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Vascular lesions following perfusion with bleomycin

Electron-microscopic observations

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Summary

During intra-arterial perfusion therapy of oral squamous cell carcinomas with bleomycin, circumscribed necrotic areas in the perfused region are observed in a few cases. These are usually located in the acral regions. As the cause, a lesion of the blood vessels with formation of microthrombosis could be demonstrated.

Electron-microscopic observations of the blood vessels in five bleomycinperfused tumor areas demonstrated lesions of the endothelium characterized by swelling of the cells, formation of intracytoplasmatic vacuoles and villous projections into the lumen of the vessel. In arterioles, separation of the endothelium from the underlying tissue, swollen smooth muscle cells and destruction of elastic lamellae were found. These were the pacemakers for the formation of thrombosis. A negative influence of the vascular lesions on the cytostatic effect on the tumor is likely. Vascular lesions also constitute one of the initial factors for the development of the bleomycin-induced lung lesion (bleomycin lung).

Zusammenfassung

Eine bisher wenig beobachtete Nebenwirkung der BLM-Perfusionstherapie von oralen Plattenepithelcarcinomen sind umschriebene Nekrosezonen an den Akren. Als Ursache ließ sich ein Gefäßschaden mit Thrombenbildung in den Arteriolen nachweisen. Die elektronenmikroskopischen Beobachtungen an 5 mit BLM perfundierten Tumorarealen und Gefäßen wiesen einen Endothelschaden mit Schwellung und vakuoliger Degeneration der Endothelzellen nach. An den Arteriolen kam es zur Ablösung von Endothelien, Schwellung der glatten Muskelfasern und Zerstörung der elastischen Lamellen. Dies bildet den Boden für eine Mikrothrombosierung. Ein negativer Einfluß des Gefäßschadens auf die Wirkung der Cytostatikatherapie wird diskutiert. Gefäßschäden im Bereich der Lungenstrombahn werden als eine Teilursache der multifaktoriell bedingten Bleomycinlunge angesehen.

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References

  • Adamson, I.Y.R., Bowden, D.H.: The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Amer. J. Path. 77, 185–198 (1974)

    Google Scholar 

  • Altschul, R.: Über eine eigenartige Reaktion der Endothelzellen. Virchows Arch. path. Anat. 300, 357–364 (1957)

    Google Scholar 

  • Altschul, R., Faul-Bochmler, E.: Endothelium in contracted arteries. Virchows Arch. path. Anat. 336, 383–388 (1963)

    Google Scholar 

  • Andres, K.H.: Elektronenmikroskopische Untersuchungen über Strukturveränderungen an Blutgefäßen und am Endoneurium in Spinalganglien von Ratten nach Bestrahlung mit 185 MEV-Protonen. Z. Zellforsch. 61, 23–51 (1963)

    Google Scholar 

  • Armiger, L.L., Gavin, J.B.: Changes in the microvasculature of ischemic and infarcted myocardium. Lab. Invest. 33, 51–56 (1975)

    Google Scholar 

  • Ashford, T.P., Freiman, D.G.: The role of the endothelium in the initial phase of thrombosis. Amer. J. Path. 50, 257–273 (1967)

    Google Scholar 

  • Bedrossian, C.W.M., Luna, M.A., McKay, B., Lichtiger, B.: Ultrastructure of pulmonary bleomycin toxicity. Cancer (Philad.) 32, 44–51 (1973)

    Google Scholar 

  • Bitter, K.: Erste Ergebnisse der zytostatischen Behandlung von Plattenepithelkarzinomen der Mundhöhle mit einer Kombination von Methotrexat und Bleomycin. Dtsch. Zahn-, Mund-u. Kieferheilk. 60, 81–93 (1973)

    Google Scholar 

  • Bitter, K.: Wirkung von Bleomycin-Methotrexat-Kombination auf experimentelle Tumoren und auf Plattenepithelkarzinome der Mundhöhle. Med. Habil. Fr. Univ. Berlin 1974

    Google Scholar 

  • Bläsig, H., Näther, B., Gerteis, W., Brölsch, Ch., Greuel, H.: Bleomycin bei gynäkologischen Plattenepithelkarzinomen. Geburtsh. u. Frauenheilk. 31, 1156–1163 (1971)

    Google Scholar 

  • Burkhardt, A., Gebbers, J.-O., Höltje, W.-J.: Die Bleomycin-Lunge. Systematische pathologischanatomische Untersuchungen an 15 Fällen. Dtsch. med. Wschr. (in press)

  • Burkhardt, A., Höltje, W.-J.: The effects of intraarterial bleomycin therapy on squamous cell carcinomas of the oral cavity. Bioptic and autoptic examinations. J. Maxillofac. Surg. 3, 217–230 (1975)

    Google Scholar 

  • Burri, P.H., Weibel, E.R.: Beeinflussung einer spezifischen cytoplasmatischen Organelle von Endothelzellen durch Adrenalin. Z. Zellforsch. 88, 426–440 (1968)

    Google Scholar 

  • Constantinides, P., Robinson, M.: Ultrastructural injury of arterial endothelium. I. Effects of pH, osmolarity, anoxia, and temperature. Arch. Path. 88, 99–105 (1969a)

    Google Scholar 

  • Constantinides, P., Robinson, M.: Ultrastructural injury of arterial endothelium. II. Effects of vasoactive amines. Arch. Path. 88, 106–112 (1969b)

    Google Scholar 

  • Constantinides, P., Robinson, M.: Ultrastructural injury of arterial endothelium. III. Effects of enzymes and surfactants. Arch. Path. 88, 113–117 (1969c)

    Google Scholar 

  • Dvorak, A.M., Mihm, M.C., Dvorak, H.F.: Morphology of delayedtype hypersensitivity reactions in man. II. Ultrastructural alterations affecting the microvasculature and the tissue mast cells. Lab. Invest. 34, 179–191 (1976)

    Google Scholar 

  • Fajardo, L.F., Stewart, J.R.: Pathogenesis of radiation induced myocardial fibrosis. Lab. Invest. 29, 244–257 (1973)

    Google Scholar 

  • Gabbiani, G., Badonnel, M.-C., Mathewson, S.M., Ryan, G.B.: Acute Cadmium intoxication. Early selective lesions of endothelial clefts. Lab. Invest. 30, 686–695 (1974)

    Google Scholar 

  • Gabbiani, G., Mathewson, S., Badonnel, M.-C.: Early lesions of endothelial clefts after chemical or physical injury. Amer. J. Path. 74, 88a-89a (1974)

    Google Scholar 

  • Gebbers, J.-O., Riesner, K., Burkhardt, A., v. Wichert, P.: Experimentelle Untersuchungen zum Problem der Bleomycinlunge. (In preparation)

  • Hagedorn, M., Petres, J., Mittermayer, C.: Bleomycin: Tumorzellveränderungen und Gefäßwirkungen beim Patienten. Arch. Derm. Forsch. 250, 71–80 (1974)

    Google Scholar 

  • Hashimoto, P.H., Takaesu, S., Chazono, M., Amano, T.: Vascular leckage through intraendothelial channels induced by cholera toxin in the skin of guinea pigs. Amer. J. Path. 75, 171–180 (1974)

    Google Scholar 

  • Höltje, W.-J., Burkhardt, A.: Gefäßschäden durch Bleomycin nach Perfusionsbehandlung von Mundhöhlencarcinomen. Vortrag auf dem 26. Kongreß der deutschen Gesellschaft für Mund-Kiefer- und Gesichtschirurgie, 31. 5.-4. 6. 1976 in Münster. Dtsch. Ztschrft. Mund-, Kieferund Gesichtschir. (in press)

  • Höltje, W.-J., Burkhardt, A., Gebbers, J.-O.: Intraarterielle Bleomycintherapie von Plattenepithelcarcinomen der Mundhöhle. Klinik und pathologische Anatomie. Z. Krebsforsch. (in press)

  • Hoff, H.F., Gottlob, R.: A fine structure study of injury to the endothelial cells of the rabbit abdominal aorta by various stimuli. Angiology 18, 440–451 (1967)

    Google Scholar 

  • Hoff, H.F., Gottlob, R., Blümel, G.: Ultrastructural changes in arteries induced by endotoxin. Naturwissenschaften 54, 287–288 (1967)

    Google Scholar 

  • Huntington, M.C., Du Priest, R.W., Fletcher, W.S.: Intra-arterial bleomycin therapy in inoperable squamous cell carcinomas. Cancer (Philad.) 31, 153–158 (1973)

    Google Scholar 

  • Kjeldsen, K., Thomsen, H.K.: The effect of hypoxia on the fine structure of the aortic intima in rabbits. Lab. Invest. 33, 533–543 (1975)

    Google Scholar 

  • Luft, J.H.: Ruthenium red and violett. I. Chemistry, purification, methods of use for electron microscopy and mechanism of action. Anat. Rec. 171, 347–368 (1971 a)

    Google Scholar 

  • Luft, J.H.: Ruthenium red and violett. II. Fine structural localization in animal tissues. Anat. Rec. 171, 369–416 (1971b)

    Google Scholar 

  • Luna, M.A., Bedrossian, C.W.M., Lichtiger, B., Salem, P.A.: Interstitial pneumonitis associated with bleomycin therapy. Amer. J. clin. Path. 58, 501–510 (1972)

    Google Scholar 

  • Majno, G., Shea, St.M., Leventhal, M.: Endothelial contraction induced by histamine-type mediators. J. Cell Biol. 42, 647–672 (1969)

    Google Scholar 

  • Mathe, G.: Study of the clinical efficiency of bleomycin in human cancer. Brit. med. J. 2, 643–645 (1970)

    Google Scholar 

  • Phelps, P.C., Luft, J.H.: Electron microscopical study of relaxation and constriction in frog arterioles. Amer. J. Anat. 125, 399–429 (1969)

    Google Scholar 

  • Sholley, M.M.: Effects of x-irradiation on the fine vasculature of the rat parotid gland. Anat. Rec. 175, 441–442 (1973)

    Google Scholar 

  • Takeda, K., Sugawa, Y., Arakawa, T.: Therapeutic effect of bleomycin for skin tumors. Gann 61, 207–218 (1970)

    Google Scholar 

  • Ts'ao, Ch.: Graded endothelial injury of the rabbit aorta. With special reference to platelet desposition. Arch. Path. 90, 222–229 (1970)

    Google Scholar 

  • Willms-Kretschmer, K., Majno, G.: Ischemia of the skin. Electronmicroscopic study of vascular injury. Amer. J. Path. 54, 327–353 (1969)

    Google Scholar 

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The authors wish to express their sincere appreciation to Miss K. Schönemann for invaluable technical assistance in this project.

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Burkhardt, A., Höltje, W.J. & Gebbers, J.O. Vascular lesions following perfusion with bleomycin. Virchows Arch. A Path. Anat. and Histol. 372, 227–236 (1976). https://doi.org/10.1007/BF00433281

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