Urothelial Cancer in Patients with Endemic Balkan Nephropathy (EN) after Renal Transplantation

Živčić-Ćosić, Stela; Gržetić, Mirjana; Valenčić, Maksim; Oguić, Romano; Maričić, Anton; Đorđević, Gordana; Balen, Sanja; Orlić, Lidija; Rački, Sanjin; Fučkar, Željko

doi:10.1080/08860220701595882

Cited by 10 publications

(11 citation statements)

References 15 publications

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“…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.…”

Section: Comparison Of the Included Studies Between The Present And Previous Systematic Reviewsmentioning

confidence: 99%

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

Kang

Chen

Lin

et al. 2021

Therapeutic Advances in Drug Safety

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Background: The risk of primary aristolochic acid (AA)-associated urothelial carcinoma (AA-UC) has been summarized by a 2013-published meta-analysis. Given that additional evidence has been continuously reported by original studies, an updated meta-analysis is needed. Meanwhile, to complete the whole picture, a systematic review of molecular alterations observed in AA-urinary tract cancers (AA-UTC) was also performed. Methods: We searched PubMed, Embase and four Chinese databases up to October 2020. Observational studies comparing risk or oncologic outcomes of UTC between patients with and without AA exposure were eligible for systematic review and meta-analysis. Studies investigating molecular alterations in AA-UTC using human tissue samples were eligible for systematic review. Results: In total, 38 and 20 studies were included in the systematic review and meta-analysis, respectively. Exposure to AA led to an overall increased risks of primary UTC [UC and renal cell carcinoma (RCC)] (OR 6.085, 95% CI 3.045–12.160) and postoperatively recurrent UC (RR 1.831, 95% CI 1.528–2.194). Subgroup analysis of postoperative primary AA-upper tract UC (AA-UTUC) showed increased risks of bladder recurrence (adjusted RR 1.949, 95% CI 1.462–2.597) and contralateral UTUC recurrence (crude RR 3.760, 95% CI 2.225–6.353), worse overall survival (adjusted HR 2.025, 95% CI 1.432–2.865) and worse disease-specific survival (adjusted HR 3.061, 95% CI 1.190–7.872), but no effect on cancer-specific survival (adjusted HR 0.772, 95% CI 0.269–2.215). High mutation load with AA mutational signature presenting largely in the putative driver genes was observed in AA-UTUC. In contrast, AA mutational signature is rarely found in the mutated RCC driver genes and the mutation load in AA-RCC is low. Therefore, AA has different roles in the genesis of UTUC and RCC. Conclusions: Implementing effective strategies to completely protect people from exposure to AA is urgently needed. Additionally, more effort should be made in identifying the precise carcinogenic mechanisms of AA to determine the future treatment strategies. Plain language summary Risk, recurrence and survival outcomes after surgery and molecular changes possibly involved in the genesis of aristolochic acid-associated urinary tract cancers Background: The association between aristolochic acid (AA) and primary urothelial carcinoma (UC) has been summarized by a 2013-published meta-analysis. Given that additional evidence has been reported in the past 7 years, an updated meta-analysis is needed. Meanwhile, to complete the whole picture, a systematic review of molecular changes possibly involved in AA-mediated urinary tract carcinogenesis was also performed. Methods: We searched PubMed, Embase and four Chinese databases for human studies up to October 2020. Studies comparing the risk of urinary tract cancer (UTC) between patients with and without AA exposure and studies investigating the molecular changes in AA-associated UTC (AA-UTC) using human tissue samples were eligible for inclusion. Thirty-eight studies were finally included. Results: The results showed that exposure to AA was associated with a 6-fold increased risk of primary UTC (UC and renal cell carcinoma, RCC) and a 1.8-fold increased risk of postoperatively recurrent UC. After studies reporting primary AA-upper tract UC (AA-UTUC) were analyzed, a 1.9-fold increased risk of bladder recurrence and a 3.8-fold increased risk of contralateral UTUC recurrence was observed. Additionally, exposure to AA worsened the postoperative survival of patients with UTUC by a 2-fold increased risk of overall death and a 3-fold increased risk of death from other diseases and recurrences. However, there was no effect on death due to cancer. Lastly, AA seemed to play different roles in the etiology of UTUC and RCC based on the observations of different mutation loads and different distributions of AA-induced mutations in AA-UTUC and AA-RCC samples. Conclusions: Implementing effective strategies to completely protect people from exposure to AA is urgently needed. Moreover, more effort should be made in identifying the precise carcinogenic mechanisms of AA-UTC to determine the future treatment strategies.

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Section: Comparison Of the Included Studies Between The Present And Previous Systematic Reviewsmentioning

confidence: 99%

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

Kang

Chen

Lin

et al. 2021

Therapeutic Advances in Drug Safety

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“…S obzirom na to da se učestalost karcinoma mokraćnoga mjehura ne razlikuje od opće populacije, cistektomija nije potrebna osim ako se ne radi o invazivnom karcinomu, međutim, ako se u tkivu mokraćnog mjehura pronađu DNA adukti aristolohične kiseline, preporučuje se cistektomija 7 . Smatra se kako oboljeli od EN-a u kojih je učinjena transplantacija bubrega predstavljaju posebno ranjivu skupinu za razvoj UTUC-a, najvjerojatnije kao posljedicu promijenjenog imunološkog odgovora zbog uzimanja imunosupresivne terapije [14][15][16][17] . Pacijenti s EN-om u kojih je učinjena transplantacija bubrega imaju značajno veću učestalost UTUC-a 7,16,17 .…”

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“…Smatra se kako oboljeli od EN-a u kojih je učinjena transplantacija bubrega predstavljaju posebno ranjivu skupinu za razvoj UTUC-a, najvjerojatnije kao posljedicu promijenjenog imunološkog odgovora zbog uzimanja imunosupresivne terapije [14][15][16][17] . Pacijenti s EN-om u kojih je učinjena transplantacija bubrega imaju značajno veću učestalost UTUC-a 7,16,17 . Studija iz našeg transplantacijskog centra pokazala je kako je u 3 od 6 pacijenata (50 %) s EN-om došlo do razvoja UTUC-a nakon transplantacije bubrega.…”

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Razvoj panurotelijalnog karcinoma nakon transplantacije bubrega u pacijenta s endemskom nefropatijom

Jakšić

Španjol

Oguić

et al. 2020

Med. Flum. (Online)

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Cilj: Endemska nefropatija (EN) je kronična bubrežna bolest koja nastaje zbog dugotrajnog izlaganja aristolohičnoj kiselini. EN je povezan s razvojem terminalnog stadija bubrežne insuficijencije, ali i s razvojem karcinoma urotela, poglavito gornjeg dijela mokraćnoga sustava. U radu ćemo prikazati pacijenticu s endemskom nefropatijom, u koje se nakon presađivanja bubrega razvio panurotelijalni karcinom. Prikaz slučaja: U 76-godišnje pacijentice s EN-om je 2013. godine učinjena uspješna kadaverična transplantacija bubrega. Nakon transplantacije otkriven joj je površinski karcinom mokraćnoga mjehura koji je više puta liječen transuretralnim putem. Zbog pojave karcinoma u gornjem dijelu mokraćnoga sustava učinjena joj je i obostrana nefroureterektomija. Unatoč promjeni imunosupresivne terapije i kirurškom liječenju razvila se metastatska bolest uz letalni ishod tri godine po transplantaciji uz funkcionirajući presadak. Zaključak: U pacijenata s EN-om može doći do razvoja panurotelijalne bolesti, a posebno su ugroženi pacijenti u kojih je učinjena transplantacija bubrega. U ove skupine pacijenata vrlo je važna prijetransplantacijska obrada, kao i praćenje nakon transplantacije bubrega.

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“…Pathological findings of AAN contained extensive chronic tubulointerstitial (TI) fibrosis but sparse of glomerulosclerosis [8], which also resulted in progression into ESRD. Furthermore, AAN was reported strongly associated with the development of UTUC [9], and high incidence of urothelial cancers (UTUC and bladder cancer) were noted in ESRD patients received either renal transplantation or dialysis [10].…”

Section: Introductionmentioning

confidence: 99%

Predominant global glomerulosclerosis in patients of upper urinary tract urothelial carcinoma with pre-existing renal function impairment is a predictor of poor renal outcomes

et al. 2019

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Background Incidence of renal dysfunction and risks of progression to end-stage renal disease (ESRD) were reported higher in upper urinary tract urothelial carcinoma (UTUC) than in renal cell carcinoma (RCC) patients after unilateral nephrectomy. Methods Totally 193 renal cancer patients, including 132 UTUC and 61 RCC, were studied to clarify whether the pathological changes of the kidney remnant removed from nephrectomy and the clinical factors might predict the risk of ESRD. Renal tubulointerstitial (TI) score and global glomerulosclerosis (GGS) rate were examined by one pathologist and two nephrologists independently under same histopathological criteria . Results The glomerular filtration rates at the time of surgery were lower in UTUC than RCC groups ( p < 0.001). Average GGS score and average TI rate were higher in UTUC than in RCC groups ( p < 0.001; p < 0.001). Competitive risk factor analysis revealed that abnormal GGS rate not related to age, predominant in UTUC with pre-existing renal function impairment, was a histopathological predictor of poor renal outcomes (creatinine doubling or ESRD) within 5 years in UTUC patients. Conclusion Pre-existing renal function and pathological change of kidney remnant in both UTUC and RCC have the value for prediction of renal outcomes. Electronic supplementary material The online version of this article (10.1186/s12885-019-5414-x) contains supplementary material, which is available to authorized users.

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Urothelial Cancer in Patients with Endemic Balkan Nephropathy (EN) after Renal Transplantation

Cited by 10 publications

References 15 publications

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

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

Razvoj panurotelijalnog karcinoma nakon transplantacije bubrega u pacijenta s endemskom nefropatijom

Predominant global glomerulosclerosis in patients of upper urinary tract urothelial carcinoma with pre-existing renal function impairment is a predictor of poor renal outcomes

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