Testicular Cancer Research Articles

P-030 Semen parameters as predictors of long-term health: a systematic review

Abstract Study question Do semen parameters predict long-term health outcomes in men? Summary answer Semen parameters do not have a good predictive value for mortality, diabetes, cardiovascular disease (CVD) or cancer. What is known already One in 3 men attending infertility clinics have suboptimal semen analysis. Assisted conception treatments are offered to them as treatment for infertility and their care usually ends there. There is now a growing body of evidence male infertility predicts future development of medical comorbidities. Multiple studies have looked into the association between clinical male infertility, involuntary childlessness or suboptimal sperm analysis and the risk of cancer, cardiovascular risks, diabetes, autoimmune diseases and mortality. However, there is still conflicting evidence regarding long-term health risk in men with suboptimal semen quality. Study design, size, duration A systematic review methodology was used using PRISMA guideline. The papers were selected from PubMed/MEDLINE, EMBASE and EBM from databases’ inception to May 2023. Reviews and case series were excluded. The selected studies were assessed for quality and risk of bias using QUADAS-2. Meta-analysis was done where appropriate. The scope of the analysis was to identify whether semen parameters could predict long-term health outcomes in men. Participants/materials, setting, methods Only papers reporting on health outcomes in men having at least one semen analysis result before diagnosis were included. A 2x2 contingency table was done for each study where data was available and true positives and negatives, false positives and negatives were calculated. The analysis was performed using MetaDTA, which generated estimates for sensitivity (Sn) and specificity (Sp), hierarchical summary receiver operating characteristic (HSROC) spaces and diagnostic odds ratio (DOR) with 95% confidence intervals (CI). Main results and the role of chance Twenty studies from three continents (USA, Europe and Asia) were included reporting on mortality (5), lifespan (1), cardiovascular disease (CVD) (2), diabetes (3), cancer (5), testicular carcinoma in situ (4), prostate-specific antigen (2), hospitalizations (2) and Charlson Comorbidity Index (1). Based on extracted data we could only analyse the predictive value of azoospermia and oligospermia for all-cause mortality, diabetes, CVD and cancer as there was insufficient data for other parameters. The results showed high specificity and low sensitivity of azoospermia and oligospermia for all outcomes (all-cause mortality: Sp 0.968, Sn 0.055 and Sp 0.839, Sn 0.162; diabetes: Sp 0.967, Sn 0.037 and Sp 0.902, Sn 0.046; cancer: Sp 0.964, Sn 0.135 and Sp 0.949, Sn 0.105; CVD: Sp 0.904, Sn 0.101 and Sp 0.932, Sn 0.074). HSROC model with 95% predictive region showed limited accuracy of sperm concentration as a test for any of the outcomes. DOR (95%CI) for azoospermia and oligospermia also showed that sperm concentration cannot be used as predictive test for any of the outcomes: all-cause mortality (1.72, 0.75-3.94 and 1.005, 0.59-1.693), diabetes (1.10, 0.77-1.56 and 0.44, 0.29-0.68), cancer (4.16, 1.45-11.97 and 2.18, 0.38-12.38) and CVD (1.05, 0.75-1.46 and 1.09, 0.83-1.44) when compared to normospermia. Limitations, reasons for caution Risk of Bias assessment showed high or unclear risk of bias in 14 studies mainly due to population selection. Not all laboratories adhered to WHO methodology, increasing the heterogeneity in reporting semen results and cut-offs. Concentration was the predominant parameter reported. Wider implications of the findings To answer the question whether poor semen quality is a predictor for adverse long-term health outcomes in men requires larger and well-designed studies. Until then, we should not be advising men that there are implications on long term health based on semen analysis results, with any confidence. Trial registration number not applicable

SEOM-GG clinical guidelines for the management of germ-cell testicular cancer (2023)

Testicular germ cell tumors are the most common tumors in adolescent and young men. They are curable malignancies that should be treated with curative intent, minimizing acute and long-term side effects. Inguinal orchiectomy is the main diagnostic procedure, and is also curative for most localized tumors, while patients with unfavorable risk factors for recurrence, or those who are unable or unwilling to undergo close follow-up, may require adjuvant treatment. Patients with persistent markers after orchiectomy or advanced disease at diagnosis should be staged and classified according to the IGCCCG prognostic classification. BEP is the most recommended chemotherapy, but other schedules such as EP or VIP may be used to avoid bleomycin in some patients. Efforts should be made to avoid unnecessary delays and dose reductions wherever possible. Insufficient marker decline after each cycle is associated with poor prognosis. Management of residual masses after chemotherapy differs between patients with seminoma and non-seminoma tumors. Patients at high risk of relapse, those with refractory tumors, or those who relapse after chemotherapy should be managed by multidisciplinary teams in experienced centers. Salvage treatment for these patients includes conventional-dose chemotherapy (TIP) and/or high-dose chemotherapy, although the best regimen and strategy for each subgroup of patients is not yet well established. In late recurrences, early complete surgical resection should be performed when feasible. Given the high cure rate of TGCT, oncologists should work with patients to prevent and identify potential long-term side effects of the treatment. The above recommendations also apply to extragonadal retroperitoneal and mediastinal tumors.

The Prevalence of Gonadal Changes in Patients with Congenital Adrenal Hyperplasia

Abstract Background Adrenal rest tumours can appear in early childhood in patients with congenital adrenal hyperplasia(CAH). The common cause of infertility in males with CAH is testicular adrenal rest tumours (TARTs). Ovarian adrenal rest tumour (OART) and polycystic ovaries (PCO) can impair the ovarian function in female patients with CAH. Objective Detect the prevalence of gonadal changes by imaging among patients with CAH andassess the patients' radiological findings in relation to their hormonal profile. Patients and Methods This observational, cross sectional study was conducted on 50 patients with CAH. Testicular ultrasonography was done to male patients and magnetic resonanceimaging (MRI) of the pelvis was done to female patients. Data on prescribed glucocorticoid dose and serum levels of 17- hydroxyprogesterone (17-OHP), androstenedione (Andro) and ACTH were obtained from medical records within endocrinology clinic, Children's Hospital, Ain Shams University. Results TARTs were detected in 10/20 (50%) of CAH patients. There was significant relationbetween presence of TARTs and each of weight standard deviation score (SDS), body mass index (BMI), BMI SDS and current bone age (p = 0.028, 0.046, 0.017 and 0.023; respectively). There was no significant relation between presence of TARTs and the laboratory parameters or the treatment received (p > 0.05). There was significant correlation between Tanner testicular volume and mean testicular volume by ultrasound (p < 0.001). Only one female patient had bilateral polycystic ovaries (prevalence 3.3%) and none had ovarian adrenal rest tumours. Conclusion The prevalence of TARTs in male patients in our study is high (50%), highlighting the importance of TARTs screening in children with CAH. We would suggest that routine ovarian imaging in CAH females is not indicated. However, when ovarian dysfunction is present, ovarian imaging is advised.

Exploring the genetic and epigenetic underpinnings of early-onset cancers: Variant prioritization for long read whole genome sequencing from family cancer pedigrees.

Despite significant advances in our understanding of genetic cancer susceptibility, known inherited cancer predisposition syndromes explain at most 20% of early-onset cancers. As early-onset cancer prevalence continues to increase, the need to assess previously inaccessible areas of the human genome, harnessing a trio or quad family-based architecture for variant filtration, may reveal further insights into cancer susceptibility. To assess a broader spectrum of variation than can be ascertained by multi-gene panel sequencing, or even whole genome sequencing with short reads, we employed long read whole genome sequencing using an Oxford Nanopore Technology (ONT) PromethION of 3 families containing an early-onset cancer proband using a trio or quad family architecture. Analysis included 2 early-onset colorectal cancer family trios and one quad consisting of two siblings with testicular cancer, all with unaffected parents. Structural variants (SVs), epigenetic profiles and single nucleotide variants (SNVs) were determined for each individual, and a filtering strategy was employed to refine and prioritize candidate variants based on the family architecture. The family architecture enabled us to focus on inapposite variants while filtering variants shared with the unaffected parents, significantly decreasing background variation that can hamper identification of potentially disease causing differences. Candidate d e novo and compound heterozygous variants were identified in this way. Gene expression, in matched neoplastic and pre-neoplastic lesions, was assessed for one trio. Our study demonstrates the feasibility of a streamlined analysis of genomic variants from long read ONT whole genome sequencing and a way to prioritize key variants for further evaluation of pathogenicity, while revealing what may be missing from panel based analyses.

Mechanisms of Bleomycin-induced Lung Fibrosis: A Review of Therapeutic Targets and Approaches.

Pulmonary toxicity is a serious side effect of some specific anticancer drugs. Bleomycin is a well-known anticancer drug that triggers severe reactions in the lungs. It is an approved drug that may be prescribed for the treatment of testicular cancers, Hodgkin's and non-Hodgkin's lymphomas, ovarian cancer, head and neck cancers, and cervical cancer. A large number of experimental studies and clinical findings show that bleomycin can concentrate in lung tissue, leading to massive oxidative stress, alveolar epithelial cell death, the proliferation of fibroblasts, and finally the infiltration of immune cells. Chronic release of pro-inflammatory and pro-fibrotic molecules by immune cells and fibroblasts leads to pneumonitis and fibrosis. Both fibrosis and pneumonitis are serious concerns for patients who receive bleomycin and may lead to death. Therefore, the management of lung toxicity following cancer therapy with bleomycin is a critical issue. This review explains the cellular and molecular mechanisms of pulmonary injury following treatment with bleomycin. Furthermore, we review therapeutic targets and possible promising strategies for ameliorating bleomycin-induced lung injury.

Clinical analysis of 23 cases of epidermoid cyst of testis in children.

This study aims to examine the clinical characteristics and surgical management of pediatric testicular epidermoid cysts, thereby contributing to the existing body of knowledge pertinent to the diagnosis and therapeutic intervention s for this condition. A retrospective analysis was conducted on the clinical records of 23 pediatric patients diagnosed with testicular epidermoid cysts, who were admitted to our institution between April 2013 and February 2024. Concurrently, a comprehensive review and analysis of pertinent literature were undertaken to augment the findings. The mean age at which the onset of epidermoid cysts was observed was 6.0 years. All cases were singular and unilateral. B-ultrasound diagnosis categorized 6 cases as epidermoid cysts, 11 as teratomas, and 6 as indeterminate, yielding a diagnostic sensitivity of 26.1%. All patients underwent testicle-sparing mass resection, and nine patients underwent rapid intraoperative frozen section analysis, revealing eight cases of testicular epidermoid cysts and one teratoma, with a diagnostic sensitivity of 88.89%. Postoperative histopathological examination confirmed the diagnosis of testicular epidermoid cyst. Pediatric testicular epidermoid cysts are an uncommon occurrence, primarily presenting as a painless scrotal mass, which can mimic the clinical features of malignant testicular tumors. Imaging modalities and histopathological assessment are pivotal in the diagnostic process for pediatric testicular epidermoid cysts. For cases where B-ultrasound is inconclusive, rapid intraoperative pathological examination should be considered.

Trials of interventions for ovarian and testicular germ cell tumors registered in ClinicalTrials.gov: A cross-sectional study

IntroductionThere is unmet need in the treatment of ovarian and testicular germ cell tumors (GCTs). This study analyzed registered trials of interventions for GCTs. Materials and methodsWe included trials of interventions for GCTs registered on ClinicalTrials.gov by July 29, 2022. We analyzed their interventions, outcome measures and study design. ResultsWe included 142 trials registrations; 42 (30 %) for ovarian GCTs, 50 (35 %) for testicular GCTs, and 50 (35 %) trials for both. The majority of the trials were completed (56 %) and did not have results available (75 %). Most trials were in Phase 2. Information about the study design were not reported for many analyzed trials. Most trials had a single-group assignment (44 %) and were open-label (68 %). The median planned number of enrolled participants was 43.Most registrations used medicine(s) (87 %), either as a single type of intervention or in combination. The most commonly used type of medicine was chemotherapy (54 %). Primary outcome was not reported in 23 % of registrations, and secondary outcomes were not reported in 35 % of registrations. Overall survival was used in 6 % of registrations as a primary outcome and in 31 % of registrations as a secondary outcome. ConclusionsFew trials on GCTs were registered on ClinicalTrials.gov, and their number was declining in recent times. Most registrations did not report relevant information about the study design, or results if completed. More effort is needed to foster trials on GCTs, as well as to optimize the management of the registrations and foster the publication of research results.

Quality and Readability of Online Health Information on Common Urologic Cancers: Assessing Barriers to Health Literacy in Urologic Oncology.

A growing number of Americans search online for health information related to urologic oncologic care each year. The American Medical Association recommends that medical information be written at a maximum sixth-grade level in order to be comprehensible by the majority of patients. As such, it is important to assess the quality and readability of online patient education material that patients are being exposed to. A Google search was performed using the terms "testicular cancer," "prostate cancer," "kidney cancer," and "bladder cancer," and the top 30 results for each were reviewed. Websites were categorized based on their source. Readability was assessed using the Flesch-Kincaid Grade Level, the Gunning Frequency of Gobbledygook, and the Simple Measure of Gobbledygook indices. Quality was assessed using the DISCERN Quality Index (1-5 scale). A total of 91 websites were included in our analysis. On average, online health information pertaining to urologic cancers is written at a 10th- to 11th-grade reading level, which is significantly higher than that of an average American adult and that recommended by the American Medical Association (P < .01). The overall quality of websites was 3.4 ± 0.7, representing moderate to high quality. There was no significant difference in readability based on cancer type or information source. Despite being of moderate to high quality, online patient education materials related to common urologic cancers are often written at a grade level that exceeds the reading level of an average American adult. This presents as a barrier to online health literacy and calls into question the utility of these resources.

Causality of genetically determined metabolites on susceptibility to prevalent urological cancers: a two-sample Mendelian randomization study and meta-analysis.

Prevalent urological cancers, including kidney, prostate, bladder, and testicular cancers, contribute significantly to global cancer incidence and mortality. Metabolomics, focusing on small-molecule intermediates, has emerged as a tool to understand cancer etiology. Given the knowledge gap in this field, we employ a two-sample Mendelian randomization (MR) analysis to investigate the causal relationships between genetically determined metabolites (GDMs) and the susceptibility to four common urological cancers. The study employs genome-wide association studies (GWAS) data from European populations, featuring the most extensive case count available for both blood metabolites and four prevalent urological cancers. Preliminary and secondary MR analyses were separately conducted, employing inverse variance weighted (IVW) as the primary method. Multiple statistical analyses, including the MR-Steiger test, Cochran's Q test, leave-one-out analysis, MR-Egger intercept analysis, and MR-PRESSO analysis, were executed to ensure robustness. Additionally, a meta-analysis was carried out to consolidate findings. The weighted median (WM) method was utilized for a relatively lenient correction (PWM < 0.05). After rigorous genetic variation filtering, 645 out of 1,400 metabolites were included in both preliminary and secondary MR analyses. Preliminary MR analysis identified 96 potential causal associations between 94 distinct metabolites and four urological cancers. Secondary analysis based on Finnish outcome data revealed 93 potential causal associations. Cross-database meta-analysis identified 68 blood metabolites associated with four urological cancers. Notably, 31 metabolites remained significant after using WM for correction, with additional 37 suggestive causal relationships. Reverse MR analysis revealed a significant causal association between genetically predicted prostate cancer and elevated 4-hydroxychlorothalonil levels (IVW, combined OR: 1.039, 95% CI 1.014-1.064, p = 0.002; WM, combined OR: 1.052, 95% CI 1.010-1.095, p = 0.014). This comprehensive MR study provides insights into the causal relationships between blood metabolites and urological cancers, revealing potential biomarkers and therapeutic targets, thereby addressing gaps in understanding and laying the foundation for targeted interventions in urological cancer research and treatment.

De Novo Urological Malignancies After Renal Transplantation: An Asian 30-Year Experience.

As the incidence of urological malignancies after renal transplantation (RT) is observed to be greater than in the general population, a better understanding of them is important. We present our experience with urological tumors in RT recipients at our transplant center, and analyze their incidence, management and outcomes. A retrospective analysis of 2177 RT recipients on follow-up at our center between 1990 and 2022 was conducted for de novo genitourinary malignancy. Patients diagnosed with malignancy before transplantation were excluded. Clinicopathological data at diagnosis and follow-up were collected and analyzed. Kaplan-Meier estimates were used to evaluate overall survival (OS) and cancer-specific survival (CSS). Statistical analysis was performed using IBM SPSS v.24 (IBM Corp., Armonk, NY, USA). The overall incidence of Urological malignancies was 3.9%, with 89 cancers diagnosed in 85 patients. Renal cell carcinoma was most common (n=61, 68.5%), followed by prostate cancer (n=10, 11.2%), urothelial carcinoma (n=10, 11.2%), squamous cell carcinoma of the penis/scrotum (n=7, 7.9%), and testicular cancer (n=1, 1.1%). Mean duration between transplantation and diagnosis of malignancy was 9.9 (0.4-20.7) years. At a median follow-up of 4.6 (018.2) years, 27 deaths were seen; 7(25.9%) were due to urological malignancy. CSS rates were 86% and 78% at five and ten years, respectively, after diagnosis. We present one of the largest series of de novo urological malignancies observed over an extended 30-year follow-up of RT recipients, demonstrating an elevated risk in line with other studies. Regular surveillance for malignancies is advised, in order to ensure early diagnosis and management.

Patients with cancer who will be cured and projections of complete prevalence in Italy from 2018 to 2030

The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking. Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis. A total of 3 347 809 people were alive in Italy in 2018 after a cancer diagnosis, corresponding to 5.6% of the resident population. They will increase by 1.5% per year to 4 012 376 in 2030, corresponding to 6.9% of the resident population, 7.6% of women and ∼22% after age 75 years. In 2030, more than one-half of all prevalent cases (2million) will have been diagnosed by ≥10 years. Those with breast (1.05 million), prostate (0.56 million), or colorectal cancers (0.47 million) will be 52% of all prevalent patients. Cure prevalence was 86% for all patients alive in 2018 (87% for patients with breast cancer and 99% for patients with thyroid or testicular cancer), increasing with time since diagnosis to 93% for patients alive after 5 years and 96% after 10 years. Among patients who survived at least 5 years, the excess risk of death (1- cure prevalence) was <5% for patients with most cancer types except for those with cancers of the breast (8.3%), lung (11.1%), kidney (13.2%), and bladder (15.5%). Study findings encourage the implementation of evidence-based policies aimed at improving long-term clinical follow-up and rehabilitation of people living after cancer diagnosis throughout the course of the disease. Updated estimates of complete prevalence are important to enhance data-driven cancer control planning.

Cost analysis of anticancer chemotherapy and chemoirradiation regimens considering the drugs marketed through Jan Aushadhi (People's Medicine) stores and their branded counterparts: First cost comparison study.

Chemotherapy in an integral part of cancer treatment, either administered alone or in combination with radiation. However, the cost of these drugs is often prohibitively high for most patients. To address this issue, the Government of India has established Jan Aushadhi (JAS) stores across the country, where affordable generic medicines are available. In the current study, we performed a cost minimization analysis comparing JAS drugs with branded chemotherapeutic drugs used in various cancer treatment regimens. This study was to conduct a cost-minimization analysis by comparing the costs of different regimens when using JAS drugs, the most expensive branded drugs, and the least expensive branded drugs in the treatment of cancer in India. The study focused on conducting a cost minimization analysis of various chemotherapy drugs used in the treatment of different cancers, considering the availability of anticancer drugs at JAS stores. The costs for different chemotherapy regimens, including both anticancer and supportive drugs, were calculated for single and complete cycles. The costs of the most expensive and least expensive branded drugs were noted from the Current Index of Medical Stores. The cost difference (CD) was calculated by subtracting the cost of the cheaper drug from that of the costliest brand. The cost ratio (CR) and the percentage of cost variation (PCV) were calculated for India-specific conditions. The study analyzed the CD for various regimens using JAS drugs for chemotherapy treatment of breast, esophagus, rectal, colon, stomach, prostate, ovary, endometrial, cervical, head and neck, lung, multiple myeloma, testicular, and lymphoma cancers. It also considered chemoirradiation regimens for brain, head and neck, anorectal, esophageal, and uterine cervical cancers. Significant CDs were observed when both anticancer and supportive drugs were obtained from JAS stores. To the best of the authors' knowledge, this is the first study to consider the CD, CR, and PCV for various regimens using JAS drugs, as well as the costliest and cheapest branded drugs in standard cancer treatment regimens. The results of this study are expected to assist healthcare professionals and pharmacists in understanding the cost-saving benefits of substituting expensive branded drugs with more affordable chemotherapeutic drugs for the treatment of cancer. This substitution can provide financial benefit for socioeconomically marginalized population.

Expression of Podocalyxin Potentially Decorated With Low-sulfated Keratan Sulfate in Human Testicular Embryonal Carcinoma.

SummaryWe previously demonstrated that among various histological types of human testicular germinal cell tumors (GCTs), embryonal carcinoma (EC) preferentially expresses low-sulfated keratan sulfate (KS) consisting of repeating N-acetyllactosamine (LacNAc) disaccharide units composed of galactose and 6-O-sulfated N-acetylglucosamine (GlcNAc), which is recognized by the R-10G antibody. Recently, we generated another anti-low-sulfated KS monoclonal antibody, 294-1B1. Immunohistochemical analysis of testicular GCTs (n=83) revealed that the low-sulfated KS recognized by 294-1B1 is also preferentially expressed in EC but minimally in other GCT histological types. Moreover, immunolabeling with R-10G and 294-1B1 antibodies was resistant to peptide-N-glycosidase F digestion, and EC was not stained with the MECA-79 antibody, indicating that low-sulfated KS expressed in EC contains mucin-type core 2 O-glycans carrying GlcNAc-6-O-sulfated oligo-LacNAc. Double immunofluorescence staining showed that R-10G and 294-1B1 antibody signals colocalized with those for podocalyxin (PODXL). Furthermore, western blot analysis of recombinant human PODXL•IgG fusion proteins secreted from low-sulfated KS-expressing human embryonic kidney 293T cells revealed that PODXL functions as a core protein for low-sulfated KS. Taken together, these findings strongly suggest that the PODXL glycoform decorated with low-sulfated KS is preferentially expressed in human testicular EC and may therefore serve as a diagnostic marker for this malignancy.

A Comparison of ChatGPT and Human Questionnaire Evaluations of the Urological Cancer Videos Most Watched on YouTube

AimTo examine the reliability of ChatGPT in evaluating the quality of medical content of the most watched videos related to urological cancers on YouTube. Material and methodsIn March 2024 a playlist was created of the first 20 videos watched on YouTube for each type of urological cancer. The video texts were evaluated by ChatGPT and by a urology specialist using the DISCERN-5 and Global Quality Scale (GQS) questionnaires. The results obtained were compared using the Kruskal-Wallis test. ResultsFor the prostate, bladder, renal, and testicular cancer videos, the median (IQR) DISCERN-5 scores given by the human evaluator and ChatGPT were (Human: 4 [1], 3 [0], 3 [2], 3 [1], P = .11; ChatGPT: 3 [1.75], 3 [1], 3 [2], 3 [0], P = .4, respectively) and the GQS scores were (Human: 4 [1.75], 3 [0.75], 3.5 [2], 3.5 [1], P = .12; ChatGPT: 4 [1], 3 [0.75], 3 [1], 3.5 [1], P = .1, respectively), with no significant difference determined between the scores. The repeatability of the ChatGPT responses was determined to be similar at 25 % for prostate cancer, 30 % for bladder cancer, 30 % for renal cancer, and 35 % for testicular cancer (P = .92). No statistically significant difference was determined between the median (IQR) DISCERN-5 and GQS scores given by humans and ChatGPT for the content of videos about prostate, bladder, renal, and testicular cancer (P > .05). ConclusionAlthough ChatGPT is successful in evaluating the medical quality of video texts, the results should be evaluated with caution as the repeatability of the results is low.

Gonadal Teratomas: A State-of-the-Art Review in Pathology.

Teratomas are neoplasms arising from germ cells and encompass tissues derived from two or more embryonic germ layers, including ectoderm, mesoderm, and endoderm. These tumours typically localize along the midline or in paramedian positions and can manifest as gonadal (20%) or extragonadal (80%) entities. Although gonadal teratomas are uncommon, they represent the predominant type of gonadal tumour in the paediatric population. They comprise approximately 20-25% of all ovarian tumours in females and about 3-5% of all testicular tumours in males. Ovarian teratomas exhibit a higher incidence in early childhood and adolescence, whereas testicular teratomas are more prevalent during the first three months of life and between the ages of 15 and 19. While the majority of paediatric gonadal teratomas are benign, malignant or mixed variants may also arise, necessitating more aggressive therapeutic interventions.

Urologic oncology considerations in transgender and gender diverse patients.

This review delves into the pressing issue of urologic oncology considerations within the transgender and gender-diverse (TGD) community. With estimates suggesting that TGD individuals constitute 0.3 to 0.5% of adults worldwide, and this number steadily rising, our review examines the barriers that impede the delivery of excellent quality care, particularly in the context of cancer diagnosis and treatment. Recent findings highlight disparities in cancer screening, diagnosis, and treatment access for TGD individuals. These challenges are compounded by a dearth of research and the failure of healthcare systems to account for gender identity and its nuances in data collection. Main themes in the literature include the impact of gender-affirming hormone therapy and surgery on cancer risk, challenges in prostate cancer screening and management, and considerations pertinent to testicular and other urological cancers in TGD patients. The implications for clinical practice and research are profound and emphasize the need for multidisciplinary approaches that cater to the unique healthcare needs of TGD individuals. This includes comprehensive strategies for inclusive and accurate data collection, alongside the development of evidence-based guidelines for cancer screening and management tailored specifically to this population.

Pathogenesis and pathobiology of testicular germ cell tumours: a view from a developmental biological perspective with guidelines for pathological diagnostics.

Testicular germ cell tumours (GCT) are divided into three different subtypes (types I-III) regarding to their developmental origin, histological differences and molecular features. Type I GCT develop from disturbed primordial germ cells and most commonly occur in children and young adolescents, which is why they are referred to as prepubertal GCT. Type II GCT develop from a non-invasive germ cell neoplasia in situ (GCNIS) and show an isochromosome 12p (i12p) or gain of 12p material as a common and characteristic molecular alteration. Type III GCT originate from distorted postpubertal germ cells (e.g. spermatogonia) in adult patients and have changes on chromosome 9 with amplification of the DMRT1 gene. Type I GCT encompass prepubertal-type teratomas and yolk-sac tumours (YST). Type II GCT include seminoma, embryonal carcinoma, choriocarcinoma, postpubertal-type teratoma and postpubertal-type YST. Types I and II GCT both show similar morphology, but are separated from each other by the detection of a GCNIS and an i12p in type II GCT. For type II GCT it is especially important to detect non-seminomatous elements, as these tumours have a worse biological behaviour and need a different treatment to seminomas. In contrast to types I and II GCT, type III tumours are equivalent to spermatocytic tumours and usually occur in elderly men, with few exceptions in young adults. The development of types I and II GCT seems to depend not upon driver mutations, but rather on changes in the epigenetic landscape. Furthermore, different pluripotency associated factors (e.g. OCT3/4, SOX2, SOX17) play a crucial role in GCT development and can be used as immunohistochemical markers allowing to distinguish the different subtypes from each other in morphologically challenging tissue specimens. Especially in metastatic sites, a morphological and immunohistochemical diagnostic algorithm is important to detect small subpopulations of each non-seminomatous GCT subtype, which are associated with a poorer prognosis and need a different treatment. Furthermore, primary extragonadal GCT of the retroperitoneum or mediastinum develop from misguided germ cells during embryonic development, and might be challenging to detect in small tissue biopsies due to their rarity at corresponding sites. This review article summarises the pathobiological and developmental aspects of the three different types of testicular GCT that can be helpful in the histopathological examination of tumour specimens by pathologists.

Effects of Chemotherapy on Aneuploidy Rates in Sperm from Male Patients with Testicular Cancer or Hodgkin's Lymphoma-A Systematic Review.

Testicular cancer and Hodgkin's lymphoma are prevalent malignancies among young males aged 20 to 39. The incidence of testicular cancer and lymphoma has risen in recent years, with orchiectomy often followed by adjuvant chemotherapy as the primary treatment for testicular cancer and chemotherapy for lymphoma. Chemotherapy has been associated with an increased risk of aneuploidy and reduced fertility. This systematic review included seven studies, both case-control and longitudinal prospective designs, from the PubMed, Embase, and Cochrane Library databases. The screening process was conducted using the online tool covidence.org. The study outcomes indicate varied impacts of chemotherapy on aneuploidy rates. An increase in the aneuploidy rates, notably for the sex chromosomes, immediately post-treatment was a common trend, followed by a decline in pretreatment values. This systematic review presents the effects of chemotherapy on the aneuploidy rates of testicular cancer and Hodgkin's lymphoma patients, with a decrease post-treatment. The findings underscore the need for larger, well-designed studies with a longer study period.

Survivorship Issues in Testicular Cancer

Testicular cancer (TC) is the most prevalent tumor in young men aged 15–40 years, with an annual incidence of 3–11 new cases per 100,000 males in Western countries. In 2020, the International Agency for Research on Cancer reported 74,458 newly diagnosed cases of TC globally. The etiology of TC is complex and includes both genetic and environmental factors. The prognosis of TC is excellent with a &gt;90% cure rate and a &gt;95% 5-year survival rate with appropriate treatment. Treatments for TC include active surveillance, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, depending on the clinical stage and tumor subtype. It is crucial that patients receive information on the diagnosis, therapeutic management options, consequences of treatments, and surveillance protocols, which allows the patient to play an active role in the decision-making process. Fear of recurrence often affects TC survivors. Therefore, it is essential to fully involve the patient in the choice of the treatment to ensure an optimal compliance, especially when selecting the active surveillance strategy. In the modern era, in light of the excellent outcomes achieved in TC management, one of the high priorities is to deliver curative treatments while minimizing long-term toxicity. This focus can have a positive impact on quality of life and life expectancy of TC survivors.

Trends in genitourinary cancer mortality in the United States: analysis of the CDC-WONDER database 1999-2020.

Sociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States. Mortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban-rural status, and geographic region using a significance level of p < 0.05. Overall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3-4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West. Significant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary cancers.