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The effect of sealing with a fixed combination of collagen matrix-bound coagulation factors on the healing of colonic anastomoses in experimental high-risk mice models

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Abstract

Purpose

Experimental and clinical studies on the sealing of colorectal anastomoses in order to reduce the rate of leakage have previously been performed with divergent results. However, comparatively few studies have been performed on anastomotic healing using a fibrin glue-coated patch. The aim of this experimental basic scientific study in mice was to investigate the effect of fibrin glue-coated collagen patches on the healing process of colonic anastomoses in situations of adverse healing process (technical deficiency and peritonitis).

Methods

Colonic anastomoses were carried out in 206 mice and randomized into six groups (I: complete anastomoses, II: sealed complete anastomoses, III: incomplete anastomoses, IV: sealed incomplete anastomoses, V: complete anastomoses in the presence of bacterial peritonitis, VI: sealed complete anastomoses in the presence of bacterial peritonitis). Tissues from the anastomoses were removed and used for functional, histochemical, molecular, and biochemical investigations.

Results

The evaluation of postoperative course data revealed the beneficial effect of additional sealing with a fixed combination of collagen matrix-bound coagulation factors I and IIa (Tachosil®, Nycomed Austria, Linz) in high-risk experimental anastomotic healing. Sealing incomplete anastomoses resulted in significantly lower lethality and leakage rates, as well as significantly higher bursting pressure values and histopathologic scores. Collagen 1 and 3 expressions and hydroxyproline concentrations are greatly increased with additional sealing in all high-risk anastomoses.

Conclusions

In our current model, we demonstrate that additionally sealing high-risk experimental colonic anastomoses provides a positive effect on the healing process. The effect on the molecular level in particular seems to be essential and requires further experimental studies to evaluate the mechanism.

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Abbreviations

ABP:

anastomotic bursting pressure

AHS:

anastomotic healing score

AL:

anastomotic leakage

cDNA:

complimentary DNA

CLP:

cecal ligation puncture

CMBCF:

collagen matrix-bound coagulation factors (Tachosil®)

Col-1:

collagen I

Col-3:

collagen III

HE:

hematoxylin–eosin

HPC:

hydroxyproline concentration

KRB:

Krebs–Ringer buffer

POD:

postoperative day

RT-PCR:

reverse transcriptase-polymerase chain reaction

WT:

wild type

8′-Ana:

complete anastomosis (eight interrupted sutures)

sl_8′Ana:

sealed complete anastomoses

4′-Ana:

incomplete anastomosis (four interrupted sutures)

sl_4′-Ana:

sealed incomplete anastomoses

p-Ana:

peritonitis/sepsis—anastomoses

sl_p-Ana:

peritonitis/sepsis—sealed anastomoses

References

  1. Stumpf M, Klinge U, Wilms A, Zabrocki R, Rosch R, Junge K, Krones C, Schumpelick V (2005) Changes of the extracellular matrix as a risk factor for anastomotic leakage after large bowel surgery. Surgery 137:229–234

    Article  PubMed  Google Scholar 

  2. Golub R, Golub RW, Cantu R Jr, Stein HD (1997) A multivariate analysis of factors contributing to leakage of intestinal anastomoses. J Am Coll Surg 184:364–372

    CAS  PubMed  Google Scholar 

  3. Garcia-Botello SA, Garcia-Granero E, Lillo R, Lopez-Mozos F, Millan M, Lledo S (2006) Randomized clinical trial to evaluate the effects of perioperative supplemental oxygen administration on the colorectal anastomosis. Br J Surg 93:698–706

    Article  CAS  PubMed  Google Scholar 

  4. Vignali A, Fazio VW, Lavery IC, Milsom JW, Church JM, Hull TL, Strong SA, Oakley JR (1997) Factors associated with the occurrence of leaks in stapled rectal anastomoses: a review of 1,014 patients. J Am Coll Surg 185:105–113

    CAS  PubMed  Google Scholar 

  5. Kanellos I, Mantzoros I, Demetriades H, Kalfadis S, Kelpis T, Sakkas L, Betsis D (2004) Healing of colon anastomoses covered with fibrin glue after immediate postoperative intraperitoneal administration of 5-fluorouracil. Dis Colon Rectum 47:510–515

    Article  CAS  PubMed  Google Scholar 

  6. Shinohara K, Kobayashi E, Yoshida T, Toyama N, Kiyozaki H, Fujimura A, Miyata M (1998) Effect of fibrin glue on small and large bowel anastomoses in the rat. Eur Surg Res 30:8–12

    Article  CAS  PubMed  Google Scholar 

  7. van der Ham AC, Kort WJ, Weijma IM, van den Ingh HFG, Jeekel H (1992) Effect of antibiotics in fibrin sealant on healing colonic anastomoses in the rat. Br J Surg 79:525–528

    Article  PubMed  Google Scholar 

  8. van der Ham AC, Kort WJ, Weijma IM, van den Ingh HFG, Jeekel J (1991) Effect of fibrin sealant on the healing colonic anastomosis in the rat. Br J Surg 78:49–53

    Article  PubMed  Google Scholar 

  9. Nordentoft T, Romer J, Sorensen M (2007) Sealing of gastrointestinal anastomoses with a fibrin glue-coated collagen patch: a safety study. J Invest Surg 20:363–369

    Article  PubMed  Google Scholar 

  10. O'Leary DP (1999) Use of the greater omentum in colorectal surgery. Dis Colon Rectum 42:533–539

    Article  PubMed  Google Scholar 

  11. Ozel SK, Kazez A, Akpolat N (2006) Does a fibrin-collagen patch support early anastomotic healing in the colon? An experimental study. Tech Coloproctol 10:233–236

    Article  CAS  PubMed  Google Scholar 

  12. Biert J, Seifert WF, Verhofstad AAJ, Wobbes T, de Man BM, Hoogenhout J, Hendriks T (1998) A semiquantitative histological analysis of repair of anastomoses in the rat colon after combined preoperative irradiation and local hyperthermia. Radiat Res 149:372–377

    Article  CAS  PubMed  Google Scholar 

  13. Verhofstad MHJ, Lange WP, van der Laak JAWM, Verhofstad AAJ, Hendriks T (2001) Microscopic analysis of anastomotic healing in the intestine of normal and diabetic rats. Dis Colon Rectum 44:423–431

    Article  CAS  PubMed  Google Scholar 

  14. Attard JAP, Raval MJ, Martin GR, Kolb J, Afrouzian M, Buie WD, Sigalet DL (2005) The effects of systemic hypoxia on colon anastomotic healing: an animal model. Dis Colon Rectum 48:1460–1470

    Article  PubMed  Google Scholar 

  15. Pantelis D, Kabba MS, Kirfel J, Kahl P, Wehner S, Buettner R, Hirner A, Kalff JC (2010) Transient perioperative pharmacologic inhibition of muscularis macrophages as a target for prophylaxis of postoperative ileus does not affect anastomotic healing in mice. Surgery. doi:10.1016/j.surg.2009.12.010

    PubMed  Google Scholar 

  16. Jamall IS, Finelli VN, Hee SSQ (1981) A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues. Anal Biochem 112:70–75

    Article  CAS  PubMed  Google Scholar 

  17. Boigk G, Stroedter L, Herbst H, Waldschmidt J, Riecken EO, Schuppan D (1997) Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. Hepatology 26:643–649

    Article  CAS  PubMed  Google Scholar 

  18. Wehner S, Behrendt FF, Lyutenski BN, Lysson M, Bauer AJ, Hirner A, Kalff JC (2007) Inhibition of macrophage function prevents intestinal inflammation and postoperative ileus in rodents. Gut 56:176–185

    Article  CAS  PubMed  Google Scholar 

  19. Kanellos I, Mantzoros I, Goulimaris I, Zacharakis E, Zavitsanakis A, Betsis D (2003) Effects of the use of fibrin glue around the colonic anastomosis of the rat. Tech Coloproctol 7:82–84

    Article  CAS  PubMed  Google Scholar 

  20. Stumpf M, Junge K, Rosch R, Krones C, Klinge U, Schumpelick V (2009) Suture-free small bowel anastomoses using collagen fleece covered with fibrin glue in pigs. J Invest Surg 22:138–147

    Article  PubMed  Google Scholar 

  21. Hillan K, Nordlinger B, Ballet F, Puts JP, Infante R (1988) The healing of colonic anastomoses after early intraperitoneal chemotherapy: an experimental study in rats. J Surg Res 44:166–171

    Article  CAS  PubMed  Google Scholar 

  22. van der Ham AC, Kort WJ, Weijma IM, Jeekel H (1993) Transient protection of incomplete colonic anastomoses with fibrin sealant: an experimental study in the rat. J Surg Res 55:256–260

    Article  PubMed  Google Scholar 

  23. Wang P, Gong G, Li Y, Li J (2009) Hydroxyethyl starch 130/0.4 augments healing of colonic anastomosis in a rat model of peritonitis. Am J Surg 199:232–239

    Article  PubMed  Google Scholar 

  24. Orlando MD, Chendrasekhar A, Bundz S, Burt ET, Moorman DW, Timberlake GA (1999) The effect of peritoneal contamination on wound strength of small bowel and colonic anastomoses. Am Surg 65:673–675

    CAS  PubMed  Google Scholar 

  25. van der Vliet JA, Willems MC, de Man BM, Lomme RM, Hendriks T (2006) Everolimus interferes with healing of experimental intestinal anastomoses. Transplantation 82:1477–1483

    Article  PubMed  Google Scholar 

  26. Lapiere CM (2003) Collagenase and impaired wound healing. J Invest Dermatol 120:12–13

    Article  CAS  PubMed  Google Scholar 

  27. Stegemann H, Stalder K (1967) Determination of hydroxyproline. Clin Chim Acta 18:267–273

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Joerg C. Kalff.

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Authors’ contributions

Study conception and design acquisition of data, analysis, and interpretation of data and drafting of manuscript were done by Dimitrios Pantelis. Acquisition of data was made by Anke Beissel and Tim O. Vilz. Acquisition of data analysis and interpretation of data were made by Philip Kahl and Sven Wehner. Jörg C. Kalff made the study conception and design analysis and interpretation of data, as well as the critical revision of the manuscript.

This study was supported by an unrestricted grant from Nycomed Germany which had no influence on the design, execution, or interpretation of the study.

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Pantelis, D., Beissel, A., Kahl, P. et al. The effect of sealing with a fixed combination of collagen matrix-bound coagulation factors on the healing of colonic anastomoses in experimental high-risk mice models. Langenbecks Arch Surg 395, 1039–1048 (2010). https://doi.org/10.1007/s00423-010-0703-5

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