Consensus Reportthe 5th 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, 2006Paris, France
June 9-10, 2006
Combined statistics622 attendees40 countries represented146 abstracts presented89 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 TopicsIBDEsophagusTumorsBleedingCeliacPreps/Prokinetics
Inflammatory Bowel Disease (IBD)
Panel Co-ChairmenE. SeidmanI. 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;101:954-964
11 studies, n=223
Published StudynEstablished or
Suspected Costamagna 2002 3Established/Suspected
Heigh 200317Established
Bloom 200319Established/Suspected
Buchman 200323Established
Goelder 20035Established
Voderholzer 20038Established
Chong 200321Established/Suspected
Eliakim 200435Suspected
Toth 200447Established/Suspected
Dubcenco 200431Established/Suspected
Marmo 200419Established
: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]
Study IY (random) Incremental Yield (random) 95% CI 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 < 0.00001
-1 -0.5 0 0.5 1
Higher yield SB radiography Higher yield CE
Triester et al Am J Gastroenterol 2006;101:954-964
CE vs. Ileoscopy
Study IY (fixed) IY (fixed) 95% CI 95% CI
Bloom 2003 0.05 [-0.26, 0.37] Heigh 2003 0.06 [-0.26, 0.37] Dubcenco 2004 0.32 [0.09, 0.55] Toth 2004 0.11 [-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 = 0.02
-1 -0.5 0 0.5 1
Higher yield Ileoscopy Higher yield CE
Triester et al Am J Gastroenterol 2006;101:954-964
Study IY (fixed) IY (fixed)
95% CI 95% CI
Heigh 2003 0.18 [-0.14, 0.50]
Voderholzer 2003 0.00 [-0.42, 0.42]
Eliakim 2004 0.57 [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 < 0.00001
-1 -0.5 0 0.5 1
Higher yield CTE Higher yield CE
Triester et al. Am J Gastroenterol 2006;101:954-964
CE vs. CT Enterography (CTE)
Summary of Incremental Yield (IY) of CE Over Other Modalities
Triester et al. Am J Gastroenterol 2006;101:954-964
Total yield
CE (%)
Total yield other
modality (%)
% IY for CE (95% CI)
vs. SB Radiography662442 (0.30-0.54)
vs. Ileoscopy614615 (0.02-0.27)
vs. CT Enterography753738 (0.23-0.54)
vs. Push Enteroscopy51744 (0.31-0.57)
vs. Small Bowel MRI604020 (0.41-0.81)
Suspected CD subgroupStudy IY (random) [95% CI] IY (random) [95% CI]
Costamagna 2002 0.00 [-0.85, 0.85]
Dubcenco 2004 0.38 [-0.04, 0.79]
Eliakim 2004 0.54 [0.35, 0.74]
Toth 2004 0.17 [-0.02, 0.37] Chong 2005 0.00 [-0.11, 0.11] Hara 2005 0.25 [-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 = 0.09
-1 -0.5 0 0.5 1
Yield higher in barium radiography Yield higher in capsule endoscopy
Study IY (random) [95% CI] IY (random) [95% CI]
Costamagna 2002 0.50 [-0.21, 1.21]
Buchman 2004 0.03 [-0.20, 0.27]
Dubcenco 2004 0.70 [0.49, 0.90]
Marmo 2004 0.45 [0.23, 0.67]
Toth 2004 0.61 [0.35, 0.87] Chong 2005 0.62 [0.38, 0.86] Hara 2005 0.67 [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 < 0.001
-1 -0.5 0 0.5 1
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;54:369-373 Hara et al. Radiology 2006;238(1):128-134
+ exams
MR Enteroclysis (n=18 pts)
Golder et al. Int’l J of Colorectal Disease 2006;21(2):97-104
+ 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;2:31-40Mascarenhas-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 CECE 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;55:978-983
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.
A B C
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
ParametersVillous AppearanceUlcerationStenosis
ScaleNormal, edematousNumber - single, few, multipleDistribution - localized, patchy,
diffuseLongitudinal extent - short, long,
whole segmentUlcer size - based on amount of
bowel wall circumference involvedStenosis - ulcerated or not,
traversed or not
Example of Score Template
Global Disease Assessment: Normal, Mild, Moderate/Severe
Parameters NumberLongitudinal Extent (%
of CE passage for tertile)
Descriptors
Normal Short Segment SingleVillous Appearance Edematous Long Segment Patchy
Whole tertile Diffuse None Short Segment <1/4 Single Long Segment 1/4-1/2
Ulcer Few Whole tertile >1/2 Multiple (Score the largest ulcer)
Stenosis - Rate for Whole Study
None Ulcerated Traversed Stenosis Single Non-Ulcerated Not traversed
Multiple
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 diarrheaSignificant weight lossGrowth failureExtra-intestinal SymptomsUnexplained recurrent feverArthritis/arthralgiasPyoderma/erythema nodosumAphthous stomatitisPerianal diseasePSC/recurrent cholangitisInflammatory MarkersIron deficiency anemiaThrombocytosis or leukocytosisElevated ESR or CRPHypoalbuminemiaPositive IBD serologyFecal 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
Positiveileocolonoscopy
Negative ileocolonoscopyor unsuccessful
Possible or knownobstruction
No obstruction
Patencycapsule
CTE/MRE(SBFT)
Capsule endoscopy
Presence of SBCD
Treat accordingly
ObstructionNo obstruction
either/or
Capsule Retention and CD
Author TypePatients (n)Capsule Retention (%)
Type
Mow504Known
Herrerias210Suspected
Fireman170Suspected
Eliakim200Suspected
Sant’Anna205Suspected
Buchman306.7Known
Chiefetz3813.0Known strictures
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 diagnosticsSimple and easyPatient-friendlyScreening tool for esophageal
diseasesEncouraging 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 20154
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 = noneF1 = smallF2 = mediumF3 = large
Modified classification for current trialNone/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
Reference #Patients Study Design
SensitivitySpecificityPPVNPV
Study 121Prospective Blinded
81%100%100%57%
Study 297Prospective Blinded
87%87%94%74%
Study 332Prospective Blinded
100%89%96%100%
1.Lapalus MG. Endoscopy 2006;38:36-4
2. Eisen GM, de Franchis R. Interim Analysis of the Evaluation of PillCam ESO in the Detection of Esophageal Varices AB 20154
3.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
Barrett’s Esophagus
Epidemiology in Barrett’s Esophagus
30-60 times > general populationup to 2% of patients with BE
30-60 times > general populationup to 2% of patients with BE
Risk of esophageal cancer in Barrett’s esophagusRisk of esophageal cancer in Barrett’s esophagus
7% of US Population havedaily GERD Symptoms
7% of US Population havedaily GERD Symptoms
10% of Chronic GERD Patientshave Barrett’s esophagus
10% of Chronic GERD Patientshave Barrett’s esophagus
Locke III et al. Gastro 1997: 112:1448-1456. 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 30-60 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;39:572-578
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;39:572-578
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;39:572-578
Multi-center Study Results:Esophagitis
EGD
+-
ECE+331
-468
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+321
-172
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 TrialsBarrett’s Esophagus
Feasibility Trial3rd ESO Trial
# of Patients1742
InvestigatorsEliakim, Yassin, Shlomi, Suissa,
Eisen
Koslowsky, Jacob, Eliakim, Adler
Adjudication Panel
nono
Sensitivity100%100%
Specificity80%100%
PublicationAPT 2004;20:1-7Endoscopy 2006;38 (1):27-30
ECE Clinical Trial Data:Barrett’s Esophagus
Reference #PatientsSensitivitySpecificityPPVNPV
VA Mason Trial 15867%84%56%89%
Kansas Trial 23273%86%86%74%
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;100:2407-2418*Marmo et al. APT 2005;22:595-604
Value of CE for Obscure GI Bleeding
Marmo et al. APT 2005;22:595-604
Value of CE for Obscure GI Bleeding
Triester et al. Am J Gastroenterol 2005;100:2407-2418
StudySensitivity(%)
Specificity(%)
PPV(%)
NPV(%)
Pennazio et al.Gastrpenterology 2004
88.9959782.6
Delvaux et al.Endoscopy 2004
94.4100
Saurin et al.Endoscopy 2005
9248
Hartmann et al.GIE 2005
95759586
Hindryckx et al.ICCE 2006
95.29896.197.6
Walsh et al. DDW 2006
1008787.9100
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 366470
7% 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 366874 Gay G. et al. ICCE 2006;AB 367198
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;39:684-688 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;101:1224-1228
49 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=0.03p=0.03
Re-bleeding Rates in Patientswith 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;60:711-13 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 intermittently1.
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;100:1058-64
Impact of CE on Patient Managementand Outcomes in Obscure GI Bleeding
Study Year Pts(n)
Yield of CE (%)
Mean follow-up
Influence on clinical outcome
Pennazio et al. 2004100 4718a+
Delvaux et al. 200444 6112+
Carey et al. 2004260 586.7+
Favre et al. 2004505011+
Chong et al. 200475694.7+
Rastogi et al. 200443426.7-
De Leusse et al.2005644513b+
Neu et al.2005566813+
Walsh et al. 20051006621+
Kinzel et al.2005477412+
De Looze et al.2005455312+
Albert et al. 20052786220c+
Viazis et al. 2005964214d+
Saurin et al. 2005567112+/- Pennazio M. GIE Clin N Am 2006; 16: 251-66
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;100:1736-1742:
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 resolutionTransfusion requirementsHLOSPatient satisfaction and HRQOLResource 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]
IleocolonoscopyEGD + 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 [3]
Negative
Institute lesion-specific treatment for clinically significant findings***
Positive
*IDA proposed definition: Hgb < 10-11.5 g/dl in women and < 12.5-13.8 g/dl for men, MCV <76, ferritin <15 ug/dl. **Celiac serologies as clinically indicated. ***medical/surgical therapy, double-balloon enteroscopy, intraoperative enteroscopy.
[1] Fireman et al. Digestive and Liver Diseases 2004;36:97-102. [2] Goddard et al. Gut 2000;46(suppl 4) 1-5.
[3] Bar-Meir et al. Gastrointest Endosc 2004;60:711-13.
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;100:1058-64
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 IncidenceUSA 1-1.4/100,000France
Men: 0.5 – 1.3/100,000 Women: 0.8/100,000
Malignant tumors of small bowel have a poor prognosisMetastases 45% - 75%Unresectable 20% - 50%Survival rate 32.7% 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 Investigationsfor Intestinal Tumors
Radiology
Small bowel follow-through with enteroclysis+
Abdominal ultrasound +
CT scanner / MRI++
CT scanner / MRI with enteroclysis+++ (if tumor > 1cm)
Endoscopy
Push enteroscopy ++
Intra-operative enteroscopy+++
Ileo-colonoscopy++
Oesogastroduodenoscopy+
Video capsule endoscopy (VCE)+++
Push and pull enteroscopy+++
Nuclear Medicine
Octreo-scanSpecific for neuroendocrine tumors
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
# PatientsNumber of Tumors
% Malignant Tumors
% with Obscure Bleeding
Corbin, 200456250 (8.9%)53 %79 %
Delvaux, 200639148 (12.3%)61 %70.8 %
Bailey, 200641626 (6.3 %)67 %81 %
Urbain, 200643311 (2.5 %)*100 %
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 SBTNo role for SB follow-through with or without enteroclysisCT ± enteroclysisMRI ± enteroclysis
In the presence of obstructive signs can one predict the risk of retention?CT/MRI with enteroclysisPatency capsule
SB Tumor Consensus
Role of VCE in diagnosing SB TumoursVCE > PE VCE ≈ PPE (DBE)
Place of VCE in the diagnostic processObscure 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 disruptionintact 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’)
MAJOR MINOR
++ ++ ++ ++ ++ ++ ++ ++High
Interme-diate
Low
+/- + + + + + + +
- - - +/- - - - -
These can be scored 3,2,1 to develop a tumor score.
SB Tumor Consensus
High probability
adenocarcinoma GIST
adenocarcinoma B-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/DBE Surgery
SB Tumor Consensus
“Mass” at VCELow probability of a tumor
Cross-sectional imaging enteroclysis
PE/DBE Surgery
Abnormal CT scan Normal CT scan
RepeatVCE
High or Intermediate Significantclinical history
PE/DBE
No significantclinical 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 treatmentHigh 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 issuesDoes VCE lead to improved outcome of SB
tumors?Yes, if VCE leads to further diagnosis1
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
tumorNeed 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 directionsAssessing 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-chairmenRoberto de FranchisBlair LewisGèrard 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 2003NIH Consensus 2004
Background:Diagnosis of Celiac Disease
Villous atrophy (duodenum) total/ subtotal partial
increased number of IEL
Circulating antibodiesanti-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: Treatment of Celiac Disease
Gluten free diet (wheat, rye, barley)Poor observance
Malignant complicationsOsteopeniaAuto-immune disorders
Consensus NIH 2004
Background:Malignancy and Celiac Disease
T- lymphoma:EATL In adults 0.5-1 per million
people, covers 35% of all small bowel lymphomas.
AdenocarcinomaOccurs in 0.6-0.7 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 CDde Franchis et al: ICCE2005: AB 015Murray et al: Gastrointest Endosc 2003;58(1):92-95Krauss et al: ICCE 2005:AB 049n > 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 CDMurray 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 20103 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 histologyAdler 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 diseasePatients symptomatic on a GFDDaly 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?
CE?
Proposed Algorithm: Celiac Disease (CD) Diagnosis
Proposed Algorithm:Complicated Celiac Disease
Failure of GFD
GFD observance
yes No
DieticianCE
Negative Positive
ObserveVA to dietician and
IEL phenotypeTumor or UJ to DBE
Consensus on Celiac DiseaseSymptomatic 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%lymphomaadenocarcinoma
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 Image Spectrum
Absent Villi Fissuring Scalloping
Mosaic pattern Fissuring and ulcerScalloping
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 patientswith 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 somecases:
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
0102030
405060708090
100
Do you routinely use a laxative prior to SB capsule exams?
Yes No
If “yes”, which laxative do you use?
0
5
10
15
20
25
30
35
PEG 0-2L
PEG > 2L
PSoda
Other
ASGE CE SIG Survey
Do you routinely use a prokinetic agent prior to SB CE?
0
10
20
30
40
50
60
70
80
90
Yes No
ASGE CE SIG Survey
0
5
1015
20
2530
35
4045
50
Tegaserod
Metoclopramide
Erythromycin
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 & Prokinetics2006 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 patientsOnly 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 314850 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;60:534-8Prospective, randomized, blinded80 patientsPEG 2L vs. clear liquids onlyGrading: “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 & Prokinetics2006 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