scholarly journals Novel Ex Vivo Model to Examine the Mechanism and Relationship of Esophageal Microbiota and Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 142
Author(s):  
Samuel Cass ◽  
Catherine Hamilton ◽  
Aaron Miller ◽  
Daniel Jupiter ◽  
Kamil Khanipov ◽  
...  

Rates of esophageal cancer have increased over the last 40 years. Recent clinical research has identified correlations between the esophageal microbiome and disease. However, mechanisms of action have been difficult to elucidate performing human experimentation. We propose an ex vivo model, which mimics the esophagus and is ideal for mechanistic studies on the esophageal microbiome and resultant transcriptome. To determine the microbiome and transcriptome profile of the human distal esophagus, the microbiome was assessed in 74 patients and the transcriptome profile was assessed in 37 patients with and without Barrett’s esophagus. Thereafter, an ex vivo model of the esophagus was created using an air–liquid interfaced (ALI) design. This design created a sterile apical surface and a nutrient-rich basal surface. An epithelial layer was grown on the apical surface. A normal microbiome and Barrett’s microbiome was harvested and created from patients during endoscopic examination of the esophagus. There was a distinct microbiome in patients with Barrett’s esophagus. The ex vivo model was successfully created with a squamous epithelial layer on the apical surface of the ex vivo system. Using this ex vivo model, multiple normal esophageal and Barrett’s esophageal cell lines will be created and used for experimentation. Each microbiome will be inoculated onto the sterile apical surface of each cell line. The resultant microbiome and transcriptome profile on each surface will be measured and compared to results in the human esophagus to determine the mechanism of the microbiome interaction.

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

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.


2012 ◽  
Vol 142 (5) ◽  
pp. S-336 ◽  
Author(s):  
Mads Sylvest Bergholt ◽  
Wei Zheng ◽  
Khek-Yu Ho ◽  
Ming Teh ◽  
Khay Guan Yeoh ◽  
...  

2000 ◽  
Vol 118 (3) ◽  
pp. 487-496 ◽  
Author(s):  
Vivian N. Shirvani ◽  
Rodica Ouatu-Lascar ◽  
Baljeet S. Kaur ◽  
M.Bishr Omary ◽  
George Triadafilopoulos

2000 ◽  
Author(s):  
Martin G. Shim ◽  
Louis-Michel Wong Kee Song ◽  
Norman E. Marcon ◽  
Shirley Hassaram ◽  
Brian C. Wilson

2017 ◽  
Vol 05 (08) ◽  
pp. E775-E783 ◽  
Author(s):  
Liang Lim ◽  
Catherine Streutker ◽  
Norman Marcon ◽  
Maria Cirocco ◽  
Alexandra Lao ◽  
...  

Abstract Background and study aims Accurate endoscopic detection of dysplasia in patients with Barrett’s esophagus (BE) remains a major clinical challenge. The current standard is to take multiple biopsies under endoscopic image guidance, but this leaves the majority of the tissue unsampled, leading to significant risk of missing dysplasia. Furthermore, determining whether there is submucosal invasion is essential for proper staging. Hence, there is a clinical need for a rapid in vivo wide-field imaging method to identify dysplasia in BE, with the capability of imaging beyond the mucosal layer. We conducted an ex vivo feasibility study using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) for known dysplasia. The objective was to characterize the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia detection and therapeutic guidance. Materials and methods EMR tissues were mounted luminal side up. The tissues were scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, and 850 nm (40 MHz acoustic central frequency). Ultrasound and photoacoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with hematoxylin and eosin staining. A total of 13 EMR specimens from eight patients were included in the analysis, which consisted of co-registration of the photoacoustic images with corresponding pathologist-classified histological images. We conducted mean difference test of the total hemoglobin distribution between tissue classes. Results Dysplastic and nondysplastic BE can be distinguished from squamous tissue in 84 % of region-of-interest comparisons (42/50). However, the ability of intrinsic PAI to distinguish dysplasia from NDBE, which is the clinically important challenge, was only about 33 % (10/30). Conclusion We demonstrated the technical feasibility of this approach. Based on our ex vivo data, changes in total hemoglobin content from intrinsic PAI (i. e. without exogenous contrast) can differentiate BE from squamous esophageal mucosa. However, most likely intrinsic PAI is unable to differentiate dysplastic from nondysplastic BE with adequate sensitivity for clinical translation.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Hany M. Elsadek ◽  
Mamdouh M. Radwan

Background. Endoscopic surveillance for early detection of dysplastic or neoplastic changes in patients with Barrett's esophagus (BE) depends usually on biopsy. The diagnostic and therapeutic role of endoscopic mucosal resection (EMR) in BE is rapidly growing. Objective. The aim of this study was to check the accuracy of biopsy for precise histopathologic diagnosis of dysplasia and neoplasia, compared to EMR in patients having BE and related superficial esophageal lesions. Methods. A total of 48 patients with previously diagnosed BE (36 men, 12 women, mean age 49.75±13.3 years) underwent routine surveillance endoscopic examination. Biopsies were taken from superficial lesions, if present, and otherwise from BE segments. Then, EMR was performed within three weeks. Results. Biopsy based histopathologic diagnoses were nondysplastic BE (NDBE), 22 cases; low-grade dysplasia (LGD), 14 cases; high-grade dysplasia (HGD), 8 cases; intramucosal carcinoma (IMC), two cases; and invasive adenocarcinoma (IAC), two cases. EMR based diagnosis differed from biopsy based diagnosis (either upgrading or downgrading) in 20 cases (41.67%), (Kappa =0.43, 95% CI: 0.170–0.69). Conclusions. Biopsy is not a satisfactory method for accurate diagnosis of dysplastic or neoplastic changes in BE patients with or without suspicious superficial lesions. EMR should therefore be the preferred diagnostic method in such patients.


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.


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