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1. Novel Diagnostic Strategies in Inflammatory Bowel Disease Mark H. Flasar, M.D.
Assistant Professor of Medicine
Division of Gastroenterology and Hepatology
2. The Short List Laboratory testing
Serologic markers
Genetic testing
Metabolite monitoring
Markers of disease activity (serum, stool)
Radiography
Enterography (CT, MRI)
Pelvic imaging (MRI)
Ultrasound
Endoscopy
Chromoendoscopy
Advanced endoscopic imaging
Rectal EUS for fistulae
3. All That in 30 Minutes???
4. Serology: The Two Jakes ASCA: The Crohns Disease Ab
+ in 60% of CD1-3
IgA + IgG vs. cell wall of S. cerevisiae
pANCA: The Ulcerative Colitis Ab
+ in 40-80% UC, 2-28% CD (UC-like CD)4
Newer assay more specific for UC
Loss of perinuclear stain after DNAse
ASCA:
Sacch=brewers yeast
Simple ELISA, standardized, easy to run
Poor correlation with mucosal S. cerevesiae Mallant-Hent RC, et al. World J Gastroenterol 2006;12:292
ANCA:
ANCA IgG, pANCA IIF, DNASE sens pANCA IIF
Results variable based on assay, personnel experience. ELISA+IFE--?60%, IFE alone?0-40% ASCA:
Sacch=brewers yeast
Simple ELISA, standardized, easy to run
Poor correlation with mucosal S. cerevesiae Mallant-Hent RC, et al. World J Gastroenterol 2006;12:292
ANCA:
ANCA IgG, pANCA IIF, DNASE sens pANCA IIF
Results variable based on assay, personnel experience. ELISA+IFE--?60%, IFE alone?0-40%
5. Other CD Abs: OmpC and CBir1 Anti-OmpC*
IgA + in 55% of CD5
Vs. E. coli outer membrane porin C protein
Anti-Cbir1t
IgA + in 50-55% CD6,7
40% Ab- CD pts are + for anti-CBir17
Anti-I2
+ in 54% CD8-9
Vs. bacterial DNA in LP monocytes
OmpC
less + in peds (24% in pediatric-onset CD) Zholudev A, et al. Am J Gastroenterol 2004;99:2235
CBir1
Induces colitis in animal models
40% CD pts - for all other Abs are + for anti-CBir1 (suggesting possible unique CD phenotype)
I2
assoc w/ Pseudomonas flouresciensOmpC
less + in peds (24% in pediatric-onset CD) Zholudev A, et al. Am J Gastroenterol 2004;99:2235
CBir1
Induces colitis in animal models
40% CD pts - for all other Abs are + for anti-CBir1 (suggesting possible unique CD phenotype)
I2
assoc w/ Pseudomonas flouresciens
6. Other Abs: PAB and anti-Glycans Anti-Glycan Abs11,12
Vs. bacterial/fungal cell wall carbohydrates
ALCA, ACCA, AMCA? + in 18-38% CD
Anti pancreatic Ab (PAB)
+ in 30% CD10
unknown relevance in CD
Low correlation between presence of AMCA, ACCA, ALCA
suggests different microorganism targets for each
Anti-laminaribocide Ab (ALCA)
Anti-chitobioside (ACCA)
Anti-mannobioside (AMCA)Low correlation between presence of AMCA, ACCA, ALCA
suggests different microorganism targets for each
Anti-laminaribocide Ab (ALCA)
Anti-chitobioside (ACCA)
Anti-mannobioside (AMCA)
7. Serology: What is it Good For? Diagnosis
IBD vs. Functional/Healthy
CD vs. UC
Pre-clinical marker
Predict disease course or complications in IBD
CD and UC phenotype
CD and UC progression/aggression
Risk of pouchitis after IPAA for UC
Following disease activity/treatment response
IBD vs. functional/healthy: Use when low index suspicion and want to avoid endoscopy/expensive testingIBD vs. functional/healthy: Use when low index suspicion and want to avoid endoscopy/expensive testing
8. ASCA, pANCA for IBD vs. Healthy How about ASCA alone?
Here, test characteristics examined as a secondary aim, looking at population with high prevalence CD (36%).
Not a very good screening testHow about ASCA alone?
Here, test characteristics examined as a secondary aim, looking at population with high prevalence CD (36%).
Not a very good screening test
9. ASCA, pANCA for IBD vs. Healthy How about ASCA AND ANCA?
The aim of this study was to see how well ACSA, ANCA and combination could tell IBD from controls.
(n = 582: 407 CD, 147 UC, and 28 indeterminate colitis), patients with non-IBD diarrheal illnesses (n = 74), and healthy controls (n = 157).
CONCLUSIONS: Specificity of serological markers for IBD is high, but low sensitivity makes them less useful as diagnostic tests.
The combination of tests is probably more powerful, although, clinical subgroups still need to be defined. How about ASCA AND ANCA?
The aim of this study was to see how well ACSA, ANCA and combination could tell IBD from controls.
(n = 582: 407 CD, 147 UC, and 28 indeterminate colitis), patients with non-IBD diarrheal illnesses (n = 74), and healthy controls (n = 157).
CONCLUSIONS: Specificity of serological markers for IBD is high, but low sensitivity makes them less useful as diagnostic tests.
The combination of tests is probably more powerful, although, clinical subgroups still need to be defined.
10. Utility of Serodiagnostics in Pediatric IBD: Use of a Two-Step Assay Used different algorithm, with more sensitive cutoffs, then traditional testing.
Serial testing such as this supposed to increase specificity. Prev=45%
Here, SENS=69% spec=95% ppv=90% npv=80%
Sens not sig. better (81% overall). Allowed 81% reduction in FP, thus possibly avoiding unneeded testing in some.
Other studies had conflicting results Khan K, et al. Inflamm Bowel Dis 2002;8:325
50% new CD pts had serology
ASCA+ also often had + routine markers inflammation
Accounting for rectal bleeding, markers of inflam and serology, Only 76% identified as possibly having IBD prior to an endoscopy
Thus, - serology may not preclude an endoscopic examUsed different algorithm, with more sensitive cutoffs, then traditional testing.
Serial testing such as this supposed to increase specificity. Prev=45%
Here, SENS=69% spec=95% ppv=90% npv=80%
Sens not sig. better (81% overall). Allowed 81% reduction in FP, thus possibly avoiding unneeded testing in some.
Other studies had conflicting results Khan K, et al. Inflamm Bowel Dis 2002;8:325
50% new CD pts had serology
ASCA+ also often had + routine markers inflammation
Accounting for rectal bleeding, markers of inflam and serology, Only 76% identified as possibly having IBD prior to an endoscopy
Thus, - serology may not preclude an endoscopic exam
11. Summary: IBD vs. Functional/healthy pANCA and ASCA are specific for UC and CD respectively
Can HELP rule in disease (if high PTP)
The moderate sensitivity and low negative predictive value preclude them as a screening test
Unable to rule out disease
Potential application in pediatric disease to avoid invasive work up
Not in recent algorithm North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America
12. Serology: What is it Good For? Diagnosis
IBD vs. Functional/Healthy
CD vs. UC
Pre-clinical marker
Predict disease course or complications in IBD
CD and UC phenotype
CD and UC progression/aggression
Risk of pouchitis after IPAA for UC
Following disease activity/treatment response
13. ASCA for CD vs. UC How did ASCA do?
Secondary aim of study that looked at performance of different assays in a known population.
Again, if ASCA+, especially in a high-prev population, it is CD. Otherwise, it offers little help. How did ASCA do?
Secondary aim of study that looked at performance of different assays in a known population.
Again, if ASCA+, especially in a high-prev population, it is CD. Otherwise, it offers little help.
14. Diagnosis: CD vs. UC 97 IC pts v for ASCA/pANCA and followed17
31/97 (32%) Declared themselves
48% pts had all Abs
85% of these, dx remained IC
Adding anti-OmpC and anti-I2 in did not help18 What about ASCA/ANCA?
97 pts w/u extensively for IC, still couldnt tell which.
Serology applied, then followed to see if declared. over 9.9 year f/u
32% declared by about 6 years. No more into about 10 yrs f/u (longer IC, longer stay in IC).
1/3 ASCA+/ANCA-, ź ASCA-/ANCA+, small amount both+, 48% all -
What about ASCA/ANCA?
97 pts w/u extensively for IC, still couldnt tell which.
Serology applied, then followed to see if declared. over 9.9 year f/u
32% declared by about 6 years. No more into about 10 yrs f/u (longer IC, longer stay in IC).
1/3 ASCA+/ANCA-, ź ASCA-/ANCA+, small amount both+, 48% all -
15. Diagnosis: CD vs. UC (IC) 238 UC pts for IPAA had preop serology19
anti-OmpC, anti CBir1, ASCA, pANCA
16 (7%) developed CD after IPAA
MV analysis? ASCA+ 3-fold risk CD
Glycan panel?gASCA, ALSA, ACCA11
1 Ab+: sens 77%, spec 90%, PPV 91%, NPV 77%
2+ Abs+ increased specificity/PPV
At expense of sens/NPV.
16. Summary: CD vs. UC (IC) Most specific test is combining ASCA/ANCA20, 21
PPV ranges 77-96% in several studies22-24
IC is likely a distinct clinical entity
Serology as adjunct
Newer markers may help (CBir1)
44% pANCA+ CD. vs 4% of pANCA+ UC pts25 differentiate ANCA+ UC-like CD (CBir1+) from ANCA+ UC (CBir1-)
differentiate ANCA+ UC-like CD (CBir1+) from ANCA+ UC (CBir1-)
17. Prevalence effects on PPV, NPV
18. Serology Panel: Effects of Prevalence
19. Serology: What is it Good For? Diagnosis
IBD vs. Functional/Healthy
CD vs. UC
Pre-clinical marker
Predict disease course or complications in IBD
CD and UC phenotype
CD and UC progression/aggression
Risk of pouchitis after IPAA for UC
Following disease activity/treatment response
20. Diagnosis: Pre-clinical markers pANCA variably present in UC relatives26-29
ASCA+ in CD relatives 5x more than controls30,31
Study of 40 IBD patients banked sera32
31% of CD pts were ASCA+ prior to dx
No ASCA+ controls
25% UC pts were pANCA+
No pANCA+ controls
No UC pts were ASCA+
Mean interval from serology to detection was 38 monthsMean interval from serology to detection was 38 months
21. Serology: What is it Good For? Diagnosis
IBD vs. Functional/Healthy
CD vs. UC
Pre-clinical marker
Predict disease course or complications in IBD
CD and UC phenotype
CD and UC progression/aggression
Risk of pouchitis after IPAA for UC
Following disease activity/treatment response
22. Relationship Between Marker Antibodies and CD Cohort Analyzed immune response heterogeneity in 330 pts33
Found ASCA 56%, OmpC 55%, I2 50%, and pANCA 23%
Described 4 distinct immune response phenotype clusters
ASCA+, OmpC and I2 +, pANCA+, All negative
15-20% had all neg Abs Eighty-five percent responded to at least 1 antigen
only 4% responded to all 4
Among microbial antigens, 78% responded to at least 1, and 57% were double positive, but only 26% responded to all 3.
The level of response was stable over time and with change in disease activity.
Among patients with the same qualitative antigen-response profiles, quantitative response differed.
Cluster analysis of these antibody responses yielded 4 groups
CONCLUSIONS: Rather than global loss of tolerance, there seem to be patient subsets with differing responses to selected microbial and autoantigens
Eighty-five percent responded to at least 1 antigen
only 4% responded to all 4
Among microbial antigens, 78% responded to at least 1, and 57% were double positive, but only 26% responded to all 3.
The level of response was stable over time and with change in disease activity.
Among patients with the same qualitative antigen-response profiles, quantitative response differed.
Cluster analysis of these antibody responses yielded 4 groups
CONCLUSIONS: Rather than global loss of tolerance, there seem to be patient subsets with differing responses to selected microbial and autoantigens
23. Antibody Expression Correlates with Clinical Characteristics This study looked at Sera from 156 consecutive CD patients and compared to clinical profiles.
higher ASCA levels were shown to be independently associated with early age of disease onset as well as both fibrostenosing and internal penetrating disease behaviours.
Higher ANCA levels were associated with later age of onset and ulcerative colitis-like behaviour. This study looked at Sera from 156 consecutive CD patients and compared to clinical profiles.
higher ASCA levels were shown to be independently associated with early age of disease onset as well as both fibrostenosing and internal penetrating disease behaviours.
Higher ANCA levels were associated with later age of onset and ulcerative colitis-like behaviour.
24. CD progression/phenotype ASCA+ ? more aggressive, complicated disease
Higher levels ? earlier disease onset35,36
In adult CD?
FS, IP, SB resection, early surgery34,37-41,45
Higher long-term health care costs46
In peds CD
3x odds relapse in children42
early onset, fistula/abscess recurrence, repeat surgery, SB dz43,44
ASCA+/pANCA-
SB involved more often than colon alone34
25. CD progression/phenotype pANCA+ identifies34,35,47,48
UC-like subgroup, good therapy response , later onset
anti-OmpC
Levels assoc w/disease progression (non-FS/IP?FS?IP)39,49
Assoc w/FS, IP and SB surgery3, 34,38,47,49
Assoc w/FS, IP in pediatrics44
Anti-I2
assoc w/ FS and SB surgery34,47-8
Anti-CBir1
assoc w/FS, IP dz and SB surgery6,7
26. Dose response of + Ab in CD Number and level of + Abs correlate w/severity
? immune reactivity may = ? immune tolerance
ASCA+/anti-OmpC+anti-I2+ assoc w/? risk vs. all -Abs
FS, IP and surgery (3-8x)38
196 pt prospective peds cohort had similar results44
ASCA+/anti-OmpC+/anti-I2+/anti-CBir1+
11x risk IP or FS w/subsequent surgery if all 4+ vs. all 4-
Time to complication significantly less if ANY + Ab
Retrospective evaluation of 303 pts
Retrospective evaluation of 303 pts
27. Dose response of + Ab in CD
28. Dose response of + Ab in CD CD behavior from presence AND level of markers38
Quartile sum (dose-response) of I2, ASCA, OmpC
Higher quartiles?higher FS, SB dz, SB surg, IP and lower UC-like
29. CD progression/phenotype Aggressive pediatric CD predicted by Abs50
If Anti-CBir1+/anti-OmpC+/ASCA+:
6x odds FS, 9x odds IP and 3x odds SB dz
Same pattern seen for higher Ab response levels
MV analysis
Anti-CBir1, anti-OmpC assoc w/IP
ASCA, anti-CBir1 assoc. w/FS
797 pt. prospective pediatric CD cohort; assessed for:
CARD15 mutations
Anti-CBir1, anti-OmpC, ASCA
797 pt. prospective pediatric CD cohort; assessed for:
CARD15 mutations
Anti-CBir1, anti-OmpC, ASCA
30. UC progression/phenotype pANCA+ higher probability of
severe L-sided dz
treatment-resistance
aggressive course with earlier surgery51
pouchitis after IPAA35,52 Appears to be dose dependent for cumulative incidence pouchitisAppears to be dose dependent for cumulative incidence pouchitis
31. Follow-up/treatment response no corr. pANCA+, titer and UC activity49
Titer same after colectomy32
ASCA stable/independent of CD activity32,35,48
ACCA, ALCA stable as well11
No corr. ASCA to anti-TNF response52
Trend to poorer response to ASCA-/pANCA+ pts
CD w/anti-OmpC+/I2+
better response to budesonide + Cipro/Flagyl
while abs better to budesonide alone54 No ASCA/ANCA relation to TNF in in 279 Belgian CD pts52
Subanalysis of RCT in moderate ileal +/- R colon CD for budesonide/FLagyl
No ASCA/ANCA relation to TNF in in 279 Belgian CD pts52
Subanalysis of RCT in moderate ileal +/- R colon CD for budesonide/FLagyl
32. Summary: progression/phenotype Antibody profiles can predict CD behavior
Stratify to therapy regimens
Multiple antibodies associated with higher risks
pANCA+ associated with pouchitis after IPAA in UC
33. Conclusion: Serology Helpful if positive in correct population
Can help Rule IN disease if high PTP
Can help Rule OUT disease if low PTP
Diagnostic ADJUNCT
Possible alternative in certain populations
Future hope for UC vs. CD
Pre-clinical?
Associated with phenotype/complications
35. Thiopurine ADRs Dose dependent (usually 2/2 toxic metabolites)
Hemotoxicity
Leukopenia: 3.8-11.5%
Pancytopenia: 0.4-2%
Thrombocytopenia: 1.2%
Hepatotoxicity: 0.3-9.9%
4.6% of 173 adult IBD patients69
Infections: 7.4-14.1%
Malaise, nausea: 11%
36. Thiopurine ADRs Dose-independent (hypersensitivity)
Flu-like symptoms (including fever):2-6.5%
GI distress: 4.6%
Pancreatitis:1.2-4.9%
NRH, HVOD, AIN, pneumonitis: rare/case reports
Malignancy:?
Purported 4x lymphoma risk in IBD70
Benefits outweigh risks in decision analysis71
37. Metabolite Monitoring 6-TG corresponds with clinical efficacy while 6-MMP corresponds with hepatotoxicity72-3
Peds clinical efficacy related to 6-TGN > 235 pmol/8x10e8 RBC
Hepatotoxicity corr w/6-MMP> 5700 pmol/8x10e8 RBC (3x risk)
38. Metabolite Monitoring Monitoring of 6-TG + 6-MMP levels may allow prediction of toxicity and guide dose titration
Mixed results from studies73,77-8
39. Metabolite Monitoring: CON No diff in 6-TGN between responders and NR79-82
No diff in 6-TGN between remission and NR78, 81, 83-85
40. Metabolite Monitoring: PRO Correlation between 6-TG and remission72-3, 86-91
Higher 6-TGN levels assoc. with greater clinical response73, 90, 92-3
Meta-analysis showed higher 6-TG assoc w/sig higher levels remission94
6-TGN >230-260 pmol/8x10e8 RBC more likely to be in remission (OR 3.27, 95% CI 1.71-6.27)
Cost-effective analysis suggested MM may decrease costs and improve outcomes vs. usual care95
41. Metabolite Monitoring Controversy whether monitoring good for predicting toxicity
Recent retrospective study reports poor test characteristics of 6-MMP levels in predicting hepatotoxicity at 5,300 and 9,800 cutoffs69
42. Summary: Metabolite Monitoring Useful in pts not achieving expected results despite appropriate dose and time intervals
Very low 6-TG and 6-MMP?noncompliance
Very rarely poor absorption form short gut
6-MMP:6-TG>10-11 suggests preferential shunting to 6-MMP
Suggests unfavorable metabolism, unlikely to be clinically effective89,96
Suboptimal 6-TG levels (<230-260 pmol/8x10e8 RBC and no shunting to 6-MMP), doses could be pushed to get optimal levels
Likely not useful for toxicity
43. CT Enterography Allows visualization of lumen, mucosa, bowel wall and extraluminal pathology
Traditional oral contrast has similar attenuation to enhancing mucosa
Multidetector CT scanner
1-2L of Low Houndsfield-unit oral contrast (<30 HU)
Water +/- methylcellulose, lactulose, PEG
barium/sorbitol (improves distension)
Traditional IV contrast
44. CT Enterography problematic in cases of suspected infection or perforation
Fluid collections/abscesses appear similar to bowel
Mucosal enhancement on CTE correlates with endoscopically and histologically active mucosal disease97-8
45. CT Enterography
46. CT Enterography
47. CT Enterography
48. CT Enterography Crohns With Neo-TI & Colonic Disease
Better evaluation of colon than with SIFTCrohns With Neo-TI & Colonic Disease
Better evaluation of colon than with SIFT
49. CT Enterography Enteroclysis
100% agreement with surgical findings of fistula and stricture99-100
SBFT
Reported 85-95% sensitivity/specificity for identification of stricture, fistula and mucosal abnormalities101
Incorrectly identified stricture number in 31% vs. operative findings102
51. CT Enterography CTE compared to operative findings in 36 CD patients103
CTE correctly identified
100% strictures (83% accuracy)
100% abscesses
94% fistulae (86% accuracy for # fistulae)
97% inflammatory mass
Overestimated or underestimated disease extent in 31%
Stricture, fistula, inflammatory mass, abscess counts
52. Chromoendoscopy (CE) Conventional Colonoscopy (CC) surveillance
2-4 bx every 10cm in colon, q5cm in rectum
Known miss rates for even for visible exophytic lesions
Tandem endoscopy studies? 15-24% adenomas <1 cm missed55-6
Similar results for colectomy specimens vs. preop colonoscopy57
53. Chromoendoscopy (CE) Flat and depressed lesions have premalignant importance58
Can look like normal mucosa endoscopically (easy miss)
Depressed can become invasive early on
Only 20-50% intraepithelial neoplasia detected with CC59
Even miss rate for CRC
4% CRC colectomy pts had normal colonoscopy in preop 6-36mo60
54. Chromoendoscopy (CE) Chromo= dyes applied to mucosa during endoscopy
highlight and better characterize specific mucosal changes
Allows visualization of otherwise invisible mucosal changes
enhancing detection and accuracy
Absorptive, reactive, and contrast staining dyes
Indigo carmine: nonabsorbed; collects in mucosal depressions
Methylene blue: absorbed in normal cytoplasm; irregularities pale
Cresyl violet: taken up in crypts of Leibeukuhn; appears as dots/pits. Pit patterns have histologic correlates. Can be used with the above 2 stains
55. Chromoendoscopy (CE) CC poorly detects flat/depressed lesions
Requires more meticulous training and examination
Chromo +/- mag. ? detection of flat/raised neoplasia
In R colon and in pts w/multiple adenomas61
In non-IBD pts with hx adenomas62
In screening population adenomas randomized to CC vs. CE63
Better detection of adenomas with pan-CE (espec. diminutive lesions)
259 pts randomized to CC vs CE (indigo carmine)
995 consecutive patients evaluated with CC vs indigo-carmine CE+mag.
260 pts randomized to pan-CE vs. targeted CE
259 pts randomized to CC vs CE (indigo carmine)
995 consecutive patients evaluated with CC vs indigo-carmine CE+mag.
260 pts randomized to pan-CE vs. targeted CE
56. Chromoendoscopy in IBD HRCE? better detection (esp. flat) in 85 UC patients64
165 UC pts randomized to CC vs CE65
CE better an defining degree/extent inflammation
CE better at dysplasia detection than CC (32 v 10 lesions)
100 UC surveillance pts got sequential CC and CE65
Pan-CE with target bx after standard CC bx protocol
CC: ALL 2,904 random bx neg; 2/43 target bx?dysplasia
CE: 7/114 target bx?dysplasia
165 UC pts: methylene blue165 UC pts: methylene blue
57. Chromoendoscopy in IBD 350 UC pts had HMCE matched to UC controls w/CC66
Target bx AND 4-quadrant randoms
HMCE
Detected sig. more lesions
Alone detected 79% of dysplasia
0.16% random bx +
8% targeted bx +
CC
0.14% random bx +
1.6% target bx + Suggests random bx not very efficient
Suggests random bx not very efficient
58. Chromoendoscopy in IBD Dye spraying adds about 10 minutes to colonoscopy67
Abandoning random bx will shorten procedure
Should be pretty even in terms of time after learning curve
Recent CCFA committee on IBD CRC/dysplasia surveillance endorses CE in appropriately trained endoscopists68
59. Rectal EUS 20-30% CD develop perianal disease103
Diagnostics include MRI, fistolography (radiating, inaccurate vs surgery, painful, cannot delineate relation to perianal structures), CT (radiating, limited for fistula), EUA
EUS has emerging role
Accurate imaging of perianal region preoperatively
Road-mapping; theoretically reduce risk incontinence
Therapeutic (abscess drainage)
Safe
Can assess response to therapy
Superficial fistula closure may not herald deep tract closure
No radiation
60. Rectal EUS Can accurately delineate EAS, IAS, and pathologic defects
Identified 82% fistula c/w EUA in unblinded series
Better performance than fistulography105
EUS detected 82% fistula vs 24% by CT c/w EUA+fistulography
No difference in abscess detection106
Anal endosonography (AES) 100% sensitive vs. 55% for MRI in detecting perianal abscesses found at EUA
AES 89% sensitive vs. 48% for MRI in fistula detection107
61. Rectal EUS Prospective, blinded study of EUS, MRI, EUA vs. consensus gold standard
Accuracy EUS 91%, MRI 87%, EUA 91%
Combination of any 2 modalities increased accuracy to 100%108
To assess medical response:
IFX trial: AES at entry and 10 weeks in 30 perianal CD pts109
54% had week 10 clinical closure; only 18% closed by AES
Those with week 10 closure on AES had sig. lower relapse rates
21 perianal CD pts with baseline, serial EUS during surgical/medical rx110
52% showed no persistent fistula activity; 64% of these able to stop rx
62. Rectal EUS Future:
Contrast-enhanced EUS: 3% Hydrogen peroxide
3D-EUS
Both methods likely comparable111
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