scholarly journals Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus

Author(s):  
Hsin-Yu Fang ◽  
Stefan Stangl ◽  
Sabrina Marcazzan ◽  
Marcos J. Braz Carvalho ◽  
Theresa Baumeister ◽  
...  

Abstract Purpose The incidence of esophageal adenocarcinoma (EAC) has been increasing for decades without significant improvements in treatment. Barrett’s esophagus (BE) is best established risk factor for EAC, but current surveillance with random biopsies cannot predict progression to cancer in most BE patients due to the low sensitivity and specificity of high-definition white light endoscopy. Methods Here, we evaluated the membrane-bound highly specific Hsp70-specific contrast agent Tumor-Penetrating Peptide (Hsp70-TPP) in guided fluorescence molecular endoscopy biopsy. Results Hsp70 was significantly overexpressed as determined by IHC in dysplasia and EAC compared with non-dysplastic BE in patient samples (n = 12) and in high-grade dysplastic lesions in a transgenic (L2-IL1b) mouse model of BE. In time-lapse microscopy, Hsp70-TPP was rapidly taken up and internalized  by human BE dysplastic patient–derived organoids. Flexible fluorescence endoscopy of the BE mouse model allowed a specific detection of Hsp70-TPP-Cy5.5 that corresponded closely with the degree of dysplasia but not BE. Ex vivo application of Hsp70-TPP-Cy5.5 to freshly resected whole human EAC specimens revealed a high (> 4) tumor-to-background ratio and a specific detection of previously undetected tumor infiltrations. Conclusion In summary, these findings suggest that Hsp70-targeted imaging using fluorescently labeled TPP peptide may improve tumor surveillance in BE patients.

2014 ◽  
Vol 28 (8) ◽  
pp. 742-749 ◽  
Author(s):  
S. S. Sami ◽  
V. Subramanian ◽  
W. M. Butt ◽  
G. Bejkar ◽  
J. Coleman ◽  
...  

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Sabrina Marcazzan ◽  
Marcos J. Braz Carvalho ◽  
Matthias Konrad ◽  
Julia Strangmann ◽  
Anna Tenditnaya ◽  
...  

Abstract Background Near-infrared (NIR) fluorescence imaging has been emerging as a promising strategy to overcome the high number of early esophageal adenocarcinomas missed by white light endoscopy and random biopsy collection. We performed a preclinical assessment of fluorescence imaging and endoscopy using a novel CXCR4-targeted fluorescent peptide ligand in the L2-IL1B mouse model of Barrett’s esophagus. Methods Six L2-IL1B mice with advanced stage of disease (12–16 months old) were injected with the CXCR4-targeted, Sulfo-Cy5-labeled peptide (MK007), and ex vivo wide-field imaging of the whole stomach was performed 4 h after injection. Before ex vivo imaging, fluorescence endoscopy was performed in three L2-IL1B mice (12–14 months old)  by a novel imaging system with two L2-IL1B mice used as negative controls. Results Ex vivo imaging and endoscopy in L2-IL1B mice showed that the CXCR4-targeted MK007 accumulated mostly in the dysplastic lesions with a mean target-to-background ratio > 2. The detection of the Sulfo-Cy5 signal in dysplastic lesions and its co-localization with CXCR4 stained cells  by confocal microscopy further confirmed the imaging results. Conclusions This preliminary preclinical study shows that CXCR4-targeted fluorescence endoscopy using MK007 can detect dysplastic lesions in a mouse model of Barrett’s esophagus. Further investigations are needed to assess its use in the clinical setting.


2013 ◽  
Vol 144 (5) ◽  
pp. S-1064
Author(s):  
Thai H. Pham ◽  
David H. Wang ◽  
Robert M. Genta ◽  
Rhonda F. Souza ◽  
Stuart J. Spechler

Endoscopy ◽  
2001 ◽  
Vol 33 (5) ◽  
pp. 391-400 ◽  
Author(s):  
M. I. Canto ◽  
S. Setrakian ◽  
J. E. Willis ◽  
A. Chak ◽  
R. E. Petras ◽  
...  

2015 ◽  
Vol 13 (6) ◽  
pp. 1068-1074.e2 ◽  
Author(s):  
Svein Olav Bratlie ◽  
Erik Johnsson ◽  
Claes Jönsson ◽  
Lars Fändriks ◽  
Anders Edebo

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 244
Author(s):  
Yuji Amano ◽  
Norihisa Ishimura ◽  
Shunji Ishihara

Given that endoscopic findings can be used to predict the potential of neoplastic progression in Barrett’s esophagus (BE) cases, the detection rate of dysplastic Barrett’s lesions may become higher even in laborious endoscopic surveillance because a special attention is consequently paid. However, endoscopic findings for effective detection of the risk of neoplastic progression to esophageal adenocarcinoma (EAC) have not been confirmed, though some typical appearances are suggestive. In the present review, endoscopic findings that can be used predict malignant potential to EAC in BE cases are discussed. Conventional results obtained with white light endoscopy, such as length of BE, presence of esophagitis, ulceration, hiatal hernia, and nodularity, are used as indicators of a higher risk of neoplastic progression. However, there are controversies in some of those findings. Absence of palisade vessels may be also a new candidate predictor, as that reveals degree of intense inflammation and of cyclooxygenase-2 protein expression with accelerated cellular proliferation. Furthermore, an open type of mucosal pattern and enriched stromal blood vessels, which can be observed by image-enhanced endoscopy, including narrow band imaging, have been confirmed as factors useful for prediction of neoplastic progression of BE because they indicate more frequent cyclooxygenase-2 protein expression along with accelerated cellular proliferation. Should the malignant potential of BE be shown predictable by these endoscopic findings, that would simplify methods used for an effective surveillance, because patients requiring careful monitoring would be more easily identified. Development in the near future of a comprehensive scoring system for BE based on clinical factors, biomarkers and endoscopic predictors is required.


2019 ◽  
Vol 156 (6) ◽  
pp. S-57-S-58
Author(s):  
Durgadevi Ravillah ◽  
Anne Baskin ◽  
Nathan A. Berger ◽  
Ronald A. Conlon ◽  
Joseph Willis ◽  
...  

Endoscopy ◽  
2017 ◽  
Vol 49 (12) ◽  
pp. 1219-1228 ◽  
Author(s):  
Gideon Lipman ◽  
Raf Bisschops ◽  
Vinay Sehgal ◽  
Jacobo Ortiz-Fernández-Sordo ◽  
Rami Sweis ◽  
...  

Abstract Background and study aims Enhanced endoscopic imaging with chromoendoscopy may improve dysplasia recognition in patients undergoing assessment of Barrett’s esophagus (BE). This may reduce the need for random biopsies to detect more dysplasia. The aim of this study was to assess the effect of magnification endoscopy with I-SCAN (Pentax, Tokyo, Japan) and acetic acid (ACA) on dysplasia detection in BE using a novel mucosal and vascular classification system. Methods BE segments and suspicious lesions were recorded with high definition white-light and magnification endoscopy enhanced using all I-SCAN modes in combination. We created a novel mucosal and vascular classification system based on similar previously validated classifications for narrow-band imaging (NBI). A total of 27 videos were rated before and after ACA application. Following validation, a further 20 patients had their full endoscopies recorded and analyzed to model use of the system to detect dysplasia in a routine clinical scenario. Results The accuracy of the I-SCAN classification system for BE dysplasia improved with I-SCAN magnification from 69 % to 79 % post-ACA (P = 0.01). In the routine clinical scenario model in 20 new patients, accuracy of dysplasia detection increased from 76 % using a “pull-through” alone to 83 % when ACA and magnification endoscopy were combined (P = 0.047). Overall interobserver agreement between experts for dysplasia detection was substantial (0.69). Conclusions A new I-SCAN classification system for BE was validated against similar systems for NBI with similar outcomes. When used in combination with magnification and ACA, the classification detected BE dysplasia in clinical practice with good accuracy.Trials registered at ISRCTN (58235785).


Endoscopy ◽  
2018 ◽  
Vol 50 (06) ◽  
pp. 618-625 ◽  
Author(s):  
André Neves ◽  
Massimiliano Di Pietro ◽  
Maria O’Donovan ◽  
Dale Waterhouse ◽  
Sarah Bohndiek ◽  
...  

Abstract Background and study aims Endoscopic surveillance for Barrett’s esophagus (BE) is limited by long procedure times and sampling error. Near-infrared (NIR) fluorescence imaging minimizes tissue autofluorescence and optical scattering. We assessed the feasibility of a topically applied NIR dye-labeled lectin for the detection of early neoplasia in BE in an ex vivo setting. Methods Consecutive patients undergoing endoscopic mucosal resection (EMR) for BE-related early neoplasia were recruited. Freshly collected EMR specimens were sprayed at the bedside with fluorescent lectin and then imaged. Punch biopsies were collected from each EMR under NIR light guidance. We compared the fluorescence intensity from dysplastic and nondysplastic areas within EMRs and from punch biopsies with different histological grades. Results 29 EMR specimens were included from 17 patients. A significantly lower fluorescence was found for dysplastic regions across whole EMR specimens (P < 0.001). We found a 41 % reduction in the fluorescence of dysplastic compared to nondysplastic punch biopsies (P < 0.001), with a sensitivity and specificity for dysplasia detection of 80 % and 82.9 %, respectively. Conclusion Lectin-based NIR imaging can differentiate dysplastic from nondysplastic Barrett’s mucosa ex vivo.


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