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Effects of teduglutide on histological parameters of intestinal anastomotic healing

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Summary

Background

Intestinal anastomotic failure continues to be one of the most relevant surgical incidents. Teduglutide is an enterotrophic long-acting equivalent of glucagon-like peptide-2 (GLP-2) recommended for the treatment of adult patients with short bowel syndrome. This study evaluates the effects of short-term teduglutide administration on histological parameters of intestinal anastomotic healing in an animal model.

Methods

Wistar rats (n = 31) were submitted to ileal resection and standard anastomosis, with or without postoperative teduglutide ministration, and sacrificed at the third or seventh day with tissue and blood sampling. Intestinal anastomotic healing was assessed with the modified Houdart–Hutschenreiter classification after hematoxylin and eosin staining. Collagen content and distribution were evaluated with the Gordon and Sweet technique; neoangiogenesis and epithelial proliferation indexes with anti-CD31 and anti-Ki67 immunostaining, respectively. GLP-2 plasma levels were determined by quantitative enzyme immunoassay.

Results

Teduglutide administration was associated with higher levels of reepithelialization (P = 0.022) and a higher neoangiogenesis index (neovessel density = 16.0 ± 10.8/mm2 vs. 5.3 ± 3.4/mm2; P = 0.0001) at the seventh postoperative day. Lower expression of type I collagen (P = 0.015) and higher content of type III collagen (P = 0.007) in the submucosa were also documented at the seventh day in teduglutide-treated animals. Drug administration was not associated with statistically significant differences of GLP-2 plasma levels.

Conclusion

These findings indicate a positive impact of teduglutide on the reepithelialization and neoangiogenesis events of the proliferative phase of intestinal anastomotic repair. Additional studies are necessary to clarify its effects on the fibrogenesis process.

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Author information

Authors and Affiliations

  1. Department of Surgery A, Coimbra University Hospital, Centro Hospitalar e Universitário de Coimbra, EPE, Praceta Mota Pinto, 3000-075, Coimbra, Portugal

    Beatriz P. Costa & Francisco Castro-Sousa

  2. University Clinic of Surgery, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Beatriz P. Costa & Francisco Castro-Sousa

  3. Department of Pathology, Coimbra University Hospital, Centro Hospitalar e Universitário de Coimbra, EPE, Coimbra, Portugal

    Maria A. Cipriano

  4. Laboratory of Oncobiology and Hematology, University Clinic of Hematology and Applied Molecular Biology Unit, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Ana C. Gonçalves & Ana B. Sarmento-Ribeiro

  5. Center for Neuroscience and Cell Biology (CNC) and Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Medicine, Coimbra, Portugal

    Ana C. Gonçalves, Ana M. Abrantes, Paulo Matafome, Raquel Seiça, Ana B. Sarmento-Ribeiro & M. Filomena Botelho

  6. Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Ana C. Gonçalves, Ana M. Abrantes, Ana B. Sarmento-Ribeiro & M. Filomena Botelho

  7. Institute of Biophysics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Ana M. Abrantes & M. Filomena Botelho

  8. Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Paulo Matafome & Raquel Seiça

  9. Department of Clinical Hematology, Coimbra University Hospital, Centro Hospitalar e Universitário de Coimbra, EPE, Coimbra, Portugal

    Ana B. Sarmento-Ribeiro

Authors
  1. Beatriz P. Costa
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  2. Maria A. Cipriano
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  3. Ana C. Gonçalves
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  4. Ana M. Abrantes
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  5. Paulo Matafome
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  7. Ana B. Sarmento-Ribeiro
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  8. M. Filomena Botelho
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  9. Francisco Castro-Sousa
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Corresponding author

Correspondence to Beatriz P. Costa.

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Conflict of interest

B.P. Costa, M.A. Cipriano, A.C. Gonçalves, A.M. Abrantes, P. Matafome,R. Seiça, A.B. Sarmento-Ribeiro, M. F. Botelho, and F. Castro-Sousa declare that they have no competing interests, including no financial or personal interests in any product mentioned or discussed in the article that could inappropriately influence their work.

Ethical standards

This experiment was authorized by the Ethics Committee of the Faculty of Medicine, University of Coimbra, Coimbra, Portugal (License nº32-06-2009) and conducted according to institutional and national animal welfare recommendations.

Additional information

Authors’ contributions Study conception and design: B. Costa; acquisition of data: B. Costa, M. A. Cipriano, A. C. Gonçalves, A. M. Abrantes, P. Matafome; analysis and interpretation of data: B. Costa; drafting of manuscript: B. Costa; critical review: M. A. Cipriano, R. Seiça, A. B. Sarmento-Ribeiro, M. F. Botelho, F. Castro Sousa

Original communication This manuscript represents original research that has not been previously published or submitted for publication elsewhere. The research leading to the results presented in this article was performed without external funding.

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Costa, B.P., Cipriano, M.A., Gonçalves, A.C. et al. Effects of teduglutide on histological parameters of intestinal anastomotic healing. Eur Surg 49, 218–227 (2017). https://doi.org/10.1007/s10353-017-0478-9

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  • DOI: https://doi.org/10.1007/s10353-017-0478-9

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