Innovations in Esophageal Innovations in Esophageal EndoscopyEndoscopy

JJüürgen Pohlrgen Pohl

Falk Symposium, Mainz, Semptember 18th, 2008Falk Symposium, Mainz, Semptember 18th, 2008

Wiesbaden

Novel techniques in esophageal endoscopyNovel techniques in esophageal endoscopy

Detection : morphology of esophageal neoplasiasDetection : morphology of esophageal neoplasias

Esophagus ColonKodama et al. Niigata HospitalGut 2000 GIE 2003(n = 1562) (n= 3644)

Protruded 0-I 15 % 50 %

Superficial elevated IIb 20 % 44 %

Flat 0-IIb 14 % < 1 %

Superficial depressed 0-IIc 45 % 5 %

Subtype

Standard protocol for screening / surveillanceStandard protocol for screening / surveillance

4-quadrant random biopsies (4RB)

every 1-2 cm along the BE segment to detect macroscopically occult lesions(SEATTLE protocol)

+

High resolution endoscopy

careful observationtargeted biopsies of suspect lesions

Virtual chromoendoscopy

Autofluorescence

Confocal endomicroscopy

Magnification

Chromoendoscopy with dyes

Disadvantages of 4RB

Time consuming, sampling errorsBlind approach (no localization of neoplasia)

no targeting for local therapy

Conventional chromoendoscopyConventional chromoendoscopy

- Equipment for dye spraying

- Extra time required to

perform the procedure

- No switchover between

chromoendoscopy and white light

- Not reversible

- No imaging of capillary patterns

Limitations:

Virtual chromoendoscopyVirtual chromoendoscopy

NBI

FICE

• Enhancement of surface contrast

• Enhancement of of vascular contrast

• No need of dye spraying

Bergmann J, 2004Arima, 2008

Effects :

Vascular contrast for detectionVascular contrast for detectionand demarcation of neoplasiasand demarcation of neoplasias

Dr. Kouzu

Squamous cell carcinoma

FICEWhite light

White light Acetic AcidFICE

Barrett‘s adenocarcinoma

Vascular contrast for detectionVascular contrast for detectionand demarcation of neoplasiasand demarcation of neoplasias

Pohl et al., Endoscopy 2007

Prospective, randomized cross-over study

57 patients: HGIN/EC = 24 patientsHGIN/EC = 30 lesions

p = n.s. Sensi- PPVtivity

Acetic acid 87 % 39 %FICE 87 % 37 %

Acetic acid chromoendoscopy vs. FICE

FICE for detection of BarrettFICE for detection of Barrett‘‘s neoplasias neoplasia

Prospective, randomized cross-over study

28 patients: HGIN / EC = 14

No neoplasia = 14

p = n.s. Sensi- PPVtivity

HRE 79 % 57 %Indigocarmine 93 % 56 %NBI 86 % 53 %

Regular HRE vs. indigocarmine 0,4% vs. NBI

..equivalent results for NBI..equivalent results for NBI

Kara et al., Endoscopy 2005

Standard procedure for screening /surveillanceStandard procedure for screening /surveillance

Despite contrast enhancing techniques:detection of early neoplasias based on their morphological appearance remains challenging

Needed: technique that detects neoplasias basedon the specific biological characteristics of neoplastic tissue

EndogeneFluorophores

Principle of Autofluorescence Endoscopy

Exposure of tissues to short wavelength light

endogenous biological substances are excited

Emission of fluorescence light

Normal and neoplastic tissues have different autofluorescence characteristics that may enable their distinction

Kara et al, GIE 2005

Strength: Sensitivity > 90 %High NPV

Limitation: Specificity < 40 %Low PPV

Red

Fluorescence Endoscopy

Strategy: Trimodal Imaging

+magnified NBI

might reduce false positive lesions

red flag high specificity

Curvers WL et al., GUT 2007Curvers WL et al., GUT 2007

Trimodal Imaging

White light AFI

Pat. with HGIN/EC 45 % (14/30) 90 % (27/30)

False positive lesions 67 % 81 %

False positive with NBI 41 % 26 %

• 3 patients (10%) with HGIN/EC were missed and detected by 4 RB only

• in 3 HGIN/EC lesions NBI predicted normal histology

Tri (four)Tri (four)--modal imaging might be too cumbersome for

modal imaging might be too cumbersome for

routine use outside expert centers

routine use outside expert centers

A less complex protocol is warranted !!

A less complex protocol is warranted !!

n = 84 patients with BE

Pohl et al., UEGW 2008

Ongoing prospective study (January 2007-May 2008)500 consecutive patients with known Barrett‘s esophagusAim: Test efficacy of AA and additional value of 4RB

The „value of 4-quadrant random biopsies“ study

Wiesbaden strategy:• HRE imaging• acetic acid chromoendoscopy• targeted biopsies (from visible suspicious lesions)• Four-quadrant random biopsies from regular Barrett‘s mucosa

according to the Seattle protocol

targeted Bx 4 QB

No. of Bx 371 3788

Mean time ------ 4,4 min

No. of Bx needed 4,7 210,4

to detect one lesion

The lesion level

The „value of 4-quadrant random biopsies“ study

Pohl et al., UEGW 2008

Indications for endoscopy :Surveillance of NDBE : 180Suspected or treated HGIN/EC : 320

targetedBx 4 QB

Pt. Detected with HGIN/EC 95,5 % (62/65)

Bx. needed 5,8 / pt.

Pt. detected with 4QB only 4,5% (3/65)

Bx. needed 1264 / pt.

The patient level

The „value of 4-quadrant random biopsies“ study

Indications for endoscopy :Surveillance of NDBE : 180Suspected or treated HGIN/EC : 320

Pohl et al., UEGW 2008

……implications

Careful endoscopic inspection with HRE combined with acetic acidchromoendoscopy has excellent (> 90 %) sensitivity for early neoplasias

Additional value of random biopsies is low !!

Dye spraying may be of additional benefit in this respect

….but we do not advocate complete abolition of non-targeted biopsying (high volume center effect ? )

On site cellular pathology assessmentOn site cellular pathology assessment

Problem: Biopsy sampling implies a time lack between endoscopy

and histopathologic diagnosis

Needed: „endohistology“ that offers reliable endoscopic in vivo histology during ongoing endoscopy for rapid diagnosis

Confocal Imaging Window

Joint venture: Pentax, Japan & Optiscan, Australia

Non-dysplastic Barrett´s-Esophagus

Laser Scanning EndomicroscopyLaser Scanning Endomicroscopy

In vivo confocal image Histopathology

Kiesslich et al., 2006

Barrett´s Early Carcinoma

Laser Scanning EndomicroscopyLaser Scanning Endomicroscopy

Confocal image Histopathology

Kiesslich et al., 2006

Barrett´s Esophagus and Cancer

“Blinded” Prediction of Barrett’s associated neoplasias:Sensitivity: 92.9%; Specificity: 98.4%, Accuracy: 97.4%

Kießlich et al. Clin Gastroenterol Hepatol 2006

Proof of principle studiesProof of principle studies

Sqaumous cell cancer

“Blinded” Prediction of squamous cell neoplasia:Sensitivity: 92 %; Specificity: 97 %

Pech et al. Clin Gastroenterol Hepatol 2007

„Endohistology“ allows reliable differentiation of neoplastic from

non-neoplastic tissue

But:- movement artefacts caused by breathing and heart beat

- Need for training of gastroenterologists for assessment of cellular

pathology

- Place in routine endoscopy is not yet defined !

Imaging technologies: the current situationImaging technologies: the current situation

HRE Lesion

Chromo, NBI, FICE, AFE 100 %

Visualization Detection

No diagnosticNo diagnostic superweapon superweapon yet !!yet !!

Endoscopic therapies Endoscopic therapies -- ControversiesControversies

Early carcinoma of the esophagus

??

Limits of endoscopic therapy ?Technical issues ?

Suck & cut (piece meal) Endoscopic submucosal dissection (en bloc)

486 pats with HGIN/EC (10/96 – 09/2002)

349 pats. with curative endoscopic therapy

337 pats. with complete remission (97%)

Sustained remission: 79 %Recurrent/metachronous lesions: 21 %

Surgery after failure of Endo-Tx; 12 pats. (3%)

Mean Follow-up

63.6 months

Major complic.:0.6%Minor complic.:17%

Wiesbaden long term results on ER for BarrettWiesbaden long term results on ER for Barrett‘‘s neoplasiass neoplasias

Pech et al., Gut 2008

follow-up [months]

140120100806040200

surv

ival

1,0

,9

,8

,7

,6

,5

,4

,3

,2

,1

0,0

Overall survival compared to normal German population

74%

75%

Calculated 10 Year Survival RateCalculated 10 Year Survival Rate

Pech et al., Gut 2008

● depth of infiltration > sm 1● L pos. (lymphatic invasion)● V pos. (vascular invasion)● G 3-4● R1 basal

Indications for ER

Limits of ER determined by histologoy of resection specimen

Principle:Principle:Patients are ideal candidates for ER, when risk of lymph nodePatients are ideal candidates for ER, when risk of lymph node

metastasis < risk of mortality from surgerymetastasis < risk of mortality from surgery

tumor-free survival

Periode A+C

time to recurrence/tumor-related death

120100806040200

tum

or-fr

ee s

urvi

val

1,0

,9

,8

,7

,6

,5

,4

,3

,2

,10,0

ablation after CR

ablation

ablation-zensiert

no ablation

no ablation-zensiert

83% with ablation

60% without ablationp = 0.002

Retrospective analysis of factors associated with recurrent neoplasia after CR

Ablation of remaining Barrett‘s mucosa might reduce risk of recurrent or metachronous neoplasia

Drawback of ER : recurrent and metachronous lesionsDrawback of ER : recurrent and metachronous lesions

Estimated tumor free-survival

Ablation of nonAblation of non--neoplastic Barrett`s after CRneoplastic Barrett`s after CR

Techniques:Argon plasma coagulation

Cryoablation

Photodynamic therapy

Endoscopic resection

Limitations:Severe complications

- strictures / perforations

Incomplete ablation / buried glands

Multiple sessions needed

Radiofrequency Ablation (HALO)Radiofrequency Ablation (HALO)

Sharma et al., GIE 2007

Ablation catheter

(BARXX Medical Corp.)

Radiofrequency Ablation (HALO)Radiofrequency Ablation (HALO)

Sharma et al., GIE 2007

Radiofrequency Ablation (HALO)

n complete ablation sessions buried glands complications

1-year 2-year

Sharma, 2007 100 70 % 1,5 0 0Fleischer 2008 70 98 % 0 0Sharma, 2008 10 70 % 90 % 1,6 0 0Hernanez, 2008 10 70 % 1 0

Excellent safety (no strictures !!!) and efficiacy

Long-term results have to be awaited

2. Endoscopic resection is safe and effective(expert centers)

3. Long-term results of endoscopic resection in early Barrett`s neoplasia are excellent

4. Circumferential ablation of remaining Barrett‘s mucosa after Endo-Tx might become standard to reduce risk of recurrent neoplasias

Conclusions

1. Surveillance endoscopises should be performed with HRE, addition of chromoendoscopy or FICE / NBI might further improve detection rates

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