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

EQUIPEQUIPTraining session 2Training session 2

Introduction to dye and Introduction to dye and optical staining and optical staining and

classification methodsclassification methods

Session 1 overviewSession 1 overview

EQUIP goals reviewEQUIP goals review

Session 2 goalsSession 2 goals

Paris classification system reviewParis classification system review

Dye and optical staining methods Dye and optical staining methods Role in detectionRole in detection Role in classification; Kudo & SanoRole in classification; Kudo & Sano

Understand settings they are useUnderstand settings they are use Utilize to differentiate neoplastic potential Utilize to differentiate neoplastic potential

The Paris ClassificationThe Paris Classification

Snare polypectomy

EMR en bloc Or piecemeal

EMR en bloc,ESD, or surgery

Adenoma

High gradeadenoma

Carcinoma

Histology Resection

I-p

I-s

II-a -b

III

mixed

-c

Paris ClassificationParis Classification

I-p (pedunculated) I-s (sessile) II-a (flat elevated)

II-b (flat flat) III (flat ulcerated)IIc (flat depressed)

Dye and optical “staining” Dye and optical “staining”

ChromoendoscopyChromoendoscopy Detection Detection Classification: Classification:

Kudo pit patternsKudo pit patterns

Narrow band imagingNarrow band imaging DetectionDetection Classification:Classification:

Sano capillary patternSano capillary pattern

Classification methods test casesClassification methods test cases

ChromoendoscopyChromoendoscopy

DetectionDetection Does pan-chromoendsocopy increase Does pan-chromoendsocopy increase

adenoma detection?adenoma detection?

ClassificationClassification Kudo pit patternsKudo pit patterns

Meta-analysis of Pan Chromo in Meta-analysis of Pan Chromo in Average Risk PatientsAverage Risk Patients

4 Randomized Controlled Trials4 Randomized Controlled Trials

Odds RatioOdds Ratio 95% CI95% CI

Patients Patients with any with any adenomaadenoma

1.611.61 1.24-2.091.24-2.09

3 or more 3 or more adenomasadenomas

2.552.55 1.49-4.361.49-4.36

Brown; Cochrane DB Syst Rev, 2007;4:6439

Kudo pit patternsKudo pit patternsObjectivesObjectives

UnderstandUnderstand What Kudo pit patterns representWhat Kudo pit patterns represent Use of dye staining to observe pit patternsUse of dye staining to observe pit patterns

Use Kudo pit patterns to:Use Kudo pit patterns to: Distinguish neoplasia from non-neoplasiaDistinguish neoplasia from non-neoplasia Differentiate neoplastic lesions in terms of Differentiate neoplastic lesions in terms of

degree of dysplasia degree of dysplasia


Developed for use in Developed for use in chromoendoscopychromoendoscopy Indigo carmine remains in depressions Indigo carmine remains in depressions

(pits)(pits) The violet dyes actually stain the The violet dyes actually stain the

mucosamucosa Results not replicated with NBI in Results not replicated with NBI in

absence of dye staining.absence of dye staining.


TechniqueTechnique Feces & mucous must be washed away Feces & mucous must be washed away

before stainingbefore staining 2 – 7ml applied to lesion, excess 2 – 7ml applied to lesion, excess

suctioned before observationsuctioned before observation Spray catheter or syringe injection for indigo Spray catheter or syringe injection for indigo

carminecarmine Violet dyes require 30 – 60 seconds to Violet dyes require 30 – 60 seconds to

stain prior to observationstain prior to observation

KudoKudo

Pits = openings of the colonic crypts Pits = openings of the colonic crypts Pit pattern = arrangement of openings on Pit pattern = arrangement of openings on

mucosal surfacemucosal surface Pit patterns categoriesPit patterns categories

Normal mucosa – pit pattern INormal mucosa – pit pattern I Hyperplastic – pit pattern IIHyperplastic – pit pattern II Adenomatous – pit pattern III-L Adenomatous – pit pattern III-L High grade adenoma: pit pattern III-s, and IVHigh grade adenoma: pit pattern III-s, and IV Cancerous – pit pattern VCancerous – pit pattern V

Kudo non-neoplastic patternsKudo non-neoplastic patternsI & III & II

Type I: Normal mucosaType I: Normal mucosa Roundish pits with Roundish pits with regularregular distribution distribution Represent Represent straight, non-branching cryptsstraight, non-branching crypts

Type II: HyperplasticType II: Hyperplastic Large star-like or “onion”-like pits, Large star-like or “onion”-like pits, regularregular Represent Represent straight, non-branching cryptsstraight, non-branching crypts

Kudo neoplastic patternsKudo neoplastic patternsIII-L : Adenomatous lesionsIII-L : Adenomatous lesions

III-L: Adenoma (low-grade)III-L: Adenoma (low-grade) Tubular or round Tubular or round eLongatedeLongated pits pits Pits are Pits are Larger Larger than normalthan normal

Non-neoplasticType II: Hyperplastic

NeoplasticType III-L: Adenoma

Large, star like (or onion)crypts.Regular pattern

Tubular or round, elongated, large pits.


Kudo neoplastic patternsKudo neoplastic patternsIII-s, IV: High grade lesionsIII-s, IV: High grade lesions

III-s: III-s: Compactly arranged tubular (or round) pits Compactly arranged tubular (or round) pits Pits are Pits are SmallerSmaller than normal than normal Tend to be depressed lesionsTend to be depressed lesions

IV: IV: Pits look Pits look branched or gyrus likebranched or gyrus like Often have a focal cancer Often have a focal cancer

Non-neoplasticType II: Hyperplastic

NeoplasticType III-s: High grade lesion

Large, star like (or onion)crypts.Regular pattern

Compact, smaller than normal pits.


AdenomaType III-L:

Advanced adenomaType V: High grade lesion

Tubular, elongated, large pits. Pits look branched or gyrus like


AdenomaType III-L:

Advanced adenomaType III-s: High grade lesion

Tubular, elongated, large pits. Pits look branched or gyrus like


Kudo neoplastic patternsKudo neoplastic patternsV: CarcinomasV: Carcinomas

V: CancerV: Cancer Irregular pit pattern; ViIrregular pit pattern; Vi Advanced cancers (Vn) may be rough & Advanced cancers (Vn) may be rough &

ulceratedulcerated May be devoid of pits or “non-structural” May be devoid of pits or “non-structural”

patternpattern

Kudo Pit PatternsKudo Pit Patterns

I

II

IIIL

IIIs

IV

V

The Kudo ClassificationThe Kudo ClassificationPit PatternsPit Patterns

Nothing

EMR en bloc Or piecemeal

EMR en bloc,ESD, or surgery

Hyperplastic

High gradeadenoma

Carcinoma

Snare polypectomy

Adenoma

Histology ManagementI

II

III-L

III-S

IV

V

KudoKudo

Sensitivity/specificity for predictionSensitivity/specificity for prediction

Narrow band imagingNarrow band imaging

DetectionDetection How can NBI be used in detection?How can NBI be used in detection? Does NBI increase adenoma detection?Does NBI increase adenoma detection?

ClassificationClassification Sano capillary patternsSano capillary patterns

overviewoverview

Does NBI Increase Does NBI Increase Adenoma Adenoma DetectionDetection

Probably Probably (compared to standard def. white light, but not (compared to standard def. white light, but not

HD white light)HD white light)

Does not increase procedure timeDoes not increase procedure time

Does NBI Increase Adenoma Does NBI Increase Adenoma DetectionDetection

Systematic Review: Randomized Systematic Review: Randomized TrialsTrials

StudyStudy Pts with Pts with adenoma adenoma NBINBI

Pts with Pts with adenomadenoma WLEa WLE

adenoma/ptadenoma/pt

NBINBIadenoma/adenoma/ptpt

WLEWLE

O.R. O.R.

NBI vs WLENBI vs WLE

Rex 2007Rex 2007

N=217N=21765%65% 67%67% 1.861.86 1.821.82 0.90 (0.61-0.90 (0.61-

1.34)1.34)

Adler Adler 20072007

N= 198N= 198

23%23% 17%17% 0.330.33 0.260.26 1.27 (0.88-1.27 (0.88-1.84)1.84)

Inoue Inoue 20082008

N=122N=122

42%42% 34%34% 0.840.84 0.550.55 1.55 (1.14-1.55 (1.14-2.11)2.11)

PooledPooled 44%44% 41%41% 1.061.06 0.960.96 1.23 (0.93-1.23 (0.93-1.61)1.61)

Van den Broek et al. GIE 2009;69:124

Does NBI Increase Adenoma Does NBI Increase Adenoma DetectionDetection

Back to Back TrialsBack to Back Trials

TrialTrial Adenoma/ptAdenoma/pt

NBINBIAdenoma/ptAdenoma/pt

WLEWLE

Rastogi 2008Rastogi 2008

N=40N=400.730.73 1.081.08

East 2007East 2007

N=62N=620.340.34 0.400.40

Gross [in press]Gross [in press]

N=91N=910.250.25 0.34*0.34*

NBI vs White Light

Tandem Double Blind Trial

Standardfirst

(n=44)

NBIfirst

(n=47)

No. of patients with > 1 adenoma

0 5 10 15 20

Standard (Std)

11/19

58%

NBI

8/19

42%

NBI

16/19

84%

Std

3/19

16%

‘Miss rate’: Standard: 42% NBI: 16% p = 0.003

Gross, Wallace et al. Gastro/DDW 2008

Adenomas per patient

Sano capillary patternsSano capillary patterns Developed with Narrow band imagingDeveloped with Narrow band imaging

Narrow spectrum allows visualization of Narrow spectrum allows visualization of capillary pattern in superficial layercapillary pattern in superficial layer

Capillary vessels appear brown on NBICapillary vessels appear brown on NBI Capillary pattern around glands change with Capillary pattern around glands change with

neoplasia neoplasia 3 capillary pattern types 3 capillary pattern types

CP I: Normal mucosa or hyperplastic lesionCP I: Normal mucosa or hyperplastic lesion CP II: Adenomatous lesionCP II: Adenomatous lesion CP III: Cancer (further subdivided into A & B)CP III: Cancer (further subdivided into A & B)

Sano capillary patternsSano capillary patternsCP ICP I

CP I: Normal mucosa and CP I: Normal mucosa and hyperplastic polypshyperplastic polyps Hyperplastic lesions appear light brown Hyperplastic lesions appear light brown

on NBIon NBI Messed capillaries not seen or faint, Messed capillaries not seen or faint, If MC seen (large lesions) will be in If MC seen (large lesions) will be in

a regular honeycomb patterna regular honeycomb pattern

Sano capillary patternsSano capillary patternsCP IICP II

CP II: Adenomatous lesionsCP II: Adenomatous lesions Adenomas appear dark brown on NBIAdenomas appear dark brown on NBI MC clearly seen MC clearly seen Round, oval or honeycomb patternRound, oval or honeycomb pattern Pattern may be elongated with Pattern may be elongated with

larger diameterlarger diameter

Sano capillary patternsSano capillary patternsCP IIICP III

CP III: Cancerous lesionsCP III: Cancerous lesions MC clearly seenMC clearly seen Increased density of microvesselsIncreased density of microvessels Unevenly sized thick capillariesUnevenly sized thick capillaries Branching and Branching and irregularityirregularity

Further subdivided based on depth of Further subdivided based on depth of invasioninvasion

CPIII A: Sub-mucosal invasion <1000CPIII A: Sub-mucosal invasion <1000 CPIII B: Sub-mucosal invasion > 1000 CPIII B: Sub-mucosal invasion > 1000

CP I:Normal mucosaHyperplastic lesions

CP II:Adenomatous lesions

Meshed capillary vessels （‐ ）

Meshed capillary vessels （ + ）

Sano capillary patternsSano capillary patterns


Differential diagnosis of small lesionsDifferential diagnosis of small lesions 92 eligible patients; 150 lesions <10mm92 eligible patients; 150 lesions <10mm

39 (26%) hyperplastic39 (26%) hyperplastic 111 (74%) adenoma111 (74%) adenoma Invasive cancers excludedInvasive cancers excluded

Magnifying NBI (no dye)Magnifying NBI (no dye) Endoscopic diagnosis (neoplastic vs. non- )Endoscopic diagnosis (neoplastic vs. non- )

Based on presence or absence of MCBased on presence or absence of MC Accuracy compared to pathologic diagnosis Accuracy compared to pathologic diagnosis

Sano capillary patternsSano capillary patternsDifferential diagnosis of small Differential diagnosis of small

lesions (I vs. II)lesions (I vs. II)

NeoplastiNeoplasticc

Non-Non-neoplasticneoplastic

MC vessels MC vessels (+)(+) 107107 33

MC vessels (-)MC vessels (-) 44 3636

MC vessels by NBI and histologic examination

Sensitivity: 96.4%, Specificity: 92.3%, Accuracy: 95.3%,NPV (negative predictive value): 90.0%, PPV (positive predictive value): 97.3%

MC, meshed capillaries

CP II:Adenomatous lesions

CP III:Cancerous lesions

Round, oval, honeycomb likepattern. May be elongated and large diameter.

No honeycomb pattern.Irregularity of size, complex branching, disruption, or irregular winding.



Prediction of early colorectal Prediction of early colorectal neoplasianeoplasia 104 patients with 139 lesions104 patients with 139 lesions Only CP II or CP III lesions includedOnly CP II or CP III lesions included

Sano capillary patternsSano capillary patternsPrediction of neoplasia (II vs. Prediction of neoplasia (II vs.

III)III)Histological diagnosisHistological diagnosis

LGDLGD HGD/ invasive HGD/ invasive CA CA

CP II CP II (n (n =103)=103)

100100 33

CP III CP III (n = 31) (n = 31) 33 2828


LGD, low grade dysplasia; HGD, high grade dysplasia

Sano capillary patternsSano capillary patternsCP III types: depth of CP III types: depth of

invasioninvasion CPIII-A: Cancerous lesion; (pSM & pSM1)CPIII-A: Cancerous lesion; (pSM & pSM1)

MC clearly seen,MC clearly seen,

CPIII-B: Cancerous lesion; (pSM2-3)CPIII-B: Cancerous lesion; (pSM2-3) MC clearly seen,MC clearly seen,

CP III A:Cancerous lesions

CP III B:Cancerous lesions

Lack of uniformityLack of uniformityHigh density of High density of capillary vesselscapillary vessels

Nearly avascular or loose Nearly avascular or loose micro capillary vesselsmicro capillary vessels


Meshed capillary vessels characterized by: blind ending, branching and curtailed irregularly


Diagnostic accuracy of depth of Diagnostic accuracy of depth of invasioninvasion• 127 patients; 130 lesions CP type 127 patients; 130 lesions CP type

IIIA/IIIBIIIA/IIIB• Endoscopic (IIIA) or surgical resection Endoscopic (IIIA) or surgical resection

(IIIB)(IIIB)

Ikematsu et al, BMC GastroenteroIkematsu et al, BMC Gastroenterology 2010, 10:33logy 2010, 10:33

Sensitivity, specificity and Sensitivity, specificity and diagnostic accuracy of CP Type diagnostic accuracy of CP Type

IIIIIIHistological diagnosisHistological diagnosis

M*, SM-M*, SM-superficial superficial (SM1)**(SM1)**

SM-deep (SM 2-SM-deep (SM 2-3)3)##

CP type IIIACP type IIIA 8686 55CP type IIIBCP type IIIB 1111 2828


*intramucosal cancer, ** SM superficial invasion (<1000 μm), # SM deep invasion (≥ 1000 μm)

I II IIIA

Endoscopic findings

IIIB

Meshed capillary vessels （‐ ）

• Meshed capillary 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

Capillary characteristics

Test cases.Test cases.

Describe the following polyps in Describe the following polyps in terms of:terms of: Paris shapeParis shape Kudo (chromo) or Sano (NBI)Kudo (chromo) or Sano (NBI)

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

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