Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Aug 27, 2024; 16(8): 2679-2688
Published online Aug 27, 2024. doi: 10.4240/wjgs.v16.i8.2679
Effect of growth hormone on colonic anastomosis after intraperitoneal administration of 5-fluorouracil, bleomycin and cisplatin: An experimental study
Ioannis Lambrou, Ioannis Mantzoros, Orestis Ioannidis, Dimitrios Tatsis, Elissavet Anestiadou, Vasiliki Bisbinas, Manousos-Georgios Pramateftakis, Efstathios Kotidis, Barbara Driagka, Ourania Kerasidou, Savvas Symeonidis, Stefanos Bitsianis, Freideriki Sifaki, Konstantinos Angelopoulos, Haralabos Demetriades, Stamatios Angelopoulos
Ioannis Lambrou, Ioannis Mantzoros, Orestis Ioannidis, Dimitrios Tatsis, Elissavet Anestiadou, Manousos-Georgios Pramateftakis, Efstathios Kotidis, Barbara Driagka, Ourania Kerasidou, Savvas Symeonidis, Stefanos Bitsianis, Freideriki Sifaki, Konstantinos Angelopoulos, Haralabos Demetriades, Stamatios Angelopoulos, Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
Vasiliki Bisbinas, Department of ENT, Royal Cornwall Hospitals NHS Trust, Cornwall TR1 3LJ, United Kingdom
Author contributions: Lambrou I, Ioannidis O, Mantzoros I contributed equally to this work; Lambrou I, Mantzoros I, Pramateftakis MG, Anestiadou E, Driagka B designed and coordinated the research, participated equally in treatment of the animals, performed the experiments and acquired the data; Ioannidis O, Tatsis D, Kotidis E, Kerasidou O, Symeonidis S, Bitsianis S, Sifaki F, Demetriades H, Angelopoulos K, Angelopoulos S analyzed and interpreted the data; Lambrou I, Ioannidis O, Mantzoros I, Tatsis D, Anestiadou E, Bisbinas V wrote the paper; Lambrou I, Ioannidis O, Mantzoros I, Tatsis D, Anestiadou E, Bisbinas V, Driagka B, Pramateftakis MG, Kotidis E, Kerasidou O, Demetriades H, Symeonidis S, Bitsianis S, Sifaki F, Angelopoulos K, Angelopoulos S significantly contributed to the linguistic formatting and correction of the manuscript, revised it critically for important intellectual content, and were responsible for final proof reading of the article.
Institutional review board statement: The study was reviewed and approved by the Faculty of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Institutional animal care and use committee statement: The research protocol was reviewed and approved by the Institutional Animal Care and Use Committee of the Veterinary Manager of the Prefecture of Thessaloniki according to the Greek Law on the protection of animals and to law 86/609 EEC of the European Union.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: All data are available upon request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Orestis Ioannidis, MD, MSc, PhD, Assistant Professor, Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Stilponos Kyriakides 1 Str, Thessaloniki 57010, Greece. telonakos@hotmail.com
Received: March 6, 2024
Revised: May 20, 2024
Accepted: June 17, 2024
Published online: August 27, 2024
Processing time: 163 Days and 6 Hours
Abstract
BACKGROUND

Growth hormone (GH) plays a crucial role in wound healing and tissue repair in postoperative patients. In particular, colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherapy agents.

AIM

To investigate whether GH can improve the healing of a colonic anastomosis following the adverse effects of intraperitoneal administration of 5-fluorouracil (5-FU), bleomycin and cisplatin.

METHODS

Eighty Wistar rats underwent laparotomy and a 1 cm-resection of the transverse colon, followed by an end-to-end anastomosis under general anesthesia. The rats were blindly allocated into four equal groups and administered a different daily intraperitoneal therapeutic regimen for 6 days. The control group (A) received normal saline. Group B received chemotherapy with 5-FU (20 mg/kg), bleomycin (4 mg/kg) and cisplatin (0.7 mg/kg). Group C received GH (2 mg/kg), and group D received the aforementioned combination chemotherapy and GH, as described. The rats were sacrificed on the 7th postoperative day and the anastomoses were macroscopically and microscopically examined. Body weight, bursting pressure, hydroxyproline levels and inflammation markers were measured.

RESULTS

All rats survived until the day of sacrifice, with no infections or other complications. A decrease in the body weight of group D rats was observed, not statistically significant compared to group A (P = 1), but significantly different to groups C (P = 0.001) and B (P < 0.01). Anastomotic dehiscence rate was not statistically different between the groups. Bursting pressure was not significantly different between groups A and D (P = 1.0), whereas group B had a significantly lower bursting pressure compared to group D (P < 0.001). All groups had significantly more adhesions than group A. Hydroxyproline, as a measurement of collagen deposition, was significantly higher in group D compared to group B (P < 0.05), and higher, but not statistically significant, compared to group A. Significant changes in group D were recorded, compared to group A regarding inflammation (3.450 vs 2.900, P = 0.016) and fibroblast activity (2.75 vs 3.25, P = 0.021). Neoangiogenesis and collagen deposition were not significantly different between groups A and D. Collagen deposition was significantly increased in group D compared to group B (P < 0.001).

CONCLUSION

Intraperitoneal administration of chemotherapy has an adverse effect on the healing process of colonic anastomosis. However, GH can inhibit the deleterious effect of administered chemotherapy agents and induce colonic healing in rats.

Keywords: Growth hormone; Colonic anastomosis; Adhesion; Bursting pressure; Collagen; Hydroxyproline; Inflammation; Neoangiogenesis; Chemotherapy

Core Tip: The present study was designed to investigate the effect of growth hormone (GH) on the healing of colonic anastomoses in rats after intraperitoneal administration of 5-fluorouracil, bleomycin and cisplatin. The application of GH was found to have a protective role in the healing of colonic anastomoses in rats by effectively reversing the detrimental effects of chemotherapy.