BIOCHEMICAL MODIFICATIONS ASSOCIATED WITH BLADDER CANCER

Bladder cancer is the most common neoplasm of the urinary system, and urothelial carcinoma is the most common histological type of bladder cancer (approximately 90%), and represents the invasion of the basement membrane or lamina propria by urothelial cells. Most people with bladder cancer have hematuria and the doctor should be consulted as soon as possible and a specialist scheduled to examine the bladder with a camera - cystoscopy. The present study is a retrospective study that includes 174 patients from the Urology Clinic of the „Sfantul Apostol Andrei” County Emergency Clinical Hospital in Constanta in the period 2016-2020. In the study, the 174 patients were divided into 2 groups. The first group is a study group and includes patients with an anatomopathologically confirmed diagnosis of urothelial carcinoma, while the second, control group, contains patients without a diagnosis of urothelial carcinoma. This study analyzes the metabolic disorders associated with bladder cancer. There is a highly statistically significant association between hematuria and urothelial carcinoma. The present study confirms a significant association between urinary tract infection and bladder cancer. The infection is associated due to the presence of blood in the urine, being an environment for the development of bacterial cultures. A significant association is observed between hemoglobin and urothelial carcinoma, with patients developing anemia due to episodes of hematuria caused by the presence of bladder tumors.


Introduction
Bladder cancer occurs when cells in the bladder begin to grow uncontrollably.A type of bladder cancer also called transitional cell carcinoma is urothelial carcinoma (1).Bladder cancer is the most common neoplasm of the urinary system, and urothelial carcinoma is the most common histological type of bladder cancer (approximately 90%).It represents the invasion of the basement membrane or lamina propria by urothelial cells (2).
Bladder cancer is a common malignancy in women and is the fourth most common malignancy in men ranging from non-aggressive and usually non-invasive tumors that recur and require long-term invasive attention to aggressive and invasive tumors with high disease-specific mortality (3).Older age, male gender and smoking are factors that contribute to the development of bladder cancer (3).
Most people with bladder cancer have hematuria and the doctor should be consulted as soon as possible and a specialist scheduled to examine the bladder with a camera -cystoscopy (4).As seen, also, in other forms of cancers, biochemical changes represent a reality (5) This study focuses on analysing a cluster of metabolic disorders, such as hypertension, obesity, and irregularities in blood sugar and hemoglobin levels, in patients with bladder cancer.

Material and method
The present study is a retrospective study that includes 174 patients from the Urology Clinic of the "Sfantul Apostol Andrei" County Emergency Clinical Hospital in Constanta in the period 2016-2020.In the study, the 174 patients were divided into 2 groups.The first group is a study group and includes patients with an anatomopathologically confirmed diagnosis of urothelial carcinoma, while the second, control group, contains patients without a diagnosis of urothelial carcinoma.
This study analyzes the metabolic disorders associated with bladder cancer.

Results and discussion
None of the social characteristics of the patients included in the study, as seen in table I, confirm significant associations with the diagnosis of urothelial carcinoma.While some patients diagnosed with bladder cancer experience this symptom, irritable bladder symptoms are not as common as hematuria.Between 80% and 90% of patients with bladder cancer experience hematuria without pain or burning during urination (6).An important proportion of patients suffer from dysuria, in the study group there are 96 people (90%), probably indicating urinary tract infection.Only 11 patients (10%) do not present this symptom.In the control group there are 56 people with dysuria (84%) and the rest without 11 (16%).Dysuria in this situation occurs either due to the coexistence of the urinary tract infection, the development of which is favored by the patient's immune deficiency, or due to tumor invasion.
The result of the Chi-square test applied to these groups, 0.23, shows that there is no statistically significant association between dysuria and urothelial carcinomas.
Hematuria is the most frequently present sign, being the one that alarms the patient and prompts him to contact the Urology Service.Hematuria is usually associated with clots that favor the occurrence of dysuria and even retention of urine.A very high proportion of patients with hematuria is observed, 105 patients (98%), possibly extraglomerular and only 2% do not present this diagnosis in the study group.For the control group there are 56 people with hematuria (84%) and a significant percentage of 16% are not patients with hematuria.
The hematuria is mostly due to the lesions occurring at the level of the tumor bed and is intermittent in nature.Painless hematuria is the most common symptom.Gross blood during urination suggests bladder cancer.Symptoms of bladder irritation, such as urinary frequency and urgency, occur more frequently in patients with bladder carcinoma in situ (7).The result of the Chi-square test (< 0.001) confirms a highly statistically significant association between hematuria and urothelial carcinoma.Acute renal failure is a common and severe complication of bladder tumors that can be lifethreatening and makes treatment of bladder tumors difficult requiring multidisciplinary management (8).Most patients in the study group, 91(85%) declare that they do not suffer from this chronic kidney disease.However, 16 of the patients (15%) in this study were diagnosed with renal failure, as shown in Table I.In the control group there are 53 patients who do not have kidney failure (79%) and 14 of them suffer from this disease in a significant percentage of 21%.
Renal failure in this situation is either an associated comorbidity of the patient, or it appears due to the expansion of the tumor bed that encompasses the Ureteral Orifices and causes this secondary renal failure.
Renal failure may be disease-related, caused by ureteral obstruction, previous nephrectomy, or, more commonly, age-related decline in glomerular filtration rate.
The result of the Chi-square test applied to the groups of the present study, 0.31, does not confirm renal failure as a symptom associated with bladder cancer A majority of the patients included in the study in the study group declared urinary tract infection, 103 (96%) and only 4 patients did not present this diagnosis of cystitis (4%).In the control group 56 patients suffer this infection (84%) and 11 (16%) do not have this disease.In this study the Chi square test has a value of 0.003 confirming a significant association between urinary tract infection and bladder cancer.A urinary tract infection (UTI) can definitely be a symptom.Of course, not everyone who has a UTI will be diagnosed with bladder cancer, but that's why it's so important to seek treatment because it can be a sign of something more serious (10).
Creatinine determines the degree of renal failure that patients have.But the result of the t test applied to the two groups, 0.16, does not confirm an association between this indicator and urothelial carcinoma.Typically, creatinine levels that are associated with a creatinine clearance of less than 60 mL/min are above 1.5 or 1.6 mg/ dl.It is a common clinical practice used to avoid treating patients with renal dysfunction with cisplatin or other nephrotoxic agents (9).Although there are analyzes that show a positive association between diabetes and the risk of bladder cancer (11), applying the t-test to the two groups, the result of 0.44 shows that there is no significant association between the blood glucose value and urothelial cancer.Consequently, additional studies are needed to show whether glycemic control can reduce the risk of bladder cancer.
For the hemoglobin indicator, applying the statistical test to the two samples indicates a significant association between hemoglobin and urothelial carcinoma.Preoperative anemia was a strong predictor of urothelial cancer recurrence and may contribute to mortality in all stages of bladder cancer.Correcting anemia, combined with malnutrition and inflammation, before initiation of targeted cancer treatment may improve outcomes for patients with bladder cancer, particularly those with non-muscle invasive bladder cancer (12).
In the present study, there are high proportions of those with hypertension and those without hypertension.50 patients with a weight of 47% were diagnosed with hypertension and will need to be carefully monitored and treated in the study group.57 of the patients included in the study do not have this condition (53%).In the control group 31 patients (46%) have hypertension symptoms, and 36 of the patients (54%) do not have these symptoms.No direct correlation can be established between arterial hypertension and bladder carcinomas.This comorbidity is a pathology specific to the elderly, but it does not directly influence the occurrence of urothelial carcinomas, but it does influence the operative risk.

Conclusions
There is a highly statistically significant association between hematuria and urothelial carcinoma.The present study confirms a significant association between urinary tract infection and bladder cancer.The infection is associated due to the presence of blood in the urine, being an environment for the development of bacterial cultures.
A significant association is observed between the hemoglobin indicator and urothelial carcinoma, with patients developing anemia due to episodes of hematuria caused by the presence of bladder tumors.