Endoscopic monitoring of IBD patients for healing and dysplasia in 2018

Transcription

1 Endoscopic monitoring of IBD patients for healing and dysplasia in 2018 Marietta Iacucci, MD, PhD, FASGE Senior Associate Professor(Reader) University of Birmingham, UK Adjunct Associate Professor of Medicine University of Calgary, Canada

2 Advanced therapeutic endoscopy in IBD: A dawn of new era Mucosal Healing How deep is deep enough? Does it really help using the Optical diagnosis to assess and monitoring Inflammation and Mucosal Healing in UC? Dye Chromoendoscopy colonoscopy is the best endoscopic real time practice to detect colonic dysplastic lesions? Is it really true?

3 Advanced therapeutic endoscopy in the colon: A dawn of new era Do we need to characterize these colonic lesions? and How do we do it? Are they endoscopically resectable? When should I perform EMR and when ESD, when Colectomy? NEW ENDOSCOPES AT HORIZON!!!

4 How can we see more at endoscopy? Standard white light endoscopy Zoom endoscopy Dye spraying endoscopy High definition endoscopy (like HD TV) Electronic virtual chromoendoscopy Confocal laser endomicroscopy Endocyto scope

5 Optical Enhancement & Electronic (Virtual) Chromoendoscopy The New OE-iscan & NBI Near Focus & BLI Post Processing of emitted light i-scan 1 and 2 Optical Narrowing of light spectrum OE and NBI Effect: Surface analyis Vessels analysis Detection Pattern characterization In Vivo diagnosis Iacucci M et al Endoscopy 2017 Effect: Vessel analyis & Characterization Vessels Characterization

6 New red flag techniques for detection and characterization Blue Laser Imaging 2 Laser sources 450nm (white-light) = White-light 410nm (blue laser) = Vascular pattern Optical Enhancement Optical Virtual Crhomoendoscopy (vascular pattern) + Digital Virtual Chromoendoscopy (surface pattern)

7 Narrow Banding Imaging

8 Mucosal Healing in Ulcerative Colitis--When Zero is Better. Boal Carvalho P, Dias de Castro F, Rosa B, Moreira MJ, Cotter J. J Crohns Colitis Jan;10(1):20-5

9 Evaluation of the Risk of Relapse in Ulcerative Colitis According to the Degree of Mucosal Healing (Mayo 0 vs 1): A Longitudinal Cohort StudyBarreiro-de Acosta M, Vallejo N, de la Iglesia D, Uribarri L, Bastón I, Ferreiro- Iglesias R, Lorenzo A, Domínguez-Muñoz JE. J Crohns Colitis Jan;10(1):13-9.

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11 Endoscopic HD-UC score for Ulcerative Colitis Mayo UC Endoscopic Score =0 (Mucosal Healing) Mayo UC Endoscopic Score =1 (Mild disease: erythema, decrease vascular pattern,mild friability) Mayo UC Endoscopic score =2 Moderate disease: marked erythema, absent vascular pattern, friability, erosioms Mayo UC Endoscopic score=3 Severe Disease: spontaneous bleeding, ulcerations.

12 UCEIS Vascular pattern Normal (0) Patchy obliteration (1) Obliterated (2) Bleeding None (0) Mucosal (1) Luminal mild (2) Luminal moderate-severe (3) Erosions and ulcers None (0) Erosions (1) Superficial ulcer (2) Deep ulcer (3) Normal vascular pattern with arborisation of capillaries clearly defined, or with blurring or patchy loss of capillary margins Patchy obliteration of vascular pattern Complete obliteration of vascular pattern No visible blood Some spots or streaks of coagulated blood on the surface of the mucosa ahead of the scope, which can be washed away Some free liquid blood in the lumen Frank blood in the lumen ahead of endoscope or visible oozing from mucosa after washing intraluminal blood, or visible oozing from a haemorrhagic mucosa Normal mucosa, no visible erosions or ulcers Tiny ( 5mm) defects in the mucosa, of a white or yellow colour with a flat edge Larger (>5 mm) defects in the mucosa, which are discrete fibrin-covered ulcers in comparison with erosions, but remain superficial Deeper excavated defects in the mucosa, with a slightly raised edge Travis S et al. Gut 2012; 61:

13 ULCERATIVE COLITIS ENDOSCOPIC INDEX OF SEVERITY (UCEIS): VASCULAR PATTERN Score 0 - Normal Score 1 - Patchy obliteration Score 2 - Obliterated BLEEDING Score 0 - None Score 1 - Mucosal Score 2 - Luminal mild Score 3 - Luminal moderate-severe ERORIONS AND ULCERS Score 0 - None Score 1 - Erosions Score 2 - Superficial ulcer Score 3 - Deep ulcer

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15 Current practice position 4.3 Patients in deep [clinical, biological, and endoscopic] remission probably have a lower risk of relapse after anti-tnf discontinuation. Therefore, anti-tnf withdrawal should probably be considered only in patients in longstanding stable clinical, biological, and endoscopic remission Current practice position 4.7 A state of deep remission [clinical, biological, and endoscopic remission] probably decreases the risk of relapse after dose de-escalation Journal of Crohn's and Colitis, 2018, 17 31

16 Iacucci M et al GIE 2017

17 Picco M. GIE 2017

18 Virtual electronic chromoendoscopy (VEC) score in ulcerative colitis (UC) Mucosal architecture 0) No mucosal defect a) Continuous/regular crypts b) Crypts not visible (scar) c) Discontinuous and or dilated/elongated crypts I) Micro-erosions / crypt abscess 1) Discrete 2) Patchy 3) Diffuse II) Erosions size <5 mm 1 3) As above III) Ulcerations size >5 mm 1 3) As above Vascular architecture 0) Vessels; no dilatation a) Roundish following crypts b) Vessels not visible (scar) c) Sparse (deep) vessels I) Vessels; with dilatation a) Roundish b) Crowded / tortuous superficial vessels II) Intramucosal bleeding III) Luminal bleeding 1) Iacucci et al. Endoscopy ) Iacucci et al. Endoscopy )Iacucci et al. GIE 2017

19 PICaSSO mucosal architecture PICaSSO vascular architecture Microerosion /erosions Sparse vessels Intramucosal bleeding. Elongtaed crypts Ulcers Crowded vessels Intraluminal bleeding Roundish dilated vessels Scars

20 Diagnostic accuracy of PIcASSO score Iacucci et al GIE 2017

21 PICASSO MUCOSAL ARCHITECTURE

22 iscan Mucosal Healing Pattern in UC iscan-1 iscan-2 Waterimmersion+zoom Continuous/regular crypts

23 Mucosal Healing Crypts not visible (scar) Scars

24 PICASSO VASCULAR ARCHITECTURE

25 0-Vessels without dilatation C- Sparse (deep) vessels without dilatation iscan 1 iscan2 iscan3

26 I Vessels with dilatation I Micro-erosion 1. Discrete A- Roundish with dilatation Roundish with dilata7on

27 VIDEO 2

28 VIDEO 3 HD iscan 2 iscan 3 Mayo score: No erythema, intact vascular pattern Mayo 0 UCEIS: Vascular pattern: Normal Bleeding: None Erosions and ulcers: None UCEIS: 0 PICaSSO Mucosal: 0- No mucosal defect c) Elongated crypts Vascular: 0- Vessels without dilatation c) Sparse (deep) vessels without dilatation

29 The First Experience with OE-iscan in UC Beyond white light endoscopy : Optical enhancement in conjunction with magnification colonoscopy for the assessment of mucosal healing in Ulcerative Colitis Iacucci et al Endoscopy 2017

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31 Sensitivity, Specificity,Accuracy,PPV & NPV of OE-iscan (relative to histology ECAP & RHI)

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33 The Paddington International virtual ChromoendoScopy ScOre (PICaSSO) in ulcerative colitis exhibits very good inter-rater agreement after computerised module training: a multi-centre study across academic and community practice. Palak J. Trivedi, 1,2,3,4 Ralf Kiesslich, 5 James Hodson, 4 Neeraj Bhala, 3 Ralph A. Boulton, 3 Rachel Cooney, 3 Xianyong Gui, 6 Tariq Iqbal, 3 Ka-kit Li, 7 Saqib Mumtaz, 8 Shri Pathmakanthan, 3 Mohammed N. Quraishi, 3 Vandana M. Sagar, 1,2 Ashit Shah, 8 Naveen Sharma, 9 Keith Siau, 8 Samuel Smith, 3 Stephen Ward, 10 Monika M. Widlak, 11,12 Raf Bisschops, 13 Subrata Ghosh 3,4,14 and Marietta Iacucci. 3,4,14 GIE 2018 Epub

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35 Summary: The approach to assessment of inflammation in IBD Novel optical virtual chromoendoscopy can better characterise mucosal and vascular pattern and aid the endoscopists to take targeted biopsies Develop and validate new and more precise endoscopic scores and relate to histological scores able to assess the full spectrum of inflammatory changes including subtle/ minimal inflammation Novel advanced electronic endoscopic techniques for real time assessment of inflammation, to assess response to treatment. Iacucci et al Gastroenterology 150(4):S129-S130 Iacucci M et al Endoscopy 2015;47:726

36 SURVEILLANCE IBD

37 The multistep endoscopy approach Detection Characterisation Treatment Follow-up

38 How do we detect the colonic lesions? Detection Characterization Treatment Follow-up

39 How do we detect the lesion? Statement 2: When performing surveillance with standard-definition colonoscopy, chromoendoscopy is recommended rather than white-light colonoscopy. (85% agreement; strong recommendation; moderatequality evidence) Statement 3: When performing surveillance with high-definition colonoscopy, chromoendoscopy is suggested rather than white-light colonoscopy. (84% agreement; conditional recommendation; lowquality evidence) SCENIC, Laine et al. Gastroenterology 2015; 148:

40 How do we do surveillance? ECCO statement 8H Colonoscopy surveillance is best performed when ulcerative colitis is in remission, because it is otherwise difficult to discriminate between dysplasia and inflammation on mucosal biopsies ECCO statement 8I Surveillance colonoscopy should take into account local expertise. Chromoendoscopy with targeted biopsies has been shown to increase dysplasia detection rate [EL2]. Alternatively, random biopsies (quadrantic biopsies every 10 cm) and targeted biopsies of any visible lesion should be performed if white light endoscopy is used [EL3]. High-definition endoscopy should be used if available ECCO guidelines Magro et al. J Crohns Colitis 2017; 11:

41 How do we do surveillance? Have optimal bowel preparation- the entire bowel mucosa should be without mucus, pus or stool. Surveillance colonoscopy should be performed in patients with minimal or no inflammation. Withdrawal time and antispasmodic agents have been clearly shown to be associated with improved adenoma detection in non-colitis patients (likely the same in IBD surveillance). Ghosh S, Iacucci M. Can J Gastroenterol. 2013; 29:236. Iacucci M et. al. Inflamm Bowel Dis. 2013; 19:

42 How do we do surveillance? Dye Chromoendoscopy (DCE) is gold standard for the surveillance. Both indigo carmine and methylene blue could be used SCENIC, Laine et al. Gastroenterology 2015; 148:

43 How do we do Dye Chromoendoscopy? Dye Chromoendoscopy Increase detection rate of intraepithelial neoplasia in IBD Characterize better the morphology and delineate margin of lesion

44 How do we do surveillance? Statement 4: When performing surveillance with standard-definition colonoscopy, narrow-band imaging (NBI) is not suggested in place of white-light colonoscopy. (84% agreement; conditional recommendation; lowquality evidence) Statement 5: When performing surveillance with high-definition colonoscopy, narrow-band imaging is not suggested in place of white-light colonoscopy. (80% agreement; conditional recommendation; moderate-quality evidence) SCENIC, Laine et al. Gastroenterology 2015; 148:

45 How do we do surveillance? NBI and CE do not differ significantly for detection of colitis associated dysplasia Given the shorter procedural time and easier applicability, NBI may replace CE in the future for surveillance of long-standing UC. Bisschops R, et al. Gut 2017;

46 How do we do surveillance? In this randomized trial VCE or HD-WLE is not inferior to dye spraying colonoscopy for detection of colonic neoplastic lesions during surveillance colonoscopy. HD-WLE alone was sufficient for detection of dysplasia, adenocarcinoma or all neoplastic lesions. Iacucci M et al Amer J Gastroenterol 2018; 113:

47 How do we characterise the colonic lesions? Detection Characterization Treatment Follow-up

48 How do we characterise the colonic lesions? Paris classification Kudo Pit pattern Characterization Margins Localization SCENIC, Laine et al. Gastroenterology 2015; 148:

49 How do we characterise the colonic lesions? Kaltenbach et al. Gastrointest Endosc 2017; 86:

50 How to characterize the colonic lesions? Kudo Pit pattern Non-Neoplastic Neoplastic Tanaka et al. Gastrointest Endosc 2006; 64:

51 How do we characterise the colonic lesions? Problems with Kudo Pit Pattern: Inflammatory activity may mimic neoplasia Regenerative hyplerplastic villous mucosa is difficult to distinguish from neoplastic pit patterns Serrated sessile adenomas (SSA) often have regular pit pattern-similar appearances as HP Iacucci M et al. Can J Gastroenterol 2014; 28: Sonwalkar S et al. Endoscopy 2006; 38:

52 HD i-scan 3 i-scan 2 Paris Classification Ulceration: Absent Kudo pit pattern: IIIL-IV Margins: Regular Histology: LGD

53 DCE NBI NBI Paris Classification Ulceration: Present Kudo pit pattern: IIO-IIIL-IV Margins: Regular Histology: LGD

54 How do we manage the lesions? Detection Characterization Treatment Follow-up

55 How do we manage the lesions? Endoscopically resectable : Margins of the lesion are identified The lesion appears to be enterely removed Histology confirms the completed removal Biopsies taken from adjagent mucosa to the removed lesion are free of dysplasia SCENIC, Laine et al. Gastroenterology 2015; 148:

56 How do we manage the lesions? Endoscopically resectable : Margins identified Enterely Removed En Block

57 How do we manage the colonic lesions? Endoscopically resectable Snare polypectomy or EMR: consider referral if necessary EMR or ESD; consider referral if necessary Resection should only be attempted by endoscopists skilled in EMR or ESD of flat/depressed lesions Biopsies takene of the flat endoscopically normal-appearing mucosa surrounding the resection site are placed in a separate container Tattoo site Review histology of resected lesion and biopsies of surrounding mucosa Yes No Close endoscopic surveillance at 1-6 and 12 months, with biopsies of resection site ASGE Guidelines, Gastrointestinal Endoscopy 2015; 81: Incomplete resection Repeat colonoscopy with attempted resection

58 How do we manage the colonic lesions? Suggested indications fro ESD in nonpolypoid colorectal dysplasia Patient selection Age >50 years; ESD in younger and healthy patients may not be suitable given the potential risk for metachronous lesions Colonoscopy shows remission to mild activity (Mayo 0 or 1) disease activity Patients with primary sclerosing cholangitis should be considered to have higher risk for colorectal cancer Number of lesions Macroscopic features Surface pattern of lesion not suitable for endoscopic resection Pathologic features Preferably with single lesion > 10 mm Lesion with clearly demarcated border Lesion without large depression Lesion with VN (invasive cancer) surface pattern Low-grade to high-grade dysplasia Sessile serrated adenoma/polyp with/out dysplasia Complete removal Well-differentiated carcinoma with invasion depth less than 1000 µm (in Japan) Not indicated: signet cell carcinoma and poorly differentiated carcinoma Follow-up Repeated colonoscopy within 6 to 12 months Biopsy scar site and surrounding tissue Team for endoscopipc resection of dysplasia in IBD Management of NP-CRD requires a team approach comprising not only an experienced endoscopy team but also a GI pathologist and an IBD surgeon Soetikno et al. Gastroenterol Endoscopy 2018; 87:

59 How do we manage the colonic lesions? Rates of metachronous dysplasia after ESD for non polypoid colorectal dysplasia Study Metachrounous dysplasia Follow-up, months (median) Pathologic features and number of lesions Iacopini et al 3/8 (38%) 24 LGD: 3 Suzuki et al 3/27 (11%) 33 Dysplasia: 3 Kinoshita et al 1/20 (5%) 21 HGD: 1 Summary 7/55 (135; 95% CI, 6%-25%) 27 Metachronous dysplasia is defined as further dysplasia occurring away from the ESD resection site. Soetikno et al. Gastroenterol Endoscopy 2018; 87:

60 HD DCE Paris Classification: IIa

61 Severe Fibrosis

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63 How do we follow-up the colonic lesions? Detection Characterization Treatment Follow-up

64 Summary: The approach to surveillance colonoscopy in IBD Dye Chromoendoscopy should be adopted in the daily practice as standard endoscopic technique for colonic lesions detection in IBD Selective virtual and dye chromoendoscopy with new optical enhancement diagnosis scopes may help to characterize the colonic lesions Optical enhancement diagnosis with or without magnification to assess margins and plan endoscopic therapeutic strategy. Local resection such as EMR or ESD in selected cases may be used to spare total colectomy. A distinct border of the lesion must be recognized for local resection Endoscopists must be dedicated to IBD patients for best diagnostic and therapeutic management. Laine L et al. Gastroenterology : Sugimoto et al GIE 2017;85:639

65 THE NEW FUTURE AT THE HORIZON

66 Endomicroscopy Mini probe Standard endoscope Field of view: 500x500µm Range: 0-250µm Lateral resolution: <1µm Kiesslich et al., Gastroenterology 2004

67 Normal colonic surface epithelium IMAGE CONTENT: Single crypt on the mucosal surface, with dark lumenal opening and mucus in the centre of each crypt. Goblet Cell Columnar Epithelial Cell Crypt Lumen

68 Confocal colon Normal crypt -daisy- Blood cells in lamina propria vessels

69 Atreya R & Neurath MF. Curr Opin Gastroenterol 2016 Molecular imaging aims at the identification and characterization of mucosal features because of their molecular composition rather than their morphological structure

70 Atreya R, et al. Nature Med 2014 Molecular imaging & response to Anti-TNFα ADALIMUMAB

71 Atreya R, et al. Nature Med 2014 Molecular imaging & response to Anti-TNFα ADALIMUMAB FITC FITC FITC FITC Fluorescein Isothiocyanate labeling

72 Atreya R, et al. Nature Med 2014 Molecular imaging & response to Anti-TNFα Ex vivo confocal imaging of mucosal specimens from patients with Crohn s disease incubated with FITC-adalimumab FITC FITC FITC FITC Fluorescein Isothiocyanate labelled Adalimumab

73 Adapted from Prof. Markus F Neurath Molecular imaging & response to Anti-TNFα In vivo colonic staining with FITC-adalimumab and confocal imaging in CD patients before anti-tnf therapy FITC FITC FITC FITC Fluorescein Isothiocyanate labelled Adalimumab

74 Rath T& Neurath MF. GIE 2017 Molecular imaging Endoscopic imaging Labelled antibody FITC-labelled antibody Antiα4/β7

75 Infrastructure

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77 Maneuverability Normal Observation Magnifying Observation Endocyto Observation Similar maneuver as conventional zoom scopes Normal Observation Magnifying Observation Endocyto Observation /5/19

78 Principle of Endocyto observation Distal end of ECS scope Light guide Objectiv e lens Scattered light Tissue Dye stained tissue /5/19

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80 The Future It s not about predicting histology It is about seeing histology

81 THANK YOU