Eliakim R, Zaman A, Schwartz J, Faigel D, Rondonotti E, Villa F, Weizman E, Yassin K, Endoscopy 2006;38(1):1-5
Esophageal Image Spectrum
Epidemiology in Barrett’s Esophagus times > general population up to 2% of patients with BE times > general population up to 2% of patients with BE Risk of esophageal cancer in Barrett’s esophagus 7% of US Population have daily GERD Symptoms 7% of US Population have daily GERD Symptoms 10% of Chronic GERD Patients have Barrett’s esophagus 10% of Chronic GERD Patients have Barrett’s esophagus Locke III et al. Gastro 1997: 112: Falk GW. Gastro Endosc 1999; 49(3):S29-34.
Screening for Barrett’s Esophagus Adenocarcinoma is a lethal disease. GERD is a firmly established risk factor for this cancer. Barrett’s esophagus, a premalignant precursor, is firmly associated with GERD symptoms, and is clearly associated with an increased risk of cancer (RR X general population).
Multi-center Study Overview Primary aims Accuracy of ECE compared with EGD for the diagnosis of esophageal pathology in patients with chronic GERD symptoms Specificity, sensitivity, PPV, NPV Safety and adverse events of ECE Secondary aims Assess capability of ECE to identify presence of Barrett’s esophagus in patients undergoing surveillance endoscopy Assess patient satisfaction with both procedures Multi-site: Prospective 7-center international study Israel (3), USA (3), Germany (1) Inclusion criteria Aged 18 years or older Confirmation of 1 of the following: Histologic confirmation of Barrett's esophagus undergoing surveillance endoscopy Chronic GERD symptoms undergoing upper endoscopy for the evaluation of GERD Eliakim R et al. J Clin Gastroenterol 2005;39:
Patient Enrollment 1 unable to swallow capsule 93 (88%) endoscoped for GERD symptoms 13 (12%) for surveillance of Barrett’s esophagus 2 technical difficulties 109 patients enrolled 106 included in per-protocol statistical analysis Eliakim R et al. J Clin Gastroenterol 2005;39:
Methods ECE swallowed using standardized ingestion protocol. Blinded investigator reviewed ECE videos. Upper endoscopy performed on the same day following ECE. Adjudication committee arbitrated if discrepancy between procedures was noted. Barrett’s cases were not biopsied for confirmation. Eliakim R et al. J Clin Gastroenterol 2005;39:
Multi-center Study Results: Esophagitis EGD +- ECE ECE Sensitivity89% Specificity99% Positive Predictive Value (PPV)97% Negative Predictive Value (NPV)94% Eliakim R, Sharma VK et al. In press. J Clin Gastro Adjudicated results
Multi-center Results: Barrett’s Esophagus EGD +- ECE ECE Sensitivity97% Specificity99% Positive Predictive Value (PPV)97% Negative Predictive Value (NPV)99% Adjudicated results Eliakim R, Sharma VK et al. In press. J Clin Gastro
ECE Clinical Trial Data: Barrett’s Esophagus NPVPPVSpecificitySensitivity# PatientsReference 89%56%84%67%58VA Mason Trial 1 74%86% 73%32Kansas Trial 2 1. Lin et al. Blinded Comparison of Esophageal Capsule Endoscopy vs. Conventional Endoscopy for Diagnosis of Barrett’s Esophagus in Patients with Chronic Gastroesophageal Reflux GIE ( in Press) 2. Sharma et al Gastroenterology 2006;130(4) April AB S1812
Conclusions ECE does offer a minimally invasive method to screen for esophageal varices and portal hypertensive gastropathy. ECE does have a role in the evaluation of patients with esophageal disease that would otherwise avoid traditional testing methods. Large scale studies are needed to confirm outcomes.
GI Bleeding Panel Co-Chairmen M. Pennazio I. Gralnek Panel Members: M. Delvaux, N. Reddy S. Bar Meir, I. Demedts, M. Keuchel June 2006
Panel Participants (Boca Raton/Paris) Martin Keuchel Ingrid Demedts Simon Bar-Meir Nageshwar Reddy Michael Delvaux Scott Ketover Morry Moskovitz Shenan Abey Colm O’Morain
Value of CE for Obscure GI Bleeding CE is a valuable diagnostic modality in evaluating obscure GI bleeding. Key advantages of CE include: ability to image entire small bowel; ability to review and share images; patient preference; safety profile; ability to conduct in variety of settings; clarity of image comparable to other endoscopy. 2 meta-analyses support role of CE in OGIB*. *Triester et al. Am J Gastro 2005;100: *Marmo et al. APT 2005;22:
Value of CE for Obscure GI Bleeding Marmo et al. APT 2005;22:
Value of CE for Obscure GI Bleeding Triester et al. Am J Gastroenterol 2005;100:
Study Sensitivity (%) Specificity (%) PPV (%) NPV (%) Pennazio et al. Gastrpenterology Delvaux et al. Endoscopy Saurin et al. Endoscopy Hartmann et al. GIE Hindryckx et al. ICCE Walsh et al. DDW Accuracy of Diagnostic Interpretation
Algorithm for CE in Obscure GI Bleeding Add algorithm OGIB Pennazio M, Eisen G, Goldfarb N. ICCE Consensus - Endoscopy 2005
“Missed Lesions” Detected by CE Selby W. et al. GIE 2005;61(5): AB M1390 Chung H. et al. DDW 2006;63(4) Supp S: AB M1247 Edery J. et al. ICCE 2006;AB % to 25% of lesions detected by CE are NOT in the small bowel. Clinical significance unknown.
“Early CE” in Overt OGIB Ben Soussan et al. ICCE 2006;AB Gay G. et al. ICCE 2006;AB Yield of CE: 70-84% Timing of CE is important.
Patient Selection for CE in Obscure GI Bleeding Patient selection for CE in OGIB is established in the literature; yet for IDA it is not. Clinical parameters to predict diagnostic yield not clearly established: transfusion requirements. May A. et al. J Clin Gastro 2005;39: Al Ali J. et al. Gastrointest Endosc 2006;63(4): AB M1346
“An initial diagnostic imaging employing CE might be followed by DBE for treatment or histopathological diagnosis.” Nakamura M, et al. Endoscopy 2006;38(1):59-66 Hadithi M, et al. Am J Gastro 2006;101:52-57 “The use of CE as a filter for DBE results in effective management of patients with various intestinal diseases. CE can also direct the choice of route of DBE.” Gay G, et al. Endoscopy 2006;38(1):49-58 Pennazio M. et al. DDW 2006;63(4) Supp S AB 496 Capsule Endoscopy and Double-balloon Enteroscopy
Lai L, et al. Am J Gastro 2006;101: OGIB patients Yield of CE: 31 (63%) Interventions: 15 (30.6%) Mean follow-up: 19 m. Re-bleeding rate: 32.7% CE -: 5.6% CE +: 48.4% p=0.03 Re-bleeding Rates in Patients with Positive and Negative CE
285 OGIB patients Yield of CE: 177 (62%) – 50% underwent treatment Re-bleeding rate: 44 (18%) FACTORRR for bleeding relapse Diagnosis “angioectasia”6.64 Age >60 yrs.2.87 Use of anticoagulants2.65 Prior bleeding events2.90 Negative CE0.54 Albert JG, et al. DDW 2006;130(4): AB T1108 Longitudinal Prospective Cohort Study
Repeating CE Bar-Meir S. et al. GIE 2004;60: Jones B.H. et al. Am J Gastro 2005;100:58-64 Dhaliwal H. et al. Gastrointest. Endosc. 2006;63(4) Supp S: AB M1247 Kimble JS. et al. Gastrointest. Endosc. 2006;63(4) Supp S:AB 497
Role of Repeat CE in Obscure GI Bleeding and IDA Repeat upper endoscopy for OGIB has a 10-26% diagnostic yield. GI mucosal disease is a dynamic process and bleeding lesions may be present intermittently 1. If initial study is non-diagnostic, repeat CE may increase diagnostic yield If initial CE study is technically inadequate (poor visualization, not reaching colon) repeat exam. Prospective comparative studies with other diagnostic modalities are needed. 1. Am J Gastroenterol 2005;100:
Impact of CE on Patient Management and Outcomes in Obscure GI Bleeding
StudyYearPts (n) Yield of CE (%) Mean follow-up Influence on clinical outcome Pennazio et al a + Delvaux et al Carey et al Favre et al Chong et al Rastogi et al De Leusse et al b + Neu et al Walsh et al Kinzel et al De Looze et al Albert et al c + Viazis et al d + Saurin et al /- Pennazio M. GIE Clin N Am 2006; 16: Follow-up Studies Assessing the Influence on Clinical Outcome of Capsule Diagnosis in Patients with OGIB
PATIENTS WITH FINDINGS ON CAPSULE ENDOSCOPY nManagement change No further bleeding Reduction of bleeding by > 50% Tumors, erosions, ulcers (due to Crohn's, NSAID, etc.) 119 (82%)6 (55%)7 (64%) Angiodysplasia, bleeding278 (30%)15 (56%)21 (78%) Negative184 (22%)14 (78%)16 (89%) PATIENTS WITH FINDINGS ON OTHER TESTS nManagement change No further bleeding Reduction of bleeding by > 50% Tumors, erosions, ulcers (due to Crohn's, NSAID, etc.) 44 (100%)2 (50%)3 (75%) Angiodysplasia, bleeding177 (41%)5 (29%)12 (71%) Negative3510 (29%)28 (80%)29 (83%) Major management and outcome changes were mainly in the groups with other than vascular lesions and of negative cases. Neu B, et al. Am J Gastro 2005;100: : Major Management Changes and Outcomes in Relation to Diagnostic Findings
Impact of CE on Patient Management and Outcomes in Obscure GI Bleeding Published studies support a role for CE in directing patient management and improving outcomes. However, these studies lack standardized treatment protocols for findings at CE. Additional prospective studies are needed to better define the impact on patient outcomes in obscure GI bleeding. Outcomes to be measured: Bleeding resolution Transfusion requirements HLOS Patient satisfaction and HRQOL Resource utilization (e.g., additional diagnostic studies)
Role of CE in Iron Deficiency Anemia (IDA) The World Health Organization estimates that approximately one- third of the population has IDA, yet it remains an under-managed complication of numerous gastrointestinal conditions*. Despite undergoing standard endoscopic evaluation of IDA with EGD and IC, up to 30% of patients with IDA remain without diagnosis. CE allows evaluation of the entire small bowel, is significantly more sensitive than radiographic examinations and standard endoscopy, and has been shown to have high diagnostic yields in patients with obscure GI bleeding and IDA*. Apostolopoulos P, Liatsos C, Gralnek IM, et al. “The Role of Wireless Capsule Endoscopy in Investigating Unexplained Iron Deficiency Anemia After Negative Endoscopic Evaluation of the Upper and Lower Gastrointestinal Tract.” Endoscopy 2006 (in Press); Isenberg G. et al. Gastrointest. Endos. 2006: 63(4);AB M1301 Milano A. et al. Gastrointest. Endos. 2006; 63(4):AB T1110
Iron Deficiency Anemia (IDA) Algorithm Unexplained IDA* [1,2] Ileocolonoscopy EGD + gastric + D2 biopsies** NEGATIVE Video capsule endoscopy (VCE) Treat with Fe and observe for 3 months; Consider additional diagnostic studies (e.g., repeat VCE, push enteroscopy, ileocolonoscopy) if no improvement or recurrent IDA  Negative Institute lesion-specific treatment for clinically significant findings*** Positive *IDA proposed definition: Hgb < g/dl in women and < g/dl for men, MCV <76, ferritin <15 ug/dl. **Celiac serologies as clinically indicated. ***medical/surgical therapy, double-balloon enteroscopy, intraoperative enteroscopy.  Fireman et al. Digestive and Liver Diseases 2004;36:  Goddard et al. Gut 2000;46(suppl 4) 1-5.  Bar-Meir et al. Gastrointest Endosc 2004;60: Consider also: age, symptoms
Take-home Messages Capsule endoscopy should be performed early in the course of the work-up of patients with obscure bleeding and IDA (algorithms). Studies assessing the cost-effectiveness and budget impact of different approaches are needed. If initial study is non-diagnostic and bleeding continues, repeat CE may increase diagnostic yield; prospective comparative studies with other diagnostic modalities are needed. A second CE may prove of value if the lesion responsible for bleeding is bleeding intermittently or If the lesion was not seen on the initial exam (bowel unclean and obscures lesion). Jones H et al. Yield of Repeat Wireless Video Capsule Endoscopy in Patients with Obscure Gastrointestinal Bleeding. Am J. Gastroenterol 2005;100:
Tumors Panel Co-Chairmen G. Gay W. Selby Panel Members: J.S. Barkin, E. Toth, S. Lo, C. Fraser, F. Hagenmueller, J.F. Rey June 2006
Small Bowel Tumors (SBT) SB tumors account for: 3 - 6% of GI tumors 1 - 2% of GI malignancies Yearly Incidence USA1-1.4/100,000 France Men: 0.5 – 1.3/100,000 Women: 0.8/100,000 Malignant tumors of small bowel have a poor prognosis Metastases45% - 75% Unresectable20% - 50% Survival rate32.7% at 5 years
Clinical Presentation of SBT Two clinical pictures Intestinal obstruction Obscure digestive bleeding Often diagnosed late in course or incidentally at laparotomy or biopsy. At least 50% of benign lesions remain asymptomatic. Approximately 80% of malignant lesions produce symptoms. Symptoms or signs are not specific for either benign or malignant tumors. Presentation depends on the pathology of the neoplasm and location.
Morphological Investigations for Intestinal Tumors Radiology +Small bowel follow-through with enteroclysis +Abdominal ultrasound ++CT scanner / MRI +++ (if tumor > 1cm)CT scanner / MRI with enteroclysis Endoscopy ++Push enteroscopy +++Intra-operative enteroscopy ++Ileo-colonoscopy +Oesogastroduodenoscopy +++Video capsule endoscopy (VCE) +++Push and pull enteroscopy Nuclear Medicine Specific for neuroendocrine tumorsOctreo-scan
SB Tumors and PillCam CE The most common indication for PillCam endoscopy in patients with SBTs was obscure GI bleeding/anemia (80%). PillCam endoscopy detected SBTs after patients had undergone an average of 4.6 negative procedures % with Obscure Bleeding % Malignant Tumors Number of Tumors # Patients 79 %53 %50 (8.9%)562Corbin, %61 %48 (12.3%)391Delvaux, %67 %26 (6.3 %)416Bailey, %11 (2.5 %)*433Urbain, 2006 Frequency of Intestinal Tumors detected by VCE *Malignant tumors only
SB Tumors and PillCam CE 60% of SBT were malignant adenocarcinoma carcinoid melanoma lymphoma sarcoma, GIST 40% of SBT were benign GIST hemangioma hamartoma adenoma
Can we predict an increased likelihood of SBT in a patient referred for VCE? presentation such as abdominal pain, weight loss, protein- losing enteropathy physical findings – mass, ascites, etc. episode of small bowel obstruction history of previous tumor The type of OGIB – occult or overt – is not helpful. Sensitivity of clinical signs for SB tumor is low. SB Tumor Consensus
Procedures available prior to VCE in patients with suspected SBT No role for SB follow-through with or without enteroclysis CT ± enteroclysis MRI ± enteroclysis In the presence of obstructive signs can one predict the risk of retention? CT/MRI with enteroclysis Patency capsule SB Tumor Consensus
Role of VCE in diagnosing SB Tumours VCE > PE VCE ≈ PPE (DBE) Place of VCE in the diagnostic process Obscure GI bleeding Directly to VCE regardless of age Obstructive-type symptoms Consider PPE (DBE) SB Tumor Consensus
Can we reliably determine criteria to indicate the presence of a mass lesion at endoscopy? mucosal disruption intact mucosa submucosal lesion extrinsic, e.g., intra-abdominal tumor false positive: is any bulging a mass? intussusceptions external compression by normal abdominal organ SB Tumor Consensus
Pancreatic rest GIST What does a mass lesion found at VCE mean? SB Tumor Consensus
adenocarcinoma GIST pancreatic carcinoma Can we predict histology/tumor type from VCE appearances? SB Tumor Consensus
Proposed score for probability of “mass” lesions seen at VCE Bleeding Mucosal Irregular Polypoid Color Delayed White Invag- disruption surface appearance passage villi ination (≥ 30’) MAJORMINOR High Interme- diate Low +/ / These can be scored 3,2,1 to develop a tumor score. SB Tumor Consensus
High probability adenocarcinomaGIST adenocarcinomaB-cell lymphoma SB Tumor Consensus
Intermediate probability adenoma GIST SB Tumor Consensus
Low probability heterotopic gastric mucosa Normal at intraoperative enteroscopy SB Tumor Consensus
Proposal of a practical approach Sequence of the procedures Procedures needed to make a decision Clinical relevance of the tumor score SB Tumor Consensus
“Mass” at VCE High or Intermediate Probability of a Tumor Cross-sectional imaging enteroclysis to assess extraluminal disease PE/DBESurgery SB Tumor Consensus
“Mass” at VCE Low probability of a tumor Cross-sectional imaging enteroclysis PE/DBESurgery Abnormal CT scanNormal CT scan Repeat VCE High or Intermediate Significant clinical history PE/DBE No significant clinical history SB Tumor Consensus
Key points of the consensus for diagnosis: VCE leads to diagnosis of SB tumors earlier in their course. SB tumors detected with VCE are frequently revealed by OGIB, whereas previously, the most common presentation was obstruction and pain. SB Tumor Consensus
Key points of the consensus for treatment High or intermediate probability lesions may lead to DBE or surgery. The treatment of lesions with low probability will depend on their clinical significance. SB Tumor Consensus
Some unsolved issues Does VCE lead to improved outcome of SB tumors? Yes, if VCE leads to further diagnosis 1 Outcome research essential Does VCE have a role in the follow-up and surveillance of treated SB tumors? Not used at present It may have a role – possibly depending on the histological type of tumor Need for further research 1. Bailey AA, Debinski H, Appleyard M, Remedios M, Hooper J, Walsh A, Selby WS. Diagnosis and outcome of small bowel tumors found by capsule endoscopy: a three-center Australian experience. Am J Gastroenterol 2006;101:In Press SB Tumor Consensus
Future directions Assessing outcomes after diagnosis of SB tumor by VCE Assessing outcomes for polyposis syndromes Predicting pathology and tumor type by VCE findings Evaluating the tumor scale Assessing size and location of lesions seen by VCE Improving visualization of duodenal/periampullary lesions Evaluating the role of VCE in specific tumors Attempting to reduce the rate of false negative VCE SB Tumor Consensus
Celiac Disease Panel Co-Chairmen C. Cellier J. Murray Panel Members: P. Collin, G. Costamagna, P.H.R. Green, G.R. Corazza, E. Rondonotti, S. Schuppan, M. Willis June 2006
Panel Participants Christophe Cellier Pekka Collin Peter Green Joe Murray Emanuele Rondonotti Moshe Rubin Detlef Schuppan Marsh Willis Consensus Co-chairmen Roberto de Franchis Blair Lewis Gèrard Gay
Clinical Challenges Celiac disease is an immune-mediated disorder that primarily affects the GI tract. It is characterized by chronic inflammation of the small intestine mucosa that may result in atrophy of intestinal villi, malabsorption, and a variety of clinical manifestations, which may begin in either childhood or adult life. NIH Consensus 2004
Diagnosing Celiac Disease: “Tip of the Iceberg” Concept Diarrhea Abdominal pain Weight loss/failure to thrive Typical forms 1:2000 population NIH Consensus 2004
Diagnosing Celiac Disease: “Tip of the Iceberg” Concept Atypical forms1% USA> 3 million population Europe > 2 million population Worldwide disease is more severe than previously indicated. Diabetes, Anemia, Osteoporosis, Irritable Bowel Syndrome, Malignant problems, Neurological problems, Behavioral changes Mäki et al, NEJM 2003 NIH Consensus 2004
Background: Diagnosis of Celiac Disease Villous atrophy (duodenum) total/ subtotal partial increased number of IEL Circulating antibodies anti-endomysial IgA anti-transglutaminase IgA sensitivity/specificity > 95% Response (clinical /histological) to a GFD HLA DQ2 or DQ8: difficult case negative predictive value (99%) Consensus NIH 2004
Diagnosis of Celiac Disease Symptoms mimicking IBS (diarrhea, bloating, abdominal pain, etc.) Anemia (iron, folate, B12) Elevated transaminases Osteoporosis >60 years old (20%) <18 years old (4.6% to 17%) Consensus NIH 2004 De Franchis et al. Gastroenterology 2005;128;Supp 2:AB 548 Krauss et. al. Gastroenterology 2005;128:Supp 2:AB 547
Background: Malignancy and Celiac Disease T- lymphoma:EATL In adults per million people, covers 35% of all small bowel lymphomas. Adenocarcinoma Occurs in per 100,000 general population;13% of these cases are associated with celiac disease. Clonal refractory sprue (CD3+/CD8-/CD103+): ulcerative jejunitis Alarm symptoms: obstruction, weight loss, bleeding,pain, fever
Current Data Highlights: Celiac Disease at diagnosis Capsule and diagnosis of CD de Franchis et al: ICCE2005: AB 015 Murray et al: Gastrointest Endosc 2003;58(1):92-95 Krauss et al: ICCE 2005:AB 049 n > 100 patients at diagnosis Comparison of capsule findings and histology: VCE equivalent to histology for the diagnosis of severe atrophy. More data required for patients with partial villous atrophy. Rondonotti et al :ICCE 2006;AB 20122
Current Data Highlights: Celiac Disease Diagnosis Mapping the extent of CD Murray et al Gastrointest Endosc 2004;59(4) AB459 Length of involvement: no correlation with GI symptoms, correlation with osteopenia Muhammad et al ICCE 2006 AB CD in duodenum and proximal intestine may be entirely normal while the distal intestine shows classic features of CD. Extent of CD can be estimated by CE which is not possible by other modalities. Patients with positive serology and negative histology Adler et al ICCE 2004 AB 1022 Patients with abdominal pain, positive celiac serology, and negative biopsy may still have organic disease in the SB.
Current Data Highlights: Complicated Celiac Disease Screening for complicated celiac disease Patients symptomatic on a GFD Daly et al Gastrointest Endosc 2004;59(5) AB 1806 (n= 47): villous atrophy: 68% ulcerations 50% cancer: 5% Krauss et al. Gastroenterol 2005;128(4) AB:547 (n=43) ulcerations: 25% tumours: 5%
CD diagnosis? tTG+ EMA+ tTG - EMA- IgA + ?stop/evaluateDuodenal biopsies Villous atrophy GFD Failure: CE Normal architecture CE? Proposed Algorithm: Celiac Disease (CD) Diagnosis
Proposed Algorithm: Complicated Celiac Disease Failure of GFD GFD observance yesNo DieticianCE NegativePositive Observe VA to dietician and IEL phenotype Tumor or UJ to DBE
Consensus on Celiac Disease Symptomatic Treated CD CE is frequently abnormal in symptomatic CD on a gluten free diet. Atrophy (60%) Ulcers common (20 -50%) significance (histological specimens) mostly in clonal refractory sprue (type II) Malignancies 2-10% lymphoma adenocarcinoma
Defining “Atrophy” The presence of scalloping, fissuring, and mosaic patterns is characteristic of villous atrophy. The lack of visualization of normal villi in several successive folds alone might suggest CD. Minimal standard terminology and validation study needed.
Celiac Consensus Conclusions Indications for CE for the diagnosis of CD: High suspicion (tTg+, EmA+, or symptoms etc) in patients unwilling or unable to undergo upper GI endoscopy CE may be helpful when there is diagnostic difficulty such as: Sero + (EMA or tTG) with negative histology (patchy disease) Ambiguous histology and negative serology
Indications for CE in patients with known CD: For alarm symptoms in patients on a strict GFD (risk of malignancy) Weight loss Bleeding Anemia Pain Fever Recurrent malabsorption symptoms Abnormal imaging (except stricture) Celiac Consensus Conclusions
Consensus on Celiac Disease: Diagnosis Celiac disease should be considered in every CE examination for any reason (1% in general pop.). All CE endoscopists need to be able to recognize features of CD. Standard terminology and inter-observer agreement needed. There is supportive data for Positive Predictive Value. Need more data for Negative Predictive Value (partial villous atrophy).
Preps & Prokinetics Panel Co-Chairmen K Mergener T Ponchon Panel Members: R. Enns, H. Nuutinen, B. Filoche, I. Schmelkin, D. DeMarco, W. Qureshi, D. Heresbach
Clinical Challenges Limitations of capsule endoscopy in some cases: Dark/opaque intestinal contents, bubbles, food/medication particles, fecal matter, impairing visualization of the mucosa
Limitations of capsule endoscopy in some cases: Slow gastric emptying and/or small bowel transit, leading to incomplete small bowel imaging in approximately 15-20% of cases Clinical Challenges (continued)
ASGE CE SIG Survey Do you routinely use a laxative prior to SB capsule exams? YesNo
If “yes”, which laxative do you use? ASGE CE SIG Survey
Do you routinely use a prokinetic agent prior to SB CE? YesNo ASGE CE SIG Survey
If “yes”, which type of prokinetic agent do you use? ASGE CE SIG Survey
Definitions Bowel preparations: Medications given with the primary aim of cleansing the small bowel. Prokinetics: Medications given with the aim of accelerating gastric emptying and/or small bowel transit times, thus improving the proportion of cases in which the colon is reached.
Preps & Prokinetics 2006 Consensus Questions 1. Has a scale been validated to evaluate SB cleanliness? 2. Do preps affect SB cleanliness? 3. Do preps affect the diagnostic yield of SB CE? 4. Do prokinetics affect (a) GTT, (b) SBTT, c) completeness of SB examination? 5. Do prokinetics affect the diagnostic yield of SB CE? 6. Are there unique side effects related to the use of preps and prokinetics? 7. Does the use of preps and prokinetics affect patient acceptance of SB CE?
General Comments – Limitations to the Consensus Review Process Approximately 70 reports Few large randomized controlled trials Fewer peer-reviewed publications Many small retrospective series Publication bias Multiple studies from same institution Different types of agents, different administration schedules, combinations of agents, etc.
Preps No validated scale is available (subjective global assessment vs. more precise analysis of individual frames) Total of 17 studies, 9 randomized Only 3 of 9 included more than 100 patients Only 1 of 9 published as peer-reviewed article
Preps – Recent Abstracts Pons et al., DDW 2006 Gastrointestinal Endosc 63(4): AB M1284: 291 patients (A) 4L clear liquids, (B) 90ml NaPhos, (C) 4L PEG NO SIGNIFICANT DIFFERENCES Lapalus et al., ICCE 2006:AB 123 patients (A) 12 hour fast, (B) 90ml NaPhos NO SIGNIFICANT DIFFERENCE Wi et al., Gastrointest Endosc 2006;63(4): AB M1310 125 patients (A) 12 hour fast, (B) 90ml NaPhos, (C) 2L PEG IMPROVED VISIBILITY AND IMPROVED DIAGNOSTIC YIELD WITH NaPHOS (BUT NOT WITH PEG)
Preps – Peer-reviewed Article Viazis et al. GIE 2004;60:534-8 Prospective, randomized, blinded 80 patients PEG 2L vs. clear liquids only Grading: “adequate” vs. “inadequate” Cleansing “adequate”: 36pts (90%) vs. 24pts (60%) Diagnosis established: 26pts (65%) vs. 12pts (30%)
Preps – Consensus Conclusions Preps may not improve small-bowel cleanliness. No definitive evidence that preps increase diagnostic yield. No basis for recommending routine use in clinical practice. No negative impact on transit times demonstrated.
Prokinetics Prokinetics have been less well-studied. The clinically relevant endpoint of complete SB examination (vs. GTT/SBTT) has not been consistently reported. Tegaserod (6 studies, none fully published) is possibly effective for increasing the percentage of complete studies. The impact on diagnostic yield is unknown. Domperidone and metoclopramide have been less well studied with conflicting results. Erythromycin shortens GTT, but an effect on the rate of complete SB exams has not been demonstrated.
Positioning / Other Issues Right lateral decubitus position 3 abstracts, non-randomized Evaluation of GTT only Statistically significant difference in 1 of 3 studies Too few data to reach firm conclusion Predictive factors for incomplete SB exam Age, inpatient status and diabetes may be among the predictive factors of incomplete SB examination Not enough data to draw firm conclusions regarding the use of preps/prokinetics or postural maneuvers in these subgroups
Preps & Prokinetics 2006 Consensus Conclusions 1. Has a scale been validated to evaluate SB cleanliness? No 2. Do preps affect SB cleanliness?Possibly No 3. Do preps affect the diagnostic yield of SB CE? Unknown 4. Do prokinetics affect (a) GTT, (b) SBTT, (c) completeness of SB examination? Yes (a) Possibly Yes (b/c) 5. Do prokinetics affect the diagnostic yield of SB CE? Unknown 6. Are there unique side effects related to the use of preps and prokinetics? No 7. Does the use of preps and prokinetics affect patient acceptance of SB CE? Probably Yes