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Strahlentherapie und Onkologie

, Volume 195, Issue 1, pp 52–61 | Cite as

Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis

  • Raimund H. M. PreidlEmail author
  • Patrick Möbius
  • Manuel Weber
  • Kerstin Amann
  • Friedrich W. Neukam
  • Marco Kesting
  • Carol-Immanuel Geppert
  • Falk Wehrhan
Original Article

Abstract

Background

Microvascular free flap reconstruction has become a standard technique in head and neck reconstructive surgery. Pre-operative radiotherapy is associated with a higher incidence of free flap malperfusion and the need for operative revision. Irradiated vessels present characteristic histomorphological and structural changes. Alterations in endothelial cells of irradiated arteries remain incompletely investigated especially with regard to long-term changes in endothelial dysfunction supporting an intraluminal pro-thrombotic and pro-inflammatory milieu.

Methods

Endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E‑ and P‑selectin, endothelial NO-synthase (eNOS), thrombomodulin and plasminogen activator inhibitor-1 (PAI-1) in irradiated and non-irradiated arteries was analysed using immunohistochemistry and Remmele scale grading. The average radiation dose was 58.7 ± 7.0 Gy; the time interval between end of radiation and tissue sampling was 106.0 ± 86.8 months.

Results

Endothelial expression of ICAM-1, VCAM-1, E‑ and P‑selectin as well as PAI-1 was significantly increased in previously irradiated arteries compared with non-irradiated controls, whereas thrombomodulin and eNOS expression did not show any differences. However, when comparing non-irradiated free flap arteries with irradiated arteries from the head and neck area in respective individuals, eNOS expression was significantly lower in irradiated vessels whereas ICAM-1, VCAM-1, E‑/p-Selectin and PAI-1 showed significantly higher expression levels.

Conclusion

There is ongoing endothelial dysfunction in terms of increased expression of pro-thrombotic and pro-inflammatory markers in irradiated arteries even years after radiotherapy. Treating this endothelial dysfunction might reduce the complication rates associated with microvascular free flap reconstructions in irradiated patients.

Keywords

Reconstructive surgery Radiotherapy Free tissue flaps Endothelial dysfunction Radiation dosage 

Langzeit-Endothelfunktionsstörung in bestrahlten Gefäßen: immunhistochemische Analyse

Zusammenfassung

Hintergrund

Freie mikrovaskuläre Transplantate stellen heute ein Standardverfahren in der rekonstruktiven Kopf-Hals-Chirurgie dar. Eine vorausgegangene Bestrahlung ist hierbei mit einer höheren Rate an transplantatbezogenen Durchblutungsstörungen und operativen Revisionen assoziiert. Bestrahlte Gefäße weisen charakteristische histomorphologische und strukturelle Änderungen auf. Die Veränderungen der Endothelzellen bestrahlter Gefäße sind bislang unvollständig verstanden. Dies trifft v. a. für die langfristige endotheliale Dysfunktion zu, die mit einem prothrombotischen und -inflammatorischen intraluminalen Milieu einhergeht.

Methoden

Bestrahlte und unbestrahlte Arterien wurden für eine immunhistochemische Untersuchung herangezogen, um die Expression von ICAM-1 („vascular cell adhesion molecule-1“), VCAM-1 („intercellular adhesion molecule-1“), E‑ und P‑Selectin, eNOS („endotheliale NO-Synthase“), Thrombomodulin sowie PAI-1 („plasminogen activator inhibitor-1“) via Remmele-Score zur Graduierung der Färbeintensität und der Endotheloberfläche zu bestimmen. Die durchschnittlich verabreichte Strahlendosis lag bei 58,7 ± 7,0 Gy, der mittlere Zeitraum nach Bestrahlung bis zur Probenentnahme betrug 106,0 ± 86,8 Monate.

Ergebnisse

Die endotheliale Expression von ICAM-1, VCAM-1, E‑ und P‑Selectin sowie PAI-1 war in bestrahlten Arterien signifikant erhöht im Vergleich zu unbestrahlten Kontrollen, wohingegen Thrombomodulin und eNOS keine Veränderungen zeigten. Im Vergleich nichtbestrahlter Transplantatarterien und bestrahlter Arterien aus der Kopf-Hals-Region bei entsprechenden Personen zeigte sich die eNOS-Expression signifikant erniedrigt in bestrahlten Gefäßen, während ICAM-1, VCAM-1, E‑/P-Selectin und PAI-1 signifikant höher exprimiert waren.

Schlussfolgerung

Noch mehrere Jahre nach einer Bestrahlung zeigt sich eine persistierende endotheliale Dysfunktion im Sinne einer verstärkten Expression prothrombotischer und -inflammatorischer Marker im Lumen bestrahlter Arterien. Die gezielte Behandlung dieser Dysfunktion könnte dazu beitragen, die Komplikationsrate bei mikrovaskulären Rekonstruktionen bestrahlter Patienten in Zukunft zu reduzieren.

Schlüsselwörter

Rekonstruktive Chirurgie Radiotherapie Freie Gewebelappen Endotheliale Dysfunktion Bestrahlungsdosierung 

Notes

Acknowledgements

This study was supported by the ELAN-Fond (University of Erlangen-Nürnberg).

Conflict of interest

R.H.M. Preidl, P. Möbius, M. Weber, K. Amann, F.W. Neukam, M. Kesting, C.-I. Geppert, and F. Wehrhan declare that they have no competing interests.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Raimund H. M. Preidl
    • 1
    Email author
  • Patrick Möbius
    • 1
  • Manuel Weber
    • 1
  • Kerstin Amann
    • 1
  • Friedrich W. Neukam
    • 1
  • Marco Kesting
    • 1
  • Carol-Immanuel Geppert
    • 2
  • Falk Wehrhan
    • 1
  1. 1.Department of Oral and Maxillofacial SurgeryUniversity of Erlangen-NurembergErlangenGermany
  2. 2.Department of PathologyUniversity of Erlangen-NurembergErlangenGermany

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