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British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Feb;82(4):794–799. doi: 10.1054/bjoc.1999.1001

Complete shutdown of microvascular perfusion upon hepatic cryothermia is critically dependent on local tissue temperature

G Schüder 1, G Pistorius 1, M Fehringer 1, G Feifel 1, M D Menger 2, B Vollmar 2
PMCID: PMC2374393  PMID: 10732748

Abstract

Since microvascular dysfunction with complete circulatory arrest and, thus, prolongation of tissue ischaemia is considered a potential mechanism for cell necrosis following hepatic cryosurgery, we determined the temperature necessary for induction of complete nutritive perfusion failure in cryothermia-treated rat livers. After localization of the cryoprobe with seven thermocouples and application of a single or double freeze–thaw cycle, in vivo fluorescence microscopy of the cryoinjured left lobe was performed over a 2-h period using a computer-controlled stepping motor, which guaranteed analysis of the identical liver tissue segments with exact allocation of the thermocouples and thus determination of tissue temperature. Cryothermia resulted in a central non-perfused part of injury, surrounded by a heterogeneously perfused peripheral zone. The non-perfused area after single and double freezing continuously increased over the first 90-min period due to a successive shutdown of perfusion within the peripheral border zone. Analysis of the thermocouples' temperature at the end of freezing revealed the 0°C-front at 11.7 mm (single freeze–thaw cycle) and 12.1 mm (double freeze–thaw cycle) distant from the centre of the cryoprobe, which exactly corresponds with the initial (30 min) expansion of the area with nutritive perfusion failure. The increased non-perfused tissue area at 2 h conformed a critical border temperature between 8.29 ± 1.63°C and 9.07 ± 0.24°C. From these findings, we conclude that freezing of liver tissue to temperatures of at least < 0°C causes complete/irreversible perfusion failure, which consequently will result in cell death and tissue necrosis, and may thus be supposed as a prerequisite for the safe and successful application of cryosurgery in hepatic tumour ablation. © 2000 Cancer Research Campaign

Keywords: cryosurgery, liver microcirculation, tissue temperature, sinusoidal perfusion failure

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Selected References

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  1. Adam R., Akpinar E., Johann M., Kunstlinger F., Majno P., Bismuth H. Place of cryosurgery in the treatment of malignant liver tumors. Ann Surg. 1997 Jan;225(1):39–50. doi: 10.1097/00000658-199701000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown N. J., Bayjoo P., Reed M. W. Effect of cryosurgery on liver blood flow. Br J Cancer. 1993 Jul;68(1):10–12. doi: 10.1038/bjc.1993.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown N. J., Pollock K. J., Bayjoo P., Reed M. W. The effect of cryotherapy on the cremaster muscle microcirculation in vivo. Br J Cancer. 1994 Apr;69(4):706–710. doi: 10.1038/bjc.1994.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Charnley R. M., Doran J., Morris D. L. Cryotherapy for liver metastases: a new approach. Br J Surg. 1989 Oct;76(10):1040–1041. doi: 10.1002/bjs.1800761018. [DOI] [PubMed] [Google Scholar]
  5. Cozzi P. J., Englund R., Morris D. L. Cryotherapy treatment of patients with hepatic metastases from neuroendocrine tumors. Cancer. 1995 Aug 1;76(3):501–509. doi: 10.1002/1097-0142(19950801)76:3<501::aid-cncr2820760322>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  6. Dalton R. R., Eisenberg B. L. Surgical management of recurrent liver tumors. Semin Oncol. 1993 Oct;20(5):493–505. [PubMed] [Google Scholar]
  7. Gage A. A. Cryosurgery for oral and pharyngeal carcinoma. Am J Surg. 1969 Nov;118(5):669–672. doi: 10.1016/0002-9610(69)90210-4. [DOI] [PubMed] [Google Scholar]
  8. Gill W., Fraser J., Carter D. C. Repeated freeze-thaw cycles in cryosurgery. Nature. 1968 Jul 27;219(5152):410–413. doi: 10.1038/219410a0. [DOI] [PubMed] [Google Scholar]
  9. Hamad G. G., Neifeld J. P. Biochemical, hematologic, and immunologic alterations following hepatic cryotherapy. Semin Surg Oncol. 1998 Mar;14(2):122–128. doi: 10.1002/(sici)1098-2388(199803)14:2<122::aid-ssu5>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  10. Jacob G., Kurzer M. N., Fuller B. J. An assessment of tumor cell viability after in vitro freezing. Cryobiology. 1985 Oct;22(5):417–426. doi: 10.1016/0011-2240(85)90152-x. [DOI] [PubMed] [Google Scholar]
  11. Johnson L. B., Krebs T. L., Van Echo D., Plotkin J. S., Njoku M., Wong J. J., Daly B. D., Kuo P. C. Cytoablative therapy with combined resection and cryosurgery for limited bilobar hepatic colorectal metastases. Am J Surg. 1997 Dec;174(6):610–613. doi: 10.1016/s0002-9610(97)00176-1. [DOI] [PubMed] [Google Scholar]
  12. Lee F. T., Jr, Mahvi D. M., Chosy S. G., Onik G. M., Wong W. S., Littrup P. J., Scanlan K. A. Hepatic cryosurgery with intraoperative US guidance. Radiology. 1997 Mar;202(3):624–632. doi: 10.1148/radiology.202.3.9051005. [DOI] [PubMed] [Google Scholar]
  13. Morris D. L., Horton M. D., Dilley A. V., Warlters A., Clingan P. R. Treatment of hepatic metastases by cryotherapy and regional cytotoxic perfusion. Gut. 1993 Sep;34(9):1156–1157. doi: 10.1136/gut.34.9.1156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Neel H. B., Ketcham A. S., Hammond W. G. Ischemia potentiating cryosurgery of primate liver. Ann Surg. 1971 Aug;174(2):309–318. doi: 10.1097/00000658-197108000-00019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rabb J. M., Renaud M. L., Brandt P. A., Witt C. W. Effect of freezing and thawing on the microcirculation and capillary endothelium of the hamster cheek pouch. Cryobiology. 1974 Dec;11(6):508–518. doi: 10.1016/0011-2240(74)90120-5. [DOI] [PubMed] [Google Scholar]
  16. Ravikumar T. S., Kane R., Cady B., Jenkins R. L., McDermott W., Onik G., Clouse M., Steele G., Jr Hepatic cryosurgery with intraoperative ultrasound monitoring for metastatic colon carcinoma. Arch Surg. 1987 Apr;122(4):403–409. doi: 10.1001/archsurg.1987.01400160029002. [DOI] [PubMed] [Google Scholar]
  17. Ravikumar T. S., Steele G. D., Jr Hepatic cryosurgery. Surg Clin North Am. 1989 Apr;69(2):433–440. doi: 10.1016/s0039-6109(16)44798-5. [DOI] [PubMed] [Google Scholar]
  18. Ravikumar T. S., Steele G., Jr, Kane R., King V. Experimental and clinical observations on hepatic cryosurgery for colorectal metastases. Cancer Res. 1991 Dec 1;51(23 Pt 1):6323–6327. [PubMed] [Google Scholar]
  19. Rubinsky B., Lee C. Y., Bastacky J., Onik G. The process of freezing and the mechanism of damage during hepatic cryosurgery. Cryobiology. 1990 Feb;27(1):85–97. doi: 10.1016/0011-2240(90)90055-9. [DOI] [PubMed] [Google Scholar]
  20. Schüder G., Vollmar B., Richter S., Pistorius G., Fehringer M., Feifel G., Menger M. D. Epi-illumination fluorescent light microscopy for the in vivo study of rat hepatic microvascular response to cryothermia. Hepatology. 1999 Mar;29(3):801–808. doi: 10.1002/hep.510290342. [DOI] [PubMed] [Google Scholar]
  21. Seifert J. K., Morris D. L. Indicators of recurrence following cryotherapy for hepatic metastases from colorectal cancer. Br J Surg. 1999 Feb;86(2):234–240. doi: 10.1046/j.1365-2168.1999.00995.x. [DOI] [PubMed] [Google Scholar]
  22. Smith J. J., Fraser J., MacIver A. G. Ultrastructure after cryosurgery of rat liver. Cryobiology. 1978 Aug;15(4):426–432. doi: 10.1016/0011-2240(78)90061-5. [DOI] [PubMed] [Google Scholar]
  23. Steele G., Jr Cryoablation in hepatic surgery. Semin Liver Dis. 1994 May;14(2):120–125. doi: 10.1055/s-2007-1007304. [DOI] [PubMed] [Google Scholar]
  24. Tatsutani K., Rubinsky B., Onik G., Dahiya R. Effect of thermal variables on frozen human primary prostatic adenocarcinoma cells. Urology. 1996 Sep;48(3):441–447. doi: 10.1016/S0090-4295(96)00199-9. [DOI] [PubMed] [Google Scholar]
  25. Vollmar B., Glasz J., Leiderer R., Post S., Menger M. D. Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion. Am J Pathol. 1994 Dec;145(6):1421–1431. [PMC free article] [PubMed] [Google Scholar]
  26. Vollmar B., Messner S., Wanner G. A., Hartung T., Menger M. D. Immunomodulatory action of G-CSF in a rat model of endotoxin-induced liver injury: an intravital microscopic analysis of Kupffer cell and leukocyte response. J Leukoc Biol. 1997 Dec;62(6):710–718. doi: 10.1002/jlb.62.6.710. [DOI] [PubMed] [Google Scholar]
  27. Weber S. M., Lee F. T., Jr, Chinn D. O., Warner T., Chosy S. G., Mahvi D. M. Perivascular and intralesional tissue necrosis after hepatic cryoablation: results in a porcine model. Surgery. 1997 Oct;122(4):742–747. doi: 10.1016/s0039-6060(97)90082-9. [DOI] [PubMed] [Google Scholar]
  28. Whittaker D. K. Mechanisms of tissue destruction following cryosurgery. Ann R Coll Surg Engl. 1984 Sep;66(5):313–318. [PMC free article] [PubMed] [Google Scholar]
  29. Zhou X. D., Tang Z. Y., Yu Y. Q., Weng J. M., Ma Z. C., Zhang B. H., Zheng Y. X. The role of cryosurgery in the treatment of hepatic cancer: a report of 113 cases. J Cancer Res Clin Oncol. 1993;120(1-2):100–102. doi: 10.1007/BF01200732. [DOI] [PMC free article] [PubMed] [Google Scholar]

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