Search Results (114)

The increasing detection of small, non-palpable testicular lesions has challenged the traditional paradigm that every solid intratesticular mass should be managed by radical orchiectomy. Many incidental lesions, particularly in infertile men and in patients with negative tumour markers, are benign or non-neoplastic, making overtreatment a clinically relevant concern. In this setting, ultrasound has become central to a more conservative and individualised diagnostic strategy. By combining high-resolution grey-scale imaging with Doppler, microvascular imaging, CEUS and elastography, multiparametric ultrasound provides complementary information on lesion morphology, vascularity, stiffness and interval change. When integrated with clinical presentation, tumour markers, fertility status, syndromic background and patient history, these features can help characterise lesions and estimate the likelihood of malignancy in the appropriate clinical context. Although imaging cannot replace histology, it can refine pre-test probability, support active surveillance in selected low-risk lesions, guide testis-sparing surgery, and improve assessment of the operated testis. This review examines the role of multiparametric ultrasound in characterisation of focal testicular lesions across different clinical settings, including incidentalomas, acute scrotal pain, trauma, bilateral disease, heterogeneous parenchyma, genetic and endocrine syndromes, and the postoperative testis. A structured, context-sensitive imaging approach may help reduce unnecessary orchiectomy while preserving timely detection of malignant, persistent, recurrent or metachronous disease. Full article

Mass spectrometry-based proteomics has become instrumental for elucidating the molecular mechanisms of neurodegeneration, enabling the identification of disease-associated proteomic alterations and protein-level responses to therapeutic interventions. Building on our previous proteomic characterization of the orchiectomized (ORX) Brown Norway male rat retina as a model of androgen deprivation, we extend this investigation to the visual cortex (VC), a key node in the visual pathway. Here we report the first comprehensive proteomic characterization of ORX-VC employing nanoflow liquid chromatography–tandem mass spectrometry complemented by bioinformatic pathway analyses and quantitative assessment of selected protein markers of ORX-induced changes. Our discovery-driven proteomics approach revealed over 500 differentially expressed proteins following ORX. Principal component analysis showed complete separation between ORX and naïve groups with no overlap, indicating a profound effect of androgen deprivation on the VC proteome. Ingenuity Pathway Analysis^® predicted that the widespread proteome dysregulation included oxidative stress as a primary contributor, alongside estrogen receptor (ESR) predominance over androgen receptor signaling, consistent with our prior findings in the ORX retina. To explore whether this ESR predominance translates to a benefit of E2 supplementation alone, independent of circulating testosterone, we utilized our DHED (10β,17β-dihydroxyestra-1,4-dien-3-one) prodrug as eye drops to target E2 formation into the retina. Quantitative assessment demonstrated that this approach resulted in attenuation of ORX-induced expression changes in a selected panel of key proteins. These findings warrant future studies to determine whether this effect extends across the full spectrum of ORX-induced proteomic shifts and confers a benefit for vision preservation. Full article

Background: Testicular germ cell tumors (TGCTs) are the most common solid malignancies in young men. In real-world clinical practice, non-random treatment allocation may result in confounding by indication, as patients with a greater disease burden are more likely to receive chemotherapy. We evaluated the association between treatment strategy and recurrence-free survival using propensity score–based inverse probability of treatment weighting (IPTW). Methods: We retrospectively analyzed 114 patients who underwent radical orchiectomy for TGCT between 2015 and 2024. Patients were classified into active surveillance and chemotherapy groups. Stabilized IPTW was used to balance baseline clinicopathological characteristics. Recurrence-free survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. Residual post-weighting imbalance was addressed by additional covariate adjustment. Results: During follow-up, 29 of 114 patients (25.4%) experienced recurrence. Unadjusted Kaplan–Meier analysis demonstrated no statistically significant difference in recurrence-free survival between treatment groups (log-rank p = 0.150). Consistently, the unadjusted Cox proportional hazards model showed no statistically significant association between treatment strategy and recurrence-free survival (HR = 1.85, 95% CI 0.79–4.34; p = 0.158). After IPTW, treatment strategy remained not significantly associated with recurrence-free survival (HR = 0.96, 95% CI 0.43–2.13; p = 0.911). Additional adjustment for residual post-weighting imbalance yielded similar results (HR = 0.94, 95% CI 0.43–2.03; p = 0.876). Conclusions: After adjustment for measured baseline differences using IPTW, treatment strategy was not statistically significantly associated with recurrence-free survival. Given the limited number of recurrence events, wide confidence intervals, residual covariate imbalance, incomplete propensity-score overlap, and evidence of non-proportional hazards, these findings should be considered exploratory and should not be interpreted as evidence of equivalence. Full article

Objectives: Testicular torsion is a time-critical pediatric urological emergency in which delayed presentation may increase the likelihood of orchiectomy. However, preoperative estimation of the immediate intraoperative outcome remains challenging. This study aimed to develop and internally validate machine-learning models integrating ischemic timing variables and complete blood count-derived inflammatory indices to predict orchiectomy versus testicular preservation at index surgical exploration in pediatric and adolescent testicular torsion. Methods: We retrospectively analyzed 165 children and adolescents who underwent surgical exploration for confirmed testicular torsion. The primary endpoint was orchiectomy at index exploration versus testicular preservation through detorsion and/or orchiopexy. Clinical timing variables and complete blood count-derived indices, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, white blood cell-to-monocyte ratio, monocyte-to-mean platelet volume ratio, hemoglobin-to-monocyte ratio, systemic inflammatory response index, and aggregate index of systemic inflammation, were evaluated. Five supervised machine-learning algorithms—logistic regression, random forest, XGBoost, LightGBM, and support vector machine—were assessed using nested stratified cross-validation with an outer 5-fold loop and inner 3-fold hyperparameter selection. Model performance was estimated from out-of-fold predictions. Results: Orchiectomy was performed in 37 patients (22.4%), whereas testicular preservation through detorsion and/or orchiopexy was performed in 128 patients (77.6%). Symptom duration was significantly longer in the orchiectomy group than in the preservation group (48.00 [30.00–72.00] vs. 6.00 [2.00–24.00] h, p < 0.001). Monocyte count was also higher in the orchiectomy group (0.92 [0.68–1.23] vs. 0.65 [0.50–0.93] × 10⁹/L, p < 0.001). Among the combined models, XGBoost achieved the highest numerical discrimination, with a ROC-AUC of 0.926 ± 0.066 and a bootstrap 95% confidence interval of 0.856–0.966. Feature-block and interpretability analyses identified symptom duration as the dominant predictor, followed by emergency department waiting time and selected monocyte-centered inflammatory indices. Conclusions: Immediate intraoperative orchiectomy in pediatric and adolescent testicular torsion was most strongly associated with prolonged symptom duration, while selected complete blood count-derived inflammatory indices provided complementary risk information. The combined XGBoost model showed strong internal discrimination and clinically interpretable predictor patterns. However, the model was internally validated only and requires external validation before clinical implementation. Full article

Fat deposition plays an important role in yak metabolism, reproduction, and meat quality, and male yaks are often castrated to facilitate management and improve production performance. The effect of castration on the characteristics of fat deposition in male yaks and the molecular mechanisms of action was explored in this study. The subcutaneous fat thickness in castrated and common male yaks was measured, further the content of fatty acids in yak subcutaneous fat was detected using gas chromatography-mass spectrometer (GC-MS); the transcriptome, metabolome in the yak subcutaneous fat were detected using mRNA-Sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), respectively; the integrative analyses of differentially expressed genes (DEGs), different metabolites (DMs), fatty acids and fat thickness were carried out. The results showed that castration can strengthen the ability of fat deposition and improve the content of fatty acids, especially PUFAs, in male yaks, and both transcriptome and metabolome were significantly different between castrated male yaks and common male yaks. The effect of castration on the male yak fat deposition was closely related to the PPAR signaling pathway, citrate cycle, and insulin resistance. Data suggests that FASN, ACACA, AGPAT2, ACLY, ACSL5, SCD, GSK3B, and SLC2A4 may be the crucial control genes for the fat amount in yaks, and that FADS2, LPL, and ACSL4 may be the crucial control genes for the polyunsaturated fatty acids (PUFAs) content in yak adipose tissue. Further functional studies will be conducted to determine the specific role of each gene in regulating fat deposition and fatty acid composition in yaks. Full article

Cryptorchidism is one of the most frequently diagnosed developmental disorders of the male canine reproductive system, defined as the failure of one or both testes to descend into the scrotum. Physiologically, testicular descent is typically completed by six to eight weeks of age, although some authors extend this period to sixteen weeks. Failure of testicular descent beyond this timeframe is considered pathological. The condition has multiple causes and affects between 1% and 10% of the canine population. Genetics is the most significant factor, indicating the hereditary basis of cryptorchidism. In addition, increasing attention has been directed toward the potential impact of environmental and epigenetic factors on the incidence of cryptorchidism, suggesting that the condition may result from complex interactions between genetic predisposition and external influences. The effect of hormones (such as INSL3 and testosterone), mechanical factors (including narrowing of the inguinal canal, abnormalities of the gubernaculum, and shortening of the spermatic cord), and environmental factors (for example, exposure to external estrogens and maternal stress during pregnancy) all contribute to the development of this disorder. Recent results have emphasized the role of the orexin system, particularly the OX2R receptor, in regulating endocrine and reproductive functions in cryptorchid testes. Computed tomography is increasingly utilized in complex cases due to its high precision in localizing retained testes. Clinically, cryptorchidism may present unilaterally or bilaterally. Unilateral cryptorchidism may preserve partial fertility, whereas bilateral cryptorchidism results in complete infertility. Undescended testes may be located in the abdominal cavity or inguinal canal. Major complications include an increased risk of testicular cancer (Sertoli cell tumors and seminomas) and endocrine disorders leading to feminization. Diagnosis is based on clinical examination and imaging modalities such as ultrasound. Orchiectomy, involving the removal of both the retained and normally descended testicles, is thought to be the gold standard for treatment. This method helps avoid complications and the transmission of the defect to offspring. According to Fédération Cynologique Internationale (FCI) standards, affected individuals should not be used for breeding or shows. Early detection, surgical intervention, and consistent exclusion from breeding programs are the primary strategies for reducing the incidence of this disorder in the canine population. Full article

Testicular tumors are the most common neoplasms of the canine male reproductive tract, corresponding to approximately 25% of all tumors in intact males. A large percentage of cases are characterized by one of three main tumor types: seminomas, interstitial Leydig cell tumors, or Sertoli cell tumors. Clinical importance is primarily associated with endocrine activity rather than malignant behavior; orchiectomy is the treatment of choice for most canine testicular cancers. Endocrine activity, particularly estrogen secretion, may result in feminization syndrome and, in severe cases, bone marrow suppression. The diagnostic approach combines physical examination, ultrasonography with hormonal assessment using endocrine testing (testosterone, estradiol, and T:E ratio), and/or tissue level evidence of the estrogen effect (preputial cytology). Management is centered on orchiectomy; unilateral surgery may be considered when the contralateral testis is clinically and ultrasonographically normal and when preservation of reproductive capacity or working ability is still a priority. Dogs with hormonally active tumors benefit from postoperative hematologic and endocrine monitoring. Recent advances in immunohistochemistry (IHC), such as Ki-67 and inhibin-α markers, and imaging techniques are improving tumor characterization and individualized clinical decision making. Full article

Elevated oxidative stress (OS) is a primary driver of ocular neurodegeneration, worsening with age-related declines in gonadal hormones. While the loss of endogenous 17β-estradiol (E2) is a recognized risk factor for retinal degeneration in females, the impact of testosterone depletion in males remains poorly understood. To address this knowledge gap, we employed mass spectrometry-based proteomics and bioinformatic pipelines to characterize retinal protein shifts triggered by orchiectomy (ORX) in the Brown Norway rat. Proteins from ORX and intact retinas were analyzed via a discovery-driven approach using nanoflow liquid chromatography–tandem mass spectrometry with data-independent acquisition. Ingenuity Pathway Analysis^® of differentially expressed proteins (DEPs) revealed nearly 300 significantly regulated canonical pathways, many associated with OS, free radical detoxification, mitochondrial dysfunction and ophthalmic disease. A selected panel of DEPs was verified by protein-targeted data extraction. Notably, pathway analysis revealed the prominence of estrogen receptor signaling over androgen receptor signaling in the retina, despite the loss of male sex hormones following ORX. These findings indicate that E2-mediated pathways play a more significant role in male retinal protection than previously recognized. Our study provides the first proteomics-based evidence of the male rat retina’s heightened susceptibility to ORX-associated OS, identifying potential targets for treating sex hormone deprivation-associated retinal neurodegeneration. Full article

Background/Objectives: Osteoporosis is a progressive systemic skeletal disease, with male osteoporosis emerging as a critical global concern due to high morbidity and mortality from fractures. This study investigated the anti-osteoporotic potential of CGAC—a herbal mixture of Cervus elaphus Linnaeus, Glycine max (L.) Merr., Angelica gigas Nakai, and Cnidium officinale Makino—and its underlying mechanisms in an orchiectomized (ORX) mouse model. Methods: C57BL/6J mice underwent ORX for 8 weeks, followed by CGAC administration (250 and 500 mg/kg) for an additional 8 weeks. Molecular mechanisms were further validated using MG63 osteoblastic and RAW 264.7 osteoclast assays. Results: ORX induced severe osteoporotic phenotypes, including significant reductions in bone mineral density (BMD) and trabecular microarchitecture. Notably, at the time point examined, ORX was associated with a suppressed bone remodeling state, reflected by reductions in both TRAP-positive osteoclasts and ALP-positive osteoblasts, together with lower serum BALP, CTX-1, and Gla/Glu-OC ratio. Conversely, CGAC normalized this stagnant state and restored physiological remodeling. This was accompanied by reduced marrow fat accumulation through the AMPK signaling axis, which upregulated Runx2 and downregulated PPAR-γ. In vitro results confirmed that CGAC promoted osteoblast differentiation and mineralization while suppressing RANKL-induced osteoclastogenesis. These actions suggest that CGAC may be involved in regulating Wnt/β-catenin signaling. Conclusions: Overall, CGAC is a promising therapeutic candidate for male osteoporosis, offering pharmacological benefits particularly relevant to aging populations. Full article

Current literature on baseline voiding function in gender-diverse patients assigned male at birth (AMAB) is limited. We conducted a retrospective analysis of patients presenting for gender-affirming orchiectomy consultation between 2021 and 2024 who completed the American Urological Association symptom score (AUA-SS) questionnaire to characterize baseline urinary symptoms and identify factors associated with symptom-related bother. Demographics, hormone therapy characteristics, and comorbidities were collected. Bother score was analyzed as both an ordinal variable (score 0 = “delighted” to 6 = “terrible”) and dichotomized (no bother = “delighted” or “pleased” and some bother = “mostly satisfied” to “terrible”). Twenty-six patients met the inclusion criteria, with a median age of 28 years. Overall symptom burden was low (median AUA-SS 4, IQR 2–7.3), with frequency and nocturia reported most commonly. Despite mild symptoms, most patients did not select the lowest possible bother score (“delighted”). Total AUA-SS and bother were not significantly associated with hormone therapy type or duration. In contrast, those with a documented history of anxiety, depression, or bipolar disorder had significantly higher bother score compared to those without (mean rank 15.3 vs. 9.6, p = 0.04). In this single-center cohort, urinary symptoms were generally mild among AMAB patients seeking gender-affirming orchiectomy. Psychiatric history was associated with a higher bother score, though this relationship was no longer significant when bother was dichotomized. These findings suggest behavioral factors may influence how urinary symptoms are experienced and reported in this population. These findings are exploratory and warrant validation in larger cohorts. Full article

Background: Inguinoscrotal sarcomas are a rare sarcoma subtype. The treatment of choice is radical inguinal orchiectomy with wide local resection of the surrounding soft tissues. However, consensus regarding prognostic factors is lacking. We present our experience at a referral sarcoma center concerning the management, oncologic results, and prognostic factors pertaining to this disease. Methods: We conducted a retrospective analysis of patients who underwent surgery for inguinoscrotal sarcomas between 2005 and 2023 at a sarcoma referral hospital. Results: The study included 39 patients. The most frequent histology was liposarcoma. Seven patients required surgical reconstruction with a microvascularized free flap. Four patients presented major postoperative complications. Mean follow-up was 46 months. Overall survival rates were 97.4%, 81.7%, and 64.8% at one, three, and five years. High-grade tumors were correlated with worse overall and disease-free survival. Conclusions: The chance finding of a sarcoma in the inguinal region poses a diagnostic and therapeutic dilemma when considering options for treatment with curative intent. Vascular and muscle resection followed by vascular and/or free flap reconstruction may be necessary to achieve complete surgical resections; therefore, a multidisciplinary approach is needed. A preoperative biopsy should be performed to establish the histological grade, which may be the main prognostic factor. Full article

Background/Objectives: Conventional Colour Doppler Ultrasonography (CDUS) is widely used to assess vascularity in focal intratesticular lesions, yet the influence of lesion size on flow detection and the diagnostic utility of vascular distribution patterns remain unclear. We evaluated (i) whether lesion size affects CDUS detection of intralesional vascularity and (ii) whether vascular patterns associated with disruption of normal intratesticular vascular architecture are linked to diagnostic groupings. Methods: This retrospective single-centre study screened 12,189 testicular ultrasound examinations (1999–2009) and included histologically confirmed focal lesions with archived greyscale and CDUS images. To avoid within-patient clustering, one lesion per patient (the largest if multiple) was analysed (99 patients/lesions). Two blinded radiologists assessed vascularity (present/absent) and, for vascularised lesions, peripheral vascularity and intralesional patterns (criss-cross; disordered/haphazard). A derived composite “disrupted” pattern comprised criss-cross or disordered/haphazard flow. Results: Intralesional vascularity was present in 85/99 (85.9%) lesions. Vascularity was more common in neoplastic vs. non-neoplastic lesions (78/82 [95.1%] vs. 7/17 [58.8%]; p < 0.001) and in malignant vs. benign lesions (64/68 [94.1%] vs. 21/31 [67.7%]; p = 0.001). Lesion size was not associated with vascularity (the smallest vascularised lesion was 2 mm; logistic regression was non-significant). Among vascularised lesions, the composite disrupted pattern was more frequent in neoplastic vs. non-neoplastic (OR 11.67) and malignant vs. benign lesions (OR 5.90). Four of 14 avascular lesions were malignant/neoplastic. Conclusions: With optimised settings, CDUS vascularity detection did not appear size-limited and was strongly associated with neoplasia and malignancy, although avascularity did not exclude malignancy. A composite disrupted vascular pattern may be a practical, reproducible reporting descriptor warranting prospective validation. Full article

The objective of the present study was to apply supervised Machine Learning to predict severe complications after equine orchiectomy. A dataset of 612 cases of orchiectomies in stallions was used for the development of a computational model, among which in 8.5% of cases severe complications (colic, continued stallion-like behaviour, evisceration, funiculitis, haemorrhage, and scrotal infection) were diagnosed post-orchiectomy. Three supervised Machine Learning tools were employed: Logistic Regression (12 different models evaluated), Random Forest (64 models), and Gradient Boosting (8 models). For the prediction of the development of severe complications post-orchiectomy, Logistic Regression was the tool that produced the best discrimination measures, where accuracy, precision and recall were 0.9134, 0.8391, and 0.9133, respectively. The results of the analysis for SHapley Additive exPlanations values for the impact of the independent variables in the prediction of the development of complications indicated that (a) the age of the horse and (b) the surgical technique employed were the two variables that mostly influenced the prediction outcome, findings that were unambiguous in the models developed by any Machine Learning tool. The findings of this study indicate that computational models could be used as adjunct tools to support clinical decisions in the peri-operative management of horses. Full article

The objectives of this work were (i) to evaluate the incidence of complications in male horses after orchiectomy performed in the field, i.e., away from a veterinary hospital, (ii) to describe the post-operative complications that occurred in these animals and (iii) to study the potential predictors for the development of such complications. This study involved 612 animals, on which orchiectomy was performed. The operative part of the study was carried out by one of three experienced veterinary surgeons. Standard pre-operative procedures were followed. Orchiectomy was performed using one of three principal surgical techniques, open, semi-closed or closed, and hemostasis was achieved by means of one of the various procedures, specifically the use of the Henderson instrument, the use of the Reimer emasculator, the ligation of the testicular artery or combinations thereof. In cases of reported complications, these were verified and identified appropriately. At least one (any) post-operative complication was recorded in 145 horses (23.7%). The most frequently observed complication was scrotal swelling/seroma formation, which was observed in 130 animals (21.2% of all animals; 89.7% of animals with at least one (any) complication). Another six different complications were observed, specifically colic, continued stallion-like behavior, evisceration, funiculitis, hemorrhage and scrotal infection. The median age of horses with complications was significantly older than that of animals with no complications: 11 versus 9 years. Animals in which the open technique was applied developed post-operative complications more frequently (30.1% of animals thus operated); further, complications were observed more frequently in animals on which operations were performed by using the Henderson instrument (84.6% of animals) versus animals on which any of the various other procedures were applied (22.4%). In multivariable analysis, the following predictors emerged for the development of complications: the surgical technique employed, the procedure applied for hemostasis, older animal age, and heavier animal bodyweight. The findings confirm that orchiectomy in stallions, even when performed in field conditions, is, in general, a safe procedure. The identification of predictors suggests that veterinarians should take additional care when planning to operate on animals at higher risk or when using surgical approaches that increase the potential for the development of complications. Full article

Postnatal testicular maturation in domestic cats remains poorly quantified despite its relevance for reproductive biology, veterinary practice, and the management of threatened felid species. This study aimed to characterize age-related changes in testicular structure from six to thirty-six months of age. Testes were collected from clinically healthy cats undergoing routine orchiectomy, and design-based stereology was used to estimate the volumes and densities of the main testicular components, including the seminiferous epithelium, interstitial tissue, Sertoli cells, and Leydig cells. Immunohistochemical detection of Desert Hedgehog, a developmental signaling molecule, was performed to assess interstitial maturation. Testicular volume and the absolute volumes of the seminiferous epithelium, Sertoli cells, and Leydig cells increased significantly with age, while the numerical density of Leydig cells remained stable, indicating hypertrophy rather than proliferation. Desert Hedgehog immunoreactivity declined progressively across age groups, consistent with the transition from immature to mature interstitial cells. Principal component analysis revealed a clear separation between immature and mature testes based on volumetric and density variables. These results demonstrate that feline testicular maturation follows a coordinated pattern of tubular and interstitial growth and provide quantitative reference values useful for reproductive assessment, comparative studies, and conservation programs in domestic and wild felids. Full article