BARRETT’S

ESOPHAGUS

BILIO-PANCREATIC

STRICTURESPANCREATIC CYSTS

Better detection leading to more informed patient management decisions

“On the spot” characterization of

indeterminate bilio-pancreatic strictures

Significantly improve diagnosis reliability and guide

therapeutic decisions on pancreatic cysts

BARRETT’S ESOPHAGUS STUDY

Surgical Endosc. 2018, Dr C. Richardsona1

172 patients with Barrett’s Esophagus, 8 centers

Gastrointest Endosc. 2013, Dr. M. Cantoa2

192 patients with Barrett’s Esophagus, 5 centers

DONT BIOPCE STUDY Gastrointest Endosc. 2011, Pr. P. Sharmaa7

101 patients with BE, 5 international centers

FOCUS STUDYGastrointest Endosc. 2015, Dr. A. Slivkab1

112 patients evaluated with indeterminate strictures

6 international centers

Surg Endosc. 2015, Dr. F. Caillolb2

61 patients with a biliary stricture without any previous histology

CONTACT 1 & 2 STUDIES Surgical Endoscopy 2019, Dr. M. Palazzoc1

206 patients with cysts

Endoscopy 2015 & 2018, Dr. B. Napoléonc6,c3 31 patients with cysts, 3 centers 71 patients with cysts, 5 centers

INDEX STUDY Clinical Gastroenterology and Hepatology 2019,

Dr. S.G. Krishnac2

144 patients with a suspected PCL (≥20 mm)

HEALTH ECONOMIC EVALUATION STUDY

Endoscopy International open 2017, Dr. C. Le Penc4

2x more dysplastic lesions detected

compared to WLEa7

1.7x more lesions detected compared

to Narrow Band Imaginga7

Improved the treatment plan in 36% of patientsa2

2x more Barrett’s Esophagus detected

compared to Seattle protocola1.

89% sensitivity for ERCP with tissue

sampling versus 56% for tissue sampling aloneb1

78% NPV for pCLE compared to 57%

for tissue sampling aloneb1

35% of patients with benign cysts prevented from any surveillancec1

nCLE identified mucinous PCLs with:

high sensitivity of 98%, 94% specificity and 97% accuracyc2

nCLE could reduce up to 23% of surgical interventionsc4

Cellvizio® PublicationsLatest Communications on probe and needle-based Confocal Laser Endomicroscopy (pCLE and nCLE)

Intestinal Metaplasia

Adenocarcinoma

Healthy Biliary Duct

Cholangiocarcinoma

Gastroenterology

Cellvizio® ImagesBARRETT’S ESOPHAGUSh1 BILIOPANCREATIC STRICTURESh1

Intraductal Papillary Mucinous Neoplasm

Over 1000+ Publications

on Endomicroscopy

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PANCREATIC CYSTSc8,c6

Serous Cystadenoma

GASTRIC LESIONS COLORECTAL LESIONS INFLAMMATORY BOWEL DISEASES

“On the spot” characterization of intestinal metaplasia and early gastric

cancer

Better characterization to enhance surveillance and treatment follow-up of

colorectal lesions

A tailored approach to patient management, based on what is happening at the

mucosal level

GASTRIC INTESTINAL METAPLASIA STUDIES

Scand J Gastroenterol 2017, Dr. H P Zhangd1

4000+ lesions - surveillance of gastric intestinal metaplasia

23 studies

J Clin Gastroenterol 2015, Dr. Z Lid2 32 patients - surveillance of gastric

intestinal metaplasia - 1 center

Gastrointest Endosc. 2013, Dr. G H Bokd3

46 patients - diagnosis of superficial gastric neoplasia - 1 center

COLORECTAL LESIONS STUDIES

Colorectal lesions surveillancee2

Lancet. 2013, Dr. L Wanders meta analysis on 11 studies

1319 lesions

Colorectal lesions follow-upe3 Gastrointest Endosc. 2011, Dr. V M Ussui

92 patients - post-EMR control 3 international centers

INFLAMMATORY BOWEL DISEASES STUDIES

Digestive Diseases and Sciences. 2019, Dr. Julia J. Liuf1

>100 patients

Gastrointest Endosc. 2017, Dr. Gian Eugenio Tontinif2

49 CD patients, 2 centers, retrospective study

Clin Trans Gastroenterol. 2012, Pr. Jean-François Turcottef6

41 patients (21 Crohn’s disease and 20 Ulcerative Colitis), 1 center

96.9% sensitivity for the diagnosis of superficial gastric neoplasia with pCLE

and biopsy versus 75% sensitivity with conventional biopsyd3

pCLE classification of gastric pit patterns and vessel architecture could predict

Atrophic gastritis, GIM and neoplasia with sensitivity of at least 89% and specificity

of 99% with substantial inter-observer agreement (k:0.7)d2

Pooled 92% sensitivity and 97% specificity for the diagnosis of gastric

intestinal metaplasia with CLEd1

100% sensitivity and NPV combination

of pCLE and virtual chromoendoscopy for neoplastic recurrencee3

93.3% of neoplastic lesions accurately

characterizede2

Increased epithelial gap density in IBD patients is an endoscopic predictor of

relapse within 12 monthsf6

CLE allows for the early prediction of relevant clinical outcomes being

hospitalizationf2 or surgeryf2

Severity of mucosal barrier dysfunction on pCLE resulted in significant

reductions in the number, length of stay

and total days of IBD-related hospitalizationsf1

Healthy mucosa

Adenocarcinoma

Cellvizio® ImagesCOLORECTAL LESIONSh1 INFLAMMATORY BOWEL DISEASESh2,h4

Epithelial gaps

Inflammation

GASTRIC INTESTINAL METAPLASIAd3,h3

High-grade dysplasia

Gastric Intestinal Metaplasia

World J Gastroenterol 2018,Dr. Lord Richarde1

1491 patients (4674 polyps)

Real-time CLE, had a pooled sensitivity and

specificity of 91% and 97% for characterization

in patients with colonic IBDe1

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BILIOPANCREATIC STRICTURES

BibliographyBARRETT’S ESOPHAGUS

a1. Richardson C, et al. Real-time diagnosis of Barrett’s esophagus: a prospective, multicenter study comparing confocal laser endomicroscopy with conventional histology for the identification of intestinal metaplasia in new users, Surgical Endoscopy, 2018.

a2. Canto M.I. et al. In vivo endoscopy improves detection of Barrett’s esophagus-related neoplasia: a multicenter international randomized controlled trial. Gastrointestinal Endoscopy, 2013.

a3. Neumann H, et al. Confocal Laser Endomicroscopy for Diagnosis of Barrett’s Esophagus. Frontiers in Oncology, 2012. a4. Johnson EA, et al. Probe-Based Confocal Laser Endomicroscopy to Guide Real-Time Endoscopic Therapy in Barrett’s Esophagus

with Dysplasia. Case Report Gastroenterology, 2012. a5. Bertani H, et al. Improved Detection of Incident Dysplasia by Probe-Based Confocal Laser Endomicroscopy in a Barrett’s

Esophagus Surveillance Program. Digestive Diseases and Sciences, 2012.

a6. Wallace MB, et al. Multicenter, randomized, controlled trial of confocal laser endomicroscopy assessment of residual metaplasia after mucosal ablation or resection of GI neoplasia in Barett’s esophagus. Gastrointestinal Endoscopy, 2012.

a7. Sharma P, et al. Real-time increased Detection of Neoplastic Tissue in Barrett’s Esophagus with Probe-based Confocal Laser Endomicroscopy: Final results of a Multi-center Prospective International Randomized Controlled Trial. Gastrointestinal Endoscopy, 2011.

a8. Gaddam S, et al. Novel Probe-Based Confocal Laser Endomicroscopy Criteria and Interobserver Agreement for the Detection of Dysplasia in Barrett's Esophagus. The American Journal of Gastroenterology, 2011.

a9. Konda VJ, et al. Confocal Laser Endomicroscopy: potential in the Management of Barrett's Esophagus. Diseases of the Esophagus, 2010.

a10. Wallace MB, et al. Preliminary Accuracy and Interobserver Agreement for the Detection of Intraepithelial Neoplasia in Barrett's Esophagus with Probe-based Confocal Laser Endomicroscopy. Gastrointestinal Endoscopy, 2010.

PANCREATIC CYSTSc1. Palazzo M, et al. Impact of needle-based confocal laser endomicroscopy on the therapeutic management of single pancreatic

cystic lesions, Surgical Endoscopy, 2019. (CONTACT 2). c2. Krishna SG, et al. Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of

Pancreatic Cystic Lesions, Clinical Gastroenterology and Hepatology, 2019. c3. Napoléon B, et al. Needle-based confocal laser endomicroscopy of pancreatic cystic lesions: a prospective multicenter validation

study in patients with definite diagnosis, Endoscopy, 2018. (CONTACT 2).

c4. Le Pen C et al. A health economic evaluation of needle-based Confocal Laser Endomicroscopy for the diagnosis of pancreatic cysts. Endoscopy International Open (2017).

c5. Napoléon, B. et al. New horizons in the endoscopic ultrasonography-based diagnosis of pancreatic cystic lesions. World J Gastroenterol, 24(26), 2853–2866, 2018.

c6. Napoléon B, et al. A novel approach to the diagnosis of pancreatic cystadenoma: needle-based confocal laser endomicroscopy, Endoscopy, 2015 (CONTACT 1).

c7. Chang K, et al. Diagnosis of pancreatic cysts: EUS-guided, through-the-needle confocal laser-induced endomicroscopy and cystoscopy trial: DETECT study. Gastrointestinal Endoscopy, 2015.

c8. Konda VJA, et al. A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscoscopy under endosonographic guidance. Endoscopy, 2013. (INSPECT).

c9. Saftaiou A, et al. Endoscopic Ultrasound-guided confocal laser endomicroscopy : using the optical needle into the acoustic haystack. European Journal of Ultrasound, 2012.

GASTRIC INTESTINAL METAPLASIA d1. Zhang H-P, et al. The diagnostic value of confocal laser endomicroscopy for gastric cancer and precancerous lesions among

Asian population: a system review and meta-analysis. Scand J Gastroenterol, 52(4), 382–388, 2017.

d2. Li Z, et al. New Classification of Gastric Pit Patterns and Vessel Architecture Using Probe-based Confocal Laser Endomicroscopy. J Clin Gastroenterol, 2015.

d3. Bok GH, et al. The accuracy of probe-based confocal endomicroscopy versus conventional endoscopic biopsies for the diagnosis of superficial gastric neoplasia (with videos). Gastrointestinal Endoscopy, 2013.

d4. Lim LG, et al. Comparison of probe-based confocal endomicroscopy with virtual chromoendoscopy and white-light endoscopy for diagnosis of gastric intestinal metaplasia. Surgical endoscopy, 2013.

d5. Pittayanon R, et al. Flexible spectral imaging color enhancement plus probe-based confocal laser endomicroscopy for gastric intestinal metaplasia detection. Journal of Gastroenterology and Hepatology, 2013.

d6. Pittayanon R, et al. The learning curve of gastric intestinal metaplasia interpretation on the images obtained by probe-based confocal laser endomicroscopy (pCLE). Diagnostic and Therapeutic Endoscopy, 2012.

d7. Pittayanon R, et al. Role of Confocal Laser Endomicroscopy for the Detection of early Gastrointestinal Malignancy. Thai Journal Gastroenterology, 2011.

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b1. Slivka et al, Validation of the diagnostic accuracy of probe-based confocal laser endomicroscopy for the characterization of indeterminate biliary strictures: results of a prospective multicenter international study, Gastrointestinal Endoscopy, 2015.

b2. Caillol et al, Evaluation of probe-based confocal laser endomicroscopy in the bile duct: final results of EMID study: pCLE: impact in the management of bile duct strictures. Surg Endosc, 2015.

b3. Caillol F, et al. Refined probe-based confocal laser endomicroscopy classification for biliary strictures: the Paris classification. Digestive Diseases and Sciences, 2013.

b4. Heif M, et al. ERCP with Probe-Based Confocal Laser Endomicroscopy for the Evaluation of Dominant Biliary Stenoses in Primary Sclerosing Cholangitis Patients. Digestive Diseases and Sciences, 2013.

b5. Meining A, et al. Classification of Probe-based Confocal Laser Endomicroscopy findings in Pancreaticobiliary Strictures. Endoscopy, 2012.

b6. Loeser CS, et al. Confocal Endomicroscopic Examination of Malignant Biliary Strictures and Histologic Correlation with Lymphatics. Journal of Clinical Gastroenterology, 2011.

b7. Meining A, et al. Direct Visualization of Indeterminate Pancreaticobiliary Strictures using Probe-based Confocal Laser Endomicroscopy - A Multicenter Experience. Gastrointestinal Endoscopy, 2011.

b8. Giovannini M, et al. Results of a phase I-II study on Intraductal Confocal Microscopy (IDCM) in patients with Common Bile Duct (CBD) Stenosis. Surgical Endoscopy, 2011.

INFLAMMATORY BOWEL DISEASESf1. Julia J. Liu et al. Personalized Inflammatory Bowel Disease Care Reduced Hospitalizations. Digestive Diseases and Sciences 2019.

f2. Tontini GE. et al. Prediction of clinical outcomes in Crohn’s disease by using confocal laser endomicroscopy: results from a prospective multicenter study. Gastrointestinal Endoscopy 2017.

f3. Karstensen J et al. Confocal laser endomicroscopy in ulcerative colitis: a longitudinal study of endomicroscopic changes and response to medical therapy (with videos). Gastrointestinal Endoscopy 2016.

f4. Karstensen J et al. Confocal laser endomicroscopy in ulcerative colitis: a longitudinal study of endomicroscopic changes and response to medical therapy (with videos). Gastrointestinal Endoscopy 2016.

f5. Musquer N, et al. Probe-based confocal laser endomicroscopy: A new method for quantitative analysis of pit structure in healthy and Crohn's disease patients. Digestive and Liver Disease, 2013.

f6. Turcotte JF, et al. Increased Epithelial Gaps in the Small Intestine Are Predictive of Hospitalization and Surgery in Patients with Inflammatory Bowel Disease. Clinical and Translational Gastroenterology, 2012.

f7. Liu JJ, et al. Increased Epithelial Gaps in the Small Intestines of Patients with Inflammatory Bowel Disease: Density Matters. Gastrointestinal Endoscopy, 2011.

f8. Neumann H, et al. Prospective Evaluation of the Learning Curve of Confocal Laser Endomicroscopy in Patients with IBD. Histology and Histopathology, 2011.

f9. Palma GD, et al. In-vivo Characterization of DALM in Ulcerative Colitis with High-Resolution Probe-based Confocal Laser Endomicroscopy. World Journal Gastroenterology, 2011.

f10. Neumann H, et al. Cancer Risk in IBD: How to Diagnose and How to Manage DALM and ALM. World Journal Gastroenterology, 2011.

e1. Lord R et al. Colonic lesion characterisation in inflammatory bowel disease : A systematic review and meta-analysis. World J Gastroenterol, 2018.

e2. Wanders LK, et al. Diagnostic performance of narrowed spectrum endoscopy, autofluorescence imaging, and confocal laser endomicroscopy for optical diagnosis of colonic polyps: a meta-analysis. Lancet, 2013.

e3. Shahid MW, et al. Diagnostic accuracy of probe-based confocal laser endomicroscopy in detecting residual colorectal neoplasia after EMR: a prospective study. Gastrointestinal Endoscopy, 2012.

e4. Shahid MW, et al. Accuracy of Real-Time vs. Blinded Offline Diagnosis of Neoplastic Colorectal Polyps using Probe-based Confocal Laser Endomicroscopy: a Pilot Study. Endoscopy, 2012.

e5. Shahid MW, et al. Diagnostic Accuracy of Probe-based Confocal Laser Endomicroscopy and Narrow Band Imaging for Small Colorectal Polyps: A Feasibility Study. The American Journal of Gastroenterology, 2012.

e6. Ussui MV, et al. Confocal Endomicroscopy of Colorectal Polyps. Gastroenterology Research and Practice, 2012.

e7. Kuiper T, et al. New Classification for Probe-based Confocal Laser Endomicroscopy in the Colon. Endoscopy, 2011.

e8. Buchner AM, et al. The Learning Curve of in vivo Probe-based Confocal Laser Endomicroscopy for Prediction of Colorectal Neoplasia. Gastrointestinal Endoscopy, 2011.

GENERAL PUBLICATIONS, REVIEWS AND OTHERg1. Y.-Q. Xiong et al. Comparison of narrow-band imaging and confocal laser endomicroscopy for the detection of neoplasia in

Barrett’s Esophagus : A meta-analysis. Clinics and Research in Hepatology and Gastroenterol, 2018.

g2. Wang K, et al. Use of probe-based confocal laser endomicroscopy (pCLE) in gastrointestinal applications. A consensus report based on clinical evidence. United European Gastroenterology journal, 2015.

g3. Turcotte JF, et al. Breaks in the wall: increased gaps in the intestinal epithelium of irritable bowel syndrome patients identified by confocal laser endomicroscopy (with videos). Gastrointestinal Endoscopy, 2013.

g4. Goetz M. Confocal Laser Endomicroscopy: Applications in Clinical and Translational Science – A comprehensive review. ISRN Pathology, 2012.

g5. Neumann H, et al. Confocal Laser Endomicroscopy: Technical Advances and Clinical Applications. Gastroenterology, 2010.

g6. Wallace MB, et al. The Safety of Intravenous Fluorescein for Confocal Laser Endomicroscopy in the Gastrointestinal Tract. Alimentary Pharmacology Therapeutics, 2010.

COLORECTAL LESIONS

Cellvizio® 100 Series Systems with Confocal MiniprobesTM are regulated Medical Device, CE marked (CE 0459) (Class IIa - NB :G-MED) and FDA cleared. Cellvizio® 100 Series Systems with Confocal MiniprobesTM are confocal laser systems with fiber optic probes that are intended to allow imaging of the internal microstructure of tissues including, but not limited to, the identification of cells and vessels and their organization or architecture. These statements and the associated reference to specific clinical studies, are not intended to represent claims of safety or effectiveness for detecting or treating any specific condition or disease state. Rather this information is intended to provide useful reference to selected published literature describing physician experiences with the associated clinical uses. Any diagnostic assessment should always be made by the attending physician, based on the evaluation of all sources of clinical, endoscopic and other relevant information. These statements have not been reviewed, cleared, or approved by the U.S. FDA. The use of this medical device is exclusively reserved for healthcare professionals.

COURTESY

h1. Image courtesy of Dr Wallace, Mayo Clinic Jacksonville, FL, USA.

h2. First image courtesy of Prof Rath, University of Erlangen, DE and second image courtesy of Dr. Dekker, AMC, Amsterdam, NE.

h3. Image courtesy of Dr. Zhen Li, Institute Shandong University, Qilu Hospital, China

h4. Image courtesy of Dr. Dekker, AMC, Amsterdam, NE

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