Necmettin Atsu

A study of the etiology of idiopathic calcium urolithiasis in children : Hypocitruria is the most important risk factor

PURPOSE To determine the association of metabolic risk factors with pediatric calcium urolithiasis we compared metabolic evaluation data on children with idiopathic calcium stones and those on healthy children. MATERIALS AND METHODS Metabolic evaluation was done in 78 calcium stone formers 1 to 15 years old (mean age 7.2) who were free of urinary tract infection, anatomical abnormalities, and metabolic, endocrinological and intestinal disorders, and in 24 healthy children. Evaluation included serum biochemistry, and measurement of daily excretion of urinary calcium, oxalate, urate, phosphorus, citrate and magnesium. RESULTS Demographic characteristics, serum parameters, and daily excretion of calcium, urate, phosphorus and magnesium did not differ statistically in the 2 groups. However, urinary oxalate was significantly higher and urinary citrate was significantly lower in stone formers than in controls (p = 0.002 and 0.028, respectively). Hypocitruria and hyperoxaluria were 4.3 and 3-fold more common in stone formers than in controls, respectively. Multivariate analysis using logistic regression showed that hypocitruria was the only significant risk factor for idiopathic calcium stones (p = 0.008). CONCLUSIONS Hypocitruria was the most important risk factor in our patients. Hyperoxaluria was also common and accompanied hypocitruria in many stone formers. In contrast to many previous reports, we failed to show that hypercalciuria is an important metabolic defect for idiopathic calcium stones, possibly because our study evaluated a different population.

Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and bladder cancer susceptibility in the Turkish population

Abstract. We investigated the effect of the GSTM1 and GSTT1 null genotypes, and GSTP1 313 A/G polymorphism on bladder cancer susceptibility in a case control study of 121 bladder cancer patients, and 121 age- and sex-matched controls of the Turkish population. The adjusted odds ratio for age, sex, and smoking status is 1.94 [95% confidence intervals (CI) 1.15–3.26] for the GSTM1 null genotype, and 1.75 (95% CI 1.03–2.99) for the GSTP1 313 A/G or G/G genotypes. GSTT1 was shown not to be associated with bladder cancer. Combination of the two high-risk genotypes, GSTM1 null and GSTP1 313 A/G or G/G, revealed that the risk increases to 3.91-fold (95% CI 1.88–8.13) compared with the combination of the low-risk genotypes of these loci. In individuals with the combined risk factors of cigarette smoking and the GSTM1 null genotype, the risk of bladder cancer is 2.81 times (95% CI 1.23–6.35) that of persons who both carry the GSTM1-present genotype and do not smoke. Similarly, the risk is 2.38-fold (95% CI 1.12–4.95) for the combined GSTP1 313 A/G and G/G genotypes and smoking. These findings support the role for the GSTM1 null and the GSTP1 313 AG or GG genotypes in the development of bladder cancer. Furthermore, gene-gene (GSTM1-GSTP1) and gene-environment (GSTM1-smoking, GSTP1-smoking) interactions increase this risk substantially.

FALSE-POSITIVE RESULTS OF THE NMP22 TEST DUE TO HEMATURIA

PURPOSE The problem with available markers for bladder cancer is their low specificity and low positive predictive value due to false-positive results. False-positive results of the NMP22 nuclear matrix protein test (Matritech, Cambridge, Massachusetts) are usually observed in some clinical categories that are usually associated with hematuria and pyuria. This problem is especially serious in bladder cancer since 85% of patients present with hematuria. We investigated the effect of the degree of hematuria and pyuria on NMP22 results in an experimental model and human subjects. MATERIALS AND METHODS This study was performed in 202 urine samples from 30 healthy individuals (group 1), 20 with symptomatic urinary tract infection (group 2) and 32 with known bladder carcinoma (group 3). In the first group to achieve 0, 10, 100, 1,000 and 5,000 red blood cells per high power field the blood obtained from each patient was added to test tubes at 0.02, 0.2, 2 and 10 microl, respectively. RESULTS In the first group median urinary NMP22 in healthy individuals was 4 units per ml. (range 1.6 to 9.5). When blood was added to the urine sample, the NMP22 increase paralleled the increase in the amount of red blood cells in the sediment. When greater than 2 microl./ml. blood or 1,039.5 red blood cells per high power field (range 278 to 1,438) were added to the urine of a healthy individual, the NMP22 level reached and surpassed the level in patients with bladder carcinoma. The leukocyte count in the urine sediment also had a significant impact on urinary NMP22 in group 2. The degree of hematuria and pyuria did not significantly effect NMP22 in group 3. The sensitivity, specificity, positive and negative predictive values of NMP22 were 78.1%, 66%, 59.5% and 82.5%, respectively. Test sensitivity increased as grade and stage progressed. CONCLUSIONS In an experimental model pyuria and hematuria significantly affected urinary NMP22. The effect of white blood cells was more pronounced than that of red blood cells. The source of NMP22 in isolated hematuria remains to be elucidated. On the other hand, in group 3 the tumor was the main source of NMP22, and urinary erythrocytes and/or leukocytes had a negligible effect.

Oral Potassium Citrate Treatment for Idiopathic Hypocitruria in Children With Calcium Urolithiasis

PURPOSE We evaluated the clinical and laboratory outcome of oral potassium citrate treatment in children with idiopathic hypocitruria and calcium stones. MATERIALS AND METHODS The charts of 64 children 1 to 15 years old with hypocitruria and calcium stones (median age 7.2) treated with oral potassium citrate were reviewed. Evaluation parameters were tolerability, adverse reactions, metabolic profile and stone recurrence. RESULTS No serious adverse reaction due to potassium citrate administration was recorded. Normal citrate excretion was restored in all patients. After treatment median urinary citrate daily plus or minus SD increased from 197 +/- 72 to 632 +/- 218 mg./1.73 m.2 (p <0.001) and mean urinary pH increased from 5.3 +/- 0.3 to 6.2 +/- 0.7 (p <0.01). Mean calcium excretion decreased from 3.5 +/- 2.7 to 2.5 +/- 2.7 mg./kg. (p <0.05). At an average followup of 22 months (range 3 to 67) the recurrence rate in the group overall was 0.07 per patient-year. The previous recurrence rate of 0.32 per patient-year in the 20 children with a history of recurrent stone disease decreased to 0.17 per patient-year after treatment. None of the 44 initial stone formers had recurrent stones. CONCLUSIONS Our results show the safety and efficacy of oral potassium citrate treatment for restoring normal urinary citrate and suggest a preventive effect for recurrent calcium stone disease in children with hypocitruria and calcium stones.

Proposal for Changes in Cystoscopic Follow–Up of Patients with Low–Grade pTa Bladder Tumor

Objectives: The cystoscopic follow–up of superficial bladder cancer accounts for a considerable workload for urologists and is also an invasive procedure with high costs. There is a potential benefit both to the urologist and the patient if unnecessary cystoscopies can be avoided. Methods: The recurrence and progression rates of 120 patients with pTa G1 or G2 and small (<4 cm) transitional cell carcinoma were evaluated retrospectively. Results: The recurrence rate was 6.5% (8/120) at 3 months. The recurrence rates at 6 and ■ months were 6.7 (8/119) and 3.6% (4/112), respectively. However, when the third month (first check) was clear, the recurrence rates at 6– and 9–month cystoscopy were 4.3 (5/116) and 2.7% (3/111), respectively. The recurrence rate at 12 months was 8% (8/99). For G1 tumors, the recurrence rates at 3, 6, 9 and 12 months were 6 (5/84), 5 (5/83), 2.5 (2/80) and 7% (5/71), respectively. The same results for G2 tumors were 8 (3/36), 8 (3/36), 6 (2/32) and 10.5% (3/28), respectively. The progression rate for the first year was lower than 1%. The difference between G1 and G2 tumors according to recurrence rate within the first year was not statistically significant (p>0.05). Conclusions: This study supports the proposal that for patients with small and welldifferentiated pTa tumors at diagnosis, if the first control cystoscopy is clear, it is appropriate to perform the second check cystoscopy 1 year from initial resection and subsequent controls yearly. One should note that the study group included the most suitable patients for cystoscopic follow–up according to size and multiplicity of the tumor. This change in policy is further supported by the fact that progression occured in less than 1% in this group of patients.

A novel surveillance protocol for stage I nonseminomatous germ cell testicular tumours.

To report the results of a novel surveillance policy for stage I nonseminomatous germ cell tumours (NSGCTs).

Ureteropelvic junction obstruction and coexisting renal calculi in children: role of metabolic abnormalities

OBJECTIVES To identify the role of metabolic risk factors in the development of renal calculi associated with ureteropelvic junction obstruction (UPJO) in children. METHODS A metabolic evaluation, including serum biochemistry and measurement of daily urinary calcium, creatinine, oxalate, citrate, magnesium, urate, and inorganic phosphorus, was carried out in three different populations as follows: UPJO group, 12 children with UPJO and coexisting nephrolithiasis (median age 6 years); calcium stone formation (CSF) group, 90 children with normal urologic anatomy and calcium urolithiasis (median age 7 years); control group, 24 healthy children (median age 7.3 years). The investigation data of the three groups were compared. RESULTS The stone composition was calcium oxalate in 9 of the 12 children with UPJO. The investigation data of the UPJO group and CSF group were not significantly different. Both groups differed from the control group in a similar manner. The UPJO and CSF groups excreted more oxalate (P = 0.067 and 0.014, respectively) and less citrate (P = 0.020 and 0.010, respectively) than did the control subjects. CONCLUSIONS Abnormal urinary biochemistry seems to have an additional role in the high incidence of nephrolithiasis in children with upper tract anatomic anomalies, and the urinary biochemistry should be screened in such children.

Comparison of BTA stat and NMP22 Tests in the Detection of Bladder Cancer

Objective: This study aimed to compare the BTA (bladder tumour antigen) stat and urinary nuclear matrix protein (NMP22) test s in the detection of bladder cancer. Material and methods: The office-based qualitative BTA stat and the laboratory-based quantitative NMP22 tests were studied in the same urine samples obtained from 49 patients with a high suspicion of bladder cancer and 20 healthy subjects. Results: A tumour was identified in 36 patients after the cystoscopy. BTA stat demonstrated a sensitivity of 89%, which was superior to the sensitivity of 66.6% with the NMP22 test in detecting the bladder cancer (p < 0.02). The sensitivities for grade I tumours with BTA stat and NMP22 were 55.5% and 33.3%, respectively. The sensitivity of BTA stat was 100% for tumour categories except for the pTa and grade I tumours. No positive result was observed with both tests among the healthy subjects. The specificities for BTA stat and NMP22 were 78.7% and 69.6%, respectively. Conclusions: The BTA stat test was significantly more sensitive than the NMP22 test in the detection of bladder cancer. Although the sensitivity of BTA stat was not sufficient to replace cystoscopy, its ease and low cost may play a role in reducing the number of control cystoscopies, especially in patients with low risk of progression.

CYSTINE CALCULI IN CHILDREN: THE RESULTS OF A METABOLIC EVALUATION AND RESPONSE TO MEDICAL THERAPY

PURPOSE We describe baseline metabolic abnormalities and evaluate mercaptopropionylglycine plus potassium citrate treatment for urinary abnormalities and to prevent new stone formation in children with cystine stones. MATERIALS AND METHODS Daily urinary excretions of calcium, oxalate, citrate, magnesium, urate and phosphorus were determined in 18 children with cystine stone and 24 healthy children. The cystine stone cases were treated with 10 to 15 mg./kg. alpha-mercaptopropionylglycine and 1 mEq./kg. potassium citrate daily for a median 15 months. The potassium citrate dose was adjusted to render urinary pH 6.5 to 7.5. RESULTS There was no significant difference in baseline metabolic profile between the cystine stone and control groups except for citrate. The cystine stone group excreted less citrate than the control group (p = 0.044). After treatment median plus or minus standard deviation urinary cystine 245 +/- 233 to 140 +/- 106 mmol./mol. creatinine decreased from (p = 0.015), and urinary citrate increased from 255 +/- 219 to 729 +/- 494 mg./1.73 m.2 (p = 0.003). No serious adverse reaction was noted. Of the 15 patients with followup data 5 (33%) had 8 recurrent calculi (recurrence rate 0.64 per patient year). CONCLUSIONS Our results suggest that further investigation of low citrate excretion is needed in cystinuric children. Potassium citrate therapy is effective in increasing urinary pH and urinary citrate. However, high recurrence rate and persistent cystinuria in our patients emphasize the inadequacy of our treatment schedule in the prevention of recurrent cystine calculi.

Evaluation of nuclear matrix protein 22 (NMP22) as a tumor marker in the detection of bladder cancer.

We prospectively evaluated the performance of urinary NMP22 test in the detection of transitional carcinoma (TCC) of the bladder. Urine samples were obtained from 39 patients with known bladder cancer, 37 patients with primary hematuria, 18 with benign urological conditions and 20 healthy subjects. Overall sensitivity and specificity of NMP22 with reference value of 10U/ml was 72 and 73%, respectively. Sensitivity for pT1 and pT2 tumors was 83%, whereas that for pTa tumors was 55%. When the test was determined before and after transurethral resection (TUR) of bladder tumor, it was shown that the TUR effected the NMP22 level. Urinary NMP22was highly sensitive for high-risk bladder cancer. However, the sensitivity of the test is somewhat lower in low grade and stage tumors. Additionally,the effect of previous resection limits its value in the follow up of patients with superficial tumors. The larger series with longer follow up may lead us to determine the time to neglect the effect of TUR on NMP22 and the test kit should be upgraded by the manufacturer to exclude the false positive results due to inflammatory conditions.