Intravesical electro-osmotic administration of mitomycin C.

Bladder cancer is very common and most cases are diagnosed as nonmuscle invasive disease, which is characterized by its propensity to recur and progress. Intravesical therapy is used to delay recurrence and progression, while cystectomy is reserved for patients who are refractory to transurethral resection and intravesical therapy. There is an increasing interest in methods to enhance the delivery of intravesical chemotherapeutic agents to improve efficacy. In vitro and in vivo studies demonstrated that electro-osmosis of mitomycin C (MMC) is more effective in delivering this drug into the urothelium, lamina propria, and superficial muscle layers of the bladder wall than is passive transport. Higher MMC tissue concentrations might have a clinical impact in the treatment of nonmuscle invasive bladder cancer (NMIBC). In randomized trials, intravesical electro-osmotic MMC was associated with superior response rate in high-risk NMIBC cancer, compared with passive diffusion MMC transport. New strategies such as intravesical Bacillus Calmette-Guerin (BCG) combined with electro-osmotic MMC as well as intravesical pre-operative electro-osmotic MMC provided promising results in terms of higher remission rates and longer remission times.Device-assisted intravesical chemotherapy may be a useful ancillary procedure in the treatment of NMIBC. Its evaluation must be planned with respect to the technical functioning of equipment and their use for a clear purpose to avoid the financial and human costs associated with incorrect therapies.

Hexaminolevulinate hydrochloride in the detection of nonmuscle invasive cancer of the bladder.

Clinical trials have shown that hexaminolevulinate (HAL) fluorescence cystoscopy improves the detection of bladder tumors compared with standard white-light cystoscopy, resulting in more efficacious treatment. However, some recent meta-analyses report controversially on recurrence-free rates with this procedure. A systematic review of literature was performed from December 2014 to January 2015 using the PubMed, Embase and Cochrane databases for controlled trials on photodynamic diagnosis (PDD) with HAL. A total of 154 publications were found up to January 2015. Three of the authors separately reviewed the records to evaluate eligibility and methodological quality of clinical trials. A total of 16 publications were considered eligible for analysis. HAL-PDD-guided cystoscopy increased overall tumor detection rate (proportion difference 19%, 95% confidence interval [CI] 0.152-0.236) although the benefit was particularly significant in patients with carcinoma in situ (CIS) lesion (proportion difference 15.7%, 95% CI 0.069-0.245) and was reduced in papillary lesions (Ta proportion difference 5.9%, 95% CI 0.014-0.103 and T1 proportion difference 1.2%, 95% CI 0.033-0.057). Moreover, there were 15% of patients (95% CI 0.098-0.211) with at least one additional tumor seen with PDD. With regard to recurrence rates, the data sample was insufficient for a statistical analysis, although the evaluation of raw data showed a trend in favor of HAL-PDD. This meta-analysis confirms the increased tumor detection rate by HAL-PDD with a most pronounced benefit for CIS lesion.

Localised prostate cancer and hemophilia A (AHA): Case report and management of the disease.

Acquired Hemophilia A (AHA) is a rare bleeding diathesis characterized by the development of autoantibodies against factor VIII (FVIII). About half of the cases are idiopathic and the other half are associated with autoimmune diseases, postpartum problems, infections, inflammatory bowel disease, drugs, lymphoproliferative disorders or solid tumors . AHA is associated with malignancies in 7-15% of cases. We report a case of AHA in a 65 year old patient with prostatic carcinoma, who underwent retropubic radical prostatectomy (RP).

Retropubic, laparoscopic, and robot-assisted radical prostatectomy: surgical, oncological, and functional outcomes: a systematic review.

OBJECTIVES: Despite the wide diffusion of minimally invasive approaches, such as laparoscopic (LRP) and robot-assisted radical prostatectomy (RALP), few studies compare the results of these techniques with the retropubic radical prostatectomy (RRP) approach. The aim of this study is to compare the surgical, functional, and oncological outcomes and cost-effectiveness of RRP, LRP, and RALP. METHODS: A systematic review of the literature was performed in the PubMed and Embase databases in December 2013. A 'free-text' protocol using the term 'radical prostatectomy' was applied. A total of 16,085 records were found. The authors reviewed the records to identify comparative studies to include in the review. RESULTS: 44 comparative studies were identified. With regard to the perioperative outcome, LRP and RALP were more time-consuming than RRP, but blood loss, transfusion rates, catheterisation time, hospitalisation duration, and complication rates were the most optimal in the laparoscopic approaches. With regard to the functional and oncological results, RALP was found to have the best outcomes. CONCLUSION: Our study confirmed the well-known perioperative advantage of minimally invasive techniques; however, available data were not sufficient to prove the superiority of any surgical approach in terms of functional and oncologic outcomes. On the contrary, cost comparison clearly supports RRP.

[Intravesical therapy with mitomycin through electromotive drug administration]. / Mitomicina intravescicale con Electromotive Drug Administration (EMDA®).

In the management of non-muscle invasive bladder cancer (NMIBC), high-level evidence supports the widespread practice of intravesical therapy with mitomycin-C (MMC). Randomized trials showed a significant reduction in short-term recurrence compared with transurethral resection of bladder tumor (TURBT) alone, but little effect on long-term and no impact at all in preventing progression. Electromotive drug administration (EMDA®) offers a means of controlling and enhancing the tissue transport of certain drugs, in order to increase their efficacy. In both laboratory and clinical studies, intravesical electromotive drug administration (EMDA) increases MMC bladder uptake, resulting in an improved clinical efficacy in NMIBC without systemic side effects. New frameworks for treatment of NMIBC - e.g., sequential intravesical BCG and EMDA/MMC, as well as intravesical EMDA/MMC immediately before TURBT - have provided promising preliminary results with higher remission rates and longer remission times, and they are a priority to minimise the costs of disease management. These findings suggest EMDA-enhanced MMC efficacy against urothelial cancer could be a major therapeutic breakthrough in the treatment of NMIBC.

Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial.

BACKGROUND: The clinical effect of intravesical instillation of chemotherapy immediately after transurethral resection of bladder tumours (TURBT) has recently been questioned, despite its recommendation in guidelines. Our aim was to compare TURBT alone with immediate post-TURBT intravesical passive diffusion (PD) of mitomycin and immediate pre-TURBT intravesical electromotive drug administration (EMDA) of mitomycin in non-muscle invasive bladder cancer. METHODS: We did a multicentre, randomised, parallel-group study in patients with primary non-muscle invasive bladder cancer in three centres in Italy between Jan 1, 1994, and Dec 31, 2003. Patients were randomly assigned to receive treatment by means of stratified blocked randomisation across six strata. Patients and physicians giving the interventions were aware of assignment, but it was masked from outcome assessors and data analysts. Patients were randomly assigned to receive TURBT alone, immediate post-TURBT instillation of 40 mg PD mitomycin dissolved in 50 mL sterile water infused over 60 min, or immediate pre-TURBT instillation of 40 mg EMDA mitomycin dissolved in 100 mL sterile water with intravesical 20 mA pulsed electric current for 30 min. Our primary endpoints were recurrence rate and disease-free interval. Analyses were done by intention to treat. Follow-up for our trial is complete. This study is registered with ClinicalTrials.gov, number NCT01149174. FINDINGS: 124 patients were randomly assigned to receive TURBT alone, 126 to receive immediate post-TURBT PD mitomycin, and 124 to receive immediate pre-TURBT EMDA mitomycin. 22 patients were excluded from our analyses because they did meet our eligibility criteria after TURBT: 11 had stage pT2 disease and 11 had carcinoma in situ. Median follow-up was 86 months (IQR 57-125). Patients assigned to receive EMDA mitomycin before TURBT had a lower rate of recurrence (44 [38%] of 117) than those assigned to receive PD mitomycin after TURBT (70 [59%] of 119) and TURBT alone (74 [64%] of 116; log-rank p<0·0001). Patients assigned to receive EMDA mitomycin before TURBT also had a higher disease-free interval (52 months, IQR 32-184) than those assigned to receive PD mitomycin after TURBT (16 months, 12-168) and TURBT alone (12 months, 12-37; log-rank p<0·0001). We recorded persistent bladder symptoms after TURBT in 18 (16%) of 116 patients in the TURBT-alone group (duration 3-7 days), 37 (31%) of 119 in the PD mitomycin post-TURBT group (duration 20-30 days), and 24 (21%) of 117 in the EMDA mitomycin pre-TURBT group (duration 7-12 days); haematuria after TURBT in eight (7%) of 116 patients in the TURBT-alone group, 16 (13%) of 119 in the PD mitomycin post-TURBT group, and 11 (9%) of 117 in the EMDA mitomycin pre-TURBT group; and bladder perforation after TURBT in five (4%) of 116 patients in the TURBT-alone group, nine (8%) of 119 in the PD mitomycin post-TURBT group, and seven (6%) of 117 in the EMDA mitomycin pre-TURBT group. INTERPRETATION: Intravesical EMDA mitomycin before TURBT is feasible and safe; moreover, it reduces recurrence rates and enhances the disease-free interval compared with intravesical PD mitomycin after TURBT and TURBT alone. FUNDING: None.

Intravesical electromotive drug administration of mitomycin-C for non-muscle invasive bladder cancer.

This article reviews intravesical application of electromotive drug administration (EMDA) for the treatment of bladder cancer and the evidence in support of intravesical passive diffusion chemotherapy in the management of non-muscle invasive bladder cancer. Two recently published randomised trials adopting protocols that use EMDA to enhance urothelial transport of intravesical mitomycin-C showed it provided a therapeutical advantage and suggested that intravesical passive diffusion administration of chemotherapeutic drugs may be suboptimal. Further studies are required to demonstrate feasibility and advantage of intravesical EMDA of mitomycin-C in the wider uro-oncological community.

QTc and autonomic neuropathy in diabetes: effects of acute hyperglycaemia and n-3 PUFA.

BACKGROUND AND AIMS: Autonomic function is also regulated by glycaemia and exerts a crucial role in the control of blood pressure and cardiac function. The disruption of this physiological mechanism impacts deeply on cardiovascular mortality in diabetes. We investigated the influence of autonomic dysfunction on QTc interval and on sympatho-vagal balance (LF/HF), in response to acute hyperglycaemia and to membrane electrical stabilization (n-3 PUFA). METHODS AND RESULTS: Twenty-four type 2 diabetic patients, without (N-: n=13) or with (N+: n=11) autonomic neuropathy and 13 healthy subjects (C) underwent BP and ECG monitoring during a 24-h period and during a 2-h hyperglycaemic clamp. Delta QTc during the night was blunted in diabetics (0.5+/-2.5 vs. C: 2.9+/-2.5%, p=0.001), and Delta LF/HF was decreased in N+ (-2.8+/-38.2 vs. C=34.8+/-28.1%, p=0.02). During hyperglycaemia, QTc increased in C; LF/HF significantly increased in C and N-. A 6-month treatment with n-3 PUFA partially restored Delta LF/HF and Delta QTc (2.1+/-1.40, p=0.04 vs. basal) only in N-. CONCLUSION: Hyperglycaemia increases QTc interval and sympathetic activity; electrical membrane stabilization improves autonomic function only in the absence of overt autonomic neuropathy. Strategies to prevent the disruption of autonomic function with newer approaches, other than just glucose control, should be implemented.