Clinicopathologic characteristics and prognosis of upper tract urothelial carcinoma complicated with aristolochic acid nephropathy after radical nephroureterectomy

Abstract

Background The purpose of this study was to identify the clinicopathologic characteristics and prognosis of upper tract urothelial carcinoma (UTUC) patients complicated with aristolochic acid nephropathy(AAN) after radical nephroureterectomy (RNU). Methods The clinical data of 42 UTUC patients with AAN (AAN group) and 238 UTUC patients without AAN (Non-AAN group) were retrospectively reviewed. All patients received a RNU with excision of bladder cuff. Demographic and clinical data, including preoperative indexes, intraoperative indexes and surgical outcomes were compared. Results There were no significant differences in age, tumor location, surgery approach, tumor pathologic grade, stage, the mean operative time and estimated blood loss between the two groups (all p > 0.05). There were more female patients in the AAN group (p < 0.001), and 57.1% were high grade tumors. The AAN group showed a higher complications rate (p = 0.003). The median follow-up time was 43.2 months. The AAN group showed a worse estimated 5-year overall survival rate (35.1% vs. 63.0%, p = 0.014), however, no significant difference was found between the two groups with regard to disease specific survival (63.5% vs. 81.5%, p = 0.091). Multivariate binary logistic regression analysis showed that AAN was an independent factor related with overall and disease specific survival. 38.9% of all patients experienced any types of recurrence, and the estimated 5-year recurrence-free survival rate was lower in the AAN group (37.1% vs. 63.7%, p = 0.001). In the comparison of subgroups stratified by recurrence type, the AAN group had a higher intravesical (p = 0.030) and contralateral recurrence rate (p = 0.040). Conclusion UTUC with AAN occurred more frequently in female patients who were more likely to develop high-grade tumors. However, these patients showed a worse overall survival and a lower recurrence-free survival rate than the other patients. AA-related UTUC might be associate with an increased risk of intravesical and contralateral recurrence after RUN.

Aristolochic acid-associated urinary tract cancers: an updated meta-analysis of risk and oncologic outcomes after surgery and systematic review of molecular alterations observed in human studies

“…73 Our subgroup analysis showed that AA exposure was associated with 1.949-fold increased risk of intravesical recurrence of UTUC, and 1.477-fold increased risk in patients diagnosed with AAN. It is worth noting that among the three studies reporting contralateral UTUC recurrence, 49,53,56 the recurrence rates of 0-5% in the control groups were similar to that of 2-6% in the general population. However, the rates in the AA groups were very high (13.75-25%), 49,53,56 which contributed to an overall 3.760-fold increased risk.…”

“…One study investigating AA-RCC 23 was excluded because the aim of the study was to find the etiology of RCC in BEN regions. Seventeen studies reporting the risk 35,37,[40][41][42][43][44][45][46][47] or oncologic outcomes 44,48,50,51,[53][54][55][56] of AA-UTC, six studies reporting the molecular alterations in AA-UTUC 57,[63][64][65] or AA-RCC, 22,60 and one study reporting both the risk and molecular alterations in AA-UTUC 68 were newly retrieved in the present systematic review.…”

“…47 In RTRs, post-transplant malignancies were reported. Ten [48][49][50][51][52][53][54][55][56]68 studies reported oncological outcomes of primary AA-UC after surgery; nine [48][49][50][51][52][53][54]56,68 of them reported recurrence, and five 50,[54][55][56]68 of them reported survival outcomes. One study reported both the risk of primary and postoperatively recurrent AA-UC.…”

“…[49][50][51][52][53][54]56,68 The standard surgical treatment, radical nephroureterectomy (RNU) with bladder cuff excision, was performed in seven 49,[51][52][53][54]56,68 of the eight studies. [49][50][51][52][53][54]56,68 Although 86.2% of patients received RNU and 13.8% of selected patients including those with BEN received conservative surgery in the other one study, 50 the different modes of operations, however, did not result in significantly different risk of bladder recurrence in the multivariate analysis. 50 The pooled RR of bladder recurrence was 1.949 (95% CI 1.462-2.597, I 2 = 0.000%) for four studies where RR adjusted for common clinicopathological risk factors were provided, [50][51][52]54 and 1.477 (95%CI 1.015-2.147, I 2 = 0.000%) for four studies where patients diagnosed with AAN were included.…”

Role of Base Excision Repair Pathway in the Processing of Complex DNA Damage Generated by Oxidative Stress and Anticancer Drugs

“…Consumption of AAs can lead to a rapid renal toxicity and, at certain levels, to liver (Ng et al, 2017;Lu et al, 2020) and kidney cancer (Vanherweghem et al, 1993;Debelle et al, 2008). Consumption of AAs-containing herbal remedies in South Asia remains a cause of serious concern for public health to date (Lu et al, 2020;Shan et al, 2020). Certain cases in Europe also have been registered in 1992; when several female patients in Belgium, after taking two Chinese herbs (Stephania tetrandra and Magnolia officinalis), as slimming treatment, suffered from rapidly progressive interstitial nephritis (Vanherweghem et al, 1993).…”