update on early gi-cancer · strategy for gi endoscopists: concerning advanced carcinomas, - there...

Update on EARLY GI-cancer

T PonchonE.Herriot HospitalLyon, France

Rationale

Epidemiology

Diagnosis

Treatment

Rationale

Epidemiology

Diagnosis

Treatment

Why do we need, as GI endoscopists, to be concerned by early GI cancer ?

1- Health care improvement

2- Strategy

Health care improvement:

A carcinoma detected at early stage meansbetter prognosis for the patientless cost for the society

* It does mean that we need to screen the whole population

Strategy for GI endoscopists:

Concerning advanced carcinomas,

- there is a increasing impact of chemotherapy (andradiotherapy) and less room for endoscopicpalliationExemples: eso SCC, colonic cancer

- there is an increasing impact of radiology for thediagnosisExemple: MRCP replaced ERCP

Strategy for GI endoscopists:

Concerning advanced carcinomas,

There is a « competition » between oncologists andgastroenterologists for the management ofcases and for fundings

Gastroenterologists and endoscopists must focuson early GI-cancer and claim that the management of early GI-cancer is part of oncology and thefuture of GI oncology.

Rationale

Epidemiology

Diagnosis

Treatment

Are we effective, as GI endoscopists, to find early GI cancer ?

Exemple: gastric carcinoma

Ratio T1/ total gastric carcinomas

Japan 40% Osaka Cancer Registry 98

France 7% Registre bourguignon 02

5y survival

Japan 47% Osaka Cancer Registry 98

Europe 22% IARC 99

USA 19% Bethesda 98

Japan

5 y survival

1975-77 26%1987-89 45%

Why are we late in Occident ?

1- Difference in incidence2- Decreasing incidence3- No limited high risk population4- No symptoms5- Low rate of polypoid lesions6- Difference in endoscopic practice

1- Difference in incidence: nber/year

car colon car gastricJapan 48 000 115 000Europe 186 000 77 000

2- Decreasing incidence 1963 1989

Japan: less 36%, Europe: less 43%

Globocan

France

60 millions inhabitants, 30 millions > 40y1 million upper GI endosc / y6000 new gastric car / y

We have to find 200 new asymptomatic cases/y

We are 2000 gastroenterologists

Each of us does 500 upper GI endoscopyEach of us has to find one superficial gastric car / 10 years orone per 5000 patientsSo 2.5 during our carreer

3- Low role of etiological factors

Atrophic gastritis: 1,8-2,5 (Inoue IJC 90 Sipponen EJGH 94)

Intestinal metaplasia, Helicobacter pyloriGastrectomy, BiermerFamilial types ++++++

Except rare familial types, no high risk population to be screened

4- No specific symptom or no symptom

5- Low ratio of polypoid lesions3223 lésions stade 0 (class. Vienne-JSGE)J Gastroenterol Mass Survey 2002

0-I 6%

0-II a17%

0-IIb

0-IIc 70%

0-III 7%

Adenoma= 10%of gastricneoplasms

0-IIc , sm 1 (M.Sasako)

6- Difference in endoscopic pratice

Japan: standard gastric endoscopy

Exploration and picture zone by zoneWithout (color abnormalities)

then with chromoscopy (pattern abnormalities)Zoom if abnormalityMinimum: 10 minutes

Sensitivity for dg of superf. neoplasm: 81%Hoskova Endoscopy 98

6- Difference in endoscopic pratice

France: standard gastric endoscopy

Mean duration of gastric exploration: 130 sec

Sensitivity for dg of superficial neoplasms ??Certainly << 80%

Japanese endoscopists are better educated and more motivated to find flat lesions than European who are mainly looking for polypoid lesions

Is it also true for colonic cancers or esophageal cancers ?

EsophagealEsophageal carcinomascarcinomas

T1/totalT1/total TmuqTmuq/total/total

J Nat Ca J Nat Ca CenterCenter 42%42% 18%18%JapaneseJapanese enquiriesenquiries 25%25% 6%6%BurgundyBurgundy enquiryenquiry 4%4% 0.8%0.8%

DespiteDespiteprevalenceprevalence ofof esoeso car car BurgundyBurgundy > > JapanJapan

Colonic carcinomas

KUDO S 2003

10357 superficial lesions: adenomas or adenocarcinomas

Adenocar & severe dysplasia: 961 (9.3%)

POURCENTAGE OF CANCERS

Polypoïds5863 (57%)

Flats4218 (41%)

Depressed276 (2.6%)

<5 mm

0%

0,1%

8.1%

6-10

1.3%

0.6%

29.2%

11-15

9.4%

1.1%

68.8%

16-20

17.4%

9.8%

83.3%

>20mm

30.7%

23%

100%

Depressed lesions = « cancer de novo »

diameter

Ca II c Ca II c

Ca II aCa II a

Earlacarcinoma

Japanese endoscopist experience in Europe

Watanabe, Stockholm232 pts with superficial neoplasms

KcFlat lesions 95 (41%) 9 (10%)

Depressed lesions 14 (6%) 6 (43%)

Fujii, Leeds722 consecutive pts, 166 superf neo.

Carpolypoïds 100 (60%) 9 (19%)flats 61 (6%) 7 (11%)depressed 5 (3%) 4 (80%) (1/200 pts)

« If we miss - the flat adenomas, we miss 35% of car- the depressed lesions, we miss 20% of car »

Saitoh 99Japanese observer in an endoscopy unit in Texas

Number of neoplastic lesions: + 125%

Teixeira 2000Brasilian endoscopist, education in Japan

13 depressed lesions found on 3.5y =1 for 100 pts

Why japanese endosc see more lesions than european endosc ?

Education of vision:Small abnormalities of reliefSmall abnormalities of colour +++:

erythroplastic (flat, depressed)or whitish (elevated)

Less lumen inflationAnalysis during peristaltic waveMore accurate analysis of the pattern

Motivation to find small lesions

Rationale

Epidemiology

Diagnosis

Treatment

Diagnosis: How to improve ?

MUCOSA (Patient)

ENDOSCOPEOPERATOR

Diagnosis: How to improve ?

MUCOSA (Patient)

ENDOSCOPEOPERATOR

How to improve ? MUCOSA

1- to select mucosa at risk

2- to make analysis of the mucosa easier

= Screening

Mass Mass screeningscreening ofof colorectal colorectal carcinomacarcinomaexemple: exemple: HemoccultHemoccult II, if positive II, if positive colonoscopycolonoscopy

((mortalitymortality/cancer /cancer decreasesdecreases))

2002

2007:National

IlleIlle--etet--VilaineVilaine

NumberNumber ofof tests: 90877tests: 90877

ComplianceCompliance to test: 54%to test: 54%

ComplianceCompliance to to colonoscopycolonoscopy if test positive: if test positive: 82%82%

NumberNumber ofof detecteddetected cancers: cancers: 207 (61% T1)207 (61% T1)

EsophagealEsophageal squamoussquamous cellcell carcinomacarcinomaSystematicSystematic lugollugol stainingstaining in in highhigh riskrisk ptsptsFrench French studystudy (SFED)(SFED)1098 1098 ptspts, 45 , 45 centerscenters, , systematicsystematic LugolLugol

RATERATE

HistoryHistory ofof ENT cancer: ENT cancer: 393 393 ptspts 6.8% 37% T16.8% 37% T1ChronicChronic pancreatitispancreatitis: : 76 76 ptspts 0%0%AlcoholicAlcoholic cirrhosiscirrhosis: : 220 220 ptspts 3.2%3.2%AlcoholAlcohol--tobaccotobacco abuse: 408 abuse: 408 ptspts 2.4%2.4%

How to improve ? MUCOSA

1- to select mucosa at risk

Only screening of colonic carcinoma and ofesophageal SC carcinoma in ENT patients could be cost effective and should beorganized

= Screening

How to improve ? MUCOSA

1- to select mucosa at risk

2- to make analysis of the mucosa easier

= Screening

= To improve patient tolerance

To improve patient tolerance =- to organize sedation- but also to reduce the need for sedation

in order to reduce cost and constraints

transnasal endoscopy upper GI

capsule

new colonoscopes lower GI

If we also suppress the need for endoscope reprocessing …..

and colonic prep……..

ExampleExample 1:1:nasogastroscopenasogastroscope

VideoVideo 5 mm5 mmoneone plan plan bendingbending

SingleSingle--useuse sheathsheathVision sciencesVision sciences65 cm65 cmoperatingoperating channelchanneldiameterdiameter: 5.1mm : 5.1mm

500 500 ptspts, 10 , 10 centerscenters, , randomizedrandomizedstudystudy oral standard vs oral standard vs nasonaso

0 1 2 3 4

SCORE

Gagging

Bloating

Discomfort

Retching

Sensation asphyxia ORAL

NASAL

P<0.0001P<0.0001

P<0.0001P<0.0001

P<0.0001P<0.0001

P<0.001P<0.001

P<0.0001P<0.0001

P<0.0001P<0.0001

NumberNumber ofof ptspts refusingrefusing anotheranother procedureprocedurein in thethe samesame conditions:conditions:

Oral Oral gastroscopygastroscopy:: 25.2%25.2%

NasogastroscopyNasogastroscopy:: 10.3%10.3%p<0.001p<0.001

500 500 ptspts, 10 , 10 centerscenters, , randomizedrandomizedstudystudy oral standard vs oral standard vs nasonaso

NasogastroscopyNasogastroscopy isis veryvery popularpopular andand consideredconsidered to to bebeveryvery helpfulhelpful in Francein FranceFirstFirst procedureprocedure in Lyon, E.Herriot in Lyon, E.Herriot HospitalHospitalThenThen rapidrapid expansion to Rhôneexpansion to Rhône--Alpes Alpes regionregionandand thenthen to Franceto France

In Lyon,In Lyon,83% 83% ofof upperupper GI diagnostic endoscopiesGI diagnostic endoscopies6 6 nasogastroscopesnasogastroscopes in in E.HerriotE.Herriot HospitalHospital3 3 nasogastroscopesnasogastroscopes in a large in a large privateprivate hospitalhospital

In France, In France, 139 139 nasogastroscopesnasogastroscopes soldsold in 2004in 2004

EliakimEliakim endosc06endosc06«« pillcampillcam »»

Exemple 2: Exemple 2: EsophagealEsophageal videocapsulevideocapsule

Esophageal CapsuleEliakim

Still under evaluation

ExampleExample 33

SelfSelf--propellingpropelling singlesingle--useuse colonoscopecolonoscope

-- AerAer--OO--scopescope-- InvendoInvendo-- ColonosightColonosight-- CathcamCathcam-- ……………………..

Still under evaluation

SOME EXEMPLES SOME EXEMPLES ……..

2 technologies2 technologies

11-- single use single use sheathsheath22-- pneumaticpneumatic advanceadvance

Still under evaluation

Still under evaluation

Diagnosis: How to improve ?

MUCOSA (Patient)

ENDOSCOPEOPERATOR

CHROMOSCOPYCHROMOSCOPYHIGH DEFINITION VIDEOHIGH DEFINITION VIDEOSTRUCTURE ENHANCEMENTSTRUCTURE ENHANCEMENTMAGNIFICATIONMAGNIFICATIONNARROW BAND IMAGING, NARROW BAND IMAGING, IHb color enhancFLUORESCENCEFLUORESCENCEINTERFEROMETRY:INTERFEROMETRY: 10 10 micrommicrom

CONFOCAL MICROSCOPY:CONFOCAL MICROSCOPY: 1 1 micrommicromENDOCYSTOSCOPYENDOCYSTOSCOPYELASTIC SCATTERING:ELASTIC SCATTERING: subcellsubcell

RAMAN SPECTROSCOPY:RAMAN SPECTROSCOPY: molecmolec

????

DIAGNOSIS = 3 DIAGNOSIS = 3 stepssteps

I I trytry to to detectdetect DetectionDetectiononeone lesionlesion

ThereThere isis a a lesionlesion CharacterizationCharacterizationWhatWhat isis itit ??

ItIt isis a a neoplasmneoplasm StagingStagingWhichWhich isis itsits extension ?extension ?

DIAGNOSISDIAGNOSIS

TheThe main main targettarget == improvementimprovement in in detectiondetection

WhyWhy ??firstfirst stepstep, , needneed ++++: ++++: nono alternativealternative

caracterisationcaracterisation = = biopsybiopsy«« opticoptic biopsybiopsy »» isis a a secondarysecondary targettargetstagingstaging = EUS, = EUS, ……. . surgerysurgery

HighHigh grade grade dysplasiadysplasia

Dysplasia

Improvement in detection

WhichWhich are are thethe bestbest candidates ?candidates ?

CHROMOSCOPYCHROMOSCOPYHIGH DEFINITION VIDEOHIGH DEFINITION VIDEOSTRUCTURE ENHANCEMENTSTRUCTURE ENHANCEMENTMAGNIFICATIONMAGNIFICATIONNARROW BAND IMAGINGNARROW BAND IMAGING, , IHb color enhancFLUORESCENCEFLUORESCENCEINTERFEROMETRY:INTERFEROMETRY: 10 10 micrommicrom

CONFOCAL MICROSCOPY:CONFOCAL MICROSCOPY: 1 1 micrommicromENDOCYSTOSCOPYENDOCYSTOSCOPYELASTIC SCATTERING:ELASTIC SCATTERING: subcellsubcell

RAMAN SPECTROSCOPY:RAMAN SPECTROSCOPY: molecmolec

Conventional

NBI

Spectrum

NBI

Indigo carmine

CHROMOSCOPYCHROMOSCOPYHIGH DEFINITION VIDEOHIGH DEFINITION VIDEOSTRUCTURE ENHANCEMENTSTRUCTURE ENHANCEMENTMAGNIFICATIONMAGNIFICATIONNARROW BAND IMAGINGNARROW BAND IMAGING, , IHb color enhancFLUORESCENCEFLUORESCENCEINTERFEROMETRY:INTERFEROMETRY: 10 10 micrommicrom

CONFOCAL MICROSCOPY:CONFOCAL MICROSCOPY: 1 1 micrommicromENDOCYSTOSCOPYENDOCYSTOSCOPYELASTIC SCATTERING:ELASTIC SCATTERING: subcellsubcell

RAMAN SPECTROSCOPY:RAMAN SPECTROSCOPY: molecmolec

Juntendo University

AutofluorescenceAutofluorescenceOlympusOlympus AFI ColonAFI Colon

AFI

AFI

AutofluorescenceAutofluorescenceOlympusOlympus AFI AFI BarrettBarrettKara GIE 05Kara GIE 05

©© AMC AmsterdamAMC Amsterdam

Kara AMC

CHROMOSCOPYCHROMOSCOPYHIGH DEFINITION VIDEOHIGH DEFINITION VIDEOSTRUCTURE ENHANCEMENTSTRUCTURE ENHANCEMENTMAGNIFICATIONMAGNIFICATIONNARROW BAND IMAGINGNARROW BAND IMAGING, , IHb color enhancFLUORESCENCEFLUORESCENCEINTERFEROMETRY:INTERFEROMETRY: 10 10 micrommicrom

CONFOCAL MICROSCOPY:CONFOCAL MICROSCOPY: 1 1 micrommicromENDOCYSTOSCOPYENDOCYSTOSCOPYELASTIC SCATTERING:ELASTIC SCATTERING: subcellsubcell

RAMAN SPECTROSCOPY:RAMAN SPECTROSCOPY: molecmolec

Toopunctual

DIAGNOSIS = 3 DIAGNOSIS = 3 stepssteps

I I trytry to to detectdetect DetectionDetectiononeone lesionlesion

ThereThere isis a a lesionlesion CharacterizationCharacterizationWhatWhat isis itit ??

ItIt isis a a neoplasmneoplasm StagingStagingWhichWhich isis itsits extension ?extension ?

CHROMOSCOPYCHROMOSCOPYHIGH DEFINITION VIDEOHIGH DEFINITION VIDEOSTRUCTURE ENHANCEMENTSTRUCTURE ENHANCEMENTMAGNIFICATIONMAGNIFICATIONNARROW BAND IMAGING, NARROW BAND IMAGING, FLUORESCENCEFLUORESCENCE

INTERFEROMETRYINTERFEROMETRY

CONFOCAL MICROSCOPYCONFOCAL MICROSCOPYENDOCYSTOSCOPYENDOCYSTOSCOPYELASTIC SCATTERINGELASTIC SCATTERING

RAMAN SPECTROSCOPYRAMAN SPECTROSCOPY

Detection

Characterization

CHROMOSCOPYCHROMOSCOPYHIGH DEFINITION VIDEOHIGH DEFINITION VIDEOSTRUCTURE ENHANCEMENTSTRUCTURE ENHANCEMENTMAGNIFICATIONMAGNIFICATIONNARROW BAND IMAGING, NARROW BAND IMAGING, FLUORESCENCEFLUORESCENCE

INTERFEROMETRYINTERFEROMETRY

CONFOCAL MICROSCOPYCONFOCAL MICROSCOPYENDOCYSTOSCOPYENDOCYSTOSCOPYELASTIC SCATTERINGELASTIC SCATTERING

RAMAN SPECTROSCOPYRAMAN SPECTROSCOPY

Détection

Characterization

Adenoma

Kiesslich

Colonic cancer

Kiesslich

DetectionDetection CharacterizationCharacterization

StagingStaging

Finally…….

Rationale

Epidemiology

Diagnosis

Treatment

Treatment of early GI cancer

We have to manage the risk of recurrence, ofmetachronous lesion, of lymph node, …

We need to apply the same principles as used in surgery

Treatment of early GI cancer

First principleRESECTION >>> TUMOR DESTRUCTION

(PDT, APC, ……)

Specimen for histopathology

ANALYZIS of the SPECIMEN

TO RECONSIDER SURGERYmain advantage on methodsbased on tumor destruction

STRETCHING ON A BOARD WITH PINS

1- Complete resection ?laterally and in depth

2- Invasiveness of carcinoma ?

Tumor

Generator of radiofrequency

Electrodes

OneOne exception to exception to thisthis rulerule ??BARRxBARRx

After tt

Swine, Ganz, 10 J/cm2

Prior tt

BARRxBARRx: : GanzGanz, , SharmaSharma DDW 05DDW 05

32 32 ptspts: : BarrettBarrett, , nono dysplasiadysplasia1 sec ablation, 10 J/cm21 sec ablation, 10 J/cm2nono residualresidual intestinal intestinal metaplasiametaplasia (357 biopsies)(357 biopsies)nono stenosisstenosis

Second principle

Complete resectionOne pieceSecurity margin

CompleteComplete resectionresection, , securitysecurity marginmargin

In situ carIn situ car

Invasive carInvasive car

PiecePiece--mealmeal to to bebe avoidedavoided

MucosalMucosal resectionresection+/+/-- piecepiece mealmeal

MucosalMucosal dissectiondissection

IT knife Needle knife

Flex knife Hook knife

Third principle

To treat our complications

Coag >> clips

NB:In case of perforation,even following clippingwe still need surgical advice andF-U with surgeons…..

Fourth principle

To prevent metachronous lesion= to treat the mucosa at risk

CircumferentialCircumferential esophagealesophageal mucmuc. . resectionresection

Lyon, E.Herriot Lyon, E.Herriot hospitalhospital:: 32 cases, 32 cases, meanmean FF--UU: 19 : 19 momo12 12 stenosesstenoses

GiovanniniGiovannini endoscendosc 04:04: 21 cases, 21 cases, meanmean FF--UU: 18 : 18 momo3 3 recurrencesrecurrences9% 9% bleedingbleeding, , nono stenosisstenosis

SoehendraSoehendra EndoscEndosc 04:04: 12 cases, 12 cases, medianmedian FF--U: 9 U: 9 momonono recurrencerecurrence2 2 stenosesstenoses

Fifth principle

To know the limits of endoscopy

= to evaluate the risk of lymph nodemetastases

EUS is not enough effective to detectmetastatic lymph node

N status is dependent of T status

Evaluation of N status related to T status has been conducted by japanese authors on surgical specimen

Definition of frontiersbased on T status

mm

sm

mp

colon

muc

stomachm1

1000 µµmm

eso

500 µµmm

Well differentiatedNo vasc or lymph invasion

How to assesssubmucosal invasion ?

II a + II c

II c + II a

EUS miniprobe 20-30 MHz

m

smpm1pm2

Musc. mucosae

9 layers

sm2

1000 μm

Case 41800 μm

sm2

7200 μm

CONCLUSIONS

1- Health care and strategy2- Japan > Occident3- Dg: not only a question of technology but ofmotivation and organization (screening)4- Technology concerns images but alsoeasiness (cost, compliance). To improvedetection is the first target.5- Treatment: same principles as surgery

Thank you