Jonathan A. Leighton, MDJonathan A. Leighton, MDMayo Clinic ArizonaMayo Clinic Arizona

leighton.jonathan@mayo.edu

Great Debates and Updates in IBDGreat Debates and Updates in IBDSan Francisco, CA March 2013San Francisco, CA March 2013

Small Bowel Evaluation –Small Bowel Evaluation –

Choosing the Best Choosing the Best

Radiologic and Endoscopic ModalitiesRadiologic and Endoscopic Modalities

Importance of Small Bowel EvaluationImportance of Small Bowel Evaluationin Crohn’s Diseasein Crohn’s Disease

• The diagnosis of SB inflammation can be challenging when The diagnosis of SB inflammation can be challenging when inflammation is mild and/or confined to the small bowelinflammation is mild and/or confined to the small bowel

• A comprehensive evaluation of the entire small bowel may be A comprehensive evaluation of the entire small bowel may be indicated to:indicated to:– Make a definitive diagnosis of CDMake a definitive diagnosis of CD– Determine extent and severity of diseaseDetermine extent and severity of disease– Determine baseline disease activity to serve as a Determine baseline disease activity to serve as a

comparator for monitoring of diseasecomparator for monitoring of disease

• Imaging TechniquesImaging Techniques

• Capsule Endoscopy Capsule Endoscopy

• CT/MR Enterography CT/MR Enterography

• Deep EnteroscoppyDeep Enteroscoppy

CD = Crohn’s disease; C+I = colonoscopy with ileoscopy.

Why Might Capsule Endoscopy (CE) Why Might Capsule Endoscopy (CE) Be Helpful?Be Helpful?

• Isolated involvement of the proximal SB can occur in Isolated involvement of the proximal SB can occur in as many as one third of casesas many as one third of cases

• Normal findings on ileocolonoscopy are not sufficient Normal findings on ileocolonoscopy are not sufficient to exclude the diagnosisto exclude the diagnosis

• Cross-sectional imaging can detect transmural Cross-sectional imaging can detect transmural inflammation but superficial mucosal inflammation inflammation but superficial mucosal inflammation may be missedmay be missed

• CE offers a comprehensive evaluation of the SB CE offers a comprehensive evaluation of the SB mucosa to identify CD missed by conventional mucosa to identify CD missed by conventional endoscopy and/or evaluate extent and severity of endoscopy and/or evaluate extent and severity of involvement involvement

• Debate still exists as to its role in the diagnosis and Debate still exists as to its role in the diagnosis and management of management of SuspectedSuspected and and EstablishedEstablished Crohn’s Crohn’s diseasedisease

Case StudyCase Study

• 42 yo male with history of ileal Crohn 42 yo male with history of ileal Crohn disease diagnosed in 2001 in Chicago disease diagnosed in 2001 in Chicago treated with 5ASAtreated with 5ASA

• Recurrent episodes of abdominal pain and Recurrent episodes of abdominal pain and SBO with otherwise negative CT scansSBO with otherwise negative CT scans

• Presented to Mayo Clinic March 2012 with Presented to Mayo Clinic March 2012 with abdominal pain and black stoolsabdominal pain and black stools

• EGD negativeEGD negative

Negative Colonoscopy and Negative Colonoscopy and IleoscopyIleoscopy

Negative MR EnterographyNegative MR Enterography

Positive CEPositive CE

Endoscopic Skipping of the Distal Endoscopic Skipping of the Distal Terminal IleumTerminal Ileum

• 189 consecutive patients with CD189 consecutive patients with CD• 153 TI intubation153 TI intubation

• 67 had normal ileoscopy67 had normal ileoscopy

• 67 patients with normal ileoscopy67 patients with normal ileoscopy• 36 had active small bowel CD36 had active small bowel CD

• Skipped distal ileum in 11Skipped distal ileum in 11• Intramural/mesentery disease only in Intramural/mesentery disease only in

2323• Upper GI tract in 2Upper GI tract in 2

Samuel S et al. CGH 2012;10:1253-59Samuel S et al. CGH 2012;10:1253-59

A Prospective Multicenter Blinded Study Comparing A Prospective Multicenter Blinded Study Comparing CE vs SBFT Before Ileocolonoscopy (IC) CE vs SBFT Before Ileocolonoscopy (IC)

in in SuspectedSuspected Crohn Disease Crohn Disease

• Aim: compare diagnostic yield of CE before IC vs SBFT and IC.Aim: compare diagnostic yield of CE before IC vs SBFT and IC.

• Results: 80 patients were included in the analyses. Results: 80 patients were included in the analyses. • Diagnostic yield of CE = IC (Diagnostic yield of CE = IC (PP=.09). =.09). • Diagnostic yield CE > SBFT (Diagnostic yield CE > SBFT (PP<.001). <.001). • 25 (31.3%) had the diagnosis of CD confirmed. 25 (31.3%) had the diagnosis of CD confirmed.

• 11 diagnosed by CE alone/5 diagnosed by IC alone 11 diagnosed by CE alone/5 diagnosed by IC alone • 9 were identified by at least 2 of the 3 modalities. 9 were identified by at least 2 of the 3 modalities.

• Conclusion: Conclusion: • IC remains the diagnostic test of choice IC remains the diagnostic test of choice • CE was clearly better than SBFT for SB inflammation and CD CE was clearly better than SBFT for SB inflammation and CD • CE demonstrated equivalency to IC for ileocecal inflammation. CE demonstrated equivalency to IC for ileocecal inflammation. • This study suggests that CE is safe and can diagnosis CD This study suggests that CE is safe and can diagnosis CD

when IC is negative. when IC is negative.

Leighton JA et al. Submitted for publicationLeighton JA et al. Submitted for publication

CE and Suspected Crohn’s DiseaseCE and Suspected Crohn’s DiseaseFinal Thoughts……Final Thoughts……

• Although CE has greater sensitivity for mucosal Although CE has greater sensitivity for mucosal inflammation than radiology, the PPV is fair at inflammation than radiology, the PPV is fair at 50%50%

• False positives and an increased risk of retention False positives and an increased risk of retention may limit the widespread usemay limit the widespread use

• The NPV at 96% suggests that CE may be better The NPV at 96% suggests that CE may be better for excluding Crohn’s disease than confirming itfor excluding Crohn’s disease than confirming it

• CE may play an even more important role in CE may play an even more important role in establishedestablished CD CD

Tukey M et al. Am J Gastro 2009;104:2734-9Tukey M et al. Am J Gastro 2009;104:2734-9Levesque BG, et al. Clin Gastro Hep 2010;261-7Goldfarb NI et al: Dis Manag 7:292-304, 2004

Tukey M et al. Am J Gastro 2009;104:2734-9Tukey M et al. Am J Gastro 2009;104:2734-9Levesque BG, et al. Clin Gastro Hep 2010;261-7Goldfarb NI et al: Dis Manag 7:292-304, 2004

CE for CE for EstablishedEstablished IBD IBD

• In the majority of cases, may be a better In the majority of cases, may be a better tool for monitoring disease extent and tool for monitoring disease extent and severity severity

• Using a standardized scoring system may Using a standardized scoring system may aid in objectively tracking disease activityaid in objectively tracking disease activity

• Potential ApplicationsPotential Applications• Postoperative recurrencesPostoperative recurrences• Indeterminate colitisIndeterminate colitis• Mucosal healingMucosal healing

Doherty GA et al. GIE 2011;74:167-75Doherty GA et al. GIE 2011;74:167-75

Impact of CE on Management of Impact of CE on Management of Known IBDKnown IBD

• 128 CE performed for symptomatic IBD (86 for Crohn's 128 CE performed for symptomatic IBD (86 for Crohn's disease, 15 for indeterminate colitis, 23 for pouchitis. disease, 15 for indeterminate colitis, 23 for pouchitis.

• ResultsResults• In CD, 61.6% had a change in meds in the 3 months In CD, 61.6% had a change in meds in the 3 months

after CE, with 39.5% initiating a new IBD after CE, with 39.5% initiating a new IBD medication medication

• Severe findings resulted in significant differences Severe findings resulted in significant differences in in

• Med changes (73.2% versus 51.1%, P = 0.04), Med changes (73.2% versus 51.1%, P = 0.04), • Addition of meds (58.5% versus 22.2%, P < 0.01)Addition of meds (58.5% versus 22.2%, P < 0.01)• Surgeries (21.9% versus 4.4%, P = 0.01). Surgeries (21.9% versus 4.4%, P = 0.01).

• CE results in management changes in the majority of CE results in management changes in the majority of cases of symptomatic IBD, regardless of the subtype cases of symptomatic IBD, regardless of the subtype of IBDof IBD

Long MD et al. IBD 2011;17:1855- 62Long MD et al. IBD 2011;17:1855- 62

CE in Patients with Perianal CE in Patients with Perianal Disease Disease

• 26 patients with perianal disease but 26 patients with perianal disease but negative endoscopic evaluation negative endoscopic evaluation (ileocolonoscopy, SBFT, CTE/MRE)(ileocolonoscopy, SBFT, CTE/MRE)

• ResultsResults• 25 underwent CE25 underwent CE• 6/25 (24%) identified SB inflammation 6/25 (24%) identified SB inflammation

consistent with CDconsistent with CD• No other variables (lab) were predictiveNo other variables (lab) were predictive

Adler, SN et al. WJGE 2012;4:185-188Adler, SN et al. WJGE 2012;4:185-188

Bottom LineBottom Line

• CE has a high diagnostic yield for evaluating CE has a high diagnostic yield for evaluating abnormalities of the SB mucosaabnormalities of the SB mucosa

• Specificity is an issue and NSAIDs should be Specificity is an issue and NSAIDs should be stopped before CE; it is critical not to prematurely stopped before CE; it is critical not to prematurely diagnose CD diagnose CD

• CE for CE for suspected CDsuspected CD may be best suited for a may be best suited for a subgroup of patients with negative subgroup of patients with negative ileocolonoscopy and a high suspicion of small ileocolonoscopy and a high suspicion of small bowel inflammationbowel inflammation

• CE may also be suited for CE may also be suited for established CDestablished CD for for monitoring extent and severity, mucosal healing, monitoring extent and severity, mucosal healing, postop recurrence, and indeterminate colitis postop recurrence, and indeterminate colitis although cost effectiveness needs to be although cost effectiveness needs to be establishedestablished

• Oral contrast: NeutralOral contrast: Neutral• Rate: 450 cc every 15 min Rate: 450 cc every 15 min • Amt: 1350 cc over 45 minAmt: 1350 cc over 45 min

• Oral contrast: NeutralOral contrast: Neutral• Rate: 450 cc every 15 min Rate: 450 cc every 15 min • Amt: 1350 cc over 45 minAmt: 1350 cc over 45 min

CT Enterography (CTE)CT Enterography (CTE)

Filtered back projectionFiltered back projectionIncreased noiseIncreased noise

Filtered back projectionFiltered back projectionIncreased noiseIncreased noise

ASIR SoftwareASIR SoftwareDecreased noiseDecreased noiseASIR SoftwareASIR Software

Decreased noiseDecreased noise

Low Dose CT30-50% less radiation30-50% less radiation

Low Dose CT30-50% less radiation30-50% less radiation

CTECTEDifferentiating Active vs Chronic CDDifferentiating Active vs Chronic CD

N = 96 pts with CTE and endoscopyN = 96 pts with CTE and endoscopy

Bodily K et al: Radiology 2006;238:505-516Bodily K et al: Radiology 2006;238:505-516

CTE Finding Sens (%)

Mural hyperenhancement 80

Bowel wall thickening 75

Mural stratification 60

Comb sign 35

Inc. mesenteric fat atten 10

CTE Finding Sens (%)

Mural hyperenhancement 80

Bowel wall thickening 75

Mural stratification 60

Comb sign 35

Inc. mesenteric fat atten 10

Enhancement: Homogeneous

Distended Bowel Wall Thickness <3 mm

Enhancement: Increased

Bowel Wall Thickness>3mm

Small BowelSmall BowelNormal vs Crohn’s DiseaseNormal vs Crohn’s Disease

CTE in Suspected CD with CTE in Suspected CD with Negative IleoscopyNegative Ileoscopy

• Retrospective study of 189 patients with Retrospective study of 189 patients with CD – TI intubation in 153CD – TI intubation in 153• 67 had normal ileoscopy67 had normal ileoscopy• 36 were found to have active SB CD36 were found to have active SB CD

• Two had gastroduodenal CDTwo had gastroduodenal CD• CTE was positive in 34 patients with CTE was positive in 34 patients with

more proximal disease (11) or more proximal disease (11) or intramural disease (23)intramural disease (23)

Samuel S et al. Clin Gastro Hep 2012;10:1253-59Samuel S et al. Clin Gastro Hep 2012;10:1253-59

Retrospective study of 20 pts with CD who underwent Retrospective study of 20 pts with CD who underwent 40 CTE evaluated while blinded to clinical history40 CTE evaluated while blinded to clinical history

Results:Results:

• Disease progression or regression by CTE Disease progression or regression by CTE correlated with symptoms in 16/20 (80%) pts correlated with symptoms in 16/20 (80%) pts

• In 4/20 (20%) pts, symptoms progressed while CTE In 4/20 (20%) pts, symptoms progressed while CTE findings were negative (n=2) or improved (n=2)findings were negative (n=2) or improved (n=2)

• Endoscopy correlated with CTE findings in 12/12 Endoscopy correlated with CTE findings in 12/12 and with symptoms in 9/12and with symptoms in 9/12

• The weighted kappa was 0.57 (95%CE=0.20 to 0.94)The weighted kappa was 0.57 (95%CE=0.20 to 0.94)

Retrospective study of 20 pts with CD who underwent Retrospective study of 20 pts with CD who underwent 40 CTE evaluated while blinded to clinical history40 CTE evaluated while blinded to clinical history

Results:Results:

• Disease progression or regression by CTE Disease progression or regression by CTE correlated with symptoms in 16/20 (80%) pts correlated with symptoms in 16/20 (80%) pts

• In 4/20 (20%) pts, symptoms progressed while CTE In 4/20 (20%) pts, symptoms progressed while CTE findings were negative (n=2) or improved (n=2)findings were negative (n=2) or improved (n=2)

• Endoscopy correlated with CTE findings in 12/12 Endoscopy correlated with CTE findings in 12/12 and with symptoms in 9/12and with symptoms in 9/12

• The weighted kappa was 0.57 (95%CE=0.20 to 0.94)The weighted kappa was 0.57 (95%CE=0.20 to 0.94)

Hara AK et al: AJR, 2008Hara AK et al: AJR, 2008

Using CTE To Monitor CD Activity Using CTE To Monitor CD Activity

T2 weighted image(fluid bright)

T2 weighted image(fluid bright)

T1 weighted image(walls bright)

T1 weighted image(walls bright)

Crohn’s DiseaseCrohn’s DiseaseMR Enterography (MRE)MR Enterography (MRE)

Crohn’s DiseaseCrohn’s DiseaseMR Enterography (MRE)MR Enterography (MRE)

Courtesy of Jeff Fidler, MDCourtesy of Jeff Fidler, MD

MRE and CTE Correlate with MRE and CTE Correlate with ColonoscopyColonoscopy

• MRE findings compared to colonoscopy and MRE findings compared to colonoscopy and ileoscopy: MRE correlates with CDEIS and this ileoscopy: MRE correlates with CDEIS and this was validated in a subsequent studywas validated in a subsequent study

• MRE vs CTE vs Ileocolonoscopy: CTE and MRE MRE vs CTE vs Ileocolonoscopy: CTE and MRE were equally accurate for assessing disease were equally accurate for assessing disease activityactivity

Rimola J et al. Gut 2009;58:1113-1120Rimola J et al. IBD 2010Fiorino G et al. IBD 2011;17:1073-1080

Rimola J et al. Gut 2009;58:1113-1120Rimola J et al. IBD 2010Fiorino G et al. IBD 2011;17:1073-1080

What we don’t know:Is mucosal healing or transmural healing or

histologic remission responsible for better clinical outcomes?

What we don’t know:Is mucosal healing or transmural healing or

histologic remission responsible for better clinical outcomes?

• CTE takes 10 secondsCTE takes 10 seconds• MRE takes 30 minutesMRE takes 30 minutes• With MRE, patients have to hold breathWith MRE, patients have to hold breath• Worse in obese patients or respiratory problemsWorse in obese patients or respiratory problems• Suboptimal MRE more common than CTESuboptimal MRE more common than CTE

• CTE takes 10 secondsCTE takes 10 seconds• MRE takes 30 minutesMRE takes 30 minutes• With MRE, patients have to hold breathWith MRE, patients have to hold breath• Worse in obese patients or respiratory problemsWorse in obese patients or respiratory problems• Suboptimal MRE more common than CTESuboptimal MRE more common than CTE

CTE MRE

CTE vs MRECTE vs MRE

Bottom LineBottom Line

• MRE and CTE show good correlation MRE and CTE show good correlation for the detection and localization of for the detection and localization of transmural CDtransmural CD

• Compared to CE, MRE and CTE are Compared to CE, MRE and CTE are inferior in the detection of superficial inferior in the detection of superficial mucosal diseasemucosal disease

• CE may be more sensitive than CTE or CE may be more sensitive than CTE or MRE, especially in proximal SBMRE, especially in proximal SB

Suspected No Fistula/CD stricture Strictures abscess

Ileoscopy

CE

CTE/MRE

SBFT

Suspected No Fistula/CD stricture Strictures abscess

Ileoscopy

CE

CTE/MRE

SBFT

Follow Known CDFollow Known CD

AA

AA

AA AA AA

BB

BB

BB

BBCC CC

Forcep channel allows biopsy and therapyForcep channel allows biopsy and therapy

Double-Balloon Double-Balloon Enteroscopy (DBE)Enteroscopy (DBE)

Double-Balloon Double-Balloon Enteroscopy (DBE)Enteroscopy (DBE)

““Deep Enteroscopy”Deep Enteroscopy”Tube or Balloon Assisted EnteroscopyTube or Balloon Assisted Enteroscopy

Single-Balloon Single-Balloon Enteroscopy (SBE)Enteroscopy (SBE)

Single-Balloon Single-Balloon Enteroscopy (SBE)Enteroscopy (SBE)

Spiral Overtube Spiral Overtube EnteroscopyEnteroscopy

Spiral Overtube Spiral Overtube EnteroscopyEnteroscopy

DBEDBE

Impact of DBE on CDImpact of DBE on CD

• Prospective study of CD patients Prospective study of CD patients suspected of SB involvement in whom suspected of SB involvement in whom distal activity had previously been distal activity had previously been excludedexcluded

• Results:Results:• 35 patients (70%) showed SB lesions35 patients (70%) showed SB lesions• 23 (46%) could not be assessed by 23 (46%) could not be assessed by

conventional endoscopyconventional endoscopy• Step up therapy in 26 patients (74%) led Step up therapy in 26 patients (74%) led

to clinical remission in 23 (88%)to clinical remission in 23 (88%)

Mensink PB et al. Scan J Gastro 2010;45:483-489Mensink PB et al. Scan J Gastro 2010;45:483-489

• DBE unsucessful in 26% with Crohn DBE unsucessful in 26% with Crohn diseasedisease

• 4/8 rectal DBE perforations occurred in 4/8 rectal DBE perforations occurred in patients with prior ileoanal or ileocolonic patients with prior ileoanal or ileocolonic anastomosesanastomoses

• In the subset of patients with available data In the subset of patients with available data regarding prior intestinal surgeries, regarding prior intestinal surgeries, perforations occurred in 6/76 (8%) patientsperforations occurred in 6/76 (8%) patients

Gerson L et al: DDW 2008Gerson L et al: DDW 2008

ComplicationsComplicationsU.S. DataU.S. Data

Diagnosis and Treatment of Diagnosis and Treatment of SB Strictures with DBESB Strictures with DBE

156 patients with strictures underwent DBE 156 patients with strictures underwent DBE Inflammatory disease in 87 and of those, Inflammatory disease in 87 and of those, Crohn’s disease in 57Crohn’s disease in 57

• Balloon dilation in 31 with long term success Balloon dilation in 31 with long term success in 22 (71%)in 22 (71%)

19 patients with symptomatic SB strictures and CD19 patients with symptomatic SB strictures and CD• DBE detected 28 stricturesDBE detected 28 strictures• 10/19 had 13 strictures from 1-4cms and 10/19 had 13 strictures from 1-4cms and

underwent 15 DBE balloon dilationsunderwent 15 DBE balloon dilations• Therapeutic success was achieved in 8 patients. Therapeutic success was achieved in 8 patients.

No complications occurredNo complications occurred

156 patients with strictures underwent DBE 156 patients with strictures underwent DBE Inflammatory disease in 87 and of those, Inflammatory disease in 87 and of those, Crohn’s disease in 57Crohn’s disease in 57

• Balloon dilation in 31 with long term success Balloon dilation in 31 with long term success in 22 (71%)in 22 (71%)

19 patients with symptomatic SB strictures and CD19 patients with symptomatic SB strictures and CD• DBE detected 28 stricturesDBE detected 28 strictures• 10/19 had 13 strictures from 1-4cms and 10/19 had 13 strictures from 1-4cms and

underwent 15 DBE balloon dilationsunderwent 15 DBE balloon dilations• Therapeutic success was achieved in 8 patients. Therapeutic success was achieved in 8 patients.

No complications occurredNo complications occurred

Fukumoto A et al: GI Endo 66:S108, 2007Pohl J et al: Eur J Gastro Hep 2007;19:529-534Fukumoto A et al: GI Endo 66:S108, 2007Pohl J et al: Eur J Gastro Hep 2007;19:529-534

DBE for CE RetrievalDBE for CE Retrieval

• 8/904 patients had capsule retention and caused 8/904 patients had capsule retention and caused acute SBO in 6 patientsacute SBO in 6 patients

• All capsules were successfully removed during All capsules were successfully removed during DBEDBE

• 5 patients underwent elective surgery for 5 patients underwent elective surgery for underlying causeunderlying cause

• One patient required emergency surgery because One patient required emergency surgery because of multiple SB perforations of multiple SB perforations

Van Weyenberg SJB et al: GIE 2010;535-541Van Weyenberg SJB et al: GIE 2010;535-541

Capsule Retrieval with BAECapsule Retrieval with BAE

Courtesy of Mark Stark Courtesy of Mark Stark

New Small Bowel Imaging TestsNew Small Bowel Imaging TestsComplimentaryComplimentary

• Capsule Endoscopy (CE)Capsule Endoscopy (CE)

• Excellent mucosal detail non-invasivelyExcellent mucosal detail non-invasively

• Identifying CD missed with conventional endoscopyIdentifying CD missed with conventional endoscopy

• Evaluating extent and severity of SB involvementEvaluating extent and severity of SB involvement

• CT and MR Enterography (CTE/MRE)CT and MR Enterography (CTE/MRE)

• Transmural assessmentTransmural assessment

• Extraintestinal lesionsExtraintestinal lesions

• Balloon-Assisted Enteroscopy (BAE)/ Rotational EnteroscopyBalloon-Assisted Enteroscopy (BAE)/ Rotational Enteroscopy

• Mucosal detailMucosal detail

• Allows for biopsy and therapeuticsAllows for biopsy and therapeutics

ObstructionObstruction

Approach to Suspected Crohn’s Disease of the Small Bowel Approach to Suspected Crohn’s Disease of the Small Bowel

SBCD=Small Bowel Crohn’s Disease; CTE=CT Enterography; MRE=MR Enterography; SBFT=Small Bowel Follow ThroughSBCD=Small Bowel Crohn’s Disease; CTE=CT Enterography; MRE=MR Enterography; SBFT=Small Bowel Follow Through

Suspected Crohn’s Disease of SB

Suspected Crohn’s Disease of SB

Positive Ileocolonoscopy

Positive Ileocolonoscopy

Negative Ileocolonoscopy or unsuccessful

Negative Ileocolonoscopy or unsuccessful

Diagnose and Treat accordingly

Diagnose and Treat accordingly

No obstructionNo obstruction

Capsule endoscopyCapsule endoscopy

Crohn’s disease of SB

Crohn’s disease of SB

Possible or know obstruction

Possible or know obstruction

CTE/MRE and/or DBE CTE/MRE

and/or DBE

either/oreither/orAgile patency capsule

Agile patency capsule

No obstructionNo obstruction

Thank You!!Thank You!!