Adelmidrol + sodium hyaluronate in IC/BPS or conditions associated to chronic urothelial inflammation. A translational study.

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by frequent urination, bladder inflammation and pain. It is a particular challenging disease and a clear unmet medical need in terms of identifying new therapeutic strategies. The aim of study was to evaluate the anti-inflammatory effects of intravesical Vessilen® (a new formulation of 2% adelmidrol (the diethanolamide derivative of azelaic acid) + 0.1% sodium hyaluronate) administration in rodent models of IC/BPS and in IC/BPS patients or other bladder disorders. Acute and chronic animal models of cystitis were induced by a single or repetitive intraperitoneal injections of cyclophosphamide (CYP); patients with IC/BPS or with bladder pain syndrome associated with symptoms of the lower urinary tract treated once weekly by bladder instillation of Vessilen® for 8 weeks. CYP instillation caused macroscopic and histological bladder alterations, inflammatory infiltrates, increased mast cell numbers, bladder pain, increased expression of nitrotyrosine, decreased expression of endothelial tight junction zonula occludens-1. Intravesical Vessilen® treatment was able to ameliorate CYP induced bladder inflammation and pain by inhibiting nuclear factor-κB pathway and inflammatory mediator levels as well as reduced mechanical allodynia and nerve growth factor levels. A significant improvement in quality of life and symptom intensity were evident in patients with IC/BPS or other bladder disorders treated with Vessilen®. Vessilen® could be a new therapeutic approach for human cystitis.

A randomized, open-label, multicenter study of the efficacy and safety of intravesical hyaluronic acid and chondroitin sulfate versus dimethyl sulfoxide in women with bladder pain syndrome/interstitial cystitis.

AIMS: Intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS) in women with bladder pain syndrome/interstitial cystitis (BPS/IC) has shown promising results. This study compared the efficacy, safety, and costs of intravesical HA/CS (Ialuril® , IBSA) to dimethyl sulfoxide (DMSO). METHODS: Randomized, open-label, multicenter study involving 110 women with BPS/IC. The allocation ratio (HA/CS:DMSO) was 2:1. Thirteen weekly instillations of HA (1.6%)/CS (2.0%) or 50% DMSO were given. Patients were evaluated at 3 (end-of-treatment) and 6 months. Primary endpoint was reduction in pain intensity at 6 months by visual analogue scale (VAS) versus baseline. Secondary efficacy measurements were quality of life and economic analyses. RESULTS: A significant reduction in pain intensity was observed at 6 months in both treatment groups versus baseline (P < 0.0001) in the intention-to-treat population. Treatment with HA/CS resulted in a greater reduction in pain intensity at 6 months compared with DMSO for the per-protocol population (mean VAS reduction 44.77 ± 25.07 vs. 28.89 ± 31.14, respectively; P = 0.0186). There were no significant differences between treatment groups in secondary outcomes. At least one adverse event was reported in 14.86% and 30.56% of patients in the HA/CS and DMSO groups, respectively. There were significantly fewer treatment-related adverse events for HA/CS versus DMSO (1.35% vs. 22.22%; P = 0.001). Considering direct healthcare costs, the incremental cost-effectiveness ratio of HA/CS versus DMSO fell between 3735€/quality-adjusted life years (QALY) and 8003€/QALY. CONCLUSIONS: Treatment with HA/CS appears to be as effective as DMSO with a potentially more favorable safety profile. Both treatments increased health-related quality of life, while HA/CS showed a more acceptable cost-effectiveness profile.

[Treatment of acute iatrogenic cystitis secondary to bladder chemo-immuno-instillation or pelvic radiotherapy]. / Trattamento della cistite acuta iatrogena secondaria a chemio-immunoinstillazioni vescicali o a radioterapia pelvica.

The onset of cystitis during intravesical chemo-immunotherapy for the treatment of non-muscle invasive transitional cell bladder tumor, or after pelvic radiotherapy mainly for prostate cancer, is a frequent clinical situation, not easily manageable due to the lack of responsiveness to symptomatic drugs, often resulting in discontinuation of cancer treatment in many cases.?The similarity of symptoms with those of the painful bladder syndrome, otherwise called interstitial cystitis, has led us to use the same treatment with intravesical sodium hyaluronate in order to obtain an improvement of symptomatology. We therefore performed a prospective study on 55 consecutive male symptomatic patients, aged from 54 to 81 years: 11 after radiotherapy, 17 after BCG and 27 after Mitomicyn C bladder instillations ,12 of whom in combination with bladder hyperthermia.?All subjects underwent bladder instillations with sodium hyaluronate 40 mg in 50 mL weekly for 8 to 24 weeks depending on the time needed to the resolution of the symptoms.?During the first 4 weeks 32 mg of dexamethasone were also instilled intravesically, mixed with hyaluronate, in order to obtain a stronger anti-inflammatory activity due also to its higher capacity of penetration in the bladder mucosa. The symptoms intensity was evaluated through a Visual Analogue Score (VAS) of the discomfort and pain perceived from 0 to 10, and bladder capacity was recorded with micturition diary before and after the treatment.?After 16 weeks VAS improved in every case of chemical cystitis from an initial mean value of 8.6 to a final mean value of 1(with 3 as a maximum value recorded). The difference was highly significant (p <0.001). Bladder capacity increased in all cases of chemical cystitis from a mean value of 56 to 276 mL with a highly significant improvement (p <0.001) and in all cases of post-actinic cystitis from a mean bladder capacity of 89 to a final mean value of 239 mL, with a significant improvement (p= 0.05). We did not observe any side effect due to our treatment. Therefore, we can conclude that bladder instillation with sodium hyaluronate for at least 8 weeks and dexamethasone in the first 4 weeks can solve the symptoms of iatrogenic cystitis secondary to chemo-immunotherapy or pelvic radiotherapy, without incurring in side effects. To our knowledge this treatment has never been published before in scientific medical literature.

Multicenter study on the use of gemcitabine to prevent recurrence of multiple-recurring superficial bladder tumors following intravesical antiblastic agents and/or BCG: evaluation of tolerance.

OBJECTIVES: The treatment of choice for superficial bladder TCC is endoscopic resection, followed or not by intravesical immuno/chemotherapy. Some patients are not responders to common intravesical therapy and are more exposed to disease progression. In this case the suitable treatment is radical cystectomy. Because gemcitabine is effective against advanced bladder cancer, we have initiated a study to evaluate the efficacy of its intravesical use to prevent relapse and disease progression, and tolerance and safety of this drug in patients with multi-treated bladders. In this preliminary study, we cite only data on tolerance. MATERIALS AND METHODS: 64 patients were selected, and 61 were evaluable (age range 39-84 years), with multiple-recurrent bladder TCC. All patients were previously treated with intravesical chemotherapy and/or immunotherapy. The protocol provided for intravesical instillation of gemcitabine (2000 mg) once per week for 8 weeks. We collected data regarding problems noted by the patients (both local and systemic). RESULTS: 53 patients out of 61 (86.9%) completed the cycle. Side effects appeared in 14 patients, 8 of these had to suspend the treatment. Severe side effects were systemic in 4 patients (1 systemic edema, 1 malaise and dysgeusia, 1 hyperthermia and severe strangury, 1 elevated transaminases and asthenia), and local in 4 patients (1 severe urinary urgency, 1 hematuria, 1 urinary incontinence, and 1 case of pelvic pain). In 6 patients we observed pelvic pain, hematuria, strangury and UTI of medium magnitude that did not require treatment interruption. CONCLUSIONS: We believe that the severe side effects requiring treatment interruption are attributable primarily to increased sensitivity in patients with multi-treated bladders. In our experience, the side effects responsible for suspension occurred at the start of treatment in 7 cases out of 8. Our study demonstrates the safety of intravesical gemcitabine in patients with recurrent and multi-treated superficial TCC of the bladder.