wiesbaden - dr. falk pharma · standard protocol for screening / surveillance 4-quadrant random...
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Innovations in Esophageal Innovations in Esophageal EndoscopyEndoscopy
JJüürgen Pohlrgen Pohl
Falk Symposium, Mainz, Semptember 18th, 2008Falk Symposium, Mainz, Semptember 18th, 2008
Wiesbaden
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Novel techniques in esophageal endoscopyNovel techniques in esophageal endoscopy
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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
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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
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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:
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Virtual chromoendoscopyVirtual chromoendoscopy
NBI
FICE
• Enhancement of surface contrast
• Enhancement of of vascular contrast
• No need of dye spraying
Bergmann J, 2004Arima, 2008
Effects :
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Vascular contrast for detectionVascular contrast for detectionand demarcation of neoplasiasand demarcation of neoplasias
Dr. Kouzu
Squamous cell carcinoma
FICEWhite light
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White light Acetic AcidFICE
Barrett‘s adenocarcinoma
Vascular contrast for detectionVascular contrast for detectionand demarcation of neoplasiasand demarcation of neoplasias
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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
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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
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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
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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
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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
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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
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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
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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
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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
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……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 ? )
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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
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Non-dysplastic Barrett´s-Esophagus
Laser Scanning EndomicroscopyLaser Scanning Endomicroscopy
In vivo confocal image Histopathology
Kiesslich et al., 2006
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Barrett´s Early Carcinoma
Laser Scanning EndomicroscopyLaser Scanning Endomicroscopy
Confocal image Histopathology
Kiesslich et al., 2006
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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 !
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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 !!
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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)
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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
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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
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● 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
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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
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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
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Radiofrequency Ablation (HALO)Radiofrequency Ablation (HALO)
Sharma et al., GIE 2007
Ablation catheter
(BARXX Medical Corp.)
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Radiofrequency Ablation (HALO)Radiofrequency Ablation (HALO)
Sharma et al., GIE 2007
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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
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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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