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result(s) for
"Zucchi, Alessandro"
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FGFR3 Alterations and Nectin-4 Expression as Therapeutic Biomarkers in Bladder Cancer: A Systematic Review and Single-Arm Meta-Analysis
by
Antonov, Petar
,
Belov, Angel
,
Ivanov, Atanas
in
Bias
,
Biomarkers
,
Biomarkers, Tumor - genetics
2026
Bladder cancer is a molecularly heterogeneous malignancy in which biomarker-driven therapies increasingly shape clinical management. Fibroblast growth factor receptor 3 (FGFR3) alterations and nectin-4 expression are key therapeutic targets, yet their integrated biological and clinical relevance remains unclear. A systematic search of PubMed, Scopus, and Cochrane Central was conducted from database inception to 22 February 2026 (PROSPERO: CRD420261309413). Studies reporting the prevalence of FGFR3 alterations and/or nectin-4 expression in bladder cancer were included. Proportions were pooled using a random-effects model with restricted maximum likelihood and Freeman-Tukey transformation. Heterogeneity was assessed with I
and Cochran's Q. Fourteen studies (three randomized and 11 observational), including 3955 patients (mean age: 67.34 years), were analyzed. The pooled prevalence of FGFR3 alterations was 52% (95% CI: 23.33-80.12; I
= 99%), while that of nectin-4 expression was 78% (95% CI: 64.23-89.81; I
= 91%). FGFR3 prevalence varied significantly by disease stage, study design, and region, with higher rates in advanced/metastatic disease and randomized trials (
< 0.05). Nectin-4 expression was generally high across included studies, although interpretation was limited by the small number of studies and assay variability. Sensitivity analyses showed the stability of estimates; however, interpretation is limited by substantial heterogeneity. The observed prevalence estimates are strongly influenced by study design, biomarker selection, and assay variability, limiting their interpretation as true biological prevalence. These results should, therefore, be interpreted cautiously and viewed as descriptive rather than definitive estimates. Separate analyses of biomarker-enriched trials and unselected cohorts are necessary to obtain clinically meaningful estimates.
Journal Article
Mechanistic Fingerprints from Chloride to Iodide: Halide vs. Ammonia Release in Platinum Anticancer Complexes
by
Baglini, Emma
,
Marzo, Tiziano
,
Pacini, Matteo
in
Ammonia
,
Ammonia - chemistry
,
Antineoplastic Agents - chemistry
2025
Platinum-based drugs play a pivotal role in contemporary cancer treatment, but their therapeutic utility is often limited by acquired resistance. The diiodido analog, cis-[PtI2(NH3)2] is a promising derivative that has demonstrated the ability to overcome cisplatin resistance in vitro. To establish the molecular basis for this superior activity, we integrated experimental (NMR) spectroscopy with computational density functional theory (DFT) methods to precisely and comparatively understand the drug activation mechanisms. Comparative 14N NMR experiments elucidated the initial ligand substitution step, confirming halide displacement and a markedly higher tendency for ammonia release from cis-[PtI2(NH3)2], particularly when reacting with sulfur-containing amino acids. Complementary DFT calculations determined the substitution energy values, revealing that the superior leaving-group ability of iodide results in a thermodynamically more favorable activation. Conceptual DFT parameters (softness, hardness, and Fukui indices) further demonstrated that initial substitution induces a strong trans effect, leading to the electronic sensitization of the remaining iodide ligand. This strong agreement between computational predictions and experimental data establishes a coherent molecular activation mechanism for cis-[PtI2(NH3)2], demonstrating that iodide substitution promotes both thermodynamic and electronic activation of the platinum center, which is the key to its distinct pharmacological profile and ability to circumvent resistance.
Journal Article
Correlation of clinically significant prostate cancer sites across multiparametric MRI, prostate biopsy, and whole-mount pathology for optimal prostate biopsy strategy
2025
Data from patients with suspicious lesions on multiparametric magnetic resonance (mpMRI) and a diagnosis of clinically significant prostate cancer (csPCa) who underwent radical prostatectomy (RP) were collected. The aim was to compare csPCa sites identified through whole-mount pathological analysis (WMA) after RP with PI-RADS ≥ 3 lesions identified on mpMRI, and with csPCa foci detected through targeted-biopsy (TB) or combined targeted + systematic biopsy (TSB). A paired Student’s t-test and Pearson correlation analysis were performed to evaluate the agreement between these diagnostic methods. A total of 106 patients were included in the TSB group and 95 in the TB group. The correlation between mpMRI, PB, and WMA was moderate and comparable in both groups. No correlation between PB and WMA was found in the TB group for PI-RADS3 lesions, while a moderate-strong correlation was observed when comparing mpMRI, PB, and WMA for PI-RADS > 3 lesions. About 50% of csPCa sites remained undetected by mpMRI. TSB was able to identify 16.5% more csPCa sites than TB. mpMRI is an accurate method in the diagnosis of PCa, especially for PI-RADS > 3 lesions, although some csPCa sites remained undetected. The use of TSB improved the location agreement between PB and WMA, increasing detection rates up to 79%.
Journal Article
Low intensity shockwave therapy in combination with phosphodiesterase-5 inhibitors is an effective and safe treatment option in patients with vasculogenic ED who are PDE5i non-responders: a multicenter single-arm clinical trial
by
Zucchi Alessandro
,
Palumbo Fabrizio
,
Cai Tommaso
in
Clinical outcomes
,
Clinical trials
,
Erectile dysfunction
2021
Low-intensity shockwave therapy (Li-ESWT) has been shown to be an effective and safe treatment for vasculogenic erectile dysfunction (ED). We aim to evaluate the effectiveness and safety of LiESWT in treating patients affected from vasculogenic ED who did not respond to oral treatment with Phosphodiesterase 5 inhibitors (PDE5-i). It is a multicentric open-label prospective study, in a cohort of patients non-responders to PDE-5i. Li-ESWT was performed in an outpatient setting by using the following schedule: 3000 shockwaves with an energy of 0.25 mJ/mm2 and a frequency of 4–6 Hz, twice a week for 3 weeks. International Index of Erectile Function, Erection Hardness Score and Sexual Quality of Life-Male questionnaires, and penile doppler ultrasound (PDU) are the outcome measurements. The Student t-test or Wilcoxon signed-rank test were applied to compare variables, with results considered statistically significant at p < 0.05. 106 (97.2%) completed treatment and performed follow-up visit after 4 weeks. At follow up visit, the mean IIEF-EF increased by 8.6 points (13.47 ± 4.61 vs 22.07 ± 5.27; p < 0.0001). A clinically significant improvement of IIEF-EF was achieved in 75 patients (70.7%). An EHS score ≥ 3, sufficient for a full intercourse, was reported by 72 patients (67.9%) at follow-up visit. 37 (34.9%) patients reported a full rigid penis (EHS = 4) after treatment. Li-ESWT treatment was also able to improve quality of life (SQOL-M: 45.56 ± 8.00 vs 55.31 ± 9.56; p < 0.0001). Li-ESWT significantly increased mean PSV (27.79 ± 5.50 vs 41.66 ± 8.59; p < 0.0001) and decreased mean EDV (5.66 ± 2.03 vs 1.93 ± 2.11; p < 0.0001) in PDU. Combination of Li-ESWT and PDE5-i represents an effective and safe treatment for patients affected from ED who do not respond to first line oral therapy.
Journal Article
Li-Eswt improves hemodynamic parameters thus suggesting neoangiogenesis in patients with vascular erectile dysfunction
by
Pezzoni, Fabio
,
Malfatto, Matteo
,
Cai, Tommaso
in
692/699/2732/2731
,
692/699/2732/515
,
Erectile dysfunction
2022
Extracorporeal treatment with low intensity shock-wave therapy (LI-ESWT) is a recently introduced non-invasive method which purposes the restoration of the pathophysiological alterations at the base of vasculogenic ED in male patients. The evidence in favour of the neoangiogenic potential of this treatment derived from in vitro studies and on animal models. The purpose of this study, in which the Power Doppler method was applied, is to demonstrate ‘objectively’ the real efficacy of LI-ESWT at the level of the microcirculation of the corpora cavernosa (neoangiogenesis) in patients affected by vasculogenic ED. Data from this study show, for the first time, that LI-ESWT treatment promotes neovascularisation of the functional arteries in patients affected by vasculogenic ED.
Journal Article
Oral Administration and Intralesional Injection of Hyaluronic Acid Versus Intralesional Injection Alone in Peyronie's Disease: Results from a Phase III Study
by
Cai, Tommaso
,
Bjerklund Johansen, Truls E.
,
Favilla, Vincenzo
in
Connective tissue diseases
,
Hyaluronic acid
,
injections intralesional
2021
PurposeThe aim of this study was to compare the effect of combined oral administration and intralesional injection of hyaluronic acid (HA) with intralesional injections alone, in patients with early onset of Peyronie's disease (PD).Materials and MethodsFor this prospective, randomized phase III clinical trial we included patients with recent diagnosis of PD. Eighty-one patients were randomized into two groups. Group A consisted of 41 patients receiving oral administration of HA in combination with weekly intralesional injection of HA for 6 weeks. Group B consisted of 40 patients group B who received weekly intralesional injections of HA for 6 weeks, only. The main outcome measures were the changes from baseline to the end of therapy after three months in penile curvature (°) and changes in the international index of erectile function (IIEF-5) score and patient's global impressions of improvement (PGI-I) score.ResultsGroup A had a significantly larger reduction in penile curvature as compared with group B (Group A: −7.8°, Group B: −4.1° [p<0.001]). Group A also showed a higher improvement in IIEF-5 and PGI-I scores in comparison with Group B (Group A: +4 IIEF-5, Group B: +2 IIEF-5 [p<0.001]; Group A: 3 PGI-I, Group B: 1 PGI-I, [p<0.001]). At three months both groups had a significant reduction of penile curvature from baseline (p<0.001).ConclusionsOral administration combined with intralesional treatment with HA shows greater efficacy to improve penile curvature and overall sexual satisfaction in comparison with intralesional HA treatment alone.
Journal Article
16 years follow-up evaluation of immediate vs delayed vs. combined hormonal therapy on fertility of patients with cryptorchidism: results of a longitudinal cohort study
2022
Background
To investigate in a longitudinal cohort study, the best treatment to preserve fertility in cryptorchid subjects. Patients treated with immediate hormonal vs. delayed vs. combined (hormone plus surgery) therapy consecutively enrolled during the period 1987–1997, were evaluated.
Methods
Two hundred fifty-five subjects were enrolled and 192 patients completed the follow-upt. One hundred fifty-six patients and 36 out 192 had monolateral and bilateral cryptorchidism, respectively. Twenty-nine out of 192 were previously treated by surgery alone (Group A), 93/192 by hormone therapy alone (Group B), 51/192 received sequential combined hormone therapy plus surgery (Group C) whilst 19/192 refused any type of treatment (Group D). The other 63 patients were considered lost to follow-up. All the patients underwent medical consultation, scrotal ultrasound scan, sperm analysis and Inhibin B, Follicular Stimulating Hormone (FSH) and Testosterone (T) serum level determination.
Results
Testicular volume was found decreased in the Group D patients whilst hormone serum levels were comparable in all groups. Statistically significant differences for sperm characteristics were found in patients treated with hormonal therapy alone or combined with surgery (Groups B and C). These two groups reported better semen quality than patients who received surgery alone or no treatment. No differences were observed between monolateral and bilateral cryptorchidism patients.
Conclusions
Early prolonged hormonal therapy is advisable in all patients with cryptorchidism independently from the surgical option of promoting testicular descent to the scrotum. Hormonal therapy provides in our study better chance to obtain adequate sperm quality in adult life.
Journal Article
Preventing Parastomal Hernias After Radical Cystectomy with Ileal Conduit: A Systematic Review Regarding Surgical Prophylactic Techniques
by
Iachimovsky, Ioana Alexandra
,
Cai, Tommaso
,
Liguori, Giovanni
in
Abdomen
,
Clinical trials
,
Hernia
2026
Background/Objective: Parastomal hernia (PSH) following radical cystectomy (RC) with ileal conduit represents a significant late complication. Preventive strategies have been described but are not yet routinely incorporated into clinical practice. We conducted a systematic review of the current literature to assess the efficacy of PSH preventive techniques for ileal conduit. Methods: A literature search of PubMed/MEDLINE, Scopus, CENTRAL, and Web of Science databases was conducted from 2010 to December 2024 following PRISMA guidelines. Inclusion criteria were patients undergoing RC with ileal conduit, evaluation of at least one PSH preventive strategy and reporting of PSH incidence or relevant postoperative outcomes. Eligible designs included RCTs and non-randomized cohort studies. Exclusion criteria included urinary diversions other than ileal conduit, non-bladder-related indications, non-extractable outcome data, and non-original publications. Results: Three randomized controlled trials (RCTs) and nine non-randomized studies were included in the analysis. Studies investigating both mesh and non-mesh preventive techniques were considered. Clinical PSH recurrence rates following mesh placement ranged from 0.0% to 11.1% among the included studies. RCTs using mesh placement reported conflicting conclusions regarding its protective effects. For non-mesh preventive strategies, clinical PSH recurrence rates ranged from 0.0% to 11.5%. The only RCT focusing on non-mesh approaches reported positive protective effects for the experimental group. All procedures were safe, with no significant increase in complication rates compared to conventional interventions. Conclusions: The low quality of current evidence prevents definitive conclusions regarding the protective effects of both mesh and non-mesh preventive approaches. High-quality evidence is needed to make conclusive statements on this topic. Patients at high risk for PSH development should be offered personalized preoperative counselling and the opportunity to participate in ongoing RCTs.
Journal Article
Incisional Negative-Pressure Wound Therapy Versus Standard Dressing for the Prevention of Surgical Site Complications Following Radical Cystectomy
by
Piasentin, Andrea
,
Cai, Tommaso
,
Liguori, Giovanni
in
Abdomen
,
Abdominal surgery
,
Bladder cancer
2025
Radical cystectomy (RC) is a complex urologic procedure that, when performed using an open surgical approach, carries a high risk of surgical site complications (SSCs), which can lead to prolonged recovery, increased healthcare costs, and higher morbidity. Incisional negative-pressure wound therapy (iNPWT) has demonstrated benefits in enhancing wound healing in various surgical settings, but its effectiveness in the context of RC remains underexplored. This study aimed to evaluate the impact of iNPWT on the incidence of SSCs following RC compared to standard surgical dressings using the PICO
system.
A cohort of 146 patients who underwent RC between 2015 and 2021 was divided into two groups: those treated with standard dressings (Group 1,
= 80) and those who received iNPWT (Group 2,
= 66). Patient-related, surgical, and pathological variables were compared between the groups. Categorical variables were analyzed using the chi-square or Fisher's exact test, while continuous variables were assessed using Student's
-test. Univariate logistic regression models were applied to evaluate the association between iNPWT use and 90-day SSCs, as well as to identify risk factors for complications.
Group 2 (iNPWT) had a higher prevalence of chronic comorbidities, including chronic kidney disease, but fewer active smokers compared to Group 1. Higher body mass index, prolonged operative time, and uncontrolled diabetes were significantly associated with the development of SSCs. The incidence of SSCs within 90 days was significantly lower in the iNPWT group (7.6%) compared to the standard dressing group (22.5%) (
= 0.03). iNPWT use was associated with a substantially reduced risk of SSCs (OR: 0.282), demonstrating a protective effect.
Prophylactic application of iNPWT following RC significantly reduced the incidence of surgical site complications compared to standard dressing. These findings support the potential of iNPWT as a valuable adjunct in perioperative wound management. While encouraging, these results warrant validation in prospective, randomized studies. Tailored postoperative strategies and identification of patient-specific risk factors remain essential components in SSC prevention and reflect the growing importance of precision medicine in surgical oncology.
Journal Article
Use of Intravesical Injections of Platelet-Rich Plasma for the Treatment of Bladder Pain Syndrome: A Comprehensive Literature Review
by
Marchesi, Alessandro
,
Pandolfo, Savio Domenico
,
Costantini, Elisabetta
in
Animal models
,
Antibiotics
,
Bladder
2021
Background: Bladder pain syndrome/interstitial cystitis (BPS/IC) or primary bladder pain syndrome (PBPS) is a complex and poorly understood condition. This comprehensive review aimed to discuss the potential application of platelet-rich plasma (PRP) in the treatment of BPS/IC. The pathophysiology of BPS/IC is characterized by urothelial damage that triggers a chain of events leading to chronic inflammation and other conditions. Frequently, in subjects affected by BPS/IC, recurrent urinary tract infection (rUTI) is associated with difficult therapeutic management. For these reasons, many oral and intravesical treatments (e.g., antibiotic therapy and intravesical anesthetic instillations) have been proposed to alleviate the symptoms of IC/BPS. However, the limitation of these treatments is the short duration of improvement. The purpose of this review is to analyze the efficacy of intravesical PRP injections in subjects with PBS/IC and to try to understand the potential therapeutic effects on the pathophysiology of this disease. Methods: A nonsystematic literature search using Pubmed, EMBASE, Scopus, Web of Science, Medline was performed from January 2000 to August 2021. The following terms were combined to capture relevant publications: “platelet-rich plasma”, “interstitial cystitis”, “PRP”, “bladder pain syndrome”, and “painful bladder syndrome”. Results: After exclusion of non-pertinent studies/articles, we have analyzed 5 studies. In detail, 2 articles concerned preclinical studies in which animal models were used. The authors showed an improvement in the histological pattern with less bleeding in treated subjects, a lower presence of inflammatory cytokines and an increase in the mitotic index of urothelial cells in animals treated with intravesical PRP. In the three prospective clinical trials analyzed, patients with BPS/IC who underwent monthly intravesical PRP injections were found to have a statistically significant improvement in symptoms with modulation of growth factors and inflammatory proteins. Conclusions: New evidence suggests that treatment with intravesical PRP could improve urothelial regeneration and reduces chronic inflammation in BPS/IC, modifying the clinical history of its pathology.
Journal Article