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Testicular cancer disproportionally affects men of reproductive age making fertility an important aspect of testicular cancer survivorship. Men with testicular cancer have more semen parameter abnormalities and a higher incidence of infertility compared to the general population. All treatment options for testicular cancer negatively affect fertility with recovery rates varying by treatment. For these reasons, clinicians should offer sperm cryopreservation, ideally before orchiectomy to maximize the possibility of biologic paternity, if desired. Several innovations have positively impacted this space including direct-to-consumer cryopreservation and bench research demonstrating the feasibility of reintroducing testicular cells post-therapy., Competing Interests: Disclosure All authors have no commercial or financial conflicts of interest and have no funding sources to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Paraneoplastic encephalitis (PE) represents a rare but significant complication in patients with testicular cancer (TC). Given the paucity of comprehensive literature on this topic, our review seeks to consolidate current knowledge and provide evidence-based recommendations for the diagnosis, prognosis, and management of PE in the context of TC., Materials and Methods: In adherence to PRISMA guidelines, a systematic literature review was conducted from 1950 to April 2024 using PubMed. The search focused on articles where TC was identified as the primary etiology of PE. The Mixed Methods Appraisal Tool and the Oxford Centre for Evidence-Based Medicine's levels of evidence tool were employed for assessing study quality, and a thematic analysis was conducted to identify trends and patterns., Results: Out of 91 articles identified, 29 met the inclusion criteria, encompassing 5 retrospective chart reviews, 3 case series, and 22 case reports. Findings indicate that PE symptoms can manifest at any stage of TC-before tumor detection, during treatment, or even years posttreatment. A notable observation was the frequent oversight of microscopic testicular tumors in ultrasound imaging, leading to diagnostic delays. The outcomes of PE in the context of TC were diverse, reflecting the heterogeneity of the studies included., Conclusion: PE, although rare, is a critical consideration in patients with TC presenting with neuropsychiatric symptoms. Early recognition and appropriate diagnostic workup, including consideration for microscopic neoplasms, are essential for timely intervention and improved patient outcomes., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Testicular malignancies commonly affect adolescent and young adult males. Although they tend to respond well to cisplatin-based chemotherapy with excellent overall survival, complications such as inferior vena cava tumor thrombus are rare and can be associated with high morbidity and mortality. We present a case of tumor thrombus in a 21-year-old active duty male with a newly diagnosed stage IIIB non-seminomatous germ cell tumor presenting with extensive left lower extremity swelling. Ultrasound with Doppler was notable for significant thrombus of the left common femoral, femoral, and popliteal vein. Computed tomography imaging revealed extensive thrombus of the inferior vena cava, left iliac veins, and left gonadal vein with sparing of the left renal vein. Endovascular thrombectomy was performed with pathologic analysis confirming the presence of malignant cells consistent with tumor thrombus. The patient continued subsequent non-seminomatous germ cell tumor treatment without complications., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Purpose: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy., Methods: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated., Results: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles., Conclusion: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: Testicular microlithiasis (TM) is thought to be associated with testicular tumors and impaired spermatogenesis; however, its etiology remains unclear., Objectives: To identify factors, other than testicular function, that are associated with testicular microlithiasis., Materials and Methods: We enrolled males who underwent ultrasound examination of the scrotum at Tokyo Dental College Ichikawa General Hospital. The patients were categorized into two groups: those with or those without testicular microlithiasis. Background and blood test data were compared between the groups., Results: Testicular microlithiasis was observed in 72 of the 828 (8.7%) patients enrolled. Ages ranged from 15 to 87 years (mean age, 40.0 years). A history of germ cell tumor was significantly more prevalent in patients with testicular microlithiasis than in those without (1.3 vs. 16.7%; p < 0.001). Blood test data showed that, patients with testicular microlithiasis had significantly higher serum creatinine levels (0.91 vs. 1.04 mg/dL; p = 0.046) and lower calcium levels (9.4 vs. 9.3 mg/dL; p = 0.031) than those without. Serum creatinine levels (> 1.00 mg/dL) and germ cell tumors were significantly associated with testicular microlithiasis in both univariate and multivariate analyses. The prevalence of testicular microlithiasis increased in patients older than 50 years. Age (> 50 years) was associated with testicular microlithiasis in univariate analysis. The mean body weight tended to be heavier (70.7 vs. 72.2 kg; p = 0.051) and epididymitis was observed more frequently (3.2 vs. 8.3%; p = 0.056) in patients with testicular microlithiasis than in those without., Discussion and Conclusion: A history of testicular tumors and elevated serum creatinine levels were associated with testicular microlithiasis. Testicular microlithiasis was observed across all age groups, with a tendency to increase in patients older than 50 years. Patients with testicular microlithiasis were slightly heavier and had a higher prevalence of epididymitis than those without. Our findings suggest that, in addition to testicular dysgenesis, other factors are involved in the development of testicular microlithiasis., (© 2023 American Society of Andrology and European Academy of Andrology.)

Transverse testicular ectopia (TTE) is an infrequent ectopic testis where both testes descend via the same inguinal canal, located in the same hemiscrotum, and augments the risk of developing testicular tumours. Type II TTE is accompanied by persistent Müllerian duct syndrome, where the Müllerian structures persist for various reasons. Here, we present a case of an adult in his early 30s, who presented with a right testicular swelling and was diagnosed as type II TTE and testicular mixed germ cell tumour after surgery. We could find only 13 similar cases of TTE and testicular tumours in the literature. Our case highlights the importance of clinical acumen with detailed history, meticulous clinical examination, radiological investigations and a detailed pathological examination while dealing with such sporadic presentations., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Persistent Müllerian duct syndrome (PMDS) is a rare sexual development disorder. It is even more rarely associated with transverse testicular ectopia (TTE), a rare form of testicular ectopia, in which both testes descend through a single inguinal canal and are present in the same hemiscrotum. PMDS with TTE is associated with 18%-33% malignant transformation. Here we report the case of a 48-year-old man who presented with a large right inguinoscrotal swelling and on evaluation was found to have a large right testicular mass with complete right inguinal hernia, undescended left testis and a central abdominal mass. On evaluation with contrast-enhanced computed tomography abdomen and pelvis and image-guided biopsy he was diagnosed with mixed germ cell tumour of the right testis (predominantly a seminoma) with a retroperitoneal nodal mass and absent left testis, for which he received chemotherapy. Post-chemotherapy he underwent surgery and was diagnosed intraoperatively with PMDS along with TTE and testicular malignancy arising from the ectopic left testis. Postoperative recovery and follow-up were uneventful. Most cases of PMDS are diagnosed early in life. They present clinically with unilateral or bilateral undescended testis with inguinal hernia. In adults, PMDS is usually associated with male infertility. However, TTE is associated with an increased risk of testicular tumours if undiagnosed until adulthood. In adults PMDS with TTE is usually an intraoperative finding and is commonly associated with malignancy in the ectopic/undescended testis.

Congenital cryptorchidism, also known as undescended testis, is the condition where one or both testes are not in place in the scrotum at birth and is one of the most common birth defects in boys. Temporal trends and geographic variation in the prevalence of cryptorchidism from 1% to 9% have been reported in prospective cohort studies. The testes develop in the abdominal cavity and descend to the scrotum in two phases, which should be completed by gestational week 35. Thus, the risk of cryptorchidism is higher in preterm boys. In many cases a spontaneous descent occurs during the first months of life during the surge of gonadotropins and testosterone. If not, the testis is usually brought down to the scrotum, typically by surgery, to increase future fertility chances and facilitate cancer surveillance. The increasing frequency of impaired semen quality and testicular cancer, with which cryptorchidism is associated, represents a concern for male reproductive health in general and a need to understand its risk factors. The risk of cryptorchidism is closely related to gestational factors (preterm birth, low birth weight and intrauterine growth restriction), and especially maternal smoking seems to be a risk factor. Evidence is accumulating that the increasing prevalence of cryptorchidism is also related to prenatal exposure to environmental chemicals, including endocrine disrupting compounds. This association has been corroborated in rodents and supported by ecological studies. Conducting human studies to assess the effect of endocrine disrupting chemicals and their interactions is, however, challenged by the widespread concomitant exposure of all humans to a wide range of chemicals, the combined effect of which and their interactions are highly complex., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Holmboe, Beck, Andersson, Main, Jørgensen, Skakkebæk and Priskorn.)

The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy.

Background: No study has quantified the impact of pain and other adverse health outcomes on global physical and mental health in long-term US testicular cancer survivors or evaluated patient-reported functional impairment due to pain., Methods: Testicular cancer survivors given cisplatin-based chemotherapy completed validated surveys, including Patient-Reported Outcomes Measurement Information System v1.2 global physical and mental health, Patient-Reported Outcomes Measurement Information System pain questionnaires, and others. Multivariable linear regression examined relationships between 25 adverse health outcomes with global physical and mental health and pain-interference scores. Adverse health outcomes with a β^  of more than 2 are clinically important and reported below., Results: Among 358 testicular cancer survivors (median age = 46 years, interquartile range [IQR] = 38-53 years; median time since chemotherapy = 10.7 years, IQR = 7.2-16.0 years), median adverse health outcomes number was 5 (IQR = 3-7). A total of 12% testicular cancer survivors had 10 or more adverse health outcomes, and 19% reported chemotherapy-induced neuropathic pain. Increasing adverse health outcome numbers were associated with decreases in physical and mental health (P < .0001 each). In multivariable analyses, chemotherapy-induced neuropathic pain (β^ = -3.72; P = .001), diabetes (β^ = -4.41; P = .037), obesity (β^ = -2.01; P = .036), and fatigue (β^ = -8.58; P < .0001) were associated with worse global mental health, while being married or living as married benefited global mental health (β^ = 3.63; P = .0006). Risk factors for pain-related functional impairment included lower extremity location (β^ = 2.15; P = .04) and concomitant peripheral artery disease (β^ = 4.68; P < .001). Global physical health score reductions were associated with diabetes (β^ = -3.81; P = .012), balance or equilibrium problems (β^ = -3.82; P = .003), cognitive dysfunction (β^ = -4.43; P < .0001), obesity (β^ = -3.09; P < .0001), peripheral neuropathy score (β^ = -2.12; P < .0001), and depression (β^ = -3.17; P < .0001)., Conclusions: Testicular cancer survivors suffer adverse health outcomes that negatively impact long-term global mental health, global physical health, and pain-related functional status. Clinically important factors associated with worse physical and mental health identify testicular cancer survivors requiring closer monitoring, counseling, and interventions. Chemotherapy-induced neuropathic pain must be addressed, given its detrimental impact on patient-reported functional status and mental health 10 or more years after treatment., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cryptorchidism presents with an incidence of 1-5% with potential long-term implications on future fertility and overall health. This review focuses on surgical treatment modalities, their impact on testicular development, and function while addressing the Nordic consensus statement as well as current European Association of Urology (EAU) and American Urological Association (AUA) guidelines. Congenital and acquired cryptorchidism present distinctive challenges in surgical management, with different implications for fertility. While congenital cryptorchidism entails a risk to fertility and warrants early intervention, both retractile testes and acquired cryptorchidism also pose risks to fertility potential, underscoring the importance of evaluating treatment options. Testicular location and the child's age form the basis of a practical classification system for undescended testicles. Early diagnosis by clinical examination enables timely treatment. Imaging is reserved for selected cases only. Following guidelines, orchidopexy is recommended between 6-12 months of age for congenital cryptorchidism. Evidence increasingly suggests the benefits of early surgery for promoting testicular health and fertility potential. Current surgical options range from open to laparoscopic techniques, with the choice largely determined by the location and accessibility of the undescended testicle. The advancement in laparoscopic approaches for non-palpable testes underscores the evolving landscape of surgical treatment. Sequential surgeries may be required depending on the mobility of the undescended testes. More research is needed to explore both the potential and limitations of hormonal therapy, which is secondary to surgical treatment and can selectively have a role as adjunct to surgery. Long-term follow-up is imperative to evaluate fertility outcomes, risk of testicular malignancy, and psychological impact. By integrating current guidelines with the latest evidence, this review intends to facilitate a comprehensive understanding of cryptorchidism, thereby optimizing patient management and outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pakkasjärvi and Taskinen.)

Background: Testicular tumors have many different manifestations. The majority of these cases are presented as an incidental finding during hydrocelectomy. Malignant mesotheliomas are uncommon tumours that can arise from the coelomic epithelium of the pleura, peritoneum, pericardium, and tunica vaginalis., Case Presentation: We present a 51-year-old South Asian (Indian) male patient with a rare case of mesothelioma, presenting with right hydrocele, to whom a right hydrocelectomy was performed. Any history of trauma or asbestos exposure was not present. Histopathological and immunohistochemistry reports revealed a malignant mesothelioma of tunica vaginalis. There was no invasion of the tumour to the epididymis and spermatic cord. Imaging studies showed no signs of metastasis. 1 month later, a high inguinal orchidectomy was performed. The patient underwent adjuvant chemotherapy thereafter and is still on follow-up., Conclusion: Although hydrocele is common, detailed evaluation is mandatory to rule out certain rare tumours-testicular and paratesticular variants., (© 2024. The Author(s).)

Background: Testicular cancer (TC) mostly occurs in men aged 14 to 44. Studies have shown that TC seriously damages male fertility, and 6% to 24% of patients with TC were even found to suffer from azoospermia when they are diagnosed. At present, some studies have pointed out that onco-microdissection testicular sperm extraction (mTESE) can extract sperm from tumor testicles. However, there are almost no reports on remedial measures after onco-mTESE failure. Given the valuable opportunity for fertility preservation in patients with TC and azoospermia, it is necessary to provide effective remedial methods for patients with failed onco-mTESE., Methods: Two young men, who were diagnosed with TC and also found to have azoospermia, tried onco-mTESE while undergoing radical orchiectomy for fertility preservation. However, sperm extraction failed in both patients. Subsequently, the isolated testicular tissue of the patient in case 1 suffered from TC again, and the patient in case 2 was scheduled to receive multiple cycles of gonadotoxic chemotherapy. Because both had a plan to have a birth in the future, we performed remedial mTESE., Results: Sperm was successfully extracted from both patients. The patient recovered well, without complications. The patient couple in case 1 underwent 1 intracytoplasmic sperm injection (ICSI) cycle but did not achieve clinical pregnancy., Conclusions: There is still an opportunity to extract sperm successfully using onco-mTESE, despite the difficulty of fertility preservation in TC patients with azoospermia. If sperm extraction from the tumor testis fails, implementing remedial mTESE as early as possible would likely preserve the last chance of fertility for these patients., Competing Interests: The authors declare that they have no funding and conflict of interests., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Patients with Down syndrome (DS) are at risk of multiorgan dysfunction; kidney and urological impairment are common. This is due to a likely increased risk of congenital kidney and urological malformations (odds ratio of 4.5 compared to the general population in one study), more frequent associated comorbidities at risk of kidney dysfunction (such as prematurity in 9-24% of children, intrauterine growth retardation or low birth weight in 20%, and congenital heart disease in 44%), and more frequent lower urinary tract dysfunction (reported in 27-77% of children with DS). If present, malformations and comorbidities at risk of kidney dysfunction warrant regular kidney monitoring in addition to their treatment. Serum creatinine in children with DS has been shown to be higher than in the general population and asymptomatic hyperuricemia is reported in 12-33% of children or young adults with DS. Moreover cryptorchidism and testicular cancer are also more common and should be detected by clinical examination. Thus, persons with DS at risk of presenting kidney and urological impairment should be identified by prenatal ultrasonography, comorbidities at risk of kidney sequelae considered, and during regular medical follow-up, clinically examined and questioned to diagnose testicular anomalies and lower urinary tract dysfunction. This is of importance as such kidney and urological impairments are associated with impaired quality of life and mental health, and risk of kidney failure., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Objectives: To identify if surgically treated cryptorchidism correlated with testicular tumor pathology at presentation., Materials and Methods: An institutional database of patients treated for testicular cancer between 2003 and 2020 was reviewed. Inclusion criteria included orchiectomy patients. Exclusion criteria included unknown cryptorchidism history or pathology or laterality of orchiectomy. Data collection included demographics, surgical history, and tumor marker status., Results: A total of 435 patients were included. Thirty-three of these patients had a history of UDT. There was no statistical difference in age at orchiectomy, laterality of orchiectomy, or lymphovascular invasion with regard to UDT history. There was a statistical difference in tumor pathology after orchiectomy, P = 0.03. On secondary analysis, benign pathology was significantly more common in patients with a history of UDT (15.2%) than without (4.7%), P = 0.01. Mixed GCT was also found at a significantly lower rate in patients with a history of UDT (18.2%) compared to those with no history of UDT (37.3%), P = 0.03. There were no statistically significant differences in other pathology., Conclusion: Previous studies have shown that there is a greater rate of seminoma in patients with testicular cancer in an undescended testis. This study shows that in patients with a history of UDT compared to those without a history of UDT, there is a greater percentage of patients with benign testicular masses after orchiectomy. Guideline based practices including monthly self-examination and testis-sparing surgery for appropriate patients may reduce rates of radical orchiectomy for benign tumors., Competing Interests: Declaration of Competing Interest The authors have no financial or personal relationships with other people or organizations that could inappropriately influence their work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Testicular germ cell tumours (TGCTs) are the most common malignancy in men aged 15-40 years, with increasing incidence worldwide. About 33 ~ 50% of the patients present with metastatic disease at diagnosis. TGCT survivors experience short- and long-term sequelae, including cancer-related fatigue (CRF). Physical activity (PA) has established effects on reducing CRF and other sequelae and improving health-related quality of life (HRQoL). However, its impact on TGCT survivors has so far received little attention. The gut microbiota plays a crucial role in various physiological functions, including cognition and metabolism, and may mediate the effects of PA on CRF and other sequelae, but this has not been investigated in randomized controlled trials., Methods: This national, multicentre, phase-III trial will evaluate the impact of a one-year supervised PA program on CRF and other short- and long-term sequelae in metastatic TGCT patients receiving cisplatin-based chemotherapy combined with etoposide+/-bleomycin. It will also investigate potential mediating effects of the gut microbiota and its metabolites involved in the gut-brain axis on the relationship between PA and CRF and other sequelae. A total of 236 men ≥ 18 years of age with metastatic TGCT (seminoma and non-seminoma) will be enrolled before starting first-line chemotherapy in several French hospitals. The primary (CRF) and secondary (cognitive/psychological/metabolic sequelae, HRQoL, etc.) outcomes and gut microbiota and relevant metabolites will be assessed at inclusion, during and at the end of the one-year intervention, and annually until 10 years since inclusion to assess long-term sequelae, more specifically CRF, cardiovascular toxicities, and second primary cancer occurrence in this population., Discussion: This trial will provide comprehensive and novel insights into the effects of a long-term supervised PA program on CRF and other sequelae in metastatic TGCT patients receiving first-line chemotherapy. It will also contribute to understanding the potential role of the gut microbiota and its metabolites in mediating the effects of PA on these outcomes. The findings of this study will help the development of effective PA interventions to improve the health of TGCT survivors and may have implications for other cancer populations as well., Trial Registration: The study was registered on ClinicalTrials.gov (NCT05588700) on 20 Oct. 2022., (© 2024. The Author(s).)

Rationale: Congenital adrenal hyperplasia (CAH) is considered one of the most common inherited disorders. In about more than 95% of all CAH cases, the deficient enzyme is 21-hydroxylase. Infertility is an important complication of this disease, and although this topic has been studied more frequently in females, cases, and literature reviews of the causes of infertility in male patients are constantly increasing., Patient Concerns: A 28 old male with congenital adrenal hyperplasia (we assume to be a nonclassical type) presented to our institution with infertility and suspected bilateral testicular masses after 4 years of stopping dexamethasone., Diagnosis: Testicular adrenal rest tumors., Interventions: Dexamethasone was reapplied in a supraphysiologic dose (1.5 mg before bedtime) with periodic monitoring of the patient., Outcomes: Treatment with supraphysiologic dose of dexamethasone led to regression of these tumors and significant improvement in sperm count, resulting in being capable of having a child., Lessons: There are many suspected causes of reduced male fertility in male CAH patients and the presence of testicular adrenal rest tumors is the main cause of infertility in this population. These benign tumors are believed to arise from ectopic adrenal cells in the testes, that grow under adrenocorticotropic hormone stimulation in poorly controlled patients. Annual scrotal ultrasound is recommended in all males with CAH for detection and treatment of these tumors as early as possible before they cause permanent damage to the seminiferous tubules and irreversible infertility., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and penis are diagnosed early and treated in relatively younger patients in which couple fertility can be an important concern. The purpose of this review is to highlight both the pathogenetic mechanisms of damage to male fertility in the context of the main urological cancers and the methods of preserving male fertility in an oncological setting, in light of the most recent scientific evidence. A systematic review of available literature was carried out on the main scientific search engines, such as PubMed, Clinicaltrials.Gov, and Google scholar. Three hundred twenty-five relevant articles on this subject were identified, 98 of which were selected being the most relevant to the purpose of this review. There is a strong evidence in literature that all of the genitourinary oncological therapies have a deep negative impact on male fertility: orchiectomy, partial orchiectomy, retroperitoneal lymphadenectomy (RPLND), radical cystectomy, prostatectomy, penectomy, as well as radiotherapy, chemotherapy, and hormonal androgen suppression. Preservation of fertility is possible and includes cryopreservation, hormonal manipulation with GnRH analogs before chemotherapy, androgen replacement. Germ cell auto transplantation is an intriguing strategy with future perspectives. Careful evaluation of male fertility must be a key point before treating genitourinary tumors, taking into account patients' age and couples' perspectives. Informed consent should provide adequate information to the patient about the current state of his fertility and about the balance between risks and benefits in oncological terms. Standard approaches to genitourinary tumors should include a multidisciplinary team with urologists, oncologists, radiotherapists, psycho-sexologists, andrologists, gynecologists, and reproductive endocrinologists., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Anti-Hu antibodies are associated with autoimmune syndromes, mainly limbic encephalitis, encephalomyelitis, and painful sensory polyneuropathy (Denny-Brown). We report the case of a 15-year-old boy presenting with epilepsia partialis continua (EPC) found to have a right middle frontal gyrus brain lesion without atrophy or contralateral involvement. After partial resection, neuropathology revealed neuronal loss, reactive gliosis and astrocytosis, and perivascular mononuclear inflammatory infiltrate and features of neuronophagia resembling Rasmussen encephalitis. Suboptimal response to antiseizure drugs and surgery prompted further workup with identification of positive serum anti-Hu antibodies and a mediastinal seminoma. The patient was treated with immunotherapy including steroids, IV immunoglobulin, azathioprine, rituximab, plasmapheresis, and mediastinal lesion resection. However, he continued to experience EPC and psychomotor impairment along with left hemiparesis and dysarthria. Given clinical progression with failure to respond to immunotherapy and antiseizure polytherapy, hemispherotomy was attempted and seizure freedom achieved. A review of the literature found only 16 cases of neurologic presentations associated with anti-Hu antibodies in children, confirming the rarity of EPC in these cases. Thus, this report provides a new observation of germ cell mediastinal tumor associated with anti-Hu antibodies in children, broadening the spectrum of anti-Hu-associated neurologic disorders in children and highlighting the importance of considering antineuronal antibody testing in children presenting with EPC and brain lesions suggestive of Rasmussen encephalitis., (© 2023 American Academy of Neurology.)

Importance: Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development., Objective: This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development., Design and Participants: This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound., Results: TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis., Conclusions and Relevance: A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life., Competing Interests: Conflict of interest: H.L.C.-v.d.G. is on the editorial board of EJE. She was not involved in the review or editorial process for this paper, on which she is listed as an author. H.L.C.-v.d.G. is also involved in clinical trials in CAH sponsored by Spruce Biosciences. S.F.A. has received an unrestricted education grant from Neurocrine Biosciences and acted as a consultant to Novo Nordisk. A.R. is involved in clinical trials in CAH sponsored by Diurnal Ltd and Neurocrine Biosciences. All other authors declared to have no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Primary mediastinal choriocarcinoma, also known as non-pregnant choriocarcinoma, is a rare malignancy unrelated to pregnancy, with a higher incidence in males. And primary mediastinal choriocarcinoma is mostly associated with organ and lymph node metastasis, with rapid progression and poor prognosis. Here, we report an extremely rare case of the primary anterior mediastinal choriocarcinoma that occurred in an 18-year-old man with multiple metastases of the lung and brain., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

We describe an unusual case of prostatitis caused by Streptococcus canis evolving to endocarditis and splenic, renal, and cerebral thromboembolism in a dog, associated with a Sertoli cell tumour in a cryptic testis and diffuse prostatic squamous metaplasia. A nine-year-old, intact male, mixed-breed dog was presented to a veterinary teaching hospital with abdominal pain and prostration. Physical examination and abdominal ultrasonography revealed an atrophic right testicle located in the subcutaneous tissue. The left testicle was in the abdominal cavity with increased dimensions and irregular contours. Complete blood count analysis showed marked neutrophilic leukocytosis and thrombocytopenia. After clinical worsening, euthanasia was performed, and the dog was submitted to post-mortem examination. The main gross findings included testicular malposition with one cryptic and one ectopic testis, enlarged prostate with purulent content, distension of the urinary bladder with cloudy urine, vegetative valvular endocarditis in the mitral valve, and spleen and renal infarcts. Histological examination showed a Sertoli cell tumour in the abdominal testis, diffuse prostatic squamous metaplasia with marked keratinization associated with bacterial prostatitis, fibrinonecrotic cystitis, bacterial endocarditis with marked myxomatous degeneration in the mitral valve, and splenic, renal, and cerebral thromboembolism. Microbiological analysis identified Streptococcus canis in the prostate and mitral valve. Sertoli cell tumour of cryptic testis increases oestrogen production and leads to squamous metaplasia of the prostate, which should be considered as predisposing factors for ascending S. canis infection from the urogenital tract to the prostate. Then, haematogenous spread of S. canis from the prostate to mitral valve cause endocarditis and subsequent thromboembolism and infarcts, all decisive to poor prognosis in this case., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Tumors of the breast and reproductive organs that occur in children, adolescents, and young adults (AYA) have different biological features and can present special challenges. Although prognosis for these tumors is generally favorable, the long-term effects of treatment can be debilitating. Treatments are often multimodal and may include surgery as well as chemotherapy and/or radiation, which can cause considerable distress and anxiety related to loss of femininity or masculinity, concern over future fertility, or sexual dysfunction. Thus, tumors of the reproductive organs in pediatric/AYA patients require special consideration of the treatment effects beyond the intended oncologic outcome. Multidisciplinary teams should be involved in their care and address issues of fertility, sexual dysfunction, and psychosexual concerns before treatment begins. This review addresses histology, risk factors, prognosis, staging and treatment of gynecologic, breast and testicular cancers in pediatric and AYA patients., (© 2021 Wiley Periodicals LLC.)

Testicular mixed germ cell tumors (TMGCTs) are aggressive neoplasms that often have metastases at the time of diagnosis, primarily in the lungs, bones, and brain. Gastrointestinal metastases are rare, occurring in less than 5% of cases, while duodenal involvement is extremely rare, with only few reported cases. Furthermore, gastrointestinal bleeding is an atypical initial presentation of metastatic TMGCTs. Herein, we present a very rare case of upper gastrointestinal bleeding caused by a duodenal metastasis of a TMGCT in a 24-year-old man. The patient was admitted to our hospital due to abdominal pain and melena with a hemoglobin level of 52 g/L. He had no history of testicular swelling, or any other symptoms or signs of a testicular tumor. Upper gastrointestinal endoscopy revealed a duodenal tumor mass with irregular bleeding, and abdominal ultrasound and computed tomography showed a duodenal mass that infiltrate retroperitoneum. Emergency surgery was performed, and the histopathological findings of the resected specimen were consistent with TMGCT metastasis. Subsequently, a testicular tumor was confirmed and surgically removed; however, multiple metastatic deposits were observed in the lungs. Due to the patient's poor general condition, chemotherapy was not performed. The patient died 3 months after the initial diagnosis. This case suggests that, although duodenal metastatic TMGCTs are rare, they should be considered in the differential diagnosis of gastrointestinal bleeding in young male patients., (© 2023 Emilija Nikolovska Trpchevska et al., published by Sciendo.)

Background and Objectives : The relationship between male infertility (MI) and testicular cancer (TC) is bilateral. On one hand, it is well-established that patients diagnosed with TC have a high risk of pre- and post-treatment infertility. On the other hand, the risk of developing TC in male infertile patients is not clearly defined. The objective of this review is to analyze the histopathological, etiological, and epidemiological associations between MI and the risk of developing testicular cancer. This review aims to provide further insights and offer a guide for assessing the risk factors for TC in infertile men. Materials and Methods : A comprehensive literature search was conducted to identify relevant studies discussing the relationship between MI and the risk of developing TC. Results : The incidence rates of germ cell neoplasia in situ (GCNIS) appear to be high in infertile men, particularly in those with low sperm counts. Most epidemiological studies have found a statistically significant risk of developing TC among infertile men compared to the general or fertile male populations. The concept of Testicular Dysgenesis Syndrome provides an explanatory model for the common etiology of MI, TC, cryptorchidism, and hypospadias. Clinical findings such as a history of cryptorchidism could increase the risk of developing TC in infertile men. Scrotal ultrasound evaluation for testis lesions and microlithiasis is important in infertile men. Sperm analysis parameters can be useful in assessing the risk of TC among infertile men. In the future, sperm and serum microRNAs (miRNAs) may be utilized for the non-invasive early diagnosis of TC and GCNIS in infertile men. Conclusions : MI is indeed a risk factor for developing testicular cancer, as demonstrated by various studies. All infertile men should undergo a risk assessment using clinical examination, ultrasound, and semen parameters to evaluate their risk of TC.

Background: Pure testicular choriocarcinoma is a rare type of non-seminomatous germ cell tumor extremely poor prognostic with the tendency to bleed at the metastatic site. At the time of the diagnosis, 70% of patients have metastatic lesions. Depending on the site of the metastasis, symptoms vary. Gastrointestinal involvement is seen in less than 5% of cases, mostly in the duodenum., Case Presentation: We present a 47 years old male with testicular choriocarcinoma involving the jejunum, lung, liver, and kidney presenting with acute abdominal pain, melena, and dyspnea with some paraneoplastic symptoms. The patient had increased, severe and constant pain in the right lower quadrant for the previous four days. Additionally, he was complaining of nausea, vomiting, anorexia, and a history of melena for the last 10 days. Dyspnea on exertion, hemoptysis, and dry cough were the symptoms he was suffering from, for almost one year. The patient's general appearance was pale, ill, and thin with 10 kg of weight loss during the last some months. The computed tomography (CT) scan reported multiple metastatic lesions in both liver lobes and the left kidney. Pathologic study of the samples of small bowel lesions showed metastatic choriocarcinoma. Following the patient had been referred to an oncologist to start the chemotherapy regime. Finally, the patient has expired after 40 days of his first admission., Conclusions: Testicular choriocarcinoma is a rare but fatal malignancy among young men. Gastrointestinal metastases are infrequent involvement represented by melena and acute abdominal pain, obstruction, and mass. Physicians should consider it as a differential diagnosis for acute abdomen and gastrointestinal bleeding causation., (© 2023. The Author(s).)

Background: Both testicular germ cell tumours (TGCT) and neurodevelopmental disorders are associated with urogenital malformations. Few studies have investigated the association between psychiatric disorders and TGCT. We investigated whether history of any psychiatric or neurodevelopmental disorder is associated with increased risk or mortality of TGCT., Method: This is a nested case-control study including 6166 TGCT patients diagnosed during 1992-2014, individually matched for age and calendar period to 61,660 controls. We calculated odds ratios (ORs) for the association between type of psychiatric diagnoses and TGCT risk. Among the cases, we used a cohort design and calculated hazard ratios (HRs) of the association between psychiatric diagnose and all-cause and TGCT-specific death., Results: History of a neurodevelopmental disorder (attention deficit hyperactivity disorder, autism spectrum disorder and intellectual disabilities) was associated with an increased risk of seminoma (OR: 1.54; 1.09-2.19). Seminoma patients with neurodevelopmental disorders were younger (34 versus 38 years, p = 0.004) and had more stage IV disease (5.4% versus 1.2%) than those without. Psychiatric history overall was not associated with TGCT. Patient history of any psychiatric disorder was associated with an increased all-cause and TGCT-specific death., Conclusions: We report an association between neurodevelopmental disorders and testicular seminoma, and an increased TGCT-specific mortality for TGCT patients with psychiatric disorders., (© 2023. The Author(s).)

Background: Disruption in androgen profiles and testicular adrenal rest tumors in males with congenital adrenal hyperplasia (CAH) can negatively affect sexual activity and fertility. Adrenal hyperandrogenism suppresses gonadotropin secretion and testicular adrenal rest tumors (TARTS), despite being noncancerous lesions, cause obstructive azoospermia and impaired testosterone (T) production. Circulating T in men with uncontrolled CAH is often predominantly adrenal in origin, which is reflected in high androstenedione/testosterone ratios (A4/T). Therefore, decreased luteinizing hormone (LH) levels and an increased A4/T are markers of impaired fertility in these individuals., Methods: Oral tildacerfont 200 to 1000 mg once daily (QD) (n=10) or 100 to 200 mg twice daily (n=9 and 7) for 2 weeks (Study 201), and 400 mg QD (n=11) for 12 weeks (Study 202). Outcomes measured changes from baseline in A4, T, A4/T, and LH., Results: Mean T levels increased in Study 201 from 375.5 ng/dL to 390.5 ng/dL at week 2 (n=9), 485.4 ng/dL at week 4 (n=4) and 420.7 ng/dL at week 6 (n=4). In Study 202, T levels fluctuated in the normal range from 448.4 ng/dL at baseline to 412.0 ng/dL at week 12. Mean LH levels increased in Study 201 from 0.68 IU/L to 1.59 IU/L at week 2 (n=10), 1.62 IU/L at week 4 (n=5) and 0.85 IU/L at week 6 (n=4). In Study 202, mean LH levels increased from 0.44 IU/L at baseline to 0.87 IU/L at week 12. Mean A4/T decreased across both studies. In Study 201, the mean A4/T changed from a baseline of 1.28 to 0.59 at week 2 (n=9), 0.87 at week 4 (n=4), and 1.03 at week 6 (n=4). In Study 202, the A4/T decreased from baseline of 2.44 to 0.68 at week 12. Four men were hypogonadal at baseline; all experienced improved A4/T and 3/4 (75%) reached levels <1., Conclusion: Tildacerfont treatment demonstrated clinically meaningful reductions in A4 levels, and A4/T with concomitant increased LH levels indicating increased testicular T production. The data suggests improvement in hypothalamic-pituitary-gonadal axis function, but more data is required to confirm favorable male reproductive health outcomes., Competing Interests: Author AK is an employee of Rutgers University, a principal investigator for clinical trials in congenital adrenal hyperplasia with Spruce Biosciences Inc, and a consultant for Antares Pharma. Author RC is an employee of Spruce Biosciences Inc. The authors declare that this study received funding from Spruce Biosciences Inc. The funder had the following involvement with the study: participated with the study design, results and the decision to submit the findings for publication., (Copyright © 2023 Khattab and Charlton.)

Introduction: The diagnosis of paraneoplastic neurologic syndromes is challenging when the primary tumor masquerades as scar tissue (i.e. "burned-out")., Methods: Case report., Results: A 45-year-old male patient presented with progressive cerebellar symptoms and hearing loss. Initial screening for malignancy and extensive testing of paraneoplastic and autoimmune neuronal antibodies gave negative results. Repeated whole-body FDG-PET CT revealed a single paraaortic lymphadenopathy, metastasis of a regressed testicular seminoma. Anti-Kelch-like protein-11 (KLHL11) encephalitis was finally diagnosed., Conclusion: Our case highlights the importance of continued efforts to find an often burned-out testicular cancer in patients with a highly unique clinical presentation of KLHL11 encephalitis., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Persistent Mullerian duct syndrome (PMDS) is a rare disorder of sexual differentiation resulting from aberrations in the Mullerian inhibiting factor (MIF) pathway, with consequent failure of regression of fetal Mullerian duct. The concomitant association of undescended testis increases the likelihood of developing testicular tumors in these patients. Due to its rarity, clinic-pathologic and treatment outcome data on testicular cancer in PMDS is sparse. We present our institutional experience and review published literature on testicular cancer in PMDS., Material and Methods: We retrospectively queried our institutional testicular cancer database for all patients with a diagnosis of testicular cancer and PMDS, between January 1980 and January 2022. Additionally, a Medline/PubMed search was performed for English language articles published during the same time period. Data on pertinent clinical, radiologic, and pathologic disease characteristics were abstracted, in addition to treatment received and outcomes., Results: Of 637 patients treated for testicular tumors during the specified time period in our institution, 4 patients had a concomitant diagnosis of PMDS. Testicular tumor was pathologically confirmed as seminoma in 3, 1 had mixed germ cell tumor. All patients in our series presented with stage 2B or higher disease and required chemotherapy, either in the neoadjuvant or adjuvant setting, in addition to surgery. With a mean follow up of 67 months, all patients were disease free. Medline/PubMed search retrieved 44 articles (49 patients) of testicular tumors associated with PMDS, with majority (59%) presenting with a large abdominal mass. Only 5 cases (10%) had a preceding history of appropriately managed cryptorchidism., Conclusions: Testicular cancer in PMDS usually presents in adults with advanced stage disease resulting from neglected or inadequate management of cryptorchidism. Appropriate management of cryptorchidism in childhood is likely to decrease malignant degeneration, if not, enable early-stage diagnosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose of Review: Testicular cancer (TC) is the leading cancer in men between 18 and 39 years of age. Current treatment involves tumor resection followed by surveillance and/or one or more lines of cisplatin-based chemotherapy (CBCT) and/or bone marrow transplant (BMT). Ten years after treatment, CBCT has been associated with significant atherosclerotic cardiovascular disease (CVD) including myocardial infarction (MI), stroke, and heightened rates of hypertension, dyslipidemia, diabetes mellitus, and metabolic syndrome (MetS). Additionally, low testosterone levels and hypogonadism contribute to MetS and may further drive CVD., Recent Findings: CVD in TCS has been associated with worse physical functioning accompanied by role limitations, decreased energy, and decreased overall health. Exercise may play a role in ameliorating these effects. Systematic CVD screening practices are needed at TC diagnosis and in survivorship. We encourage a multidisciplinary partnership between primary care physicians, cardiologists, cardio-oncologists, medical oncologists, and survivorship providers to address these needs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Declaration of interests We declare no competing interests.

This case report describes Fournier's gangrene in a 35-year-old male following elective inguinal orchiectomy for testicular cancer. The aetiology was unknown, possibly beginning in the bottom of the scrotum following orchiectomy, alternatively through the scrotal skin after hair removal prior to surgery. Survivors from Fournier's gangrene often suffer from severe long-term morbidity, and multidisciplinary treatment is important for outcome optimization.

Background: Elevated intrascrotal temperature has been suggested as a risk factor for testicular cancer, which is the most common neoplasm among young men. Varicocoele was linked to increased intrascrotal temperature, but whether it is associated with testicular cancer is unclear., Objective: To explore the possible association between varicocoele at adolescence and the incidence of testicular cancer at adulthood., Design, Setting, and Participants: This nationwide, population-based, historical cohort study includes 1,521,661 Israeli male adolescents (mean age 17.5 ± 0.4 years), who were screened for varicocoele during the years 1967-2012, as part of their medical assessment prior to compulsory military service. The mean follow-up was 18 ± 4.2 years., Outcome Measurements and Statistical Analysis: The diagnosis of testicular cancer was ascertained from linkage of records to the the Israeli National Cancer Registry. Survival analysis was applied., Results: In total, 53,210 adolescents were diagnosed with varicocoele stages 2 and 3 prior to military service. Of 1988 (0.13% of the total cohort) men who were diagnosed with testicular cancer during follow-up, 54 (0.1%) had varicocoele prior to military service, while 1934 (99.9%) did not; p = 0.213. The age at cancer diagnosis and the distribution of seminomas versus non-seminomas did not differ significantly between those with and without varicocoele in adolescence. In a multivariable analysis controlling for sociodemographic factors, varicocoele was not associated with testicular cancer; odds ratio = 0.816 (CI: 0.615-1.083)., Conclusions: Varicocoele in adolescents was not found to be associated with testicular cancer in young adults., Patient Summary: In light of the theoretical association between varicocoele and testicular cancer, we conducted this large population study. We found no association between varicocoele in young adulthood and testicular cancer later in life., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: Androgen insensitivity syndrome (AIS) is a disorder of sexual differentiation caused by complete or partial resistance to the biological action of androgens. The common malignant tumors associated with this syndrome are seminomas. However, the risk of malignancy in childhood remains low. Case Report: A 8-month-old child with a female phenotype and a 46, XY karyotype, presented with bilateral inguinal hernia. The patient underwent right radical inguinal orchiectomy with high ligation of the spermatic cord and laparoscopic percutaneous extra-peritoneal herniorrhaphy. Final pathology confirmed a pure yolk sac tumor (YST) from the right testis. Androgen receptor (AR) gene mutation was found in the children. The follow-up ultrasonography shown no recurrence, with serum AFP returned to normal within 3 months. Conclusion: The case we presented is relatively infrequent in the literature with yolk sac tumor in a AIS children presented with a palpable lump inguinal region.

Background: Paraneoplastic limbic encephalitis is a rare neurologic syndrome that affects patients with cancer and commonly presents with symptoms of personality changes, visual disturbances, seizures, vertigo, and memory loss. It has an immune-mediated pathophysiology and is associated with antibodies directed against both the tumor and limbic structures in the nervous system. Here, we report a case of paraneoplastic limbic encephalitis with an unusual presentation with initial symptoms of panhypopituitarism., Case Presentation: A 28-year-old Caucasian man with history of testicular cancer in remission for almost 2 years was admitted to our hospital for altered mental status, syncope, vertical gaze palsy, ataxia, and tremor. Three months prior to admission, he began to have initial symptoms of fatigue, weight gain, and hypogonadism. A few weeks before admission, he also developed worsening neurological symptoms that led him to present to the hospital. While hospitalized, he had an episode of syncope. Evaluation of his syncope revealed that he was hypovolemic due to polyuria, concerning for diabetes insipidus. While the patient did not meet criteria for diabetes insipidus, further endocrine laboratory testing to evaluate his central hormonal axes revealed panhypopituitarism. He also underwent a neurologic work-up with brain magnetic resonance imaging and lumbar puncture, with results consistent with encephalitis. He received high-dose steroids, plasmapheresis, and intravenous immunoglobulin, which did not significantly improve his physical examination or mental status. Extensive testing did not show any recurrence of his testicular cancer. Paraneoplastic antibodies were also ordered, with anti-Ma2 antibodies eventually returning positive, consistent with anti-Ma2 paraneoplastic limbic encephalitis., Conclusion: Paraneoplastic limbic encephalitis is often a difficult diagnosis due to its variable presentation and timeline of presentation, leading to delays in both diagnosis and treatment. While paraneoplastic limbic encephalitis usually presents with neurological symptoms, it may also present with panhypopituitarism. A high index of suspicion is warranted for paraneoplastic syndromes in patients with history of malignancy, even if the malignancy is in remission., (© 2022. The Author(s).)

Background: Testicular adrenal rest tumors (TART) are a common complication of unknown cellular origin in patients with congenital adrenal hyperplasia (CAH). These benign tumors have both adrenal and testicular characteristics and are hypothesized to either derive from cells of adrenal origin from the fetal adrenogonadal primordium or by atypical differentiation of adult Leydig-progenitor cells., Objective: This study aims to unravel the identity and etiology of TART., Methods: Co-expression of adrenal-specific CYP11B1 and Leydig cell-specific HSD17B3 in TART was studied using immunohistochemistry. We studied the possibility of TART being derived from atypical differentiation of adult Leydig-progenitor cells by the quantification of adrenal-specific enzyme expression upon adrenocorticotrophic hormone (ACTH)-like stimulation of ex vivo cultured platelet-derived growth factor receptor alpha-positive cells. By comparing the transcriptome of TART (n = 16) with the transcriptome of fetal adrenal (n = 13), fetal testis (n = 5), adult adrenal (n = 11), and adult testis (n = 10) tissues, we explored the identity of TART., Results: We demonstrate co-expression of adrenal-specific CYP11B1 and testis-specific HSD17B3 in TART cells, indicating the existence of a distinct TART cell exhibiting both adrenal and testicular characteristics. Ex vivo cultured adult Leydig-progenitor cells did not express the ACTH-receptor MC2R but did express CYP11B1 upon stimulation. Unsupervised clustering of transcriptome data showed that TART was most similar to adult adrenal tissue, followed by adult testis tissue, and least similar to either fetal tissue., Conclusion: Our data suggest that TART is induced - most likely via activation of a cAMP/protein kinase A-dependent receptor - from a progenitor cell into a unique mature adrenal-like cell type, sometimes exhibiting both adrenal and testicular features.

Summary: Intussusception from a testicular germ cell tumour is extremely rare. Metastatic gastrointestinal implants outgrow their blood supply leading to central necrosis. This results in erosions and ulcerations, which can be visualised as submucosal polypoid masses. These masses can then serve as a lead point for intussusception. We report a case of a 25-year-old patient with small bowel obstruction due to an intussuscepted choriocarcinoma in the absence of any other apparent retroperitoneal disease. Urologists must exclude gastrointestinal tract (GIT) involvement in testicular cancers, and similarly, surgeons need to exclude testicular tumours in young men with unexplained GIT haemorrhage, bowel obstruction or intussusception., (Copyright© Authors.)

Subfertility is a risk factor for testicular cancers (TT), and conversely, TT may induce subfertility due to local and regional toxic effects. We aimed to identify the association between TT characteristics and pre-orchidectomy azoospermia. A systematic review of the literature was performed according to the PRISMA checklist. Overall, eight non-randomised studies involving 469 men with TT (azoospermia, n = 57; no azoospermia n = 412) were included in the qualitative analysis. Bilateral TT (12.3% vs 2.9% in non-azoospermia), non-seminoma germ cell tumours (6.4% vs 1.9%), germ cell neoplasia in-situ (GCNIS) (11.1% vs 1.2%), stage 2-3 disease (22.2% vs 0%), Sertoli Cell only (SCO) on biopsy (60% vs 37.5%) and a history of undescended testis (UDT) (66.7% vs 50%) were more common in azoospermic men. FSH levels are higher (18.7-23.2 mIU/L vs <0.1-8 mIU/L in non-azoospermia), testosterone is lower, and testis size are smaller (lower range 1 mL vs 10 mL) in men with azoospermia. Leydig cell tumours and hyperplasia were only detected in men with azoospermia. In summary, bilateral TT, GCNIS, higher tumour stage, smaller testes, SCO and history of UDT may have direct effects on spermatogenesis. Small testis, raised FSH and low testosterone may reflect reduced testicular function in azoospermic men. Performing a pre-orchidectomy semen analysis is important to identify those with azoospermia or severe oligospermia in order to plan for cryopreservation or onco-TESE in young men who wish to conceive., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Abstract: Polyorchidism, a very rare congenital anomaly, refers to the presence of more than 2 testes. It is often associated with many other pathologies including cryptorchidism, varicocele, testicular malignancy, and inguinal hernias.In this report, we describe a 40-year-old man who presented with an intermittently painful left groin, initially appearing as inguinal hernia. On ultrasound examination, a supernumerary testes and epididymis were found in the inguinal canal. The testes appeared sonographically normal with no evidence of associated pathologies. There was no evidence of an inguinal hernia containing fat or bowel.Ultrasound is essential in first-line diagnosis and classification of polyorchidism. Color Doppler ultrasound and magnetic resonance imaging can be used to clarify findings if sonographic images are inconclusive. We also review relevant literature as it pertains to classification, embryology, and treatment options. Patient treatment is based on imaging findings; if associated pathologies or malignancy is suspected, aggressive treatment such as surgical excision may be necessary. Otherwise, conservative treatment may be all that is needed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Hyperemesis gravidarum is characterized by severe nausea and vomiting in pregnancy, frequently resulting in severe maternal nutritional deficiency. Maternal undernutrition is associated with adverse offspring health outcomes. Whether hyperemesis gravidarum permanently affects offspring health remains unclear. This review aimed to evaluate the effects of maternal hyperemesis gravidarum on offspring health., Data Sources: MEDLINE and Embase were searched from inception to September 6, 2021., Study Eligibility Criteria: Studies reporting on health at any age beyond the perinatal period of children born to mothers with hyperemesis gravidarum were included., Methods: Two reviewers independently selected studies and extracted data. The Newcastle-Ottawa Quality Assessment Scale was used to assess risk of bias. We conducted a narrative synthesis and meta-analysis where possible. In meta-analyses with high heterogeneity (I 2 >75%), we did not provide a pooled odds ratio., Results: Nineteen studies were included in this systematic review (n=1,814,785 offspring). Meta-analysis (n=619, 2 studies: 1 among adolescents and 1 among adults) showed that hyperemesis gravidarum was associated with anxiety disorder (odds ratio, 1.74; 95% confidence interval, 1.04-2.91; I 2 , 0%) and sleep problems in offspring (odds ratio, 2.94; 95% confidence interval, 1.25-6.93; I 2 , 0%). Hyperemesis gravidarum was associated with testicular cancer in male offspring aged up to 40 years on meta-analysis (5 studies, n=20,930 offspring), although heterogeneity was observed on the basis of a wide 95% prediction interval (odds ratio, 1.60; 95% confidence interval, 1.07-2.39; I 2 , 0%; 95% prediction interval, 0.83-3.08). All 6 studies reporting on attention deficit (hyperactivity) disorder and autism spectrum disorder reported an increase among children of mothers with hyperemesis gravidarum in comparison with children of unaffected mothers. Meta-analysis showed high heterogeneity, precluding us from reporting a pooled odds ratio. Most studies reporting on cognitive and motor problems found an increase among hyperemesis gravidarum-exposed children. One study investigated brain structure and found smaller cortical volumes and areas among children from hyperemesis gravidarum-affected pregnancies than among those from unaffected pregnancies. Studies evaluating anthropometry and cardiometabolic disease risk of hyperemesis gravidarum-exposed children had inconsistent findings., Conclusion: Our systematic review showed that maternal hyperemesis gravidarum is associated with small increases in adverse health outcomes among children, including neurodevelopmental disorders, mental health disorders, and possibly testicular cancer, although evidence is based on few studies of low quality., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)