Infertile couples still undergo assisted reproductive treatments without initial andrological evaluation in the real-life setting: A failure to adhere to guidelines?

BACKGROUND: The EAU guidelines on male sexual and reproductive health state that both partners of the infertile couple should undergo simultaneous investigation. OBJECTIVES: To assess the prevalence and the characteristics of infertile men who were referred for an andrological evaluation after failed attempts of Assisted Reproductive Technology (ART) with those who were evaluated at the beginning of their infertility pathway at a single academic centre over a 17-year period. MATERIALS AND METHODS: Data of 3213 primary infertile couples assessed between 2003 and 2020 were analysed. Descriptive statistics compared the overall characteristics of male partners of couples with (+ART) or without (-ART) previous ART prior to andrological consultation. Logistic regression models analysed variables associated with +ART. Local polynomial regression models explored the probability of +ART over the analysed time frame. RESULTS: Of all, 493 (15.3%) participants were +ART. Patients and female partners' age was higher in +ART couples (all p ≤ 0.04). Sperm concentration, progressive sperm motility and normal sperm morphology were lower in +ART than in -ART patients (all p < 0.001), along with a greater percentage of non-obstructive azoospermia in +ART compared to -ART men (p < 0.0001). At univariable analysis, patient age and partner age >35 years and a less recent assessment were associated with +ART status (all p ≤ 0.04). Male age and less recent years of assessment were also independent predictors of +ART, after accounting for partner's age >35 years (all p < 0.01). A not significant decrease of this pattern was observed throughout the last 7 years at local polynomial regression models. DISCUSSION: Overall awareness towards the importance of a comprehensive evaluation for the male partner of every infertile couple should therefore be further strengthened. CONCLUSIONS: Approximately 15% of couples still undergo ART without any initial andrological evaluation in the real-life setting. A not significant decrease in this trend was observed over most recent years.

Correlation among isolated teratozoospermia, sperm DNA fragmentation and markers of systemic inflammation in primary infertile men.

AIM: To assess the prevalence of isolated teratozoospermia (iTZS) in a cohort of infertile and fertile men; explore the relationship between iTZS, inflammatory parameters and sperm DNA fragmentation index (SDF) in the same cohort. MATERIALS AND METHODS: 1824 infertile men and 103 fertile controls. Semen analysis, the neutrophil-to-lymphocyte ratio (NLR) and serum hormones were investigated. DFI was tested in infertile men only. According to 2010 WHO semen analysis, patients were categorized in 3 sub-groups of isolated sperm defects: isolated oligozoospermia (iOZS), isolated asthenozoospermia (iAZS) and iTZS. Descriptive statistics and linear regression models tested the association between clinical variables and inflammatory markers. RESULTS: Among infertile men, iAZS, iTZS, and iOZS were found in 13.9%, 11.9% and 4.1% participants, respectively. iTZS was found in 37 (35.9%) fertile men. Infertile men with iTZS had higher NLR values than those with iOZS, iAZS and men with normal semen parameters (all p<0.001). FSH and LH were higher and inhibin B lower in iOZS infertile men compared to all other groups (p≤0.001). Hormonal characteristics were similar between iTZS infertile and fertile men. Similarly, iTZS infertile men had higher SDF than all other groups (all p<0.001). Infertile men with iTZS had higher NLR values than fertile men with iTZS (p<0.01). Linear regression analysis showed that, in infertile men, iTZS was associated with SDF and NLR (all p≤0.01). CONCLUSIONS: iTZS was found in 11.9% of infertile men but it was even more prevalent in fertile controls. Infertile men with iTZS had higher NLR than fertile controls and increased SDF values than infertile participant with iAZS, iOZS, or normal semen parameters. No differences in hormonal characteristics were found between infertile and fertile men with iTZS.

Endoplasmic reticulum oxidoreductase 1 alpha modulates prostate cancer hallmarks.

BACKGROUND: Therapies available for late stage prostate cancer (PCa) patients are limited and mostly palliative. The necessary development of unexplored therapeutic options relies on a deeper knowledge of molecular mechanisms leading to cancer progression. Redox signals are known to modulate the intensity and duration of oncogenic circuits; cues originating from the endoplasmic reticulum (ER) and downstream exocytic organelles are relevant in secretory tumors, including PCa. Ero 1α is a master regulator of redox homeostasis and oxidative folding. METHODS: We assessed Ero 1α mRNA expression by bioinformatic analysis of three public datasets and protein expression levels in PCa cell lines representing different degrees of tumor progression and different human prostate specimens. Transient Ero 1α knockdown was achieved by RNA interference (siRNA). Consequences of Ero 1α downregulation were monitored by PCa proliferation, migration and invasion properties. RESULTS: Ero 1α mRNA and protein levels are upregulated in PCa cell lines compared to non-tumorigenic cells (P=0.0273). Ero 1α expression increases with the grade of malignancy, reaching the highest level in the androgen resistant PC3. In patients' samples from 3 datasets, Ero 1α mRNA expression correlates with pathological Gleason scores. Ero 1α knockdown inhibits proliferation (P=0.0081), migration (P=0.0085) and invasion (P=0.0007) of PC3 cells and alters the levels of integrin ß1 (P=0.0024). CONCLUSIONS: Results indicate that Ero 1α levels correlate with PCa aggressiveness; Ero 1α silencing inhibits key steps over the PCa metastatic process. Therefore, Ero 1α has the potential to be exploited as a novel biomarker and a therapeutic target in PCa.

Postoperative peripheral neuropathies associated with patient positioning during robot-assisted laparoscopic radical prostatectomy (RARP): A systematic review of the literature.

OBJECTIVE: To perform a systematic review of the literature concerning postoperative peripheral neuropathies associated with patient positioning during robot-assisted laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS: A systematic review on articles published from January 1, 1990 to March 15, 2020 was performed in accordance with the PRISMA declaration (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). The electronic search was done searching through the Cochrane Registry, PubMed/EMBASE, Medline, and Scopus. Relevant papers addressing postoperative peripheral neuropathies related to patient positioning during RARP were integrated into the analyses. RESULTS: After screening 4975 articles, one randomized controlled trial and five retrospective studies with a total of 63,667 patients were included in this review. Peripheral neuropathies of the upper extremities were documented in three articles with a total of 15 patients, peripheric neuropathies of the lower extremities were reported in five articles with a total of 76 patients. Analysis of the data was exploratory, since screening techniques, systematically reporting, and description of positioning techniques was not standardized or not reported. CONCLUSIONS: The incidence of peripheral neuropathies at RARP varies between 1.3% and 10.8%. Lower extremities are more affected than upper extremities and the most important risk factors are intraoperative time duration, patients comorbidities, and ASA score. High-quality prospective randomized studies to better assess the impact of patient positioning during RARP on the development postoperative peripheral neuropathies are needed.

Objective gustatory and olfactory dysfunction in COVID-19 patients: a prospective cross-sectional study.

PURPOSE: To determine the prevalence of objective gustatory (GD) and olfactory (OD) dysfunction in COVID-19 patients. METHODS: This is a prospective, cross-sectional study of 51 COVID-19 positive patients diagnosed using RT-PCR-based testing. Of these study participants, 41 reported having present GD and OD at the time of enrollment and ten patients were without symptomatic OD and GD. All participants were objectively tested for OD by Brief Smell Identification Test (BSIT) and for GD by Burghart taste strip test, which were mailed to the participants. The subjective presence and severity of COVID-19 symptoms of smell loss, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough and shortness of breath were also assessed. RESULTS: Of the 41 patients with GD and OD, only 25.6% (10/39; p ≤ 0.0001) objectively presented GD and 39.1% (16/41; p ≤ 0.0001) OD at the time of their subjective dysfunction. Regarding GD, 23.1% (9/39) suffered from total hypogeusia, 2.6% (1/39) from ageusia. A significant loss of sour (33.3% (13/39)) and salty taste (17.9% (7/39)) could be recognized. Only 10.3% (4/39) showed a reduction in sweet and bitter taste. Concerning OD, 9.8% (4/41) showed a deficit relative to younger age in the BSIT and 29.3% (12/41) results abnormal relative to age. CONCLUSION: Subjective and objective findings in GD and OD differ significantly. Most patients suffering from objective dysgeusia present a deficit in sour and salty taste. TRIAL REGISTRATION NUMBER: DRKS00021516; 22/04/2020.

The impact of preoperative nutritional status on post-surgical complication and mortality rates in patients undergoing radical cystectomy for bladder cancer: a systematic review of the literature.

PURPOSE: To investigate the impact of preoperative nutritional factors [body mass index (BMI)], hypoalbuminemia (< 3.5 g/dL, sarcopenia) on complication and mortality rates after radical cystectomy (RC) for bladder cancer. METHODS: The PubMed database was systematically searched for studies investigating the effect of nutritional status on postoperative outcomes after RC. English-language articles published between March 2010 and March 2020 were reviewed. For statistical analyses odds ratios (ORs) and hazard ratios (HRs) weighted mean was applied. RESULTS: Overall, 81 studies were included. Twenty-nine studies were enrolled in the final analyses. Patients with a 25-29.9 kg/m2 BMI (OR 1.55, 95% confidence interval [CI] 1.14-2.07) and those with a BMI ≥ 30 kg/m2 (OR 1.73, 95% CI 1.29-2.40) had a significantly increased risk of 30 day complications after RC. Preoperative hypoalbuminemia increased the risk of 30 day complications (OR 1.56, 95% CI 1.07-2.35); it was a predictor of worse 3 year overall survival (OS) (HR 1.86, 95% CI 1.32-2.66). Sarcopenic patients had a higher risk of 90 day complications than non-sarcopenic ones (OR 2.49, 95% CI 1.22-5.04). Sarcopenia was significantly associated with unfavorable 5 year cancer-specific survival (CSS) (HR 1.73, 95% CI 1.07-2.80), and OS (HR 1.60, 95% CI 1.13-2.25). CONCLUSION: High BMI, hypoalbuminemia, and sarcopenia significantly increased the complication rate after RC. Hypoalbuminemia predicted worse 3 year OS and sarcopenia predicted unfavorable 5 year CSS and OS. Preoperative assessment of RC patients' nutritional status is a useful tool to predict perioperative and survival outcomes.

Trends in risk-group distribution and Pentafecta outcomes in patients treated with nerve-sparing, robot-assisted radical prostatectomy: a 10-year low-intermediate volume single-center experience.

PURPOSE: To evaluate the trends in risk-group distribution and Pentafecta outcomes in patients treated with nerve-sparing (NS), robot-assisted radical prostatectomy (RARP) in a single low-intermediate volume prostate cancer (PCa) center over a 10-year period. MATERIALS AND METHODS: We queried a prospectively maintained database for patients who underwent NS RARP between 2009 and 2018 in a low-intermediate volume PCa center. Risk-groups were defined according to the D'Amico classification. Pentafecta outcomes referred to the postsurgical presence of potency and continence, and the absence of biochemical recurrence (BCR), positive surgical margins (PSM), and perioperative complications. The Kruskall-Wallis test, the t test and the Mann-Whitney tests were used when appropriate. RESULTS: 603 patients underwent NS RARP and 484 patients were evaluated for Pentafecta outcomes. Median postsurgical follow-up was 28 months. Overall, 137 (22.7%), 376 (62.3%), and 90 (15%) patients were diagnosed in the low-, intermediate-, and high-risk groups, respectively. Patients undergoing NS RARP shifted from 33 to 20% in the low-risk group, from 52 to 62% in the intermediate-risk group, and from 10 to 13% in the high-risk group. Patients reaching Pentafecta increased from 38 to 44%. No postoperative potency was the main reason for non-achieving Pentafecta (71%). BCR strongly limited Pentafecta achievement in the high-risk group (61%), but not in intermediate (24%) and low-risk (30%) groups. CONCLUSIONS: Low-intermediate volume PCa centers show similar trends to high-volume centers regarding risk group distributions over time in PCa patients undergoing NS RARP. We reported an increase in Pentafecta outcomes achievement over time even for experienced surgeons. Pentafecta outcomes achievement is risk-group dependent.

Immediate Shockwave Lithotripsy vs Delayed Shockwave Lithotripsy After Urgent Ureteral Stenting in Patients with Ureteral or Pyeloureteral Urolithiasis: A Matched-Pair Analysis.

Introduction: The most common cause of acute renal colic is a ureteral obstruction caused by ureterolithiasis. Urgent intervention is often necessary due to intractable pain. Early extracorporeal shockwave lithotripsy (SWL) as an alternative treatment option to ureteral stenting becomes forgotten in times of rising ureterorenoscopy. However, definitive guidelines are lacking, in which urgent treatment should be preferred in the absence of signs of infection. Therefore, we assessed efficacy and safety of early SWL (eSWL) to secondary SWL (sSWL) after urgent ureteral stenting. Patients and Methods: One hundred four patients treated between January 2015 and November 2017 for obstructive ureterolithiasis were matched regarding stone size, stone localization, and assigned to group eSWL (n = 52) or group sSWL (n = 52). The eSWL group received shock waves (without prior ureteral stenting) and sSWL group ureteral stenting within 48 hours from diagnosis. Thereafter, patients in group sSWL were treated with shock waves for a median of 23 ± 14.6 days after ureteral stenting. Stone-free rates, complication rates, and reintervention rates were assessed. Univariable and multivariable logistic regression was applied to find predictors of outcomes in the two treatment groups. Results: Overall, there was no statistically significant difference between both groups regarding stone-free rate and complication rate. Reinterventions were more often addressed for patients in group sSWL (p = 0.05). eSWL was significantly superior to sSWL regarding stone-free rates for stones between 6 and 9 mm (p = 0.04). At the multivariable multinomial logistic regression none of the two treatment modalities was associated with better outcomes. A body mass index ≥30 was associated with a reduced 6-week stone-free status (p = 0.04), whereas stones ≥8 mm were associated with an increased need of reintervention (p = 0.04). Conclusion: eSWL seems to be an effective and safe emergency procedure compared with sSWL after urgent stenting within 6 weeks and should be considered as a treatment option in patients without absolute indications for immediate ureteral drainage. Clinical trial registration number: 2019-00155.

Performance and safety of treatment options for erectile dysfunction in patients with spinal cord injury: A review of the literature.

BACKGROUND: For a large proportion of patients with spinal cord injury, sexuality and reproduction are important issues. However, sparse data exist regarding available treatment options for this patient population. OBJECTIVES: We sought to review performance and safety rates of all currently available treatment options for erectile dysfunction in spinal cord injury men. MATERIALS AND METHODS: A systematic literature review without time restrictions was performed using PubMed/EMBASE database for English-, Italian-, German-, and Spanish-language articles. Articles' selection was performed according to the PRISMA guidelines. Relevant papers on erectile dysfunction in spinal cord injury patients were included in the final analyses. RESULTS AND DISCUSSION: Overall, 47 studies were eligible for inclusion in this review. Of these, most evidence dealt with phosphodiesterase 5-inhibitors and intracavernous drug injection. Both treatment options are associated with high levels of performance and with patients/partners' satisfaction; side effects are acceptable. Overall, penile prostheses and vacuum erection devices are in general less approved by spinal cord injury patients and are correlated with increased rates of complications in comparison with phosphodiesterase 5-inhibitors and intracavernous drug injection. Sacral neuromodulation, transcutaneous electrical nerve stimulation, and intraurethral suppositories have been poorly studied, but preliminary studies did not show convincing results. CONCLUSION: The best treatment options for erectile dysfunction in spinal cord injury patients emerged to be phosphodiesterase 5-inhibitors and intracavernous drug injection. The choice of erectile dysfunction treatment should be based on several aspects, including residual erectile function, spinal cord injury location, and patients' comorbidities. Future studies assessing the applicability of less well-studied treatments, as well as evaluating innovative options, are needed in this specific population.

Radical Cystectomy in Pathological T4a and T4b Bladder Cancer Patients: Is There Any Space for Sub Stratification?

INTRODUCTION: According to TNM staging, pathological T4ab are comprehensive of the invasion of prostate, seminal vesicles, uterus or vagina and pelvic or abdominal wall. However, few data are available on the perioperative and oncological outcomes of specific organ invasion. MATERIALS AND METHODS: A total of 917 consecutive bladder cancer (BCa) patients treated with radical cystectomy (RC) at a single institution between 1990 and 2015 were studies. Cox regression analyses were used to stratify pT4ab according to the site of invasion and survival. RESULTS: Overall, 176 (19.2%) and 40 (4.4%) patients harbored pT4a or pT4b disease. Specifically, 84 (9.2%) patients reported prostate and/or SVI invasion, 62 (6.8%) prostate only, 16 (1.7%) uterus, 14 (1.5%) vaginal, 24 (2.6%) pelvic wall, and 16 (1.7%) abdominal wall invasion. The median follow-up in pT4 patients was 48 months. The 1-year cancer-specific mortality (CSM) rates were 71, 65, 24, 50, 50, and 72%, for vaginal, uterus, prostate only, prostate and/or seminal vesicles, pelvic wall, and abdominal wall invasions, respectively. At multivariable Cox regression, the invasion of prostate only (hazard ratio [HR] 3.53), prostate and/or SVI (HR 4.98), uterus (HR 7.16), vagina (HR 6.12), pelvic (HR 11.81), abdominal (8.36) were associated with adverse CSM. CONCLUSIONS: Our study described the differences in survival related to invasion site in pT4 patients, confirming poor survival expectancies in this subgroup. Patients with prostate invasion only seem to be associated with better survival than those affected by concomitant invasion of seminal vesicles. Uterus and vaginal invasions were associated with poor survival outcomes. Patients Summary: In this study, we looked at the outcome of locally advanced invasive BCa (stage pT4) in patients treated with RC at a tertiary referral hospital. We analyzed the differences in survival related to the specific organ invasion. We confirmed poor survival in this subgroup of patients. Only patients who had prostate invasion only seem to have a better survival.

Pattern of node metastases in patients treated with radical cystectomy and extended or superextended pelvic lymph node dissection due to bladder cancer.

BACKGROUND: Pelvic lymph node dissection (PLND) has a diagnostic and therapeutic role during radical cystectomy in bladder cancer patients. However, at the time, no prospective data supports the value of extended PLND in improving survival expectances. We sought to describe incidence and location of node metastases in patients treated with extended and superextended PLND. METHODS: We evaluated 653 contemporary patients with clinically nonmetastatic high risk nonmuscle invasive or muscle-invasive bladder cancer treated with radical cystectomy and extended or superextended PLND without neoadjuvant chemotherapy at a single tertiary referral center between 1990 and 2013. Limited PLND is defined as the removal of obturator and internal iliac nodes. Standard included also the external iliac nodes. Extended includes also common and presacral nodes. Finally, superextended PLND includes all the nodes removed along the inferior mesenteric artery. We evaluated incidence of pathologically node metastases. Logistic regression analyses evaluate preoperative and pathologic characteristics to the risk of harboring node metastases in the extended and superextended template. RESULTS: Overall, 191 (29.3%) patients were found with pathologically node confirmed metastases. Of these, 56 (29.3%) patients were found with a single node metastasis, while 135 (70.7%) had multiple node metastases. The vast majority of patients were found with node metastases standard template (n = 172, 26.3%), on the other hand 30 (4.6%) and 21 (3.2%) patients had node metastases in extended and superextended templates, respectively. However, of these only 2 patients were found without concomitant lymph node metastases in the limited or standard templates. On multivariable analyses, cN+ status (odds ratio = 4.40, P<0.001) and cT3-4 vs. cT1-2 (odds ratio = 2.25, P<0.001) were associated with an increased risk of harboring node metastases in the extended or superextended template. CONCLUSIONS: We found that the majority of patients harbored node disease in the limited or standard node dissection pattern. On the other hand, only a minority of patient were found with a disease in extended or superextended template without harboring a concomitant node disease in the limited pattern.

Surgical treatment for clinical node-positive bladder cancer patients treated with radical cystectomy without neoadjuvant chemotherapy.

OBJECTIVE: Growing literature supports good survival expectancies in bladder cancer (BCa) patients affected by clinical node metastases (cN+) treated with multimodal therapy. We evaluated the role of adjuvant chemotherapy in cN+BCa patients treated with radical cystectomy (RC) and pelvic lymph node dissection (PLND) without neoadjuvant chemotherapy (NAC). METHODS: We evaluated a total of 192 patients with BCa and cN+. All patients were treated with RC and PLND without NAC between 2001 and 2013. Kaplan-Meier analyses and Cox regression analyses were used to assess the impact of adjuvant chemotherapy (ACT) on recurrence, cancer-specific mortality (CSM) and overall mortality (OM) after surgery. RESULTS: Overall, 99 patients (51.6%) were found without node metastases at RC, while 18 (9.4%), 58 (30.2%) and 17 (8.9%) patients were found pN1, pN2 and pN3, respectively. With a median follow-up of 48 months, in cN+ patients we recorded 5-year recurrence, CSM and OM of 55, 53 and 51%, respectively. Overall, 36 (18.8%) patients were treated with adjuvant chemotherapy. At univariable analyses, ACT was associated with improved overall survival [Hazard ratio (HR): 0.42, confidence interval (CI) 0.20-0.86, p = 0.02) in pN+ subgroup only. These results were confirmed at multivariable analyses, where ACT was associated with improved CSS (HR: 0.45, CI 0.21-0.89, p = 0.03) and OS (HR: 0.37, CI 0.17-0.81, p = 0.01). CONCLUSIONS: We report good survival outcomes in cN+ patients treated with RC. The use of ACT after surgery increases survival expectancies, especially in those patients with pathological node disease. Our data need to be further evaluated in prospective setting.