[Cryotherapy of malignant tumors: studies with MRI in an animal experiment and comparison with morphological changes].
OBJECTIVE
Aim of our study was to investigate the efficacy of 7 F cryoprobes for percutaneous use morpho- and histologically, to examine the role of apoptosis after cryotherapy, and to compare contrast-enhanced MRI with histopathological findings at different time intervals in a tumor-mouse model.


METHODS
Percutaneous cryotherapy was performed in 15 immunocompromised nude mice with subcutaneously implanted tumors using the non-small-cell lung cancer cell line Lu 1. In group a) 7 mice were sacrificed after definite time intervals and histological examinations were done for evaluation of necrosis and apoptosis (HE; TUNEL assay); 2 mice are in long-term follow-up. In group b) in 6 mice tumor destruction and perfusion before and after freezing were investigated with native and contrast-enhanced MR imaging (T1- and T2-weighted spin-echo) and compared with histopathological findings. Histological control were done in 2 untreated mice.


RESULTS
We observed fast tumor-reduction within two weeks (ca. 50%). On long-term follow-up (> 6 months) no recurrence has been noticed so far. Tumors were well vascularized prior to treatment and did not-show contrast enhancement an any time after cryotherapy. A narrow contrast-enhanced zone was seen on the tumor border subcutaneously as a sign of peripheral hyperemia and central vascular stasis after cryotherapy. On histology there was evidence of both apoptosis and necrosis.


CONCLUSIONS
We have established a tumor-mouse model for further investigations. Two minutes freezing of a 2-cm tumor in the mouse model is sufficient for tumor ablation with scarred healing. Apoptosis may play a role in cryotherapy of experimental tumors. Contrast-enhanced MRI is suitable for the estimation of the cryolasion.
Romaneehsen
B
B
Klinik und Poliklinik für Radiologie, Johannes Gutenberg-Universität Mainz. roman@radiologie.klinik.uni-mainz.de
Anders
M
M
Röhrl
B
B
Hast
H J
HJ
Hengstler
J G
JG
Schiffer
I
I
Neugebauer
B
B
Teichmann
E
E
Schreiber
W G
WG
Thelen
M
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D017679:Cryotherapy; D006801:Humans; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured / Q000473:pathology
Kryotherapie maligner Tumoren: Untersuchungen mittels MRT im Tierexperiment und Vergleich mit morphologischen Veränderungen.