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Malignancy in renal transplant recipients
Malignancy in Renal Transplant Recipients S.K. Min, S. Huh, M.S. Ahn, I.M. Jung, J. Ha, C. Ahn, Y.J. Bang, J.K. Chung, and S.J. Kim
D
EVELOPMENT of de novo malignancies in renal transplant recipients is one of the most troublesome problems during long-term follow-up. Long-term immunosuppression to prevent rejection episode after renal transplant results in a decrease in host resistance to infectious organisms or tumors. The incidence of cancer after renal transplant is reported to be 4% (1% to 16%) in western societies1 and 1% to 3% in Asian countries.2– 4 We analyze and report our experience of malignancies in renal transplant recipients in a single center.
Table 1. Time Interval Between Transplantation and Development of Cancer According to Tumor Type Cancer Type
No.
Time Post-Tx (mo)
Kaposi’s sarcoma Mucocutaneous* PTLD† Bladder Hepatoma Stomach
6 5 2 2 2 1
9.3 (4 –123) 75.0 (11–130) 78.0 (3–153) 133.5 (89 –178) 134.5 (82–187) 42.0 Mean: 69.9 mo.
*2 melanoma, 1 squamous, conjunctival, and trichilemmal cancer. † 1 small bowel (B-cell), 1 transplant kidney (B-cell).
PATIENTS AND METHODS We reviewed 625 patients who received renal transplantation (570 from living donor and 55 from cadaveric donor) and were followed up in the Transplantation Center, Seoul National University Hospital, Seoul, Korea, from July 1969 to July 1998. Patients who developed histologically proven malignancy after renal transplantation with no evidence of malignancy before transplantation were enrolled. Statistical analyses were performed using the KaplanMeier method for patient and graft survival and a chi-square test and log rank test for comparison.
RESULTS
Eighteen cases of cancer developed in 17 of 625 patients (2.7%) in our follow-up. The types of cancer were Kaposi’s sarcoma (6 cases), mucocutaneous cancer (5), posttransplant lymphoproliferative disease (2), bladder cancer (2), hepatoma (2), and stomach cancer (1). Mucocutaneous cancer included two melanomas, one squamous cell cancer, basal cell cancer, and trichilemmal cancer. The cumulative incidences of cancer at 1, 5, and 10 years after renal transplant were 1.24%, 1.75%, and 2.63%, respectively. Malignancy was diagnosed at the mean age of 44.1 (range, 25 to 59) years and 69.9 (range, 2 to 177) months after kidney transplantation. Mean interval between cancer diagnosis and renal transplant was shortest in Kaposi’s sarcoma (9.3 mo) and longest in hepatoma (134.5 m) (Table 1). The mean age of those in the cancer group was older than the overall patient group (44.1 versus 31.0 years). The male-tofemale ratio was higher in cancer group (16:1 versus 2.8:1). Four cancers in three patients (2.8%) developed among the 109 patients who received azathioprine-based immunosuppression, and 14 cancers (2.7%) in cyclosporine based immunosuppression. Acute rejection episodes happened in
11 patients (64.7%) in the cancer group, which was higher than the incidence in overall patients (20.8%). During treatment, reduction, or withdrawal of immunosuppression was performed in all patients except five, who were treated with curative local excision. Nine patients received surgical treatment including curative local excision in five and graft nephrectomy in one with posttransplant lymphoproliferative disease in the allograft. Chemotherapy and radiotherapy was performed in seven and two patients, respectively. Transarterial embolization was performed in one patient with multiple hepatoma. A total of nine patients died and three graft losses occurred among eight survivors due to chronic rejection and allograft nephrectomy. Median follow-up duration after the development of cancer was 24 months. Median survival duration was 46 months and the 1and 5-year survival rate after the diagnosis of cancer was 75.6% and 32.4%, respectively. The 1-, 5- and 10-year survival rate after renal transplant in the patients with cancer was 93.7%, 79.3%, and 50.5%, respectively, which were poorer than those without cancer (94.2%, 88.6%, and 83.0%, respectively) with statistical significance (P ⬍ .001).
From the Department of Surgery (S.K.M., S.H., M.S.A., J.H., J.K.C., S.J.K.), Department of Internal Medicine (C.A., Y.J.B.), Seoul National University College of Medicine, Seoul, Korea; and the Department of Surgery (I.M.J.), Chungnam National University Hospital, Daejeon, Korea. Address reprint requests to Sang Joon Kim, MD, Department of Surgery, Seoul National University Hospital, 28 Yongon Dong, Chongno Gu, Seoul 110-744, Korea.
0041-1345/00/$–see front matter PII S0041-1345(00)01520-7
© 2000 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
1980
Transplantation Proceedings, 32, 1980–1981 (2000)
MALIGNANCY IN RENAL TX PATIENTS
DISCUSSION
It is well-recognized that an increased incidence of cancer is a complication of organ transplantation. The incidence of cancer is 2.7% in our series, which is similar to other Asian countries and slightly lower than those found in western society. As Penn has mentioned, the incidence may be underestimated.1 Providing more aggressive tumor surveillance, we expect to find more cancer earlier than before. There are some racial, environmental, and topographical differences in the type of cancer occurring in renal transplant recipients. It was reported that skin cancer, lymphoma, and Kaposi’s sarcoma after renal transplant are the major cancers found in western countries.1,5 In our series, Kaposi’s sarcoma was the most common malignancy, which was followed by mucocutaneous cancer. The most common cancer found in Korea, such as stomach, lung and liver cancer, is relatively rare in renal transplant recipients. We found no significant difference in cancer development according to the immunosuppression regimen. Acute rejection episodes were more frequent in the cancer group. It is possible that overdosed immunosuppression for antirejection therapy will decrease the immune surveillance mecha-
1981
nism of the patient and results in increase of cancer development.6 The causes of cancer developing under long-term immunosuppression are thought to be multifactoral.7 Reduction or cessation of immunosuppression was performed in all the cancer patients. Five were treated with curative local excision. We applied multimodality treatment in the other patients according to tumor type, but the prognosis was poor due to more aggressive tumor behavior. Therefore, early diagnosis and treatment is essential for the treatment of cancer in renal transplant recipients. Careful surveillance of malignancy in renal allograft recipients should be considered during long-term follow-up. REFERENCES 1. Penn I: Transplant Proc 23:1101, 1991 2. Kim SJ: J Kor Med Asso 38:6, 1996 3. Yokota K, Fukumitsu M: Transplant Proc 26:1977, 1994 4. Hoshida Y, Tsukuma H, Yasunaga Y, et al: Int J Cancer 71:517, 1997 5. Sheil AGR: Transplant Proc 24:1946, 1992 6. Kinlen LJ, Sheil AGR, Peto J, et al: Br Med J 2:1461, 1979 7. Penn I: Transplant Proc 16:492, 1984
D
EVELOPMENT of de novo malignancies in renal transplant recipients is one of the most troublesome problems during long-term follow-up. Long-term immunosuppression to prevent rejection episode after renal transplant results in a decrease in host resistance to infectious organisms or tumors. The incidence of cancer after renal transplant is reported to be 4% (1% to 16%) in western societies1 and 1% to 3% in Asian countries.2– 4 We analyze and report our experience of malignancies in renal transplant recipients in a single center.
Table 1. Time Interval Between Transplantation and Development of Cancer According to Tumor Type Cancer Type
No.
Time Post-Tx (mo)
Kaposi’s sarcoma Mucocutaneous* PTLD† Bladder Hepatoma Stomach
6 5 2 2 2 1
9.3 (4 –123) 75.0 (11–130) 78.0 (3–153) 133.5 (89 –178) 134.5 (82–187) 42.0 Mean: 69.9 mo.
*2 melanoma, 1 squamous, conjunctival, and trichilemmal cancer. † 1 small bowel (B-cell), 1 transplant kidney (B-cell).
PATIENTS AND METHODS We reviewed 625 patients who received renal transplantation (570 from living donor and 55 from cadaveric donor) and were followed up in the Transplantation Center, Seoul National University Hospital, Seoul, Korea, from July 1969 to July 1998. Patients who developed histologically proven malignancy after renal transplantation with no evidence of malignancy before transplantation were enrolled. Statistical analyses were performed using the KaplanMeier method for patient and graft survival and a chi-square test and log rank test for comparison.
RESULTS
Eighteen cases of cancer developed in 17 of 625 patients (2.7%) in our follow-up. The types of cancer were Kaposi’s sarcoma (6 cases), mucocutaneous cancer (5), posttransplant lymphoproliferative disease (2), bladder cancer (2), hepatoma (2), and stomach cancer (1). Mucocutaneous cancer included two melanomas, one squamous cell cancer, basal cell cancer, and trichilemmal cancer. The cumulative incidences of cancer at 1, 5, and 10 years after renal transplant were 1.24%, 1.75%, and 2.63%, respectively. Malignancy was diagnosed at the mean age of 44.1 (range, 25 to 59) years and 69.9 (range, 2 to 177) months after kidney transplantation. Mean interval between cancer diagnosis and renal transplant was shortest in Kaposi’s sarcoma (9.3 mo) and longest in hepatoma (134.5 m) (Table 1). The mean age of those in the cancer group was older than the overall patient group (44.1 versus 31.0 years). The male-tofemale ratio was higher in cancer group (16:1 versus 2.8:1). Four cancers in three patients (2.8%) developed among the 109 patients who received azathioprine-based immunosuppression, and 14 cancers (2.7%) in cyclosporine based immunosuppression. Acute rejection episodes happened in
11 patients (64.7%) in the cancer group, which was higher than the incidence in overall patients (20.8%). During treatment, reduction, or withdrawal of immunosuppression was performed in all patients except five, who were treated with curative local excision. Nine patients received surgical treatment including curative local excision in five and graft nephrectomy in one with posttransplant lymphoproliferative disease in the allograft. Chemotherapy and radiotherapy was performed in seven and two patients, respectively. Transarterial embolization was performed in one patient with multiple hepatoma. A total of nine patients died and three graft losses occurred among eight survivors due to chronic rejection and allograft nephrectomy. Median follow-up duration after the development of cancer was 24 months. Median survival duration was 46 months and the 1and 5-year survival rate after the diagnosis of cancer was 75.6% and 32.4%, respectively. The 1-, 5- and 10-year survival rate after renal transplant in the patients with cancer was 93.7%, 79.3%, and 50.5%, respectively, which were poorer than those without cancer (94.2%, 88.6%, and 83.0%, respectively) with statistical significance (P ⬍ .001).
From the Department of Surgery (S.K.M., S.H., M.S.A., J.H., J.K.C., S.J.K.), Department of Internal Medicine (C.A., Y.J.B.), Seoul National University College of Medicine, Seoul, Korea; and the Department of Surgery (I.M.J.), Chungnam National University Hospital, Daejeon, Korea. Address reprint requests to Sang Joon Kim, MD, Department of Surgery, Seoul National University Hospital, 28 Yongon Dong, Chongno Gu, Seoul 110-744, Korea.
0041-1345/00/$–see front matter PII S0041-1345(00)01520-7
© 2000 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
1980
Transplantation Proceedings, 32, 1980–1981 (2000)
MALIGNANCY IN RENAL TX PATIENTS
DISCUSSION
It is well-recognized that an increased incidence of cancer is a complication of organ transplantation. The incidence of cancer is 2.7% in our series, which is similar to other Asian countries and slightly lower than those found in western society. As Penn has mentioned, the incidence may be underestimated.1 Providing more aggressive tumor surveillance, we expect to find more cancer earlier than before. There are some racial, environmental, and topographical differences in the type of cancer occurring in renal transplant recipients. It was reported that skin cancer, lymphoma, and Kaposi’s sarcoma after renal transplant are the major cancers found in western countries.1,5 In our series, Kaposi’s sarcoma was the most common malignancy, which was followed by mucocutaneous cancer. The most common cancer found in Korea, such as stomach, lung and liver cancer, is relatively rare in renal transplant recipients. We found no significant difference in cancer development according to the immunosuppression regimen. Acute rejection episodes were more frequent in the cancer group. It is possible that overdosed immunosuppression for antirejection therapy will decrease the immune surveillance mecha-
1981
nism of the patient and results in increase of cancer development.6 The causes of cancer developing under long-term immunosuppression are thought to be multifactoral.7 Reduction or cessation of immunosuppression was performed in all the cancer patients. Five were treated with curative local excision. We applied multimodality treatment in the other patients according to tumor type, but the prognosis was poor due to more aggressive tumor behavior. Therefore, early diagnosis and treatment is essential for the treatment of cancer in renal transplant recipients. Careful surveillance of malignancy in renal allograft recipients should be considered during long-term follow-up. REFERENCES 1. Penn I: Transplant Proc 23:1101, 1991 2. Kim SJ: J Kor Med Asso 38:6, 1996 3. Yokota K, Fukumitsu M: Transplant Proc 26:1977, 1994 4. Hoshida Y, Tsukuma H, Yasunaga Y, et al: Int J Cancer 71:517, 1997 5. Sheil AGR: Transplant Proc 24:1946, 1992 6. Kinlen LJ, Sheil AGR, Peto J, et al: Br Med J 2:1461, 1979 7. Penn I: Transplant Proc 16:492, 1984