Die isolierte hypertherme Extremitätenperfusion mit Vindesin, Dacarbazin und Cis-Platin bei der Behandlung maligner Melanome

Aigner, Karl Reinhard; Jungbluth, Achim A.; Link, Karl-Heinrich; Walther, Hans‐Otto; Müller, H.; Schwemmle, K; Ringenberg, T.; Borger, G; Ruppel, Raimund; Illig, L; Voigt, H.

doi:10.1159/000215480

Cited by 12 publications

(1 citation statement)

References 2 publications

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“…Daher kOnnen Cytostatica, die w~ihrend dieses Zeitabschnittes verabreicht werden, den Tumor nicht erreichen.Die Hyperthermie maligner Tumoren wird in der Onkologie zunehmend als therapeutisches Adjuvans eingesetzt[1, 2,14,15,22,23,33]; zudem konnte die Verl~ngerung des rezidivfreien Intervails nach Extremit~itenperfusion maligner Melanome erstmals durch eine kontrollierte Studie gesichert werden[10]. die arteriol~ire Konstriktion, die trotz massivster Gewebehypoxie nach lokaler Hyperthermie im amelanotischen Melanom bestehen blieb, nicht nur die capill~ire Durchblutung weiter reduzierte, sondern den Tumor for 72 h vonder Perfusion durch den Systemkreislauf ausschloB.…”

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Die mikrovascul�re Perfusion maligner Tumoren ?eine therapeutische Gr��e zur Steigerung des Hyperthermieeffektes?

Endrich

Hammersen²,

Meßmer

1988

Langenbecks Arch Chiv

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Hypoxic regions of malignant tumors are poorly vascularized; they appear to be more susceptible to hyperthermia in vivo than tumor cells in vitro after an exposure to heat. In an attempt to explain this discrepancy, changes of microcirculatory flow in the tumor have been proposed as key mechanism for destroying adjacent tumor cells in particular. This study was conducted to define the impact of the microcirculation on tumor destruction after local hyperthermia. A transparent chamber was implanted in the dorsal skin fold and two permanent indwelling catheters placed in carotid artery and jugular vein of 45 Syrian golden hamsters. 48 h later, 4 X 10(4) cells of the amelanotic melanoma A-Mel-3 were implanted into the s.c. tissue covered by the chamber. 5 days later, at a tumor diameter of 3 mm, the microcirculation of this tumor was studied using intravital microscopy, a platinum multiwire electrode, television as well as micropuncture techniques for the determination of local PO2, microcirculatory blood flow and microvascular pressure. Measurements were taken at 30 degrees C and 15 min after reaching a tumor temperature of 35 degrees and 42.5 degrees C. When heating up the melanoma to 35 degrees C, an increase in capillary perfusion by 35% was noted. With an apparent maximum of capillary perfusion, there was no change in arteriolar pressure but a significant drop in venular pressure from 11.0 +/- 1.1 to 7.4 +/- 0.6 mmHg resulting in an increase of the arteriolo-venular pressure gradient while the systemic pressures were unchanged. At a tumor temperature of 42.5 degrees C, prestasis and stasis became apparent in capillaries and collecting venules. This was accompanied by a rise in capillary and venular pressure by 5 mmHg. At the same time, pronounced tissue hypoxia was present in the tumor with more than 50% of the values within the hypoxic range between 0 and 5 mmHg. Despite tissue hypoxia, the constriction of all tumor arterioles became evident 15-30 min after reaching a tumor temperature of 42.5 degrees C. The deterioration of tumor oxygenation was associated with damage of tumor cells such as swelling and destruction of mitochondria which was seen under the electron microscope. After 40 min at 42.5 degrees C, the attenuation of the endothelial lining around the entire vascular perimeter was seen in tumor capillaries.(ABSTRACT TRUNCATED AT 400 WORDS)

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Die mikrovascul�re Perfusion maligner Tumoren ?eine therapeutische Gr��e zur Steigerung des Hyperthermieeffektes?

Endrich

Hammersen²,

Meßmer

1988

Langenbecks Arch Chiv

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Hyperthermic isolated limb perfusion with Cis‐diamminedichloro‐platinum. II. An experimental study in dogs with a balloon‐occlusion technique for repeated high‐dose treatment

Wessalowski¹,

Wilhelm²,

Torsello³

et al. 1994

Med. Pediatr. Oncol.

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Isolated organ perfusion is attractive for regional high-dose chemotherapy because of its advantage to reduce whole body toxicity. Intraoperative hyperthermic isolated perfusion procedures involving a heart-lung machine have been developed, but repeated treatments carry a high risk of vessel and tissue damage. Therefore, a study of isolated hyperthermic limb perfusion in four dogs was conducted using a balloon-occlusion technique including a hyperthermia unit, two low-flow rotary pumps, a bubble oxygenator, and two polyurethane balloon catheters. After 15 min infusion of cisplatinum the concentrations of serum platinum (Pt) in the isolated limb and in the whole body were measured by atomic absorption spectroscopy. Regional exposure to Pt was more than 10-fold higher than systemic exposure. After 60 min isolated limb perfusion, the area under the curve (AUC) of Pt concentrations in the isolated limb showed values between 767.4 and 1055.6 micrograms/l x 60 min, whereas in the whole body values between 59.8 and 75.9 micrograms/l x 60 min were obtained. Repeated isolated limb perfusions with the balloon-occlusion technique were performed in three dogs without systemic side effects. This model of regional chemotherapy may be useful for preoperative chemotherapy in malignant tumors of the limbs.

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Chirurgische Therapie des malignen Melanoms

Aigner¹,

Link²,

Walther³

1986

Malignes Melanom

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Die isolierte hypertherme Extremitätenperfusion mit Vindesin, Dacarbazin und Cis-Platin bei der Behandlung maligner Melanome

Cited by 12 publications

References 2 publications

Die mikrovascul�re Perfusion maligner Tumoren ?eine therapeutische Gr��e zur Steigerung des Hyperthermieeffektes?

Die mikrovascul�re Perfusion maligner Tumoren ?eine therapeutische Gr��e zur Steigerung des Hyperthermieeffektes?

Hyperthermic isolated limb perfusion with Cis‐diamminedichloro‐platinum. II. An experimental study in dogs with a balloon‐occlusion technique for repeated high‐dose treatment

Chirurgische Therapie des malignen Melanoms

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