Treatment Of Testicular Cancer Research Articles

O-306 Sperm DNA methylome changes in testicular cancer patients following chemotherapy treatment

Abstract Study question Does chemotherapy (CT) treatment for testicular cancer induce sperm methylome changes? Summary answer The analysis of 27 pre- and post-CT samples from testicular cancer survivors identified 65 differentially methylated regions. What is known already Research has shown that cancer treatment can cause DNA damage and aneuploidy in sperm, even years after the treatment. However, there is limited information available on the impact of CT on the sperm epigenome, and most of the information has been obtained from rodent models. Two recent studies, one involving one patient and the other involving three, have investigated this topic in humans. Both studies have suggested that cancer survivors may experience changes in sperm’s DNA methylation following oncological treatment. Study design, size, duration This is a multicenter prospective study. We included 27 patients [31.23 years (CI 95% 29.29-33.17)] diagnosed with testicular cancer who cryopreserved semen before CT (2009-2020). After receiving oncological treatment, these patients recovered their spermatogenesis. Patients who agreed to participate in this IRB-approved study, donated a second semen sample after their recovery, which was also frozen. Participants/materials, setting, methods Semen samples were thawed; sperm DNA was isolated and subsequently hybridized using the Human Infinitum DNA Methylation 850K EPIC BeadChip array platform (Illumina). A paired differential methylation analysis was performed between pre-CT and post-CT samples from the same patient, fitting a linear model of the methylated positions and regions. Minfi and DMRcate R packages were used to find differentially methylated positions (DMPs) and regions (DMRs). Subsequently, the functional impact of involved genes was evaluated. Main results and the role of chance DNA methylation data were available for the 54 sperm samples (27 collected before CT and 27 after CT treatment). Results were controlled by age and time elapsed between the cryopreservation of pre-CT and post-CT samples, which was 4.01 years (CI 95%: 3.42-5.64). After filtering for initial QC, the assessment was done on 445.000 CpGs per sample. The analysis revealed that a total of 228 CpG positions showed a tendency towards statistical significance. DMRcate identified 65 DMRs (40 hypomethylated and 25 hypermethylated) that reached a smoothed FDR p-value < 0.05 when compared post-CT samples to pre-CT within the same patient. We observed that 61 genes were located within DMRs, being TBC1D20, EN1, HOXB1 and SCNN1A the ones within the most significant DMRs (min-smoothed-FDR < 0.001). The functional enrichment analysis of putatively affected genes revealed that the biological processes more affected were: Regulation of macromolecule biosynthetic process, hormone receptor binding, signaling pathways regulating pluripotency of stem cells and pathways in cancer. Limitations, reasons for caution Epigenetics may be affected during cryopreservation and thawing. To ensure comparability, we also froze the samples after undergoing the CT process. Due to the high-throughput nature of the study and the limited access to samples, we only achieved marginal significance. Therefore, our results should be further validated. Wider implications of the findings This is the largest study suggesting distinct sperm DNA methylation signatures in testicular cancer survivors. Our findings emphasize the importance of counseling cancer patients in pretreatment sample collection and may explain the reported increase in birth defects after treatment. Trial registration number NOT APPLICABLE

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.

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.

Testicular Cancer Treatments and Sexuality: A Narrative Review.

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.

Contemporary Perioperative Outcomes of Open Retroperitoneal Lymph Node Dissection for Testicular Cancer

Purpose: Retroperitoneal lymph node dissection (RPLND) is an essential component of multimodal treatment of testicular cancer. The latest data on the perioperative outcomes of RPLNDs performed using the open approach (O-RPLND) dates back over a decade. We report our contemporary institutional perioperative outcomes with O-RPLND. Materials and Methods: We retrospectively identified all patients who underwent O-RPLND between 2013 and 2022 across our institution. Clinical and demographic data were reviewed and recorded. Descriptive statistics and univariate analysis were performed with patients stratified according to primary RPLND and post-chemotherapy RPLND (PC-RPLND). Results: Our cohort included a total of 144 men. Seventy-seven percent of all cases were PC-RPLND. The PC-RPLND cohort showed higher preoperative clinical stages (81% vs 26% above cN1, P < .001; 41% vs 1% Stage 3, P < .001). PC-RPLND pathologies were more likely to be teratoma and necrosis or fibrosis (43% vs 6% and 39% vs 33%, P < .001). Estimated blood loss was significantly higher in the PC-RPLND group (291 vs 125 cc, P = .004). Operative time was longer for PC-RPLND (242 vs 196 minutes, P = .011). Length of stay and 30-day readmission rate were not significantly different between groups and averaged 4.3 days and 12%, respectively. Our most common complication was ileus (5%), followed by chyle leak (3%). Conclusions: While PC-RPLND becomes prominent for treating advanced testicular cancer, our recent data suggest positive perioperative results with O-RPLND. With long-term outcome data needed to appropriately select patients for robotic RPLND, O-RPLND in experienced hands continues to improve its outcome and remains the standard approach in the modern era.

Retroperitoneal lymph node dissection: the past, present, and future, a review

Testicular cancer is a malignancy that impacts young men worldwide. The modern treatment of testicular cancer has evolved due to innovations in medical approaches and surgical techniques. The retroperitoneal lymph node dissection (RPLND) is an integral component in the treatment of testicular cancer. We aim to highlight the advances in surgical approaches and oncologic considerations noted over the past century. Once recognized as a highly morbid procedure, innovations in the understanding of anatomy and minimally invasive approaches have greatly improved patient outcomes. In addition to surgical approaches, we describe oncologic principles associated with modern dissection templates for both non-seminomatous germ cell tumors as well as more recent indications for surgery in seminomatous germ cell tumors. The overall goal of this review is to provide a summary in the utility and recent advances in RPLND techniques.

Diagnosis and Treatment of Early-Stage Testicular Cancer: AUA Guideline Amendment 2023.

The purpose of this American Urological Association (AUA) guideline amendment is to provide a useful reference on the effective evidence-based treatment strategies for early-stage testicular cancer. The original methodology protocol included searches of PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 through August 2018. The search strategy used medical subject heading (MeSH) terms and key words relevant to the diagnosis and treatment of early-stage testicular cancer. The searches conducted for the update presented herein utilized the same methodological protocol to capture literature published through March 2023. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. Updates were made to statements on imaging, seminoma management, non-seminoma management, surveillance for stage I testicular cancer, and additional survivorship. Further revisions were made to the methodology and reference sections as appropriate. This guideline seeks to improve clinicians' ability to evaluate and treat patients with early-stage testicular cancer based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Long-term effects of testicular cancer treatment and implications for follow-up

SamenvattingTestiskanker is goed te behandelen. De vijfjaarsoverleving is momenteel > 90%. Testiskanker wordt meestal vóór het 40e jaar gediagnosticeerd, en patiënten kunnen na een succesvolle behandeling nog 40 tot 50 jaar leven. Er is echter een verhoogd risico op langdurige en late effecten van deze behandeling. Tweede primaire maligniteiten en hart- en vaatziekten zijn daarvan de meest voorkomende en potentieel levensbedreigende. Andere zijn nefrotoxiciteit, neurotoxiciteit, verminderde vruchtbaarheid, hypogonadisme, chronische vermoeidheid en psychosociale problemen. Over de onderliggende mechanismen en de genetische gevoeligheid voor de verschillende bijwerkingen is nog weinig bekend, waardoor het niet goed mogelijk is om patiënten met een hoog risico op bepaalde late effecten te identificeren. Wij presenteren de huidige stand van zaken betreffende verschillende somatische en psychosociale langetermijneffecten na behandeling en formuleren aanbevelingen voor algemene medische evaluaties, die moeten beginnen bij start van de behandeling en doorgaan na voltooien van de behandeling en de follow-up.

Understanding the health-related quality of life and treatment-related side-effects in patients who have been in remission from testicular cancer for 12–24 months

IntroductionDespite the excellent long-term prognosis after treatment for testicular cancer (TCa), therapy-related side effects can be persistent and severe. The aim of this study was to determine the nature and prevalence of post-treatment symptoms and their impact on health-related quality of life (HRQoL) in TCa patients 12 to 24 months after treatment.Materials and methodsCross-sectional, single-center study. All patients who were aged 18 and over, had completed TCa treatment 12–24 months previously and had no evidence of disease recurrence were considered eligible. Participants were stratified into four groups: 1) orchidectomy only; 2) orchidectomy and single dose adjuvant carboplatin; 3) multi-agent induction chemotherapy (CBOP-BEP, BEPx3 or x4, or Epx4 regimens); and 4) post-chemo retroperitoneal lymph node dissection (PC-RPLND). Eligible patients were asked to complete the EQ-5D-5L questionnaire and the EORTC QLQ-TC26 questionnaire. We performed a thematic analysis of free-text commentary to evaluate the sensitivity of PROMs used across the treatment groups. Descriptive results were reported. For categorical variables, numbers and percentages were used, and for continuous variables median and IQR values were used.ResultsThe EQ-5D-5L questionnaire showed that patients treated with orchidectomy only and orchidectomy and adjuvant carboplatin experienced only minor physical medium- to long-term side-effects. In contrast, more intensive treatment regimens, such as multi-agent chemotherapy or PC-RPLND, were associated with a higher burden of medium- to long-term side-effects. Similar results were obtained with the EORTC QLQ-TC26 questionnaire.ConclusionsThis study reports the medium- to long-term HRQoL and side effects of TCa treatments, using both EQ-5D-5L and EORTC QLQ-TC26 questionnaires, and identifies possibly “unasked” questions from a patient perspective in relation to supportive care needs following TCa treatment. This information will help clinicians to better understand the consequences of treatment and in turn provide better patient counseling before treatment.

Sexual function using the EORTC QLQ-TC26 in testicular cancer survivors: A multi-institutional, cross-sectional study.

To evaluate sexual function after treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 (EORTC QLQ-TC26) questionnaire in Japanese testicular cancer (TC) survivors in a multi-institutional, cross-sectional study. This study enrolled TC survivors who visited any of eight high-volume institutions in Japan from 2018 to 2019. After obtaining informed consent, participants completed the EORTC QLQ-TC26 questionnaires. We evaluated sexual function after treatment for TC using the EORTC QLQ-TC26 and analyzed the impact of treatment on sexual function in TC survivors. A total of 567 TC survivors responded to the EORTC QLQ-TC26. Median age at the time of response was 43 years (interquartile range [IQR] 35-51 years), and median follow-up period after treatment was 5.2 years (IQR 2.2-10.0 years). Sexual function, particularly ejaculatory function, was significantly lower after post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) than after Surveillance or Chemotherapy groups (p < 0.05). In the PC-RPLND group, nerve-sparing procedure preserved postoperative ejaculatory function after RPLND compared with the non-nerve-sparing and offered improved ejaculatory function with time. On multivariate analysis, RPLND was a significant predictor of post-treatment ejaculatory dysfunction, particularly without nerve-sparing (odds ratio 3.0, 95% CI 1.2-7.7, p < 0.05). In addition, TC survivors with nerve-sparing RPLND had higher sexual activity than those without. This survey of the EORTC QLQ-TC26 showed that sexual function and activity in TC survivors after RPLND was reduced in the absence of nerve-sparing techniques.

Management of an accidental mass in a monorchidic patient discovered during infertility: a case report.

The authors report the case of a patient presented for primary infertility, a clinical examination for left-sided gynecomastia without inflammatory signs. A testicular MRI revealed a 7mm suspicious nodule in the posterior-inferior aspect of the right testicle, with contrast enhancement in the juxta-tumoral area corresponding to a heterogeneous area on ultrasound. Due to the lesion described on MRI, monorchidism, and azoospermia, a TSS combined with testicular biopsy and testicular sperm extraction was indicated. The reference treatment for testicular cancer is the radical orchiectomy, but in some selected situations, partial orchiectomy or TSS is indicated, as many experiences have shown that many small masses found incidentally turn out to be benign. This case suggests that TSS or partial orchiectomy for small nonpalpable testicular masses in monorchidic patients can provide an excellent outcome for the patient.

Risk analysis of subsequent therapies after first-line chemotherapy in advanced testicular cancer patients.

Testicular cancer is the most common solid cancer diagnosed among young men. Despite good response to chemotherapy and a high survival rate, subsequent salvage therapies may still be required for some patients in advanced stages. The predictive and prognostic markers are crucial unmet needs. We retrospectively analyzed advanced testicular cancer patients who had received first-line chemotherapy between January 2002 and December 2020. The associations between baseline characteristics and clinical outcomes were evaluated. Of the 68 included patients, the median age was 29 years. Among them, 40 patients received only first-line chemotherapy while the remaining 28 received subsequent chemotherapy or surgeries. Data reveal that 82.5% (33/40) of the patients in the chemotherapy-only group were recorded as a good prognostic risk using the International Germ Cell Cancer Collaborative Group classification when compared with 35.7% (10/28) in the second-line therapy group. In the chemotherapy-only group, 53.8% of patients were presented with lymph node metastasis compared with 78.6% in the second-line therapy group ( p = 0.068). Fifteen percent of patients (6/40) were recorded as S stage 2-3 in the chemotherapy-only group, whereas 85.2% (23/28) were recorded as such in the second-line therapy group ( p < 0.001). The 5-year overall survival estimation was 92.9% in the chemotherapy-only group and 77.3% in the second-line therapy group. Univariate analysis for overall survival revealed that those patients at the S 2-3 stage and those receiving second-line therapies showed a trend of having an increased death risk (hazard ratio [HR] = 8.26, 95% confidence interval (CI), 0.99-68.67, p = 0.051; HR = 7.76, 95% CI, 0.93-64.99, p = 0.059, respectively). The S 2-3 stage was also independently associated with the risk of subsequent therapy (HR = 33.13; 95% CI, 2.55-430.64, p = 0.007). Our real-world data show the predictive role of serum tumor marker stage 2-3 to be associated with any subsequent therapies after first-line chemotherapy. This can facilitate clinical decision making during the testicular cancer treatment process.

Changes in male sexuality after urologic cancer: a narrative review.

To describe the most common sexual problems and changes experienced by male urological cancer survivors, focusing on evidence-based practices for assessment and intervention. We search the PubMed, Embase, and SciELO databases between 1994 and 2022, using the following key words: "urological cancer", "urological malignances", "genitourinary cancer", "male sexual health", and "male sexual dysfunction". This narrative review provides an overview of the current literature involving the impact of diagnosis and treatment of urological cancers on male sexual function. Male "genital" or "reproductive" tumors, such as prostate, penile, and testicular tumors, clearly appear to affect sexual function. However, tumors that do not involve genital parts of the body, such as the bladder and kidney, can also affect male sexual function. Male sexual dysfunction is very common after urologic cancer diagnosis and treatment. Changes in body image and anatomical damage can be associated with impaired masculinity and sexual function, especially after prostate, penile or testicular cancer treatment. Moreover, anxiety, depression, and fear of recurrence have an impact on quality of life and sexual function regardless of the cancer location. Therefore, patients need be counseled about the likely changes in sexual function before treatment of any urological cancer.

Saudi Nursing Students' Knowledge and Perception of Testicular Cancer Assessment and Management: A Cross-Sectional Study.

Testicular cancer (TC) incidence is increasing worldwide. This study aimed to investigate Saudi nursing students' knowledge and perception about TC. This cross-sectional study was done using convenience sampling method. In this study, 280 nursing students from different nursing schools in six cities of Saudi Arabia were recruited. A structured self-report questionnaire was used to collect data. About 49.2% of the participants received education about TC in their nursing schools. The findings showed lack of enough knowledge about TC among Saudi nursing students. Mostly, the participants reported that heredity factor and having family history of TC (48.9%) and age between 56 and 70 years (41.8%) were the most common risk factors of TC. According to the participants, physical examination was the most common diagnostic test usually used for early detection of TC (40.4%) and biopsy test was the most accurate test to confirm TC diagnosis (45.4%). Only one third of the participants (34.6%) knew that between 75% and 100% of TC cases can be cured in case of early detection. About half of the participants (51.8%) reported that surgical procedure was the most common treatment for TC. The nursing students who had high GPA (r=0.86, p<0.001), were unwilling to get more information on TC (r=0.24, p=0.04), had family history of TC (r= 0.53, p=0.02), medical problems with testicles (r= 0.69, p=0.01), received education about TC in their school of nursing (r=0.65, p=0.02), and were more self-confident in assessing and managing TC (r=0.38, p=0.03) had higher level knowledge about TC. Conclusion: Despite the importance of nurses' roles in assessing and managing TC, nursing students in Saudi Arabia still did not have enough knowledge about TC. Improving nursing programs' curricula and conducting health education programs are recommended.

Management of testicular tumours in patients with undescended testes- a challenging but rewarding task: experience from a tertiary care cancer centre in India.

Primary objective: To study patients' clinical profile and outcomes with germ cell tumours developing in undescended testes. Case records of patients enlisted in the prospectively maintained 'testicular cancer database' at our tertiary cancer care hospital from 2014 to 2019 were retrospectively reviewed. Any patient who presented with testicular germ cell tumour with a documented history/diagnosis of undescended testes, whether surgically corrected or not, was considered for this study. The patients were managed along the standard lines of treatment for testicular cancer. We evaluated clinical features, difficulties and delays in diagnosis and complexities in management. We evaluated event-free survival (EFS) and overall survival (OS) using the Kaplan-Meier Method. Fifty-four patients were identified from our database. The mean age was 32.4 years (median age 32, range: 15-56 years). Seventeen (31.4%) had developed cancer in orchidopexy testes, and 37 (68.6%) presented with testicular cancer in uncorrected cryptorchid testes. The median age at orchidopexy was 13.5 years (range: 2-32 years). The median time from symptom onset to diagnosis was 2 months (1-36 months). There was a delay in the initiation of treatment of more than 1 month in 13 patients, with the longest delay being 4 months. Two patients were initially misdiagnosed as gastrointestinal tumours. Thirty-two (59.25%) patients had seminoma, and 22 (40.7%) patients had non-seminomatous germ cell tumours (NSGCT). Nineteen patients had metastatic disease at presentation. Thirty (55.5%) patients underwent orchidectomy upfront while in 22 (40.7%) patients, orchidectomy was done after chemotherapy. The surgical approach included high inguinal orchidectomy, exploratory laparotomy or laparoscopic surgery per the clinical situation. Post-operative chemotherapy was offered as clinically indicated. At a median follow-up of 66 months (95% CI: 51-76), there were four relapses (all NSGCT) and one death. The 5-year EFS was 90.7% (95% CI: 82.9-98.7). The 5-year OS was 96.3% (95% CI: 91.2-100). The tumours in undescended testes, particularly those without prior orchiopexy, often presented late and with bulky masses, requiring complex multidisciplinary management. Despite the complexity and challenges, our patient's OS and EFS matched that of patients with tumours in normally descended testes. Orchiopexy may help in earlier detection. In the first such series from India, we show that testicular tumours in the cryptorchid are also as curable as the germ cell tumours developing in the descended testis.A multidisciplinary disease management group with expertise in managing complex cases is crucial for a favourable outcome in these groups of patients. We also found that orchiopexy done even later in life confers an advantage in terms of early detection in a subsequently developing testicular tumour.

Sperm DNA methylome abnormalities occur both pre- and post-treatment in men with Hodgkin disease and testicular cancer

BackgroundCombination chemotherapy has contributed to increased survival from Hodgkin disease (HD) and testicular cancer (TC). However, questions concerning the quality of spermatozoa after treatment have arisen. While studies have shown evidence of DNA damage and aneuploidy in spermatozoa years following anticancer treatment, the sperm epigenome has received little attention. Our objectives here were to determine the impact of HD and TC, as well as their treatments, on sperm DNA methylation. Semen samples were collected from community controls (CC) and from men undergoing treatment for HD or TC, both before initiation of chemotherapy and at multiple times post-treatment. Sperm DNA methylation was assessed using genome-wide and locus-specific approaches.ResultsImprinted gene methylation was not affected in the sperm of HD or TC men, before or after treatment. Prior to treatment, using Illumina HumanMethylation450 BeadChip (450 K) arrays, a subset of 500 probes was able to distinguish sperm samples from TC, HD and CC subjects; differences between groups persisted post-treatment. Comparing altered sperm methylation between HD or TC patients versus CC men, twice as many sites were affected in TC versus HD men; for both groups, the most affected CpGs were hypomethylated. For TC patients, the promoter region of GDF2 contained the largest region of differential methylation. To assess alterations in DNA methylation over time/post-chemotherapy, serial samples from individual patients were compared. With restriction landmark genome scanning and 450 K array analyses, some patients who underwent chemotherapy showed increased alterations in DNA methylation, up to 2 to 3 years post-treatment, when compared to the CC cohort. Similarly, a higher-resolution human sperm-specific assay that includes assessment of environmentally sensitive regions, or “dynamic sites,” also demonstrated persistently altered sperm DNA methylation in cancer patients post-treatment and suggested preferential susceptibility of “dynamic” CpG sites.ConclusionsDistinct sperm DNA methylation signatures were present pre-treatment in men with HD and TC and may help explain increases in birth defects reported in recent clinical studies. Epigenetic defects in spermatozoa of some cancer survivors were evident even up to 2 years post-treatment. Abnormalities in the sperm epigenome both pre- and post-chemotherapy may contribute to detrimental effects on future reproductive health.

Identification and validation of Sertoli cell homing peptides as molecular steering for testis targeted drug delivery

The testicle, an organ privileged with immunity because of Blood-Testis Barrier (BTB), poses a major impediment to developing and delivering drugs to the testes. These problems can be prevented by targeting testicular cells using specific ligands, such as homing peptides. This is the first study to demonstrate the successful selection of Sertoli cell homing peptides using a phage display peptide library. The identification of peptides is performed with Sanger sequencing and high-throughput NGS. The Sertoli cell and testis targeting potential of the SCHP1 and SCHP2 was confirmed using confocal microscopy and flow cytometry of the FITC-labelled peptides and in vivo bio-distribution of the corresponding Cy5.5-tagged peptides. Secondary structures were predicted in the setting of different polarity by circular dichroism. The results suggest that SCHP1 and SCHP2 can effectively target Sertoli cells. In vivo bio-distribution in mouse models indicated significantly higher uptake of SCHP1 and SCHP2 by testes compared with the heart, brain, and spleen. SCHP1 and SCHP2 can be adopted as molecular steering for targeted male contraceptive delivery, treatment of testicular cancer, and male infertility. Further development of the peptides into peptidomimetics may increase their stability, and information on the molecular targets of these peptides may reveal their therapeutic potential.

A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention).

Elevated luteinizing hormone (LH) in combination with low-normal testosterone (mild Leydig cell insufficiency) is common in testicular cancer (TC) survivors and is associated with impaired insulin sensitivity and metabolic syndrome. The aim was to evaluate if testosterone replacement therapy (TRT) improves metabolic health in this subgroup of TC survivors. This was a single-center, double-blind, randomized, controlled trial. The main eligibility criterion was LH above the age-adjusted upper limit of normal in combination with free testosterone in the lower half of the age-adjusted normal range (mild Leydig cell insufficiency) >1 year after TC treatment. Eligible patients were randomly assigned (1:1) to 12 months transdermal TRT (Tostran, gel, 2%) or placebo with a maximum daily dose of 40 mg. The primary outcome was difference in Δ2 hour glucose measured with oral glucose tolerance test between groups assessed at 12 months. Outcomes were assessed after 6-, 12- and 3 months post-treatment. The study was registered at www. gov (NCT02991209) and ended June 2019. Between October 2016 and February 2018, 140 patients were screened for eligibility and 69 were randomized to testosterone (n=35, 51%) or placebo (n=34, 49%). TRT was not associated with a statistically significant difference in Δ2 hour glucose compared to placebo after 12 months of treatment (0.04 mmol/L (95% CI: -0.53, 0.60)). There was no statistically significant difference in Δ2 hour insulin between the groups after 12 months of treatment (28.23 pmol/L (95% CI: -34.40, 90.86)). Similarly, TRT was not associated with significant improvement in components of metabolic syndrome. TRT was associated with a decrease in fat mass after 12 months compared to placebo (-1.35 kg, (95% CI: -2.53, -0.18)). In TC survivors with mild Leydig cell insufficiency, TRT was not associated with improvement of metabolic health. These findings do no not support routine use of TRT in these patients.

Late ECG Changes after Cisplatin-Based Chemotherapy in Testicular Cancer Survivors

Introducing cisplatin-based therapy into testicular cancer treatment represents a substantial progress in therapy leading to a longer survival of patients and less adverse effects; currently it represents the standard therapy.

Factors impacting the delay in diagnosis and treatment of testicular cancer: A review

Early diagnosis and management of testicular cancer can improve mortality and prognosis. This systematic review found extensive patient-, physician-, and system-related factors that increased the length of time to diagnosis. Future preventative strategies should target the modifiable factors such as lack of awareness, embarrassment, accessibility, general practitioner education, and clinical training and streamlined imaging processes.