Recent advances in GI diagnostic & therapeutic endoscopy

Recent advancesRecent advances
in GI diagnostic &in GI diagnostic &
therapeutictherapeutic
endoscopyendoscopy
HOSSAM GHONEIM, MDHOSSAM GHONEIM, MD

► Endoscopic Diagnosis & Therapy of GERDEndoscopic Diagnosis & Therapy of GERD
 BRAVO Capsule.BRAVO Capsule.
 MII.MII.
 Endoscopic therapyEndoscopic therapy
► EndocinchEndocinch 1995.1995.
► StrettaStretta 1997.1997.
► EnteryxEnteryx 1999.1999.
► Gate KeeperGate Keeper 2002.2002.
► New imaging modalities of small & large bowelNew imaging modalities of small & large bowel
 Capsule endoscopy.Capsule endoscopy.
 Magnetic Colonoscpy imaging.Magnetic Colonoscpy imaging.
 CT colonography (virtual colonoscopy).CT colonography (virtual colonoscopy).
► Screening early GI malignancy (Interface Endoscopy)Screening early GI malignancy (Interface Endoscopy)
 Magnification chromoendoscopy.Magnification chromoendoscopy.
 NBI.NBI.
 AFI.AFI.
 OCT.OCT.
 Laser-scanning confocal microscopy.Laser-scanning confocal microscopy.
 Raman Spectroscopy.Raman Spectroscopy.
 Light scattering spectroscopy.Light scattering spectroscopy.
 Bioendoscopy.Bioendoscopy.
► Endotherapy of early GI malignancyEndotherapy of early GI malignancy
 EMREMR
 Photodynamic therapyPhotodynamic therapy

Endoscopic Diagnosis ofEndoscopic Diagnosis of
GERDGERD

MultichannelMultichannel
Intraluminal ImpedanceIntraluminal Impedance
(MII)`(MII)`

That's non-acid reflux identified
by impedance. You would not
know it was happening if you
merely did a pH study as most
of us today.
This is an acid reflux episodeThis is an acid reflux episode
Because the pH dropped belowBecause the pH dropped below
4. pH electrode merely to tell4. pH electrode merely to tell
what type of reflux thewhat type of reflux the
impedance has identified.impedance has identified.

Endotherapy ofEndotherapy of
GERDGERD

Endoscopic Suturing DeviceEndoscopic Suturing Device
(from Wilson Cook)(from Wilson Cook)

Comparison between EndocinchComparison between Endocinch
andand
ESD Wilson CookESD Wilson Cook
►Better viewBetter view
►Better flexibilityBetter flexibility
►Only one scope passageOnly one scope passage
►Easy handlingEasy handling
►Deeper sutureDeeper suture

Full Thickness PlicatorFull Thickness Plicator

StrettaStretta
• Entails delivery of radiofrequency energy to the
gastroesophageal junction and gastric cardia.
• Improvement in heartburn score and GERD quality of
life score after 6 to 12 months.
• PPI requirement fell from 88% to 30% with significant
reduction in oesophageal acid exposure time.
• Procedure was well tolerated by patients, with self-
limited complications of 8.6%.

A balloon catheter, nickel titanium electrodes which supply radiofrequencyA balloon catheter, nickel titanium electrodes which supply radiofrequency
energy in a series of small thermal injuries applied to the sphincterenergy in a series of small thermal injuries applied to the sphincter
muscle, have been shown to reduce transient LES relaxations and perhapsmuscle, have been shown to reduce transient LES relaxations and perhaps
alter the dynamics by which reflux takes place.alter the dynamics by which reflux takes place.

Enteryx
► Deviere et al.,2003 reported the effects
of the injection of ethylene vinyl alcohol
polymer (Enteryx, Boston Scientific
Corp.) into the muscular layer of the LES
to increase its bulk.
► The procedure increased the LES
pressure and led to a sustained
reduction in heartburn score in most
patients at 6 months.
► More than two thirds of patients were
able to discontinue their acid
suppression therapy.

Gate KeeperGate Keeper
• Gate keeper reflux repair
system
• Hydrogel prothesis implanted
in submucosa
• Pilot study showed safety
(no prothesis migration)
• One definite advantage over
other procedures ..
reversible
• No data available to
compare it with medical
therapy
∀ ∴ considered , so far ,
experimental
P. Fockens, 2003

GatekeeperGatekeeper
Stabilize Site Create Pocket
Access Pocket Prosthesis Delivery

► CapsuleCapsule
EndoscopyEndoscopy
 DisposableDisposable
 50,000 – 60,000 images50,000 – 60,000 images
 5 hours of recording5 hours of recording
storedstored
 9GB hard drive9GB hard drive
 Transmitted to a recorderTransmitted to a recorder
worn by patientworn by patient
 Analized in 20 min videoAnalized in 20 min video
clipclip
 Ability to localise place ofAbility to localise place of
lesion during analysislesion during analysis
 Future coupling withFuture coupling with
tempreture & PHtempreture & PH
measurmentsmeasurments

►Magnetic colonoscope imagingMagnetic colonoscope imaging

► C.T. Colonography (virtual colonscopyC.T. Colonography (virtual colonscopy))
 10 min. procedure10 min. procedure
 C.T. scannerC.T. scanner
 No sedationNo sedation
 Polyps & CaPolyps & Ca
 False positive:False positive:
Residual stoolResidual stool
 False negative:False negative:
flat lesionsflat lesions
polyps<10mmpolyps<10mm
? Insuflation? Insuflation
 Colonoscopy needed forColonoscopy needed for
biopsybiopsy
 Sensitivity 75%Sensitivity 75%
 Specificity 90%Specificity 90%

► Endoscopic Diagnosis & Therapy of GERDEndoscopic Diagnosis & Therapy of GERD
 BRAVO Capsule.BRAVO Capsule.
 MII.MII.
 Endoscopic therapyEndoscopic therapy
► EndocinchEndocinch 1995.1995.
► StrettaStretta 1997.1997.
► EnteryxEnteryx 1999.1999.
► Gate KeeperGate Keeper 2002.2002.
► New imaging modalities of small & large bowelNew imaging modalities of small & large bowel
 Capsule enteroscopy.Capsule enteroscopy.
 Magnetic Colonoscpy imaging.Magnetic Colonoscpy imaging.
 CT colonography (virtual colonoscopy).CT colonography (virtual colonoscopy).
► Screening early GI malignancy (InterfaceScreening early GI malignancy (Interface
Endoscopy)Endoscopy)
 Magnification chromoendoscopy.Magnification chromoendoscopy.
 NBI.NBI.
 AFI.AFI.
 OCT.OCT.
 Laser-scanning confocal microscopy.Laser-scanning confocal microscopy.
 Raman Spectroscopy.Raman Spectroscopy.
 Light scattering spectroscopy.Light scattering spectroscopy.
 Bioendoscopy.Bioendoscopy.
► Endotherapy of early GI malignancyEndotherapy of early GI malignancy
 EMREMR
 Photodynamic therapyPhotodynamic therapy

Screening early GI malignancyScreening early GI malignancy
(Interface Endoscopy)(Interface Endoscopy)
Magnification chromoendoscopy.Magnification chromoendoscopy.
NBI.NBI.
AFI.AFI.
OCT.OCT.
Laser-scanning confocal microscopy.Laser-scanning confocal microscopy.
Raman Spectroscopy.Raman Spectroscopy.
Light scattering spectroscopy.Light scattering spectroscopy.
Bioendoscopy.Bioendoscopy.

Conceptual BackgroundConceptual Background
►TerminologyTerminology
- Interface EndoscopyInterface Endoscopy
- SpectroscopySpectroscopy
- Optical biopsyOptical biopsy
- BioendoscopyBioendoscopy

► Key optical principles and Definitions:Key optical principles and Definitions:
 Light spectrum travels at different wave lengths (BlueLight spectrum travels at different wave lengths (Blue
shortest, red longest).shortest, red longest).
 Light interaction with tissue:Light interaction with tissue:
► ReflectedReflected  image seen on WL conventional endoscopy.image seen on WL conventional endoscopy.
► Scattered within tissue and outside (reaching back toScattered within tissue and outside (reaching back to
source).source).
► Transfer energy to excitable molecules within tissue (calledTransfer energy to excitable molecules within tissue (called
fluorophores or fluorochromes) making them Fluoresce (i.e.fluorophores or fluorochromes) making them Fluoresce (i.e.
emit radiation or light of different wave length than that ofemit radiation or light of different wave length than that of
original).original).
► Absorbed (and converted to heat) by other molecules calledAbsorbed (and converted to heat) by other molecules called
chromophores.chromophores.

► All of the above may produce changes in theAll of the above may produce changes in the
intensity and/or wavelength (frequency) of lightintensity and/or wavelength (frequency) of light
emanating from tissue.emanating from tissue.
► The nature and magnitude of these changes inThe nature and magnitude of these changes in
light is determined by the physiochemicallight is determined by the physiochemical
composition and architecture of tissue, whichcomposition and architecture of tissue, which
varies with its biological states (inflammation,varies with its biological states (inflammation,
dysplasia, and neoplasia) i.e. light returning fromdysplasia, and neoplasia) i.e. light returning from
tissue carries itstissue carries its “signature”.“signature”.

► Spectroscopy is the general term forSpectroscopy is the general term for
obtaining and analyzing information containedobtaining and analyzing information contained
in light signals based on their wave length/orin light signals based on their wave length/or
intensity. It can be used to interpret thisintensity. It can be used to interpret this
“signature”“signature” to provide information onto provide information on
pathologic changes in tissues.pathologic changes in tissues.
► Different systems allows the transfer of suchDifferent systems allows the transfer of such
interpreted data as electrical signals for realinterpreted data as electrical signals for real
time display and recording.time display and recording.
► Ideal system for application:Ideal system for application:
 Convenient (easy to use).Convenient (easy to use).
 Integrated.Integrated.

MagnificationMagnification
ChromoendoscopyChromoendoscopy
► Allows fine topographical details to be seen.Allows fine topographical details to be seen.
► Scopes available from x8 to x170 magnification.Scopes available from x8 to x170 magnification.
► Lens has to be close to surface of mucosaLens has to be close to surface of mucosa
(interface) due to narrow range of focus.(interface) due to narrow range of focus.
► With dye (MB or LI) healthy mucosa isWith dye (MB or LI) healthy mucosa is
homogenously stained, non healthy mucosahomogenously stained, non healthy mucosa
heterogeneous pattern or not stained.heterogeneous pattern or not stained.
► Allows differentiation of adenomatous fromAllows differentiation of adenomatous from
hyperplastic tissue according to mucosal patternhyperplastic tissue according to mucosal pattern
(Kudo classification).(Kudo classification).

Narrow Band Imaging (NBI)Narrow Band Imaging (NBI)
► Based on the fact that light penetration is wave lengthBased on the fact that light penetration is wave length
dependant; the shorter the WL the shallower thedependant; the shorter the WL the shallower the
penetration.penetration.
► ∴∴NBI system consists of a filter with narrow band pass-NBI system consists of a filter with narrow band pass-
ranges, increased blue light (WL 437nm) & decreasedranges, increased blue light (WL 437nm) & decreased
red light (WL 630 nm) contribution.red light (WL 630 nm) contribution.
► Real time endoscopic technique that enhances visibilityReal time endoscopic technique that enhances visibility
of mucosal surface structures without use dye ( mucosalof mucosal surface structures without use dye ( mucosal
pattern ).pattern ).
► Integrated system with HRE mode & possibility ofIntegrated system with HRE mode & possibility of
switching between both modes.switching between both modes.
► Few studies performed in comparison to conventionalFew studies performed in comparison to conventional
endoscopy in BE, showing better Intestinal metaplasia &endoscopy in BE, showing better Intestinal metaplasia &
HGD detection with NBI system.HGD detection with NBI system.
Endoscopy, 2003Endoscopy, 2003

►The aim of this new technology is toThe aim of this new technology is to
improve and enhance the reproduction ofimprove and enhance the reproduction of
the important tissue features such as thethe important tissue features such as the
capillary network and mucosalcapillary network and mucosal
microstructure.microstructure.

•The capillary pattern
classified into 4 types (I-
IV) according to the
degree of change in the
intrapapillary capillary
loop (IPCL) pattern;
dilatation, tortuosity,
or caliber change in
one IPCL, or various
shapes in multiple IPCLs.
[i],[ii]
[i]
Kumagai Y, Inoue H, Nagai K, et al. Magnifying
endoscopy, stereoscopic microscopy, and the
microvascular architecture of superficial esophageal
carcinoma. Endoscopy 2002;34:369-375
[ii]
Tatsuya Y, Haruhiro I, Shinsuke U, et al. Narrow-band
imaging system with magnifying endoscopy for
superficial esophageal lesions. Gastrointest Endosc
2004;59:288-295

Autofluorescence Imaging (AFI)Autofluorescence Imaging (AFI)
► ““Auto” is the native ability of tissues to fluoresceAuto” is the native ability of tissues to fluoresce
when transferred energy excites the moleculeswhen transferred energy excites the molecules
within it (Fluorophores) in contrast to fluorescencewithin it (Fluorophores) in contrast to fluorescence
due to exogenous photosentizers.due to exogenous photosentizers.
► AF is observation of the tissues fluorescence whenAF is observation of the tissues fluorescence when
exposed to (excited by) UV or blue light.exposed to (excited by) UV or blue light.
► As normal tissue transforms to dysplasia andAs normal tissue transforms to dysplasia and
thickens to cancer, it develops neovasculature inthickens to cancer, it develops neovasculature in
which haemoglobin absorbs light (Chromophore)which haemoglobin absorbs light (Chromophore)
thus interfering with penetration and emission.thus interfering with penetration and emission.
► Dysplasia =Dysplasia =↓↓ fluorescence.fluorescence.
► Superior results of dysplasia detection to white lightSuperior results of dysplasia detection to white light
endoscopy in all studies conducted.endoscopy in all studies conducted.
Endoscopy, 2000; Gut, 2003Endoscopy, 2000; Gut, 2003

AFI System OperationAFI System Operation
► Blue light (WL=437nm) from mercury lampBlue light (WL=437nm) from mercury lamp
passed through excitation filter and throughpassed through excitation filter and through
endoscope working channel.endoscope working channel.
► AF from tissue is amplified by high-AF from tissue is amplified by high-
sensitivity CCD camera attached to the endsensitivity CCD camera attached to the end
of endoscope, then detected.of endoscope, then detected.
► Image is processed by image processor inImage is processed by image processor in
real time and displayed on monitor.real time and displayed on monitor.
► Future: Integrated systems (with foot switvhFuture: Integrated systems (with foot switvh
to/from white light endoscopy on demand).to/from white light endoscopy on demand).

Optical Coherence Tomography (OCT)Optical Coherence Tomography (OCT)
►Basic Principles:Basic Principles:
 Coherence time= temporal scale intrinsic to aCoherence time= temporal scale intrinsic to a
certain type of light.certain type of light.
 Coherence length= Coherence time x lightCoherence length= Coherence time x light
speed.speed.
 Axial resolution (in depth)Axial resolution (in depth) αα CoherenceCoherence
length. The shorter the coherence length, thelength. The shorter the coherence length, the
better the axial resolution.better the axial resolution.
 OCT uses low coherence light sourceOCT uses low coherence light source
(Superluminescent diode) to measure optical(Superluminescent diode) to measure optical
back scattering of light from different tissue.back scattering of light from different tissue.

OCTOCT
► Basic Principles (cont.):Basic Principles (cont.):
 Light source emits a beam.Light source emits a beam.
 This beam is split in two by an optical filter splitter.This beam is split in two by an optical filter splitter.
 One beam directed to tissue, the other directed to a mirror.One beam directed to tissue, the other directed to a mirror.
 Back scattered light from tissue & mirror interfere onlyBack scattered light from tissue & mirror interfere only
when the path length match to within the specifiedwhen the path length match to within the specified
coherence length of the original light source (coherence length of the original light source (≅≅2020µµm).m).
 By measuring the degree of interference at each mirrorBy measuring the degree of interference at each mirror
position as the mirror is moved, a quantitativeposition as the mirror is moved, a quantitative
measurement of optical back scattering at different depthsmeasurement of optical back scattering at different depths
is obtained.is obtained.
 Thus coherence length of light source determines theThus coherence length of light source determines the
maximal axial resolution (in depth) that can be obtained.maximal axial resolution (in depth) that can be obtained.
 Transverse resolution (along tissue surface) is determinedTransverse resolution (along tissue surface) is determined
by the spot size of the focused beam directed at the tissue.by the spot size of the focused beam directed at the tissue.

OCTOCT
► Basic Principles (cont.):Basic Principles (cont.):
 B-mode U/S:B-mode U/S:
►cross-sectional image is constructed based oncross-sectional image is constructed based on
reflection of deflected energy from tissues back toreflection of deflected energy from tissues back to
detector.detector.
►““time-of-flight” (time taken for this energy deflectionstime-of-flight” (time taken for this energy deflections
from various layers) is measured electronically usingfrom various layers) is measured electronically using
pulse-echo technology.pulse-echo technology.
 OCT:OCT:
►Waves used are optical not sound (10Waves used are optical not sound (1055X faster).X faster).
►∴∴OCT resolution is 10 times greater even thanOCT resolution is 10 times greater even than
HFEUS (resolution=15-20HFEUS (resolution=15-20µµm, near histology-lightm, near histology-light
microscopy).microscopy).
►““time-of-flight” is measured by “opticaltime-of-flight” is measured by “optical
interferometry” based on the principles of lowinterferometry” based on the principles of low
coherence interferometry.coherence interferometry.

► OCT device and operation:OCT device and operation:
 Probes passed through working channel of scope.Probes passed through working channel of scope.
 Probe is approximated to query pathological mucosalProbe is approximated to query pathological mucosal
area, aided by a red beam light for targeting.area, aided by a red beam light for targeting.
 Images acquired inImages acquired in ≅≅3 seconds.3 seconds.
 Interpretation of images needs training for which oneInterpretation of images needs training for which one
session is usually enough.session is usually enough.
AJG, 2001AJG, 2001
OCTOCT

OCT uses in GITOCT uses in GIT
►Locate lesions likely to harbor HGDLocate lesions likely to harbor HGD
in BE and UC.in BE and UC.
►Disease activity and diagnosis of UCDisease activity and diagnosis of UC
as it shows glands, crypts, andas it shows glands, crypts, and
mucosal thickness.mucosal thickness.
►Differentiate dysplastic fromDifferentiate dysplastic from
hyperplastic polyps.hyperplastic polyps.
►Cancer staging.Cancer staging.

OCT LimitationsOCT Limitations
►Long time required to obtain image (blurringLong time required to obtain image (blurring
with patient movements) and probe mustwith patient movements) and probe must
be almost in contact to mucosa.be almost in contact to mucosa.
►Not suitable for surveillance of longNot suitable for surveillance of long
segment BE for dysplasia.segment BE for dysplasia.
►Image resolution (15-20Image resolution (15-20µµm) not sufficient tom) not sufficient to
replace histopathology (so far).replace histopathology (so far).
►1-2mm depth.1-2mm depth.
►OCT requires gastroenterologists to beOCT requires gastroenterologists to be
more knowledgeable in histopathology.more knowledgeable in histopathology.

OCT in the FutureOCT in the Future
► Ultra-high resolution OCT:Ultra-high resolution OCT:
 Ultra short-pulse laser (higher effective depth).Ultra short-pulse laser (higher effective depth).
► Spectroscopic OCT:Spectroscopic OCT:
 Analyzing spectrum of back scattered lightAnalyzing spectrum of back scattered light
 Enhances image contrast.Enhances image contrast.
 Functional imaging.Functional imaging.
► 3-D OCT:3-D OCT:
 3D dataset was able to track migration of a single cell3D dataset was able to track migration of a single cell
over few hours.over few hours.
 4D OCT (against time).4D OCT (against time).
► Doppler OCT and OCT biopsy needles:Doppler OCT and OCT biopsy needles:
 Potential for surveillance and grading of O.V.Potential for surveillance and grading of O.V.
 Evaluation of gastric and duodenal lesions.Evaluation of gastric and duodenal lesions.
 Guidance in locating blood vessels, pancreatic cysts ,Guidance in locating blood vessels, pancreatic cysts ,
L.N. and small liver nodules.L.N. and small liver nodules.

Laser Scanning Confocal MicroscopyLaser Scanning Confocal Microscopy
(LSC)(LSC)
► Ex-vivo technique.Ex-vivo technique.
► Potential for endoscopic application.Potential for endoscopic application.
► Scanning time < 2 seconds.Scanning time < 2 seconds.
► Diagnostic accuracy in specimens of GI cancerDiagnostic accuracy in specimens of GI cancer
89.9%89.9% (Inaue, Endoscopy, 2000)(Inaue, Endoscopy, 2000) ..
► Recent results shown on LCM of fresh biopsyRecent results shown on LCM of fresh biopsy
samples during endoscopy, equivalent in accuracysamples during endoscopy, equivalent in accuracy
to histopathology.to histopathology.
► Future potential: “Virtual histopathology” byFuture potential: “Virtual histopathology” by
endoprobe.endoprobe.
Gut, 2003Gut, 2003

Light Scattering SpectroscopyLight Scattering Spectroscopy
(LSS)(LSS)
► Absorption and scattering are tissue-specific characteristics ofAbsorption and scattering are tissue-specific characteristics of
light, depending on which wave lengths are absorbed andlight, depending on which wave lengths are absorbed and
scattered by different tissues.scattered by different tissues.
► Absorption depends on tissue concentration of specificAbsorption depends on tissue concentration of specific
biochemicals.biochemicals.
► Scattering depends on size and density of space occupyingScattering depends on size and density of space occupying
structures (collagen, nuclei, etc…)structures (collagen, nuclei, etc…)
► Mathematical measurement:Mathematical measurement:
““Mie Scattering theory” :Mie Scattering theory” : spectrum of carried lightspectrum of carried light
carries information about size and refractive index of scatterer).carries information about size and refractive index of scatterer).
““Fourier transformation”:Fourier transformation”: oscillations occuring duringoscillations occuring during
scattering is directly related to size of scatterer (cell nuclei).scattering is directly related to size of scatterer (cell nuclei).

LSSLSS
►Conventional WL endoscopy used with aConventional WL endoscopy used with a
point spectroscopy multifibre probe.point spectroscopy multifibre probe.
►Detects enlargement and crowding of nucleiDetects enlargement and crowding of nuclei
which are typical features of dysplasia.which are typical features of dysplasia.
►Detection of dysplasia equivalent to otherDetection of dysplasia equivalent to other
optical techniques, with a sensitivity andoptical techniques, with a sensitivity and
specificity of 90%.specificity of 90%.
►Advantages over AFI, use of white light, andAdvantages over AFI, use of white light, and
a strong signal.a strong signal.
Gastroenetrology, 2001Gastroenetrology, 2001

Raman SpectroscopyRaman Spectroscopy
► Based on principle that incident light canBased on principle that incident light can
cause molecules within a tissue to vibratecause molecules within a tissue to vibrate
or rotate.or rotate.
► Charged molecules resonate, emittingCharged molecules resonate, emitting
energy that can be measured spectrally.energy that can be measured spectrally.
► Resultant resonance spectrumResultant resonance spectrum
represents tissue specific contents (e.g.represents tissue specific contents (e.g.
distinct nucleic acid and proteins)distinct nucleic acid and proteins)
“Finger-Print”“Finger-Print” ..
► Optical Fiber Probe used throughOptical Fiber Probe used through
endoscope channel to give “on-the-spot”endoscope channel to give “on-the-spot”
information.information.
► preliminary results in GIT dysplasia ofpreliminary results in GIT dysplasia of
85% sensitivity and 93% specificity.85% sensitivity and 93% specificity.
Photobiology, 2000Photobiology, 2000

BioendoscopyBioendoscopy
►Fluorescently labeled CEAab stainsFluorescently labeled CEAab stains
gastric tumours.gastric tumours.
►IV injection of fluorescent probes (usingIV injection of fluorescent probes (using
Cathepsin B),Cathepsin B), 5050µµm-smallm-small adenomasadenomas
were detected in colonic mucosa.were detected in colonic mucosa.
►Endoscopic immunospray in BE:Endoscopic immunospray in BE:
 αα-MucSac-MucSac stains gastric metaplasia.stains gastric metaplasia.
 αα-Muc2-Muc2 stains intestinal metaplasia.stains intestinal metaplasia.

IS THIS THE BEGINNING OF AIS THIS THE BEGINNING OF A
NEW ERA OF MOLECULARNEW ERA OF MOLECULAR
ENDOSCOPY ?ENDOSCOPY ?
WILL WE BECOME ENDOSCOPICWILL WE BECOME ENDOSCOPIC
PATHOLOGISTS ?PATHOLOGISTS ?
ARE WE LIVING TOMORROW ?ARE WE LIVING TOMORROW ?
STAY TUNED !!!STAY TUNED !!!

Recent advances in GI diagnostic & therapeutic endoscopy

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