PD-L1 immunohistochemical expression in bladder urothelial cancer with SP263, SP142 and 22C3 antibodies: A comparative study.

Programmed death ligand 1 (PD-L1) is currently the only biomarker used for the selection of patients with bladder urothelial cancer for immunotherapy. Several platforms, antibodies and scores are currently available for the evaluation of the expression of PD-L1 in immunohistochemistry (IHC). In this study three different antibodies (SP263, SP142 and 22C3) were compared to establish their performances and concordance rates. Twenty-four consecutive cases of surgically resected urothelial cancers of the bladder were enrolled. All cases were revised, and appropriate tumor areas were selected for IHC. Three commercially available PD-L1 antibodies were tested: 22C3 pharmDx with Dako Autostainer Link 48 (Dako, Carpinteria, Ca), and SP263 and SP142 with the Ventana BenchMark (Ventana Medical Systems, Tucson, AZ) platform. All slides were evaluated by an expert pathologist and both the tumor proportion score (TPS) and the combined positive score (CPS) were determined and compared at two different cut-off levels (≥ 1 and ≥ 10). The SP263 and 22C3 clones produced more positive results with the CPS and TPS scores, respectively. The CPS score identified more positive cases than the TPS score, irrespectively of the clone or the cut-off used; the difference was statistically significant in both the SP263 and SP142 clones with the ≥1 cut-off. No statistically significant differences were found between the clones when the ≥1 cut-off was used, irrespectively of the score. At the contrary, a statistically significant difference (p = 0.024) and a trend to significance (p = 0.082) were respectively found for the TPS and CPS scores, when the SP22C3 and the SP142 clones were compared at a cut-off level of ≥10. The ICC test using CPS was 0.676 and 0.578 for the ≥1 and ≥ 10 cut-offs respectively, and 0.729 and 0.467 respectively for the same cut-offs using TPS. This suggests that the three antibodies under investigation cannot be used interchangeably, especially the 22C3 and SP142 clones which showed statistically significant difference when TPS was tested at a ≥ 10 cut-off.

Use of etonogestrel subcutaneous implant in Sardinia, Italy: women's compliance and satisfaction.

PURPOSE OF THE ARTICLE: The main aim of the study was to analyze the population of women who used etonogestrel implant, the reason that led them to this type of contraception, and the degree of compliance with it. Materials and methods: We carried out a retrospective study on women who had etonogestrel subcutaneous implant placed (n°47) over a 6-year period (2015-2021). We submitted the women a series of questions by telephone questionnaire (range 10-72 months after placements, mean 40 months) that investigated the comorbidities and side effects related to etonogestrel implant. MATERIALS AND METHODS: We carried out a retrospective study on women who had etonogestrel subcutaneous implant placed (n°47) over a 6-year period (2015-2021). We submitted the women a series of questions by telephone questionnaire (range 10-72 months after placements, mean 40 months) that investigated the comorbidities and side effects related to etonogestrel implant. RESULTS: The average age of placement of etonogestrel implant was 33.8 ± 3.45 years. As regards level of education, 16/47 (34%) of the women had a university degree, 21/47 (44%) had a high school diploma and 10/47 (21%) had a secondary school diploma. The 12/47 (25%) of the women were, at the time of the counselling, unemployed and only 8% did not use in the past contraceptive methods other than etonogestrel implant. The 92% of women choose etonogestrel implant because it offered safe, comfortable and long-lasting contraception. Among the main side effects evaluated, we reported spotting in 24 out of 47 (51%), headache in 4 out of 47 (8.5%). The 85% of the women recommended etonogestrel implant to their friends as a contraceptive method, with an approval rating for the implant, expressed a rating from 1 to 10 with the mean that was 7.79, the median 8. CONCLUSIONS: Our results are of interest because they derive from a region of Italy in which the Long acting reversible contraception (LARC) is strongly underused. Etonogestrel implant was a safe and effective, long-acting, reversible hormonal contraception (LARC) and majority of women recommended the etonogestrel implant to their friends as a contraceptive method.

Etonogestrel implant is a safe and effective, long-acting, reversible hormonal contraception (LARC). The majority of women in our study choose the etonogestrel implant for its characteristics; among the main side effects evaluated we reported spotting and headache. The majority of women recommended the etonogestrel implant to their friends as a contraceptive method.

Association of HLA-A*11:01, -A*24:02, and -B*18:01 with Prostate Cancer Risk: A Case-Control Study.

The major histocompatibility complex (MHC) loci, the most polymorphic regions within the human genome, encode protein complexes responsible for antigen presentation and CD4+ and CD8+ cell activation. In prostate cancer (PCa), the second most diagnosed cancer in the male population, MHC loci undergo significant changes in their expression patterns, which affect the ability of the immune system to attack and eliminate malignant cells. The purpose of this study was to explore the genetic diversity of human leukocyte antigen (HLA)-A and HLA-B in patients with PCa and healthy controls (HCs) by performing HLA genotyping using NGS technology. The analysis highlighted statistically significant differences (p < 0.05) in the prevalence of three alleles (A*11:01, A*24:02, and B*18:01). Among the HCs analyzed, 14.89% had A*11:01, 20.21% had A*24:02, and 30.61% had B*18:01; while 5.21% of patients with PCa presented A*11:01, 9.38% presented A*24:02, 18.08% presented B*18:01. Odds ratio (OR) calculations underlined a negative association between the three alleles and the risk of PCa (OR < 1). The results presented in this study suggest a protective role of A*11:01, A*24:02, and B*18:01 in PCa.

A Multigene-Panel Study Identifies Single Nucleotide Polymorphisms Associated with Prostate Cancer Risk.

The immune system plays a critical role in modulating cancer development and progression. Polymorphisms in key genes involved in immune responses are known to affect susceptibility to cancer. Here, we analyzed 35 genes to evaluate the association between variants of genes involved in immune responses and prostate cancer risk. Thirty-five genes were analyzed in 47 patients with prostate cancer and 43 healthy controls using next-generation sequencing. Allelic and genotype frequencies were calculated in both cohorts, and a generalized linear mixed model was applied to test the relationship between prostate cancer risk and nucleotide substitution. Odds ratios were calculated to describe the association between each single nucleotide polymorphism (SNP) and prostate cancer risk. Significant changes in allelic and genotypic distributions were observed for IL4R, IL12RB1, IL12RB2, IL6, TMPRSS2, and ACE2. Furthermore, a generalized linear mixed model identified statistically significant associations between prostate cancer risk and SNPs in IL12RB2, IL13, IL17A, IL4R, MAPT, and TFNRS1B. Finally, a statistically significant association was observed between IL2RA and TNFRSF1B and Gleason scores, and between SLC11A1, TNFRSF1B and PSA values. We identified SNPs in inflammation and two prostate cancer-associated genes. Our results provide new insights into the immunogenetic landscape of prostate cancer and the impact that SNPs on immune genes may have on affecting the susceptibility to prostate cancer.

Assessing the Predictive Power of the Hemoglobin/Red Cell Distribution Width Ratio in Cancer: A Systematic Review and Future Directions.

Background and Objectives: The hemoglobin (Hb)/red cell distribution width (RDW) ratio has emerged as an accessible, repeatable, and inexpensive prognostic factor that may predict survival in cancer patients. The focus of this systematic review is to investigate the prognostic role of the Hb/RDW ratio in cancer and the implications for clinical practice. Materials and Methods: A literature search of PubMed, Scopus, and Web of Science databases was performed by an independent author between 18 March and 30 March 2023 to collect relevant literature that assessed the prognostic value of the Hb/RDW ratio in cancer. Overall survival (OS), progression-free survival (PFS), and the association of these with the Hb/RDW ratio were considered to be the main endpoints. Results: Thirteen retrospective studies, including 3818 cancer patients, were identified and involved in this review. It was observed that, when patients with a high vs. low Hb/RDW ratio were compared, those with a lower Hb/RDW ratio had significantly poorer outcomes (p < 0.05). In lung cancer patients, a one-unit increase in the Hb/RDW ratio reduces mortality by 1.6 times, whilst in esophageal squamous-cell carcinoma patients, a lower Hb/RDW ratio results in a 1.416-times greater risk of mortality. Conclusions: A low Hb/RDW ratio was associated with poor OS and disease progression in patients with cancer. This blood parameter should be considered a standard biomarker in clinical practice for predicting OS and PFS in cancer patients. Future searches will be necessary to determine and standardize the Hb/RDW cut-off value and to assess whether the Hb/RDW ratio is optimal as an independent prognostic factor or if it requires incorporation into risk assessment models for predicting outcomes in cancer patients.

The role of surgery in platinum-resistant ovarian cancer: A call to the scientific community.

In the last decade, a growing attention has been focused on identifying effective therapeutic strategies also in the orphan clinical setting of women with platinum-resistant disease. In this context, secondary cytoreductive surgery (SCS) remains a potential approach only in women with platinum sensitive relapse, but experimental data have been published supporting the role of SCS also in patients with platinum-resistant recurrence. In particular, surgery is emerging as a potential option in specific subgroups of women, such as those patients with low-grade serous histology, or low-volume relapse with disease located in the so-called pharmacological sanctuaries. Furthermore, contrasting evidences have suggested a potential role in this clinical setting of SCS combined with intraperitoneal hyperthermic chemotherapy. In this complex scenario we review here the available evidences regarding the role surgery in ovarian cancer patients with platinum resistant disease, trying also to understand which patients may benefit from this challenging, experimental approach.

Serenoa repens + selenium + lycopene vs tadalafil 5 mg for the treatment of lower urinary tract symptoms secondary to benign prostatic obstruction: a Phase IV, non-inferiority, open-label, clinical study (SPRITE study).

OBJECTIVE: To compare in a randomised, open-label, non-inferiority clinical study, the efficacy and tolerability of Serenoa repens (SeR) + selenium (Se) + lycopene (Ly) (SeR-Se-Ly) therapy vs tadalafil 5 mg in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: From May 2015 to January 2017, 427 patients were enrolled in 21 different centres (International Standard Randomised Controlled Trial Number Register [ISRCTN] 73316039). Inclusion criteria included: age between 50 and 80 years, International Prostate Symptom Score (IPSS) ≥12, maximum urinary flow rate (Qmax ) ≤ 15 mL/s, and post-void residual (PVR) <100 mL. Patients were randomised into two groups in a 2:1 ratio: Group A (SeR-Se-Ly, 1 tablet daily for 6 months) and Group B (tadalafil 5 mg, 1 tablet daily for 6 months). The primary endpoint of the study was the non-inferior variation in the IPSS and Qmax in Group A vs Group B after 6 months of treatment. RESULTS: In all, 404 patients completed the full protocol. When comparing both therapies, Group A was statistically not inferior to Group B considering the median change in IPSS (-3.0 vs -3.0; P < 0.01), IPSS quality of life (-2.0 vs -2.0; P < 0.05), and Qmax (2.0 vs 2.0 mL/s; P < 0.01). We found statistically significant differences in the increase of at least 3 points in Qmax (38.2% vs 28.1%; P = 0.04) and of at least 30% of Qmax (39.2% vs 27.3%; P < 0.01) in Group A compared to Group B. The percentage of patients with an increase of at least 3 points in the IPSS and a decrease of at least 25% of the IPSS was not statistically different between the two groups. For adverse events, four patients in Group A (1.44%) and 10 in Group B (7.81%) (P < 0.05) reported side-effects. CONCLUSION: We have shown that treatment with SeR-Se-Ly was not inferior to tadalafil 5 mg for improving IPSS and Qmax in men with LUTS.

Association between dietary phytoestrogens intakes and prostate cancer risk in Sicily.

OBJECTIVE: In this study we aimed to investigate the association between dietary phytoestrogen consumption and prostate cancer in a sample of southern Italian individuals. METHODS: A population-based case-control study on the association between prostate cancer and dietary factors was conducted from January 2015 to December 2016 in a single institution of the municipality of Catania, southern Italy (Registration number: 41/2015). A total of 118 histopathological-verified prostate cancer (PCa) cases and a total of 222 controls were collected. Dietary data was collected by using two food frequency questionnaires. RESULTS: Patients with PCa consumed significantly higher levels of phytoestrogens. Multivariate logistic regression showed that lignans (Q[quartile]4 vs. Q1, OR [odds ratio] = 4.72; p < .05) and specifically, lariciresinol (Q4 vs. Q1, OR = 4.60; p < .05), pinoresinol (Q4 vs. Q1, OR = 5.62; p < .05), matairesinol (Q4 vs. Q1, OR = 3.63; p < .05), secoisolariciresinol (Q4 vs. Q1, OR = 4.10; p < .05) were associated with increased risk of PCa. Furthermore, we found that isoflavones (Q3 vs. Q1, OR = 0.28; p < .05) and specifically, genistein (Q4 vs. Q1, OR = 0.40; p < .05) were associated with reduced risk of PCa. CONCLUSION: We found of an inverse association between dietary isoflavone intake and PCa, while a positive association was found with lignans intake.

Dietary Consumption of Phenolic Acids and Prostate Cancer: A Case-Control Study in Sicily, Southern Italy.

Dietary polyphenols gained the interest of the scientific community due to their wide content in a variety of plant-derived foods and beverages commonly consumed, such as fruits, vegetables, coffee, tea, and cocoa. We aimed to investigate whether there was an association between dietary phenolic acid consumption and prostate cancer (PCa) in South Italy. We conducted a population-based case-control study from January 2015 to December 2016 in a single institution of the municipality of Catania, southern Italy (Registration number: 41/2015). Patients with elevated PSA and/or suspicious PCa underwent transperineal prostate biopsy. A total of 118 histopathological-verified PCa cases were collected and a total of 222 controls were selected from a sample of 2044 individuals. Dietary data were collected by using two food frequency questionnaires and data on the phenolic acids content in foods was obtained from the Phenol-Explorer database (www.phenol-explorer.eu). Association between dietary intake of phenolic acids and PCa was calculated through logistic regression analysis. We found lower levels of caffeic acid (2.28 mg/day vs. 2.76 mg/day; p < 0.05) and ferulic acid (2.80 mg/day vs. 4.04 mg/day; p < 0.01) in PCa when compared to controls. The multivariate logistic regression showed that both caffeic acid (OR = 0.32; p < 0.05) and ferulic acid (OR = 0.30; p < 0.05) were associated with reduced risk of PCa. Higher intake of hydroxybenzoic acids and caffeic acids were associated with lower risk of advanced PCa. High intake of caffeic acid and ferulic acid may be associated with reduced risk of PCa.

Pneumatic lithotripsy versus holmium:YAG laser lithotripsy for the treatment of single ureteral stones: a prospective, single-blinded study.

OBJECTIVE: The aim of this prospective single-blinded study was to analyze the stone-free (SF) rates between pneumatic lithotripsy (PL) and laser lithotripsy (LL) for the treatment of single and primary ureteral stones and to evaluate potentially predictive factors of a SF status. MATERIAL AND METHODS: From January 2010 to January 2011, 133 consecutive patients with single and primary ureteral stones were prospectively enrolled. Uni- and multivariate logistic regression were performed to estimate predictive factors of a SF status. RESULTS: The SF rate in the PL group was 80.7 and 86.1% in the LL group (p = 0.002). Success rates with regard of stone position were not significantly different between groups. At univariate logistic regression, middle ureteral stone (OR 3.33, p = 0.04), distal ureteral stone (OR 4.4, p = 0.02), LL (OR 3.05, p = 0.04) and Hounsfield units (HUs) (OR 1.07, p = 0.03) were significantly predictive factors of a SF status. At a multivariate logistic regression, middle ureteral stone (OR 5.58, p = 0.01), distal ureteral stone (OR 7.87, p < 0.01), LL (OR 2.4, p = 0.02) and HUs ≥1,200 (OR 1.15, p = 0.02) were significantly associated with a SF status. CONCLUSIONS: LL significantly influences the SF status after ureteroscopy, allowing a higher SF rate when compared to PL. HUs may significantly influence this success rate.

Efficacy and 9 years' follow-up of posterior intravaginal slingplasty for genital prolapse.

AIM: The aim of this study was to assess the long-term efficacy and complication rates of posterior intravaginal slingplasty (IVS) in women suffering from genital prolapse. MATERIAL AND METHODS: Posterior IVS or infracoccygeal sacropexy is a minimally invasive procedure for suspension of the vagina with the goal of creating new uterosacral ligaments through the insertion of a polypropylene tape. Forty-four patients were enrolled: 25 patients, affected by uterovaginal prolapse, were subjected to vaginal hysterectomy and posterior IVS; and 19 patients, diagnosed with vaginal vault prolapse, were subjected to posterior IVS alone. The primary outcome for posterior IVS was 12-month, 24-month and annual 9-year postoperative efficacy that is based on a Pelvic Organ Prolapse Quantitative score of -5 at point C, which describes the vaginal apex. RESULTS: Of the 44 patients who underwent posterior IVS, none required blood transfusions with an average reduction of perioperative hemoglobin of 1.2 ± 0.4 g/dl, and the average time of hospitalization was 4.3 ± 0.6 days. The rate of success was 93.18% (41/44) at 9 years' follow-up. We had only one case of extrusion (2.27%) and three cases of recurrence (6.82%), such as two cases of cystocele and of rectocele. CONCLUSIONS: Most patients interviewed confirmed that their quality of life improved after surgery, 86.36% of the operated patients reported that their sexual performance improved and that they would recommend this surgery for their friends. Posterior IVS was a minimally invasive surgical procedure with a high success rate for genital prolapse.

Tailored treatment including radical prostatectomy and radiation therapy + androgen deprivation therapy versus exclusive radical prostatectomy in high-risk prostate cancer patients: results from a prospective study.

PURPOSE: To evaluate outcomes of patients with high risk prostate cancer (PCa) who underwent radical prostatectomy (RP) in a context of a multidisciplinary approach including adjuvant radiation (RT) + androgen deprivation therapy (ADT). MATHERIALS AND METHODS: 244 consecutive patients with high risk localized PCa underwent RP and bilateral extended pelvic lymph node dissection at our institution. Adjuvant RT + 24 months ADT was carried out in subjects with pathological stage ≥ T3N0 and/or positive surgical margins or in patients with local relapse. RESULTS: After a median follow-up was 54.17 months (range 5.4-117.16), 13 (5.3%) subjects had biochemical progression, 21 (8.6%) had clinical progression, 7 (2.9%) died due to prostate cancer and 15 (6.1%) died due to other causes. 136 (55.7%) patients did not receive any adjuvant treatment while 108 (44.3%) received respectively adjuvant or salvage RT+ADT. Multivariate Cox proportional hazard analysis showed that pre-operative PSA value at diagnosis is a significant predictive factor for BCR (HR: 1.04, p < 0.05) and that Gleason Score 8-10 (HR: 2.4; p < 0.05) and PSMs (HR: 2.01; p < 0.01) were significant predictors for clinical progression. Radical prostatectomy group was associated with BPFS, CPFS, CSS and OS at 5-years of 97%, 90%, 95% and 86% respectively, while adjuvant radiation + androgen deprivation therapy group was associated with a BPFS, CPFS and CSS at 5-years of 91%, 83%, 95% and 88%, without any statistical difference. CONCLUSIONS: Multimodality tailored treatment based on RP and adjuvant therapy with RT+ADT achieve similar results in terms of OS after 5-years of follow-up.

Erectile function in men with failed hypospadias repair.

OBJECTIVES: While efforts have been made to study erectile function in patients with urethral stricture, very few prior investigations have specifically assessed erectile function in men with failed hypospadias surgery. We set forth to assess the baseline erectile function of men with hypospadias failure presenting for urethroplasty as adults. METHODS: Retrospective data was analyzed on 163 adult patients with prior failed hypospadias repair who presented for urethroplasty from 2002-2007 at two sites in the United States and Italy. All patients had completed the International Index of Erectile Function (IIEF) pre-operatively. Standard IIEF-6 categories were used to assess baseline level of erectile dysfunction (ED) defined as none (≥ 26), minimal (18-25) ,moderate (11-17), and severe (≤ 10). A subset of 13 hypospadias patients prospectively completed the IIEF questionnaire pre and post- operatively. RESULTS: The mean age at presentation for urethroplasty was 39.7 years. Based on IIEF-6 scores, 54% of patients presented with some degree of ED with 22.1%, 3.7%, and 28.2% reporting severe, moderate and mild ED respectively. While the oldest patient population (>50) had the highest incidence of severe ED (38.9%), the youngest age group (=30) had a 60% rate of ED with 18% classified as severe (Table I). Subset analysis of 13 failed hypospadias patients following urethroplasty revealed that 11 (85%) patients had the same or improved erectile function following surgery. CONCLUSIONS: Patients presenting for repair after hypospadias failure often require complex penile reconstruction impacting both urinary as well as sexual quality of life. Among these patients there appears to be a high baseline prevalence of ED. Older patients had a higher incidence of more severe ED; however, the majority of younger patients still presented with some form of ED and a significant number with severe ED. Urethroplasty does not appear to negatively impact erectile function in men with previous hypospadias failure; however a disease specific questionnaire is needed to fully address this issue.

Diagnosis and treatment of unusual multiorgan Echinococcus hydatid cysts.

Background: Echinococcosis is a zoonotic disease caused by Echinococcus granulosus. Usually, the liver is the most affected organ, accounting for approximately 70% to 85% of cases. The lungs represent 20% of the cases. Fewer than 10% are found in other sites, including the bone, brain, spleen, and kidneys. Case presentation: A young man was referred to a local hospital for dull pain in the right flank, fever, and mild cough. Computed tomography showed 2 large cysts: the first involved the left lung and measured 130 × 90.5 × 120 mm, whereas the second cyst was located in the right kidney and measured 130 × 100 × 120 mm. Surgery was performed to remove both lesions in 2 separate surgical sessions. Conclusions: Echinococcosis is a compulsorily notifiable disease. Collaboration between medical doctors from different specializations is necessary. A multidisciplinary approach is important for the correct therapeutic management of the disease. Furthermore, the high possibility of recurrence makes the long-term follow-up mandatory.

Regional Versus Systematic Biopsy in Addition to Targeted Biopsy: Results from a Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Intensification of targeted biopsy (TBx) around a magnetic resonance imaging (MRI)-visible lesion with regional biopsy (RBx) could obviate the need for systematic biopsy (SBx). We aimed to compare the detection yields of clinically significant prostate cancer (csPCa)-defined as International Society of Urological Pathology (ISUP) grade group ≥2-between TBx + RBx and the reference standard (TBx + SBx). METHODS: RBx was defined as perilesional or ipsilateral biopsy. A literature search was conducted up to September 2023 using PubMed, Embase, and Web of Science databases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Included studies were eligible when presenting data from SBx, TBx, and TBx + RBx cores and their detection yields. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria were used to assess the risk of bias of the included studies. KEY FINDINGS AND LIMITATIONS: Twenty-one studies were included for a meta-analysis. The overall detection yield of csPCa was not statistically different between TBx + SBX and TBx + RBx (46.1% vs 44.2%; odds ratio [OR] 1.07, 95% confidence interval [CI] 0.99-1.16, p = 0.07); similar findings were found also for ISUP grade group ≥3 prostate cancer (PCa; OR 1.06, 95% CI 0.92-1.22, p = 0.43) and in different subgroup analyses. TBx + SBx was associated with higher cancer detection of ISUP grade group 1 PCa (OR 1.16, 95% CI 1.04-1.30, p = 0.008). The main limitations include the retrospective nature of most of the selected studies, heterogeneity of RBx definition, and template. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study supports the use of the TBx + RBx template in the early detection pathway for the detection of csPCa. SBx can be omitted when targeting lesions visible on MRI. PATIENT SUMMARY: A prostate biopsy strategy consisting of taking biopsy in and around an magnetic resonance imaging-visible lesion reduces the risk of detecting indolent prostate cancers without affecting the detection of aggressive tumours.

Modulation of adipose-derived stem cell behavior by prostate pathology-associated plasma: insights from in vitro exposure.

Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.

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.

Current Trends in Mucosal Melanomas: An Overview.

Primary mucosal melanomas (MMs) are uncommon tumors originating from melanocytes located in the mucous membranes at various anatomic sites within the body. MM significantly differs from cutaneous melanoma (CM) regarding epidemiology, genetic profile, clinical presentation, and response to therapies. Despite these differences, that have important implications for both disease diagnosis and prognosis, MMs are usually treated in the same way as CM but exhibit a lower response rate to immunotherapy leading to a poorer survival rate. Furthermore, a high inter-patient variability can be observed in relation to therapeutic response. Recently, novel "omics" techniques have evidenced that MM lesions have different genomic, molecular, and metabolic landscapes as compared with CM lesions, thus explaining the heterogeneity of the response. Such specific molecular aspects might be useful to identify new biomarkers aimed at improving the diagnosis and selection of MM patients who could benefit from immunotherapy or targeted therapy. In this review, we have focused on relevant molecular and clinical advancements for the different MM subtypes in order to describe the updated knowledge relating to main diagnostic, clinical, and therapeutic implications as well as to provide hints on likely future directions.

HERV-K and HERV-H Env Proteins Induce a Humoral Response in Prostate Cancer Patients.

A higher expression of human endogenous retroviruses (HERVs) has been associated with several malignancies, including prostate cancer, implying a possible use as a diagnostic or prognostic cancer biomarker. For this reason, we examined the humoral response against different epitopes obtained from the envelope protein of HERV-K (HERV-K env-su19-37, HERV-K env-su109-126), HERV-H (HERV-H env-su229-241, HERV-H env387-399) and HERV-W (HERV-W env-su93-108, HERV-W env-su248-262) in the plasma of patients affected by prostate cancer (PCa), and compared to that of benign prostate hyperplasia (BPH) and a borderline group of patients with atypical small acinar proliferation (ASAP) and prostate intraepithelial neoplasia (PIN) and healthy controls. A significant antibody response was observed against HERV-K env-su109-126 (p = 0.004) and HERV-H env-su229-241 (p < 0.0001) in PCa patients compared to HCs, BPH and borderline cohorts, whilst no significance difference was found in the antibodies against HERV-W env-su93-108 and HERV-W env-su248-262 in patients with PCa. Our results provided further proof of the association between HERV-K and PCa and added new evidence about the possible involvement of HERV-H in PCa pathogenesis, highlighting their possibility of being used as biomarkers of the disease.

Plasma Polyamine Biomarker Panels: Agmatine in Support of Prostate Cancer Diagnosis.

Prostate cancer is the most frequent malignant tumour among males (19%), often clinically silent and of difficult prognosis. Although several studies have highlighted the diagnostic and prognostic role of circulating biomarkers, such as PSA, their measurement does not necessarily allow the detection of the disease. Within this context, many authors suggest that the evaluation of circulating polyamines could represent a valuable tool, although several analytical problems still counteract their clinical practice. In particular, agmatine seems particularly intriguing, being a potential inhibitor of polyamines commonly derived from arginine. The aim of the present work was to evaluate the potential role of agmatine as a suitable biomarker for the identification of different classes of patients with prostate cancer (PC). For this reason, three groups of human patients-benign prostatic hyperplasia (BPH), precancerous lesion (PL), and prostate cancer (PC)-were recruited from a cohort of patients with suspected prostate cancer (n = 170), and obtained plasma was tested using the LC-HRMS method. Statistics on the receiver operating characteristics curve (ROC), and multivariate analysis were used to examine the predictive value of markers for discrimination among the three patient groups. Statistical analysis models revealed good discrimination using polyamine levels to distinguish the three classes of patients. AUC above 0.8, sensitivity ranging from 67% to 89%, specificity ranging from 74% to 89% and accuracy from 73% to 86%, considering the validation set, were achieved. Agmatine plasma levels were measured in PC (39.9 ± 12.06 ng/mL), BPH (77.62 ± 15.05 ng/mL), and PL (53.31 ± 15.27 ng/mL) patients. ROC analysis of the agmatine panel showed an AUC of 0.959 and p ≤ 0.001. These results could represent a future tool able to discriminate patients belonging to the three different clinical groups.