Renal Cell Carcinomas in Patients on Long-Term Hemodialysis

Ishikawa, Isao

doi:10.1159/000059977

Cited by 11 publications

(11 citation statements)

References 47 publications

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“…It has been reported that ACDK develops in 90% of patients treated with dialysis for more than 10 years, and that 30% of those ACDK patients have atypical renal cysts 8 . Furthermore, adenoma, a likely precursor of RCC, has been reported to develop in 15% of ACDK patients 8 . Investigations in major dialysis hospitals demonstrate that RCC develops in 0.5–1.5% of dialysis patients 8,9 .…”

Section: Discussionmentioning

confidence: 99%

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Renal cell carcinoma in dialysis patients: A single center experience

Kojima

Takahara

Miyake³

et al. 2006

Int J of Urology

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Aim: Renal cell carcinoma (RCC) is a life-threatening complication of end-stage renal disease with an unclear pathogenesis. We evaluated RCC developing in patients undergoing dialysis. Methods: In 2624 patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis at our hospital between July 1993 and March 2004, we performed annual screening for RCC using abdominal computed tomography and ultrasonography. Patients diagnosed with RCC underwent radical nephrectomy as well as clinical and pathologic evaluation. Results: RCC was detected in 44 patients (1.68%; 31 males and 13 females). The age of RCC patients was 55.5 ± 11.1 years. Dialysis duration before RCC diagnosis was 11.2 ± 7.2 years. Most RCC were early stage and low stage by TNM classification, 43 patients had N0M0 RCC, whereas one had N1M0. Tumor size was 2.9 ± 1.9 cm. The predominant histological type of RCC was common or conventional cell-type carcinoma (clear cell carcinoma and granular cell carcinoma). Of patients, 5(11.4%) had bilateral RCC, and satellite tumor lesions in RCC were detected in 13 (29.5%). In 36 patients (81.8%) RCC was accompanied by acquired cystic disease of the kidney. These patients had longer dialysis durations (P = 0.01) and smaller tumors (P = 0.048). RCC metastasized postoperatively in 4 patients (9.1%), while one (2.3%) died of cancer. Conclusions: Our dialysis patients showed a higher incidence of RCC than the general population. Prognosis was favorable because tumors were detected by screening when they were small. Therefore, periodical screening for RCC seems very important in dialysis patients.Key words acquired cystic disease of the kidney, dialysis, end-stage renal disease, renal cell carcinoma.

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Section: Discussionmentioning

confidence: 99%

“…Renal biopsy gives a definite evidence of malignancy. However, we did not use biopsy, because the possibility of cystic fluid leakage leading to dissemination in patients with ACDK could not be ruled out, and also because retroperitoneal hemorrhage has been reported in ACDK patients 8 …”

Section: Discussionmentioning

confidence: 99%

Renal cell carcinoma in dialysis patients: A single center experience

Kojima

Takahara

Miyake³

et al. 2006

Int J of Urology

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“…Clinical and epidemiologic studies demonstrated that RCC in ESRD occurs at earlier ages and with 9 -18 times higher incidence than that in the general population (Matson and Cohen, 1990;Ishikawa, 1999). Most of the RCCs in ESRD/ ACDK are histopathologically clear-cell and papillary carcinomas, like the sporadic tumors in patients who have not had dialysis; however, the prevalence of papillary RCC increases with the duration of dialysis (Ishikawa and Kovacs, 1993;Ishikawa, 1999). The cytomorphologic features of both clear-cell and papillary RCCs in patients with ESRD/ACDK are similar to those in sporadic cases of clear-cell and papillary RCCs without ESRD/ ACDK (Ishikawa and Kovacs, 1993).…”

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confidence: 99%

“…Histopathologically, RCCs in dialysis kidneys are classified as clear-cell or papillary carcinomas (Ishikawa and Kovacs, 1993;Ishikawa, 1999). Clear-cell RCCs tend to occur in patients with a relatively short-term dialysis history.…”

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confidence: 99%

“…On the other hand, papillary RCCs occur in disproportionately high numbers of patients with a longer dialysis period (5 years or more) and are considered to be closely related to ACDK because papillary cystic hyperplasia and papillary adenoma are often observed concomitantly with papillary carcinoma in ESRD/ACDK kidneys (Hughson et al, 1980;Ishikawa and Kovacs, 1993;Ishikawa, 1999). Cytogenetic and microsatellite analyses demonstrated that clear-cell RCC in cases of ESRD frequently showed 3p allelic loss, like that found in sporadic clear-cell tumors in patients with no history of dialysis, and thus similar molecular genetic mechanisms, especially tumor-suppressor gene(s) on 3p, may be implicated in both sporadic and ESRD-associated clear-cell RCCs (Ishikawa et al, 1996;Chudek et al, 1998;Gronwald et al, 1999;Hughson et al, 1999;Ishikawa, 1999). The data we present here are the first evidence that the VHL tumor-suppressor gene at 3p25 is involved in clear-cell tumorigenesis occurring in cases of ESRD/ACDK.…”

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Somatic von Hippel–Lindau disease gene mutation in clear‐cell renal carcinomas associated with end‐stage renal disease/acquired cystic disease of the kidney

Yoshida

Yao

Ishikawa

et al. 2002

Genes Chromosomes & Cancer

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It has been documented that renal cell carcinomas (RCCs) occur frequently in patients treated with long-term dialysis, especially in cases of end-stage renal disease (ESRD)/acquired cystic disease of the kidney (ACDK). To address the molecular pathogenesis of ESRD/ACDK-associated RCCs, we examined 14 RCCs (7 clear-cell and 7 papillary carcinomas) in patients receiving dialysis for somatic mutations of the von Hippel-Lindau disease (VHL) gene as well as of the tyrosine kinase domain of the MET oncogene. Direct sequencing analyses revealed that three tumors exhibited VHL frameshifts (618delA, 386-395del10-bp, and 723-724insTC). One of the VHL mutated tumors showed additional loss of heterozygosity at the VHL gene locus. Histopathologic and clinical data demonstrated that the three tumors having VHL mutations were clear-cell RCCs occurring in ESRD with 55, 106, and 156 months of dialysis history, respectively. We did not find any tumors with mutations in the tyrosine kinase domain of the MET. These results demonstrated that the VHL tumor-suppressor gene is also involved in a subset of clear-cell RCCs occurring in ESRD/ACDK, as in the case of sporadic clear-cell RCCs. However, mutations of the MET oncogene could not be found in the seven ESRD/ACDK-associated papillary RCCs examined.

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Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising in patients on dialysis

Hori

Oda

Kiyoshima

et al. 2007

The Journal of Pathology

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Renal cell carcinoma (RCC) is more frequently observed in patients on dialysis than in patients with normal renal function. However, the mechanism underlying carcinogenesis in RCC patients on dialysis is still unclear. We hypothesized that oxidative stress affects patients on dialysis and generates new neoplasms, and therefore analysed the correlation between the influences of various markers of oxidative stress and carcinogenesis in those patients. We evaluated the immunohistochemical expression of oxidative stress markers, such as iNOS, 8-OHdG, and COX-2 in 42 cases on dialysis and 51 cases with normal renal function as a control. The methylation status of p16INK4a, p14ARF, VHL, and RASSF1A was analysed together with clinicopathological factors. Histologically, the papillary type was observed more frequently in dialysis RCC than in sporadic RCC. Immunohistochemically, overexpression of iNOS (p < 0.0001) and COX-2 (p = 0.0002) was more frequently observed in dialysis RCC. Furthermore, the 8-OHdG labelling index was significantly higher in dialysis RCC than in sporadic RCC. Hypermethylation of p16INK4a was more frequently found in dialysis RCC (p < 0.05). However, no significant correlations between oxidative stress markers and DNA hypermethylation status were observed. The overexpression of iNOS, COX-2, and 8-OHdG in dialysis RCC suggests that patients on dialysis are affected by oxidative stress and that this effect plays an important role in the genesis of dialysis RCC.

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Renal Cell Carcinomas in Patients on Long-Term Hemodialysis

Cited by 11 publications

References 47 publications

Renal cell carcinoma in dialysis patients: A single center experience

Renal cell carcinoma in dialysis patients: A single center experience

Somatic von Hippel–Lindau disease gene mutation in clear‐cell renal carcinomas associated with end‐stage renal disease/acquired cystic disease of the kidney

Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising in patients on dialysis

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