Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer

Abstract

Background&Aim: High grade non-muscle invasive bladder cancer (NMIBC) is common in urological practice. Most of these cancers are or become refractory to intravesical immunotherapy and chemotherapy. Here we evaluated the efficacy of combined local bladder hyperthermia and intravesical mitomycin-C (MMC) instillation in patients with high-risk recurrent NMIBC. Materials and methods: Between February 2014 and December 2015, 18 patients with high risk NMIBC were enrolled. Patients were treated in an outpatient basis with 6 weekly induction sessions followed by monthly maintenance sessions with intravesical MMC in local hyperthermia with bladder wall thermo-chemotherapy (BWT) system (PelvixTT system, Elmedical Ltd., Hod Hasharon, Israel). The follow-up regimen included cystoscopy after the induction cycle and thereafter with regular intervals. Time to disease recurrence was defined as time from the first intravesical treatment to endoscopic or histological documentation of a new bladder tumour. Adverse events were recorded according to CTC 4.0 (Common Toxicity Criteria) score system. Results: Mean age was 72 (32-87) years. 10 patients had multifocal disease, 9 had CIS, 6 had recurrent disease and 2 had highly recurrent disease (> 3 recurrences in a 24 months period). 6 patients underwent previous intravesical chemotherapy with MMC. The average number of maintenance sessions per patient was 7.6. After a mean follow-up of 433 days, 15 patients (83.3%) were recurrence-free. 3 patients had tumour recurrence after a mean period of 248 days without progression. Side effects were limited to grade 1 in 2 patients and grade 2 in 1 patient. Conclusions: BWT seems to be feasible and safe in high grade NMIBC. More studies are needed to identify the subgroup of patients who may benefit more from this treatment.

Role of Protopine and Nuciferine in the Management of Nocturia, Urgency, and Dysuria in Pre- and Postmenopausal Women: A Prospective Pilot Study

“…In the literature, protopine and nuciferine show a multisystemic effect, reducing stress, anxiety, and inflammatory pain, promoting the process of falling asleep and the maintenance of sleep [25]. This effect is probably related to a combined action on the GABA and anti-HI receptors of protopine, which was also found to inhibit human serotonin and noradrenaline reuptake, showing antidepressant-like effects in animal models [7][8][9][10][11][12][13][14]17].…”

“…It exerts a specific vasodilatory, anticholinergic, antihistaminic (H1 receptors) effect, and it is also a GABA A receptor agonist [7][8][9]. Influence on cholinergic receptors results in a specific smooth muscle relaxation effect, focusing mainly on the genitourinary district, while the GABAergic action guarantees an antinociceptive, sedative, and anxiolytic effect [10][11][12][13][14].…”

The role of Protopine associated with Nuciferine in controlling adverse events during hyperthermic intravesical chemotherapy instillations. A nutraceutical approach to control adverse event during intravesical instillations

“…Hyperthermia increases drug uptake into the cancer cells, affects drug metabolism, and impairs cellular DNA repair mechanisms that normally counteract drug effect (7)(8)(9). This treatment might be a feasible option in BCG unresponsive NMIBC patients, potentially avoiding or postponing the need for radical surgery in a proportion of these patients (3,10,11). Nevertheless, this treatment can increase the rate of local adverse events than passive mitomycin-C like urinary frequency, haematuria and bladder spasm (4).…”

“…cholinergic-antimuscarinic (11,12) and GABAergic (12)(13)(14)(15) action and it is able to influence some neurological systems responsible of bladder functions. Moreover, its anti-acetylcholinesterase action give it an antiamnesic property that may hold significant therapeutic value in alleviating certain memory impairments observed in dementia (15,16).…”