




































Copyright © CC-BY-NC 2020, CRIBFB | AIJMSR 

 

                     American International Journal of Multidisciplinary Scientific Research; Vol. 6, No. 1; 2020 
                                       ISSN 2638-1249   E-ISSN 2638-1273 

Published by Centre for Research on Islamic Banking & Finance and Business, USA 
 

     1 
 

 

Epidemiological and Morphological Characteristics of Urothelial Bladder 
Cancer in a Bulgarian and a French Sample of Patients 

 
 

Milena Gulinac 
Medical Faculty 

Department of General and Clinical Pathology 
Medical University-Plovdiv, Bulgaria 

E-mail: mgulinac@hotmail.com 
 

Dorian Dikov  
Grand Hospital de l’Este Francilien, Jossigny, France 

Medical Faculty, Department of General and Clinical Pathology 
Medical University-Plovdiv, Bulgaria 

 
Ts. Velikova 

Medical Faculty 
Department of Clinical Immunology 

University Hospital Lozenetz-Sofia, Bulgaria 
 
 
 
 
Abstract 
Bladder carcinoma (BC) is one of the most common malignancies of the urinary system in developed countries, and it is also 
characterized by a high number of recurrences and progression rates despite multimodal treatment. BC is a biological and 
clinically heterogeneous tumor with a great propensity of divergent differentiation. Around the world, bladder cancer is 

responsible for 549.000 new cases и 200.000 deaths each year. In Bulgaria, bladder carcinoma is the 18th most common 
neoplasia. Our results on 105 proven bladder carcinoma cases confirmed that this tumor arises at 70 years at average (60-90 
years), it affects men predominantly and there was no difference regarding the nationality of patients. In conclusion, it remains a 
diagnostic challenge. 
 
Keywords: Bladder Cancer, Urothelial Carcinoma, Urinary Tract.  
 
1. Introduction 
Urothelial bladder cancer is a common disease that takes the 9 th rank in worldwide cancer incidence (Ploeg et al., 2009). The 
incidence of bladder cancer is three times greater in males than in females (Hartge et al., 1990). These differences in gender 
prevalence explained largely by differences in exposure to certain risk factors. In the developed country, the major risk factor is 
smoking (Aydin et al., 2017; Battista Di Pierro et al., 2012; Gilbert et al., 2004). In Western countries, smoking is responsible 
for around 50% of urothelial bladder cancer in males and 35% in females (Ploeg et al., 2009). On the other hand, in countries 
where the infection caused by Schistosoma haematobium is endemic, like Egypt, primary squamous cell carcinoma of the bladder 
is the dominant histological type. The third most important risk factor for bladder cancer development is occupational exposure, 
as chronic exposure to arsenic.  
           Carcinoma of the bladder is a 7th most common malignant disease in men and 17th in women.  The majority of bladder 
cancer is composed of urothelial carcinoma (90%), where the remaining less common types include primary bladder’s 
adenocarcinoma, squamous cell carcinoma, and neuroendocrine carcinomas (small cell carcinoma) (Carneiro et al., 2015). 
           Urothelial carcinoma of the bladder is usually admixed with other morphologically recognizable differentiations (Beltran 
et al., 2017). In recent years, the spectrum of microscopic forms of urothelial carcinoma has been expanded to include several 
histological variants. Most of them are described in the World Health Organization (WHO2016) book (Moch et al., 2016). 
The recognition of histological variants in urothelial neoplasia is essential for a pathologist and oncologist because different 

https://www.ncbi.nlm.nih.gov/pubmed/?term=Hartge%20P%5BAuthor%5D&cauthor=true&cauthor_uid=2213906
https://www.ncbi.nlm.nih.gov/pubmed/?term=Gilbert%20D%5BAuthor%5D&cauthor=true&cauthor_uid=15203798
https://www.ncbi.nlm.nih.gov/pubmed/?term=Carneiro%20BA%5BAuthor%5D&cauthor=true&cauthor_uid=25498841
https://www.ncbi.nlm.nih.gov/pubmed/?term=Moch%20H%5BAuthor%5D&cauthor=true&cauthor_uid=26935559


Copyright © CC-BY-NC 2020, CRIBFB | AIJMSR 

 

www.cribfb.com/journal/index.php/aijmsr     American International Journal of Multidisciplinary Scientific Research   Vol. 6, No. 1; 2020 
 

2 
                         
 

histology subtypes of urothelial cancer of the bladder may be associated with different clinical outcomes and have a different 
therapeutic approach.  
 
2. Materials and Methods 
We examined 105 cases of urothelial carcinoma from tissue database of University Hospital “St. George “Plovdiv, Bulgaria and 
Grand Hospital de l’Este Francilien, Jossigny, France, and reviewed the period from 2016 to 2020. All analyzed patients in this 
study have been diagnosed with invasive or non-invasive high-grade (HG) and low-grade (LG) urothelial carcinomas of the 
bladder.  

Histological analysis of the tissues was performed using automatic tissue processor „DIAPATH EN ISO 9001:2000“ 

and 4-5 μm formalin-fixed paraffin-embedded tissue sections underwent routine staining with hematoxylin-eosin (HE) and 
hematoxylin-eosin-safran (HES) to determine the presence of individual histological features. 

Statistical analysis was performed with the software package for statistical analysis (SPSS®, 92 IBM 2009, version 19) 
using descriptive statistics and dispersion analysis (ANOVA). We considered the results for significant if p<0.05.   
 
3. Results 
The analyzed 105 patients in our study were diagnosed with proven urothelial carcinoma. Still, we must clarify that we included 
a few cases of urothelial carcinoma of renal pelvis and ureter. The patients only with urothelial carcinoma of bladder were 
95.2%. Nevertheless, all analyzed patients were characterized and separated by two features: 1) by localization and 2) by age and 
gender. 
        The most common site of urothelial carcinoma was in the bladder, presented by 100 (95.2%) cases. Second by 
frequency urothelial carcinoma was in the distal part of the ureter, observed in 3(2.9%) cases. The least of the urothelial 
carcinoma included in our study were 3(1.9%) cases in the renal pelvis.  These results are presented in Table 1.      
 
       Table 1. Number and percentage of patients with urothelial carcinoma according to its location 
 

 Bladder Renal pelvis Ureter Total 

Number of patients 100 2 3 105 

Percentages of patients 95.2 1.9 2.9 100 

 
Although we analyzed our result according to the average age, the mean age of our patients was 70±10.98 years, as the 

youngest patient was 42 years old, while the oldest was 93 years old. Because of that heterogeneity of the age, we separated all 
patients in our study into six decades, as it is shown in Figure 2. The majority of our patients fit in the 60-89 years of age. 
 

 
Figure 2. The number and % of patients with urothelial carcinoma according to age divided into decades 

 
In regards to the age and nationality of our patients with urothelial carcinoma of the bladder, we did not find a 

significant difference between them. The median age of the patients from Bulgaria was 70.14 ±11.16 years, and from France 
was 69.62 ±10.09 years, p=0.873. This is graphically presented in Figure 3 
 

40-49 50-59 60-69 70-79 80-89 90-99 

0 

5 

10 

15 

20 

25 

30 

35 

40 



Copyright © CC-BY-NC 2020, CRIBFB | AIJMSR 

 

www.cribfb.com/journal/index.php/aijmsr     American International Journal of Multidisciplinary Scientific Research   Vol. 6, No. 1; 2020 
 

3 
                         
 

 
 

Figure 3. Differences in the average age of patients according to the nationality 
 

We have obtained the following results according to the gender of the patients form cohort comprised of 105 patients 
with urothelial carcinoma: 72.4% (76/105) were males, and 27.6% (29/105) were females. The data are graphically presented 
in Figue 4.  
 

 
 

Figure 4. Distribution of patients according to the gender 
                                                             

72% 

28% 

Men Women 

 

р=0.873 



Copyright © CC-BY-NC 2020, CRIBFB | AIJMSR 

 

www.cribfb.com/journal/index.php/aijmsr     American International Journal of Multidisciplinary Scientific Research   Vol. 6, No. 1; 2020 
 

4 
                         
 

 
 

Figure 5. Distribution of the patients according to their nationality 
 

Figures 4 and 5 show the distribution of urothelial carcinoma of bladder by gender, in Bulgarian and French samples 
of patients with a significant difference between male and female, for both countries. In essence, 65/92 (70.7%) for Bulgarian 
patients and 11/13 (84.6%) for France were males, and 27/92 (29.3%) in Bulgaria and 2/13 (15.4%) in France were females. 
Descriptive statistical methods showed no significant differences in patient’s samples for both countries, p=0.292.  
 
 4. Discussion 
Bladder carcinoma still presents a diagnostic challenge, and it remains the 7th most common malignant disease and the 2nd most 
common neoplasia of the excretory system right after prostatic carcinoma. It is also characterized by a high tendency for 
recurrence, necessitating expensive life-long clinical surveillance with repeated surgical interventions. Even in highly developed 
countries where standards of medical care and treatment are high, outcomes remain unchanged from 20 years ago. Urothelial 
carcinoma of the bladder is a significant public health problem in South Europe (especially in Greece, Spain, and Italy) and the 
most common cause for the lethal outcome of malignancies in males, and in Lebanon - in females (Bray et al., 2018). 
       This study demonstrated that the urothelial carcinoma of the bladder is a high-risk tumor. Moreover, among men, this is 
the most commonly diagnosed malignancy in Bulgaria and France, which is in correspondence with the data from other studies. 
According to literature, Bulgaria is the only country where males had a significant increase in both incidence and mortality 
(Wong et al. ,2018). In our study, we also established the ratio between man and women was 3.2:1, and the average age of the 
patients with urothelial carcinoma of the bladder is 70.14 years on average, which is similar to the results of almost all published 
studies (Horstmann et al., 2008; Gandomani et al., 2017). 
 
5. Conclusion 
This study demonstrated that bladder carcinoma is not a “simple” pathology but a common and aggressive malignant disease. It 
remains a diagnostic challenge. As we described in the interdiction, many factors affect its epidemiology. Still, most of them 
might be controlled with all common forces for one purpose only – reduces its incidence and mortality.   
 
Conflict of interests 
The authors state no conflict of interest. 
 
References 
Aydin, A. M., Woldu, S. L., Hutchinson, R. C., Boegemann, M., Bagrodia, A., Lotan, Y., ... & Krabbe, L. M. (2017). Spotlight 

on atezolizumab and its potential in the treatment of advanced urothelial bladder cancer. OncoTargets and therapy, 
10, 1487. 

Beltran LA. Cheng I, Raspollini MR, Marques RC, Scarpelli M, Gasparrini S, Montironi R. (2017). Variants of Bladder 
Cancer: The Pathologist's Point of View. European Urology Supplements, 16(12), 210–222. 

Bulgaria France 

0% 

10% 

20% 

30% 

40% 

50% 

60% 

70% 

80% 

90% 

100% 

Male Female 

https://www.ncbi.nlm.nih.gov/pubmed/?term=Horstmann%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19108811


Copyright © CC-BY-NC 2020, CRIBFB | AIJMSR 

 

www.cribfb.com/journal/index.php/aijmsr     American International Journal of Multidisciplinary Scientific Research   Vol. 6, No. 1; 2020 
 

5 
                         
 

Battista Di Pierro, G., Gulia, C., Cristini, C., Fraietta, G., Marini, L., Grande, P., ... & Piergentili, R. (2012). Bladder cancer: a 
simple model becomes complex. Current genomics, 13(5), 395-415. 

Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: 
GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal 
for clinicians, 68(6), 394-424. 

Carneiro, B. A., Meeks, J. J., Kuzel, T. M., Scaranti, M., Abdulkadir, S. A., & Giles, F. J. (2015). Emerging therapeutic targets 
in bladder cancer. Cancer Treatment Reviews, 41(2), 170-178. 

Gandomani, H. S., Tarazoj, A. A., Siri, F. H., Karimi Rozveh, A., Hosseini, S., Borujeni, N. N., ... & Salehiniya, H. (2017). 
Essentials of bladder cancer worldwide: incidence, mortality rate and risk factors. Biomedical Research and Therapy, 
4(9), 1638-55. 

Gilbert, D. G., McClernon, F. J., Rabinovich, N. E., Sugai, C., Plath, L. C., Asgaard, G., ... & Botros, N. (2004). Effects of 
quitting smoking on EEG activation and attention last for more than 31 days and are more severe with stress, 
dependence, DRD2 A1 allele, and depressive traits. Nicotine & Tobacco Research, 6(2), 249-267. 

Hartge, P., Harvey, E. B., Linehan, W. M., Silverman, D. T., Sullivan, J. W., Hoover, R. N., & Fraumeni, J. F. (1990). 
Unexplained excess risk of bladder cancer in men. JNCI: Journal of the National Cancer Institute, 82(20), 1636-
1640. 

Horstmann, M., Witthuhn, R., Falk, M., & Stenzl, A. (2008). Gender-specific differences in bladder cancer: a retrospective 
analysis. Gender medicine, 5(4), 385-394. 

Moch, H., Cubilla, A. L., Humphrey, P. A., Reuter, V. E., & Ulbright, T. M. (2016). The 2016 WHO classification of 
tumours of the urinary system and male genital organs—part A: renal, penile, and testicular tumours. European 
urology, 70(1), 93-105. 

Ploeg, M., Aben, K. K., & Kiemeney, L. A. (2009). The present and future burden of urinary bladder cancer in the world. 
World journal of urology, 27(3), 289-293. 

Wong, M. C., Fung, F. D., Leung, C., Cheung, W. W., Goggins, W. B., & Ng, C. F. (2018). The global epidemiology of 
bladder cancer: a joinpoint regression analysis of its incidence and mortality trends and projection. Scientific reports, 
8(1), 1-12. 

 
 

 
Copyrights  
Copyright for this article is retained by the author(s), with first publication rights granted to the journal. This is an open-access 
article distributed under the terms and conditions of the Creative Commons Attribution license 
(http://creativecommons.org/licenses/by/4.0/). 


