The role of device-assisted therapies in the management of non-muscle invasive bladder cancer: A systematic review.

OBJECTIVE: Despite optimal treatment, patients affected by non-muscle invasive bladder cancer (NMIBC) suffer from high risk of recurrence and progression. Intravescical device assisted therapies such as radiofrequency induced thermochemotherapeutic effect (RITE) and electromotive drug administration (EMDA) have shown promising effect in enhancing the effect of intravescical chemotherapies. The aim of the study was to assess clinical outcomes of these two devices in non-muscle invasive bladder cancer. METHODS: A systematic literature review was performed in December 2019 using the Medline, Embase, and Web of Science databases. Only articles published in the last 10 years were considered (2009-2019). The articles were selected using the following keywords association: "bladder cancer" AND "EMDA' AND "synergo" AND "hyperchemotherapy" AND "electromotive drug administration", AND "radiofrequency induced thermochemotherapeutic" AND "RITE". RESULTS: We found 16 studies published in the last ten years regarding the efficacy of RITE (12 studies) and EMDA (4 studies) in the treatment of NMIBC. Both RITE and EMDA showed promising results in the treatment of intermediate and high risk NMIBC as well as in patients affected by recurrent BCa after BCG failure. In high-risk BCG naïve NMIBC patients treated with EMDA recurrence and progression rates were 68% and 95%, respectively. Considering RITE, recurrence and progression range rates were 43%-88% and 62%-97%, respectively. Discordance results were reported regarding its effect on patients with carcinoma in situ. However, only few studies could be compared since differences exist regarding inclusion criteria with high patients' heterogeneity. Considering recurrence after BCG, recurrence and progression range rates were 29%-29.2% and 62%-83% for RITE and 25% and 75% for EMDA, respectively. CONCLUSION: Delivery of intravescical hyperthermia seems to enhance the normal effect of intravescical chemotherapy instillation. Although prospective trials supported its effect on both BCG naïve and BCG failure patients, data are urgently required to validate these findings and to understand its effect on patients with carcinoma in situ. LEVEL OF PROOF: 3.

Direct quantitative imaging of the writing stage in a photosensitive azopolymer by digital holography.

In this paper, we demonstrated that the gradual formation of a surface relief grating (SRG) in azopolymer thin films under continuous light exposure could be directly observed in situ and in real-time, allowing full-field characterization with high spatial resolution. We reported here for the first time, to the best of our knowledge, that digital holography (DH) can be adopted for investigating and monitoring an inscribed holographic surface relief grating (SRG) of azopolymers by two-beam laser interference lithography over a wide area. The writing process could be assessed through quantitative phase imaging (QPI). The reported results show that the proposed method is a truly valuable diagnostic tool that can be useful for investigating the spatial distribution of the writing process, which can eventually contribute to shedding light on the still unclear origin and related mechanism of SRG formation in azopolymers.

Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics.

BACKGROUND: Tumor recurrence is the most expected clinical event after the resection of non-muscle invasive bladder cancer, depending on histological findings of the initial lesion. In patients with low and intermediate risk of disease, the intravesical instillation of chemotherapy agents is recommended as a standard treatment to reduce recurrences. METHODS: A comprehensive review covering various aspects of different treatments with intravesical drugs is presented. RESULTS: Drugs may be instilled into the bladder starting with a single, 'early' postoperative administration or, after tumor resection with adjuvant intent or, before tumor resection under a neo-adjuvant regimen. Both latter protocols would consist of weekly treatments followed by monthly maintenance treatments. Different methods of administering drugs intravesically have been proposed to enhance the depth of drug penetration and its absorption into the bladder wall thus increasing the rate of drug-DNA reaction. These device-assisted therapies therefore have set a goal to potentiate the drug's effect and efficaciousness. The Radiofrequency-Induced Thermochemotherapeutic Effect (RITE) and the Electromotive-Drug Administration (EMDA) are the two most relevant modalities used to increase the activity of intravesical chemotherapy. Despite the widely adopted international guidelines' recommendations, and recent clinical trials of device-assisted chemotherapy instillations showing markedly enhanced recurrence-free survival compared even to the standard of care, clinicians and pharmacologists are not familiar with the in-depth physical aspects, pharmacokinetics and systemic absorption of chemotherapeutic drugs following their intravesical administration. CONCLUSION: Knowledge of drug diffusion mechanisms into the tissue and cellular cytoplasm following bladder instillation is a key to understand the safety profile and clinical activity of chemotherapy.

Surface plasmon resonance imaging by holographic enhanced mapping.

We designed, constructed and tested a holographic surface plasmon resonance (HoloSPR) objective-based microscope for simultaneous amplitude-contrast and phase-contrast surface plasmon resonance imaging (SPRi). SPRi is a widely spread tool for label-free detection of changes in refractive index and concentration, as well as mapping of thin films. Currently, most of the SPR sensors rely on the detection of amplitude or phase changes of light. Despite the high sensitivities achieved so far, each technique alone has a limited detection range with optimal sensitivity. Here we use a high numerical aperture objective that avoids all the limitations due to the use of a prism-based configuration, yielding highly magnified and distortion-free images. Holographic reconstructions of SPR images and real-time kinetic measurements are presented to show the capability of HoloSPR to provide a versatile imaging method for high-throughput SPR detection complementary to conventional SPR techniques.

A rare case of necrotic thymoma.

The Authors report the case of a patient who underwent resection of a huge anterior mediastinal mass, revealing to be a necrotic thymoma. The patient had been previously submitted to surgical biopsies of the mass yielding non-diagnostic results due to extensive necrosis. A sternotomy was then performed to resect the mediastinal mass originating from the thymus, en-bloc with the mediastinal fat and the apparently infiltrated lung. Histopathology showed a possible cyst/thymoma in massive necrosis, not further definable; revision by a specialized experienced pathologist (J. Rosai) confirmed total mass necrosis and no lung infiltration, thus orientating diagnosis towards a necrotic thymoma and excluding a lymphoblastic lymphoma, with similar histopathological features but more frequent in children or characterized by neoplastic infiltration of surrounding lung. Total body computed tomography (CT) scan and fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/CT, show neither local recurrence, nor distant metastases two years after surgery. In case of anterior mediastinal mass with difficult histopathological diagnosis due to massive necrosis, the hypothesis of a necrotic thymoma should be considered. After radical removal prognosis is generally favourable and no adjuvant treatment is required.

Spontaneous assembly of carbon-based chains in polymer matrixes through surface charge templates.

Stable chains of carbon-based nanoparticles were formed directly in polymer matrixes through an electrode-free approach. Spontaneous surface charges were generated pyroelectrically onto functionalized ferroelectric crystals, enabling the formation of electric field gradients that triggered the dipole-dipole interactions responsible for the alignment of the particles, while embedded in the polymer solution. The phenomenon is similar to the dielectrophoretic alignment of carbon nanotubes reported in the literature. However, here the electric fields are generated spontaneously by a simple heat treatment that, simultaneously, aligns the particles and provides the energy necessary for curing the host polymer. The result is a polymer sheet reinforced with well-aligned chains of carbon-based particles, avoiding the invasive implementation of appropriate electrodes and circuits. Because polymers with anisotropic features are of great interest for enhancing the thermal and/or the electrical conductivity, the electrode-free nature of this technique would improve the scaling down and the versatility of those interconnections that find applications in many fields, such as electronics, sensors, and biomedicine. Theoretical simulations of the interactions between the particles and the charge templates were implemented and appear in good agreement with the experimental results. The chain formation was characterized by controlling different parameters, including surface charge configuration, particle concentration, and polymer viscosity, thus demonstrating the reliability of the technique. Moreover, micro-Raman spectroscopy and scanning electron microscopy were used for a thorough inspection of the assembled chains.

Analysis of radical cystectomy and urinary diversion complications with the Clavien classification system in an Italian real life cohort.

INTRODUCTION: Standardized methods of reporting complications after radical cystectomy (RC) and urinary diversions (UD) are necessary to evaluate the morbidity associated with this operation to evaluate the modified Clavien classification system (CCS) in grading perioperative complications of RC and UD in a real life cohort of patients with bladder cancer. MATERIALS AND METHODS: A consecutive series of patients treated with RC and UD from April 2011 to March 2012 at 19 centers in Italy was evaluated. Complications were recorded according to the modified CCS. Results were presented as complication rates per grade. Univariate and binary logistic regression analysis were used for statistical analysis. RESULTS AND LIMITATIONS: 467 patients were enrolled. Median age was 70 years (range 35-89). UD consisted in orthotopic neobladder in 112 patients, ileal conduit in 217 patients and cutaneous ureterostomy in 138 patients. 415 complications were observed in 302 patients and were classified as Clavien type I (109 patients) or II (220 patients); Clavien type IIIa (45 patients), IIIb (22 patients); IV (11 patients) and V (8 patients). Patients with cutaneous ureterostomy presented a lower rate (8%) of CCS type ≥IIIa (p = 0.03). A longer operative time was an independent risk factor of CCS ≥III (OR: 1.005; CI: 1.002-1.007 per minute; p = 0.0001). CONCLUSIONS: In our study, RC is associated with a significant morbidity (65%) and a reduced mortality (1.7%) when compared to previous experiences. The modified CCS represents an easily applicable tool to classify the complications of RC and UD in a more objective and detailed way.

[The role of Proxelan in the treatment of chronic prostatitis. Results of a randomized trial]. / Ruolo di Proxelan nel trattamento delle prostatitit croniche. Risultati di un trial randomizzato.

AIM: Inflammatory diseases of the prostate are one of the most difficult problems to manage in the fertile male aged between 20 and 50. Antibiotics are the gold standard for the treatment of both bacterial (category II-NIH) and non bacterial prostatitis (category III-NIH). However, antibiotics need to be associated with other therapies focused on reducing symptoms and providing a better quality of life. In the present study we sought to test the effectiveness of antibiotics and the medical device Proxelan suppositories taken together. METHODS: Starting in January 2011, we conducted a randomized controlled trial involving 60 subjects with bacterial and non bacterial chronic prostatitis, who were divided into two groups. Subjects allocated in group A received only antibiotics for 28 days; subjects in group B received antibiotics + Proxelan, for 28 days as well. Before randomization all subjects underwent Meares-Stamey test, IPSS and NIH-CPSI questionnairs. All of those were repeated 60 and 120 days after randomization. Microbiological and clinical efficacy were compared using specific statistical analyses. RESULTS: Data were obtained from 29 subjects allocated in group A and 31 in group B. Minor side effects were observed which did not cause study interruption in any case. Of the total population, 68,3% resulted positive to the Meares-Stamey test at study start. Proxelan was not better than antibiotics alone under a microbiological point of view (OR)=0.9; (IR) 0.3-2.8; P=0.46. According to the answers provided at the NIH-CPSI questionnaire, subjects in the group B obtained a better score compared to group A, either after 2 months (OR:2.8; 95%IC 1.2-4.1; P=0.017) and after 4 months (OR:1.67; 95%IC 0.9-2.9; P=0.04). With regards to the IPSS questionnaire, 2 months after treatment start, subjects in the group A had a probability of having urinary symptoms 2 times higher compared to subjects in group B (OR:1.9; 95%IC 1.0-3.5; P=0.028). Although Proxelan seems to improve IPSS also after 4 months, the difference does not reach the level of statistical significance. CONCLUSION: Compared to antibiotics alone, the combination of antibiotics and Proxelan improve both symptoms associated to chronic prostatitis and urinary symptoms, however microbiological results are not different. Future studies may be required to confirm our results and to explain the mechanism of action of Proxelan.

Sexual dysfunction in patients under dialytic treatment.

AIM: Erectile dysfunction (ED) is very common in patients with renal failure, probably as a side effect of long-term treatments and dialysis, among other etiologic factors. Over the last few years, new highly effective oral treatments for ED have been introduced in the market. We designed a prospective trial in 42 dialytic patients with ED, focusing on the therapeutic effect of syldenafil and apomorphine. METHODS: Forty-two patients aged 57 years (range 34-71), [40 on hemodialysis (HD) and 2 on peritoneal dialysis (PD)] were enrolled in a prospective study comparing sildenafil with apomorphine. After a careful nephrologic anamnesis and uroandrological examination, all patients underwent, before and after each treatment, the International Index Erectile Function (IIEF) test, and the Life Satisfaction test. Expert opinion was based on grading of evidence based medical literature, widespread internal committee discussion, public presentations and debates. RESULTS: The 2 patients on PD were the only responders to 25 mg sildenafil; 25 patients on HD had a clear improvement of the IIEF score after 50 mg sildenafil administration; finally, 11 patients on HD would benefit only from 100 mg sildenafil; the nonresponders to sildenafil were only 4 patients, having to switch to PgE1. When apomorphine was tested on the same patients, a mild response was seen only in 6 patients at the 3 mg dose. No response was seen in the 2 patients on PD. CONCLUSIONS: There was a statistically significant difference in the therapeutic role of sildenafil versus apomorphine, the first producing an overall improvement of the IIEF in 90.5% of patients, compared to 14% of the same patients receiving apomorphine (P<0.001).