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Editorial: Renal Tumors
0022-5347/94/1521-0043$03.00/0 Vol. 152, 43-44, July 1994 Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1994 by AMERICAN
UROLOGICAL AssoCIATION, INC.
EDITORIAL: RENAL TUMORS The preceding 3 papers on renal tumors address a wide variety of issues that might be of concern to the reader. Nakagawa et al (page 29) investigated the use of nephrocalcin (an acidic glycoprotein that inhibits calcium oxalate crystal growth) as a tumor marker. This compound can be found in a nonpredictable pattern in the urine of patients with renal cell cancer and postoperatively in its different bfochemical forms . The postoperative urinary nephrocalcin concentration remained at a similar level in 7 patients, was decreased in 8 and was still increased in 4 compared to that of a control group. There was no correlation between pathological variables and nephrocalcin levels before and after treatment. The author s did not provide information in regard to the half-life of nephrocalcin. Although there was a dramatic decrease in nephrocalcin levels in 6 of 19 patients who underwent surgery, it seems by no mea ns a marker for followup in patients who have undergone nephrectomy. The unpredictability of the test makes one wonder whether the polyclonal antibody to nephrocalcin was specific enough. For 5 years after the initial imaging study van Baal et al (page 35) used ultrasonography only to follow a group of 20 patients who had tuberous sclerosis with renal angiomyolipoma. There was no change in the size of the lesion in 14 patients (70%). Four patients (29%) experienced severe hemorrhage during the interval and 1 of them died of hemorrhage. A total of 4 patients (20%) had increased lesion size, and 7 (35%) had significant hemorrhage from the tumors necessitating treatment. Of these patients 5 had tumors larger than 3.5 cm. but hemorrhage developed in only 1 of 13 with a tumor smaller than 3.5 cm. In a similar ~eries from our institution 33 patients underwent multiple studies during intervals of 3 to 13 years.1 New angiomyolipomas appeared in 6 patients with negative initial studies. An increase in the number and/or size of angiomyolipomas was observed in 9 of 13 patients who already had lesions at initial evaluation. The rate of growth of the lesions ranged from 1 to 12 mm. per year (mean 5). These data show convincingly that patients with angiomyolipomas (with or without tuberous sclerosis) should be carefully followed for changes in the recognized lesion. The association of renal cell carcinoma with tuberous sclerosis complex should be considered in cases of enlarging lesions with no fatty tissue demonstrable by sonography, computerized tomography or magnetic resonance imaging, and when intratumoral calcifications, which occur rarely with uncomplicated angiomyolipomas, are present. Of 403 patients with the tuberous sclerosis complex seen at our center 4 had renal cancer and 2 died of m etastatic disease. Recently, Washecka and Hanna reviewed 16 cases in the literature and noted 3 death s from metastatic disease.2 In this review 81 % were female patients. Median age at diagnosis was 28 years, and 43% of the carcinomas were bilateral. This observation suggests that the natural history of renal cell carcinoma associated with the tuberous sclerosis complex is not as benign as once believed. For these reasons, when there is a change on imaging studies (preferably computerized tomography scanning) we recommend exploration with a renal conserving operation. This is true not only because of the potential danger of h emorrhage but also because of the occurrence of renal cell cancer and/or local parenchymal destruction. An operation, however, depends on the site and number of lesions, patient age and the lung disease in some patients who may have the concomitant findings of pulmonary lymphangioleiomyomatosis.
The article by Licht et al (page 39) provides information on patients with suspected versus incidental renal cell cancer who have undergone conservative surgical treatment for renal cell carcinoma. They found that incidental renal cell tumors were usually smaller (median 3.6 cm.), of lower stage (81 % of the patients had stage I disease) and unilateral. However, there was no difference in multifocality of tumors between the 2 groups. Similar to previous reports from their institution and ours, 3 cause-specific survival was excellent, particularly for incidental cancers. Cause-specific survival for stage I disease can be expected to be in excess of 90% and can be still favorable with bilateral renal cell cancer. We found that asynchronous bilateral disease was associated with survival similar t o that of patients with syn chronous bilateral disease. 4 In the study by Licht et al local recurrence differed for patients with suspected disease (6.6%) compared to those with incidental cancer (1.1%). This difference seems to be related to the difference in tumor characteristics, namely the incidental cancer was smaller, oflower stage and usually also oflower grade as shown in our experience. 3 • 5 Also, 17 of 216 patients in their study underwent surgical treatment with a normal contralateral kidney without evidence of local recurrence. These and other recent data provide evidence that under appropriate circumstances, considering patient age, medical status and renal function, small (4 cm. or less) renal tumors can be safely removed by a parenchyma sparing operation, even in the presence of a normal contralateral unit, yielding survival similar to that after radical nephrectomy. 5 Also, there seems to be no difference in outcome whether patients undergo partial nephrectomy or enucleation. 3 • 5 Local tumor recurrence (which in the discussed article is only 4%, similar to our data)5 is probably the result ofmultifocality rather than tr ue tumor-bed recurrence. A previous study (including tumors 8 cm. or smaller only) has shown that half of these multifocal tumors (incidence 7%) are visible on careful renal exploration, which is a sine qua non to minimize local recurrence.6 These findings agree with the clinical results of the Cleveland Clinic and Mayo Clinic studies, which show a local recurrence rate ofless than 5%. However, in the Cleveland Clinic study, the incidence of multifocality was 13%, similar to the original report by Mukamel et al, 7 which makes us reconsider this issue. Presently a prospective clinicopathological study is being completed that shows a multifocality incidence of 16% in renal tumors of all sizes, with only 2 grade 1 tumors showing multifocality.8 Finally, contrary to the commonly held opinion , renal cell cancer can occur at any size and, clearly although rarely, adenomas can exceed th e previously believed magical limit of 2.5 to 3 cm. Horst Zincke and Michael L. Blute Department of Urology Mayo Clinic and Mayo Foundation Rochester, Minnesota REFERENCES 1. Torres, V. E., King, B. F., Holley, K. E., Blute, M. L. and Gomez, M. R. : The kidney and the t uberous sclerosis complex. Adv. Nephrol. , 23: 43, 1994. 2. Washecka, R. and Hanna, M.: Malignant renal t umors in tuberous sclerosis. Urology, 37: 340, 1991. 3. Morgan , W. R. and Zincke, H.: Progression and survival after renal-conserving surgery for renal cell carcinoma: experience 43
44
RENAL TUMORS
in 104 patients and extended followup. J . Urol. , 144: 852, 1990. 4. Kerr, L. A. and Zincke, H.: Bilateral renal cell cancer treated surgically is associated with favorable disease outcome. Int. J . Oncol., 2: 1009, 1993. 5. Hawkins, C. A. , Wollan, P . C., Grabner, A. and Zincke, H.: Disease outcome in patients with low grade (:s2) low stage (:sT2) renal cell cancer is similar when treated by nephronpreserving or radical surgery. J . Urol., part 2, 151:, 000, abstract 000, 1994. 6. Cheng, W. S., Farrow, G. M. and Zincke, H .: The incidence of
multicentricity in renal cell carcinoma. J . Urol., 146: 1221, 1991. 7. Mukamel, E ., Konichezky, M., Engelstein, D. and Servadio, C.: Incidental small renal tumors accompanying clinically overt renal cell carcinoma. J. Urol. , 140: 22, 1988. 8. Kletscher, B. A., Qian, J., Bostwick, D. G., Andrews, P . E. and Zincke, H.: Prospective analysis of multifocal renal cell carcinoma (RCC): influence of histologic pattern, grade, stage, number, volume and DNA ploidy. J. Urol., part 2, 151: 314A, abstract 348, 1994.
THE JOURNAL OF UROLOGY
Copyright© 1994 by AMERICAN
UROLOGICAL AssoCIATION, INC.
EDITORIAL: RENAL TUMORS The preceding 3 papers on renal tumors address a wide variety of issues that might be of concern to the reader. Nakagawa et al (page 29) investigated the use of nephrocalcin (an acidic glycoprotein that inhibits calcium oxalate crystal growth) as a tumor marker. This compound can be found in a nonpredictable pattern in the urine of patients with renal cell cancer and postoperatively in its different bfochemical forms . The postoperative urinary nephrocalcin concentration remained at a similar level in 7 patients, was decreased in 8 and was still increased in 4 compared to that of a control group. There was no correlation between pathological variables and nephrocalcin levels before and after treatment. The author s did not provide information in regard to the half-life of nephrocalcin. Although there was a dramatic decrease in nephrocalcin levels in 6 of 19 patients who underwent surgery, it seems by no mea ns a marker for followup in patients who have undergone nephrectomy. The unpredictability of the test makes one wonder whether the polyclonal antibody to nephrocalcin was specific enough. For 5 years after the initial imaging study van Baal et al (page 35) used ultrasonography only to follow a group of 20 patients who had tuberous sclerosis with renal angiomyolipoma. There was no change in the size of the lesion in 14 patients (70%). Four patients (29%) experienced severe hemorrhage during the interval and 1 of them died of hemorrhage. A total of 4 patients (20%) had increased lesion size, and 7 (35%) had significant hemorrhage from the tumors necessitating treatment. Of these patients 5 had tumors larger than 3.5 cm. but hemorrhage developed in only 1 of 13 with a tumor smaller than 3.5 cm. In a similar ~eries from our institution 33 patients underwent multiple studies during intervals of 3 to 13 years.1 New angiomyolipomas appeared in 6 patients with negative initial studies. An increase in the number and/or size of angiomyolipomas was observed in 9 of 13 patients who already had lesions at initial evaluation. The rate of growth of the lesions ranged from 1 to 12 mm. per year (mean 5). These data show convincingly that patients with angiomyolipomas (with or without tuberous sclerosis) should be carefully followed for changes in the recognized lesion. The association of renal cell carcinoma with tuberous sclerosis complex should be considered in cases of enlarging lesions with no fatty tissue demonstrable by sonography, computerized tomography or magnetic resonance imaging, and when intratumoral calcifications, which occur rarely with uncomplicated angiomyolipomas, are present. Of 403 patients with the tuberous sclerosis complex seen at our center 4 had renal cancer and 2 died of m etastatic disease. Recently, Washecka and Hanna reviewed 16 cases in the literature and noted 3 death s from metastatic disease.2 In this review 81 % were female patients. Median age at diagnosis was 28 years, and 43% of the carcinomas were bilateral. This observation suggests that the natural history of renal cell carcinoma associated with the tuberous sclerosis complex is not as benign as once believed. For these reasons, when there is a change on imaging studies (preferably computerized tomography scanning) we recommend exploration with a renal conserving operation. This is true not only because of the potential danger of h emorrhage but also because of the occurrence of renal cell cancer and/or local parenchymal destruction. An operation, however, depends on the site and number of lesions, patient age and the lung disease in some patients who may have the concomitant findings of pulmonary lymphangioleiomyomatosis.
The article by Licht et al (page 39) provides information on patients with suspected versus incidental renal cell cancer who have undergone conservative surgical treatment for renal cell carcinoma. They found that incidental renal cell tumors were usually smaller (median 3.6 cm.), of lower stage (81 % of the patients had stage I disease) and unilateral. However, there was no difference in multifocality of tumors between the 2 groups. Similar to previous reports from their institution and ours, 3 cause-specific survival was excellent, particularly for incidental cancers. Cause-specific survival for stage I disease can be expected to be in excess of 90% and can be still favorable with bilateral renal cell cancer. We found that asynchronous bilateral disease was associated with survival similar t o that of patients with syn chronous bilateral disease. 4 In the study by Licht et al local recurrence differed for patients with suspected disease (6.6%) compared to those with incidental cancer (1.1%). This difference seems to be related to the difference in tumor characteristics, namely the incidental cancer was smaller, oflower stage and usually also oflower grade as shown in our experience. 3 • 5 Also, 17 of 216 patients in their study underwent surgical treatment with a normal contralateral kidney without evidence of local recurrence. These and other recent data provide evidence that under appropriate circumstances, considering patient age, medical status and renal function, small (4 cm. or less) renal tumors can be safely removed by a parenchyma sparing operation, even in the presence of a normal contralateral unit, yielding survival similar to that after radical nephrectomy. 5 Also, there seems to be no difference in outcome whether patients undergo partial nephrectomy or enucleation. 3 • 5 Local tumor recurrence (which in the discussed article is only 4%, similar to our data)5 is probably the result ofmultifocality rather than tr ue tumor-bed recurrence. A previous study (including tumors 8 cm. or smaller only) has shown that half of these multifocal tumors (incidence 7%) are visible on careful renal exploration, which is a sine qua non to minimize local recurrence.6 These findings agree with the clinical results of the Cleveland Clinic and Mayo Clinic studies, which show a local recurrence rate ofless than 5%. However, in the Cleveland Clinic study, the incidence of multifocality was 13%, similar to the original report by Mukamel et al, 7 which makes us reconsider this issue. Presently a prospective clinicopathological study is being completed that shows a multifocality incidence of 16% in renal tumors of all sizes, with only 2 grade 1 tumors showing multifocality.8 Finally, contrary to the commonly held opinion , renal cell cancer can occur at any size and, clearly although rarely, adenomas can exceed th e previously believed magical limit of 2.5 to 3 cm. Horst Zincke and Michael L. Blute Department of Urology Mayo Clinic and Mayo Foundation Rochester, Minnesota REFERENCES 1. Torres, V. E., King, B. F., Holley, K. E., Blute, M. L. and Gomez, M. R. : The kidney and the t uberous sclerosis complex. Adv. Nephrol. , 23: 43, 1994. 2. Washecka, R. and Hanna, M.: Malignant renal t umors in tuberous sclerosis. Urology, 37: 340, 1991. 3. Morgan , W. R. and Zincke, H.: Progression and survival after renal-conserving surgery for renal cell carcinoma: experience 43
44
RENAL TUMORS
in 104 patients and extended followup. J . Urol. , 144: 852, 1990. 4. Kerr, L. A. and Zincke, H.: Bilateral renal cell cancer treated surgically is associated with favorable disease outcome. Int. J . Oncol., 2: 1009, 1993. 5. Hawkins, C. A. , Wollan, P . C., Grabner, A. and Zincke, H.: Disease outcome in patients with low grade (:s2) low stage (:sT2) renal cell cancer is similar when treated by nephronpreserving or radical surgery. J . Urol., part 2, 151:, 000, abstract 000, 1994. 6. Cheng, W. S., Farrow, G. M. and Zincke, H .: The incidence of
multicentricity in renal cell carcinoma. J . Urol., 146: 1221, 1991. 7. Mukamel, E ., Konichezky, M., Engelstein, D. and Servadio, C.: Incidental small renal tumors accompanying clinically overt renal cell carcinoma. J. Urol. , 140: 22, 1988. 8. Kletscher, B. A., Qian, J., Bostwick, D. G., Andrews, P . E. and Zincke, H.: Prospective analysis of multifocal renal cell carcinoma (RCC): influence of histologic pattern, grade, stage, number, volume and DNA ploidy. J. Urol., part 2, 151: 314A, abstract 348, 1994.