Consensus Report the 5th International Conference on Capsule Endoscopy

1
Consensus Reportthe 5th International Conference
on Capsule Endoscopy

• Conference Chairs
• Blair S. Lewis
• Roberto de Franchis
• Gèrard Gay

2
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

3
Consensus Activities

• Reviewed last years 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

4
Inflammatory Bowel Disease (IBD)
June 2006

• Panel Co-Chairmen
• E. Seidman
• I. Bjarnason
• Panel Members J. Leighton, P. Legnani, M.
  Gassull, J.F. Columbel, V. Manoury, A. Kornbluth

5
IBD Consensus

• Capsule Endoscopy (CE) for IBD
• Higher sensitivity for assessing small bowel
  mucosal lesions compared to other imaging
  techniques

6
Meta-analysis of Prospective Comparative Crohns
Disease Studies CE vs. Other Modalities
Established or Suspected n Published Study
Established/Suspected 3 Costamagna 2002
Established 17 Heigh 2003
Established/Suspected 19 Bloom 2003
Established 23 Buchman 2003
Established 5 Goelder 2003
Established 8 Voderholzer 2003
Established/Suspected 21 Chong 2003
Suspected 35 Eliakim 2004
Established/Suspected 47 Toth 2004
Established/Suspected 31 Dubcenco 2004
Established 19 Marmo 2004
11 studies, n223
Triester et al Am J Gastroenterol 2006101954-964
7
CE vs. SB Radiography




Study
IY (random)
Incremental Yield (random)
95 CI
95 CI
Costamagna 2002
0.33 -0.42, 1.09
Bloom 2003
0.37 0.08, 0.66
Chong 2003
0.48 0.22, 0.73
Heigh 2003
0.47 0.17, 0.77
Buchman 2004
0.00 -0.27, 0.27
Dubcenco 2004
0.61 0.42, 0.81
Eliakim 2004
0.54 0.35, 0.74
Marmo 2004
0.53 0.26, 0.80
Toth 2004
0.34 0.17, 0.51
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 lt 0.00001
-1
-0.5
0
0.5
1
Higher yield SB radiography
Higher yield CE
Triester et al Am J Gastroenterol 2006101954-964
8
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 2006101954-964
9
CE vs. CT Enterography (CTE)


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 lt 0.00001
-1
-0.5
0
0.5
1
Higher yield CTE
Higher yield CE
Triester et al. Am J Gastroenterol
2006101954-964
10
Summary of Incremental Yield (IY) of CE Over
Other Modalities
IY for CE (95 CI) Total yield other modality () Total yield CE ()
42 (0.30-0.54) 24 66 vs. SB Radiography
15 (0.02-0.27) 46 61 vs. Ileoscopy
38 (0.23-0.54) 37 75 vs. CT Enterography
44 (0.31-0.57) 7 51 vs. Push Enteroscopy
20 (0.41-0.81) 40 60 vs. Small Bowel MRI
Triester et al. Am J Gastroenterol
2006101954-964
11
CE vs. Barium Radiography
Suspected CD subgroup
Study
IY (random) 95 CI
IY (random) 95 CI
0.00 -0.85, 0.85
Costamagna 2002
0.38 -0.04, 0.79
Dubcenco 2004
0.54 0.35, 0.74
Eliakim 2004
0.17 -0.02, 0.37
Toth 2004
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 lt 0.001, I² 85.6
Test for overall effect P 0.09
0
1
-1
0.5
-0.5
Yield higher in barium radiography
Yield higher in capsule endoscopy
Established CD subgroup
Study
IY (random) 95 CI
IY (random) 95 CI
0.50 -0.21, 1.21
Costamagna 2002
0.03 -0.20, 0.27
Buchman 2004
0.70 0.49, 0.90
Dubcenco 2004
0.45 0.23, 0.67
Marmo 2004
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 lt 0.001
-1
-0.5
0
0.5
1
Yield higher in barium radiography
Yield higher in capsule endoscopy
12
CE vs. CT Enterography (n58 pts) CE detects
more proximal disease
exams
Voderholzer et al. Gut 200554369-373 Hara et
al. Radiology 2006238(1)128-134
13
MR Enteroclysis (n18 pts)
exams
Golder et al. Intl J of Colorectal Disease
200621(2)97-104
14
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.

15
IBD Consensus
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 2004231-40 Mascarenhas-Saraiv
a M, et al. ICCE 2005 AB 115 Hume G, et al. ICCE
2004 AB 1054
16
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 200357(5)AB
1889
17
IBD Consensus

• Role of CE in assessing for early post-
• operative recurrence
• 32 post-op ileocecal resection
• CE ileo-colonoscopy lt 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 200655978-983
18
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 2006130(4)Supp
S2 AB S1336
19
IBD Consensus

• Capsule endoscopy (CE) for suspected IBD
• Useful and safe in patients with suspected
  Crohns 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.

20
Capsule Endoscopy Are All Ulcers Crohns?
A
B
C
Which image is an ulcer from Crohns disease?
The answer is all three. However, patient
history will define if another cause, such as
NSAID damage or radiation enteropathy caused the
ulceration.
21
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).

22
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

23
Example of Score Template
Global Disease Assessment Normal, Mild,
Moderate/Severe
24
Suspected Crohns 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

25
Suspected SB CD
Positive ileocolonoscopy
Negative ileocolonoscopy or unsuccessful
Possible or known obstruction
No obstruction
Patency capsule
either/or
Obstruction
No obstruction
CTE/MRE (SBFT)
Capsule endoscopy
Presence of SBCD
Treat accordingly
Figure 1. Algorithm for the approach to
suspected small bowel Crohns 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 CDsmall bowel Crohns Disease, CTECT
enterography, MREMR enterography, SBFTsmall
bowel follow through.
26
Capsule Retention and CD
Type Capsule Retention () Patients (n) Author Type
Known 4 50 Mow
Suspected 0 21 Herrerias
Suspected 0 17 Fireman
Suspected 0 20 Eliakim
Suspected 5 20 SantAnna
Known 6.7 30 Buchman
Known strictures 13.0 38 Chiefetz
27
Capsule Retention in Crohns 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.

28
Conclusions

• CE has a higher sensitivity for assessing small
  bowel mucosal lesions compared to other imaging
  techniques.
• CE is helpful diagnosing suspected Crohns 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
  Crohns disease and negative endoscopic small
  bowel imaging.

29
Esophagus
June 2006
Panel Co-Chairmen R. Eliakim G. Eisen Panel
Members J.P. Galmiche, T. Roesch, F.
Schnoll-Sussman, J. Herrerias, V.K. Sharma, E.
Coron
30
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

31
Consensus Statement Varices

• 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.

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
32
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
33
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 gt 25 circumference

Eisen G, Eliakim R, Zaman A, Schwartz J,Faigel D,
Rondonotti E, Villa F, Weizman E, Yassin K, de
Franchis R. Endoscopy 2006381-5
34
Comparison of PillCam ESO and EGD Esophageal
Varices
NPV PPV Specificity Sensitivity Study Design Patients Reference
57 100 100 81 Prospective Blinded 21 Study 1
74 94 87 87 Prospective Blinded 97 Study 2
100 96 89 100 Prospective Blinded 32 Study 3
1.Lapalus MG. Endoscopy 20063836-4 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 200638(1)1-5
35
Esophageal Image Spectrum
36
Barretts Esophagus
37
Epidemiology in Barretts Esophagus
7 of US Population have daily GERD Symptoms
10 of Chronic GERD Patients have Barretts
esophagus
Risk of esophageal cancer in Barretts esophagus
30-60 times gt general population up to 2 of
patients with BE
Locke III et al. Gastro 1997 1121448-1456.
Falk GW. Gastro Endosc 1999 49(3)S29-34.
38
Screening for Barretts Esophagus

• Adenocarcinoma is a lethal disease.
• GERD is a firmly established risk factor for this
  cancer.
• Barretts 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).

39
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
  Barretts 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
200539572-578
40
Patient Enrollment
109 patients enrolled
1 unable to swallow capsule
2 technical difficulties
106 included in per-protocol statistical analysis
93 (88) endoscoped for GERD symptoms
13 (12) for surveillance of Barretts esophagus
Eliakim R et al. J Clin Gastroenterol
200539572-578
41
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.
• Barretts cases were not biopsied for
  confirmation.

Eliakim R et al. J Clin Gastroenterol
200539572-578
42
Multi-center Study ResultsEsophagitis
    EGD EGD  
    -  
ECE 33 1  
ECE - 4 68  
        ECE
Sensitivity Sensitivity Sensitivity Sensitivity 89
Specificity Specificity Specificity Specificity 99
Positive Predictive Value (PPV) Positive Predictive Value (PPV) Positive Predictive Value (PPV) Positive Predictive Value (PPV) 97
Negative Predictive Value (NPV) Negative Predictive Value (NPV) Negative Predictive Value (NPV) Negative Predictive Value (NPV) 94

 
Adjudicated results
Eliakim R, Sharma VK et al. In press. J Clin
Gastro
43
Multi-center ResultsBarretts Esophagus
    EGD EGD  
    -  
ECE 32 1  
ECE - 1 72  
        ECE
Sensitivity Sensitivity Sensitivity Sensitivity 97
Specificity Specificity Specificity Specificity 99
Positive Predictive Value (PPV) Positive Predictive Value (PPV) Positive Predictive Value (PPV) Positive Predictive Value (PPV) 97
Negative Predictive Value (NPV) Negative Predictive Value (NPV) Negative Predictive Value (NPV) Negative Predictive Value (NPV) 99
Adjudicated results
Eliakim R, Sharma VK et al. In press. J Clin
Gastro
44
ECE Clinical TrialsBarretts Esophagus
Feasibility Trial 3rd ESO Trial
of Patients 17 42
Investigators Eliakim, Yassin, Shlomi, Suissa, Eisen Koslowsky, Jacob, Eliakim, Adler
Adjudication Panel no no
Sensitivity 100 100
Specificity 80 100
Publication APT 2004201-7 Endoscopy 200638 (1)27-30
45
ECE Clinical Trial DataBarretts Esophagus
NPV PPV Specificity Sensitivity Patients Reference
89 56 84 67 58 VA Mason Trial 1
74 86 86 73 32 Kansas Trial 2
1.Lin et al. Blinded Comparison of Esophageal
Capsule Endoscopy vs. Conventional Endoscopy for
Diagnosis of Barretts Esophagus in Patients with
Chronic Gastroesophageal Reflux GIE ( in
Press) 2.Sharma et al Gastroenterology
2006130(4) April AB S1812
46
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.

47
GI Bleeding
June 2006
Panel Co-Chairmen M. Pennazio I. Gralnek Panel
Members M. Delvaux, N. Reddy S. Bar Meir,
I. Demedts, M. Keuchel
48
Panel Participants(Boca Raton/Paris)

• Martin Keuchel
• Ingrid Demedts
• Simon Bar-Meir
• Nageshwar Reddy
• Michael Delvaux
• Scott Ketover
• Morry Moskovitz
• Shenan Abey
• Colm OMorain

49
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 20051002407-2418 M
armo et al. APT 200522595-604
50
Value of CE for Obscure GI Bleeding
Marmo et al. APT 200522595-604
51
Value of CE for Obscure GI Bleeding
Triester et al. Am J Gastroenterol
20051002407-2418
52
Accuracy of Diagnostic Interpretation
Study Sensitivity () Specificity () PPV () NPV ()
Pennazio et al. Gastrpenterology 2004 88.9 95 97 82.6
Delvaux et al. Endoscopy 2004 94.4 100
Saurin et al. Endoscopy 2005 92 48
Hartmann et al. GIE 2005 95 75 95 86
Hindryckx et al. ICCE 2006 95.2 98 96.1 97.6
Walsh et al. DDW 2006 100 87 87.9 100
53
Algorithm for CE in Obscure GI Bleeding

• Add algorithm OGIB

Pennazio M, Eisen G, Goldfarb N. ICCE Consensus -
Endoscopy 2005
54
Missed Lesions Detected by CE

• Selby W. et al. GIE 200561(5) AB M1390
• Chung H. et al. DDW 200663(4) Supp S AB M1247
• Edery J. et al. ICCE 2006AB 366470
• 7 to 25 of lesions detected by CE
• are NOT in the small bowel.
• Clinical significance unknown.

55
Early CE in Overt OGIB

• Ben Soussan et al. ICCE 2006AB 366874
• Gay G. et al. ICCE 2006AB 367198
• Yield of CE 70-84
• Timing of CE is important.

56
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 200539684-688
Al Ali J. et al. Gastrointest Endosc 200663(4)
AB M1346
57
Capsule Endoscopy and Double-balloon Enteroscopy

• An initial diagnostic imaging employing CE might
  be followed by DBE for treatment or
  histopathological diagnosis.
• 
  Nakamura M, et al. Endoscopy 200638(1)59-66
• 
  Hadithi M, et al. Am J Gastro 200610152-57
• 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 200638(1)49-58
• 
  Pennazio M. et al. DDW 200663(4) Supp S AB 496

58
Re-bleeding Rates in Patientswith Positive and
Negative CE

• 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

p0.03
Lai L, et al. Am J Gastro 20061011224-1228
59
Longitudinal Prospective Cohort Study

• 285 OGIB patients
• Yield of CE 177 (62) 50 underwent treatment
• Re-bleeding rate 44 (18)

FACTOR RR for bleeding relapse
Diagnosis angioectasia 6.64
Age gt60 yrs. 2.87
Use of anticoagulants 2.65
Prior bleeding events 2.90
Negative CE 0.54
Albert JG, et al. DDW 2006130(4) AB T1108
60
Repeating CE

• Bar-Meir S. et al. GIE 200460711-13
• Jones B.H. et al. Am J Gastro 200510058-64
• Dhaliwal H. et al. Gastrointest. Endosc.
  200663(4) Supp S AB M1247
• Kimble JS. et al. Gastrointest. Endosc.
  200663(4) Supp SAB 497

61
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 20051001058-64
62
Impact of CE on Patient Managementand Outcomes
in Obscure GI Bleeding
63
Follow-up Studies Assessing the Influence on
Clinical Outcome of Capsule Diagnosis in
Patients with OGIB
Study Year Pts (n) Yield of CE () Mean follow-up Influence on clinical outcome
Pennazio et al. 2004 100 47 18a
Delvaux et al. 2004 44 61 12
Carey et al. 2004 260 58 6.7
Favre et al. 2004 50 50 11
Chong et al. 2004 75 69 4.7
Rastogi et al. 2004 43 42 6.7 -
De Leusse et al. 2005 64 45 13b
Neu et al. 2005 56 68 13
Walsh et al. 2005 100 66 21
Kinzel et al. 2005 47 74 12
De Looze et al. 2005 45 53 12
Albert et al. 2005 278 62 20c
Viazis et al. 2005 96 42 14d
Saurin et al. 2005 56 71 12 /-
Pennazio M. GIE Clin N Am 2006 16 251-66
64
Major Management Changes and Outcomes in
Relation to Diagnostic Findings
PATIENTS WITH FINDINGS ON CAPSULE ENDOSCOPY n Management change No further bleeding Reduction of bleeding by gt 50
Tumors, erosions, ulcers (due to Crohn's, NSAID, etc.) 11 9 (82) 6 (55) 7 (64)
Angiodysplasia, bleeding 27 8 (30) 15 (56) 21 (78)
Negative 18 4 (22) 14 (78) 16 (89)
PATIENTS WITH FINDINGS ON OTHER TESTS n Management change No further bleeding Reduction of bleeding by gt 50
Tumors, erosions, ulcers (due to Crohn's, NSAID, etc.) 4 4 (100) 2 (50) 3 (75)
Angiodysplasia, bleeding 17 7 (41) 5 (29) 12 (71)
Negative 35 10 (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 20051001736-1742
65
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)

66
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

67
Iron Deficiency Anemia (IDA) Algorithm
Unexplained IDA 1,2
Ileocolonoscopy EGD gastric D2
biopsies NEGATIVE
Consider also age, symptoms
Video capsule endoscopy (VCE)
Negative
Positive
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
Institute lesion-specific treatment for
clinically significant findings
IDA proposed definition Hgb lt 10-11.5 g/dl in
women and lt 12.5-13.8 g/dl for men, MCV lt76,
ferritin lt15 ug/dl. Celiac serologies as
clinically indicated. medical/surgical
therapy, double-balloon enteroscopy,
intraoperative enteroscopy. 1 Fireman et al.
Digestive and Liver Diseases 20043697-102.
2 Goddard et al. Gut 200046(suppl 4)
1-5. 3 Bar-Meir et al. Gastrointest Endosc
200460711-13.
68
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
20051001058-64
69
Tumors
June 2006
Panel Co-Chairmen G. Gay W. Selby Panel
Members J.S. Barkin, E. Toth, S. Lo, C. Fraser,
F. Hagenmueller, J.F. Rey
70
Small Bowel Tumors (SBT)

• SB tumors account for 3 - 6 of GI tumors
• 1 - 2 of GI malignancies
• Yearly Incidence
• USA 1-1.4/100,000
• France
• Men 0.5 1.3/100,000
• Women 0.8/100,000
• Malignant tumors of small bowel have a poor
  prognosis
• Metastases 45 - 75
• Unresectable 20 - 50
• Survival rate 32.7 at 5 years

71
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.

72
Morphological Investigationsfor Intestinal Tumors
Radiology
Small bowel follow-through with enteroclysis
Abdominal ultrasound
CT scanner / MRI
(if tumor gt 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 tumors Octreo-scan
73
SB Tumors and PillCam CE
Frequency of Intestinal Tumors detected by VCE
with Obscure Bleeding Malignant Tumors Number of Tumors Patients
79 53 50 (8.9) 562 Corbin, 2004
70.8 61 48 (12.3) 391 Delvaux, 2006
81 67 26 (6.3 ) 416 Bailey, 2006
100 11 (2.5 ) 433 Urbain, 2006

• 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

Malignant tumors only
74
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

75
SB Tumor Consensus

• 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.

76
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

77
SB Tumor Consensus

• Role of VCE in diagnosing SB Tumours
• VCE gt 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)

78
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

79
SB Tumor Consensus
What does a mass lesion found at VCE mean?
Pancreatic rest
GIST
80
SB Tumor Consensus
Can we predict histology/tumor type from VCE
appearances?
adenocarcinoma
GIST
pancreatic carcinoma
81
SB Tumor Consensus

• Proposed score for probability of mass lesions
  seen at VCE

MAJOR
MINOR

• Bleeding Mucosal Irregular Polypoid
  Color Delayed White Invag-
• disruption surface appearance passage
  villi ination
• ( 30)

High
Interme-diate
/-

Low
- - - /- - -
- -
These can be scored 3,2,1 to develop a tumor
score.
82
SB Tumor Consensus
High probability
adenocarcinoma
GIST
adenocarcinoma
B-cell lymphoma
83
SB Tumor Consensus
Intermediate probability
adenoma
GIST
84
SB Tumor Consensus
Low probability
heterotopic gastric mucosa
Normal at intraoperative enteroscopy
85
SB Tumor Consensus

• Proposal of a practical approach
• Sequence of the procedures
• Procedures needed to make a decision
• Clinical relevance of the tumor score

86
SB Tumor Consensus
Mass at VCE High or Intermediate Probability
of a Tumor
Cross-sectional imaging ? enteroclysis to assess
extraluminal disease
PE/DBE
Surgery
87
SB Tumor Consensus
Mass at VCE Low probability of a tumor
Cross-sectional imaging ? enteroclysis
Abnormal CT scan
Normal CT scan
High or Intermediate
Significant clinical history
No significant clinical history
PE/DBE
Surgery
Repeat VCE
PE/DBE
88
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.

89
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.

90
SB Tumor Consensus

• Some unsolved issues
• Does 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 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 2006101In Press
91
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

92
Celiac Disease
June 2006
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
93
Panel Participants

• Consensus Co-chairmen
• Roberto de Franchis
• Blair Lewis
• Gèrard Gay

• Christophe Cellier
• Pekka Collin
• Peter Green
• Joe Murray
• Emanuele Rondonotti
• Moshe Rubin
• Detlef Schuppan
• Marsh Willis

94
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
95
Diagnosing Celiac DiseaseTip of the Iceberg
Concept
Diarrhea
Typical forms 12000 population
Abdominal pain
Weight loss/failure to thrive
NIH Consensus 2004
96
Diagnosing Celiac DiseaseTip of the Iceberg
Concept
Atypical forms1 USAgt 3 million population Europe
gt 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
97
BackgroundDiagnosis of Celiac Disease

• Villous atrophy (duodenum)
• total/ subtotal
• partial
• increased number of IEL
• Circulating antibodies
• anti-endomysial IgA
• anti-transglutaminase IgA
• sensitivity/specificity gt 95
• Response (clinical /histological) to a GFD
• HLA DQ2 or DQ8 difficult case
• negative predictive value (99)

Consensus NIH 2004
98
Diagnosis of Celiac Disease

• Symptoms mimicking IBS (diarrhea, bloating,
  abdominal pain, etc.)
• Anemia (iron, folate, B12)
• Elevated transaminases
• Osteoporosis
• gt60 years old (20)
• lt18 years old (4.6 to 17)

Consensus NIH 2004 De Franchis et al.
Gastroenterology 2005128Supp 2AB 548 Krauss
et. al. Gastroenterology 2005128Supp 2AB 547
99
Background Treatment of Celiac Disease

• Gluten free diet (wheat, rye, barley)
• Poor observance
• Malignant complications
• Osteopenia
• Auto-immune disorders

• Consensus NIH 2004

100
BackgroundMalignancy and Celiac Disease

• T- lymphomaEATL
• In adults 0.5-1 per million people, covers 35 of
  all small bowel lymphomas.
• Adenocarcinoma
• Occurs in 0.6-0.7 per 100,000 general
  population13 of these cases are associated with
  celiac disease.
• Clonal refractory sprue (CD3/CD8-/CD103)
• ulcerative jejunitis
• Alarm symptoms obstruction, weight loss,
  bleeding,pain, fever

101
Current Data HighlightsCeliac Disease at
diagnosis

• Capsule and diagnosis of CD
• de Franchis et al ICCE2005 AB 015
• Murray et al Gastrointest Endosc
  200358(1)92-95
• Krauss et al ICCE 2005AB 049
• n gt 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 2006AB 20122
102
Current Data HighlightsCeliac Disease Diagnosis

• Mapping the extent of CD
• Murray et al Gastrointest Endosc 200459(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
  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.

103
Current Data Highlights Complicated Celiac
Disease

• Screening for complicated celiac disease
• Patients symptomatic on a GFD
• Daly et al Gastrointest Endosc 200459(5) AB 1806
• (n 47)
• villous atrophy 68
• ulcerations 50
• cancer 5
• Krauss et al. Gastroenterol 2005128(4) AB547
• (n43)
• ulcerations 25
• tumours 5

104
Proposed Algorithm Celiac Disease (CD) Diagnosis
105
Proposed AlgorithmComplicated Celiac Disease
106
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
• lymphoma
• adenocarcinoma

107
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.

108
Celiac Image Spectrum
Absent Villi
Fissuring
Scalloping
Mosaic pattern
Fissuring and ulcer
Scalloping
109
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

110
Celiac Consensus Conclusions

• 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)

111
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).

112
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
113
Clinical Challenges

• Limitations of capsule endoscopy in some
• cases
• Dark/opaque intestinal contents, bubbles,
  food/medication particles, fecal matter,
  impairing visualization of the mucosa

114
Clinical Challenges (continued)

• 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

115
ASGE CE SIG Survey
Do you routinely use a laxative prior to SB
capsule exams?
Yes
No
116
ASGE CE SIG Survey
If yes, which laxative do you use?
117
ASGE CE SIG Survey
Do you routinely use a prokinetic agent prior to
SB CE?
Yes
No
118
ASGE CE SIG Survey
If yes, which type of prokinetic agent do you
use?
119
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.

120
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?
121
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.

122
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

123
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 2006AB 314850
• 123 patients
• (A) 12 hour fast, (B) 90ml NaPhos
• NO SIGNIFICANT DIFFERENCE
• Wi et al., Gastrointest Endosc 200663(4) AB
  M1310
• 125 patients
• (A) 12 hour fast, (B) 90ml NaPhos, (C) 2L PEG
• IMPROVED VISIBILITY AND IMPROVED DIAGNOSTIC
  YIELDWITH NaPHOS (BUT NOT WITH PEG)

124
Preps Peer-reviewed Article

• Viazis et al. GIE 200460534-8
• 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)

125
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.

126
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.

127
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

128
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