Haluk Ozen

The Effect of Repeat Transurethral Resection on Recurrence and Progression Rates in Patients With T1 Tumors of the Bladder Who Received Intravesical Mitomycin: A Prospective, Randomized Clinical Trial

PURPOSE We compared the outcomes of repeat transurethral resection plus intravesical mitomycin C with initial transurethral resection of bladder plus intravesical MMC in patients with newly diagnosed pT1 transitional cell carcinoma of the bladder in terms of recurrence, progression and overall survival. MATERIALS AND METHODS Of 148 newly diagnosed patients with T1 bladder cancer 142 were prospectively randomized in 2 groups between January 2001 and January 2005. A total of 74 patients underwent second TURB and received adjuvant MMC intravesically (group 1) and 68 patients received adjuvant MMC following the initial TURB (group 2). All repeat TURB operations were performed 2 to 6 weeks following initial TURB. Patients with incomplete resection, Cis or muscle invasive disease were excluded from study. The first dose of mitomycin C (40 mg per week for a total of 8 weeks) was instilled intravesically in all patients during the first 24 hours after the last surgery. RESULTS Mean followup was 31.5 months (range 6 to 48) with no difference between the 2 groups. The rate of recurrence-free survival was 86.35% (SE 0.4%), 77.67% and 68.72% in group 1, and 47.08%, 42.31% and 37.01% in group 2 for the first, second and third year, respectively (overall 74.32% vs 36.76%, log rank 0.0001). Recurrence was observed in 19 of the 74 (25.68%) patients in group 1 and in 43 of the 68 (63.24%) patients in group 2. Ten of the 19 (52.63%) patients in group 1 and 35 of the 43 (81.39%) patients in group 2 had recurrence within 12 months. Recurrence was observed in 17.6%, 25% and 60% of patients with G1, G2 and G3 tumors, respectively, in group 1. The same rates for group 2 were 25%, 64% and 90%. The RFS rate was significantly worse in the high grade group (G2 and G3) (p <0.001). Progression was observed at 4.05% for group 1 compared to 11.76% for group 2 (log rank 0.0974). OS was 91.89% and 89.71% in group 1 and 2, respectively (log rank 0.732). CONCLUSIONS The high recurrence rate in patients who did not undergo ReTUR is due to a high residual tumor rate following initial TURB. The benefit of ReTUR is especially true for high grade tumors. Since intravesical MMC was present in both groups, this study has shown that intravesical chemotherapy does not compensate for inadequate resection. Progression does not seem to be affected by ReTUR although there was a trend favoring the ReTUR group. We recommend ReTUR for patients with primary high grade T1 disease to achieve better recurrence-free survival.

Prognostic Significance of Bladder Tumor History and Tumor Location in Upper Tract Transitional Cell Carcinoma

PURPOSE We studied prognostic factors for 5-year disease specific and recurrence-free survival in patients treated for upper urinary tract transitional cell carcinoma. MATERIALS AND METHODS Since July 1987, 72 patients with a mean age of 58.9 years have undergone nephroureterectomy with bladder cuff excision. Median followup was 62.2 months (range 6 to 192). Patient age, sex, detection duration and mode, bladder tumor history, smoking habit, stone disease history, and tumor stage, grade and location were evaluated as prognostic factors. RESULTS Overall 5-year disease specific and recurrence-free survival rates were 74.9% and 67.8%, respectively. Univariate analysis revealed anemia, positive bladder tumor history, T stage, grade and tumor location in the upper tract as significant prognostic factors. On multivariate analysis T stage, grade and tumor location in the urothelium were the only significant variables for the 5-year disease specific and recurrence-free survival rates. CONCLUSIONS High tumor stage and grade, and ureteral location were significantly associated with worse disease specific and recurrence-free survival in patients with upper urinary tract transitional cell carcinoma. Our results may help define the patient groups that need adjuvant therapy and they may form a basis for further controlled studies.

Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus

BACKGROUND The successful excision of a renal cell carcinoma (RCC) invading the inferior vena cava (IVC) remains a technical intraoperative challenge and requires a careful preoperative surgical management planning. Although a radical operation remains the mainstay of the therapy for RCC, the optimal management of the patients with RCC causing IVC tumor thrombus remains unresolved. In this study, we reviewed our experience in this group of patients and herein report the results. METHODS Between July 1990 and August 1998, 11 patients with RCC with IVC tumor thrombus underwent surgical treatment. The mean patient age was 54.2 years and the male to female ratio was 1.75. The cephalad extension of the tumor was suprarenal in all cases, being infrahepatic in 6 patients, intrahepatic in 2, and suprahepatic with right atrial extension in 3 patients. All tumors were resected via inferior vena cava isolation and, when necessary, extended hepatic mobilization and Pringle maneuver, with primary or patch closure of vena cavotomy. Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) were used in 3 patients. RESULTS The mortality rate was 9.1% (1 patient was lost on the 11th postoperative day). Complications occurred in 3 patients. The remaining 10 patients (90.9%) could be successfully discharged from hospital. Two of them were lost during follow-up because of tumor progression at the 43rd and 54th postoperative months. The 10-year Kaplan-Meier survival estimate was 71.4%, with a mean follow-up of 4.6 years. The presence of lymph node metastases and perinephric spread seemed to possess an adverse effect on the survival. Although the groups included small numbers of patients, there was no significant difference in survival in regard to the different levels of tumor thrombus extension into the vena cava. CONCLUSIONS Surgical treatment is the preferred approach to patients with RCC and IVC tumor thrombi as it provides markedly better results when compared with the other therapeutical modalities. We believe that complete surgical excision of the tumor and the resulting thrombus with appropriate preoperative staging and a well-planned surgical approach, using CPB and DHCA when necessary, provide an acceptable long-term survival with a good quality of life expectation.

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.

Prospective long-term followup of patients with asymptomatic lower pole caliceal stones.

PURPOSE The intervention time of asymptomatic lower pole calculi remains controversial. In this prospective study we evaluated the natural history and progression rate of asymptomatic lower pole stones. MATERIALS AND METHODS Patients were followed every 6 months. Computerized tomography in even years, ultrasound scan in odd years after initial visit and abdominal plain films between these visits were evaluated. The largest diameter was measured for each calculus and the cumulative diameter was calculated for cases of multiple stones. Disease progression was defined as pain experienced during followup, stone growth or the need for intervention. RESULTS A total of 24 patients, 14 male and 10 female, were followed for a mean of 52.3 months (range 24 to 72). Of the 24 patients 3 had bilateral lower pole stones. Mean cumulative stone diameter at presentation was 8.8 mm (range 2.0 to 26.0). Progression in stone size was demonstrated in 9 of 27 renal units (33.3%) with 2 (11.1%) requiring intervention. There was no need for intervention during the first 2 years of followup. Three stones passed spontaneously without any symptoms. Pain developed in 3 patients during followup, and 2 of them passed a stone and responded to the analgesics without further treatment. None of the patients had a pyelonephritic attack during followup. CONCLUSIONS Our results showed that observation could be considered for patients with asymptomatic lower pole stones. However, patients should be counseled about the 33% disease progression and 11% intervention rates.

Is a Second Transurethral Resection Necessary for Newly Diagnosed pT1 Bladder Cancer

PURPOSE We evaluated the potential benefit of a second transurethral resection in patients with newly diagnosed pT1 transitional cell carcinoma of the bladder. MATERIALS AND METHODS Between January 2001 and May 2003, 80 patients with stage T1 bladder cancer were included in this protocol in which all patients prospectively received second TUR within 2 to 6 weeks following the initial resection. Patients with incomplete resections were excluded from study. The pathological findings of the second TUR were reviewed. RESULTS Of the 80 patients who underwent second resection, 18 (22.5%) had macroscopic tumors before resection. However, with the addition of microscopic tumors, overall residual disease was determined in 27 (33.8%) patients. Of the 27 patients 7 had pTa, 14 had pT1, 3 had pT1+pTis and 3 had pT2 disease. Residual cancers were detected in 5.8%, 38.2% and 62.5% in G1, G2 and G3 tumors, respectively. The risk of residual tumor directly correlated with the grade of the initial tumor (p = 0.009). CONCLUSIONS Although second TUR dramatically changed the treatment strategy in a small percentage of cases, we strongly recommend performing second TUR in all cases of primary pT1 disease, especially in high grade cases.

Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide.

Study Type – Therapy (RCT)

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.

Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer: results of the European compassionate-use programme

BACKGROUND Cabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access programmes (EAPs) were established worldwide, allowing access to cabazitaxel before its commercial availability. Preliminary results of the European CUP/EAP, focusing on the elderly population (aged > or =70 years), are reported. PATIENTS AND METHODS Enrolled patients with progressive mCRPC received cabazitaxel (25 mg/m2) plus 10mg oral prednisone/prednisolone every 3 weeks until disease progression, death, unacceptable toxicity or physician/patient decision. Safety was analysed by age group (<70, 70-74 and > or =75 years). The influence of selected variables on grade > or =3 neutropenia and/or neutropenic complications was analysed in multivariate analysis. RESULTS 746 men were enrolled (<70 years, n=421; 70-74, n=180, > or =75 years, n=145). Number of cabazitaxel cycles, dose reductions for any cause, dose delays possibly related to cabazitaxel adverse events, and tolerability were similar in the three age groups. Prophylactic granulocyte colony-stimulating factor (G-CSF) use was more common in men aged > or =0 years. In multivariate analysis, age > or =75 years, treatment cycle 1, and neutrophil count <4000/mm3 before cabazitaxel injection were associated with increased risk of developing grade > or =3 neutropenia and/or neutropenic complications. Prophylactic use of G-CSF at a given cycle significantly reduced this risk by 30% (odds ratio 0.70, p=0.04). CONCLUSION The results suggest that cabazitaxel has a manageable safety profile in everyday clinical practice. Prophylactic use of G-CSF, especially at cycle 1 and in men aged > or =75 years, is important and improves tolerability in senior adults treated with cabazitaxel.