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Kidney cancer is a common malignancy that constitutes around 5% of all cancer cases. Males are twice as likely to acquire renal cell carcinoma (RCC) compared to females and experience a higher rate of mortality. These disparities indicate that sex hormone (SH)-dependent pathways may have an impact on the aetiology and pathophysiology of RCC. Examination of SH involvement in conventional signalling pathways, as well as genetics and genomics, especially the involvement of ribonucleic acid, reveal further insights into sex-related differences. An understanding of SHs and their influence on kidney cancer is essential to offer patients individualized medicine that would better meet their needs in terms of prevention, diagnosis and treatment. This review presents the understanding of sex-related differences in the clinical manifestation of kidney cancer patients and the underlying biological processes.

Background Current guidelines recommend repeat computed tomography (CT) imaging in high-grade blunt renal injury within 48–96 h, yet diagnostic value and clinical significance remain controversial. The aim of this work was to determine the possible gain of CT re-imaging in uncomplicated patients with blunt renal trauma at 48 h after injury, presenting one of the largest case series. Methods A retrospective database of patients admitted to our centre with isolated blunt renal trauma due to sporting injuries was analysed for a period of 20 years (2000–2020). We included only patients who underwent repeat imaging at 48 h after trauma irrespective of AAST renal injury grading (grade 1–5) and initial management. The primary outcome was intervention rates after CT imaging at 48 h in uncomplicated patients versus CT scan at the time of clinical symptoms. Results A total of 280 patients (mean age: 37.8 years; 244 (87.1%) male) with repeat CT after 48 h were included. 150 (53.6%) patients were classified as low-grade (grade 1–3) and 130 (46.4%) as high-grade (grade 4–5) trauma. Immediate intervention at trauma was necessary in 59 (21.1%) patients with high-grade injuries: minimally invasive therapy in 48 (81.4%) and open surgery in 11 (18.6%) patients, respectively. In only 16 (5.7%) cases, intervention was performed based on CT re-imaging at 48 h (low-grade vs. high-grade: 3.3% vs. 8.5%; p  = 0.075). On the contrary, intervention rate due to clinical symptoms was 12.5% (n = 35). Onset of clinical progress was on average (range) 5.3 (1–17) days post trauma. High-grade trauma (odds ratio [OR] grade 4 vs. grade 3 , 14.62;  p  < 0.001; OR grade 5 vs. grade 3 , 22.88, p  = 0.004) and intervention performed at the day of trauma (OR 3.22;  p  = 0.014) were powerful predictors of occurrence of clinical progress. Conclusion Our data suggest that routine CT imaging 48 h post trauma can be safely omitted for patients with low- and high-grade blunt renal injury as long as they remain clinically stable. Patients with high-grade renal injury have the highest risk for clinical progress; thus, close surveillance should be considered especially in this group.

Introduction Clinical trials investigating efficacy of immune checkpoint inhibitors (ICI) revealed sex-specific divergent outcomes in urothelial cancer (UC), suggesting that sex hormones might play an important role in gender-specific dimorphisms of response upon ICI. However, further clinical investigations are still needed to understand the influence of sex hormones in UC. The aim of this study was to get further insights on the prognostic and predictive value of sex hormone levels in patients with metastatic UC (mUC) who underwent ICI. Material and methods Sex hormone levels of patients with mUC including luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH ratio, prolactin, testosterone and 17β-estradiol (E2) were evaluated at baseline and during ICI at 6/8 weeks and 12/14 weeks. Results Twenty-eight patients (10 women, 18 men) with a median age of 70 years were included. Metastatic disease was confirmed in 21 patients (75%) after radical cystectomy while seven patients showed mUC at first diagnosis. Twelve patients (42.8%) received first line and 16 patients second line pembrolizumab. The objective response rate (ORR) was 39% (CR in 7%). The median progression-free survival (PFS) and overall survival (OS) was 5.5 and 20 months. Focusing on changes of sex hormone levels during ICI, a significant increase in FSH levels and decrease of the LH/FSH ratio was noticed in responders ( p  = 0.035), yet without sex-specific significance. When adjusted for sex and treatment line, a significant increase of FSH levels was confirmed in men during second line pembrolizumab. Focusing on baseline levels, LH/FSH ratio was significantly higher in female responders ( p  = 0.043) compared to non-responders. In women, increased LH levels and LH/FSH ratio were associated with better PFS ( p  = 0.014 for LH, p  = 0.016 for LH/FSH ratio) and OS ( p  = 0.026 and p  = 0.018). In male patients, increased E2 levels were linked with improved PFS ( p  < 0.001) and OS ( p  = 0.039). Conclusion Increased LH and LH/FSH values in women as well as high E2 levels in men were significant predictors of better survival. Elevated LH/FSH ratio was predictive of better response to ICI in women. These results show first clinical evidence of the potential role of sex hormones as prognostic and predictive biomarker in mUC. Further prospective analyses are needed to corroborate our findings. Plain language summary Urothelial carcinoma (UC) presents as aggressive disease with a greater incidence in men, yet a more aggressive course of disease in women. Patients with metastatic UC receive a chemotherapy regimen as the gold standard, based on an included platin substance. In the case of having contraindications to chemotherapy, checkpoint immunotherapy, priming the immune system to the tumor, is the treatment of choice. Furthermore, immunotherapy is used as second line therapy in progressive disease after chemotherapy and as maintenance therapy in stable tumor conditions after completing the chemotherapy regimen. Evidence shows that sex hormones of the hypothalamus–hypophysis axis influence development and course of UC. The sex hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) stimulate estrogen (E2) production with a negative feedback function on the LH and FSH secretion. High levels of E2 present with a protective effect against UC. Sex has furthermore shown to predict potential response to immunotherapy. This study therefore focused on monitoring and correlating changes of sex hormone levels in 28 patients during therapy with checkpoint inhibitors. This first study assessing changes in sex hormones and the influence of baseline sex hormone values on survival in UC shows that responders to immunotherapy had significantly increased FSH levels. FSH furthermore increased in male patients receiving second line immunotherapy. High values of LH and a high LH/FSH ratio at baseline correlated with better overall survival in female patients. High E2 levels were indicative of better survival in male patients. The study results represent first suggestive prognostic and predictive results to the response of immunotherapy in UC. Highlights Increased LH and LH/FSH values in women as well as high E2 levels in men were significant predictors of better survival. Elevated LH/FSH ratio was predictive of better response to immunotherapy in women. First clinical evidence of the potential role of sex hormones as prognostic and predictive biomarkers in metastatic urothelial cancer.

BackgroundAim of this study was to evaluate feasibility and effects of individualised flow-controlled ventilation (FCV), based on compliance guided pressure settings, compared to standard of pressure-controlled ventilation (PCV) in a porcine intra-abdominal hypertension (IAH) model. The primary aim of this study was to investigate oxygenation. Secondary aims were to assess respiratory and metabolic variables and lung tissue aeration.MethodsPigs were randomly assigned to FCV (n = 9) and PCV (n = 9). IAH was induced by insufflation of air into the abdomen to induce IAH grades ranging from 0 to 3. At each IAH grade FCV was undertaken using compliance guided pressure settings, or PCV (n = 9) was undertaken with the positive end-expiratory pressure titrated for maximum compliance and the peak pressure set to achieve a tidal volume of 7 ml/kg. Gas exchange, ventilator settings and derived formulas were recorded at two timepoints for each grade of IAH. Lung aeration was assessed by a computed tomography scan at IAH grade 3.ResultsAll 18 pigs (median weight 54 kg [IQR 51–67]) completed the observation period of 4 h. Oxygenation was comparable at each IAH grade, but a significantly lower minute volume was required to secure normocapnia in FCV at all IAH grades (7.6 vs. 14.4, MD − 6.8 (95% CI − 8.5 to − 5.2) l/min; p < 0.001). There was also a significant reduction of applied mechanical power being most evident at IAH grade 3 (25.9 vs. 57.6, MD − 31.7 (95% CI − 39.7 to − 23.7) J/min; p < 0.001). Analysis of Hounsfield unit distribution of the computed tomography scans revealed a significant reduction in non- (5 vs. 8, MD − 3 (95% CI − 6 to 0) %; p = 0.032) and poorly-aerated lung tissue (7 vs. 15, MD − 6 (95% CI − 13 to − 3) %, p = 0.002) for FCV. Concomitantly, normally-aerated lung tissue was significantly increased (84 vs. 76, MD 8 (95% CI 2 to 15) %; p = 0.011).ConclusionsIndividualised FCV showed similar oxygenation but required a significantly lower minute volume for CO2-removal, which led to a remarkable reduction of applied mechanical power. Additionally, there was a shift from non- and poorly-aerated lung tissue to normally-aerated lung tissue in FCV compared to PCV.

Objective: To elaborate clinical predictors to safely distinguish between testicular torsion (TT) and the appendix testis torsion (ATT) and emphasize a diagnostic algorithm to reduce unnecessary exploration rates. TT requires prompt assessment and surgical intervention to achieve tissue function. Torsion of the ATT is the most common differential diagnosis, which can usually be treated conservatively. Colour-Doppler ultrasonography (CDUS) remains controversial for detection of TT. Materials and Methods: Data were retrospectively collected from patients under the age of 20 years admitted to our hospital with acute scrotal pain from 2017 to 2020. The main outcome measures were the onset of symptoms, clinical criteria of absent cremasteric reflex, testicular swelling and high-riding testis, perfusion in CDUS and pathology found during scrotal exploration. Results: Seventy-one patients met the inclusion criteria. Mean age was 10.6 years. 53.2% were diagnosed with TT, 41.6% with ATT, 1.3% with epididymitis and in 3.9%, no pathology was found. Patients with TT were significantly older compared to patients with ATT (p<0.004). TT showed a more frequent onset of symptoms during night-time (p<0.006). 87.8% of TT had two of the three defined clinical criteria, compared with 18.8% of ATT (p<0.001). The limitations of this study were the retrospective design and interobserver variability. Conclusion: Our findings support the safety and importance of clinical criteria to distinguish between TT and ATT. CDUS should not supersede clinical evaluation. The decision to surgically explore should be made on clinical grounds as a standard approach for assessing acute scrotum. Keywords: Acute scrotal pain, acute scrotum, testicular torsion, torsion of the appendage testis, scrotal elastography

Renal cell carcinoma (RCC) is a highly vascularized and immunogenic tumor, being an ideal candidate for checkpoint blockade-based immunotherapy. Accordingly, checkpoint inhibitors have demonstrated clinical efficacy in patients with metastatic RCC (mRCC). Sex-specific differences in cancer immunotherapy may be explained by the interaction of sex hormone signaling, genetic and environmental factors, affecting the innate and adaptive immune response in men and women in different ways. The aim of this prospective study was to monitor for the first time changes in sex hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH ratio and 17-ß-estradiol (E2) in 22 mRCC patients (12 male and 10 female) receiving nivolumab therapy. In contrast to female patients, male patients showed a significant increase in E2 (p = 0.006) and LH/FSH ratio (p = 0.013) from the beginning of nivolumab therapy to week 12 of follow-up. Moreover, survival analysis revealed a significant negative association between LH/FSH ratio and progression-free survival (PFS) (p = 0.022) as well as between therapy response (p = 0.009) in males compared to females at interim evaluation (week 6/8). Our findings may therefore be the first reference to sex hormone changes during immunotherapy.

Lynch syndrome, known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal-dominant familial cancer syndrome with an increased risk for urothelial cancer (UC). Mismatch repair (MMR) deficiency, due to pathogenic variants in MLH1, MSH2, MSH6, and PMS2, and microsatellite instability, are known for development of Lynch syndrome (LS) associated carcinogenesis. UC is the third most common cancer type in LS-associated tumors. The diversity of germline variants in the affected MMR genes and their following subsequent function loss might be responsible for the variation in cancer risk, suggesting an increased risk of developing UC in MSH2 mutation carriers. In this review, we will focus on LS-associated UC of the upper urinary tract (UUT) and bladder, their germline profiles, and outcomes compared to sporadic UC, the impact of genetic testing, as well as urological follow-up strategies in LS. In addition, we present a case of metastatic LS-associated UC of the UUT and bladder, achieving complete response during checkpoint inhibition since more than 2 years.

Purpose Despite the high incidence of perioperative complications following cystectomy, there is a lack of evidence regarding patients’ perceptions. Moreover, discrepancies between established complication grading systems and the patient’s perspective remain unexplored. Methods We prospectively evaluated perioperative complications after cystectomy using the Clavien-Dindo Classification (CDC) and the Comprehensive Complication Index (CCI). The CDC and CCI were compared to patient-reported complication grades through Spearman correlation analysis. Discrepancies between physician-assessed and patient-reported complication grades were then evaluated. The study was registered at ClinicalTrials.gov (NCT05153694). Results Between December 2021 and March 2024, 172 patients underwent open cystectomy at our department. Of those, 154 provided written consent to participate in the study, and 111 completed the post-discharge questionnaire. We found a moderate correlation between physician-assessed and patient-reported complication grades (CDC: r  = 0.34, CCI: r  = 0.39; p  < 0.001). Patients with matching grades were defined as realists (50%). Those who reported lower complication grades than assessed by physicians were defined as optimists (38%), while those who reported higher grades were defined as pessimists (12%). Optimists rated the preoperative medical information better than pessimists (“very good”: 79% vs. 38%, p  = 0.006). We found no significant differences between optimists and pessimists regarding age, gender, tumor characteristics or educational level. Conclusion In our prospective study, the correlation between physician-assessed and patient-reported complication grades was only moderate. Only half of the cystectomy patients accurately perceived the severity of their complications. Our findings represent the first study to investigate patients’ perspectives on complications in urology and underscore the importance of thorough preoperative medical information.

PurposeTo report on the oncological outcome of organ-sparing surgery (OSS) compared to (total or partial) penectomy regarding recurrence patterns and survival in squamous cell carcinoma (SCC) of the penis.MethodsThis was a retrospective study of all patients with penile SCC and eligible follow-up data of at least 2 years at our institution. Patients with tumors staged ≥ pT1G2 underwent invasive lymph node (LN) staging by dynamic sentinel-node biopsy or modified inguinal lymphadenectomy. Radical inguinal lymphadenectomy was performed when LNs were palpable at diagnosis and in those with a positive LN status after invasive nodal staging. Follow-up visits were assessed, and local, regional and distant recurrences were defined and analyzed.Results55 patients were identified with a mean follow-up of 63.7 months. Surgical management was OSS in 26 patients (47.2%) and partial or total penectomy in 29 cases (52.8%). Histopathological staging was: pTis (12.7%), pTa (16.3%), pT1a (18.2%), pT1b (5.5%), pT2 (29.1%) and pT3 (18.2%), respectively. Patients in the penectomy group were significantly older (mean 68 vs. 62 years; p = 0.026) with a higher rate of advanced tumor stage (≥ pT2: 44.8% vs. 11.5%; p = 0.002). The local recurrence rate was 42.3% (n = 11) following OSS compared to 10.3% (n = 3) after penectomy (p = 0.007). Kaplan–Meier curves showed no significant differences between the two groups regarding metastasis-free and overall survival.ConclusionsOSS is associated with a higher local recurrence rate compared to penectomy, yet it has no negative impact on overall and metastasis-free survival.

Aim: Torsion of the testicular appendages represents the most common cause of an acute scrotum in prepubertal boys. Its sonographic appearances on gray-scale US and color Doppler US have already been presented in several studies. The aim of this analysis was to expand those already established techniques with strain elastography and thus present typical features of this entity on multiparametric US.Material and methods: Retrospective analysis of all patients presented to the urological department with an acute scrotum between January 2018 and July 2020 identified eleven patients 6-17 years old (mean, 11.1 years), discharged with the diagnosis torsion of the testicular appendages that were examined with a high-end ultrasound device. Results: On gray-scale US all patients showed a round lesion with heterogenous echotexture adjacent to the upper pole of the testis/epididymis with a diameter of 4 to 11.1 mm (mean, 7.7 mm). Scrotal skin thickening and a concomitant hydrocele were found in 9 (81.8%) and 7 (63.6%) cases, respectively. On color Doppler images, all torsed appendages were avascular and in 9 (81.8%) patients we observed hyperemia of the adjacent epididymis. Strain elastography showed increased tissue stiffness in all documented images.Conclusion: Torsion of the testicular appendages has a set of features on multiparametric US. Awareness of this features can facilitate diagnosis of torsion of the testicular appendages and reduce unnecessary surgicalscrotal exploration or unwarranted antibiotic treatment.