Carcinoma uroteliale in cisti pielogena

Urothelial carcinoma in a pyelocaliceal cyst Renal complex cysts are lesions whose nature can be either benign or malignant. Depending on the presence of septa, solid components, enhancement or calcifications, they are distinguished according to the Bosniak classi- fication based on CT findings, as well as MRI and ETG. We report a rare case of urothelial carcinoma, originating over a pyelocalyceal cyst in a 50-year-old man, and classified as Bosniak IIF by CT and MRI investigations

Mitomycin C from birth to adulthood

Mitomycin C (MMC) intravesical therapy for "superficial" papillary bladder tumors was firstly introduced in the early seventies with promising results. In the following years, several pharmacokinetic studies investigated its mechanism of action to optimize the intravesical administration. Numerous studies confirmed thereafter both the ablative and the prophylactic efficacy and the low toxicity of MMC when intravesically given. In 1984, a complete response rate of 42% in 60 patients not responsive to thiotepa was reported with intravesical MMC at the dose of 40 mg diluted in 40 ml for 8 weeks. In the following decades, many large randomized studies showed the benefit of intravesical prophylaxis with MMC versus transurethral resection (TUR) alone. Since 2002, the role of adjuvant intravesical chemotherapy and of an early MMC instillation in preventing recurrence compared with TUR alone has been confirmed by large meta-analyses and stated by the European Association of Urology (EAU) guidelines. The need for further intravesical chemotherapy after the early instillation in patients at intermediate-high risk of recurrence has been proved by several trials. Although intravesical Bacillus Calmette-Guerìn (BCG) is considered the best choice for high-risk patients and MMC for the low-risk group, both MMC and BCG can be given to prevent recurrence in intermediate-risk patients. However, the higher efficacy of BCG over MMC is evident only if maintenance regimen is administered. Despite its proven efficacy, immediate intravesical MMC is not yet fully entered in common clinical practice and efforts should be made by the urologists to optimize its adoption

Does the Compliance to Intravesical BCG Differ between Common Clinical Practice and International Multicentric Trials?

INTRODUCTION: The aim of this study was to analyze the reasons for intravesical BCG interruption in clinical practice. BCG for at least one year is advocated as the best regimen to treat high-risk non-muscle invasive bladder cancer (NMIBC). However, almost 50% of patients don't complete it. Toxicity accounts for 10% of dropouts in international trials. MATERIALS AND METHODS: Patients with T1HG NMIBC undergoing 1-year BCG were enrolled in this study. BCG was administered for one year. Toxicity and causes of treatment interruption were recorded. RESULTS: A total of 411 patients were enrolled in the study. Out of these total number of patients, 380 (92.5%) completed the induction cycle and 215 (52.3%) completed one year. Toxicity requiring interruption or postponement was recorded in 25 (6.1%) and 60 (14.6%) patients. Ninety-three patients (30.2%) stopped BCG, 9 (9.7%) for recurrence and 14 (15.1%) for grade-3 toxicity. Intriguingly, 55 (59.1%) patients refused BCG due to mild discomfort and deterioration in quality of social life. CONCLUSIONS: Grades 2-3 toxicity causes BCG interruption in a few cases. Almost 60% of interruptions are attributable to persistent grade-1 toxicity, which is inadequately treate

Genitourinary Symptoms-Patient Help-Seeking and General Practitioner Management: An Outpatient Based Survey at a Tertiary Hospital in Southern Italy

Introduction: General knowledge of most common genitourinary diseases is often lacking. In this survey we evaluated the attention given by patients and general practitioners to genitourinary symptoms, and particularly to hematuria and potential early signs of genitourinary cancer. Methods: A structured self-administered questionnaire was administered to outpatients before the urological consultation. The questionnaire consisted of 4 multiple choice questions to record the level of patient awareness of urological symptoms, the importance given to gross hematuria, the interval between the onset and the visit, the regularity of physical examination and the first-level investigations indicated by the general practitioner before the urological consultation. Results: A total of 327 self-administered questionnaires were obtained from 358 consecutive patients for a compliance rate of 91.3%. Asymptomatic gross hematuria was present in 91 cases (27.8%). The first episode of hematuria was not reported by 20% of the patients, with a median delay of 11 months. Only 77 patients (23.6%) in the last 5 years had received a physical examination including the external genitalia. Laboratory and/or imaging investigations were indicated before urological counseling in 172 (52.6%) patients. Conclusions: The majority of patients underestimated urological symptoms. Less than 25% and 50% of patients had a physical examination and first-level investigations performed before urological counseling, respectively. Our survey reveals an important lack of awareness of genitourinary symptoms that could be responsible for delayed diagnosis and inappropriate treatment

MULTI-ISTITUTIONAL CONTROLLED STUDIES DO NO REFLECT THE PATIENT’S COMPLIANCE TO BCG ENCOUNTERED IN CLINICAL PRACTICE. RESULTS ON 411 PATIENTS

INTRODUCTION AND OBJECTIVES BCG maintenance for at least one year is advocated by urological guidelines as the best intravesical regimen in high-risk non muscle invasive bladder cancer (NMIBC), conservatively treated. Noteworthy, a relevant percentage of patients does not complete the planned treatment. The aim of this study was to analyze the reasons for treatment interruption and low compliance. METHODS Consecutive patients affected by T1HG NMIBC undergoing conservative management with adjuvant BCG entered the study. The Connaught BCG strain was administered intravesically according to the South West Oncology Group schedule for one year, 81mg diluted in 50 ml of saline solution, starting 21-30 days after TUR. Toxicity and causes of treatment interruption were recorded. RESULTS Between 2000 and 2012, intravesical BCG with 1-year maintenance regimen was proposed to 411 patients. Out of them, 380 (92,5%) completed the induction cycle and 308 (81%) started the maintenance. A total of 215 (52.3%) completed the scheduled one-year treatment. Toxicity requiring treatment interruption was recorded in 25 (6.1%) patients only. In 60 patients (14.6%) a delay of one or more instillations was necessary. Grade-I toxicity, not requiring therapy interruption or delay, was recorded in 193 (46.9%) cases. In our experience, the patient's compliance registered during the induction cycle reached 92%, confirming the low toxicity and the good patients' acceptance of the 6-week induction. However, between the end of the induction course and the first maintenance instillation, 50 patients (13%) became reluctant to treatment for many personal reasons unrelated to toxicity and 22 (6%) were excluded for suspicious bladder lesion at cystoscopy. Moreover, patients' compliance to maintenance decreased from 81% at 3 months to 56.6% at 12 months. Surprisingly, the rate of drop-out (15%) remained stable at 6 and 12 months. Mild toxicity and social discomfort were the mean reasons for dropout during maintenance (60%). CONCLUSIONS Severe toxicity caused BCG interruption in a limited amount of cases. Almost 60% of treatment interruptions was attributable to low grade toxicity, inadequately considered by the urologists. The personal difficulties related to the prolonged treatment and the limited patients' awareness of the therapeutic value of maintenance were other important reasons. A structured periodical counseling and a timely recognition and therapy of mild but persistent symptoms, might significantly ameliorate patients' acceptance of BCG maintenance

THE ROLE OF INTRAVESICAL GLYCOSAMINOGLYCANS IN TOXICITY INDUCED BY ADJUVANT INTRAVESICAL THERAPY: GENETIC LABORATORY EVIDENCE

Introduction and Objectives: The intravesical administration of hyaluronic acid and chondroitin sulphate solution (HA-CS) has been proven active in patients affected by interstitial cystitis (1). The gene expression of fibronectin (FN) in bladder washings has recently been correlated with local toxicity of adjuvant intravesical therapy (2). The aim of the study was to investigate the genetic evidence of the healing or protective action that HA-CS could carry out also in patients suffering from topical toxicity induced by intravesical adjuvant therapy given for non-muscle invasive bladder cancer. Materials and Methods: The study included 50 patients submitted to adjuvant intravesical therapy with mitomycin, epirubicin or bacillus Calmette–Guérin (BCG). Ten age-matched healthy patients were enrolled as control group. Before, during and after intravescical therapy, bladder washing samples were collected to investigate the gene expression of FN. In 9 more patients the samples were collected also immediately before and a week after the instillation of HA-CS. Topical toxicity was classified into 3 grades: 0-1, light (no medical therapy); 2, moderate (medical therapy); 3, severe (instillation postponed). Bladder washing samples were analyzed by isolation of cellular RNA using a miRNeasy Mini Kit (Qiagen®). RT-PCR was performed in order to analyze FN gene expression. Changes in the FN content were calculated using the ΔΔCt method after normalization with endogenous reference 18s rRNA and calibrating Ct value for each RNA obtained for triplicate reactions. Statistical analysis was performed to correlate the FN gene expression to tumor characteristics, treatment, topical toxicity and intravesical administration of HA-CS. Results: FN median value before the adjuvant treatment was 1.1-fold, with higher levels in patients with multiple tumors (median FN=1.5; mean=3.9; p=0.0003). Twenty patients (34%) showed grade 2-3 toxicity. Compared to controls (FN=1), FN increased during therapy a median of 4-fold (range=0.2-45.2; mean=7.5) in presence of grade 2-3 toxicity, remaining stable in asymptomatic patients (median FN=0.6; range=0.1-3.2), with a statistically significant difference (p=0.0005). In 9 patients, one week after single instillation of HA-CS, the median FN gene expression decreased from 3.2 to 0.33 with concomitant symptomatic relief. Discussion and Conclusion: Fibronectin is a fundamental element for the repair of urothelial damage. FN gene is probably activated by the need of fibronectin for healing process and down-regulated by the integrity of bladder urothelium. In our preliminary experience FN gene expression in bladder washings resulted strictly related to local toxicity induced by intravesical therapy. It increases after transurethral resection (TUR) of multiple tumors due to the greater urothelial damage. It increases also during intravesical therapy reaching the highest levels in case of severe toxicity due to the extensive urothelial damage. A single instillation of intravesical hyaluronic acid and chondroitin sulphate solution induces a rapid reduction of FN gene expression levels, particularly when high levels are present. The FN gene downregulation induced in patients with toxicity is due to intravesical therapy and might represent an objective and measurable indicator of the healing activity of intravesical instillation of HA-CS. 1 Van Agt S et al: Treatment of interstitial cystitis by intravesical instillation of hyaluronic acid: A prospective study on 31 patients, Prog Urol 21: 218-225, 2011. 2 Serretta V et al: Fibronectin (FN), Epidermal Growth Factor-Receptor (EGF-R) and Heparin-Binding Epidermal Growth Factor-like Growth Factor (HB- EGF) urinary expression and topical toxicity of adjuvant intravesical therapy for non muscle invasive bladder cancer (NMI-BC). 28th EAU Congress, Stockholm, 2014. Eur Urol Suppl 13: e409, 2014

CORRELATION BETWEEN FIBRONECTIN GENE EXPRESSION AND LOCAL TOXICITY INDUCED BY ADJUVANT INTRAVESICAL THERAPY

Discomfort and local toxicity often cause interruption of intravesical adjuvant therapy for non muscle invasive bladder cancer (NMIBC). A marker of urothelial damage could be helpful for early detection and monitoring of topical toxicity to ameliorate the tolerability of the intrravesical therapy. The aim of the study is to investigate the correlation between the gene expression of Fibronectin (FN) in bladder washings and local toxicity of adjuvant intravesical therapy