1. EQUIP Training session 2
Introduction to dye and optical staining and classification methods

2. Session 1 overview
EQUIP goals review

3. Session 2 goals Paris classification system review
Dye and optical staining methods
Role in detection
Role in classification; Kudo & Sano
Understand settings they are use
Utilize to differentiate neoplastic potential
By the end of this session, participants will be understand the three major classification systems (Paris, Kudo, Sano), understand the settings in which they are used, understand the utility each has in detection and classification and show proficiency in their application

4. The Paris Classification
Snare
polypectomy
EMR en bloc
Or piecemeal
EMR en bloc,
ESD, or surgery
Adenoma
High grade
adenoma
Carcinoma
Histology Resection
I-p
I-s
II-a -b -c
Paris class if probably the most recognized and used. It refers to the morphology of a lesion.
III
mixed

5. Paris Classification I-p (pedunculated) I-s (sessile)
II-a (flat elevated)
II-b (flat flat)
IIc (flat depressed)
III (flat ulcerated)

6. Dye and optical “staining”
Chromoendoscopy
Detection
Classification:
Kudo pit patterns
Narrow band imaging
Sano capillary pattern
Classification methods test cases

7. Chromoendoscopy Detection Classification
Does pan-chromoendsocopy increase adenoma detection?
Classification
Kudo pit patterns

8. Pan Chromo in Average Risk Persons A Randomized Controlled Trial
Lapalus, Endoscopy, 2006;38:444

9. Chromo in Average Risk N = 292 Chromo (146) Standard (146)
Pts with Adenomas
40%
36% (p=0.47)
Total adenomas
115
(p= 0.18)
Total
Hyperplastic
110
(p=0.03)
Colonoscopy time
27 min [14-75]
18 [8-60] (p<0.001)

10. Meta-analysis of Pan Chromo in Average Risk Patients
4 Randomized Controlled Trials
Odds Ratio
95% CI
Patients with any adenoma
1.61
3 or more adenomas
2.55
Brown; Cochrane DB Syst Rev, 2007;4:6439

11. Does Routine “Pan Chromoendoscopy” Increase Adenoma Detection?
Yes, but with longer procedure times

12. Kudo pit patterns Objectives
Understand
What Kudo pit patterns represent
Use of dye staining to observe pit patterns
Use Kudo pit patterns to:
Distinguish neoplasia from non-neoplasia
Differentiate neoplastic lesions in terms of degree of dysplasia

13. Kudo pit patterns Developed for use in chromoendoscopy
Indigo carmine remains in depressions (pits)
The violet dyes actually stain the mucosa
Results not replicated with NBI in absence of dye staining.

14. Kudo pit patterns Technique
Feces & mucous must be washed away before staining
2 – 7ml applied to lesion, excess suctioned before observation
Spray catheter or syringe injection for indigo carmine
Violet dyes require 30 – 60 seconds to stain prior to observation

15. Kudo Pits = openings of the colonic crypts
Pit pattern = arrangement of openings on mucosal surface
Pit patterns categories
Normal mucosa – pit pattern I
Hyperplastic – pit pattern II
Adenomatous – pit pattern III-L
High grade adenoma: pit pattern III-s, and IV
Cancerous – pit pattern V

16. Kudo non-neoplastic patterns I & II
Type I: Normal mucosa
Roundish pits with regular distribution
Represent straight, non-branching crypts
Type II: Hyperplastic
Large star-like or “onion”-like pits, regular
Explain

17. Kudo neoplastic patterns III-L : Adenomatous lesions
III-L: Adenoma (low-grade)
Tubular or round eLongated pits
Pits are Larger than normal
Explain

18. Kudo pit patterns Non-neoplastic Neoplastic Type II: Hyperplastic
Type III-L: Adenoma
Non-neoplastic lesions can be distinquished from neoplastic lesions based on the shape, size and regularity of the crypt.
Compare the Kudo II Hyperplastic lesion shown on the left with the Type III-L adenoma on the right. Notice that the crypts become elongated and larger in the adenoma compared to the hyperlastic lesion.
Tubular or round, elongated, large pits.
Large, star like (or onion)
crypts.
Regular pattern

19. Kudo neoplastic patterns III-s, IV: High grade lesions
Compactly arranged tubular (or round) pits
Pits are Smaller than normal
Tend to be depressed lesions
IV:
Pits look branched or gyrus like
Often have a focal cancer
Explain

20. Kudo pit patterns Non-neoplastic Neoplastic Type II: Hyperplastic
Type III-s: High grade lesion
Non-neoplastic lesions can be distinquished from neoplastic lesions based on the shape, size and regularity of the crypt.
Compare the Kudo II Hyperplastic lesion shown on the left with the Type III-L adenoma on the right. Notice that the crypts become elongated and larger in the adenoma compared to the hyperlastic lesion.
Compact, smaller than normal pits.
Large, star like (or onion)
crypts.
Regular pattern

21. Kudo pit patterns Adenoma Advanced adenoma Type III-L:
Type V: High grade lesion
Neoplastic lesions can be further distinguished as adenomatous vs. cancerous based on the organization of the MC structure.
Here the question doesn’t become whether the Meshed capillaries are present but rather the organization of the capillary pattern around the glands
Pits look branched or gyrus like
Tubular, elongated, large pits.

22. Kudo pit patterns Adenoma Advanced adenoma Type III-L:
Type III-s: High grade lesion
Neoplastic lesions can be further distinguished as adenomatous vs. cancerous based on the organization of the MC structure.
Here the question doesn’t become whether the Meshed capillaries are present but rather the organization of the capillary pattern around the glands
Pits look branched or gyrus like
Tubular, elongated, large pits.

23. Kudo neoplastic patterns V: Carcinomas
V: Cancer
Irregular pit pattern; Vi
Advanced cancers (Vn) may be rough & ulcerated
May be devoid of pits or “non-structural” pattern

24. Kudo Pit Patterns
IIIs IV V I II
IIIL

25. The Kudo Classification Pit Patterns
Histology Management
Hyperplastic
Nothing II
Snare
polypectomy
III-L
Adenoma
III-S
High grade
adenoma
EMR en bloc
Or piecemeal IV
EMR en bloc,
ESD, or surgery V
Carcinoma

26. Kudo
Sensitivity/specificity for prediction

27. Narrow band imaging Detection Classification
How can NBI be used in detection?
Does NBI increase adenoma detection?
Classification
Sano capillary patterns
overview

28. Does NBI Increase Adenoma Detection
Probably
(compared to standard def. white light, but not HD white light)
Does not increase procedure time

29. Does NBI Increase Adenoma Detection
White Light
NBI
Hyperplasia Adenoma Advanced Ad

30. Does NBI Increase Adenoma Detection Systematic Review: Randomized Trials
Study
Pts with adenoma NBI
Pts with adenoma WLE
adenoma/pt
NBI
WLE
O.R.
NBI vs WLE
Rex 2007
N=217
65%
67%
1.86
1.82
0.90 ( )
Adler 2007
N= 198
23%
17%
0.33
0.26
1.27 ( )
Inoue 2008
N=122
42%
34%
0.84
0.55
1.55 ( )
Pooled
44%
41%
1.06
0.96
1.23 ( )
Van den Broek et al. GIE 2009;69:124

31. Does NBI Increase Adenoma Detection Back to Back Trials
Adenoma/pt
NBI
WLE
Rastogi 2008
N=40
0.73
1.08
East 2007
N=62
0.34
0.40
Gross [in press]
N=91
0.25
0.34*

32. Mayo Clinic, Jacksonville, FL, USA
A PROSPECTIVE RANDOMIZED BACK-TO-BACK TRIAL COMPARING NARROW BAND IMAGING TO CONVENTIONAL COLONOSCOPY FOR ADENOMA DETECTION
Gross SA, Buchner AM, Cangemi JR, Wolfsen HC, DeVault KR, Crook J, Picco MF, Loeb DS, Woodward TA, Raimondo M, Wallace MB
Mayo Clinic, Jacksonville, FL, USA

33. Tandem Double Blind Trial
NBI vs White Light
Tandem Double Blind Trial
Adenomas per patient
Standard (Std)
11/19
58%
NBI
8/19
42%
Standard
first
(n=44)
‘Miss rate’:
Standard: 42%
NBI: %
p = 0.003
NBI
16/19
84%
Std
3/19
16%
NBI
first
(n=47)
Gross, Wallace et al.
Gastro/DDW 2008
No. of patients with > 1 adenoma

34. Sano capillary patterns
Developed with Narrow band imaging
Narrow spectrum allows visualization of capillary pattern in superficial layer
Capillary vessels appear brown on NBI
Capillary pattern around glands change with neoplasia
3 capillary pattern types
CP I: Normal mucosa or hyperplastic lesion
CP II: Adenomatous lesion
CP III: Cancer (further subdivided into A & B)

35. Sano capillary patterns CP I
CP I: Normal mucosa and hyperplastic polyps
Hyperplastic lesions appear light brown on NBI
Messed capillaries not seen or faint,
If MC seen (large lesions) will be in a regular honeycomb pattern
The first distinction; hyperplastic vs adenoma

36. Sano capillary patterns CP II
CP II: Adenomatous lesions
Adenomas appear dark brown on NBI
MC clearly seen
Round, oval or honeycomb pattern
Pattern may be elongated with larger diameter

37. Sano capillary patterns CP III
CP III: Cancerous lesions
MC clearly seen
Increased density of microvessels
Unevenly sized thick capillaries
Branching and irregularity
Further subdivided based on depth of invasion
CPIII A: Sub-mucosal invasion <1000
CPIII B: Sub-mucosal invasion > 1000

38. Sano capillary patterns
CP I:
Normal mucosa
Hyperplastic lesions
CP II:
Adenomatous lesions
First we’ll look at hyperplastic vs. adenomatous lesions.
When using Sano to make this distinction, the first question is whether you can see the capillary patterns. If they are not visible or only faintly visible then it’s either normal mucosa or a hyperplastic lesion.
If the meshed vessels are clearly visible then what is the pattern?
With current resolution, a honeycomb pattern may be faintly seen in large hyperplastic lesions. However the meshed capillaries in adenomas are very clearly seen and are elongated and large in comparison.
Meshed capillary
vessels （‐）
Meshed capillary
vessels （+）

39. Sano capillary patterns
Differential diagnosis of small lesions
92 eligible patients; 150 lesions <10mm
39 (26%) hyperplastic
111 (74%) adenoma
Invasive cancers excluded
Magnifying NBI (no dye)
Endoscopic diagnosis (neoplastic vs. non- )
Based on presence or absence of MC
Accuracy compared to pathologic diagnosis

40. Sano capillary patterns Differential diagnosis of small lesions (I vs
Sano capillary patterns Differential diagnosis of small lesions (I vs. II)
MC vessels by NBI and histologic examination
Neoplastic
Non-neoplastic
MC vessels (+)
107 3
MC vessels (-) 4 36
Simple distinction between presence or absence of meshed capillaries by NBI had high diagnostic accuracy, negative and positive predictive values, sensitivity and specificity.
Sensitivity: 96.4%, Specificity: 92.3%, Accuracy: 95.3%,
NPV (negative predictive value): 90.0%, PPV (positive predictive value): 97.3%
MC, meshed capillaries

41. Sano capillary patterns
CP II:
Adenomatous lesions
CP III:
Cancerous lesions
Neoplastic lesions can be further distinguished as adenomatous vs. cancerous based on the organization of the MC structure.
Here the question doesn’t become whether the Meshed capillaries are present but rather the organization of the capillary pattern around the glands
No honeycomb pattern.
Irregularity of size, complex branching, disruption, or irregular winding.
Round, oval, honeycomb like
pattern. May be elongated and
large diameter.

42. Sano capillary patterns
Prediction of early colorectal neoplasia
104 patients with 139 lesions
Only CP II or CP III lesions included

43. Sano capillary patterns Prediction of neoplasia (II vs. III)
Histological diagnosis
LGD
HGD/ invasive CA
CP II (n =103)
100 3
CP III (n = 31) 28
Sensitivity: 90.3%, Specificity: 97.1%, Accuracy: 95.5%,
NPV (negative predictive value): 97.1%, PPV (positive predictive value): 90.3%
LGD, low grade dysplasia; HGD, high grade dysplasia

44. Sano capillary patterns CP III types: depth of invasion
CPIII-A: Cancerous lesion; (pSM & pSM1)
MC clearly seen,
CPIII-B: Cancerous lesion; (pSM2-3)
Sano capillary pattern type III are the cancerous lesions. They have been further subdivided into two subtypes based on depth of invasion.

45. Sano capillary patterns
CP III A:
Cancerous lesions
CP III B:
Cancerous lesions
Neoplastic lesions can be further distinguished as adenomatous vs. cancerous based on the organization of the MC structure.
Here the question doesn’t become whether the Meshed capillaries are present but rather the organization of the capillary pattern around the glands
Meshed capillary vessels characterized by:
blind ending, branching and curtailed irregularly
Lack of uniformity
High density of
capillary vessels
Nearly avascular or loose
micro capillary vessels

46. Sano capillary patterns
Diagnostic accuracy of depth of invasion
127 patients; 130 lesions CP type IIIA/IIIB
Endoscopic (IIIA) or surgical resection (IIIB)

47. Sensitivity, specificity and diagnostic accuracy of CP Type III
Histological diagnosis
M*, SM-superficial (SM1)**
SM-deep (SM 2-3)#
CP type IIIA 86 5
CP type IIIB 11 28
Sensitivity: 84.8%, Specificity: 88.7%, Accuracy: 87.7%,
NPV (negative predictive value): 94.5%, PPV (positive predictive value): 71.8%
*intramucosal cancer, ** SM superficial invasion (<1000 μm), # SM deep invasion (≥ 1000 μm)
Ikematsu et al, BMC Gastroenterology 2010, 10:33

48. I II IIIA IIIB Capillary pattern Schema Endoscopic findings
Meshed capillary
vessels （‐）
vessels （+）
Capillary vessel
surrounds mucosal
glands
Meshed capillary vessels characterized by:
blind ending, branching and curtailed irregularly
Lack of uniformity
High density of
capillary vessels
Nearly avascular or loose
micro capillary vessels
Schema
Capillary
pattern
characteristics
In summary, when analyzing a lesion using Sano there are three questions.
Are the meshed capillaries visible?
If visible what is the pattern?
Is the structure organized or disorganized.

49. Test cases. Describe the following polyps in terms of: Paris shape
Kudo (chromo) or Sano (NBI)