Cargando…

Case Report: Morphologic and Functional Characteristics of Intestinal Mucosa in a Child With Short Bowel Syndrome After Treatment With Teduglutide: Evidence in Favor of GLP-2 Analog Safety

Teduglutide is a glucagon-like peptide-2 (GLP-2) analog employed in patients with short bowel syndrome (SBS) to reduce the need of parenteral nutrition in these patients, by virtue of its effects on enteric function. The experimental studies reported that the stimulating action of GLP-2 on epithelia...

Descripción completa

Detalles Bibliográficos
Autores principales: Falco, Enrico Costantino, Lezo, Antonella, Calvo, Pierluigi, Rigazio, Caterina, Opramolla, Anna, Verdun, Ludovica, Cenacchi, Giovanna, Pellegrini, Marianna, Spada, Marco, Canavese, Gabriella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261410/
https://www.ncbi.nlm.nih.gov/pubmed/35811959
http://dx.doi.org/10.3389/fnut.2022.866048
_version_ 1784742271886819328
author Falco, Enrico Costantino
Lezo, Antonella
Calvo, Pierluigi
Rigazio, Caterina
Opramolla, Anna
Verdun, Ludovica
Cenacchi, Giovanna
Pellegrini, Marianna
Spada, Marco
Canavese, Gabriella
author_facet Falco, Enrico Costantino
Lezo, Antonella
Calvo, Pierluigi
Rigazio, Caterina
Opramolla, Anna
Verdun, Ludovica
Cenacchi, Giovanna
Pellegrini, Marianna
Spada, Marco
Canavese, Gabriella
author_sort Falco, Enrico Costantino
collection PubMed
description Teduglutide is a glucagon-like peptide-2 (GLP-2) analog employed in patients with short bowel syndrome (SBS) to reduce the need of parenteral nutrition in these patients, by virtue of its effects on enteric function. The experimental studies reported that the stimulating action of GLP-2 on epithelial turnover implies the potential development of dysplastic and neoplastic lesion. However, the clinical trials could not detect preneoplastic lesions on histologic material, and in a recent pilot study the occurrence of polyps was similar before and after treatment and included only low-grade dysplastic lesions. Another clue in GLP-2 function in stimulating mucosal restore is its enhancement through cooperation with epidermal growth factor (EGF). In this study, we analyzed gastroscopy and colonoscopy samplings from a child successfully weaned off parenteral nutrition with teduglutide. Villous and crypt structure was regular both in duodenal and in colonic samplings; in properly oriented villi, villus/crypt ratio was regular. The absorptive epithelium demonstrated a regular morphology. No atypia was detected in enterocytes, along epithelial structures. At the ultrastructural analysis, only a few enterocytes with vacuolized cytoplasm were observed. An S-phase marker Ki67 stained nuclei in the transitional amplifying zone, while nuclei stained by the cell cycle regulatory proteins p21 and p27 were placed in the differentiated epithelium of the duodenal villi and colonic crypts, as in the control cases. The counts of enterocytes immunostained with the same antisera, evaluated with image analysis software, were in the range of control cases. The ratio of the number of epidermal growth factor receptor (EGFR) signals/the number of centromere probe of chromosome 7 (CEP7) signals was less than 2. The findings available from this single patient are consistent with good preservation of functional capability of intestinal epithelium after treatment with GLP-2, given the histologic and ultrastructural features of enterocytes. In addition, the findings from cell cycle regulatory proteins immunolocalization and quantitative analysis show that cell renewal machinery in our case is comparable to control cases. The gene of the receptor EGFR is regularly expressed in enteric epithelium of our case. Morphologic and functional data from our patient improve evidence in favor of the safety of GLP-2 employ in SBS.
format Online
Article
Text
id pubmed-9261410
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92614102022-07-08 Case Report: Morphologic and Functional Characteristics of Intestinal Mucosa in a Child With Short Bowel Syndrome After Treatment With Teduglutide: Evidence in Favor of GLP-2 Analog Safety Falco, Enrico Costantino Lezo, Antonella Calvo, Pierluigi Rigazio, Caterina Opramolla, Anna Verdun, Ludovica Cenacchi, Giovanna Pellegrini, Marianna Spada, Marco Canavese, Gabriella Front Nutr Nutrition Teduglutide is a glucagon-like peptide-2 (GLP-2) analog employed in patients with short bowel syndrome (SBS) to reduce the need of parenteral nutrition in these patients, by virtue of its effects on enteric function. The experimental studies reported that the stimulating action of GLP-2 on epithelial turnover implies the potential development of dysplastic and neoplastic lesion. However, the clinical trials could not detect preneoplastic lesions on histologic material, and in a recent pilot study the occurrence of polyps was similar before and after treatment and included only low-grade dysplastic lesions. Another clue in GLP-2 function in stimulating mucosal restore is its enhancement through cooperation with epidermal growth factor (EGF). In this study, we analyzed gastroscopy and colonoscopy samplings from a child successfully weaned off parenteral nutrition with teduglutide. Villous and crypt structure was regular both in duodenal and in colonic samplings; in properly oriented villi, villus/crypt ratio was regular. The absorptive epithelium demonstrated a regular morphology. No atypia was detected in enterocytes, along epithelial structures. At the ultrastructural analysis, only a few enterocytes with vacuolized cytoplasm were observed. An S-phase marker Ki67 stained nuclei in the transitional amplifying zone, while nuclei stained by the cell cycle regulatory proteins p21 and p27 were placed in the differentiated epithelium of the duodenal villi and colonic crypts, as in the control cases. The counts of enterocytes immunostained with the same antisera, evaluated with image analysis software, were in the range of control cases. The ratio of the number of epidermal growth factor receptor (EGFR) signals/the number of centromere probe of chromosome 7 (CEP7) signals was less than 2. The findings available from this single patient are consistent with good preservation of functional capability of intestinal epithelium after treatment with GLP-2, given the histologic and ultrastructural features of enterocytes. In addition, the findings from cell cycle regulatory proteins immunolocalization and quantitative analysis show that cell renewal machinery in our case is comparable to control cases. The gene of the receptor EGFR is regularly expressed in enteric epithelium of our case. Morphologic and functional data from our patient improve evidence in favor of the safety of GLP-2 employ in SBS. Frontiers Media S.A. 2022-06-23 /pmc/articles/PMC9261410/ /pubmed/35811959 http://dx.doi.org/10.3389/fnut.2022.866048 Text en Copyright © 2022 Falco, Lezo, Calvo, Rigazio, Opramolla, Verdun, Cenacchi, Pellegrini, Spada and Canavese. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Falco, Enrico Costantino
Lezo, Antonella
Calvo, Pierluigi
Rigazio, Caterina
Opramolla, Anna
Verdun, Ludovica
Cenacchi, Giovanna
Pellegrini, Marianna
Spada, Marco
Canavese, Gabriella
Case Report: Morphologic and Functional Characteristics of Intestinal Mucosa in a Child With Short Bowel Syndrome After Treatment With Teduglutide: Evidence in Favor of GLP-2 Analog Safety
title Case Report: Morphologic and Functional Characteristics of Intestinal Mucosa in a Child With Short Bowel Syndrome After Treatment With Teduglutide: Evidence in Favor of GLP-2 Analog Safety
title_full Case Report: Morphologic and Functional Characteristics of Intestinal Mucosa in a Child With Short Bowel Syndrome After Treatment With Teduglutide: Evidence in Favor of GLP-2 Analog Safety
title_fullStr Case Report: Morphologic and Functional Characteristics of Intestinal Mucosa in a Child With Short Bowel Syndrome After Treatment With Teduglutide: Evidence in Favor of GLP-2 Analog Safety
title_full_unstemmed Case Report: Morphologic and Functional Characteristics of Intestinal Mucosa in a Child With Short Bowel Syndrome After Treatment With Teduglutide: Evidence in Favor of GLP-2 Analog Safety
title_short Case Report: Morphologic and Functional Characteristics of Intestinal Mucosa in a Child With Short Bowel Syndrome After Treatment With Teduglutide: Evidence in Favor of GLP-2 Analog Safety
title_sort case report: morphologic and functional characteristics of intestinal mucosa in a child with short bowel syndrome after treatment with teduglutide: evidence in favor of glp-2 analog safety
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261410/
https://www.ncbi.nlm.nih.gov/pubmed/35811959
http://dx.doi.org/10.3389/fnut.2022.866048
work_keys_str_mv AT falcoenricocostantino casereportmorphologicandfunctionalcharacteristicsofintestinalmucosainachildwithshortbowelsyndromeaftertreatmentwithteduglutideevidenceinfavorofglp2analogsafety
AT lezoantonella casereportmorphologicandfunctionalcharacteristicsofintestinalmucosainachildwithshortbowelsyndromeaftertreatmentwithteduglutideevidenceinfavorofglp2analogsafety
AT calvopierluigi casereportmorphologicandfunctionalcharacteristicsofintestinalmucosainachildwithshortbowelsyndromeaftertreatmentwithteduglutideevidenceinfavorofglp2analogsafety
AT rigaziocaterina casereportmorphologicandfunctionalcharacteristicsofintestinalmucosainachildwithshortbowelsyndromeaftertreatmentwithteduglutideevidenceinfavorofglp2analogsafety
AT opramollaanna casereportmorphologicandfunctionalcharacteristicsofintestinalmucosainachildwithshortbowelsyndromeaftertreatmentwithteduglutideevidenceinfavorofglp2analogsafety
AT verdunludovica casereportmorphologicandfunctionalcharacteristicsofintestinalmucosainachildwithshortbowelsyndromeaftertreatmentwithteduglutideevidenceinfavorofglp2analogsafety
AT cenacchigiovanna casereportmorphologicandfunctionalcharacteristicsofintestinalmucosainachildwithshortbowelsyndromeaftertreatmentwithteduglutideevidenceinfavorofglp2analogsafety
AT pellegrinimarianna casereportmorphologicandfunctionalcharacteristicsofintestinalmucosainachildwithshortbowelsyndromeaftertreatmentwithteduglutideevidenceinfavorofglp2analogsafety
AT spadamarco casereportmorphologicandfunctionalcharacteristicsofintestinalmucosainachildwithshortbowelsyndromeaftertreatmentwithteduglutideevidenceinfavorofglp2analogsafety
AT canavesegabriella casereportmorphologicandfunctionalcharacteristicsofintestinalmucosainachildwithshortbowelsyndromeaftertreatmentwithteduglutideevidenceinfavorofglp2analogsafety