Targeting CXCR4 impaired T regulatory function through PTEN in renal cancer patients.

BACKGROUND: Tregs trafficking is controlled by CXCR4. In Renal Cell Carcinoma (RCC), the effect of the new CXCR4 antagonist, R54, was explored in peripheral blood (PB)-Tregs isolated from primary RCC patients. METHODS: PB-Tregs were isolated from 77 RCC patients and 38 healthy donors (HDs). CFSE-T effector-Tregs suppression assay, IL-35, IFN-γ, IL-10, TGF-ß1 secretion, and Nrp-1+Tregs frequency were evaluated. Tregs were characterised for CTLA-4, PD-1, CD40L, PTEN, CD25, TGF-ß1, FOXP3, DNMT1 transcriptional profile. PTEN-pAKT signalling was evaluated in the presence of R54 and/or triciribine (TCB), an AKT inhibitor. Methylation of TSDR (Treg-Specific-Demethylated-Region) was conducted. RESULTS: R54 impaired PB-RCC-Tregs function, reduced Nrp-1+Tregs frequency, the release of IL-35, IL-10, and TGF-ß1, while increased IFN-γ Teff-secretion. The CXCR4 ligand, CXCL12, recruited CD25+PTEN+Tregs in RCC while R54 significantly reduced it. IL-2/PMA activates Tregs reducing pAKT+Tregs while R54 increases it. The AKT inhibitor, TCB, prevented the increase in pAKT+Tregs R54-mediated. Moreover, R54 significantly reduced FOXP3-TSDR demethylation with DNMT1 and FOXP3 downregulation. CONCLUSION: R54 impairs Tregs function in primary RCC patients targeting PTEN/PI3K/AKT pathway, reducing TSDR demethylation and FOXP3 and DNMT1 expression. Thus, CXCR4 targeting is a strategy to inhibit Tregs activity in the RCC tumour microenvironment.

Micro-Ultrasound in the Diagnosis and Staging of Prostate and Bladder Cancer: A Comprehensive Review.

Background and Objectives: Multiparametric magnetic resonance imaging (mpMRI) of the prostate and prostate-specific membrane antigen positron emission tomography (PSMA PET) are some examples of how the advancement of imaging techniques have revolutionized the diagnosis, staging, and consequently management of patients with prostate cancer (PCa). Although with less striking results, novel radiological modalities have also been proposed for bladder cancer (BCa) in recent years. Micro-ultrasound (MUS) is an imaging examination characterized by high real-time spatial resolution, recently introduced in the urological field. This article aimed to describe the current evidence regarding the application of MUS for the diagnosis and staging of PCa and BCa. Materials and Methods: We designed a narrative review. A comprehensive search in the MEDLINE, Scopus, and Cochrane Library databases was performed. Articles in English-language and published until July 2022 were deemed eligible. Retrospective and prospective primary clinical studies, as well as meta-analyses, were included. Results: MUS-guided prostate biopsy showed high sensitivity (0.91, 95% CI, 0.79-0.97) in the diagnosis of clinically significant PCa (csPCa). It was associated with a higher detection rate of csPCa than a systematic biopsy (1.18, 95% CI 0.83-1.68). No significant difference was found between MUS and mpMRI-guided biopsy in the total detection of PCa (p = 0.89) and in the detection of Grade Groups ≥ 2 (p = 0.92). The use of MUS to distinguish between non-muscle-invasive and muscle-invasive BCa was described, highlighting an up-staging with MUS only in a minority of cases (28.6%). Conclusions: Promising findings have emerged regarding the feasibility and accuracy of MUS in the diagnosis and staging of PCa and BCa. However, the available evidence is limited and should be considered preliminary.

Silodosin 8 mg improves benign prostatic obstruction in Caucasian patients with lower urinary tract symptoms suggestive of benign prostatic enlargement: results from an explorative clinical study.

BACKGROUND: To preliminary investigate the effects of silodosin 8 mg once daily on obstruction urodynamic parameters and subjective symptoms in Caucasian patients with lower urinary tract symptoms suggestive of benign prostatic enlargement. METHODS: We performed a single-center, open-label, single-arm, post-marketing interventional clinical trial. Inclusion criteria were: Caucasian subjects aged ≥50 years waiting to undergo surgery for lower urinary tract symptoms suggestive of benign prostatic enlargement, international prostate symptom total score ≥ 13, international prostate symptom-quality of life score ≥ 3, prostate volume ≥ 30 ml, maximum urine flow rate ≤ 15 mL/s, bladder outlet obstruction index > 40. Eligible subjects received one capsule of silodosin 8 mg once daily for 8 weeks. Invasive urodynamic evaluations were performed at baseline and at 8-weeks follow-up. International prostate symptom questionnaire was administered at baseline, after 4-weeks and 8-weeks of treatment. RESULTS: Overall, 34 subjects were included. Mean bladder outlet obstruction index significantly decreased from 70.6 to 39.2 and bladder outlet obstruction index class improved in 16 patients (53.3%). Statistically significant improvements of mean total international prostate symptom score, mean storage sub-score, mean voiding sub-score and mean quality of life sub-score were evident after 4-weeks of treatment with further improvements after 8-weeks. At the end of the treatment, all patients declared that their condition improved enough to spare or delay surgery. CONCLUSIONS: Silodosin 8 mg once daily significantly improves benign prostatic obstruction in Caucasian patients with lower urinary tract symptoms suggestive of benign prostatic enlargement waiting for surgery. TRIAL REGISTRATION: EudraCT n. 2015-002277-38 Date of registration: 15th December 2017.

Prevalence and risk factors of erectile dysfunction in patients with hepatitis B virus or hepatitis C virus or chronic liver disease: results from a prospective study.

Background Approximately 300million people are affected by hepatitis B virus (HBV) or hepatitis C virus (HCV) infection worldwide. Erectile dysfunction (ED) is a frequent condition that impairs the quality of life and can be associated with several chronic disorders (type 2 diabetes mellitus, atherosclerosis, depression). Few studies have evaluated the prevalence of ED in patients with HBV and HCV chronic infection. The aim of this study was to evaluate the prevalence and the risk factors of ED in a cohort of patients with HBV or HCV-related chronic liver diseases. METHODS: Consecutive patients with HCV and HBV chronic infection were enrolled. RESULTS: In total, 89 out (49 with cirrhosis, 21 with HBV and 68 with HCV infection) were included in this study. ED was diagnosed in 76.4% of patients. The use of phosphodiesterase type 5 inhibitors was reported by 21.3% of patients. Patients with ED were older and had a higher rate of cirrhosis and diabetes mellitus compared with patients without ED. At multivariate analysis, diabetes mellitus and stage of liver disease (cirrhosis vs chronic hepatitis) were the only independent predictors of ED. CONCLUSION: Due to the high rate of ED in outpatients with viral-related liver disease and the underuse of phosphodiesterase type 5 inhibitors, a larger study focussed on these patients is needed.

External validation of a nomogram for outcome prediction in management of medium-sized (1-2 cm) kidney stones.

BACKGROUND: Stone nomogram by Micali et al., able topredict treatment failure of shock-wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PNL) in the management of single 1-2 cm renal stones, was developed on 2605 patients and showed a high predictive accuracy, with an area under ROC curve of 0.793 at internal validation. The aim of the present study is to externally validate the model to assess whether it displayed a satisfactory predictive performance if applied to different populations. METHODS: External validation was retrospectively performed on 3025 patients who underwent an active stone treatment from December 2010 to June 2021 in 26 centers from four countries (Italy, USA, Spain, Argentina). Collected variables included: age, gender, previous renal surgery, preoperative urine culture, hydronephrosis, stone side, site, density, skin-to-stone distance. Treatment failure was the defined outcome (residual fragments >4 mm at three months CT-scan). RESULTS: Model discrimination in external validation datasets showed an area under ROC curve of 0.66 (95% 0.59-0.68) with adequate calibration. The retrospective fashion of the study and the lack of generalizability of the tool towards populations from Asia, Africa or Oceania represent limitations of the current analysis. CONCLUSIONS: According to the current findings, Micali's nomogram can be used for treatment prediction after SWL, RIRS and PNL; however, a lower discrimination performance than the one at internal validation should be acknowledged, reflecting geographical, temporal and domain limitation of external validation studies. Further prospective evaluation is required to refine and improve the nomogram findings and to validate its clinical value.

Comparison of laparoscopic versus open simple nephrectomy in patients with xanthogranulomatous pyelonephritis: A singlecenter analysis of outcomes and predictors of surgical approaches and complications.

Background: The aim of this study was to compare the outcomes of open simple nephrectomy and laparoscopic simple nephrectomy in patients with xanthogranulomatous pyelonephritis (XGP) in a single-institutional retrospective study and to identify predictive factors of surgical approaches and complications. Materials and methods: We retrospectively analyzed the data of 67 consecutive patients with a histopathological diagnosis of XGP who underwent either open simple nephrectomy (ON) or laparoscopic simple nephrectomy (LN) from January 2014 to April 2020. The primary endpoint was the evaluation of perioperative outcomes and complications. Secondary endpoints were to define factors influencing the surgical approach and the likelihood of postoperative complications. Results: Overall, 44 out of 67 patients (65.67%) underwent ON, while 23 (34.33%) underwent LN. Patients in the ON group experienced more postoperative pain according to the visual analogic scale (p = 0.032). Moreover, time to deambulation and time to return to full daily activities, assessed according to the 12-Item Short Form Survey physical and mental component summary scores questionnaires, were significantly shorter in the LN group (p = 0.021, p < 0.001, and p < 0.001, respectively). Of note, there were no significant differences in intraoperative and postoperative complication rates among the groups (p = 0.258 and p = 0.317, respectively). No conversion to open surgery was described. Logistic regression analysis demonstrated that urgency (p = 0.025) was the only predictor associated with a higher risk of intraoperative complications. However, no independent factors associated with postoperative complications or with the surgical approach of choice were found. Conclusions: Based on our results, laparoscopic treatment of XGP represents a feasible alternative to ON, resulting in less postoperative pain and faster recovery. In skilled hands, LN should be considered as the treatment of choice for XGP.

MRI-Cavernosography: A New Diagnostic Tool for Erectile Dysfunction Due to Venous Leakage: A Diagnostic Chance.

Erectile dysfunction caused by venous leakage is a vascular disease in which blood fails to accumulate in the corpora cavernosa due to the abrupt drainage of blood from the penis secondary to an abnormal venous network that affects 1 to 2% of men under 25 years old and about 10 to 20% over 60 years old, who do not raise a sufficient erection for penetrative sex. The study of the venous leak and its characterization in young patients with erectile dysfunction represent a diagnostic challenge, and imaging remains the best way to diagnose this condition. In the article, it is described the methods of execution and the diagnostic role of the cavernous MRI in the study of vasogenic erectile dysfunction from the venous leak, proposing it as a good alternative to the cavernous CT, considering the satisfactory results in terms of diagnostic interpretation, the absence of ionizing radiation, the higher soft tissue resolution of the imaging method and the lower administration of contrast agent.

In-vitro and in-vivo new evidence for Flexor® Vue™ deflecting endoscopic system use: optimization of the stone free rate (SFR) after flexible ureteroscopy and Ho:YAG laser lithotripsy.

To test in-vitro and in-vivo the Flexor® Vue™ deflecting endoscopic system (FVDES) as a new technology able to improve the removal of residual intrarenal fragments.This is an observational prospective "proof of concept" study performed in patients with renal calculi treated with flexible ureteroscopy and Ho:YAG laser lithotripsy (f-URS) in Humanitas Research Hospital (Rozzano, Italy). We assessed feasibility, efficacy and safety of FVDES as an in-vivo tool for removing residual fragments after f-URS. The stone-free rate (SFR) at 30 days post-operatively was evaluated using CT. An in-vitro model was developed to evaluate the FVDES when used for this purpose.Eleven patients (M/F ratio: 7/4, mean age 63.5 ± 8.3) were treated. The stones were located in the lower calyces and the renal pelvis in 3 and 8 patients, respectively. Mean stone size was 18 ± 3.2 mm. The procedure with FVDES was feasible and effective in all the patients. Mean operative time was 82 ± 13.7 min and median hospitalization was of 1.5 days. The SFR after 90 days was 81% (9/11). We reported no relevant complications (Clavien-Dindo > 2); one patient had fever and was treated with antibiotics. The experimental in-vitro model demonstrated the efficacy of FVDES, allowing the removal of about 90% of fragments.Our study showed that FVDES is effective when used as a tool for retrieval of residual fragments at the end of f-URS. This technology could ensure a complete cleaning of the intrarenal collecting system and represent a safe alternative to basketing.

Laparoscopic versus open partial nephrectomy for the management of highly complex renal tumors with PADUA score ⩾10: A single center analysis.

INTRODUCTION: The aim of this study was to compare laparoscopic and open partial nephrectomy (PN) for renal tumors of high surgical complexity (PADUA score ⩾10). METHODS: We retrospectively evaluated 93 consecutive patients who underwent PN at our department from January 2015 to September 2019. 21 patients underwent open partial nephrectomy (OPN) (Group A) and 72 underwent laparoscopic partial nephrectomy (LPN) (Group B). All OPNs were performed with a retroperitoneal approach, while all LPNs were performed with a transperitoneal approach by a single surgical team. Post-operative complications were classified according to the Clavien-Dindo system. RESULTS: The two groups showed no difference in terms of patients' demographics as well as tumor characteristics in all variables. Group A was found to be similar to group B in terms of operation time (p = 0.781), conversion to radical nephrectomy (p = 0.3485), and positive surgical margins (p = 0.338) while estimated blood loss (p = 0.0205), intra-operative (p = 0.0104), and post-operative (p = 0.0081) transfusion rates, drainage time (p = 0.0012), pain score at post-operative day 1 (<0.0001) were significantly lower in Group B. The rate of enucleation and enucleoresection/polar resection was similar (p = 0.1821) among the groups. Logistic regression analysis indicated that preoperative factors were not independently associated with the surgical approach. There was a statistically significant difference in complication rate (<0.0001) between the two groups even if no significant difference in terms of grade ⩾3 post-operative complications (p = 0.3382) was detected. DISCUSSION: LPN represents a feasible and safe approach for high complex renal tumors if performed in highly experienced laparoscopic centers. This procedure offers good intraoperative outcomes and a low rate of post-operative complications.

A Randomized, Controlled Trial Comparing the Impact of a Low-Calorie Ketogenic vs a Standard Low-Calorie Diet on Fat-Free Mass in Patients Receiving an Elipse™ Intragastric Balloon Treatment.

BACKGROUND: The Elipse™ intragastric balloon (EIGB) is a new swallowable balloon for weight loss (WL). Preserving metabolically active fat-free mass (FFM) and resting metabolic rate (RMR) during WL are crucial to maximize fat mass (FM) loss. After EIGB placement, a standard low-calorie diet (LCD) is generally prescribed. A low-calorie ketogenic diet (LCKD) has proven to be safe and effective in reducing FM while preserving FFM and RMR. OBJECTIVE: To prospectively compare the effects on WL, FM, FFM, and RMR in two groups of patients who were randomized to two different diets: LCKD and a standard LCD after EIGB placement. METHODS: WL, FM, FFM, and RMR were measured before EIGB and at 4 months in 48 patients who received either a LCKD (n = 24) or a standard LCD (n = 24). Compliance in following the prescribed diet was determined with food frequency questionnaires in all patients. The impact of LCKD and LCD on renal function was also evaluated. RESULTS: The LCKD group showed a significantly lower decrease in FFM and RMR when compared with the LCD group (3.55 vs 14.3%, p < 0.001; 9.79 vs 11.4%, p < 0.001, respectively). FM decreased more significantly with LCKD compared to LCD (41.6 vs 33.1%, p = 0.0606). Compliance in following the prescribed diets, without negative impact on renal function, was found. CONCLUSION: Based on our findings, despite the small sample size, we were able to support the hypothesis that LCKD is associated with an increased FM loss while reducing the FFM loss and the RMR, without interfering with renal function after EIGB.

Oncology and complications.

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy.

Detection of colo-rectal liver metastases: prospective comparison of contrast enhanced US, multidetector CT, PET/CT, and 1.5 Tesla MR with extracellular and reticulo-endothelial cell specific contrast agents.

BACKGROUND: To compare contrast-enhanced US (CE-US), multidetector-CT (MDCT), 1.5 Tesla MR with extra-cellular (Gd-enhanced) and intracellular (SPIO-enhanced) contrast agents and PET/CT, in the detection of hepatic metastases from colorectal cancer. MATERIALS AND METHODS: A total of 34 patients with colo-rectal adenocarcinoma underwent preoperatively CE-US, MDCT, Gd- and SPIO-enhanced MR imaging (MRI), and PET/CT. Each set of images was reviewed independently by two blinded observers. The ROC method was used to analyze the results, which were correlated with surgical findings, intraoperative US, histopathology, and MDCT follow-up. RESULTS: A total of 57 hepatic lesions were identified: 11 hemangiomas, 29 cysts, 1 focal fatty liver, 16 metastases (dimensional distribution: 5/16 < 5 mm; 3/16 between 5 mm and <10 mm; 8/16 ≥ 10 mm). Six of 34 patients were classified as positive for the presence of at least one metastasis. Considering all the metastases and those ≥ 10 mm, ROC areas showed no significant differences between Gd- and SPIO-enhanced MRI, which performed significantly better than the other modalities (P < 0.05). Considering the lesions <10 mm, ROC areas showed no significant differences between all modalities; however MRI presented a trend to perform better than the other techniques. Considering the patients, ROC areas showed no significant differences between all the modalities; however PET/CT seemed to perform better than the others. CONCLUSIONS: Gd- and SPIO-enhanced MRI seem to be the most accurate modality in the identification of liver metastases from colo-rectal carcinoma. PET/CT shows a trend to perform better than the other modalities in the identification of patients with liver metastases.

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.

OBJECTIVES: The aim of this study was to analyse the role of two alkaloid, Protopine and Nuciferine, in the prevention and the treatment of the low and mild grade adverse events related to the use of HIVEC® (Hyperthermic IntraVEsical Chemotherapy) instillations. MATERIALS AND METHODS: From September 2017 to September 2019, 100 patients were prospectively randomized into two groups: Group A = Protopine and Nuciferine syrup, 10 ml, once a day, for 8 weeks; Group B = placebo (flavoured coloured water), 10 ml, once a day, for 8 weeks. The primary endpoint was the evaluation of the efficacy of the therapy with Protopine and Nuciferine in controlling of the irritative symptoms. The secondary endpoint was the evaluation of the influences of the treatment on the uroflowmetric parameters. RESULTS: The patients of Group A showed a better International Prostatic Symptoms Score (IPSS) score, a better control of urgency symptoms (PPIUS) and tolerate well the pain (VAS score). The treatment doesn't modify Uroflow-Qmax and seems to improve the Uroflow-Voided Volume (ml) without influencing the Uroflow-Post Void Residual volume (PVR). Moreover, the treatment with Protopine and Nuciferine has been proven to be effective in the treatment of overactive bladder (OAB) symptoms. Patients' evaluation of the two different treatments assessed with Patient Global Impression of Improvement questionnaire (PGI-I), demonstrated improvements in the Group A, while the Group B showed a lower satisfaction. CONCLUSIONS: Protopine and Nuciferine can be interesting nutraceutical compounds useful to control irritative and pain related symptoms of intravesical chemo/immunotherapy.

Efficacy and safety of low-intensity shockwave therapy plus tadalafil 5 mg once daily in men with type 2 diabetes mellitus and erectile dysfunction: a matched-pair comparison study.

Low-intensity extracorporeal shockwave therapy (LiESWT) represents a promising treatment for patients with erectile dysfunction (ED). We investigated the efficacy of LiESWT combined with tadalafil 5 mg once daily in men with type 2 diabetes mellitus (T2DM) and ED and compared LiESWT protocols administering different number of shockwaves. We performed a retrospective matched-pair comparison using data from a prospectively maintained database. Seventy-eight patients who received tadalafil 5 mg once daily for 12 weeks + LiESWT performed with an electrohydraulic source for 3 weeks (Group A) were matched 1:1 to patients who received tadalafil 5 mg once daily alone for 12 weeks (Group B). A subgroup analysis was performed according to the number of shockwaves delivered during each session (1500, 1800, and 2400 in subgroup A1, A2, and A3, respectively). The mean International Index of Erectile Function-5 (IIEF-5) score variations with respect to baseline recorded at 4, 12, and 24 weeks after the end of the treatment were investigated as treatment outcomes. The mean IIEF-5 scores significantly improved in all groups and subgroups at 4-week follow-up without intergroup differences. At 12- and 24-week follow-up, the mean IIEF-5 improvement was significantly higher among patients in the A3 subgroup (+5.0 ± 2.1 [P < 0.001] and +4.7 ± 2.3 [P < 0.001], respectively). The combined approach with tadalafil 5 mg once daily and LiESWT with a protocol involving 2400 shockwaves provides significant advantages in terms of IIEF-5 improvement and durability compared to tadalafil 5 mg once daily alone in patients with T2DM and ED.

Detection of Extraprostatic Extension of Cancer on Biparametric MRI Combining Texture Analysis and Machine Learning: Preliminary Results.

RATIONALE AND OBJECTIVES: Extraprostatic extension of disease (EPE) has a major role in risk stratification of prostate cancer patients. Currently, pretreatment local staging is performed with MRI, while the gold standard is represented by histopathological analysis after radical prostatectomy. Texture analysis (TA) is a quantitative postprocessing method for data extraction, while machine learning (ML) employs artificial intelligence algorithms for data classification. Purpose of this study was to assess whether ML algorithms could predict histopathological EPE using TA features extracted from unenhanced MR images. MATERIALS AND METHODS: Index lesions from biparametric MRI examinations of 39 patients with prostate cancer who underwent radical prostatectomy were manually segmented on both T2-weighted images and ADC maps for TA data extraction. Combinations of different feature selection methods and ML classifiers were tested, and their performance was compared to a baseline accuracy reference. RESULTS: The classifier showing the best performance was the Bayesian Network, using the dataset obtained by the Subset Evaluator feature selection method. It showed a percentage of correctly classified instances of 82%, an area under the curve of 0.88, a weighted true positive rate of 0.82 and a weighted true negative rate of 0.80. CONCLUSION: A combined ML and TA approach appears as a feasible tool to predict histopathological EPE on biparametric MR images.

Abbreviated Protocols versus Multiparametric MRI for Assessment of Extraprostatic Extension in Prostatic Carcinoma: A Multireader Study.

BACKGROUND/AIM: Prostate multiparametric magnetic resonance imaging (mpMRI) is the reference imaging modality for extraprostatic extension of disease (EPE) assessment. We aimed to compare the diagnostic accuracy of different abbreviated MRI protocols to the standard prostate mpMRI in the identification of EPE of PCa. PATIENTS AND METHODS: Fifty patients were retrospectively enrolled. Dual-pulse (dpMRI) and biparametric (bpMRI) abbreviated protocols were obtained from mpMRI. The performance of two experienced radiologists and two radiology residents was correlated with a reference standard and compared. Inter and intra-reader agreements were evaluated. RESULTS: All protocols were strongly correlated to the reference standard (p≤0.001). A significant difference was found between dpMRI and mpMRI (p=0.009), no differences emerged between bpMRI and mpMRI (p=0.27). All readers showed moderate agreement (ĸ=0.47, ĸ=0.50 and ĸ=0.53 for dpMRI, bpMRI and mpMRI, respectively). Intra-reader agreement was good (all ĸ values ≥0.70). CONCLUSION: Only bpMRI showed similar diagnostic performance to mpMRI, thus appearing as a feasible alternative to the standard protocol for EPE detection.

A very large leiomyoma of the urethra: A case report.

INTRODUCTION: Leiomyomas are benign mesenchymal tumours of smooth muscle origin. They are the most common uterine masses in women of reproductive age group and may be related to the hormonal status. Urethral leiomyomas are very rare. According to the literature, the mean diameter of the urethral leiomyomas is 3.7 cm. CASE REPORT: We report a case of a very large leiomyoma of the urethra. A 40-year-old women woman was admitted to our department for a giant vaginal mass. She complained of haematuria, dysuria, recurrent urinary tract infections and dyspareunia. The physical evaluation demonstrated a 6 × 5.5 cm neoformation involving the distal tract of the urethra. The patient underwent an ultrasonography and then a magnetic resonance that suggested the diagnosis of leiomyoma. The neoformation was excised through a suburethral incision. CONCLUSIONS: The patient was discharged after 3 days and no intraoperative and postoperative complications occurred. The Foley catheter was removed after a week. The patient was continent to urine, and at 6 months follow-up, the patient was symptom free and no recurrences occurred.

PSA-density does not improve bi-parametric prostate MR detection of prostate cancer in a biopsy naïve patient population.

PURPOSE: Bi-parametric prostate MR (bp-MR) is a valuable tool for detection and characterization of prostate cancer (PCa). Recent studies suggested that PSA-density (PSA-D) in combination with multi-parametric prostate MR as well as bp-MR may achieve a higher diagnostic accuracy than either alone. We aimed to evaluate the diagnostic performance of bp-MR, PSA-D and their combination in biopsy-naïve patients. METHODS AND MATERIALS: We retrospectively analyzed 334 consecutive patients who underwent prostate MR on a 3T scanner. Only patients (n = 114) who underwent TRUS-biopsy within 30 days following MR with no previous prostate biopsies were considered. Our protocol included T2-weighted and DWI sequences. A Likert score based on PI-RADS v2 was used for bp-MR evaluation. Lesions were graded histopathologically using the ISUP score. We assessed three scenarios: detection of lesions independently of ISUP score (ISUP ≥ 1), detection of both intermediate and clinically significant lesions (ISUP ≥ 2) and detection of clinically significant lesions alone (ISUP ≥ 3). Predictive value of bp-MR and PSA-D was evaluated by ROC curves and logistic regression analysis. A p value < 0.05 was considered statistically significant. RESULTS: In all evaluated scenarios, bp-MR showed a significantly higher predictive power (AUC = 0.87-0.95) compared to the performance of PSA-D (AUC = 0.73-0.79), while their combination (AUC = 0.91-0.95) showed no statistically significant improvement compared to bp-MR alone. CONCLUSION: Our results confirm that bp-MR is a powerful tool in detection of clinically significant PCa. Contrary to findings in the recent literature, PSA-D does not appear to significantly improve its diagnostic performance.

Targeting CXCR4 reverts the suppressive activity of T-regulatory cells in renal cancer.

With the intent to identify biomarkers in renal cell carcinoma (RCC) the functional status of T-regulatory cells (Tregs) was investigated in primary RCC. Tregs were isolated from tumoral-(TT), peritumoral tissue-(PT) and peripheral blood-(PB) of 42 primary RCC patients and function evaluated through effector T cells (Teff) proliferation, cytokines release and demethylation of Treg Specific Region (TSDR). The highest value of Tregs was detected in TT with the uppermost amount of effector-Tregs-(CD4+CD25hiFOXP3hiCD45RA-). PB-RCC Tregs efficiently suppress Teff proliferation compared to healthy donor (HD)-Tregs and, at the intrapatient evaluation, TT-derived Tregs were the most suppressive. Higher demethylation TSDR was detected in TT- and PB-RCC Tregs vs HD-Tregs (P <0,001). CXCR4 is highly expressed on Tregs, thus we wished to modulate Tregs function through CXCR4 inhibition. CXCR4 antagonism, elicited by a new peptidic antagonist, Peptide-R29, efficiently reversed Tregs suppression of Teff proliferation. Thus Tregs functional evaluation precisely reflects Tregs status and may be a reliable biomarker of tumoral immune response. In addition, treatment with CXCR4 antagonist, impairing Tregs function, could improve the anticancer immune response, in combination with conventional therapy and/or immunotherapy such as checkpoints inhibitors.

Uterine dehiscence in term pregnant patients with one previous cesarean delivery: growth factor immunoexpression and collagen content in the scarred lower uterine segment.

OBJECTIVE: This study aimed at investigating the relationship between the occurrence of uterine dehiscence in term pregnant scarred uteri and the presence of altered biochemical behavior of the scarring process. STUDY DESIGN: Collagen content and the expression of transforming growth factor-beta and its isoforms transforming growth factor-beta1 and transforming growth factor-beta3, connective tissue growth factor, basic fibroblast growth factor, vascular endothelial growth factor, platelet-derived growth factor, and tumor necrosis factor-alpha in myometrium of lower uterine segment were assessed in 19 otherwise healthy term patients with one previous cesarean delivery who were not in labor. We were searching for differences between patients who showed uterine dehiscence (9 cases) and patients who showed a normal-appearing scarred lower uterine segment (10 cases). We also evaluated all these features in lower uterine segment from unscarred uteri of 10 otherwise healthy patients who were not in labor. RESULTS: In the case of uterine dehiscence, the scarred lower uterine segment showed a higher collagen content, a reduction of pan transforming growth factor-beta expression because of a marked decrease or absence of transforming growth factor-beta3, a reduction of connective tissue growth factor, an increase in basic fibroblast growth factor and a slight enhancement in vascular endothelial growth factor, platelet-derived growth factor, and tumor necrosis factor-alpha expression. CONCLUSION: These findings contribute to meliorate our knowledge about uterine scar healing and allow us to hypothesize that uterine dehiscence of a scarred uterus may be related to altered biochemical behavior of the scarring process.