|Year : 2018 | Volume
| Issue : 3 | Page : 151-155
Urinary bladder thickness, tumor antigen, and lower urinary tract symptoms in a low Schistosoma haematobium-endemic rural community of Nigeria
Oyetunde Oyeyemi1, Adekunle Adefalujo2, Kolawole Ayeni3, Williams Nabofa4, Chinomso Nwozichi5, Adeyemi Dada6, Adebola Yusuf2
1 Department of Basic Sciences, Babcock University, Ilishan Remo, Ogun State; Department of Biological Sciences, University of Medical Sciences, Ondo, Ondo State, Nigeria
2 Department of Radio-Diagnosis, Babcock University Teaching Hospital, Ilishan Remo, Ogun State, Nigeria
3 Department of Microbiology, Babcock University, Ilishan Remo, Ogun State, Nigeria
4 Department of Physiology, Babcock University, Ilishan Remo, Ogun State, Nigeria
5 Department of Adult Health Nursing, School of Nursing, Babcock University, Ilishan Remo, Ogun State, Nigeria
6 Department of Chemical Pathology, Babcock University Teaching Hospital, Ilishan Remo, Ogun State, Nigeria
|Date of Web Publication||27-Jun-2018|
Department of Biological Sciences, University of Medical Sciences, Ondo, Ondo State
Source of Support: None, Conflict of Interest: None
Objective: Bladder tumor antigen (BTA) is a common biomarker for urothelial carcinoma while bladder wall thickening (BWT) is a sign of urinary bladder irritation which suggests cystitis or early-stage bladder cancer pathology, most especially in the absence of bladder outlet obstruction. The aim of this study was to find the incidence of urinary bladder thickness and evaluate the relationship between BTA and BWT in a low schistosomiasis-endemic Nigerian village. Materials and Methods: The study was descriptive and cross-sectional. Freshly passed mid-day urine samples of 56 individuals were screened using chemical reagent strips and then diagnosed microscopically for Schistosoma haematobium. Subsequent follow-up involving ultrasound examination was carried out on distended bladder. The lower urinary tract symptoms (LUTS) were also recorded. Urinary BTA analysis was carried out on the urine samples using enzyme-linked immunosorbent assay. Results: The prevalence of urogenital schistosomiasis in the area was 3.6%. The overall prevalence of human BTA and BWT in the individuals was 44.6 and 35.7%, respectively. The LUTS were associated with BWT (P = 0.004; odds ratio = 6.0; 95% confidence interval = 1.8–20.3). BTA, BWT, and LUTS were not sex and age dependent (P > 0.05). In addition, there was no association between urinary BTA, BWT, and LUTS (P > 0.05). The sensitivity of BWT and LUTS (60.0%) was improved than when either was used to diagnose BTA. Conclusion: The high occurrence of BTA and BWT in the individuals suggests that they may be prone to urothelial carcinoma and urinary bladder irritation, respectively. The role of urogenital schistosomiasis in urinary BTA levels needs to be further explored.
Keywords: Bladder tumor antigen, bladder wall thickness, lower urinary tract symptoms, urogenital schistosomiasis, Nigeria
|How to cite this article:|
Oyeyemi O, Adefalujo A, Ayeni K, Nabofa W, Nwozichi C, Dada A, Yusuf A. Urinary bladder thickness, tumor antigen, and lower urinary tract symptoms in a low Schistosoma haematobium-endemic rural community of Nigeria. Urol Sci 2018;29:151-5
|How to cite this URL:|
Oyeyemi O, Adefalujo A, Ayeni K, Nabofa W, Nwozichi C, Dada A, Yusuf A. Urinary bladder thickness, tumor antigen, and lower urinary tract symptoms in a low Schistosoma haematobium-endemic rural community of Nigeria. Urol Sci [serial online] 2018 [cited 2019 May 19];29:151-5. Available from: http://www.e-urol-sci.com/text.asp?2018/29/3/151/228287
| Introduction|| |
The last decade epidemiological statistics on bladder cancer ranked it as the 11th most commonly diagnosed cancer and the 14th leading cause of cancer-associated deaths worldwide, with 382,700 estimated new cases and 150,300 deaths in 2008. Cystoscopy combined with cytology is used as diagnostic gold standard for bladder cancer surveillance and those suspicious for the disease. Although cystoscopy with cytology is favored by its high sensitivity for most tumors, it is practically limited at some instances. Its application is limited by its inability to sometimes recognize smaller lesions, and carcinoma in situ. Procedures are also invasive causing anxiety in patients and cystoscopic monitoring is not cost effective.,
The search for noninvasive indicators of bladder cancer for early detection of incipient lesions is necessitated by its frequent late detection and significant disease-associated morbidity and mortality. Over 20 known urine-based biomarkers with high sensitivity and/or specificity have been identified  but only bladder tumor antigen (BTA) stat ®, BTA TRAK ®, NMP22, UroVysion ™, and ImmunoCyt ™/uCyt+™ have been approved by the Food and Drug Administration (FDA) for diagnosis and follow-up of bladder cancer.
The BTA test is a test based on specific antibodies recognition of the complement factor H-related protein in voided urine. This protein shares similar structure and function with human complement factor H and is released by self and cultured tumor cells, thus may play an important role in tumor cells' ability to evade the host's immune defense system. The BTA test can complement cystoscopy and cytology in bladder cancer diagnosis and therefore can be used to monitor early bladder pathology which could result in urothelial carcinoma.
Diffuse bladder wall thickening (BWT) is commonly diagnosed in patients with abnormal urinary complaints. It is a sign of urinary bladder irritation due to cystitis in the absence of bladder outlet obstruction and signs of neurogenic bladder (radiopedia). The trabeculation of bladder inner wall observable by cystoscopy is considered a sign of detrusor muscle hypertrophy. The use of transabdominal ultrasonography for assessment of BWT is a noninvasive and simple method and has been widely adopted in the last few years., This study will find out the incidence of thickened bladder wall and its association with symptoms of lower urinary tract. Correlation of BTA with BWT which may be an early pathology of bladder cancer is new and has not been reported. The aim of this study therefore was to find out the incidence of thickened bladder wall and its association with BTA and symptoms of lower urinary tract in a low schistosomiasis endemic rural community of Nigeria.
| Materials and Methods|| |
The study was conducted in Jewo village within Ijebu North-East Local Government Area in Ogun State, Nigeria. The village has about 300 dwellers. The study area is a typical rural setting lacking in basic amenities such as good roads, electricity, and good water supply. All health-related issues of the dwellers are referred to an underequipped local area community health center located in Ilumafon, a neighboring village which is about 2 km from the study area. The people subsist on river water, which is often polluted by human feces, as a result of lack of toilet facilities.
A descriptive and cross-sectional study was conducted. Due to the limitation of resources, about one-fifth (n = 56) of the total population were selected for participation in the study by simple random sampling. Individuals with history of surgical treatment or instrumentation in about 2 weeks before study were excluded from the study. Previous administration of praziquantel in the last 5 years was also excluded. Only those who gave consent were included.
A questionnaire was administered to determine the demography of the participants, length of stay in the village, and other information related to signs and symptoms of lower urinary tract disease. All questions were asked in Yoruba, the local language of the participants.
Freshly passed mid-day and mid-stream urine samples (collected between 10 and 14 h) of 56 individuals were collected. Ten milliliters of urine sample were collected from each individual, into a well-labeled sterile universal bottle. These were inspected macroscopically for macrohematuria, turbidity, and then screened for microhematuria, bilirubin, urobilinogen, protein, and nitrite using commercially available urine reagent strips (Medi-Test Combi 9®, Neumann-Neander-Str. 6-8. D-52355, 'Düren). The strip testing was performed in accordance with the manufacturer's instructions. The urine samples were further processed for parasitological examination and egg count using a standard WHO procedure. Each sample was well mixed and 10 mL of the urine was subjected to centrifugation at 5000 rpm for 5 min. The supernatant was decanted and the sediment was viewed under a light microscope to determine the presence of terminally spined S. haematobium eggs.
Subsequently, pelvic ultrasound examination was carried out on each individual by a consultant radiologist, after ensuring a full (well distended) urinary bladder. The examinations was done blind to the individuals' S. haematobium infection statuses. The volunteers were examined using a Mindray, DP2200 portable ultrasound apparatus with a 3.5 MHz curvilinear probe. Diffuse bladder wall thickness greater than 3 mm was diagnosed as thickened.
Urine samples (10 mL) collected separately for BTA analysis was centrifuged, and about 2 mL of the supernatant was stored at −20°C. Human BTA enzyme-linked immunosorbent assay (ELISA) Kit (Catalog No: E-EL-H0579, Elabscience, China) which uses the Sandwich-ELISA principle was used. This test was performed in accordance with the manufacturer's instructions and blinded to S. haematobium and bladder wall thickness results. Briefly, 100 μL standard of the sample was added to each well and incubated for 90 min at 37°C. Supernatant was removed and 100 μL of biotinylated detection antibody was added and then incubated for 1 h at 37°C. The well content was aspirated and washed 3 times. 100 μL of avidin-horseradish peroxidase conjugate was added and incubated for 30 min at 37°C. The well content was aspirated and washed 5 times. Substrate reagent (90 μL) was added followed by incubation at 37°C for 15 min. Stop solution (50 μL) was added, and the plate was read immediately at 450 nm wavelength. The BTA values were graded as 0.476–1.182, 1.183–5.320, and 5.321–14.867 ng/mL for low, moderate, and high level, respectively.
Permission was sought from the communities' leaders before study. Communities' heads were contacted in advance of the survey to ensure maximum participation of the participants. Oral informed consent was obtained from adult participants, and in case of children, consent was obtained through their parents or guardians. The study was voluntary, and participants were permitted to opt out at any time. Ethical approval was obtained from Babcock University Research Ethics Committee.
Data generated was analyzed using GraphPad Prism 5 (GraphPad Software, Inc., La Jolla, CA, USA). Chi-square analysis and Fisher's exact test were used to test for association between occurrence of bladder pathology, BTA, and lower urinary tract symptoms (LUTS). Sensitivity of bladder pathology and symptoms of urological disorder in diagnosing BTA was calculated. The sensitivity of symptoms of urological disorder in diagnosing bladder wall thickness was also determined. P < 0.05 was considered statistically significant.
| Results|| |
The prevalence of urogenital schistosomiasis in the area was 3.6%. The overall prevalence of positive human BTA in the individuals was 44.6% with 14.3%, 16.1%, and 14.3%, representing the proportion of low, moderate, and high urinary BTA in the individuals, respectively. BWT (35.7%) was the most prevalent bladder pathology while bladder wall contracture (1.8%) was the least [Table 1]. The overall prevalence of LUTS was 64.3%. Urgency, dysuria (16.1% each), and frequency (3.6%) were the most and least reported LUTS, respectively [Table 1]. There was an association between LUTS and BWT (P = 0.004; odds ratio = 6.0; 95% confidence interval = 1.8–20.3). BTA, BWT, and LUTS were not gender and age dependent (P > 0.05) although higher values were recorded in male participants in BTA (54.5%), BWT (39.4%), and some other LUTS than in their female counterparts. In addition, there was no association between urinary BTA, occurrence of BWT, and LUTS (P > 0.05) [Table 2]. Individuals who had stayed between 6 and 10 years in the study area showed highest BTA occurrence in urine (50.0%) [Table 3]. BTA occurrence was not associated with duration of stay in the community [Table 3]. BWT was also highest (45.0%) in individuals who had stayed between 6 and 10 years in the village [Table 4] and was generally not associated with duration of stay (P > 0.05).
|Table 1: Occurrence of bladder tumor antigen and indicators of urological disorder with respect to sex and age|
Click here to view
|Table 2: Associations between bladder tumor antigen and indicators of urological disorder|
Click here to view
|Table 3: Association between bladder tumor antigen and duration of stay in the community|
Click here to view
|Table 4: Association between bladder wall thickness and duration of stay in the community|
Click here to view
In single assessment of clinical examination of bladder and symptoms of urological disorder, dysuria (55.6%), urgency (55.6%), and suprapubic pain (57.1%) were the most sensitive in indirect diagnosis of urinary BTA [Table 5]. Sensitivity was improved (60.0%) when clinical examination (BWT) was combined with other self-reported LUTS [Table 5]. The frequency of urination (0.0%) was not sensitive in diagnosing BWT. Nocturia (75.0%) was the most sensitive self-reported LUTS for indirect diagnosis of BWT [Table 6].
|Table 5: Sensitivity of bladder pathology and symptoms of urological disorder in diagnosing bladder tumor antigen|
Click here to view
|Table 6: Sensitivity of symptoms of urological disorder in diagnosing bladder wall thickness|
Click here to view
| Discussion|| |
This study is the first to correlate positive human urinary BTA with bladder structural pathology and LUTS with a view to monitoring the pathophysiology of bladder pathology at the community level. The study area showed low endemicity of S. haematobium unlike Ilumafon, a nearby village which showed a 20% prevalence level in an unpublished preliminary study. The few cases of schistosomiasis in our study area were due to imported infection from endemic areas. Although BTA has not been directly linked with Schistosoma- induced bladder cancer, other urinary biomarkers such as BLCA-4 test (urine) and nuclear morphometry or quantitative nuclear grading of epithelial cells (urine sediment) have been explored. These biomarkers were used to evaluate specific effects of long-term exposure to S. haematobium., The low schistosomiasis cases in the present study made it difficult to correlate the disease with urinary BTA and BWT.
The similar patterns in BTA and BWT occurrence in male and female individuals could suggest some correlations in the etiologies of the two abnormalities. Their higher occurrences, especially in the male individuals, are indications of higher risk of exposure or practices that could potentiate these conditions. Smoking and alcoholism are two important practices noticed among some of the adult male individuals in the area. These practices could work synergistically to suppress the immune system and increase exposure to urinary tract infections (UTIs), thus resulting in the observed higher bladder pathology and LUTS in the male individuals. Higher positive BTA and BWT in children compared with the adults could be associated with higher exposure to the risk factors. Higher rate of UTIs in the group could be the likely cause of higher occurrence of BWT which could in turn increase the urinary BTA level. The zero prevalence of nitrite in urinalysis results could indicate product's inability to detect it and the need to carry out standard microbiological tests to detect UTIs in the individuals. The prevalence of LUTS reported in our study is higher than in a previous study conducted on some Southwestern men  but lies within the range (13%–67%) documented in previous epidemiologic surveys across the world., Dysuria and urgency which are the most frequently reported symptoms have been previously documented as some of the most frequent LUTS in Nigerian population.
The lack of associations between BTA or BWT occurrence and duration of stay in the community suggests that the risk factors for these disorders are not localized to the community. Smoking, alcoholism, and exposure to UTIs have been earlier suggested are factors not affected by length of stay in the present or previous individuals' locations. Although urinary BTA occurrence was not generally dependent on the LUTS, pain-associated symptoms such as dysuria and suprapubic pain seem to increase the risk of urinary BTA. This is further supported by the moderate sensitivity of the two symptoms for indirect diagnosis of BTA. However, this observation needs further investigation with a larger sample size. Poor sensitivity of BWT to indirectly diagnose BTA is not desirable as individuals with significant BTA levels could be left unnoticed and this could eventually prone them to the risk of urothelial carcinoma. False-positive BTA results associated with some genitourinary conditions such as hematuria as reported by the individuals or diagnosed during urinalysis could be the cause of this low sensitivity. The false-positive result could be caused by the reaction of complement factor H in the urinary blood with the antibody in the test kit., In practice, the combination of BWT and LUTS to indirectly diagnose abnormal BTA level can be useful owning to the observed improved sensitivity. While nocturia was sensitive for diagnosing BWT, the combination of all the symptoms gave better specificity.
| Conclusion|| |
This study showed that schistosomiasis is not endemic in our study area and the few encountered cases of S. haematobium infection were imported from endemic areas during the previous visit or stay in the areas. The relationship between BTA, BWT, and schistosomiasis therefore cannot be studied owning to this limitation. The high occurrence of BTA and BWT in the individuals indicates high risk of urothelial carcinoma and urinary bladder irritation, respectively. Combination of BWT and other self-reported LUTS could moderately diagnose BTA in urine. The role of urogenital schistosomiasis in urinary BTA levels needs to be further explored.
We acknowledge the co-operation of the villagers. Also, Dr. Chibundu Ezekiel for proofreading the manuscript.
Financial support and sponsorship
This study was funded by a Babcock University Research Grant (BU/RIIC/2016/005) awarded to OO.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM, et al.
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.
Lotan Y, Svatek RS, Sagalowsky AI. Should we screen for bladder cancer in a high-risk population? A cost per life-year saved analysis. Cancer 2006;107:982-90.
Budman LI, Kassouf W, Steinberg JR. Biomarkers for detection and surveillance of bladder cancer. Can Urol Assoc J 2008;2:212-21.
Dey P. Urinary markers of bladder carcinoma. Clin Chim Acta 2004;340:57-65.
Smith ZL, Guzzo TH. Urinary markers for bladder cancer. F1000Prime Rep 2013;5:21.
Cheng ZZ, Corey MJ, Pärepalo M, Majno S, Hellwage J, Zipfel PF, et al.
Complement factor H as a marker for detection of bladder cancer. Clin Chem 2005;51:856-63.
Wu SY, Jhang JF, Jiang YH, Kuo HC. Increased bladder wall thickness is associated with severe symptoms and reduced bladder capacity in patients with bladder pain syndrome. Urol Sci 2016;27:263-8.
Szabó L, Lombay B, Borbás E, Bajusz I. Videourodynamics in the diagnosis of urinary tract abnormalities in a single center. Pediatr Nephrol 2004;19:326-31.
Cvitković-Kuzmić A, Brkljacić B, Ivanković D, Grga A. Ultrasound assessment of detrusor muscle thickness in children with non-neuropathic bladder/sphincter dysfunction. Eur Urol 2002;41:214-8.
Yeung CK, Sreedhar B, Leung YF, Sit KY. Correlation between ultrasonographic bladder measurements and urodynamic findings in children with recurrent urinary tract infection. BJU Int 2007;99:651-5.
Salawu OT, Odaibo AB. Schistosomiasis among pregnant women in rural communities in Nigeria. Int J Gynaecol Obstet 2013;122:1-4.
Levy AD, Murakata LA, Abbott RM, Rohrmann CA Jr. From the archives of the AFIP. Benign tumors and tumorlike lesions of the gallbladder and extrahepatic bile ducts: Radiologic-pathologic correlation. Armed forces institute of pathology. Radiographics 2002;22:387-413.
Shiff C, Veltri R, Naples J, Quartey J, Otchere J, Anyan W, et al.
Ultrasound verification of bladder damage is associated with known biomarkers of bladder cancer in adults chronically infected with Schistosoma haematobium
in Ghana. Trans R Soc Trop Med Hyg 2006;100:847-54.
Eissa S, Ahmed MI, Said H, Zaghlool A, El-Ahmady O. Cell cycle regulators in bladder cancer: Relationship to schistosomiasis. IUBMB Life 2004;56:557-64.
Ojewola RW, Oridota ES, Balogun OS, Ogundare EO, Alabi TO. Lower urinary tract symptoms: Prevalence, perceptions, and healthcare-seeking behavior amongst Nigerian men. World J Mens Health 2016;34:200-8.
Boyle P, Robertson C, Mazzetta C, Keech M, Hobbs FD, Fourcade R, et al.
The prevalence of male urinary incontinence in four centres: The UREPIK study. BJU Int 2003;92:943-7.
Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S, et al.
Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: Results of the EPIC study. Eur Urol 2006;50:1306-14.
Nasuti JF, Gomella LG, Ismial M, Bibbo M. Utility of the BTA stat test kit for bladder cancer screening. Diagn Cytopathol 1999;21:27-9.
Oge O, Kozaci D, Gemalmaz H. The BTA stat test is nonspecific for hematuria: An experimental hematuria model. J Urol 2002;167:1318-9.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]