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Upper urinary tract carcinoma after intake of aristolochia fangchi: Value of urinary cytology in end-stage "Chinese-herb nephropathy"

par Nortier, Joëlle ;Zlotta, Alexandre ;Petein, Michel ;Depierreux, Michel ;Muniz Martinez, Marie Carmen;Vanherweghem, Jean-Louis
Editeur scientifique Nuñez, Kelvin R.
Référence Trends in Kidney Cancer Research, Nova Science Publishers, Inc., New York, page (77-87)
Publication Publié, 2006

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Résumé :

Chinese-herb nephropathy (CHN) is a progressive interstitial fibrosis associated with the use of Aristolochia species, a Chinese herb regularly replacing Stephania tetrandra, Akebia, Asarum, Clematis and Cocculus species in herbal remedies and containing nephrotoxic and carcinogenic aristolochic acids (AA). Moderate to end-stage renal disease (ESRD) may develop, requiring renal replacement therapy by dialysis or transplantation. Experimental models reproducing the clinical entity are available in rabbits and rats. Aristolochic acids are powerful carcinogens in animal experiments. Removal of the native kidneys and ureters in CHN patients with ESRD has confirmed a high prevalence of upper urinary tract carcinoma (46 %). Tissue samples contained AA-related DNA adducts, which are not only specific markers of prior exposure to AA but are also involved in the tumorigenesis. We took the opportunity of planned nephroureterectomies in our 41 end-stage CHN patients treated by dialysis (N=10) or renal transplantation (N=31) to assess the diagnostic value of urinary cytologic tests prior to surgery. Fresh voided urine samples were available in 37 cases (4 hemodialysed patients were anuric). Cystoscopy with bilateral ureteral brushings and random bladder biopsies (if no bladder lesions were visible) were performed. Cytologic data were compared to histologic findings in the surgical specimens. All preoperative bladder biopsies were normal, except in 5 patients with mild-to-moderate dysplasia and one with superficial pTa bladder cancer. Neoplastic lesions were almost equally distributed between the renal pelvis and ureters. Of the 37 voided urine samples, 3 only showed atypia in relation with upper urinary tract carcinoma, whereas 18 patients had cancer diagnosed histologically. By contrast, bilateral ureteral brushings enabled to detect 14 out of 26 malignant lesions (in those 18 patients) by cytologic examinations. According to these results, specificity of cytologic analyses on voided urine and brushing samples were 100% and 96%, respectively and sensitivity 17% and 54%, respectively. In this specific population where the urinary output from native kidneys was impaired by terminal renal failure, the sensitivity of cytologic analysis of voided urine was much less helpful as compared to what could be expected in the general population. In summary, exposure to Aristolochia species is associated with the development of renal interstitial fibrosis (CHN) and urothelial cancer in humans. Cystoscopy with ureteral brushings should be considered as a first-line screening procedure in patients with renal failure at risk of developing upper urinary tract carcinoma. © 2006 Nova Science Publishers, Inc. All rights reserved.