Minimally invasive retroperitoneal lymph node dissection for men with testis cancer: a retrospective cohort study of safety and feasibility.

PURPOSE: To describe the perioperative safety, functional and immediate post-operative oncological outcomes of minimally invasive RPLND (miRPLND) for testis cancer. METHODS: We performed a retrospective multi-centre cohort study on testis cancer patients treated with miRPLND from 16 institutions in eight countries. We measured clinician-reported outcomes stratified by indication. We performed logistic regression to identify predictors for maintained postoperative ejaculatory function. RESULTS: Data for 457 men undergoing miRPLND were studied. miRPLND comprised laparoscopic (n = 56) or robotic (n = 401) miRPLND. Indications included pre-chemotherapy in 305 and post-chemotherapy in 152 men. The median retroperitoneal mass size was 32 mm and operative time 270 min. Intraoperative complications occurred in 20 (4%) and postoperative complications in 26 (6%). In multivariable regression, nerve sparing, and template resection improved ejaculatory function significantly (template vs bilateral resection [odds ratio (OR) 19.4, 95% confidence interval (CI) 6.5-75.6], nerve sparing vs non-nerve sparing [OR 5.9, 95% CI 2.3-16.1]). In 91 men treated with primary RPLND, nerve sparing and template resection, normal postoperative ejaculation was reported in 96%. During a median follow-up of 33 months, relapse was detected in 39 (9%) of which one with port site (< 1%), one with peritoneal recurrence and 10 (2%) with retroperitoneum recurrences. CONCLUSION: The low proportion of complications or peritoneal recurrences and high proportion of men with normal postoperative ejaculatory function supports further miRPLND studies.

Acute Kidney Injury at Hospital Admission for SARS-CoV-2 Infection as a Marker of Poor Prognosis: Clinical Implications for Triage Risk Stratification.

BACKGROUND/AIMS: The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of effects, including acute kidney injury (AKI) in up to 40% of hospitalized patients. Given the established relationship between AKI and poor prognosis, whether AKI might be a prognostic indicator for patients admitted to the hospital for SARS-CoV-2 infection would allow for a straightforward risk stratification of these patients. METHODS: We analyzed data of 623 patients admitted to San Raffaele Hospital (Milan, IT) between February 25 and April 19, 2020, for laboratory-confirmed SARS-CoV-2 infection. Incidence of AKI at hospital admission was calculated, with AKI defined according to the KDIGO criteria. Multivariable Cox regression models assessed the association between AKI and overall mortality and admission to the intensive care unit (ICU). RESULTS: Overall, 108 (17%) patients had AKI at hospital admission for SARS-CoV-2 infection. After a median follow-up for survivors of 14 days (interquartile range: 8, 23), 123 patients died, while 84 patients were admitted to the ICU. After adjusting for confounders, patients who had AKI at hospital admission were at increased risk of overall mortality compared to those who did not have AKI (hazards ratio [HR]: 2.00; p = 0.0004), whereas we did not find evidence of an association between AKI and ICU admission (HR: 0.95; p = 0.9). CONCLUSIONS: These data suggest that AKI might be an indicator of poor prognosis for patients with SARS-CoV-2 infection, and as such, given its readily availability, it might be used to improve risk stratification at hospital admission.

Normal sperm parameters per se do not reliably account for fertility: A case-control study in the real-life setting.

A proportion of men are infertile despite having normal medical history/physical examination and normal semen analysis. We aimed to assess whether normal sperm parameters per se account for male factor fertility. 1,957 infertile men were compared with 103 age-comparable fertile controls. Semen analysis was based on 2010 World Health Organization reference criteria. Of all, 12.1% of infertile men and 40.8% of fertile men presented with normal sperm parameters. Among fertile men, 36.9% had isolated sperm abnormalities and 22.3% men showed two or more concomitant sperm abnormalities. Serum total testosterone was higher in infertile men with normal sperm parameters compared to those with ≥2 sperm abnormalities or azoospermia, but similar to those with isolated sperm abnormalities (p ≤ .001). Circulating hormones were similar among sperm parameters groups in fertile men. At multivariable analyses, testicular volume (OR 1.12, p ≤ .001) and FSH (OR 0.8, p ≤ .001) were associated with normal sperm parameters. Overall, the longer the infertility period, the greater the number of sperm parameters abnormalities (p < .01). In conclusion, we found that 12% of infertile men and only 41% of fertile men present with normal sperm parameters. Normal sperm parameters per se do not reliably account for fertility in the real-life setting.

Opioid Use after Radical Prostatectomy: Nationwide, Population Based Study in Sweden.

PURPOSE: North American studies have revealed that about 3% to 7% of opioid naïve surgical patients transition to chronic opioid use after a single prescription. We examined the risk of chronic opioid use following radical prostatectomy using nationwide Swedish data. MATERIALS AND METHODS: A total of 25,703 men in the National Prostate Cancer Register of Sweden who underwent radical prostatectomy were linked to the Prescribed Drug Register. Opioid use was assessed at 3 times, including baseline (13 months to 1 month preoperatively), perioperatively (1 month before and after) and postoperatively (1 to 12 months). Multivariable logistic regression was done to identify predictors of new late use (1 or more opioid prescriptions in 3 consecutive months more than 2 months after surgery). RESULTS: Overall 16,368 men (64%) filled an opioid prescription during the 13 months before or after surgery. The use of strong opioids increased with time and the use of weak opioids decreased. Of the men 1.9% had opioid prescriptions during the baseline period, followed by a spike to 59% around the time surgery, which sharply decreased in month 2 postoperatively. However, thereafter the proportion of men with opioid prescriptions remained slightly higher at 2.2% compared to the baseline before radical prostatectomy. Of chronic late users 57% were previous users and 43% were new chronic users. Higher cancer risk category, greater comorbidity, unmarried status and low educational level were associated with the risk of new chronic opioid use. CONCLUSIONS: Slightly more than half of male Swedish patients filled an opioid prescription after radical prostatectomy and less than 1% became chronic opioid users. These rates are lower than in previous studies of postoperative opioid use from North America.

High-risk human papillomavirus in semen is associated with poor sperm progressive motility and a high sperm DNA fragmentation index in infertile men.

STUDY QUESTION: Does the presence of human papillomavirus (HPV) in semen impact seminal parameters and sperm DNA quality in white European men seeking medical help for primary couple's infertility? SUMMARY ANSWER: HPV seminal infections involving high-risk (HR) genotypes are associated with impaired sperm progressive motility and sperm DNA fragmentation (SDF) values. WHAT IS KNOWN ALREADY: HPV is commonly present in semen samples. However, whether the presence of HPV in semen is actually associated with impaired sperm parameters and SDF values have yet to be elucidated. STUDY DESIGN, SIZE, DURATION: In this cross-sectional study, complete demographic, clinical and laboratory data from 729 infertile men were analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Health-significant comorbidities were scored with the Charlson comorbidity index (CCI). Serum hormones and SDF index (measured by the sperm chromatin structure assay [SCSA]) were measured in every patient (SDF ≥30% was defined as pathological). Semen analysis was based on 2010 World Health Organisation reference criteria. Amplification by nested PCR was used to detect HPV-DNA sequences in semen samples. Descriptive statistics and linear regression models were used to test the association between the presence of HPV and clinical and seminal characteristics in the whole cohort. MAIN RESULTS AND THE ROLE OF CHANCE: The overall rate of HPV positivity was 15.5% (113/729). Overall, 78/729 (10.7%) and 35/729 (4.8%) patients had HR HPV+ and low-risk HPV+, respectively. HPV16 was the most prevalent type (22.1%), followed by HPV43 (10.6%), HPV56 and HPV42 (both 8.8%). No differences were found in terms of clinical and hormonal characteristics between patients with or without seminal HPV. Sperm progressive motility was significantly lower (P = 0.01) while SDF values were higher (P = 0.005) in HPV+ men compared to those with no HPV. In particular, HR HPV+ men had lower sperm progressive motility (P = 0.007) and higher SDF values (P = 0.003) than those with a negative HPV test. Univariable analysis showed that HR HPV+ was associated with impaired sperm progressive motility (P = 0.002) and SDF values (P = 0.003). In the multivariable analysis, age, FSH levels and testicular volume were significantly associated with impaired sperm progressive motility (all P ≤ 0.04). Conversely BMI, CCI, smoking habits and HPV status were not. Only age (P = 0.02) and FSH (P = 0.01) were significantly associated with SDF, after accounting for BMI, CCI, testicular volume, smoking habits and HPV status. LIMITATIONS, REASONS FOR CAUTION: Main limitations are the cross-sectional design of our study and the relatively small sample size of the subgroups. Additional limitations are the lack of a control group of normal fertile men and the lack of follow-up testing to check the clearance or the persistence of HPV in semen after a 6-12 months. WIDER IMPLICATIONS OF THE FINDINGS: Overall, these observations point out the importance of an accurate investigation of seminal HPV presence in everyday clinical practice in the diagnostic work-up of infertile men. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used. There are no competing interests.

Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study.

OBJECTIVE: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s. PATIENTS AND METHODS: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR. RESULTS: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47). CONCLUSIONS: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

The duration of infertility affects semen parameters in primary infertile men: results of a single-centre, cross-sectional study.

OBJECTIVE: To assess the relationship between the duration of infertility (DI) and the seminal parameters of a cohort of White-European primary infertile men. PATIENTS AND METHODS: Data from 1644 infertile men were analysed. Patients were grouped according to the self-reported DI into 12-month time frames. Semen analysis values were assessed based on 2010 World Health Organisation reference criteria. Descriptive statistics tested the difference in clinical, hormonal and seminal parameters between groups. Logistic regression models assessed the impact of DI on semen parameters. RESULTS: A DI of <12, 13-24, 25-36, 37-48, 49-60 and >60 months was found in 207 (12.6%), 651 (39.6%), 387 (23.5%), 168 (10.2%), 92 (5.6%) and 139 (8.4%) men, respectively. Patient's age (P < 0.001) and body mass index (P < 0.001) significantly increased along with DI. Hormonal values were similar across groups. Sperm concentration significantly decreased with DI (P = 0.01). Similarly, a higher rate of non-obstructive azoospermia (NOA) was more frequently found in men with a longer DI (P = 0.03). There were no differences in semen volume, sperm progressive motility, total motile sperm count (TMSC), and normal morphology across groups. Multivariable logistic regression analysis showed that DI was significantly associated with the risk of oligozoospermia (P < 0.001), TMSC <5 × 106 (P < 0.001), and NOA (P < 0.001). CONCLUSIONS: This cross-sectional study showed that DI had a negative impact on semen parameters in primary infertile men. Sperm concentration was negatively associated with DI and patients with a longer DI reported higher rates of azoospermia. Furthermore, DI was significantly associated with a higher risk of oligozoospermia, low TMSC, and NOA.

Undiagnosed prediabetes is highly prevalent in primary infertile men - results from a cross-sectional study.

OBJECTIVE: To study the prevalence and the risk associated with prediabetes (PreDM) in primary infertile men. PATIENTS AND METHODS: Data from 744 infertile men were analysed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Serum hormones were measured in every man. Semen analysis was based on 2010 World Health Organization (WHO) reference criteria. PreDM was defined according to the clinical criteria detailed by the American Diabetes Association (Diabetes Care 2014; 37 (Suppl. 1): S81). Descriptive statistics and logistic regression analyses tested the association between PreDM status, hormonal milieu and seminal parameters. The predictive accuracy of all variables was evaluated using the area under the curve, and the clinical net benefit estimated by decision curve analysis (DCA). RESULTS: Of the 744 men, PreDM was found in 114 (15.4%). Men with PreDM (+PreDM) were older, had higher CCI scores, lower total testosterone and sex hormone-binding globulin but higher follicle-stimulating hormone (FSH) and 17ß-oestradiol values compared to those without PreDM (-PreDM) (all P ≤ 0.04). Higher sperm DNA fragmentation index (DFI; P = 0.014) and idiopathic non-obstructive azoospermia (iNOA; P < 0.001) were found more frequently in +PreDM men. At multivariable logistic regression analysis, older age, FSH and iNOA (all P ≤ 0.04) were significantly associated with +PreDM status. DCA demonstrated a clinical net benefit in discriminating men at higher risk of a +PreDM status. CONCLUSIONS: About 15% of primary infertile men had criteria suggestive of undiagnosed PreDM. A PreDM status was associated with a greater risk of hypogonadism, higher DFI values and iNOA status. Age, FSH values and iNOA status could be considered as useful parameters to recognise men with PreDM and implement early preventive interventions in those men at risk of the consequences from poor glycaemic control.

The side and the location of the primary tumor does not affect the probability of lymph node invasion in patients with renal cell carcinoma.

PURPOSE: To evaluate the role of side and location of the primary renal cell carcinoma (RCC) on the risk of lymph node invasion (LNI) and/or nodal progression (NP) during follow-up. MATERIALS AND METHODS: We evaluated 2485 patients with unilateral RCC, surgically treated in a single tertiary care referral center. Outcomes were LNI at surgery and/or NP during follow-up. We studied if RCC side (left vs. right) and location (upper vs. middle vs. hilar vs. lower area vs. more than one area) affected the probability of LNI and/or NP at follow-up. RESULTS: Overall, 43 and 15% of patients underwent lymph node dissection and had LNI at surgery, respectively. During follow-up, 2.2% of patients had NP. Higher rates of LNI and NP were observed for patients with primary tumor located in more than one anatomical kidney area relative to patients with tumor in a single area (upper 11% vs. middle 10% vs. hilar 0%, vs. lower 12% vs. more than one area 26%, p < 0.01). cM1, cN1, pT2/pT3/pT4 disease and Fuhrman grade 3/4 were independent predictors of the study outcome (all p ≤ 0.01). Neither the RCC side nor the location reached the independent predictor status (all p > 0.1). CONCLUSIONS: Patients with single-side and more than one anatomical kidney area affected by RCC have higher rate of LNI at surgery and/or NP at follow-up. Neither side nor location of primary RCC tumor is related to the risk of harboring LNI at surgery and/or developing NP at follow-up.