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Background: Testicular microlithiasis is the presence of small calcifications in the testicular parenchyma. The association between testicular microlithiasis and germ cell neoplasia in situ, a precursor to testicular cancer, is still unclear., Objectives: To determine the incidence of germ cell neoplasia in situ in men with testicular microlithiasis and evaluate the indication for testicular biopsy according to risk factors in the form of male infertility/reduced semen quality, testicular atrophy, and history of cryptorchidism., Materials and Methods: This retrospective case series included all patients diagnosed with testicular microlithiasis who underwent testicular biopsies at three hospitals in Denmark between 2007 and 2021. The medical records of 167 patients were reviewed, and data on patient demographics, testicular microlithiasis characteristics, risk factors, histological findings, and treatments were collected. The main outcome measure was the incidence of germ cell neoplasia in situ in relation to each risk factor. The data were analyzed using descriptive statistics. Logistic regression was used to examine the odds ratio of germ cell neoplasia in situ in patients with testicular microlithiasis and testicular atrophy., Results: Germ cell neoplasia in situ was found in 13 out of 167 patients (7.8% [95% confidence interval: 4.3, 13.2]). Eleven of these had testicular atrophy resulting in a significantly higher incidence in this group than other risk factors (odds ratio 9.36 [95% confidence interval: 2.41, 61.88]; p = 0.004)., Discussion: The study comprises the largest cohort to date of men who have undergone testicular biopsies because of testicular microlithiasis and additional risk factors. Limitations include its retrospective design, and relatively low absolute numbers of patients with germ cell neoplasia in situ on biopsies., Conclusion: This study found that men with testicular microlithiasis and testicular atrophy are at an increased risk of germ cell neoplasia in situ. Additionally, our results indicate that biopsies should be considered in men with a combination of subfertility and bilateral testicular microlithiasis. Our findings do not support testicular biopsies for men with testicular microlithiasis and other risk factors., (© 2024 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

No study has comprehensively examined associated factors (adverse health outcomes, health behaviors, and demographics) affecting cognitive function in long-term testicular cancer survivors (TC survivors). TC survivors given cisplatin-based chemotherapy completed comprehensive, validated surveys, including those that assessed cognition. Medical record abstraction provided cancer and treatment history. Multivariable logistic regression examined relationships between potential associated factors and cognitive impairment. Among 678 TC survivors (median age = 46; interquartile range [IQR] = 38-54); median time since chemotherapy = 10.9 years, IQR = 7.9-15.9), 13.7% reported cognitive dysfunction. Hearing loss (odds ratio [OR] = 2.02; P = .040), neuropathic pain (OR = 2.06; P = .028), fatigue (OR = 6.11; P < .001), and anxiety/depression (OR = 1.96; P = .029) were associated with cognitive impairment in multivariable analyses. Being on disability (OR = 9.57; P = .002) or retired (OR = 3.64; P = .029) were also associated with cognitive decline. Factors associated with impaired cognition identify TC survivors requiring closer monitoring, counseling, and focused interventions. Hearing loss, neuropathic pain, fatigue, and anxiety/depression constitute potential targets for prevention or reduction of cognitive impairment in long-term TC survivors., (© The Author(s) 2024. Published by Oxford University Press.)

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 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.)

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.)

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.)

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.)

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).)

Introduction: Paraneoplastic hyperthyroidism (PH) has been reported in patients with testicular germ cell tumors (GCTs), sporadically. This disorder is caused by extremely elevated serum levels of beta-human chorionic gonadotropin (bHCG). To date, little is known about the prevalence of PH, and its clinical features are poorly understood. The aim of the present study was to analyze the relative frequency and clinical features of PH in GCTs and evaluate their effects on therapeutic outcomes., Methods: A cohort of 438 patients treated for testicular GCT from 2017 to 2023 was retrospectively analyzed for histology, age, clinical stage, and presence of PH. The clinical features of the patients with PH were evaluated descriptively. The relative frequency of PH was compared among the subgroups using descriptive statistical methods., Results: Three patients with PH were identified; all had clinical symptoms of hyperthyroidism, suppressed serum levels of thyroid-stimulating hormone (TSH), and increased levels of tri-iodothyronin (fT3). All the patients had advanced, metastasized, and non-seminomatous GCTs. Serum bHCG levels ranged from 225,00 U/L to 1,520,000 U/L. The prevalence of PH was 0.7% in the entire GCT population and 60% in those with very high bHCG serum levels. All the patients received standard cisplatin-based chemotherapy along with thyrostatic treatment. The clinical symptoms of the hyperthyroidism rapidly disappeared. TSH levels normalized with decreasing bHCG levels. The PH treatment did not affect the therapeutic outcomes of the patients., Conclusion: PH may occur in 0.7% of all patients with GCT but may be present in up to 60% of patients with very high levels of bHCG. Measuring serum levels of TSH and fT3 should be performed in addition to routine diagnostic measures in all patients with poor prognosis GCTs. Thyrostatic medication is recommended for patients with the clinical symptoms of hyperthyroidism. Early recognition of hyperthyroidism and prompt intervention will reduce comorbidity and help optimize therapeutic outcomes., (© 2024 S. Karger AG, Basel.)