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.

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.

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.

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.

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.

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. .

Función eréctil en hombres tras fracaso de reparación del hipospadias / Erectile function in men with failed hypospadies repair

OBJETIVO: Aunque se han hecho esfuerzos para estudiar la función eréctil en pacientes con estenosis de uretra, muy pocas investigaciones previas han evaluado específicamente la función eréctil en varones en los que ha fracasado la cirugía del hipospadias. Buscamos evaluar la función eréctil basal de los varones con fracaso de la reparación del hipospadias que acuden para uretroplastia en edad adulta. MÉTODOS: Análisis retrospectivo de los datos de 163 pacientes adultos con fallo de reparación previa de hipospadias que consulta para uretroplastia entre los años 2000-2007 en dos centros en los Estados Unidos de América e Italia. Todos los pacientes habían rellenado el IIEF (índice internacional de función eréctil) en el preoperatorio. Las categorías del IIEF-6 Standard se utilizaron para evaluar el nivel basal de disfunción eréctil (DE) definido como nada (≥26), mínima (18-25), moderada (11-17) y grave (£10). Un subgrupo de 13 pacientes con hipospadias completaron el cuestionario IIEF de forma prospectiva antes y después de la cirugía. RESULTADOS: La edad media de los pacientes en el momento de la consulta era 39,7 años. En base a los resultados del IIEF-6, el 54% de los pacientes presentaban algún grado de DE con 22.1%, 3.7% y 28.2% comunicando DE grave, moderada y leve respectivamente. Mientras que la población de pacientes más mayor (>50) tenía la incidencia más alta de DE grave (38,9%), el grupo de edad más joven (≤30) tenía una tasa de DE del 60% con el 18% clasificada como grave (Tabla 1). El análisis del subgrupo de 13 pacientes con hipospadias fallidos después de uretroplastia reveló que 11 (85%) de los pacientes tenían la misma función eréctil o mejor después de la cirugía. CONCLUSIONES: Los pacientes que consultan para reoperación después del fracaso de la cirugía del hipospadias con frecuencia requieren reconstrucciones peneanas complejas que tienen impacto sobre la calidad de vida urinaria y sexual. Entre estos pacientes parece existir una alta prevalencia de DE. Los pacientes más mayores tienen una incidencia mayor de DE más grave; sin embargo, la mayoría de los pacientes más jóvenes también presentan algo de DE y un número significativo DE grave. La uretroplastia no parece impactar negativamente la función eréctil en hombres con cirugía de hipospadias previa fallida; sin embargo es necesario un cuestionario específico de la enfermedad para tratar completamente este problema

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