International Journal of Urology (2011) 18, 806812

doi: 10.1111/j.1442-2042.2011.02852.x

Original Article: Clinical Investigation

iju_2852

806..812

Prognosis and characteristics of renal cell carcinoma in hemodialysis patients: Bilateral occurrence does not inuence cancer-specic survival
Toshio Takagi, Tsunenori Kondo, Jyunpei Izuka, Hirohito Kobayashi, Eri Tomita, Yasunobu Hashimoto and Kazunari Tanabe
Department of Urology, Tokyo Womens Medical University, Tokyo, Japan

Objectives: To compare characteristics and prognosis unilateral and bilateral renal cell carcinoma (RCC) in hemodialysis (HD) patients. Methods: Overall 246 HD patients who had undergone a radical nephrectomy for RCC were enrolled in this study. Unilateral RCC occurred in 201 patients, synchronous bilateral RCC in 15 and metachronous bilateral RCC in 30. Cancerspecic survival (CSS) was accessed by the KaplanMeier method. Results: Five-year CSS was not signicantly different between the two groups (unilateral, 90%; bilateral, 90%; P = 0.9509). In total 17 of the 201 patients (8.5%) with unilateral occurrence and four of the 45 patients (8.9%) with bilateral occurrence died from kidney cancer during the follow-up period. The presence of acquired cystic disease of kidney (unilateral, 73%; bilateral 91%; P = 0.00319) and the mean duration of HD before surgery (unilateral: 157 91 months, bilateral: 189 83.5, P = 0.0319) were signicantly different between the two groups. There were more multifocal tumors in bilateral than in unilateral occurrence (bilateral: 74%, unilateral: 30%, P < 0.0001). There were signicant differences in CSS according to HD duration before surgery (5-year CSS >180 months 82%, 180 months 95%; P = 0.0004), tumor grade (G1 100%, G2 90%, G3 38%; P < 0.0001), and tumor size (>4 cm 75%, 4 cm 98%; P < 0.0001). Conclusions: The type of occurrence of RCC, unilateral or bilateral, in HD patients does not appear to inuence CSS. Patients with a longer duration of HD have to be followed up rigorously because they tend to have poor cancer prognosis. Key words: end-stage kidney disease, hemodialysis, nephrectomy, renal cell carcinoma, survival.

Introduction
Patients with end-stage renal disease (ESRD) requiring hemodialysis (HD) have a higher incidence of renal cell carcinoma (RCC) than the general population.1 Several factors are thought to contribute to this higher risk, including impaired antioxidant defense mechanisms, increased synthesis of reactive oxygen species and acquired renal cystic formation.2,3 On the other hand , those who get RCC disease associated with ESRD are characteristically young, predominantly male patients, and the tumors are frequently multicentric and bilateral, and are less aggressive than in sporadic RCC.4 Patients with bilateral sporadic RCC have a poor prognosis compared to those with unilateral RCC.5 Moreover, a bilateral metachronous occurrence of sporadic RCC has been associated with an unfavorable prognosis compared with a bilateral synchronous occurrence of the disease.6 Although previous reports have suggested that
Correspondence: Toshio Takagi M.D., Department of Urology, Tokyo Womens Medical University, 8-1, Kawada-cho, Shinjukuku, Tokyo 162-8666, Japan. Email: himmeno1192@yahoo.co.jp Received 24 June 2011; accepted 21 August 2011. Online publication 14 September 2011
806

tumor stage, performance status, presence of symptoms, tumor grade, and HD duration before surgery were the prognostic factors for cancer-specic survival (CSS) in HD patients with RCC,7,8 bilaterality has not been discussed. In the present study, we compared the characteristics of unilateral and bilateral occurrences of RCC in HD patients after a radical nephrectomy. We also analyzed CSS according to several variables.

Methods
Patients
Between April 1992 and December 2009, 306 RCC patients with ESRD requiring HD were treated in our hospital. Subsequently, 291 radical nephrectomies were performed on 201 patients with unilateral RCC and on 45 patients with bilateral RCC. Of the 45 patients with bilateral RCC, 15 had a synchronous occurrence and 30 patients had a metachronous occurrence of the disease. A synchronous occurrence was dened as the presence of bilateral tumors at the time of initial surgery or when a contralateral tumor occurred within 6 months after initial surgery.9,10 In the metachronous case, the contralateral tumor had occurred at least 6 months after
2011 The Japanese Urological Association

Radical nephrectomy for RCC with ESRD

Table 1 Comparison of patients characteristics and clinical data between unilateral and bilateral occurrence of renal cell carcinoma Unilateral Patients N (%) 201 (82) Bilateral 45 (18) Synchronous (15) Metachronous (30) 52.2 (8.49) 52 (2368) 39 (87) 6 (13) 189 (83.5) 187 (10384) 2 (4%) 43 (96%) 76.7 (56.7) 77 (1170) 41 (91) 4 (9) Total 246 P

Age (years) Mean SD Median (range) Gender N (%) Male Female HD duration before surgery (month) Mean SD Median (range) Cause of ESRD (DM or not) DM Others Mean follow-up periods (months) Mean SD Median (range) ACDK N (%) Yes No

0.0752 55.4 (11.7) 56 (1780) 163 (81) 38 (19) 157 (91.3) 148 (7375) 12 (6%) 189 (94%) 62.7 (56.5) 49 (1279) 147 (73) 54 (27) 54.73 (10.9) 56 (1780) 0.5187 222 (82) 44 (18) 0.0319 170 (91.9) 165 (7.10385) 1.0000 14 (6%) 232 (94%) 0.1321 63.0 (55.9) 48.7 (1205) 0.0107 188 (76) 58 (24)

ACDK, acquired cystic disease of the kidney; DM, diabetes mellitus: HD, hemodialysis.

initial surgery. Patients who had undergone kidney transplantation were excluded. Survival was calculated from the date of initial surgery. The criteria used for the diagnosis of an acquired cystic disease of the kidney (ACDK) were in accordance with previous reports.11,12 The tumors were classied according to the 1997 Union for International Cancer Control/American Joint Committee on Cancer consensus and the World Health Organization (2004) classication systems. Tumor size was dened as the diameter of the largest tumor if there were multiple cancerous lesions in the same kidney. With regard to the evaluation of the tumor stage, the 1997 TNM classication was used. The patients were evaluated for postoperative recurrence using computed tomography every 6 months for the rst 2 years. Subsequently, a follow-up examination was performed every 612 months. Patients with a higher tumor stage or higher grades were checked according to their condition. The study outcome is the 5-year CSS rate according to several variables. Clinical and laboratory information was extracted from electronic databases and patient medical records. The study was performed according to the principles of the Helsinki Declaration.

parameters were compared using the unpaired two-sample t-test, and qualitative parameters were compared using Fishers exact test. P-values of less than 0.05 were considered to indicate statistical signicance. The 5-year CSS rates were calculated using the KaplanMeier method , and statistical signicance was determined by the logrank test. Patients characterstics and clinicopathological parameters were evaluated using a Cox proportional hazards model to determine the variables that were independently correlated with CSS.

Results
Patients characteristics
The patients characteristics are shown in Table 1. Unilateral RCC occurred in 201 patients (82%) and bilateral RCC in 45 (18%), including synchronous in 15 (6%) and metachronous occurrences in 30 (12%). The mean length of time between initial surgery and contralateral kidney surgery in patients with metachronous occurrence was 37.8 months. There was no signicant difference in gender and cause of ESRD (diabetes mellitus [DM] or not) between the two groups. The mean duration of HD before surgery was signicantly longer in patients with bilateral RCC than in those with unilateral RCC (unilateral: 157 91, bilateral: 189 83.5,
807

Statistical analysis
All statistical analyses were performed using JMP 8.0.1 software (SAS Institute, Cary, NC, USA). Quantitative
2011 The Japanese Urological Association

T TAKAGI ET AL.

Table 2 Comparison of pathological characteristics between unilateral and bilateral occurrence of renal cell carcinoma Unilateral N (%) 201 patients; 201 renal units Histological ndings Clear cell Papillary Chromophobe Mucinous tubular and spindle Undifferentiated Tumor stage pT1a pT1b pT2 pT3a pT3b Pathological stage Stage 1 Stage 2 Stage 3 Stage 4 Tumor grade G1 G2 G3 Tumor Unifocal Multifocal Tumor size (mm) Mean SD Median (range) 168 29 3 1 0 129 38 14 14 6 159 13 16 13 (84) (14) (1.5) (0.5) Bilateral N (%) 45 patients; 90 renal units 0.2412 68 20 1 0 1 49 26 6 7 2 73 4 3 10 (76) (22) (1) (1) (54) (29) (7) (8) (2) (81) (4.5) (3.5) (11) 236 49 4 1 1 178 64 20 21 8 232 17 19 23 (81) (17) (1.4) (0.3) (0.3) 0.4092 (64) (20) (7) (7) (3) (79) (6.5) (8.0) (6.5) (61) (22) (7) (7) (3) 0.2406 (80) (6) (7) (8) 0.4802 65 (32) 118 (59) 18 (9) 140 (70) 61 (30) 37.3 21.8 32 (7140) 23 (26) 57 (63) 10 (11) 23 (26) 67 (74) 42.0 27.9 37.5 (10190) 88 (30) 175 (60) 28 (10) <0.0001 163 (56) 128 (44) 0.1068 39.4 24.8 34 (7190) Total N (%) P

P = 0.0319). Bilateral RCC was more likely to be accompanied by ACDK than unilateral RCC (unilateral: 73%, bilateral: 91%, P = 0.0107). Mean age (unilateral: 55.4 11.7; bilateral: 52.2 8.49; P = 0.0752), gender (unilateral: male 81%, female 19%; bilateral: male 87%, female 13%; P = 0.5187) and mean follow-up periods (unilateral: 62.7 56.5 months; bilateral: 76.6 56.7; P = 0.1321) were not signicantly different between the two groups.

occurrence tended to have more multifocal tumors than the unilateral occurrence (bilateral: 74%, unilateral: 30%, P < 0.0001). Table 3 shows the histology of both sides in patients with bilateral occurrence. In total 32 of 45 patients (71%) had same pathological ndings in both kidneys.

CSS
As shown in Figure 1, the 5-year CSS rate was 90% in both groups, which was not signicantly different between the two groups (P = 0.9509). Overall 17 patients out of 201 (8.5%) with a unilateral occurrence and four patients out of 45 (8.9%) with a bilateral occurrence died from kidney cancer in the follow-up period.

Pathological ndings
Table 2 shows the histological ndings and tumor stage classication. Although the clear cell type was more dominant than other histological types in any of the groups, there was no signicant difference between the two groups (P = 0.2412). There was also no signicant difference in the pathological stage (P = 0.2406), tumor stage (P = 0.4092), tumor grade (P = 0.4802) and tumor size (P = 0.1068) between the two groups. Bilateral
808

Prognostic factors for death from cancer

Table 4 shows the prognostic factors for death from cancer on univariate and multivariate analysis. A longer duration of
2011 The Japanese Urological Association

Radical nephrectomy for RCC with ESRD

Table 3 Clinicopathological characteristics of 45 patients with bilateral renal cell carcinoma The other side Clear cell One side Clear cell Papillary Chromophobe Undifferentiated Total 27 7 Papillary 4 5 Chromophobe 1 1 33 12 Undifferentiated Total

34

45

1.0 Cancer-specific survival 0.8 0.6 0.4 0.2 0.0 0 12 24 36 48 60 72 84 Time after surgery (month) Number at risk Unilateral 201 144 45 35 Bilateral 102 28 70 25 44 22 27 14 21 8 14 3

Fig. 1 Cancer-specic survival between ( ) unilateral and ( ) bilateral occurrence. Logrank: P = 0.9509.

HD before surgery (P = 0.0091), a larger tumor size (P = 0.00112) and a higher tumor grade (0.0062) were positively associated with death from cancer. Age, gender, the presence of ACDK, multifocality and bilateral occurrence did not inuence the likelihood of death from cancer. Figures 24 show the comparison of CSS according to the duration of HD before surgery (5-year CSS > 180 months 82%, HD duration 180 months 95%; P = 0.0004), tumor grade (G1 100%, G2 90%, G3 38%; P < 0.0001) and tumor size (>4 cm 75%, 4 cm 98%; P < 0.0001), respectively.

Discussion
In the present study, we show that the bilateral occurrence of RCC in HD patients does not inuence CSS. A longer duration of HD before surgery, a larger tumor size and a higher tumor grade were unfavorable prognostic factors for death from RCC. In sporadic RCC, Haferkamp et al. reported that the bilateral occurrence of RCC and Fuhrmans grade 3 were independent prognostic factors in patients undergoing nephron-sparing surgery for imperative indications.5 On
2011 The Japanese Urological Association

the other hand , some reports show that the prognosis of synchronous bilateral RCC is comparable to that of unilateral RCC.13,14 Our group previously reported that a metachronous occurrence of RCC in the contralateral kidney is associated with an unfavorable prognosis compared to synchronous occurrence, suggesting that metachronous contralateral tumors might be metastases of the original tumors.6 This result has not been previously reported in RCC with ESRD patients. In our study there was no signicant difference between synchronous and metachronous occurrence over 5 years (bilateral synchronous RCC 88%, bilateral metachronous RCC 100%, P = 0.6567, data not shown) similar to the comparison between unilateral and bilateral occurrence. We have shown that bilateral occurrence favored CSS and signicant prognostic factors for death from cancer were the duration of preoperative HD, tumor size and tumor grade. Except for the duration of HD, prognostic factors for cancer death were similar to those for sporadic RCC, which was thought to depend on the cause of RCC with HD patients. Denton et al. reported that patients with RCC had a higher mean age and a trend towards a longer duration of dialysis than those without.15 Moreover, most RCC patients (91%) had underlying ACDK and 73% had coexisting papillary adenomas.15 In our study, patients with bilateral RCC had a longer duration of HD and a higher incidence of ACDK than those with unilateral RCC. Several factors have been reported to be the cause of RCC occurrence in HD patients with ACDK. An increased expression of growth factors or uremic metabolites has been demonstrated in end-stage kidney disease. The stimulation of tubular and cystic cells by these renotropic substances seems to promote the development of ACDK with progressively orid degrees of papillary hyperplasia and papillary neoplasms either developing simultaneously or subsequently.16 A sequence of the phenomena mentioned above has persisted in HD patients so that it is natural to consider that a longer duration of HD has contributed to a higher incidence of RCC. Of course, it is possible for RCC without ACDK to have occurred before dialysis therapy.
809

T TAKAGI ET AL.

Table 4 Univariate and multivariate Cox regression analysis for death from cancer Univariate P-value Duration of HD Maximum tumor size Tumor grade Age Multifocal/monofocal ACDK (Yes/no) Bilateral/unilateral Gender (male/female) Original disease (DM/others) <0.0001 <0.0001 <0.0001 0.0129 0.6694 0.2277 0.9508 0.4588 0.8867 HR (95% CI) 1.01 (1.001.02) 1.03 (1.021.04) 9.17 (4.2120.8) 1.06 (1.011.10) 1.21 (0.502.87) 2.00 (0.688.55) 0.97 (0.282.63) 0.67 (0.262.07) 1.16 (0.065.67) Multivariate P-value 0.0091 0.0112 0.0062 0.1206 HR (95% CI) 1.01 (1.001.01) 1.02 (1.001.03) 3.23 (1.387.07) 1.05 (0.991.11)

ACKD, acquired cystic disease of the kidney; DM, diabetes mellitus; HR, hazards risk.

1.0 Cancer-specific survival 0.8 0.6 0.4 0.2 0.0 0 12 24 36 48 60 72 84 Time after surgery (month)
Number at risk HD duration >180 104 HD duration 180 142

1.0 Cancer-specific survival 0.8 0.6 0.4 0.2 0.0 0

Number at risk G1 78 G2 146 G3 22

12

24

36

48

60

72

84

Time after surgery (month)

80 122 66 112 64 97 61 83 47 66 37 57 29 50

Fig. 2 Cancer-specic survival in a subset of patients who were classied by duration of HD ( ) >180 months and ( ) 180 months). Logrank: P = 0.0004

71 117 13

66 101 11

61 89 9

58 67 6

55 51 3

49 43 3

42 38 3

Fig. 3 Cancer-specic survival according to tumor grade ( ) GI; ( ) G2 and ( ) G3. Logrank: P = 0.0001.

We also examined the prognosis between unilateral and bilateral occurrence accompanied with ACDK. There were 147 and 41 patients with unilateral and bilateral occurrence, respectively. CSS was not signicantly different between two groups at 5 years follow-up (unilateral 89%, bilateral 90%; P = 0.7686, table not shown). In our study, 13% (30/ 231) of patients with unilateral RCC developed contralateral RCC with a mean duration between the initial operation and the second operation of 37.1 months. Our report suggests that most bilateral RCC in HD patients, whether metachronous or synchronous, is a result of multiple de novo primary events rather than primary RCC with contralateral renal metastasis. Moreover, HD patients have more frequent regular checkups than the general population in Japan. These factors contributed to the fact that bilaterality favored a good prognosis in HD patients with RCC. Previous reports suggested that bilateral RCC occurred in 536% of HD patients and multifocal tumors occurred in
810

6080% of HD patients.15,1719 In our present study, 18% of patients had bilateral RCC, whether synchronous (6%) or metachronous (12%), and 44% of those had multifocal RCC. There is a question whether both kidneys should be removed in patients with ESRD and with a tumor on one side only that has been diagnosed by computed tomography, especially during a scheduled kidney transplantation. Kojima et al. evaluated the development of RCC in 2624 patients undergoing dialysis, including tumors with the pathological extent of pT1 in 46 kidneys (93.9%), pT2 in one (2.0%) and pT3 in two (4.1%). In the present study, we found pT1 in 83.5%, pT2 in 6.5% and pT3 in 10% of the participants. These statistics suggest that RCC in dialysis patients is of a lower pathological extent than sporadic RCC. This might be attributed to routine screening. Multifocality seems to be one risk factor for the development of bilateral RCC in sporadic settings. Haferkamp et al.
2011 The Japanese Urological Association

Radical nephrectomy for RCC with ESRD

1.0 Cancer-specific survival 0.8 0.6 0.4 0.2 0.0 0 12 24 36 48 60 72 84 Time after surgery (month) Number at risk Tumor size40 Tumor size>40 158 88 137 65 125 53 112 46 89 41 74 34 61 33 51 31

Fig. 4 Cancer-specic survival according to tumor size ( >4 cm and ( ) 4 cm). Logrank: P = 0.0001.

reported that in their study 26% of patients with bilateral RCC had multifocality, compared to only 6% of patients with unilateral tumors.5 Klatte et al. and Bani-Hani et al. described multifocality as an independent risk factor for contralateral RCC in their studies of metachronous RCC.20,21 In our study, 74% of bilateral tumors had multifocality. Moreover, 55% of patients with bilateral kidney tumors had multifocal tumors in both kidneys. On the basis of our results, there is no need to remove the contralateral kidney with respect to cancer control, but regular checkups will be needed to detect RCC at an early stage, especially in patients with a longer duration of HD or multifocal tumors. Most (4271%) renal cell neoplasms occurring in patients with ESRD, particularly with ACDK, have been reported to be papillary renal cell carcinomas (PRCC).15,22,23 However, in our setting, only 17% of patients showed PRCC. There were thought to be two reasons for this result. One is the racial feature. Although PRCC constitutes up to 18% of renal epithelial tumors in the general population in Western countries,24 only 6% of the patients who had undergone partial nephrectomy for T1a RCC displayed PRCC in a pathological examination in our hospital. The incidence of PRCC in Asian counties is thought to be lower than that in Western countries. The other is classication of epithelial neoplasm in ESRD. Tickoo et al. suggested RCC with ESRD should be classied into two main groups. One consisted of tumors similar to those seen in sporadic settings, including 18% in clear cell, 15% in PRCC and 8% in chromophobic RCC. The other group consisted of two subtypes of RCC that appear to be unique to ESRD, including 36% in ACDK-associated RCC and 23% in clear cell PRCC of the end-stage kidneys.25 Prognostic factors for death from RCC in HD patients have been discussed in previous reports.7,8 Sassa et al. reported that 10-year CSS before surgery <10 years,
2011 The Japanese Urological Association

1020 years and >20 years were 100, 84.2 and 37.3% (P < 0.05), respectively.8 Moreover, the tumor grade and pathological stage developed as the duration of HD increased. In our study, although there was no difference if the cut-off period was dened as 10 years, a signicant difference was shown if the cut-off period was dened as 15 years (P < 0.0001). Moreover, tumor grade (P = 0.001) and pathological stage (P = 0.0125) were signicantly different between two groups (when the HD duration was >15 years and 15 years, table not shown), as Sassa et al. have reported. Overall, patients who received long-term HD tended to have a higher risk for developing high-grade RCC. In our study the tumor grade and size also impacted on poor prognosis. Neuzillet et al. and Sassa et al. reported similar results. Although the oncogenesis mechanism in ESRD RCC tumors was thought to be different from that in sporadic RCC, high grade tumors and tumor stage cancer inuence cancer prognosis. The present study has some limitations including the retrospective nature of the study and the small sample size. Further studies are needed to determine what variables contribute to CSS in HD patients.

Acknowledgment
The authors thank Ms Clare Dover and Barbara Levene for the English correction of this manuscript. We also thank Ms Yukiko Hirane for secretarial work.

Conict of interest
None declared.

References
1 Ishikawa I. Re: acquired cystic disease of the kidney: a management dilemma. J. Urol. 1993; 149: 11468. 2 Hori Y, Oda Y, Kiyoshima K et al. Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising in patients on dialysis. J. Pathol. 2007; 212: 21826. 3 Yoshimura S, Suemizu H, Nomoto Y et al. Plasma glutathione peroxidase deciency caused by renal dysfunction. Nephron 1996; 73: 20711. 4 Maisonneuve P, Agodoa L, Gellert R et al. Cancer in patients on dialysis for end-stage renal disease: an international collaborative study. Lancet 1999; 354: 939. 5 Haferkamp A, Kurosch M, Pritsch M et al. Prognostic factors inuencing long-term survival of patients undergoing nephron-sparing surgery for nonmetastatic renal-cell carcinoma (RCC) with imperative indications. Ann. Surg. Oncol. 2009; 17: 54451. 6 Amano H, Kondo T, Hashimoto Y et al. Contralateral metachronous tumor occurrence is more frequently
811

T TAKAGI ET AL.

10

11 12

13

14

15

16

associated with distant metastases or postoperative intrarenal recurrence in renal cell carcinoma patients. Int. J. Urol. 2010; 17: 61522. Neuzillet Y, Tillou X, Mathieu R et al. Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared with RCC in the general population. Eur. Urol. 2011; 60: 36673. Sassa N, Hattori R, Tsuzuki T et al. Renal cell carcinomas in haemodialysis patients: does haemodialysis duration inuence pathological cell types and prognosis? Nephrol. Dial. Transplant. 2011; 26: 167782. Siemer S, Uder M, Zell A et al. [Bilateral kidney tumor. Therapy management and histopathological results with long-term follow-up of 66 patients]. Urologe A 2001; 40: 11420. (In German.) Zincke H, Swanson SK. Bilateral renal cell carcinoma: inuence of synchronous and asynchronous occurrence on patient survival. J. Urol. 1982; 128: 91315. Ishikawa I. Uremic acquired renal cystic disease. Natural history and complications. Nephron 1991; 58: 25767. Grantham JJ, Levine E. Acquired cystic disease: replacing one kidney disease with another. Kidney Int. 1985; 28: 99105. Boorjian SA, Crispen PL, Lohse CM, Leibovich BC, Blute ML. The impact of temporal presentation on clinical and pathological outcomes for patients with sporadic bilateral renal masses. Eur. Urol. 2008; 54: 85563. Klatte T, Wunderlich H, Patard JJ et al. Clinicopathological features and prognosis of synchronous bilateral renal cell carcinoma: an international multicentre experience. BJU Int. 2007; 100: 215. Denton MD, Magee CC, Ovuworie C et al. Prevalence of renal cell carcinoma in patients with ESRD pre-transplantation: a pathologic analysis. Kidney Int. 2002; 61: 22019. Hughson MD, Bigler S, Dickman K, Kovacs G. Renal cell carcinoma of end-stage renal disease: an analysis of

17

18

19

20

21

22

23

24

25

chromosome 3, 7, and 17 abnormalities by microsatellite amplication. Mod. Pathol. 1999; 12: 3019. Kojima Y, Takahara S, Miyake O, Nonomura N, Morimoto A, Mori H. Renal cell carcinoma in dialysis patients: a single center experience. Int. J. Urol. 2006; 13: 10458. Boileau M, Foley R, Flechner S, Weinman E. Renal adenocarcinoma and end stage kidney disease. J. Urol. 1987; 138: 6036. Satoh S, Tsuchiya N, Habuchi T, Ishiyama T, Seimo K, Kato T. Renal cell and transitional cell carcinoma in a Japanese population undergoing maintenance dialysis. J. Urol. 2005; 174: 174953. Blute ML, Itano NB, Cheville JC, Weaver AL, Lohse CM, Zincke H. The effect of bilaterality, pathological features and surgical outcome in nonhereditary renal cell carcinoma. J. Urol. 2003; 169: 127681. Bani-Hani AH, Leibovich BC, Lohse CM, Cheville JC, Zincke H, Blute ML. Associations with contralateral recurrence following nephrectomy for renal cell carcinoma using a cohort of 2,352 patients. J. Urol. 2005; 173: 3914. Hughson MD, Schmidt L, Zbar B et al. Renal cell carcinoma of end-stage renal disease: a histopathologic and molecular genetic study. J. Am. Soc. Nephrol. 1996; 7: 24618. Ishikawa I, Kovacs G. High incidence of papillary renal cell tumours in patients on chronic haemodialysis. Histopathology 1993; 22: 1359. Amin MB, Amin MB, Tamboli P et al. Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: an experience of 405 cases. Am. J. Surg. Pathol. 2002; 26: 28191. Tickoo SK, dePeralta-Venturina MN, Harik LR et al. Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia. Am. J. Surg. Pathol. 2006; 30: 14153.

812

2011 The Japanese Urological Association

Copyright of International Journal of Urology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.