Efficacy and safety of a new device for intravesical thermochemotherapy in non-grade 3 BCG recurrent NMIBC: a phase I-II study.

PURPOSE: We report for the first time the activity and safety of Unithermia(®) (Elmedical Ltd, Hod-Hasharon, Israel), a novel device for administration of MMC-C with hyperthermia (HT), that employs conductive heating, in a series of non-grade 3 non-muscle-invasive bladder cancer (NMIBC) that failed Bacillus Calmette-Guerin (BCG). METHODS: Patients with non-grade 3 NMIBC recurring after at least a full induction course of BCG were eligible for this phase I-II prospective single-arm study. Six weekly instillations with Unithermia(®) were scheduled following complete TUR. Primary end points were treatment safety and response rate (RR), and the latter defined as the absence of any unfavourable outcome at 12 months. Any grade 3 and/or muscle-invasive (T > 1) recurrence was considered disease progression. Kaplan-Meier estimation of the time to recurrence and progression, cancer-specific survival and overall survival was taken as secondary end points. RESULTS: Thirty-four eligible patients entered the study between January 2009 and April 2011. RR was documented in 20/34 (59%). Among the 14/34 (41%) non-responders, four developed G3 disease, one developed carcinoma in situ, and one progressed to muscle-invasive bladder cancer, with an overall 18% progression rate at 1 year. At a median follow-up of 41 months, recurrence and progression rates were 35.3 and 23.5%, respectively. Toxicity did not go beyond grade 2 except in five cases. CONCLUSIONS: Initial experience with MMC-HT with Unithermia(®) showed an interesting activity and safety profile in non-grade 3 NMIBC recurring after BCG, suggesting a role as second-line therapy in this selected subgroup of NMIBC.

The impact of intravesical gemcitabine and 1/3 dose Bacillus Calmette-Guérin instillation therapy on the quality of life in patients with nonmuscle invasive bladder cancer: results of a prospective, randomized, phase II trial.

PURPOSE: Bacillus Calmette-Guérin and intravesical chemotherapy represent viable adjuvant options for intermediate risk nonmuscle invasive bladder cancer. Although bacillus Calmette-Guérin is perceived as less tolerable than intravesical chemotherapy, to our knowledge no comparative studies have addressed quality of life issues. We compared the quality of life of patients with nonmuscle invasive bladder cancer who received adjuvant intravesical gemcitabine or 1/3 dose bacillus Calmette-Guérin. MATERIALS AND METHODS: Our multicenter, prospective, randomized, phase II study included 120 patients with intermediate risk nonmuscle invasive bladder cancer. Of these patients 88 remained assessable at 1-year followup. Only 1 patient was withdrawn because of adverse events. Overall 61 patients received 2,000 mg/50 cc gemcitabine weekly for 6 weeks (maintenance monthly for 1 year) while 59 received 1/3 dose bacillus Calmette-Guérin Connaught weekly for 6 weeks (maintenance 3 weekly instillations at 3, 6 and 12 months). Quality of life was measured by the EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0) and QLQ-BLS24 (Quality of Life Superficial Bladder Cancer-Specific 24) questionnaires. Group differences were calculated using ANOVA (ANOVA/MANOVA). RESULTS: Treatment was well tolerated in both groups, although local and systemic side effects were more frequently reported in the bacillus Calmette-Guérin arm. Multivariate analyses showed no significant differences between the 2 groups in all quality of life dimensions. No significant changes over time in quality of life domains were detected for patients on bacillus Calmette-Guérin and gemcitabine except for physical functioning, which decreased significantly in both groups (p = 0.002). No significant differences were detected in terms of recurrence and progression between the 2 groups at 1-year followup. CONCLUSIONS: While a higher rate of side effects, albeit mild to moderate, was detected with 1/3 dose bacillus Calmette-Guérin compared to gemcitabine, our study failed to show significant differences between the 2 drugs in terms of quality of life.

Transurethral resection of the prostate in kidney transplant recipients: urological and renal functional outcomes at long-term follow-up.

OBJECTIVES: To assess prospectively the safety and efficacy of transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH) in patients who have undergone renal transplantation (RT). To assess the impact of TURP on renal graft function. PATIENTS AND METHODS: Urological and renal functional outcomes of TURP performed in RT recipients for treatment of lower urinary tract obstruction attributable to BPH were prospectively assessed in a series of 32 consecutive patients with follow-up of ≥48 months. Maximum urinary flow rate (Qmax ) at uroflowmetry, International Prostate Symptom Score (IPSS), post-void residual urine volume (PVR), haemoglobin and serum creatinine (sCr) levels were recorded before TURP and 1, 6, 24 and 48 months after the procedure. The trends in these variables after TURP were evaluated. Early and delayed complications were assessed and graded according to the Clavien classification system. RESULTS: TURP was performed at a mean of 6 months after RT. No intraoperative complications occurred. Seven postoperative complications were observed (21.9%): two Clavien grade II and five Clavien grade IIIa. Qmax , IPSS and PVR improved significantly after surgery and the improvement was maintained until 48 months. No patient required a repeat TURP during follow-up. SCr levels significantly decreased 1 and 6 months after TURP and did not significantly increase at long-term follow-up. CONCLUSIONS: TURP for lower urinary tract obstruction attributable to BPH in RT recipients is safe and effective since it improves urinary flow, bladder emptying and related urinary symptoms. TURP allows an early significant improvement of graft function that is maintained at a follow-up of 48 months.

Are referral centers for non-muscle-invasive bladder cancer compliant to EAU guidelines? A report from the vesical antiblastic therapy Italian study.

INTRODUCTION: Adherence to international guidelines is viewed as a prerequisite for optimal medical care delivery. Previously reported surveys for non-muscle-invasive bladder cancer (NMIBC) employed mailed questionnaires to urologists or patients resulting in conflicting degrees of agreement with existing guidelines. In the current study, contemporary information on the management of NMIBC was generated from a sample of italian centers. PATIENTS AND METHODS: Eight Italian referral centers for the treatment of NMIBC were asked to collect information relative to all consecutive patients with a histology-proven NMIBC undergoing a transurethral resection from January 1 to March 31, 2009. The primary study objective was to verify the level of adherence of disease management with European guidelines. RESULTS: 344 patients resulted in being evaluable. 49.2% of high-risk patients underwent a repeat transurethral resection. Bacillus Calmette-Guérin was employed in 35% of cases, while chemotherapy was in 22%. An early single regimen was adopted in 136 patients and only in 1 out of 3 low-risk patients. High-risk NMIBC received bacillus Calmette-Guérin and chemotherapy as first-line therapy in 66 and 12.5% respectively. After 3 months, cystoscopy had been reported for 82.5% of patients with a recurrence rate of 13%. CONCLUSION: Adherence of Italian Institutions to EAU guidelines was optimal when reporting baseline variables. Significant degrees of discrepancy emerged in treatment choices.

Morbidity and quality of life in elderly patients receiving ileal conduit or orthotopic neobladder after radical cystectomy for invasive bladder cancer.

OBJECTIVES: The objectives of the study were to evaluate morbidity, survival, and quality of life (QoL) in elderly patients with invasive bladder cancer who received an orthotopic neobladder or an ileal conduit. METHODS: The charts of 85 patients, aged 75 or older (median age 78), who had received an ileal conduit (n = 53) or an orthotopic neobladder (n = 32) after radical cystectomy at 3 Italian institutions in the period January 2000 to September 2004 were retrospectively reviewed. Perioperative and postoperative complications were recorded, as well as survival data at last follow-up. QoL was evaluated in 34 of 37 patients who were alive at the time of analysis by using the European Organisation for Research and Treatment of Cancer (EORTC) instruments quality of life questionnaire C30 (QLQ-C30) and QLQ-muscle-invasive bladder cancer module (QLQ-BLM). RESULTS: Multiple regression analysis showed that stage significantly affected survival whereas the type of urinary diversion did not. Global Health Status (GHS) scores in the neobladder group were higher than in the ileal conduit group but the difference was not statistically significant. The scores of all the QLQ multi-item scales and single-item measures were comparable in the 2 groups. Overall, 56% and 25% daytime and nighttime complete continence rates were observed in patients with an orthotopic neobladder. CONCLUSIONS: The results of our retrospective analysis suggest that an orthotopic neobladder can be suitable for elderly patients with no additional morbidity compared with an ileal conduit. Both types of diversion seem to result in acceptable scores for most aspects of QoL, including urinary symptoms and continence rate. These figures may be helpful in the preoperative counselling of elderly patients with bladder cancer.

Primary adenocarcinoma of the rete testis: diagnostic problems and therapeutic dilemmas.

We describe a rare case of a malignant tumour of the rete testis which was diagnosed incidentally during scrotal surgery for an apparently benign left hydrocele. Adenocarcinoma of the rete testis is a malignancy with a poor prognosis. The beneficial role of prophylactic retroperitoneal lymphadenectomy is controversial due to the extremely low number of reported cases and the occasional description of primary lymphatic spread outside the retroperitoneal space.

Is radical prostatectomy feasible in all cases of locally advanced non-bone metastatic prostate cancer? Results of a single-institution study.

OBJECTIVES: Previous prospective studies of the surgical treatment of locally advanced prostate cancer have enrolled patients selected on the basis of a limited T3 disease extension. The aim of the present study was to assess the feasibility and the oncologic outcome of radical prostatectomy administered to a consecutive unselected series of advanced, non-bone metastatic prostate cancers. METHODS: Between March 1998 and February 2003 radical prostatectomy was offered at our institution to any patient diagnosed with prostate cancer with no sign of extranodal metastatic disease. Data on morbidity and survival for 51 clinically advanced cases (any T>/=3, N0-N1, or any N1 or M1a disease according to the TNM 2002 classification system) operated on by a single expert surgeon were compared with a series of 152 radical prostatectomies performed during the same period by the same operator for clinically organ-confined disease. Adjuvant treatment was administered according to current guidelines. RESULTS: The two groups did not differ significantly in surgical morbidity except for blood transfusion, operative time, and lymphoceles, which showed a higher rate in patients with advanced disease. The Kaplan-Meier estimate of overall survival and prostate cancer-specific survival at 7 yr were 76.69% and 90.2% in the advanced disease group and 88.4% and 99.3% in the organ-confined disease group, respectively. CONCLUSIONS: Even in the scenario of extensive surgical indications up to M1a disease, radical prostatectomy proved to be technically feasible and to have an acceptable morbidity rate compared with organ-confined disease. Our initial survival data strengthen the role for surgery as an essential part in the multimodal approach to treating advanced prostate cancer.

An unusual presentation of ureteric colic.

A patient presented with acute pain in the right iliac fossa and was found to have a small stone in the lower ureter of a crossed ectopic right kidney. This unique presentation highlights the potential pitfalls that may occur when assessing an acute pain in the right iliac fossa and reminds the invaluable role of IVP.

Phase II study to investigate the ablative efficacy of intravesical administration of gemcitabine in intermediate-risk superficial bladder cancer (SBC).

OBJECTIVE: Phase I studies have so far demonstrated that intravesical Gemcitabine up to a 40 mg/ml concentration is well tolerated and has a substantial ablative activity on high-risk BCG refractory SBC. New treatment options are needed for intermediate-risk SBC recurring after conventional intravesical treatments. The purpose of the present study was to investigate the ablative efficacy of intravesical Gemcitabine on intermediate-risk SBC. METHODS: The study was designed as a two-stage phase II trial, with a sample size of 39 patients. The efficacy of intravesical Gemcitabine at a concentration of 40 mg/ml (2000 mg in 50 ml saline solution) administered weekly for 6 weeks was assessed on a single marker tumour left in the bladder after a complete TUR of all other lesions. Patients underwent TUR or biopsy at the site of the marker lesion 2 weeks after completion of the treatment. RESULTS: Complete response was observed in 22 out of 39 patients (56%). No progression was observed among the 17 non-responders. Neither systemic nor local side effects generally exceeded grade I toxicity. CONCLUSION: The ablative effect of Gemcitabine produced a higher number of responses than the minimum required by the protocol to indicate a significant probability of drug efficacy. It is worth testing the drug in phase III trials to assess for durability of response.

Upper urinary tract complications in pregnant women with an ileal conduit. Lessons learned from two cases.

We describe the occurrence of severe upper urinary tract complications during pregnancy in two women with an ileal conduit. The first patient developed several episodes of left pyelonephritis throughout the duration of her pregnancy but never received proper antibiotic prophylaxis. Intravenous urography performed after delivery documented bilateral staghorn kidney stones and a non-functioning left kidney. The second patient developed severe left loin pain and a high temperature during the fourth month of pregnancy after discontinuing antibiotic prophylaxis. An MRI urogram demonstrated compression of the ureter by the foetus. Symptoms were relieved as soon as the antibiotic prophylaxis was resumed and the pain remained under control with the occasional use of paracetamol until delivery. Based on these observations it appears that the left upper urinary tract may be more prone to dilatation in pregnant patients with an ileal conduit and antibiotic prophylaxis is mandatory throughout the duration of the pregnancy in order to minimize the risk of severe upper urinary tract complications.