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 chemothera-peutic 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

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

Background: More effective chemotherapies are urgently needed for bladder cancer, a major cause of morbidity and mortality worldwide. We therefore explored the efficacy of the combination of gemcitabine and AZD7762, a checkpoint kinase 1/2 (CHK1/2) inhibitor, for bladder cancer. Methods: Viability, clonogenicity, cell cycle distribution and apoptosis were assessed in urothelial cancer cell lines and various non-malignant urothelial cells treated with gemcitabine and AZD7762. DNA damage was assessed by ?H2A.X and 53-BP1 staining and checkpoint activation was followed by Western blotting. Pharmacological inhibition of CHK1 and CHK2 was compared to downregulation of either CHK1 or CHK2 using siRNAs. Results: Combined use of gemcitabine and AZD7762 synergistically reduced urothelial carcinoma cell viability and colony formation relative to either single treatment. Non-malignant urothelial cells were substantially less sensitive to this drug combination. Gemcitabine plus AZD7762 inhibited cell cycle progression causing cell accumulation in S-phase. Moreover, the combination induced pronounced levels of apoptosis as indicated by an increase in the fraction of sub-G1 cells, in the levels of cleaved PARP, and in caspase 3/7 activity. Mechanistic investigations showed that AZD7762 treatment inhibited the repair of gemcitabine-induced double strand breaks by interference with CHK1, since siRNA-mediated depletion of CHK1 but not of CHK2 mimicked the effects of AZD7762. Conclusions: AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy

Risk factors for peri-operative high-grade complications in patients with prostate cancer treated with robotic radical prostatectomy

Aim of our study was to evaluate the risk factors for high-grade complications (Clavien Classification System ≥3a) in patients treated with with robotic assisted radical prostatectomy (RARP). Between 2012 and 2017, a consecutive series of patients with prostate cancer were treated with robotic radical prostatectomy (RRP). Demographic, clinical and histological characteristics of the patients were recorded. Histological specimens were graded according to the new PGG classification. Complications were classified according to the modified Clavien classification system (CCS). Logistic regression analysis was performed to evaluate the risk of high grade complications (CCS>3a)

Mortars and screeds containing polymeric aggregates recycled from industrial waste and tyres

Given the growing market demand for products containing recycled components dictated by European and national policies, the presented research aimed to replace part of the natural aggregates in construction mortars and screeds with recycled polymeric aggregates (RA): industrial technopolymers and ground tyre rubber (GTR). The strategy involved the substitution of aggregates, both in market products and in the design of standard mortars, first verifying the CE certification and then the achievable mechanical performance. The whole process has been discussed in the context of a circular approach, extended to the analysis of the aggregate production phase, highlighting factors that influence environmental and economic impacts

Effect of NeuroSAFE-guided RARP versus standard RARP on erectile function and urinary continence in patients with localised prostate cancer (NeuroSAFE PROOF): a multicentre, patient-blinded, randomised, controlled phase 3 trial

BACKGROUND: Sparing the periprostatic neurovascular bundles during robot-assisted radical prostatectomy (RARP) improves postoperative erectile function and early urinary continence recovery. The NeuroSAFE technique, a standardised frozen section analysis, enables accurate real-time detection of positive surgical margins during nerve-sparing, increasing the likelihood of successful nerve preservation. However, the impact of the technique on patient outcomes remains uncertain. We aimed to assess the effect of NeuroSAFE-guided RARP versus standard RARP on erectile function and urinary continence. METHODS: NeuroSAFE PROOF was a multicentre, patient-blinded, randomised, controlled phase 3 trial done at five National Health Service hospitals in the UK. Key eligibility criteria were a diagnosis of non-metastatic prostate cancer deemed suitable to undergo RARP, good erectile function (defined as a score of ≥22 on the first 5 items of the International Index of Erectile Function [IIEF]) without medical erectile function assistance, and no previous prostate cancer treatment. No age limits were applied. Participants were randomly assigned (1:1) to standard RARP or NeuroSAFE-guided RARP using block randomisation, stratified by site. Masking of participants to allocation was maintained throughout, but patients were informed of their nerve-sparing status after the operation. Due to the nature of the intervention, operating teams were aware of treatment group. Nerve-sparing was guided by a preoperative plan in the standard RARP group and by intraoperative NeuroSAFE assessment in the NeuroSAFE group. The primary outcome was erectile function at 12 months, assessed using the IIEF-5 score, in the modified intention-to-treat population, which included all randomly assigned participants who had surgery. Secondary endpoints were urinary continence scores at 3 and 6 months, evaluated using the International Consultation on Incontinence Questionnaire (ICIQ), and the erectile function domain of the IIEF (IIEF-6) scores at 12 months. The trial is registered at ClinicalTrials.gov, NCT03317990. FINDINGS: Between Jan 6, 2019, and Dec 6, 2022, 407 patients were recruited, of whom 381 had surgery (190 participants in the NeuroSAFE group and 191 participants in the standard RARP group), and were included in the modified intention-to-treat population. Data for the primary outcome (IIEF-5 score at 12 months) were available for 344 participants (173 in the NeuroSAFE group and 171 participants in the standard RARP group). Median follow-up was 12·3 months (IQR 11·8–12·7). At 12 months, the mean IIEF-5 score was 12·7 (SD 8·0) in the NeuroSAFE group versus 9·7 (7·5) in the standard RARP group (adjusted mean difference 3·18 [95% CI 1·62 to 4·75]; p<0·0001). At 3 months, the ICIQ score was significantly lower in the NeuroSAFE group than the standard RARP group (adjusted mean difference –1·41 [95% CI –2·42 to –0·41]; p=0·006). At 6 months, no significant difference in ICIQ score was observed between groups (adjusted mean difference –0·37 [95% CI –1·35 to 0·62]; p=0·46). At 12 months, the mean IIEF-6 score was higher in the NeuroSAFE group than in the standard RARP group (15·3 [SD 9·7] vs 11·5 [SD 9·0]; adjusted mean difference 3·92 [95% CI 2·01 to 5·83]; p<0·0001). Serious adverse events occurred in six (3%) of 190 patients in the NeuroSAFE group, and and in five (3%) of 191 patients in the standard RARP group. All adverse events were postoperative complications; no serious adverse events or deaths were attributed to the study intervention. INTERPRETATION: The use of NeuroSAFE to guide nerve-sparing during RARP improves patient-reported IIEF-5 scores at 12 months and short-term urinary continence. The erectile function benefit is enhanced in patients who would not otherwise have undergone bilateral nerve-sparing by standard practice. FUNDING: National Institute of Healthcare Research, JP Moulton Charitable Foundation, UCLH Charity, St Peters Trust, and Rosetrees Trust

Notulae to the Italian alien vascular flora: 7

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, and status changes for Italy or for Italian administrative regions of taxa in the genera Abies, Actinidia, Alooe, Amaryllis, Anredera, Arctotheca, Bidens, Cardiospermum, Celosia, Commelina, Cotoneaster, Cyclamen, Eclipta, Euphorbia, Grevillea, Hedera, Hibiscus, Impatiens, Juglans, Kalanchoe, Koelreuteria, Lindernia, Melinis, Myriophyllum, Nandina, Nicotiana, Oenothera, Oxalis, Parthenocissus, Phoenix, Phyllanthus, Physalis, Plumbago, Pteris, Quercus, Setaria, Symphytum, Tagetes, and Washingtonia. Nomenclatural and distribution updates, published elsewhere are provided as Suppl. material 1