Thulium laser transurethral incision of the prostate with ejaculation-sparing intent: 2-year follow-up outcomes from a high-volume centre.

Introduction: Several 'ultra-minimally-invasive' surgical treatments (uMISTs) have been developed, aiming to relieve benign prostatic obstruction (BPO) and spare ejaculatory function; however, such techniques do not always ensure substantial improvements in uroflowmetry parameters. The aim of the present study was to evaluate the 2-year functional outcomes of thulium laser transurethral incision of the prostate (ThuIP) as an alternative to uMISTs. Material and methods: Data of consecutive patients affected by BPO with indication to surgical intervention and a strong will to spare ejaculatory function were collected on a dedicated prospectively maintained database. A specific "trifecta" was identified as the contemporary presence of: (1) post-operative Qmax ≥15 ml/s; (2) absence of early (within 90 days) complications; and (3) preserved antegrade ejaculation. Results: 120 patients underwent ThuIP and were analysed. Median catheterisation time was 2 days (IQR 2-2). Significant improvements in IPSS and IPSS-QoL scores and uroflowmetry parameters were observed at all follow-up times. At the last follow-up visit (24 months) the median ΔIPSS was -12 (-17; -9), median ΔIPSS-QoL was -3 (-4; -2), median ΔQmax was +7.7 ml/s (+5.2; +11.0), and median ΔPVR was -50 ml (-100; 0) (all p-values <0.001). Fourteen patients reported postoperative absence of antegrade ejaculation (11.7%). Overall, trifecta was achieved in 86 patients (71.7%) at 6 months, in 79 patients (65.8%) at 12 months, and in 75 patients (62.5%) at 24 months. Conclusions: ThuIP allows for a significant improvement in uroflowmetry parameters and patient-reported outcomes at 2-year follow-up. Moreover, antegrade ejaculation is preserved in approximately 90% of cases.

Oral supplementation with probiotics, potassium citrate, and magnesium in reducing crystalluria in stone formers: A phase II study.

INTRODUCTION: Crystalluria is an important indicator of renal stone recurrence. Mechanisms underlying urinary stone formation are still not fully understood and raising interests has been giving to intestinal commensal bacteria for their contribute in maintaining urinary solutes equilibrium. The aim of our phase II study was to examine the administration of potassium citrate, magnesium and probiotics in order to reduce crystalluria. MATERIALS AND METHODS: Since May 2021, we enrolled 23 patients candidates for ureterorenolithotripsy for calcium oxalate kidney stones with crystalluria and a normal metabolic profile. The analysis was validated by the Institution's Ethical Committee (no. approval STS CE Lazio 1/N-823). At discharge, patients were provided with daily food supplementation for 20 days of 1 billion Lactobacillus paracasei LPC09, 1 billion Lactobacillus plantarum LP01, 1 billion Bifidobacterium breve BR03, potassium (520 mg), citrate (1400 mg), and magnesium (80 mg). Crystalluria was re-assessed at 1, 3, 6, and 12-months follow-up by polarized light microscopy. RESULTS: After one month from the oral supplementation, no patient reported crystalluria; at 3 months, among the 20 participants available for re-evaluation, still no patient reported crystalluria. Instead, crystalluria was reported in three patients (15%) at 6 months, and in five patients (25%) at 12 months follow-up. CONCLUSIONS: The oral supplementation with Lactobacillus spp. and Bifidobacterium spp. was found able to reduce the prevalence of crystalluria in a cohort of patients with diagnosis of calcium oxalate kidney stones with crystalluria candidate to ureterorenolithotripsy.

Transperineal Laser Ablation for Focal Therapy of Localized Prostate Cancer: 12-Month Follow-up Outcomes from a Single Prospective Cohort Study.

INTRODUCTION AND OBJECTIVES: To evaluate the oncological and functional outcomes of transperineal laser ablation (TPLA) as the focal therapy for localized prostate cancer (PCa) after a 12-month follow-up. MATERIALS AND METHODS: Patients with low- and intermediate-risk localized PCa were prospectively treated with focal TPLA between July 2021 and December 2022. The inclusion criteria were the following: clinical stage < T2b; PSA < 20 ng/mL; International Society of Urological Pathology (ISUP) grade ≤ 2; MRI-fusion biopsy-confirmed lesion classified as PI-RADS v2.1 ≥ 3. Intra-, peri-, and post-operative data were collected. Variables including age, PSA, prostate volume (PVol), Charlson's Comorbidity Index (CCI), International Prostate Symptom Score (IPSS) with QoL score, International Index of Erectile Function (IIEF-5), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and Male Sexual Health Questionnaire-Ejaculatory Dysfunction Short Form (MSHQ-EjD) were collected at baseline and at 3, 6 and 12 months after TPLA. Post-operative mpMRI was performed at 3 and 12 months. Finally, all patients underwent prostatic re-biopsy under fusion guidance at 12 months. The success of this technique was defined as no recurrence in the target treated lesion at the 12-month follow up. RESULTS: Twenty-four patients underwent focal TPLA. Baseline features were age [median 67 years (IQR 12)], PSA [5.7 ng/mL (3.9)], PVol [49 mL (27)], CCI [0 (0)], IPSS [11 (9)], IPSS-QoL [2 (2)], IIEF-5 [21 (6)], ICIQ-SF [0 (7)], MSHQ-EjD ejaculation domain [14 (4)] and bother score [0 (2)]. Median operative time was 34 min (IQR 12). Median visual analogue scale (VAS) 6 h after TPLA was 0 (IQR 1). The post-operative course was regular for all patients, who were discharged on the second post-operative day and underwent catheter removal on the seventh post-operative day. No patient had incontinence at catheter removal. A significant reduction in PSA (p = 0.01) and an improvement in IPSS (p = 0.009), IPSS-QoL (p = 0.02) and ICIQ-SF scores (p = 0.04) compared to baseline were observed at the 3-month follow-up. Erectile and ejaculatory functions did not show any significant variation during the follow-up. No intra- and peri-operative complications were recorded. Three Clavien-Dindo post-operative complications were recorded (12%): grade 1 (two cases of urinary retention) and grade 2 (one case of urinary tract infection). At the 12-month follow-up, eight patients showed mpMRI images referable to suspicious recurrent disease (PIRADS v2.1 ≥ 3). After re-biopsy, 7/24 patients' (29%) results were histologically confirmed as PCa, 3 of which were recurrences in the treated lesion (12.5%). The success rate was 87.5%. CONCLUSIONS: The focal TPLA oncological and functional results seemed to be encouraging. TPLA is a safe, painless, and effective technique with a good preservation of continence and sexual outcomes. Recurrence rate at 12 months was about 12.5%.

Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project.

Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method. Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized. Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations. Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.

Molecular profiling of a bladder cancer with very high tumour mutational burden.

The increasing incidence of urothelial bladder cancer is a notable global concern, as evidenced by the epidemiological data in terms of frequency, distribution, as well as mortality rates. Although numerous molecular alterations have been linked to the occurrence and progression of bladder cancer, currently there is a limited knowledge on the molecular signature able of accurately predicting clinical outcomes. In this report, we present a case of a pT3b high-grade infiltrating urothelial carcinoma with areas of squamous differentiation characterized by very high tumor mutational burden (TMB), with up-regulations of immune checkpoints. The high TMB, along with elevated expressions of PD-L1, PD-L2, and PD1, underscores the rationale for developing a personalized immunotherapy focused on the use of immune-checkpoint inhibitors. Additionally, molecular analysis revealed somatic mutations in several other cancer-related genes, including TP53, TP63 and NOTCH3. Mutations of TP53 and TP63 genes provide mechanistic insights on the molecular mechanisms underlying disease development and progression. Notably, the above-mentioned mutations and the elevated hypoxia score make the targeting of p53 and/or hypoxia related pathways a plausible personalized medicine option for this bladder cancer, particularly in combination with immunotherapy. Our data suggest a requirement for molecular profiling in bladder cancer to possibly select appropriate immune-checkpoint therapy.

Open questions on lower urinary tract infections: Results of a Delphi consensus study.

BACKGROUND AND OBJECTIVE: This is a Delphi study that aims to explore expert consensus regarding open questions in current literature evidence on lower urinary tract infections (UTIs). This manuscript deals with adults and analyzed the most recent guidelines and meta-analysis on the topic. METHODS: A panel of leading urologists and urogynaecologists participated in a consensus-forming project using a Delphi method to reach consensus on gray zone issues on recurrent lower UTIns (rUTIs), asymptomatic bacteriuria (AB) in pregnant women, and catheter-associated UTIs (CAUTI) in adults. All the panelists were invited to participate the four phases consensus. Consensus was defined as ≥75% agreement. An ordinal scale (0-10) was used. A systematic literature review was analyzed for diagnostic workup and prevention of rUTIs, AB, and CAUTI. RESULTS: In total, 37 experts participated. All panelists participated in the four phases of the consensus process. Consensus was reached if ≥75% of the experts agreed on the proposed topic. Online meetings and a face-to-face consensus meeting was held in Milan in March 2023. Formal consensus was achieved for 12/13 items. CONCLUSIONS: This manuscript is a Delphi survey of experts that showed interest on some debated points on rUTIs, AB in pregnancy, and prevention of CAUTI. There is still little data on nonantibiotic prevention of UTIs and CAUTI; quite old studies have been reported on AB in pregnancy. The emerging problem of antibiotic resistance is relevant and nonantibiotic prophylaxis may play a role in its prevention.

Percutaneous tibial nerve stimulation in the treatment of neurogenic detrusor overactivity in multiple sclerosis patients: a historically controlled study.

Background: Percutaneous tibial nerve stimulation (PTNS) is widely used in the treatment of neurogenic detrusor overactivity (NDO) in multiple sclerosis (MS); however, controlled studies are still lacking.Objective:: To assess effectiveness of PTNS in MS patients with NDO unresponsive to pharmacological and behavioural therapies. Methods: MS patients with NDO were enrolled. Inclusion criteria were NDO not responding to pharmacological and behavioural therapies. Exclusion criteria were the presence of relevant comorbidities and urinary tract infections. Patients were evaluated using 3-day bladder diaries and validated questionnaires at baseline, after 4 weeks of educational therapy and after 12 PTNS sessions. The primary outcome measure was the percentage of patients considered responders after the behavioural therapy and after the PTNS in a historical controlled fashion (definition of 'responder' was reduction ⩾50% of urgency episodes). Results: A total of 33 patients (26 women, 7 men) were enrolled. Two patients dropped out for reasons not related to the protocol. Two out of 31 patients (6.5%) and 21/29 (72.4%) were considered responders at visits 1 and 2, respectively. In PTNS responders, a statistically significant improvement in both bladder diary results and standardized questionnaire scores was recorded, compared with that obtained with behavioural therapy alone. No serious adverse events were reported. Conclusion: This historically controlled study suggests that PTNS may be effective in improving NDO in MS patients.

Ejaculatory function following transperineal laser ablation vs TURP for benign prostatic obstruction: a randomized trial.

OBJECTIVES: To evaluate the reliability of transperineal interstitial laser ablation of the prostate (TPLA) in preserving antegrade ejaculation compared to transurethral resection of the prostate (TURP). PATIENTS AND METHODS: In this single-centre, prospective, randomized, open-label study, consecutive patients with indication for surgical treatment for benign prostatic obstruction (BPO) were enrolled between January 2020 and September 2021 (NCT04781049). Patients were randomized to one of two treatment arms: Group A: TPLA (experimental group) and Group B: TURP (reference standard group). The primary endpoint was change in ejaculatory function (assessed by the Male Sexual Health Questionnaire - Ejaculatory function domain [EJ-MSHQ]) at 1 month after surgery. Secondary endpoints included comparison of visual analogue scale (VAS) scores, changes in sexual function (assessed using the five-item International Index of Erectile Function [IIEF-5]), change in International Prostate Symptom Score [IPSS], change in quality of life score, and maximum urinary flow rate [Qmax ] improvement at 1-6 months, as appropriate. RESULTS: Fifty-one patients (26 TPLA vs 25 TURP) were analysed. No differences in the perception of pain assessed by VAS and no differences in IIEF-5 score were found between the groups. The distribution of ejaculatory function assessed by the EJ-MSHQ remained unmodified after TPLA (P = 0.2), while a median 30% decrease in EJ-MSHQ score was observed after TURP (P = 0.01). Absence of antegrade ejaculation was reported in one patient in the TPLA group (vs 18 patients in the TURP group). A statistically significant difference between the treatment groups was found in terms of postoperative Qmax (TPLA vs TURP: 15.2 [interquartile range 13.5-18.3] mL/s vs 26.0 [interquartile range 22.0-48.0] mL/s; P < 0.001). Both treatments significantly improved Qmax , with a mean 23.9 mL/s improvement after TURP (95% confidence interval [CI] 17.1-30.7) vs 6.0 mL/s after TPLA (95% CI 5.0-7.0), and IPSS, with a mean decrease of 11.6 (95% CI 9.7-13.5) vs 5.8 after TPLA (95% CI.2-9.6) with respect to baseline. CONCLUSION: In our study, TPLA preserved ejaculatory function in 96% of cases in addition to providing significant relief from BPO.

The bladder contractility and bladder outlet obstruction indices in children. Results of a global Delphi consensus study.

AIMS: This Delphi study was planned to examine global expert consensus with regard to utility, accuracy, and categorization of Bladder Contractility Index (BCI), Bladder Outlet Obstruction Index (BOOI), and the related evidence. This manuscript deals with children and follows previous manuscripts reporting on adult men and women. METHODS: Eighteen experts were invited to answer the two-round survey including three foundation questions and four survey questions. Consensus was defined as ≥75% agreement. The ordinal scale (0-10) in Round 1 was classified into "strongly agree," "agree," "neutral," "disagree," and "strongly disagree" for the final round. A systematic search for evidence was conducted for therapeutic studies that have examined outcome stratified by the indices in children. RESULTS: Eleven experts participated in the survey with 100% completion. Consensus was not noted with regard to any of the questions. There was a general trend toward disagreement with the utility of the BCI and BOOI in children. Systematic search yielded one publication pertaining the value of the indices in predicting long-term outcome in boys treated for posterior urethral valves. CONCLUSIONS: This global Delphi survey of experts showed a general disinclination to use numerical indices for bladder contractility and bladder outflow obstruction in children. There is very little data on the use of the BCI and BOOI indices in children. The establishment of urodynamic indices in children might help refine the treatment of functional urological disorders in children.

The bladder contractility and bladder outlet obstruction indices in adult men: Results of a global Delphi consensus study.

AIMS: This Delphi study was planned to examine global expert consensus with regard to utility, accuracy, and categorization of Bladder Contractility Index (BCI) and Bladder Outlet Obstruction Index (BOOI) and the related evidence. METHODS: Twenty-eight experts were invited to answer the two-round survey including three foundation questions and 15 survey questions. Consensus was defined as ≥75% agreement. The ordinal scale (0-10) in round 1 was classified into "strongly agree," "agree," "neutral," "disagree," and "strongly disagree" for the final round. A systematic search for evidence was conducted for therapeutic studies that have examined outcome stratified by the indices in men. RESULTS: Nineteen experts participated in the survey with 100% completion. Consensus was noted with regard to 6 of 19 questions. Experts strongly agreed with utility of quantifying bladder contractility and bladder outflow obstruction with near unanimity regarding the latter. There was consensus that BCI and BOOI were accurate, that BCI was clinically useful, and for defining severe bladder outflow obstruction as BOOI > 80. Systematic search yielded 69 publications (BCI 45; BOOI 50). Most studies examined the indices as a continuous variable or by standard cutoffs (BCI 100, 150; BOOI 20, 40). CONCLUSION: There is general agreement among experts on need for indices to quantify bladder contractility and bladder outflow obstruction as well as with regard to accuracy and utility of BCI and BOOI indices. Few studies have examined the discriminant power of existing cutoffs or explored new ones. This is an extraordinary knowledge gap in the field of urology.

The bladder contractility and bladder outlet obstruction indices in adult women. Results of a global Delphi consensus study.

AIMS: This Delphi study was planned to examine global expert consensus with regard to utility, accuracy, and categorization of the bladder contractility index (BCI), bladder outlet obstruction index (BOOI), and the related evidence. This manuscript deals with adult women and follows a previous manuscript reporting on adult men. METHODS: Twenty-nine experts were invited to answer the two-round survey including three foundation questions and 12 survey questions. Consensus was defined as ≥75% agreement. The ordinal scale (0-10) in round 1 was classified into "strongly agree," "agree," "neutral," "disagree," and "strongly disagree" for the final round. A systematic search for evidence was conducted for therapeutic studies that have examined outcome stratified by the indices in women. RESULTS: Eighteen experts participated in the survey with 100% completion. Consensus was noted with regard to 2 of 12 questions, both in the negative. The experts had a consensus that BOOI was neither accurate nor useful and a similar negative trend was noted with regard to BCI. However, there was support, short of consensus, for the utility on an index of bladder contractility and bladder outflow obstruction. Systematic search yielded eight publications pertaining to stress urinary incontinence (n = 6), pelvic organ prolapse (n = 1), and intra-sphincteric botulinum toxin (n = 1). CONCLUSIONS: Experts had significant concerns with regard to the use of the male BCI and BOOI in adult women despite a general recognition of the need for numerical indices of contractility and obstruction. Systematic search showed a striking lack of evidence in this regard.

Non-transecting dorsal mucosal anastomosis plus ventral oral graft for the treatment of urethral bulbar strictures: single surgeon experience.

PURPOSE: To report our experience with the non-transecting dorsal mucosal anastomosis plus ventral oral graft urethroplasty (NTAVOG) for the repair of tight bulbar urethral strictures. METHODS: Data of 68 men with tight bulbar strictures underwent NTAVOG urethroplasty between 2012 and 2019 were retrospectively revised. The urethra was opened ventrally; the dorsal scarred mucosa was excised preserving the spongiosum; the mobilized mucosal edges were anastomosed to recreate the dorsal urethral plate; the repaired urethral plate was augmented by the ventral oral graft and the spongiosum was closed over it. Successful urethral reconstruction was defined as normal voiding without the need for any postoperative procedure. Sexual function was investigated using a validated questionnaire. RESULTS: Median follow-up was 58 months (IQR 38-63) and mean stricture length was 1 cm (IQR 1-1.5). Of 68 cases, 56 (82.4%) were successful and 12 (17.6%) were failures requiring re-treatment. At multivariable analysis, no preoperative factor was significantly associated with recurrence. None of the preoperatively sexually active 53 patients reported postoperative erectile impairment and all were satisfied with their sexual life. The main limitation is the retrospective design. CONCLUSIONS: In cases of tight bulbar stricture, the NTAVOG urethroplasty provides adequate urethral augmentation by preserving the spongiosum and avoiding postoperative sexual complications. We presented a series of patients undergone non-transecting dorsal anastomosis plus ventral oral graft urethroplasty for tight bulbar stricture. This treatment seems to be safe and with limited postoperative complications thanks to the preservation of the corpus spongiosum.

Clampless Laparoscopic Tumor Enucleation for Exophytic Masses Greater Than 4 cm: Is Renorrhaphy Necessary?

Objective: To demonstrate the safety of clampless 3D laparoscopic tumor enucleation (cLTE) for exophytic T1b kidney masses, avoiding suture to achieve hemostasis. Methods: Between January 2010 and January 2021, 241 consecutive patients with an exophytic renal tumor underwent sutureless cLTE. Patients with predominantly endophytic growth or tumors 4 mm closer to the collecting system less were excluded. In all cases, an attempt was made to accomplish surgery without suturing kidney parenchyma. Data were obtained from a retrospective review of history and physical examinations, operative and pathology reports, anesthesia records during the hospital stay, and follow-up visits. Results: Among 241 patients who underwent cLTE, 148 had cT1a and 93 had cT1b renal tumor. The median tumor size was 32 mm, and the median R.E.N.A.L. (radius exophytic/endophytic nearness anterior/posterior location) score was 6. Renorrhaphy was necessary in 5 cases. The median operative time (OT) was 100 minutes, and the estimated blood loss (EBL) was 150 mL. The median 24-hour decrease in hemoglobin was 1.8 g/dL. The median length of stay was 4 days. Nineteen patients had postoperative complications: 3 cases had Clavien-Dindo (CD) 3a or more, 6 had CD2, and 10 had CD1. Comparing the T1a and T1b groups, except for the median OT and the EBL, no significant differences were observed in all the other variables analyzed. In both groups, renal function was preserved after 1 year from surgery. Conclusion: Our experience showed that sutureless cLTE is safe and feasible for T1b tumors leading to radical oncological outcomes and preserving renal function.

Thulium laser enucleation of prostate versus laparoscopic trans-vesical simple prostatectomy in the treatment of large benign prostatic hyperplasia: head-to-head comparison

ABSTRACT Objectives: To compare thulium laser enucleation of prostate (ThuLEP) versus laparoscopic trans-vesical simple prostatectomy (LSP) in the treatment of benign prostatic hyperplasia (BPH). Materials and Methods: Data of patients who underwent surgery for "large" BPH (>80mL) at three Institutions were collected and analyzed. Two institutions performed ThuLEP only; the third institution performed LSP only. Preoperative (indwelling catheter status, prostate volume (PVol), hemoglobin (Hb), Qmax, post-voiding residual volume (PVR), IPSS, QoL, IIEF-5) and perioperative data (operative time, enucleated adenoma, catheterization time, length of stay, Hb-drop, complications) were compared. Functional (Qmax, PVR, %ΔQmax) and patient-reported outcomes (IPSS, QoL, IIEF-5, %ΔIPSS, %ΔQoL) were compared at last follow-up. Results: 80 and 115 patients underwent LSP and ThuLEP, respectively. At baseline, median PVol was 130 versus 120mL, p <0.001; Qmax 9.6 vs. 7.1mL/s, p=0.005; IPSS 21 versus 25, p <0.001. Groups were comparable in terms of intraoperative complications (1 during LSP vs. 3 during ThuLEP) and transfusions (1 per group). Differences in terms of operative time (156 vs. 92 minutes, p <0.001), Hb-drop (-2.5 vs. −0.9g/dL, p <0.001), catheterization time (5 vs. 2 days, p <0.001) and postoperative complications (13.8% vs. 0, p <0.001) favored ThuLEP. At median follow-up of 40 months after LSP versus 30 after ThuLEP (p <0.001), Qmax improved by 226% vs. 205% (p=0.5), IPSS decreased by 88% versus 85% (p=0.9), QoL decreased by 80% with IIEF-5 remaining almost unmodified for both the approaches. Conclusions: Our analysis showed that LSP and ThuLEP are comparable in relieving from BPO and improving the patient-reported outcomes. Invasiveness of LSP is more significant.

Concurrent Nivolumab and Metformin in Diabetic Cancer Patients: Is It Safe and More Active?

BACKGROUND/AIM: Recent evidence suggests potential synergistic antitumor effects of the combination of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors with the oral hypoglycemic agent metformin. The aim of this study was to investigate the safety and activity of metformin combined with nivolumab in diabetic cancer patients. PATIENTS AND METHODS: Patients with advanced melanoma, renal cell carcinoma or lung cancer receiving nivolumab with concurrent diabetes treated with metformin were retrospectively collected. The primary endpoint was the safety of nivolumab plus metformin combination. RESULTS: We collected 40 patients with solid tumors who received metformin for concomitant diabetes and nivolumab as anticancer therapy in four Italian Hospitals. The concomitant use of nivolumab and metformin was well tolerated; adverse events (AEs) of any grade occurred in 75% of patients (mainly fatigue, pruritus, rash, and asthenia). Grade 3 AEs occurred only in 20% of cases; no grade 4 AEs were observed. A statistically significant correlation was found between higher doses of metformin (>1,000 mg daily) and longer progression-free survival (p=0.021), overall survival (p=0.037) and higher overall response rate. CONCLUSION: The combination of nivolumab and metformin was safe and might have an antitumor activity, supporting further investigations on the synergistic antitumor effect of this combination.

Thulium laser enucleation of prostate versus laparoscopic trans-vesical simple prostatectomy in the treatment of large benign prostatic hyperplasia: head-to-head comparison.

OBJECTIVES: To compare thulium laser enucleation of prostate (ThuLEP) versus laparoscopic trans-vesical simple prostatectomy (LSP) in the treatment of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Data of patients who underwent surgery for "large" BPH (>80mL) at three Institutions were collected and analyzed. Two institutions performed ThuLEP only; the third institution performed LSP only. Preoperative (indwelling catheter status, prostate volume (PVol), hemoglobin (Hb), Qmax, post-voiding residual volume (PVR), IPSS, QoL, IIEF-5) and perioperative data (operative time, enucleated adenoma, catheterization time, length of stay, Hb-drop, complications) were compared. Functional (Qmax, PVR, %ΔQmax) and patient-reported outcomes (IPSS, QoL, IIEF-5, %ΔIPSS, %ΔQoL) were compared at last follow-up. RESULTS: 80 and 115 patients underwent LSP and ThuLEP, respectively. At baseline, median PVol was 130 versus 120mL, p <0.001; Qmax 9.6 vs. 7.1mL/s, p=0.005; IPSS 21 versus 25, p <0.001. Groups were comparable in terms of intraoperative complications (1 during LSP vs. 3 during ThuLEP) and transfusions (1 per group). Differences in terms of operative time (156 vs. 92 minutes, p <0.001), Hb-drop (-2.5 vs. -0.9g/dL, p <0.001), catheterization time (5 vs. 2 days, p <0.001) and postoperative complications (13.8% vs. 0, p <0.001) favored ThuLEP. At median follow-up of 40 months after LSP versus 30 after ThuLEP (p <0.001), Qmax improved by 226% vs. 205% (p=0.5), IPSS decreased by 88% versus 85% (p=0.9), QoL decreased by 80% with IIEF-5 remaining almost unmodified for both the approaches. CONCLUSIONS: Our analysis showed that LSP and ThuLEP are comparable in relieving from BPO and improving the patient-reported outcomes. Invasiveness of LSP is more significant.

The efficacy of a suppository based on Phenolmicin P3 and Bosexil (Mictalase®) in control of irritative symptoms in patients undergoing thulium laser enucleation of prostate: a single-center, randomized, controlled, open label, phase III study.

BACKGROUND: Several studies described post-operative irritative symptoms after laser enucleation of prostate, sometimes associated with urge incontinence, probably linked to laser-induced prostatic capsule irritation, and potential for lower urinary tract infections We aimed to evaluate the efficacy of a suppository based on Phenolmicin P3 and Bosexil (Mictalase®) in control of irritative symptoms in patients undergoing thulium laser enucleation of prostate (ThuLEP). METHODS: In this single-center, prospective, randomized, open label, phase-III study, patients with indication to ThuLEP were enrolled (Dec2019-Feb2021-Institutional ethics committee STS CE Lazio approval no.1/N-726-ClinicalTrials.gov NCT05130918). The report conformed to CONSORT 2010 guidelines. Eligible patients were 1:1 randomized. Randomization defined Group A: patients who were administered Mictalase® suppositories twice a day for 5 days, then once a day for other 10 days; Group B: patients who did not receive Mictalase® ("controls"). Study endpoints were evaluated at 15 and 30 days postoperation. Primary endpoint included evaluation of effects of the suppository on irritative symptoms by administering IPSS + QoL questionnaire. Secondary endpoint included evaluation of effects on urinary tract infections by performance of urinalysis with urine culture. RESULTS: 111 patients were randomized: 56 in Group A received Mictalase®. Baseline and perioperative data were comparable. At 15-days, no significant differences were found in terms of IPSS + QoL scores and urinalysis parameters. A significant difference in the rate of positive urine cultures favored Group A (p = 0.04). At 30-days follow-up, significant differences were found in median IPSS score (6 [IQR 3-11] versus 10 [5-13], Group A vs B, respectively, p = 0.02). Urinalysis parameters and rate of positive urine cultures were not significantly different. CONCLUSIONS: The present randomized trial investigated the efficacy of Mictalase® in control of irritative symptoms and prevention of lower urinary tract infections in patients undergoing ThuLEP. IPSS improvement 30-days postoperation was more pronounced in patients who received Mictalase®. Lower rate of positive urine culture favored Mictalase® group 15-days postoperatively. TRIAL REGISTRATION: The clinical trial has been registered on ClinicalTrials.gov on November 23rd, 2021-Registration number NCT05130918.

Botulinum toxin for treating overactive bladder in men: A systematic review.

PURPOSE: We sought to systematically review the literature on the use of botulinum toxin (BTX-A) injections in the bladder to treat overactive bladder (OAB) in men. MATERIALS AND METHODS: A systematic review was performed to identify clinical trials on efficacy and safety of BTX-A injections in the detrusor for treatment of OAB in men published from inception to October 2020. Quality assessment was performed using the Cochrane Collaboration's tool for assessing risk of bias and study characteristics were extracted by two reviewers independently. RESULTS: After screening 75 abstracts, 12 trials were included in the qualitative synthesis, of which 6 were conducted exclusively in men (mean age: 66.7 years). Only two were randomized controlled studies and the remaining were observational studies, mostly case series. Total number of participants in each study ranged from 28 to 146. Therapeutic response to intravesical BTX-A injection was assessed differently across the studies, which used quality-of-life symptom questionnaires and voiding diary parameters. Urodynamics findings were reported separately for men before and after intravesical injection of BTX-A in two studies only. Pooling of outcome data was possible with adverse events reported after BTX-A by seven studies, which showed urinary tract infection, urinary retention, increased postvoid residual, de novo interstitial cystitis, and hematuria rates of 29.8%, 20.0%, 37.3%, 28.3%, and 12.4%, respectively. CONCLUSIONS: Limited information regarding the efficacy and safety of BTX-A bladder injections for male OAB from relatively low evidence is available. Further research is needed to better understand the risk-benefit profile of BTX-A in the male population.

International Continence Society (ICS) report on the terminology for sexual health in men with lower urinary tract (LUT) and pelvic floor (PF) dysfunction.

INTRODUCTION: The terminology for sexual health in men with lower urinary tract (LUT) and pelvic floor (PF) dysfunction has not been defined and organized into a clinically based consensus terminology report. The aim of this terminology report is to provide a definitional document within this context that will assist clinical practice and research. METHODS: This report combines the input of the members of sexual health in men with LUT and PF Dysfunction working group of the International Continence Society (ICS), assisted at intervals by external referees. Appropriate core clinical categories and a sub-classification were developed to give coding to definitions. An extensive process of 18 rounds of internal and external review was involved to exhaustively examine each definition, with decision-making by collective opinion (consensus). The Committee retained evidence-based definitions, identified gaps, and updated or discarded outdated definitions. Expert opinions were used when evidence was insufficient or absent. RESULTS: A terminology report for sexual health in men with LUT and PF dysfunction, encompassing 198 (178 NEW) separate definitions, has been developed. It is clinically based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different speciality groups involved. Conservative and surgical managements are major additions and appropriate figures have been included to supplement and clarify the text. Emerging concepts and measurements, in use in the literature and offering further research potential, but requiring further validation, have been included as an appendix. Interval (5-10 years) review is anticipated to keep the document updated. CONCLUSION: A consensus-based terminology report for sexual health in men with LUT and PF dysfunction has been produced to aid clinical practice and research. The definitions that have been adopted are those that are most strongly supported by the literature at this time or are considered clinical principles or consensus of experts' opinions.

The microbiological profile of patients with Fournier's gangrene: A retrospective multi-institutional cohort study.

OBJECTIVES: To evaluate the role of the microbiological profile and of disease-related factors in the management of patients affected with Fournier's gangrene (FG). PATIENTS AND METHODS: Data regarding patients admitted for FG at nine Italian Hospitals (March 2007-June 2018) were collected. Patients were stratified according to the number of microorganisms documented: Group A - one microorganism; Group B - two microorganisms; Group C - more than three microorganisms. Baseline blood tests, dedicated scoring systems, predisposing risk factors, disease's features, management and post-operative course were analyzed. UpSet technique for visualizing set intersections in a matrix layout and Cuzick's nonparametric test for trend across ordered groups were used. RESULTS: Eighty-one patients were available for the analysis: 18 included in Group A, 32 in Group B, 31 in Group C. The most common microorganism isolated was Escherichia coli. In Group B-C, Escherichia coli was often associated to Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Statistically significant positive association was highlighted among the number of pathogens (Group A vs B vs C) and serum C-reactive Protein (p < 0.001), procalcitonin (p = 0.02) and creatinine (p = 0.03). Scoring systems were associated with the number of microorganisms detected (p < 0.02). A significant association between the number of microorganisms and the use of VAC therapy and need of a fecal diversion was found (p < 0.02). The number of microorganisms was positively associated with the length of stay (LOS) (p = 0.02). Ten weeks after initial debridement, wound closure was achieved in 11 (91.7%), 22 (84.6%) and 20 (80%) patients in Group A, B, and C, respectively, with no differences in overall survival. CONCLUSION: Polymicrobial infections in FG are positively associated with inflammatory scores, the need for fecal diversion and the LOS. This results may help the counseling and the clinical management of this rare niche of patients.