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Renal Impairment in Hepatic Cryotherapy
36, 263–267 (1998) CY982085
CRYOBIOLOGY ARTICLE NO.
Renal Impairment in Hepatic Cryotherapy J. S. Bagia, D. S. Perera, and D. L. Morris1 Department of Surgery, The University of New South Wales, St. George Hospital, Kogarah, Sydney, New South Wales 2217, Australia Cryoshock is a syndrome of coagulopathy, renal, and pulmonary injury following cryotherapy, and its etiology is unknown. The aim of this study was to assess the impact of hepatic cryotherapy on renal function, and whether this effect is related to volume of cryotherapy, and to identify any predictors of renal impairment in patients who undergo cryotherapy. A retrospective analysis of all patients with primary or secondary hepatic malignancy treated with cryotherapy from April 1990 to October 1996 was conducted. Ten of 204 patients with renal impairment (elevation in creatinine of greater than 0.02 mmol/L for more than 2 days postprocedure) were identified. One patient had postoperative pancreatitis with late renal impairment (20 days) and was excluded. The severity of renal impairment was usually modest (mean rise in creatinine of 0.31 mmol/L; SD, 0.19). Two patients required temporary hemodialysis. Only one patient, who had significant cardiac disease, had associated pulmonary injury and shock. Demographic data in both groups were comparable, except for a trend toward more noncolorectal cancer patients in the renal impairment group (4/9 vs 33/194). Patients in the renal impairment group had a greater number of lesions than those of the nonrenal impairment group (3.4 vs 2.1, P , 0.01), as well as larger lesion diameter (2.9 vs 1.9, P , 0.01), increased freezing time (74.7 vs 44.3, P , 0.01), and a higher aspartate transaminase (AST) (2254 vs 1157, P , 0.01). This study suggests that renal impairment is more likely to be seen in patients undergoing more extensive cryotherapy. The number and diameter of lesions together with AST data link renal injury with magnitude of liver injury—all renal impairment patients had an AST . 1000, compared with only 28% of patients who did not. © 1998 Academic Press Key Words: hepatic cryotherapy; renal impairment; thrombocytopenia.
Hepatic cryotherapy is a relatively safe modality for unresectable liver tumors, which involves the direct freezing of tumor with liquid nitrogen (5, 6, 7). The insulated probe system used, is designed to allow in situ cryodestruction of lesions without injury to overlying tissue. Intraoperative ultrasound is essential in the identification and localization of tumors, probe placement, and control of extent of freezing process (7). Because cryotherapy is a focal treatment, less normal tissue is sacrificed than in surgical resection, allowing the treatment of multiple lesions and treatment of tumors where parenchymal function is poor. Cryotherapy may also enhance the possibility of retreatment for liver recurrence. Cryotherapy is well tolerated by large vessels, so tumors in difficult locations can be treated (9, 8, 15). In the case of metastases confined to the liver, cryosurgery inReceived October 5, 1997; accepted March 3, 1998. 1 To whom correspondence should be addressed. Fax: 161 2 9350 3997.
creases the number of patients that can be made potentially disease free or at least without evidence of disease (10, 14). A number of the postoperative changes in biochemical and hematologic data in patients who have undergone cryotherapy have been described by our group. In particular, the use of serum aspartate transaminase (AST) as a marker of hepatocellular injury, with a peak rise immediately subsequent to cryotherapy and an exponential fall thereafter, has been documented (12, 13). Fall in platelet count following hepatic cryotherapy for the treatment of colorectal metastases has also been correlated with the rise in day 1 AST and hence with hepatocellular injury (3). This thrombocytopenia may be a subclinical manifestation of cryoshock, a syndrome of acute renal failure, adult respiratory distress syndrome, and disseminated intravascular coagulation (7, 9). The aim of this study was to assess the impact of hepatic cryotherapy on renal function, and whether this effect is related to
263 0011-2240/98 $25.00 Copyright © 1998 by Academic Press All rights of reproduction in any form reserved.
264
BAGIA, PERERA, AND MORRIS
volume of cryotherapy, and to identify any predictors of renal impairment in patients who undergo cryotherapy. METHODS
A retrospective analysis of all patients with primary or secondary hepatic malignancy treated with cryotherapy from April 1990 to October 1996 was conducted. Data collected included age, diagnosis, operative details, and perioperative hematological and biochemical profiles. Cryotherapy data regarding lesions, resection margins, concurrent resection, or other treatments including insertion of hepatic arterial catheter or injection of alcohol to hepatic lesions were noted. Details of the number and size of lesions treated and total cryotherapy time were noted. Specific details of the procedure and perioperative care have been previously described. Patients with an elevation of creatinine of greater than 0.02 mmol/L for more than 2 days postoperatively were identified as having renal impairment (RI). This group was then compared to the group of patients who did not have renal impairment (NRI). Data have been statistically analyzed using the x2 test with Yates correction and correlation of proportionate differences. RESULTS
Two hundred four patients with hepatic malignancy treated with cryotherapy were identified. Ten of these were found to have renal impairment (4.9%). One patient had postoperative pancreatitis with late renal impairment (at
TABLE 1 Demographic Details Demographic data
Renal impairment
Non-renal impairment
No. of patients Age (years) Tumor Type CRC Other
9 63.7
194 58.7
6 3
161 33
20 days), and was excluded. The demographic details of patients in both groups were comparable, except for a trend toward more noncolorectal cancer patients in the renal impairment group (3/9 vs 33/194) (see Table 1). It is notable that 33% of the patients with renal impairment had malignancies other than colorectal, compared to 18% in the non-renal impairment group. Of the four patients in the renal impairment group with noncolorectal malignancies, two had neuroendocrine malignancy and one had a hepatocellular carcinoma. The severity of renal impairment was usually modest (mean rise in creatinine of 0.31 mmol/L (SD 5 0.19)). However two patients required temporary hemodialysis. One patient with significant cardiac disease had associated pulmonary edema and circulatory failure. Only 2 of the 95 patients who underwent synchronous placement of hepatic artery catheter developed renal impairment compared with 7 of 91 patients who did not. This result was not statistically significant with a P-value: 0.1 , P , 0.5 (see Table 2 for tabulated results).
TABLE 2 Results Results
Renal impairment
Non-renal impairment
P value
Mean lesion number (SD) Mean lesion diameter (SD) (cm) Mean total freeze time (SD) (min) Patients with AST .1000 (%) Mean AST (SD) (U/L) Percentage fall in platlets (SD) Percentage twin freeze (SD)
3.4 (2.0) 2.9 (1.4) 74.7 (43.0) 9 (100%) 2254 (968) 54.3% (23.4%) 66.7%
2.1 (2.0) 1.9 (1.9) 44.3 (36.1) 63 (28%) 1157 (979) 44.4% (18.3%) 80.9%
0.001 , P . 0.0027 0.001 , P , 0.0027 0.01 , P , 0.046 P , 0.001 P , 0.05 0.1 , P , 0.5
RENAL IMPAIRMENT IN HEPATIC CRYOTHERAPY
265
FIG. 1. Relationship of change in creatinine to volume of cryotherapy.
Patients in the renal impairment group had a greater number of lesions (P , 0.01), larger lesions (P , 0.01), increased freeze time (P , 0.01), and a higher mean day 1 AST (P , 0.01) than those in the non-renal impairment group. However, there was no relationship between volume of cryotherapy and change in creatinine (see Fig. 1). There was no correlation between volume of cryotherapy and change in creatinine in the NRI group (r∧2 5 0.000024), or in the RI group (r∧2 5 0.000286). DISCUSSION
This study indicates that significant renal impairment after cryotherapy is rare, the incidence in our series being 4.4%. Other centers have
reported incidence of significant renal impairment ranging from 0 to 16.6% (9, 10, 14). Our center has previously illustrated the correlation between the postoperative day 1 rise in AST and the extent of hepatocellular injury (12). The significantly higher AST in our group of patients with renal impairment is consistent with this observation. The number and diameter of lesions, and cryotherapy time, together with the AST data, links renal injury with the magnitude of liver injury—all RI patients had AST .1000 compared to only 28% of those who did not. Cozzi et al. (3) observed that the degree of thrombocytopenia following hepatic cryotherapy corresponded to the magnitude of rise in day 1 AST and hence hepatocellular injury, and further
266
BAGIA, PERERA, AND MORRIS
noted that the use of double freeze/thaw cycles caused a more marked thrombocytopenia than single freeze/thaw cycle cryotherapy. The absence of the spleen was found to protect against this thrombocytopenia. The etiology of this platelet fall is not known, though the spleen is thought to be associated with the process. Our center is currently looking at cryotherapy in animal models. Large volume double freezes of normal liver in rats has been shown to be followed by significant cytokine release and thrombocytopenia as well as myoglobinuria acute tubular necrosis—further studies are necessary to gain insight into the mechanisms of these changes (11). The degree of postoperative thrombocytopenia in the renal impairment group was not significantly greater than in the group with unimpaired renal function. It must be noted however that the percentage of patients who underwent double freeze/thaw cryotherapy in the group with renal impairment (66.7%) was less than in the no renal impairment group (80.9%). Our observation of a greater percentage of patients with noncolorectal malignancies in the renal impairment group may be attributable to the currently accepted management protocols. Because of the clear demonstration that survival after liver resection is closely related to the number of lesions (1), we have seldom treated more than four such lesions by cryotherapy and would usually use regional chemotherapy. In neuroendocrine tumors the reduction of liver tumor bulk is an effective form of palliation and we have no specific rule for maximum number (2). Indeed, in one of our patients in whom a dramatic rise of creatinine (from 0.09 to 0.49 mmol/L) was observed, cryotherapy had been used to decrease the volume of symptomatic hepatic carcinoid disease. Renal impairment is one of the most serious but uncommon complications of hepatic cryotherapy and may be seen as part of the clinical syndrome of cryoshock, comprising coagulopathy, pulmonary edema, renal impairment, and circulatory failure, described by the Pittsburgh group (14). We have not seen this complete syndrome, although one patient did develop pulmonary changes in addition to renal impairment. We do not yet know the mechanism of production of renal injury in hepatic cryotherapy—
transient renal impairment may be of course seen following many major operation procedures. The specific risks of cryotherapy may involve myoglobinuria (2), but this was not studied in our patients. We are currently studying the production of myoglobin following hepatic cryotherapy in an animal model. The use of mannitol together with preoperative hydration for the prevention of postoperative renal impairment has been suggested (4). It has been used in prostate cryotherapy with no RI shown in 50 subsequent patients treated with cryosurgery to the prostate. To date there is no conclusive evidence that this is useful in the prevention of renal failure after cryotherapy. Patients at our center are all prehydrated but mannitol has not been used. At present we can give no specific recommendations on the avoidance of renal injury following hepatic cryotherapy, but this paper provides reassurance that it is uncommon and apparently quite benign in its outcome. REFERENCES 1. Cady, B., Stone, M. D., McDermott, W. V., Jenkins, R. L., Bothe, A., and Lavin, P. T. Technical and biological factors in disease free survival after hepatic resection for colorectal cancer metastases. Arch. Surg. 127, 561–569 (1991). 2. Cozzi, P. J., Englund, R., and Morris, D. L. Cryotherapy treatment of patients with hepatic metastases from neuroendocrine tumors. Cancer 76(3), 501–509 (1995). 3. Cozzi, P. J., Stewart, G. J., and Morris, D. L. Thrombocytopaenia after hepatic cryotherapy for colorectal metastases: Correlates with hepatocellular injury. World J. Surg. 18, 774 –777 (1994). 4. Kohn, I. J., Heifets, M., Fisher, S., and Seidmon, E. J. Acute renal failure with thrombocytopaenia after cryosrgery of the prostate. Techniques Urol. 2(4), 230 –233 (1997). 5. Goodie, D. B., Horton, M. D. A., Morris, R. W., Nagy, L. S., and Morris, D. L. Anaesthetic experience with cryotherapy for the treatment of hepatic malignancy. Anaesthesiol. Intensive Care 20, 491– 496 (1992). 6. McCall, J. L., Booth, M. W., and Morris, D. L. Hepatic cryotherapy for metastatic liver tumors. Br. J. Med. 54(8), 378 –381 (1995). 7. Morris, D. L., Horton, M. D. A., Dilley, A. V., Warlters, A., and Clingan, P. R. Treatment of hepatic metastases by cryotherapy and regional cytotoxic perfusion. Gut 34, 1156 –1157 (1993). 8. Onik, G. M. Ultrasound-guided cryosurgery. Sci. Am. Sci. Med. 62–71 (1996).
RENAL IMPAIRMENT IN HEPATIC CRYOTHERAPY 9. Onik, G., Rubinsky, B., Zemel, R., Weaver, L., Diamond, D., Cobb, C., and Porterfield, B. Ultrasound-guided hepatic cryotherapy in the treatment of metastatic colon carcinoma. Cancer 67, 901–907 (1991). 10. Ravikumar, T. S., Steele, G., Kane, R., and King, V. Experimental and clinical observation on hepatic cryotherapy for colorectal metastases. Cancer Res. 51, 6323– 6327 (1991). 11. Seifert, J. K., Finlay, I., Armstrong, N., and Morris, D. L. Thrombocytopenia and cytokine release following hepatic cryosurgery. ANZ J. Surg., in press. [abstract] 12. Stewart, G. J., Preketes, A. P., Horton, M. D., Ross, W. B., and Morris, D. L. Hepatic cryotherapy: Dou-
267
ble freeze with partial thaw cycle achieves greater hepatocellular injury. Cryobiology 32, 215–19 (1995). 13. Tandon, B. N., and Archarya, S. K. Viral diseases involving the liver. Baillieres Clin. Gastroenterol. 1(2), 211 (1987). 14. Tandon, B. N., and Archarya, S. K. Viral diseases involving the liver. Baillieres Clin. Gastroenterol. 1(2), 211 (1987). 15. Xin-Da, Zhou, Zhao-You, Tang, and Ye-Qin, Yu. Cryosurgery for liver tumors. In ‘‘Novel Regional Therapies for Liver Tumors’’ (S. Kawasaki and M. Makuuchi, Eds.), pp. 187–196. Landes Co., 1995.
CRYOBIOLOGY ARTICLE NO.
Renal Impairment in Hepatic Cryotherapy J. S. Bagia, D. S. Perera, and D. L. Morris1 Department of Surgery, The University of New South Wales, St. George Hospital, Kogarah, Sydney, New South Wales 2217, Australia Cryoshock is a syndrome of coagulopathy, renal, and pulmonary injury following cryotherapy, and its etiology is unknown. The aim of this study was to assess the impact of hepatic cryotherapy on renal function, and whether this effect is related to volume of cryotherapy, and to identify any predictors of renal impairment in patients who undergo cryotherapy. A retrospective analysis of all patients with primary or secondary hepatic malignancy treated with cryotherapy from April 1990 to October 1996 was conducted. Ten of 204 patients with renal impairment (elevation in creatinine of greater than 0.02 mmol/L for more than 2 days postprocedure) were identified. One patient had postoperative pancreatitis with late renal impairment (20 days) and was excluded. The severity of renal impairment was usually modest (mean rise in creatinine of 0.31 mmol/L; SD, 0.19). Two patients required temporary hemodialysis. Only one patient, who had significant cardiac disease, had associated pulmonary injury and shock. Demographic data in both groups were comparable, except for a trend toward more noncolorectal cancer patients in the renal impairment group (4/9 vs 33/194). Patients in the renal impairment group had a greater number of lesions than those of the nonrenal impairment group (3.4 vs 2.1, P , 0.01), as well as larger lesion diameter (2.9 vs 1.9, P , 0.01), increased freezing time (74.7 vs 44.3, P , 0.01), and a higher aspartate transaminase (AST) (2254 vs 1157, P , 0.01). This study suggests that renal impairment is more likely to be seen in patients undergoing more extensive cryotherapy. The number and diameter of lesions together with AST data link renal injury with magnitude of liver injury—all renal impairment patients had an AST . 1000, compared with only 28% of patients who did not. © 1998 Academic Press Key Words: hepatic cryotherapy; renal impairment; thrombocytopenia.
Hepatic cryotherapy is a relatively safe modality for unresectable liver tumors, which involves the direct freezing of tumor with liquid nitrogen (5, 6, 7). The insulated probe system used, is designed to allow in situ cryodestruction of lesions without injury to overlying tissue. Intraoperative ultrasound is essential in the identification and localization of tumors, probe placement, and control of extent of freezing process (7). Because cryotherapy is a focal treatment, less normal tissue is sacrificed than in surgical resection, allowing the treatment of multiple lesions and treatment of tumors where parenchymal function is poor. Cryotherapy may also enhance the possibility of retreatment for liver recurrence. Cryotherapy is well tolerated by large vessels, so tumors in difficult locations can be treated (9, 8, 15). In the case of metastases confined to the liver, cryosurgery inReceived October 5, 1997; accepted March 3, 1998. 1 To whom correspondence should be addressed. Fax: 161 2 9350 3997.
creases the number of patients that can be made potentially disease free or at least without evidence of disease (10, 14). A number of the postoperative changes in biochemical and hematologic data in patients who have undergone cryotherapy have been described by our group. In particular, the use of serum aspartate transaminase (AST) as a marker of hepatocellular injury, with a peak rise immediately subsequent to cryotherapy and an exponential fall thereafter, has been documented (12, 13). Fall in platelet count following hepatic cryotherapy for the treatment of colorectal metastases has also been correlated with the rise in day 1 AST and hence with hepatocellular injury (3). This thrombocytopenia may be a subclinical manifestation of cryoshock, a syndrome of acute renal failure, adult respiratory distress syndrome, and disseminated intravascular coagulation (7, 9). The aim of this study was to assess the impact of hepatic cryotherapy on renal function, and whether this effect is related to
263 0011-2240/98 $25.00 Copyright © 1998 by Academic Press All rights of reproduction in any form reserved.
264
BAGIA, PERERA, AND MORRIS
volume of cryotherapy, and to identify any predictors of renal impairment in patients who undergo cryotherapy. METHODS
A retrospective analysis of all patients with primary or secondary hepatic malignancy treated with cryotherapy from April 1990 to October 1996 was conducted. Data collected included age, diagnosis, operative details, and perioperative hematological and biochemical profiles. Cryotherapy data regarding lesions, resection margins, concurrent resection, or other treatments including insertion of hepatic arterial catheter or injection of alcohol to hepatic lesions were noted. Details of the number and size of lesions treated and total cryotherapy time were noted. Specific details of the procedure and perioperative care have been previously described. Patients with an elevation of creatinine of greater than 0.02 mmol/L for more than 2 days postoperatively were identified as having renal impairment (RI). This group was then compared to the group of patients who did not have renal impairment (NRI). Data have been statistically analyzed using the x2 test with Yates correction and correlation of proportionate differences. RESULTS
Two hundred four patients with hepatic malignancy treated with cryotherapy were identified. Ten of these were found to have renal impairment (4.9%). One patient had postoperative pancreatitis with late renal impairment (at
TABLE 1 Demographic Details Demographic data
Renal impairment
Non-renal impairment
No. of patients Age (years) Tumor Type CRC Other
9 63.7
194 58.7
6 3
161 33
20 days), and was excluded. The demographic details of patients in both groups were comparable, except for a trend toward more noncolorectal cancer patients in the renal impairment group (3/9 vs 33/194) (see Table 1). It is notable that 33% of the patients with renal impairment had malignancies other than colorectal, compared to 18% in the non-renal impairment group. Of the four patients in the renal impairment group with noncolorectal malignancies, two had neuroendocrine malignancy and one had a hepatocellular carcinoma. The severity of renal impairment was usually modest (mean rise in creatinine of 0.31 mmol/L (SD 5 0.19)). However two patients required temporary hemodialysis. One patient with significant cardiac disease had associated pulmonary edema and circulatory failure. Only 2 of the 95 patients who underwent synchronous placement of hepatic artery catheter developed renal impairment compared with 7 of 91 patients who did not. This result was not statistically significant with a P-value: 0.1 , P , 0.5 (see Table 2 for tabulated results).
TABLE 2 Results Results
Renal impairment
Non-renal impairment
P value
Mean lesion number (SD) Mean lesion diameter (SD) (cm) Mean total freeze time (SD) (min) Patients with AST .1000 (%) Mean AST (SD) (U/L) Percentage fall in platlets (SD) Percentage twin freeze (SD)
3.4 (2.0) 2.9 (1.4) 74.7 (43.0) 9 (100%) 2254 (968) 54.3% (23.4%) 66.7%
2.1 (2.0) 1.9 (1.9) 44.3 (36.1) 63 (28%) 1157 (979) 44.4% (18.3%) 80.9%
0.001 , P . 0.0027 0.001 , P , 0.0027 0.01 , P , 0.046 P , 0.001 P , 0.05 0.1 , P , 0.5
RENAL IMPAIRMENT IN HEPATIC CRYOTHERAPY
265
FIG. 1. Relationship of change in creatinine to volume of cryotherapy.
Patients in the renal impairment group had a greater number of lesions (P , 0.01), larger lesions (P , 0.01), increased freeze time (P , 0.01), and a higher mean day 1 AST (P , 0.01) than those in the non-renal impairment group. However, there was no relationship between volume of cryotherapy and change in creatinine (see Fig. 1). There was no correlation between volume of cryotherapy and change in creatinine in the NRI group (r∧2 5 0.000024), or in the RI group (r∧2 5 0.000286). DISCUSSION
This study indicates that significant renal impairment after cryotherapy is rare, the incidence in our series being 4.4%. Other centers have
reported incidence of significant renal impairment ranging from 0 to 16.6% (9, 10, 14). Our center has previously illustrated the correlation between the postoperative day 1 rise in AST and the extent of hepatocellular injury (12). The significantly higher AST in our group of patients with renal impairment is consistent with this observation. The number and diameter of lesions, and cryotherapy time, together with the AST data, links renal injury with the magnitude of liver injury—all RI patients had AST .1000 compared to only 28% of those who did not. Cozzi et al. (3) observed that the degree of thrombocytopenia following hepatic cryotherapy corresponded to the magnitude of rise in day 1 AST and hence hepatocellular injury, and further
266
BAGIA, PERERA, AND MORRIS
noted that the use of double freeze/thaw cycles caused a more marked thrombocytopenia than single freeze/thaw cycle cryotherapy. The absence of the spleen was found to protect against this thrombocytopenia. The etiology of this platelet fall is not known, though the spleen is thought to be associated with the process. Our center is currently looking at cryotherapy in animal models. Large volume double freezes of normal liver in rats has been shown to be followed by significant cytokine release and thrombocytopenia as well as myoglobinuria acute tubular necrosis—further studies are necessary to gain insight into the mechanisms of these changes (11). The degree of postoperative thrombocytopenia in the renal impairment group was not significantly greater than in the group with unimpaired renal function. It must be noted however that the percentage of patients who underwent double freeze/thaw cryotherapy in the group with renal impairment (66.7%) was less than in the no renal impairment group (80.9%). Our observation of a greater percentage of patients with noncolorectal malignancies in the renal impairment group may be attributable to the currently accepted management protocols. Because of the clear demonstration that survival after liver resection is closely related to the number of lesions (1), we have seldom treated more than four such lesions by cryotherapy and would usually use regional chemotherapy. In neuroendocrine tumors the reduction of liver tumor bulk is an effective form of palliation and we have no specific rule for maximum number (2). Indeed, in one of our patients in whom a dramatic rise of creatinine (from 0.09 to 0.49 mmol/L) was observed, cryotherapy had been used to decrease the volume of symptomatic hepatic carcinoid disease. Renal impairment is one of the most serious but uncommon complications of hepatic cryotherapy and may be seen as part of the clinical syndrome of cryoshock, comprising coagulopathy, pulmonary edema, renal impairment, and circulatory failure, described by the Pittsburgh group (14). We have not seen this complete syndrome, although one patient did develop pulmonary changes in addition to renal impairment. We do not yet know the mechanism of production of renal injury in hepatic cryotherapy—
transient renal impairment may be of course seen following many major operation procedures. The specific risks of cryotherapy may involve myoglobinuria (2), but this was not studied in our patients. We are currently studying the production of myoglobin following hepatic cryotherapy in an animal model. The use of mannitol together with preoperative hydration for the prevention of postoperative renal impairment has been suggested (4). It has been used in prostate cryotherapy with no RI shown in 50 subsequent patients treated with cryosurgery to the prostate. To date there is no conclusive evidence that this is useful in the prevention of renal failure after cryotherapy. Patients at our center are all prehydrated but mannitol has not been used. At present we can give no specific recommendations on the avoidance of renal injury following hepatic cryotherapy, but this paper provides reassurance that it is uncommon and apparently quite benign in its outcome. REFERENCES 1. Cady, B., Stone, M. D., McDermott, W. V., Jenkins, R. L., Bothe, A., and Lavin, P. T. Technical and biological factors in disease free survival after hepatic resection for colorectal cancer metastases. Arch. Surg. 127, 561–569 (1991). 2. Cozzi, P. J., Englund, R., and Morris, D. L. Cryotherapy treatment of patients with hepatic metastases from neuroendocrine tumors. Cancer 76(3), 501–509 (1995). 3. Cozzi, P. J., Stewart, G. J., and Morris, D. L. Thrombocytopaenia after hepatic cryotherapy for colorectal metastases: Correlates with hepatocellular injury. World J. Surg. 18, 774 –777 (1994). 4. Kohn, I. J., Heifets, M., Fisher, S., and Seidmon, E. J. Acute renal failure with thrombocytopaenia after cryosrgery of the prostate. Techniques Urol. 2(4), 230 –233 (1997). 5. Goodie, D. B., Horton, M. D. A., Morris, R. W., Nagy, L. S., and Morris, D. L. Anaesthetic experience with cryotherapy for the treatment of hepatic malignancy. Anaesthesiol. Intensive Care 20, 491– 496 (1992). 6. McCall, J. L., Booth, M. W., and Morris, D. L. Hepatic cryotherapy for metastatic liver tumors. Br. J. Med. 54(8), 378 –381 (1995). 7. Morris, D. L., Horton, M. D. A., Dilley, A. V., Warlters, A., and Clingan, P. R. Treatment of hepatic metastases by cryotherapy and regional cytotoxic perfusion. Gut 34, 1156 –1157 (1993). 8. Onik, G. M. Ultrasound-guided cryosurgery. Sci. Am. Sci. Med. 62–71 (1996).
RENAL IMPAIRMENT IN HEPATIC CRYOTHERAPY 9. Onik, G., Rubinsky, B., Zemel, R., Weaver, L., Diamond, D., Cobb, C., and Porterfield, B. Ultrasound-guided hepatic cryotherapy in the treatment of metastatic colon carcinoma. Cancer 67, 901–907 (1991). 10. Ravikumar, T. S., Steele, G., Kane, R., and King, V. Experimental and clinical observation on hepatic cryotherapy for colorectal metastases. Cancer Res. 51, 6323– 6327 (1991). 11. Seifert, J. K., Finlay, I., Armstrong, N., and Morris, D. L. Thrombocytopenia and cytokine release following hepatic cryosurgery. ANZ J. Surg., in press. [abstract] 12. Stewart, G. J., Preketes, A. P., Horton, M. D., Ross, W. B., and Morris, D. L. Hepatic cryotherapy: Dou-
267
ble freeze with partial thaw cycle achieves greater hepatocellular injury. Cryobiology 32, 215–19 (1995). 13. Tandon, B. N., and Archarya, S. K. Viral diseases involving the liver. Baillieres Clin. Gastroenterol. 1(2), 211 (1987). 14. Tandon, B. N., and Archarya, S. K. Viral diseases involving the liver. Baillieres Clin. Gastroenterol. 1(2), 211 (1987). 15. Xin-Da, Zhou, Zhao-You, Tang, and Ye-Qin, Yu. Cryosurgery for liver tumors. In ‘‘Novel Regional Therapies for Liver Tumors’’ (S. Kawasaki and M. Makuuchi, Eds.), pp. 187–196. Landes Co., 1995.