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Surgery for Metachronous Solitary Liver Metastases of Renal Cell Carcinoma
0022-5347/97/1582-0375$03.00/0
THEJOURNAL OF UROLoCY Copyright 0 1997 by AMERICAN U R O ~ I CASSOCIATION, AL INC.
VoI. 158.3 7 W 7 7 , August 1997 Printed i n U S A .
SURGERY FOR METACHRONOUS SOLITARY LIVER METASTASES OF RENAL CELL CARCINOMA CHRISTIAN G. STIEF, JOACHIM J m N E , JORN H. HAGEMA", MARKUS KUCZYK AND UDO JONAS From the Departments of Urology and Surgery, Medizinische Hochschule, Hannover, Germany
ABSTRACT
Purpose: The postoperative outcome and survival of patients undergoing surgery for metachronous solitary liver metastases of renal cell carcinoma were evaluated. Materials and Methods: Between 1983 and 1993, 17 patients with metachronous liver metastases of renal cell carcinoma underwent laparotomy for metastatic liver disease. All patients had undergone radical nephrectomy a mean of 3.6 years before the diagnosis of liver metastases. Results: Surgical resection was feasible in 13 of 17 patients with right hemihepatectomy in 9 (3 multivisceral resections), wedge resection in 4 and ex situ (mobilization and eversion out of the abdomen) resection in 1. Stage RO resection (complete removal, negative surgical margins with no macroscopic disease left behind) was possible in 11 of 13 cases (85%).In patients with metastatic liver tissue resection the mortality rate was 31%(4 of 13) with additional significant morbidity in another 2. Mean survival of patients with nonresectable disease was 4 months, which increased t o 16 months after resection. Conclusions: Complete resection of metachronous liver metastases can be achieved in the majority of patients. However, significant morbidity and mortality as well as the limited prognosis even after RO resection strongly suggest careful patient selection. KEY WORDS: carcinoma, renal cell; neoplasm metastasis; liver; surgery; prognosis At diagnosis approximately a third of the patients with renal cell carcinoma exhibit evidence of metastatic disease.' The prognosis for patients with metastatic renal cell carcinoma is poor with an average survival of 4 months and only 10% surviving 1 year.13 Metachronous metastases will develop in approximately 50% of patients with renal cell carcinoma and no evidence of metastatic disease at radical nephrectomy.4 Compared to patients with synchronous metastases, the prognosis is marginally better, with an average survival of 11 months and 73% surviving 1 year.4 As determined in autopsy series 8 to 11%of patients with metachronous metastases will have a solitary lesion or several lesions of 1organ.5 Liver involvement is found in 41%of multifocal metastatic lesions of renal cell carcinoma but in only 5% of solitary metachronous tumors. A solitary metachronous pulmonary metastasis was reported to represent a favorable prognostic factor with 5-year survival rates of 35 to 50% when aggressive surgical resection was applied.6.7 Contrary to these solitary metachronous pulmonary metastases in renal cell carcinoma, the occurrence of liver metastases was regarded as a severe adverse prognostic f e a t ~ r e . 3 . ~ Although the introduction of immunotherapy or immunochemotherapy for advanced renal cell carcinoma improved survival for a subset of patients,g-'* surgical resection of the renal tumor and solitary metastases is still the treatment of choice for these lesions. We evaluated the postoperative outcome of patients with renal cell carcinoma who underwent surgery for 1 or several metachronous solitary liver metastases.
were men 27 to 80 years old (mean age 58.0) and 5 were women 55 to 70 years old (mean age 53.4). All patients underwent radical nephrectomy as primary treatment after the initial diagnosis. At diagnosis there was no radiographic evidence of metastases on computerized tomography of the abdomen and pelvis (available in 14 of 17 patients), chest x-ray or bone scan. All tumors were stage pNO. Three patients received postoperative radiotherapy and l received immunochemotherapy. In 2 patients solitary pulmonary metastases diagnosed 2 and 10 years after the initial diagnosis were resected with stage RO margins in both patients. Patients were followed regularly a t 3-month intervals for the first 2 years and a t 6-month intervals thereafter for 3 years. One or several metachronous solitary liver metastases were diagnosed 7 to 120 months (mean 42) aRer radical nephrectomy. In 1 patient another intrahepatic metastatic focus was observed 36 months after the initial liver wedge resection. Preoperatively, blood laboratory studies included measurements of s e w glutamic-oxaloacetic transaminase, serum glutamate pyruvate transaminase, glutamate dehydrogenase, lactate dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase, cholinesterase, bilirubin and amylase. RESULTS
The general health of all patients allowed for possible extensive liver resection. A m o n g the liver enzymes gammaglutamyl transferase was elevated in 7 of 17 patients with global liver function parameters (albumin, coagulation proMATERIALS AND METHODS file, cholinesterase) being abnormal in 2. Alkaline phosBetween 1983 and 1993, liver metastases from 539 pa- phatase was elevated in 5 of 17 patients. Preoperative tients with colorectal and noncolorectal metastases disease ultrasound and/or computerized tomography of the liver were resected, including 17 (3.2%)with metachronous liver suggested extensive metastatic disease with uncertain remetastases of a renal cell carcinoma. Of the 17 patients 12 sectability in 2 of 17 patients. Exploratory laparotomy was performed in all 17 patients and 4 had technically unresectable disease. There were no Accepted for publication December 27,1996. 375
376
SURGERY FOR METACHRONOUS SOLITARY LIVER METASTASES OF RENAL CELL CANCER
intraoperative or postoperative complications in these 4 patients (mean postoperative survival 4 months). In all 4 patients a significant elevation of serum alkaline phosphatase (269to 935 units per l., mean 588,normal 40 to 190) and serum gamma-glutamyl transferase (75to 205 units per ml., mean 155,normal 0 to 18 in women and 0 to 28 in men) was observed compared to 1 of 13 (97 units per ml.) with liver resection, Cholinesterase was 1.8to 4.5 kilounits per 1. (mean 2.9, normal 3.5 to 8) in the 4 patients with unresectable disease. In 13 of 17 patients the liver metastases were excised via right hemihepatectomy in 9 (including 3 multivisceral resections), wedge resection in 4 and ex situ resection in 1 (see table). Stage RO resection was achieved in 11 of 13 cases (85%).Transfueion of packed red blood cells (3 units) was needed in only 1patient with right hemihepatectomy due to laceration of the left hepatic vein. However, 2 patients required immediate reoperation after admission into the intensive care unit due to severe hypovolemic reactions caused by diffuse postoperativebleeding. Four of 13 patients (31%) died postoperatively (all 4 underwent hemihepatectomy). In 1 patient with the leR hepatic vein laceration pulmonary embolism occurred 5 days postoperatively, while 1 had anastomotic insuf€iciency after a Whipple procedure and died of peritonitis and pancreatitis at 33 days, 1 with postoperative bleeding and multiple organ failure died at 6 days and 1 died of pulmonary insufliciency at 20 days. Mean postoperative survival was 16 months (range 7 to 74)as of November 1995,with 2 patients alive and 3 lost to followup. DISCUSSION
disease. From these observations one may conclude that a surgical attempt in patients presenting with large liver metastases and elevated alkaline phosphatase and gammaglutamyl transferase levels, and decreased cholinesterase is not indicated. The outcome of our patients undergoing surgical excision of hepatic metastases is ambivalent. On one hand we experienced a high postoperative mortality rate of 31%. Compared to the resection of liver metastases of different tumors, in which postoperative mortality rates were 3 to 6% in other studies19.20 and in our series,21 the postoperative mortality rate in our present series may be explained by the larger size of metastases necessitating wider excisions, with 2 of 4 patients requiring multivisceral surgery. On the other hand, the survival time of the patients (mean 16 months, with 2 still alive at present) is dramatically improved compared to that of the nonresedable group and seems comparable to that of other solitary parenchymal metastases of renal cell carcinoma.% However, it is clearly inferior to the survival time of other metastatic hepatic lesions, for example of breast cancer.21 CONCLUSIONS
Considering that mortality was exceedingly high, with 2 of 3 patients requiring multivisceral excisions, we believe that careful selection to avoid excessively extended surgery may improve survival and quality of life in patients with solitary metachronous liver metastases of renal cell carcinoma. However, prospective multicenter trails with matched controls without surgery are needed to determine the role of this operation.
Metastatic renal cell disease compromises a poor prognosi~~ with an expected survival of several months. Therefore, mean survival of patients with synchronous metastatic renal cell carcinoma is 4 months with a slightly superior mean life expectancy of 11 months for metachronous metastatic disease.1-4 Whereas metachronous pulmonary metastases appear to be of favorable prognostic significance, the OccUITence of metachronous liver metastases is an ominous sign for the patient.3-6-8 There are only anecdotal reports on the surgical treatment of metachronous liver metastases of renal cell carcinoma,13.14 so that significant data on survival of the small subset of patients are missing. However, it is known from colorectal metastatic involvement of the liver that the natural history results in a 2 to &month survival.16 These data, together with the fact that adjuvant medical therapies showed a limited response rate, prompted us and others’s-18 to offer surgical resection to patients with solitary metachronous liver metastases of renal cell carcinoma. In our limited series patients with nonreeectable solitary liver metastases had a mean survival of 4 months, which is in agreement with the natural course of the disease.3.4 All of theae patients with nonreeectable liver metastases had large tumors on preoperative imaging and a significant elevation of alkaline phosphatase and gamma-glutamyl transferase levels that was not observed in the group with resectable
lsrpcs of liver rescctwn and poatopemtiw complications TYD0ofReSecti0n
No. pts.
REFERENCES
1. deKernion, J. B.:Renal tumors. In: Campbell’s Urology, 5th ed. Edited by P. C. Walsh, R. F. Gittes, A. D. Perlmutter and T. A. Stamey. Philadelphia: W.B. Saunders Co., vol. 2, chapt. 29, pp. 1294-1342, 1986. 2. Frank,W.,Stuhldreher, D., Saffrin, R., Shott, S.and Guinan, P.: Stage lV renal cell carcinoma. 3. Urol., 162 1998,1994. 3. Maldaqs, J. D. and deKernion, J. B.: Prognostic factors in metastatic renal cell carcinoma. J. Urol.,136 376,1986. 4. Giuliani, L., Giberti, G., Martorana, M. and Rovida, S.: Radical extensive surgery for renal cell carcinoma: long-term results and prognostic factors. J. Urol., 143: 468,1990. 5. Hajdu, S. I. and Thomas, A. G.: Renal cell carcinoma a t autopsy. J. Urol., 91: 978,1967. 6. Middleton, R. G.: Surgery for metastatic renal cell carcinoma. J. Urol., 97: 973,1967. 7. Tolia, B. M.and Whitmore, W.F., Jr.: Solitary metastases from renal cell carcinoma. J. Urol., 114:836,1975. 8. deKernion, J. B., Ramming, K P. and Smith, R. B.: The natural history of metastatic renal cell carcinoma: a computer analysis. J. Urol., 120:148,1978. 9. Kirchner, H. H., Anton, P. and Azpodien, J.:Adjuvant treatment of locally advanced renal cancer with autologous virusmodified tumor vaccines. World J. Urol., 13 171,1995. 10. Atzpodien, J., Kirchner, H., Duensing, S.,Lopez Hanninen, E., Franzke, A., Buer, J., Probst, M., Anton, P. and Poliwoda, H.: Biochemotherapy of advanced metastatic renal-cell carcinoma: results of the combination of interleukin-2, alphainterferon, 5-fluorouracil, vinblastine and B-cis-retinoic acid. World J. Urol.,13174,1995. 11. Belldegrun, A., Franklin, J. R. and Figlin, R.: Commentary on prognostic factors in renal cell carcinoma. J. Urol., 154:1274, 1995. 12. Liimmen, G., Goepel, M., Mollhoff, S.,Hinke, A., Otto, T. and Rubben, H.: Phase I1 study of interferon-a versw interleukin-2 and interferon-a2b in metastatic renal cell carcinoma. J. Urol., 165: 455,1996. 13. Hohenberger,H.: Possibilities and limitations of surgery for liver metastases of renal cell carcinoma. In: Contemporary Research on Renal Cell Carcinoma. Edited by G. Staeler and s. Pomer. New York Springer-Verlag, 1994. 14. Bennet, B. C., Selby, R. and Bahnson, R. R.: Surgical resection
SURGERY FOR METACHRONOUS SOLITARY LIVER METASTASES O F RENAL CELL CANCER for management of renal cancer with hepatic involvment. J. Urol., 154: 972,1995. 15. Foster, J.H.: Survival after liver resection for secondary tumors. Amer. J. Surg., 135: 289, 1978. 16. Thrasher, J. B. and Paulson, D. F.: Prognostic factors in renal cancer. Urol. Clin. N. Amer., 2 0 247,1993. 17. Skinner, D. G., Colvin, R. B. and Vermillon, C. D.: Diagnosis and management of renal cell carcinoma: a clinical and pathological study of 309 cases. Cancer, 2 8 1165,1971. 18. O’Dea, M. J.,Zincke, H., Utz, D. C. and Bernatz, P. E.: The treatment of renal cell carcinoma with solitary metastases.
377
J . Urol., 120 540, 1978. 19. Iwatsuki, S.,Shaw, B. W., J r . and Starzl, T. E.: Experience with 150 liver resections. Ann. Surg., 197:247,1983. 20. Pommier, R. F.,Woltering, E. A., Campbell, J. R. and Fletcher, W. S.: Hepatic resection of primary and secondary neoplasms of the liver. Amer. J. Surg., 153: 428, 1987. 21. Raab, R., Nussbaum, K. T., Werner, U. and Pichlmayr, R.: Lebermetastasen bei Mammacaninom. Chirurg, 61:234, 1996. 22. Cozzoli, A., Milano, S., Cancarini, G., Zanotelli, T. and Cosciani Cunico, S.: Surgery of lung metastases in renal cell carcinoma. Brit. J . Urol., 75: 445, 1995.
THEJOURNAL OF UROLoCY Copyright 0 1997 by AMERICAN U R O ~ I CASSOCIATION, AL INC.
VoI. 158.3 7 W 7 7 , August 1997 Printed i n U S A .
SURGERY FOR METACHRONOUS SOLITARY LIVER METASTASES OF RENAL CELL CARCINOMA CHRISTIAN G. STIEF, JOACHIM J m N E , JORN H. HAGEMA", MARKUS KUCZYK AND UDO JONAS From the Departments of Urology and Surgery, Medizinische Hochschule, Hannover, Germany
ABSTRACT
Purpose: The postoperative outcome and survival of patients undergoing surgery for metachronous solitary liver metastases of renal cell carcinoma were evaluated. Materials and Methods: Between 1983 and 1993, 17 patients with metachronous liver metastases of renal cell carcinoma underwent laparotomy for metastatic liver disease. All patients had undergone radical nephrectomy a mean of 3.6 years before the diagnosis of liver metastases. Results: Surgical resection was feasible in 13 of 17 patients with right hemihepatectomy in 9 (3 multivisceral resections), wedge resection in 4 and ex situ (mobilization and eversion out of the abdomen) resection in 1. Stage RO resection (complete removal, negative surgical margins with no macroscopic disease left behind) was possible in 11 of 13 cases (85%).In patients with metastatic liver tissue resection the mortality rate was 31%(4 of 13) with additional significant morbidity in another 2. Mean survival of patients with nonresectable disease was 4 months, which increased t o 16 months after resection. Conclusions: Complete resection of metachronous liver metastases can be achieved in the majority of patients. However, significant morbidity and mortality as well as the limited prognosis even after RO resection strongly suggest careful patient selection. KEY WORDS: carcinoma, renal cell; neoplasm metastasis; liver; surgery; prognosis At diagnosis approximately a third of the patients with renal cell carcinoma exhibit evidence of metastatic disease.' The prognosis for patients with metastatic renal cell carcinoma is poor with an average survival of 4 months and only 10% surviving 1 year.13 Metachronous metastases will develop in approximately 50% of patients with renal cell carcinoma and no evidence of metastatic disease at radical nephrectomy.4 Compared to patients with synchronous metastases, the prognosis is marginally better, with an average survival of 11 months and 73% surviving 1 year.4 As determined in autopsy series 8 to 11%of patients with metachronous metastases will have a solitary lesion or several lesions of 1organ.5 Liver involvement is found in 41%of multifocal metastatic lesions of renal cell carcinoma but in only 5% of solitary metachronous tumors. A solitary metachronous pulmonary metastasis was reported to represent a favorable prognostic factor with 5-year survival rates of 35 to 50% when aggressive surgical resection was applied.6.7 Contrary to these solitary metachronous pulmonary metastases in renal cell carcinoma, the occurrence of liver metastases was regarded as a severe adverse prognostic f e a t ~ r e . 3 . ~ Although the introduction of immunotherapy or immunochemotherapy for advanced renal cell carcinoma improved survival for a subset of patients,g-'* surgical resection of the renal tumor and solitary metastases is still the treatment of choice for these lesions. We evaluated the postoperative outcome of patients with renal cell carcinoma who underwent surgery for 1 or several metachronous solitary liver metastases.
were men 27 to 80 years old (mean age 58.0) and 5 were women 55 to 70 years old (mean age 53.4). All patients underwent radical nephrectomy as primary treatment after the initial diagnosis. At diagnosis there was no radiographic evidence of metastases on computerized tomography of the abdomen and pelvis (available in 14 of 17 patients), chest x-ray or bone scan. All tumors were stage pNO. Three patients received postoperative radiotherapy and l received immunochemotherapy. In 2 patients solitary pulmonary metastases diagnosed 2 and 10 years after the initial diagnosis were resected with stage RO margins in both patients. Patients were followed regularly a t 3-month intervals for the first 2 years and a t 6-month intervals thereafter for 3 years. One or several metachronous solitary liver metastases were diagnosed 7 to 120 months (mean 42) aRer radical nephrectomy. In 1 patient another intrahepatic metastatic focus was observed 36 months after the initial liver wedge resection. Preoperatively, blood laboratory studies included measurements of s e w glutamic-oxaloacetic transaminase, serum glutamate pyruvate transaminase, glutamate dehydrogenase, lactate dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase, cholinesterase, bilirubin and amylase. RESULTS
The general health of all patients allowed for possible extensive liver resection. A m o n g the liver enzymes gammaglutamyl transferase was elevated in 7 of 17 patients with global liver function parameters (albumin, coagulation proMATERIALS AND METHODS file, cholinesterase) being abnormal in 2. Alkaline phosBetween 1983 and 1993, liver metastases from 539 pa- phatase was elevated in 5 of 17 patients. Preoperative tients with colorectal and noncolorectal metastases disease ultrasound and/or computerized tomography of the liver were resected, including 17 (3.2%)with metachronous liver suggested extensive metastatic disease with uncertain remetastases of a renal cell carcinoma. Of the 17 patients 12 sectability in 2 of 17 patients. Exploratory laparotomy was performed in all 17 patients and 4 had technically unresectable disease. There were no Accepted for publication December 27,1996. 375
376
SURGERY FOR METACHRONOUS SOLITARY LIVER METASTASES OF RENAL CELL CANCER
intraoperative or postoperative complications in these 4 patients (mean postoperative survival 4 months). In all 4 patients a significant elevation of serum alkaline phosphatase (269to 935 units per l., mean 588,normal 40 to 190) and serum gamma-glutamyl transferase (75to 205 units per ml., mean 155,normal 0 to 18 in women and 0 to 28 in men) was observed compared to 1 of 13 (97 units per ml.) with liver resection, Cholinesterase was 1.8to 4.5 kilounits per 1. (mean 2.9, normal 3.5 to 8) in the 4 patients with unresectable disease. In 13 of 17 patients the liver metastases were excised via right hemihepatectomy in 9 (including 3 multivisceral resections), wedge resection in 4 and ex situ resection in 1 (see table). Stage RO resection was achieved in 11 of 13 cases (85%).Transfueion of packed red blood cells (3 units) was needed in only 1patient with right hemihepatectomy due to laceration of the left hepatic vein. However, 2 patients required immediate reoperation after admission into the intensive care unit due to severe hypovolemic reactions caused by diffuse postoperativebleeding. Four of 13 patients (31%) died postoperatively (all 4 underwent hemihepatectomy). In 1 patient with the leR hepatic vein laceration pulmonary embolism occurred 5 days postoperatively, while 1 had anastomotic insuf€iciency after a Whipple procedure and died of peritonitis and pancreatitis at 33 days, 1 with postoperative bleeding and multiple organ failure died at 6 days and 1 died of pulmonary insufliciency at 20 days. Mean postoperative survival was 16 months (range 7 to 74)as of November 1995,with 2 patients alive and 3 lost to followup. DISCUSSION
disease. From these observations one may conclude that a surgical attempt in patients presenting with large liver metastases and elevated alkaline phosphatase and gammaglutamyl transferase levels, and decreased cholinesterase is not indicated. The outcome of our patients undergoing surgical excision of hepatic metastases is ambivalent. On one hand we experienced a high postoperative mortality rate of 31%. Compared to the resection of liver metastases of different tumors, in which postoperative mortality rates were 3 to 6% in other studies19.20 and in our series,21 the postoperative mortality rate in our present series may be explained by the larger size of metastases necessitating wider excisions, with 2 of 4 patients requiring multivisceral surgery. On the other hand, the survival time of the patients (mean 16 months, with 2 still alive at present) is dramatically improved compared to that of the nonresedable group and seems comparable to that of other solitary parenchymal metastases of renal cell carcinoma.% However, it is clearly inferior to the survival time of other metastatic hepatic lesions, for example of breast cancer.21 CONCLUSIONS
Considering that mortality was exceedingly high, with 2 of 3 patients requiring multivisceral excisions, we believe that careful selection to avoid excessively extended surgery may improve survival and quality of life in patients with solitary metachronous liver metastases of renal cell carcinoma. However, prospective multicenter trails with matched controls without surgery are needed to determine the role of this operation.
Metastatic renal cell disease compromises a poor prognosi~~ with an expected survival of several months. Therefore, mean survival of patients with synchronous metastatic renal cell carcinoma is 4 months with a slightly superior mean life expectancy of 11 months for metachronous metastatic disease.1-4 Whereas metachronous pulmonary metastases appear to be of favorable prognostic significance, the OccUITence of metachronous liver metastases is an ominous sign for the patient.3-6-8 There are only anecdotal reports on the surgical treatment of metachronous liver metastases of renal cell carcinoma,13.14 so that significant data on survival of the small subset of patients are missing. However, it is known from colorectal metastatic involvement of the liver that the natural history results in a 2 to &month survival.16 These data, together with the fact that adjuvant medical therapies showed a limited response rate, prompted us and others’s-18 to offer surgical resection to patients with solitary metachronous liver metastases of renal cell carcinoma. In our limited series patients with nonreeectable solitary liver metastases had a mean survival of 4 months, which is in agreement with the natural course of the disease.3.4 All of theae patients with nonreeectable liver metastases had large tumors on preoperative imaging and a significant elevation of alkaline phosphatase and gamma-glutamyl transferase levels that was not observed in the group with resectable
lsrpcs of liver rescctwn and poatopemtiw complications TYD0ofReSecti0n
No. pts.
REFERENCES
1. deKernion, J. B.:Renal tumors. In: Campbell’s Urology, 5th ed. Edited by P. C. Walsh, R. F. Gittes, A. D. Perlmutter and T. A. Stamey. Philadelphia: W.B. Saunders Co., vol. 2, chapt. 29, pp. 1294-1342, 1986. 2. Frank,W.,Stuhldreher, D., Saffrin, R., Shott, S.and Guinan, P.: Stage lV renal cell carcinoma. 3. Urol., 162 1998,1994. 3. Maldaqs, J. D. and deKernion, J. B.: Prognostic factors in metastatic renal cell carcinoma. J. Urol.,136 376,1986. 4. Giuliani, L., Giberti, G., Martorana, M. and Rovida, S.: Radical extensive surgery for renal cell carcinoma: long-term results and prognostic factors. J. Urol., 143: 468,1990. 5. Hajdu, S. I. and Thomas, A. G.: Renal cell carcinoma a t autopsy. J. Urol., 91: 978,1967. 6. Middleton, R. G.: Surgery for metastatic renal cell carcinoma. J. Urol., 97: 973,1967. 7. Tolia, B. M.and Whitmore, W.F., Jr.: Solitary metastases from renal cell carcinoma. J. Urol., 114:836,1975. 8. deKernion, J. B., Ramming, K P. and Smith, R. B.: The natural history of metastatic renal cell carcinoma: a computer analysis. J. Urol., 120:148,1978. 9. Kirchner, H. H., Anton, P. and Azpodien, J.:Adjuvant treatment of locally advanced renal cancer with autologous virusmodified tumor vaccines. World J. Urol., 13 171,1995. 10. Atzpodien, J., Kirchner, H., Duensing, S.,Lopez Hanninen, E., Franzke, A., Buer, J., Probst, M., Anton, P. and Poliwoda, H.: Biochemotherapy of advanced metastatic renal-cell carcinoma: results of the combination of interleukin-2, alphainterferon, 5-fluorouracil, vinblastine and B-cis-retinoic acid. World J. Urol.,13174,1995. 11. Belldegrun, A., Franklin, J. R. and Figlin, R.: Commentary on prognostic factors in renal cell carcinoma. J. Urol., 154:1274, 1995. 12. Liimmen, G., Goepel, M., Mollhoff, S.,Hinke, A., Otto, T. and Rubben, H.: Phase I1 study of interferon-a versw interleukin-2 and interferon-a2b in metastatic renal cell carcinoma. J. Urol., 165: 455,1996. 13. Hohenberger,H.: Possibilities and limitations of surgery for liver metastases of renal cell carcinoma. In: Contemporary Research on Renal Cell Carcinoma. Edited by G. Staeler and s. Pomer. New York Springer-Verlag, 1994. 14. Bennet, B. C., Selby, R. and Bahnson, R. R.: Surgical resection
SURGERY FOR METACHRONOUS SOLITARY LIVER METASTASES O F RENAL CELL CANCER for management of renal cancer with hepatic involvment. J. Urol., 154: 972,1995. 15. Foster, J.H.: Survival after liver resection for secondary tumors. Amer. J. Surg., 135: 289, 1978. 16. Thrasher, J. B. and Paulson, D. F.: Prognostic factors in renal cancer. Urol. Clin. N. Amer., 2 0 247,1993. 17. Skinner, D. G., Colvin, R. B. and Vermillon, C. D.: Diagnosis and management of renal cell carcinoma: a clinical and pathological study of 309 cases. Cancer, 2 8 1165,1971. 18. O’Dea, M. J.,Zincke, H., Utz, D. C. and Bernatz, P. E.: The treatment of renal cell carcinoma with solitary metastases.
377
J . Urol., 120 540, 1978. 19. Iwatsuki, S.,Shaw, B. W., J r . and Starzl, T. E.: Experience with 150 liver resections. Ann. Surg., 197:247,1983. 20. Pommier, R. F.,Woltering, E. A., Campbell, J. R. and Fletcher, W. S.: Hepatic resection of primary and secondary neoplasms of the liver. Amer. J. Surg., 153: 428, 1987. 21. Raab, R., Nussbaum, K. T., Werner, U. and Pichlmayr, R.: Lebermetastasen bei Mammacaninom. Chirurg, 61:234, 1996. 22. Cozzoli, A., Milano, S., Cancarini, G., Zanotelli, T. and Cosciani Cunico, S.: Surgery of lung metastases in renal cell carcinoma. Brit. J . Urol., 75: 445, 1995.