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