P0827BALKAN ENDEMIC NEPHROPATHY AND UPPER TRACT UROTHELIAL CANCER INCIDENCE - 40 YEAR FOLLOW
Authors: Glogovac Stevan , Dimitrijevic Zorica , Stojanovic Miomir , Tasic Danijela , Paunovic Karolina , Apostolovic Branislav , Prokopovic Miomir , Pertovic Milan , Ljubenovic Stanimir , Mitic Branka 
Published: June 2020

Abstract

Background and Aims
Balkan endemic nephropathy (BEN) is a chronic tubulointestitial kidney disease prevalent in Serbia, Bosnia, Croatia, Bulgaria and Romania. One of its most peculiar characteristics is a strong association with upper tract urothelial carcinoma (UTUC).
The aim of the paper is to assess the basic epidemiological characteristics of UTUC, such as the incidence, sex, age geographic distribution of the diseased from Jablanica region in the 40-year period, as well as determining the linear trend of UTUC frequency in regions with BEN compared to non-endemic regions, bearing in mind those recent studies that have shown a significant decrease in the incidence of the diseased from BEN.

Method
The research period lasted from 1978 to 2017. In the analysis of the frequency of UTUC, we used the operative material of Urology Department, Health Care Center, Leskovac, and Urology Clinic, Clinical Center, Nis. The patients were divided according to the place of residence-certain areas of Jablanica region. The data from the Institutes of Nephrology and Hemodialysis were used for the classification of the area(A-endemic settlements for BEN; B-hypo-endemic; C-non-endemic urban type; and D-non-endemic rural type. The average annual incidence rate (AAIR) was calculated per 100 000 people. Finally, e jointly observed groups C and D(non-endemic areas) for UTUC. For practical reasons, this period was divided into the first(1978-1997) and the second one(1998-2017).

Results
The highest AAIR of UTUC was registered in endemic settlements(11.82) and the lowest one in non-endemic urban settlements(0.83). Association of UTUC and other tumours were observed in 39.13% in endemic regions compared to 22.53% in non-endemic regions. In endemic settlements in the first observed period, the frequency of UTUC was registered five times higher than in the second. The linear trend of UTUC in the 40-year-period shows a slow decrease(y=-0.0797x+4.2846; r2=0.2028). In addition, there was strong positive linear trend toward urinary bladder cancer occurence(y=1.6415 + 3.45; r2=0.85). However, trend of occurence of bladder cancer in endemic regions were positive, but without significance(y=0.023x+57; r2=0.0004). The results show that UTUC in endemic settlements are 2.63 times more frequent than in hypo-endemic ones; 14.24 times more frequent than in non-endemic settlements.
Our research in Jablanica region also demonstrated unexpectedly high frequency of on UTUC not only in certain endemic settlements with BEN but also in the non-endemic area-Brejanovac village-1 tumour per 99.63 people and AAIR of 40.50, Rudare village-1 tumour per 139.50 people and AAIR 28.67. This occurrence of UTUC frequency in some non-endemic settlements refers to the first observed period until no occurrence was recorded in the second observed period.

Conclusion
The high frequency of UTUC in the regions with BEN in Jablanica region possibly point to the common nephropathogenic and carcinogenic etiologic factor and confirms the existence of a positive correlation between BEN and UTUC. It is necessary that additional investigations be carried out in certain non-endemic settlements in which the frequency of UTUC and hemodialyzed patients in still high.