Herein, for the first time, the potential relationships between the cytoskeleton-associated proteins DAAM1 and PREP with different testicular disorders, such as classic seminoma (CS), Leydig cell ...tumor (LCT), and Sertoli cell-only syndrome (SOS), were evaluated. Six CS, two LCT, and two SOS tissue samples were obtained during inguinal exploration in patients with a suspect testis tumor based on clinical examination and ultrasonography. DAAM1 and PREP protein levels and immunofluorescent localization were analyzed. An increased DAAM1 protein level in CS and SOS as compared to non-pathological (NP) tissue was observed, while LCT showed no significant differences. Conversely, PREP protein level increased in LCT, while it decreased in CS and SOS compared to NP tissue. These results were strongly supported by the immunofluorescence staining, revealing an altered localization and signal intensity of DAAM1 and PREP in the analyzed samples, highlighting a perturbed cytoarchitecture. Interestingly, in LCT spermatogonia, a specific DAAM1 nuclear localization was found, probably due to an enhanced testosterone production, as confirmed by the increased protein levels of steroidogenic enzymes. Finally, although further studies are needed to verify the involvement of other formins and microtubule-associated proteins, this report raised the opportunity to indicate DAAM1 and PREP as new potential markers, supporting the cytoskeleton dynamics changes occurring during normal and/or pathological cell differentiation.
Glans penis augmentation: when, how, and why? Califano, Gianluigi; Arcaniolo, Davide; Ruvolo, Claudia Collà ...
International journal of impotence research,
05/2022, Letnik:
34, Številka:
4
Journal Article
Recenzirano
The growing demand for glans penis augmentation (GPA) makes it a hot topic in the field of andrological surgery, albeit still widely debated. The lack of high supporting evidence and its technically ...challenging aspects are the main concerns. The aim of this study was to review the current literature about GPA in order to provide an easy and comprehensive overview of the topic. GPA is suitable for managing both cosmetic and functional issues. Counseling should be the cornerstone of the decision-making process. A thorough understanding of the glans anatomy and treatment strategies remain essential to safely and effectively address the patient's needs. GPA can be performed using injectable fillers or surgical grafting. Glans-shaft penis asymmetries, small glans size, and loss of glans tumescence can be managed by both injectable fillers and surgery. On the other hand, patients with lifelong premature ejaculation can mainly benefit from using injectable fillers. Currently, available studies show promising results but are limited by small sample's size and non-randomized design. Furthermore, treatment-related complications are poorly reported. The long-term efficacy and safety profiles of GPA techniques should be further investigated.
Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic ...factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.
Purpose
To evaluate the efficacy and safety of
Escherichia coli
Nissle 1917 (EcN) in association with levofloxacin in patients with chronic bacterial prostatitis (CBP).
Methods
Patients with CBP ...referred to our clinic from September 2017 to July 2019 were enrolled. At baseline, the symptomatology was assessed with the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), while the Meares–Stamey test was used to diagnose the infection. Patients were randomized (1:1) in two groups (A and B). All subjects underwent oral administration of Levoxacin® 500 mg once daily for 4 weeks. Only the patients in Group B underwent oral administration of EcN® 320 mg, twice daily for 4 weeks and then once daily for 8 weeks. After 3 months, each patient repeated the NIH-CPSI questionnaire, while the Meares–Stamey test was repeated at 3 and 6 months in patients who reported persistent symptoms. All adverse events (AEs) were recorded.
Results
A total of 110 patients were enrolled. After 3 months patients in Group B reported a significantly lower NIH-CPSI score (5.85 ± 3.07 vs. 7.64 ± 3.86;
p
= 0.009) and biological recurrences rate (9.8 vs. 26.9%;
p
= 0.043). At 6 months the biological recurrences rate was significantly lower in Group B (8.7 vs. 28.9%;
p
= 0.038). Only three patients in Group A and six in Group B (
p
= 0.25) complained mild AEs.
Conclusions
Combination therapy with EcN and levofloxacin allows a better control of symptoms and biological recurrences in patients with CBP, without worsening the safety of the treatment.
Prothymosin α (PTMA) is a phylogenetically conserved polypeptide in male gonads of Vertebrates. In Mammals, it is a ubiquitous protein, and, possessing a random-coil structure, it interacts with many ...other partners, in both cytoplasmic and nuclear compartments. PTMA has been widely studied during cell progression in different types of cancer because of its anti-apoptotic and proliferative properties. Here, we provided the first evidence of PTMA expression and localization in human testis and in two testicular cancers (TC): classic seminoma (CS) and Leydig cell tumor (LCT). Data showed that its protein level, together with that of proliferating cell nuclear antigen (PCNA), a cell cycle progression marker, increased in both CS and LCT samples, as compared to non-pathological (NP) tissue. Moreover, in the two-cancer tissue, a decreased apoptotic rate and an increased autophagic flux was also evidenced. Results confirmed the anti-apoptotic action of PTMA, also suggesting that it can act as a switcher from apoptosis to autophagy, to favor the survival of testicular cancer cells when they develop in adverse environments. Finally, the combined data, even if they need to be further validated, add new insight into the role of PTMA in human normal and pathological testicular tissue.
Purpose
To perform a cumulative analysis of the current evidence on the surgical and functional outcomes of bipolar endoscopic enucleation of the prostate (b-EEP) versus bipolar transurethral ...resection of the prostate (b-TURP).
Methods
A systematic review of the literature was performed on PubMed, Ovid
®
, and Scopus
®
according to Preferred Reporting Items for Systematic Review and Meta-analysis Statement (PRISMA Statement). The meta-analysis was conducted using the Review Manager 5.3 software. Parameters of interest were surgical and functional outcomes. Weighted mean difference, and odds ratio with 95% confidence interval were calculated for continuous and binary variables, respectively. Pooled estimates were calculated using the random-effect model.
Results
Fourteen comparative studies were included. No statistically significant difference in terms of overall baseline characteristics was found. b-EEP had higher amount of resected tissue (
p
< 0.0001), shorter catheter time (
p
= 0.006), lower Hb drop (
p
= 0.03), and shorter length of stay (
p
< 0.0001). Equally, overall post-operative complications were lower (
p
= 0.01) as well as short (
p
= 0.04), and long-term complication rate (
p
= 0.04). There was higher re-intervention rate in the b-TURP group (
p
= 0.02) whereas b-EEP group had smaller residual prostate volume (
p
= 0.03), and lower post-operative PSA values (
p
< 0.00001). At long term, b-EEP presented lower IPSS (
p
= 0.04), higher
Q
max
(
p
= 0.002), and lower PVR (
p
< 0.00001).
Conclusions
b-EEP is an effective and safe surgical treatment for BPO. This procedure might offer several advantages over standard b-TURP, including the resection of a larger amount of tissue within the same operative time, shorter hospitalization, lower risk of complications, and lower re-intervention rate.
This was submitted to PROSPERO registry: CRD42019126748.
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. Large-scale metabolomic data have associated metabolic alterations with the pathogenesis and progression of renal ...carcinoma and have correlated mitochondrial activity with poor survival in a subset of patients. The aim of this study was to determine whether targeting mitochondria-lysosome interaction could be a novel therapeutic approach using patient-derived organoids as avatar for drug response.
RNAseq data analysis and immunohistochemistry were used to show overexpression of Purinergic receptor 4 (P2XR4) in clear cell carcinomas. Seahorse experiments, immunofluorescence and fluorescence cell sorting were used to demonstrate that P2XR4 regulates mitochondrial activity and the balance of radical oxygen species. Pharmacological inhibitors and genetic silencing promoted lysosomal damage, calcium overload in mitochondria and cell death via both necrosis and apoptosis. Finally, we established patient-derived organoids and murine xenograft models to investigate the antitumor effect of P2XR4 inhibition using imaging drug screening, viability assay and immunohistochemistry.
Our data suggest that oxo-phosphorylation is the main source of tumor-derived ATP in a subset of ccRCC cells expressing P2XR4, which exerts a critical impact on tumor energy metabolism and mitochondrial activity. Prolonged mitochondrial failure induced by pharmacological inhibition or P2XR4 silencing was associated with increased oxygen radical species, changes in mitochondrial permeability (i.e., opening of the transition pore complex, dissipation of membrane potential, and calcium overload). Interestingly, higher mitochondrial activity in patient derived organoids was associated with greater sensitivity to P2XR4 inhibition and tumor reduction in a xenograft model.
Overall, our results suggest that the perturbed balance between lysosomal integrity and mitochondrial activity induced by P2XR4 inhibition may represent a new therapeutic strategy for a subset of patients with renal carcinoma and that individualized organoids may be help to predict drug efficacy.
Low-intensity shockwave therapy (Li-ESWT) has been shown to be an effective and safe treatment for vasculogenic erectile dysfunction (ED). We aim to evaluate the effectiveness and safety of LiESWT in ...treating patients affected from vasculogenic ED who did not respond to oral treatment with Phosphodiesterase 5 inhibitors (PDE5-i). It is a multicentric open-label prospective study, in a cohort of patients non-responders to PDE-5i. Li-ESWT was performed in an outpatient setting by using the following schedule: 3000 shockwaves with an energy of 0.25 mJ/mm.sup.2 and a frequency of 4-6 Hz, twice a week for 3 weeks. International Index of Erectile Function, Erection Hardness Score and Sexual Quality of Life-Male questionnaires, and penile doppler ultrasound (PDU) are the outcome measurements. The Student t-test or Wilcoxon signed-rank test were applied to compare variables, with results considered statistically significant at p < 0.05. 106 (97.2%) completed treatment and performed follow-up visit after 4 weeks. At follow up visit, the mean IIEF-EF increased by 8.6 points (13.47 plus or minus 4.61 vs 22.07 plus or minus 5.27; p < 0.0001). A clinically significant improvement of IIEF-EF was achieved in 75 patients (70.7%). An EHS score greater than or equal to 3, sufficient for a full intercourse, was reported by 72 patients (67.9%) at follow-up visit. 37 (34.9%) patients reported a full rigid penis (EHS = 4) after treatment. Li-ESWT treatment was also able to improve quality of life (SQOL-M: 45.56 plus or minus 8.00 vs 55.31 plus or minus 9.56; p < 0.0001). Li-ESWT significantly increased mean PSV (27.79 plus or minus 5.50 vs 41.66 plus or minus 8.59; p < 0.0001) and decreased mean EDV (5.66 plus or minus 2.03 vs 1.93 plus or minus 2.11; p < 0.0001) in PDU. Combination of Li-ESWT and PDE5-i represents an effective and safe treatment for patients affected from ED who do not respond to first line oral therapy.
XX male syndrome is part of the disorders of sex development (DSD). The patients generally have normal external genitalia and discover their pathology in adulthood because of infertility. There are ...no guidelines regarding XX male syndrome, so the aim of our study was to evaluate the literature evidence in order to guide the physicians in the management of these type of patients.
We performed a systematic review of the available literature in September 2018, using MEDLINE, Web of Science, Embase and Google Scholar database to search for all published studies regarding XX male syndrome according to PRISMA guidelines. The following search terms were used: "46 XX male", "DSD", "infertility", "hypogonadism".
After appropriate screening we selected 37 papers. Mean (SD) age was 33.14 (11.4) years. Hair distribution was normal in 29/39 patients (74.3%), gynecomastia was absent in 22/39 cases (56.4%), normal testes volume was reported in 0/14, penis size was normal in 26/32 cases (81.2%), pubic hair had a normal development in 6/7 patients (85.7%), normal erectile function was present in 27/30 cases (90%) and libido was preserved in 20/20 patients (100%). The data revealed the common presence of hypergonadotropic hypogonadism. All patients had a 46,XX karyotype. The sex-determining region Y (
) gene was detected in 51/57 cases. The position of the
was on the Xp in the 97% of the cases.
An appropriate physical examination should include the evaluation of genitalia to detect cryptorchidism, hypospadias, penis size, and gynecomastia; it is important to use a validated questionnaire to evaluate erectile dysfunction, such as the International Index of Erectile Function (IIEF). Semen analysis is mandatory and so is the karyotype test. Abdominal ultrasound is useful in order to exclude residual Müllerian structures. Genetic and endocrine consultations are necessary to assess a possible hypergonadotropic hypogonadism. Testicular sperm extraction is not recommended, and adoption or in vitro fertilization with a sperm donor are fertility options.
In the past decades, several treatments have been proposed for the management of metastatic renal cell carcinoma (mRCC). Among these, cytoreductive nephrectomy (CN) represents a controversial and ...open issue in the era of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Two important studies, CARMENA and SURTIME, analyzed therapy with sunitinib with or without CN, and immediate CN followed by sunitinib versus a deferred CN after three cycles of sunitinib, respectively. CARMENA showed the non-inferiority of sunitinib alone versus sunitinib plus CN, whereas SURTIME showed no difference in progression-free survival (PFS), but a better median OS among patients with deferred CN. Therefore, more prospective clinical trials and appropriate patient identification are necessary to support CN in this new scenario. This review provides a snapshot of the current evidence for CN in mRCC, discusses the management strategies, and offers perspectives on the direction of future research.
PDF
