Orchiectomy Research Articles

8528 An Unusual Case Of Adrenal Hemorrhage As An Initial Manifestation Of Castleman Disease In A 29 yo Male With Unsuspected Late-Onset Congenital Adrenal Hyperplasia

Abstract Disclosure: L.M. Martel: None. F. Mercier: None. S. Parisien-La Salle: None. A. Lacroix: None. A. Liberman: None. N. Bettache: None. H. Olney: None. I. Bourdeau: None. Background: Castleman disease is a lymphoproliferative disorder with no clear etiology. We report the case of a 29 yo man presenting with an adrenal hemorrhage as initial manifestation of Castleman disease and unsuspected late-onset congenital adrenal hyperplasia. Clinical case: A 29-year-old male with no significant past medical history except for unilateral orchiectomy at 1 year-old for a possible testicular mass was referred to our adrenal clinic for a 6,2x7,5 cm left adrenal mass showing at CT scan necrosis and an hemorrhagic component (HU52). The patient presented initially with acute left abdominal pain. The adrenal mass showed at peripheral high uptake at PET-FDG (SUVmax 5,3) with no central uptake. His physical exam was unremarkable except for obesity. The hormonal work-up for the adrenal mass revealed normal metanephrines, and normal 1mg-dexamethasone suppression test with morning cortisol of 18 nmol/L (N<50). Further hormonal investigations based on the high adrenal mass uptake and possible adrenocortical carcinoma included: 17-OH Progesterone: 7.7 nmol/L (N:1.1-7.0), Androstenedione: 14.1 nmol/L (N: 1.5-9.0), Testosterone: 11.3 nmol/L (N: 9.0-28.3) and DHEAS: 3.6 umol/L (2.3-18.7). The ACTH levels were increased at 21.2 pmol/L (N:2-11) with morning cortisol of 220 nmol/L. During the consultation, the patient reported a pleuritic chest pain and underwent an urgent CT pulmonary angiography showing a pulmonary embolism with lung infarction in addition to mediastinal lymphadenopathy (biopsy negative) and a mass in his thymus. He underwent thymectomy and the pathology report described Castleman disease (hyaline vascular type). Taking into account the increased level of 17-OH progesterone, we performed an ACTH stimulation test (250 mcg) that showed an increase of cortisol levels from 333nmol/L to 874nmol/L at 60 minutes and of 17OH Progesterone levels from 5.2nmol/L to 44.2nmo/L excluding adrenal insufficiency, but confirming the diagnosis of late-onset congenital adrenal hyperplasia. Genetic analyses: After written consent, the patient underwent genetic analysis of the CYP21A2 gene by direct sequencing and MLPA. The analyses revealed a heterozygous pathogenic variant in the CYP21A2 gene (c.293-13A/C>G). No other genetic variant was identified in the gene. Follow-up: Subsequent adrenal MRIs showed decreasing size of the left adrenal mass; 3 cm at 3 months, 2 cm at 6 months and no residual mass was seen at 9 months supporting the diagnosis of adrenal hemorrhage. Conclusion: To our knowledge, we report a first case of Castleman disease presenting with adrenal hemorrhage as initial symptom with the association of late-onset congenital adrenal hyperplasia. The possible link between these diseases remains to be explored. Presentation: 6/3/2024

Oncological treatments have limited effects on the fertility prognosis in testicular cancer: A systematic review and meta-analysis.

Testicular cancer is the most common solid tumour among young men in the reproductive phase. After completing cancer treatment, up to 77% of cancer survivors report an interest in paternity after completing cancer treatment. To preserve fertility, most guidelines recommend that physicians should counsel their patients about sperm cryopreservation before initiating gonadotoxic therapy. However, few studies have assessed fertility parameters after testicular cancer therapies over the last 20 years. To close the gap of data regarding gonadotoxicity of testicular cancer therapies to enable more accurate counselling regarding fertility preservation. A systematic literature search was conducted in Medline, Embase and Cochrane until December 2022. The systematic review included studies of men who had undergone all types of unilateral testicular cancer treatment, whereas the meta-analysis excluded studies with unspecified treatments, less than 10 patients for outcome evaluation or rare tumours. Infertility (i.e. azoospermia, failure to achieve paternity or the usage of cryosperm) was defined as outcome. The qualitative analysis included 30 studies with a total of 13,718 men after unilateral testicular cancer. Treatment comprised active surveillance after unilateral orchidectomy (32.7%), radiotherapy (23.1%), standard- or low-dose chemotherapy (33.7%) and high-dose chemotherapy (1.4%). Post-treatment spermiograms were analysed in 17 studies. The quantitative synthesis included 23 studies, revealing an overall pooled prevalence of infertility (95% CI) of 14% (9%-21%). Azoospermia occurred in 8% (6%-12%). For good-prognosis patients who received standard therapy, the overall prevalence of infertility was only 4% (2%-10%). So far, this very first meta-analysis of overall infertility prevalence provides the best approximation of fertility prognosis for men who have undergone testicular cancer therapy. Despite the low prevalence of infertility, it is still recommended to undergo sperm cryopreservation because of the uncertainty of the subsequent therapy and the lack of large longitudinal data on individual treatment effects.

O-311 Oncological treatments have limited effects on the fertility prognosis in testicular cancer: A systematic review and meta-analysis

Abstract Study question What is the prevalence of infertility defined by azoospermia, failure to achieve paternity or the usage of cryosperm after oncological treatments in testicular cancer? Summary answer The overall prevalence of infertility (95% CI) is 14% (9-21%) after all therapy types and 4% (2-10%) in a pooled subgroup of good-prognosis patients. What is known already Testicular cancer is the most common solid tumor among young men in the reproductive phase between 15 and 45 years. More than 95% of the patients become long-term survivors and up to 77% of cancer survivors report an interest in paternity after completing cancer treatment. Most guidelines recommend that physicians should counsel their patients about sperm cryopreservation before initiating gonadotoxic therapy. However, few studies have assessed fertility parameters after testicular cancer therapies over the last twenty years. Thus, this very first meta-analysis in a large pooled study population of patients functions as the best approximation of fertility prognosis so far. Study design, size, duration The systematic review and meta-analysis is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. It was performed on all published studies since 2000 that have reported the prevalence of azoospermia, the failure to achieve a pregnancy over 12 months of regular unprotected sexual intercourse or the usage of cryosperm after oncological treatments of unilateral testicular cancer. Participants/materials, setting, methods A systematic literature search was conducted in Medline, Embase and Cochrane in December 2022. For the systematic review, studies with men after all types of unilateral testicular cancer were included. For the meta-analysis, studies with unspecified treatments, < 10 patients for outcome evaluation or rare tumours were excluded. Infertility was defined as azoospermia, failure to achieve paternity or the usage of cryosperm. The quality of the individual studies was assessed using the Newcastle-Ottawa Scale. Main results and the role of chance A total of 126 studies remained following screening of the abstracts and fulltext for the subject of the study. Of these, 30 studies including 13718 men with a history of unilateral testicular cancer were eligible and analysed for qualitative synthesis. Sample sizes ranged from 17 to 4846 patients with a follow-up from 1-30 (mean 6.5) years. Histology included seminomas (43.9%), non-seminomas (49.6%) and sex cord or stromal tumors (0.01%). Treatment comprised active surveillance after unilateral orchidectomy (32.7%), radiotherapy (23.1%), standard or low-dose chemotherapy (33.7%) and high-dose chemotherapy (1.4%). Spermiograms after treatment were analysed in 17 studies. A quantitative synthesis was performed in 23 studies. To account for heterogeneity observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The overall pooled prevalence of infertility (95% CI) in men with unilateral testicular cancer after standard oncological treatment was 14% (9-21%). Azoospermia after all types of oncological treatments appeared in 8% (6-12%) of the pooled study population. For good-prognosis patients who received standard therapy (i.e. surgery with or without retroperitoneal lymph node dissection, low- or standard dosed platin-based chemotherapy up to four cycles and / or radiotherapy), the overall prevalence of infertility was only 4% (2-10%). Limitations, reasons for caution First, the majority of the studies based on either questionnaire or register data with evident selection bias. Second, further subgroup analysis was impossible due to predominantly mixed treatment cohorts allowing only an approximation of standard therapy effects. Third, infertility might have occurred due to factors besides the oncological therapy. Wider implications of the findings Our meta-analysis includes all men with fertility outcome after testicular cancer therapy. Despite the overall low prevalence of infertility, sperm cryopreservation should still be recommended since it is unclear which therapy will follow after surgery and since there is no large longitudinal data for the various individual treatment effects. Trial registration number PROSPERO (Registry number CRD42023384057)

Distinct actions of testicular endocrine and lumicrine signaling on the proximal epididymal transcriptome.

The epididymal function and gene expression in mammals are under the control of the testis. Sex steroids are secreted from the testis and act on the epididymis in an endocrine manner. There is another, non-sex steroidal secreted signaling, named lumicrine signaling, in which testis-derived secreted proteins go through the male reproductive tract and act on the epididymis. The effects of such multiple regulations on the epididymis by the testis have been investigated for many genes. The recent development of high-throughput next-generation sequencing now enables us a further comparative survey of endocrine and lumicrine action-dependent gene expression. In the present study, testis-derived endocrine and lumicrine actions on epididymal gene expression were comparatively investigated by RNA-seq transcriptomic analyses. This investigation utilized experimental animal models in which testis-derived endocrine and/or lumicrine actions were interfered with, such as unilateral or bilateral orchidectomy. By bilateral orchidectomy, which interferes with both endocrine and lumicrine actions, 431 genes were downregulated. By unilateral orchidectomy, which also interferes with endocrine and lumicrine actions by the unilateral testis, but the endocrine action was compensated by the contralateral testis, 283 genes were downregulated. The content of such genes downregulated by unilateral orchidectomy was like those of lumicrine action-interfered efferent duct-ligation, W/Wv, and Nell2-/- mice. When genes affected by unilateral and bilateral orchidectomy were compared, 154 genes were commonly downregulated, whereas 217 genes were specifically downregulated only by bilateral orchidectomy, indicating the distinction between endocrine and lumicrine actions on the proximal epididymal transcriptome. Comparative transcriptome analyses also showed that the expressions of genes emerging since Amniota were notably impacted by bilateral orchidectomy, unilateral orchidectomy, and lumicrine action-interfering treatments; the degree of influence from these treatments varied based on the evolutionary stage beyond Amniota. These findings unveil an evolutional transition of regulated gene expression in the proximal epididymis by two different testis-derived signaling mechanisms.

(246) Age Dependent Effect on Contralateral Testicular Compensation Following Testicular Loss

Abstract Introduction The human testicle is susceptible to loss from events like torsion, trauma, cancer, or cryptorchidism. Most paired organs are known to undergo compensatory hypertrophy following unilateral organ loss. The testicle is physiologically distinct in that it is thought to undergo a period of quiescence in childhood. Previous work has demonstrated testicular hypertrophy occurs if the loss of the contralateral testis occurs before puberty. However, it is unknown if compensatory physiology and growth differs by age of pre-pubertal loss. Objective This study aimed to investigate compensatory changes in testicular growth and the hormonal axis following unilateral orchiectomy in a neonatal, pre-pubertal and pubertal/adult murine model. Methods C57BL/6 mice were divided into experimental groups: neonatal (days of life 2-4), pre-pubescent (days of life 12-21), and post-pubescent (days of life 42-44) to undergo unilateral orchiectomy. A control group that did not undergo orchiectomy was utilized. Mice were sacrificed at maturity (over 80 days of life), blood samples were drawn, and the remaining testis was removed. Body and testis weight and testicular length in the long axis were measured in blinded fashion. Similarly, testosterone, luteinizing hormone (LH), and Follicle stimulating hormone (FSH) were assessed and expressed as a median and an interquartile range. Results Contralateral testes from neonatal and pre-pubertal mice who underwent orchiectomy weighed more (110.5, 12.2 and 103.0, 7.2 mg respectively. Figure 1.) (p < 0.05) than the control mice (91, 11.9 mg, respectively). There was no difference between post-pubertal group and control group. The degree of compensatory hypertrophy was greater in the neonatal group but not the pre-pubertal group when compared to the post-pubertal group. When examining the ratio of testicular weight to body weight, only the neonatal group was significantly higher than that of the control. Differences in FSH and testosterone were not statistically significant between experimental and control arms (p > 0.05). LH was significantly elevated in all experimental groups as compared to the control (p < 0.05). Conclusions This is the first study to assess testicular compensatory hypertrophy following contralateral testicular loss using a neonatal mouse survival surgery model. Testicular hypertrophy occurs when unilateral loss occurs prior to puberty, but not in adulthood in mice. Earlier testis loss may contribute to a greater degree of growth. Functionally, the unilateral testis can maintain eugonadal testosterone levels, but higher levels of LH are required following hemicastration to sustain eugonadal testosterone levels. Future studies are warranted to identify testicular transcriptomics in this model to evaluate for candidate genes potentially responsible for this phenotypic change. Disclosure No.

Combined orchiectomy and limb immobilization recapitulate early age‐related changes to skeletal muscle in mice

AbstractBackgroundMuscle mass and function decline in middle age, ultimately resulting in sarcopenia in the elderly and poor health outcomes, reducing quality of life. There is a lack of cost‐ and time‐effective murine models that recapitulate the physiological changes associated with muscle mass decline to study possible interventions to delay sarcopenia. We aimed to evaluate the effectiveness of combining orchiectomy (ORC) surgery to simulate age‐related androgen decline and hindlimb immobilization (IM) in inducing age‐related skeletal muscle changes.MethodsFour‐month‐old male C57BL/6J mice (n = 10) were subjected to ORC, followed by IM (right hindlimb casting) for 14 days. Upon completion of the casting period, ex vivo muscle contractile function, histology, and various mitochondrial markers were assessed, and results were compared with age‐matched controls (CON; n = 8) and middle‐aged (MA; 12 ± 1 months, n = 9) animals.ResultsIM combined with ORC induced a 30%–40% decrease in muscle mass across multiple hindlimb muscles (P < 0.0001), with the magnitude of muscle loss comparable with the MA group when corrected for body weight (P < 0.0001). In the IM limb of ORC mice, soleus muscle force significantly decreased when compared with the contralateral limb (P < 0.05) and aged‐matched CON group (P < 0.05). The decrements in muscle force and mass present in the IM limb of ORC mice were accompanied by a 70% reduction in the expression of the muscle structural protein dystrophin and various mitochondrial markers, including cytochrome C (−55%), peroxisome proliferator‐activated receptor gamma co‐activator 1‐beta (PGC1‐β) (−49%), and cytochrome oxidase IV (COX‐IV) (−73%) when compared with CON animals (P < 0.001). Lastly, our model also demonstrated specific fibre‐type shifts in fast‐ and slow‐twitch muscles, which mimicked changes in the MA group.ConclusionsApplying treatments during IM could target acute muscle atrophy in MA adults, while applying them following cast removal in a low‐testosterone environment could represent a window for rehabilitation therapeutics.

Long-term impact of commonly performed operations in pediatric urology on reproductive and sexual health.

Sexual dysfunction is highly prevalent among men of reproductive age. Clinical practice guidelines have been established to assist providers in identification and education of patients who are at increased risk for infertility and sexual dysfunction with certain congenital and acquired urogenital disorders. The authors sought to review the reproductive and sexual health implications of treating common childhood urological conditions with commonly performed surgical procedures. To ensure the inclusion of influential and highly regarded research, we prioritized citations from the most-frequently cited articles on our respective review topics. Our inclusion criteria considered studies with substantial sample sizes and rigorously designed methodologies. Several topics were reviewed, including penile chordee, hypospadias, posterior urethral valves, varicoceles, undescended testicles, and testicular torsion. For chordee, surgical plication or corporal grafting may be employed. Erectile function remains unaltered post-surgery, while penile length may decrease after repair, which may be avoided using dermal grafts. Hypospadias repair hinges on severity and availability of the urethral plate. Those who underwent hypospadias repair report decreased penile length, but sexual satisfaction, libido, and semen quality are comparable to controls. Posterior urethral valves are usually treated with valve ablation. While valve ablation and bladder neck incision have not been found to affect ejaculatory function, high degree of concurrent renal dysfunction related to nephrogenic and bladder dysfunction may impact semen parameters and erectile function. Regarding varicocele, earlier management has been associated with better long-term fertility outcomes, and surgical intervention is advisable if there is observable testicular atrophy. Earlier repair of undescended testicle with orchiopexy has been found to improve fertility rates as well as decrease malignancy rates. Unilateral orchiectomy for testicular torsion without the ability for salvage has been shown to have decreased semen parameters but unaffected fertility rates. Infertility and sexual dysfunction are multivariable entities, with etiologies both congenital and acquired. At the same time, many common pediatric urology surgeries are performed to correct anatomic pathology that may lead to reproductive dysfunction in adulthood. This review highlights the need for diagnosis and management of pediatric urologic conditions as these conditions may impact long-term sexual function post-operatively.

The Outcome of Diffuse Large B-Cell Lymphoma Patients with Testicular Involvement - Real World Data

Introduction: Patients (pts) with testicular lymphoma (TL) have an increased risk of central nervous system (CNS) relapse. In rituximab era, the reported incidence vary from 10% (in limited disease) to 25% (advanced disease). More data is needed to guide the managment of TL pts in current era. Optimal strategy for CNS relapse prevention is uncertain. Methods: We studied consecutive pts diagnosed between 2000 and 2022 with testicular diffuse large B-cell lymphoma (DLBCL) prospectively observed in the Czech Lymphoma Study Group Project NiHiL (Clinical Trial gov. NCT03199066). Objectives were to analyze the cumulative incidence of CNS relapse, time to CNS relapse, PFS and OS. The impact of various treatment strategies on CNS relapse was analyzed. Results: We identified 229 pts with testicular involvement: 157 pts with primary testicular lymphoma (PTL) in clinical stage I or II and 72 pts in advanced stage (AD) III or IV. Median age was 70 years (range 33 - 87). Rituximab-based chemotherapy received 192 (83.8%) pts including 127 (81%) cases with PTL. Following localized treatments were used more often in PTL compared to AD: unilateral orchiectomy [148 (94.3%) vs. 47 (65.3%); p < 0.0001], testicular irradiation (RT) [116 (61.7%) vs. 40 (38.7%); p = 0.005]. Most patients (85%) received some form of CNS prophylaxis. There were similar rates in use of prophylactic methotrexate (MTX) between PTL and AD (p = 0.88): intrathecal (i.t.) MTX 64 (40.8%) vs. 29 (40.3%), intravenous (i.v.) MTX with or without cytarabine 20 (12.8%) vs. 7 (9.7%); combined i.t. and i.v. MTX 38 (24.2%) vs. 20 (27.8%). Out of 229 cases 25 (15.9%) PTL and 11 (15.3%) AD pts did not receive any CNS prophylaxis. Median follow-up was 51.8 months.Overall 63 (27.5%) pts relapsed including 14 (6.1%) relapses in CNS. Median time to CNS relapse was 21.9 months and to other systemic relapse was 14.7 months (p = 0.63). The 5-year cumulative incidence of CNS relapse in PTL was 4.55% (95% confidence interval [CI], 0.1 - 28.6) and in AD 12.07% (95% CI 0.8 - 39.6), respectively. In univariate analyses, MTX prophylaxis (i.v. and/or i.t.) and testicular RT had no impact on CNS relapse (p = 0.49 and p = 0.60, respectively). Orchiectomy was the single significant factor associated with lower risk of CNS relapse in PTL (hazard ratio [HR] = 0.11[95% CI 0 - 0.124]; p = 0.001). Rituximab significantly reduced CNS relapse in AD with testicular involvement (HR = 0.1002 [95% CI 0.0 - 0.45]; p = 0.0005). Out of 14 pts with CNS relapse 8 died due to lymphoma progression. Median progression-free survival (PFS) and overall survival (OS) in PTL was significantly better when compared to AD (PFS 92.9 vs. 28.1 months, p < 0.0006; OS 108.7 vs. 56.7 months, p = 0.0002). Median PFS2 and OS2 since CNS relapse was dismal in AD compared to PTL (PFS2 1.6 vs. 37.8 months, p = 0.04 and OS2 2.3 vs. 37.8 months, p = 0.05). Conclusions: The rate of CNS relapses in PTL and advanced disease with testicular involvement is lower than previously reported. This study confirmed a significant favorable impact of rituximab in prevention of CNS relapse. Notably, methotrexate prophylaxis i.v. or i.t. did not alter the CNS relapse risk. Prognosis of CNS relapse is particularly poor in advanced disease. This work was supported by grant AZV NU21-03-00411 from the Ministry of Health of the Czech Republic and by the Cooperatio Program, research area “Oncology and Haematology”

FRI428 VTE And Testosterone Therapy: What Is The Risk?

Abstract Disclosure: C. Cheatham: None. J. Colburn: None. M. Kemm: None. Testosterone replacement therapy (TRT) to treat hypogonadism from a variety of underlying etiologies remains increasingly prevalent within the United States. While VTE is a known potential risk, the prevalence, underlying mechanism, and associated risk factors remain incompletely understood. Men initiating TRT for hypogonadism often do not receive adequate pre-treatment evaluation or have therapy initiated despite normal testosterone levels. While a 2021 meta-analysis 1 did not demonstrate significantly increased VTE risk associated with TRT, the wide confidence interval, reported low quality of evidence, and lack of studies examining VTE as a primary outcome with data obtained via adverse event reporting demonstrates the importance of further investigation. Case 1: 55-year-old male with unilateral orchiectomy and associated primary hypogonadism started on TRT 10years prior presented to the hospital with acute onset chest pain and shortness of breath. CT angiography demonstrated right lower lobe segmental pulmonary emboli with parenchymal infarction. At the time of presentation, he was on IM testosterone cypionate 200mg weekly and anastrozole with total testosterone970 ng/dL, free testosterone 298 pg/mL, undetectable estradiol, and hematocrit 41.5%. His testosterone and anastrozole were discontinued at discharge, and he had a negative hypercoagulability workup by a hematologist. Case 2: 61-year-old male with history of OSA, obesity, and TRT initiated 8 months prior for erectile dysfunction presented to the hospital with dyspnea. CT angiography demonstrated large bilateral pulmonary artery emboli with right heart strain consistent with submassive PE. Review of clinical records preceding TRT initiation indicate normal testosterone values of 533 ng/dL with free testosterone 60.6 pg/dL. At the timeof presentation, his total testosterone was 685 ng/dL, free testosterone 139 pg/mL, and hematocrit of 54%with history of polycythemia since TRT initiation and no documented intervention. He was treated withIR thrombectomy and anticoagulation, and TRT was discontinued at discharge. His hematocrit normalized at follow-up and, after negative hypercoagulability evaluation by a hematologist, TRT was felt to be the most likely etiology of his VTE. These reported cases of VTE in men of different ages, underlying pathology, testosterone levels at time of event, presence of polycythemia, and time since testosterone initiation highlights the importance of further investigation on the true risk of thrombotic events in TRT patients and necessity of increased patient counseling of potential adverse outcomes. 1. Ayele HT, Brunetti VC, Renoux C, Tagalakis V, Filion KB. Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials. Thromb Res. 2021;199:123-131. doi:10.1016/j.thromres.2020.12.029 Presentation: Friday, June 16, 2023

Human Tularemia Epididymo-Orchitis Caused by Francisella tularensis Subspecies holartica, Austria.

A previously healthy man in Austria had tularemia epididymo-orchitis develop, leading to unilateral orchiectomy. Francisella tularensis subspecies holartica was detected by 16S rRNA gene sequencing analysis of inflamed granulomatous testicular tissue. Clinicians should suspect F. tularensis as a rare etiologic microorganism in epididymo-orchitis patients with relevant risk factors.

Age-dependent effect on contralateral testicular compensation after testicular loss

To study compensatory changes in testicular growth and the hormonal axis after unilateral orchiectomy in a neonatal, prepubertal, and pubertal/adult murine model. This is the first study to use a neonatal mouse survival surgery model. A laboratory-based study examining a control, neonatal, prepubertal, and pubertal/adult mouse model. University-based basic science research laboratory. Control, neonatal (2-4 days of life), prepubertal (12-21 days of life), and pubertal/adult (42-44 days of life) C57BL/6 mouse models. Unilateral orchiectomy in the neonatal, prepubertal, and pubertal/adult mouse models at their respective ages. Body and testis weight and testicular length in the long axis were measured in a blinded fashion. In a similar way, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone were assessed. Testes from neonatal and prepubertal mice weighed more (110.5, 12.2 and 103.0, 7.2 mg, respectively) than the control mice (91, 11.9 mg). There was no difference between the postpubertal group and the control group. The degree of compensatory hypertrophy was greater in the neonatal group but not in the prepubertal group when compared with the postpubertal group. Differences in follicle-stimulating hormone and testosterone were not statistically significant between the experimental and control arms. LH was significantly elevated in all experimental groups compared with the control. This is the first study to assess testicular compensatory hypertrophy using a neonatal mouse survival surgery model. Testicular hypertrophy occurs when unilateral loss occurs before puberty, but not in adulthood in mice. Earlier testis loss may contribute to a greater degree of growth. Functionally, the unilateral testis can maintain eugonadal testosterone levels, but higher levels of LH are required after hemicastration to sustain eugonadal testosterone levels.

Testicular lymphoma - An easily underestimated malignancy in geriatric patients

To evaluate the clinical features and outcomes of testicular lymphoma for patients receiving unilateral orchiectomy following by chemotherapy and radiotherapy at our hospital.

Unilateral Orchiectomy and Its Impact on Male Fertility: A Retrospective Study of Testicular Trauma Patients

Background: Testicular injury has been shown to occur in less than 1% of trauma. Objective: To evaluate the fertility of patients underwent unilateral orchiectomy and live with unilateral testis. Materials and method: In this retrospective study, 86 male trauma patients that admitted to Alsadi hospital and Hatroom Urology Center between January 2015 to December 2018 were studied. All patients underwent unilateral orchiectomy. Married patients were included in this study. Information was collected from the medical records of the patients. The following parameters were included: patient age (years), injury type (blunt vs penetrating), mechanism of injury, conceive and period of conceive after orchiectomy. SPSS program, version 22, was used to analyze the data. The data were tabulated and statistical analysis was done by estimating rates, means and standard deviations, Fisher test was used and p-value < 0.05 was considered as statistically significant. Results: The total study patients were 86. Their age at orchiectomy ranged between 20 – 35 and the mean age was 27 ± 4.3 years. Blunt trauma accounted for (79.1%), while penetrating trauma accounted for (20.9%). The causes were vehicle accident (25.6%), gunshot wounds (20.9%), pedestrian collision (18.6%), sport trauma (15.1%), work site (10.5%), and motor collision (9.3%). Most of unilateral orchiectomy men succeeded to conceive (73.3) while (26.7%) failed to conceive (p > 0.05). After 1 year (27.9%) occurred conceive then after 2 years (23.2%) occurred conceive and after 3 years (22.2%), (p < 0.05). Conclusion: The total study patients who underwent orchiectomy were 86. Blunt trauma was predominant. The causes of the testicular trauma were vehicle accident, gunshot wounds, pedestrian collision, sport trauma, and motor collision. We found the most of unilateral orchiectomy men succeeded to conceive. Further studies are in need. Keywords: Unilateral orchiectomy, male fertility, testicular trauma, Aden, Yemen

PD12-05 TESTICULAR INVOLVEMENT IN FOURNIER’S GANGRENE: IS ORCHIECTOMY OVERUTILIZED?

You have accessJournal of UrologyCME1 Apr 2023PD12-05 TESTICULAR INVOLVEMENT IN FOURNIER’S GANGRENE: IS ORCHIECTOMY OVERUTILIZED? Amr A. Elbakry, Kareem Wasef, Andrea Pettit, Katharina Mitchell, Jennifer Mihalo, Stanley Kandzari, and John Barnard Amr A. ElbakryAmr A. Elbakry More articles by this author , Kareem WasefKareem Wasef More articles by this author , Andrea PettitAndrea Pettit More articles by this author , Katharina MitchellKatharina Mitchell More articles by this author , Jennifer MihaloJennifer Mihalo More articles by this author , Stanley KandzariStanley Kandzari More articles by this author , and John BarnardJohn Barnard More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003259.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The objective of our study is to evaluate the extent of testicular involvement in patients with genital soft tissue necrotizing fasciitis (Fournier’s Gangrene [FG]). The primary endpoint is to report the incidence of orchiectomy during initial or subsequent debridement. Secondary endpoints include the presence or absence of pathologic evidence of necrosis and thus concordance with clinical non-viability on intraoperative examination. METHODS: We identified patients who underwent radical debridement of FG our tertiary care center over the period of 10 years from January 2012 to June 2022. Careful review of the preoperative imaging and the operative details was conducted to confirm the diagnosis FG. We then identified the patients who underwent orchiectomy during the initial or the subsequent debridements. The reason for orchiectomy was collected from the operative notes as reported by the surgeon. We reviewed the pathology reports for all the orchiectomy specimen and recorded the reported findings. RESULTS: A total of 106 patients who underwent radical debridement for FG were identified. We found that 8 patients (7.5%) underwent orchiectomy at the time of initial or subsequent debridement. Two patients underwent bilateral, while 6 patients underwent unilateral orchiectomy. The most common reported reason for orchiectomy that was documented by the surgeon was “non-viable testicle with evidence of necrosis”; however, other etiologies such as “difficult wound care” were also encountered. Pathology report showed that all 10 submitted testicles were viable and free of necrosis. Mild chronic inflammation and partial degeneration with no necrosis was reported in two testicles in the same patient. Atrophic changes with no evidence of necrosis were reported in a 77-year-old patient and a 76-year-old patient. Tunica vaginalis was involved in inflammation or necrosis in 6 patients. CONCLUSIONS: Our study suggests significant discordance between clinical determination of testicular involvement in FG on exam and the pathologic findings. Orchiectomy may thus be overutilized in this cohort. The findings may guide treatment decisions particularly in situations where uncertainty exists regarding the extent of debridement (ie including tunica vaginalis but deferring orchiectomy when possible) and necessity for orchiectomy in FG. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e401 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amr A. Elbakry More articles by this author Kareem Wasef More articles by this author Andrea Pettit More articles by this author Katharina Mitchell More articles by this author Jennifer Mihalo More articles by this author Stanley Kandzari More articles by this author John Barnard More articles by this author Expand All Advertisement PDF downloadLoading ...

Testicular torsion and subsequent testicular function in young men from the general population

Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population? In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle. Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group. A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020. All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses. The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed. A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences. Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility. Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare. N/A.

Connexin Lateralization Contributes to Male Susceptibility to Atrial Fibrillation.

Men have a higher risk of developing atrial fibrillation (AF) than women, though the reason for this is unknown. Here, we compared atrial electrical and structural properties in male and female mice and explored the contribution of sex hormones. Cellular electrophysiological studies revealed that action potential configuration, Na+ and K+ currents were similar in atrial myocytes from male and female mice (4–5 months). Immunofluorescence showed that male atrial myocytes had more lateralization of connexins 40 (63 ± 4%) and 43 (66 ± 4%) than females (Cx40: 45 ± 4%, p = 0.006; Cx43: 44 ± 4%, p = 0.002), with no difference in mRNA expression. Atrial mass was significantly higher in males. Atrial myocyte dimensions were also larger in males. Atrial fibrosis was low and similar between sexes. Orchiectomy (ORC) abolished sex differences in AF susceptibility (M: 65%; ORC: 38%, p = 0.050) by reducing connexin lateralization and myocyte dimensions. Ovariectomy (OVX) did not influence AF susceptibility (F: 42%; OVX: 33%). This study shows that prior to the development of age-related remodeling, male mice have more connexin lateralization and larger atria and atrial myocyte than females. Orchiectomy reduced AF susceptibility in males by decreasing connexin lateralization and atrial myocyte size, supporting a role for androgens. These sex differences in AF substrates may contribute to male predisposition to AF.

Hypogonadism as a Risk Factor for Metabolic Syndrome and Vascular Diseases in Patients with Germ Cell Tumors of the Testis After Treatment

In the last few decades the rate of testicular germ cell tumors (TGCTs) has been increased worldwide. This type of neoplasia is one of the main causes of cancer mortality in young men. But in the case of correct management, rational chemotherapy (CT) regimens and timely diagnosis, almost 95% of patients can achieve full recovery. At the same time, there is an increased risk of side effects after CT, namely: infertility, hypogonadism, osteoporosis, cardiovascular diseases. Metabolic syndrome (MS) as a set of metabolic disorders based on hypertension, obesity, dyslipidemia, is associated with an increased risk of cardiovascular diseases. The objective: to determine the incidence of metabolic syndrome (MS) in patients with TGCTs in five or more years after initial treatment. Materials and methods. 68 patients with TGCTs 18-55 years old were examined. Unilateral high orchiectomy and follow-up observed management were performed in 14 patients, adjuvant chemotherapy for 1-2 cycles of PE (cisplatin + etoposide) or REВ (cisplatin + etoposide + bleocin) – in 22 persons, standard CT PE or REВ (<850 mg cisplatin) – 20 individuals, highdose CT for more than 4 cycles with the inclusion of cisplatin (total dose> 850 mg) – 12 patients. The control group included 29 men of the appropriate age. During the study we determined: total testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), high-density lipoprotein, triglycerides, glucose, waist circumference, blood pressure, body mass index (BMI). A comparative analysis of the results of treatment of all groups with the control group was performed. Results. The analysis of risk factors for MS in patients with TGCTs after CT performed the significantly higher levels of triglycerides, high-density lipoproteins, elevated BMI. At the same time, the level of T was reduced in patients with MS. Hypogonadism was found in 12 (22 %) patients after CT and in 1 (6 %) patient with seminoma stage I after unilateral orchiectomy. MS was detected in 3 (24 %) of 12 patients with hypogonadism and in 9 (22 %) of the 42 patients in the CT group. However, in the patients with TGCTs with hypogonadism after CT, higher BMI and lower T levels were determined. T levels were lower and LH and FSH were higher in patients who received CT compared with the persons control group. Conclusions. In the patients with testicular germ cell tumors with signs of hypogonadism there is a significantly higher risk of development of metabolic syndrome after chemotherapy. Such patients require long-term annual examination and monitoring of sex hormone levels.

Dehydroepiandrosterone (DHEA) Improves the Metabolic and Haemostatic Disturbances in Rats with Male Hypogonadism

Objectives: The current work was designed to study the effect of dehydroepiandrosterone (DHEA) on glucose homeostasis, liver functions and hemostatic disturbances in a rat model of bilateral orchidectomy (ORCH). Methods: 32 male rats (n = 8) were randomly assigned into 4 groups; (i) control (sham operated) group; were normal rats in which all surgical procedures were done without ORCH, (ii) Control + DHEA group: as control group but rats were treated with DHEA for 12 weeks, (iii) orchiectomized (ORCH) group: rats had bilateral orchidectomy and (iv) ORCH + DHEA group: orchiectomized rats treated with DHEA for 12 weeks. Four weeks after ORCH, DHEA treatment began and lasted for twelve weeks. By the end of the experiment, the parameters of glucose homeostasis, lipid profile, liver enzymes, bleeding and clotting times (B.T. and C.T.), prothrombin time (P.T.), activated partial thromboplastin time (aPTT), platelet count and aggregation, von-Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor (PAI-1), fibrin degradation products (FDP), intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelin-1 were measured. Results: ORCH caused significant deteriorations in the parameters of glucose homeostasis, lipid profile, and liver functions (p < 0.05). In addition, lower androgenicity-induced by ORCH caused a significant rise in PAI-1, fibrinogen, FDPs, ET-1 (p < 0.01) with significant shortening of bleeding and clotting times. DHEA replacement therapy significantly decreased glucose, insulin, PAI-1, fibrinogen, ICAM-1, and VCAM-1 when compared to ORCH rats. Conclusion: DHEA ameliorated the metabolic, hepatic, hypercoagulable, and hypofibrinolysis disturbances induced by ORCH.

Malignancy Yield of Testis Pathology in Older Boys and Adolescents with Cryptorchidism.

We performed a retrospective, single-institution study to characterize the pathological findings of testis tissue specimens from older boys and adolescents with cryptorchidism. With institutional review board approval, pathology reports were obtained for testicular specimens from patients age 10 years or older at a pediatric hospital from 1994 to 2016. Reports were excluded if they lacked clinical records, lacked testicular parenchyma, were from a descended testis or were from a patient with differences of sexual development. Variables of interest included age, testis location, procedure and pathological findings. Presence of malignancy among intra-abdominal versus extra-abdominal undescended testes was compared using Fisher's Exact Test. Seventy-one patients met inclusion criteria. The median age was 15.3 years (range 10.1-27.7). None had a history of testicular malignancy. Forty-five unilateral orchiectomies, 22 unilateral orchiopexies with biopsy and 4 bilateral procedures were performed. Seventeen testes (22.7%) were intra-abdominal, 42 (56.0%) were in the inguinal canal, 9 (12.0%) were at the external inguinal ring, 3 (4.0%) were in the superficial inguinal pouch and 4 (5.3%) were in the scrotum. Malignancy was detected in 2/71 patients (2.8%). By location, 2/16 patients (12.5%) with intra-abdominal testis and 0/55 patients (0%) with extra-abdominal testis demonstrated malignancy (p=0.048). Among males with cryptorchidism ages 10 years and older without differences of sexual development, 2/16 patients with intra-abdominal testis and 0/55 patients with extra-abdominal testis demonstrated malignancy. In older boys and adolescents, orchiectomy or biopsy is indicated for intra-abdominal testes but may not be necessary for extra-abdominal undescended testes.

Abstract 17234: Cisplatin Induced Coronary Artery Atherosclerosis Leading To St-elevation Myocardial Infarction: A Case Report

Introduction: Cisplatin-based chemotherapeutic regimen (CBCR) is known for increasing risk of venous thromboembolic (TE) disease. We report a unique case of STEMI associated with CBCR which we believe was caused by coronary artery thrombosis. Case description: A 31-yo man with a past history of germ cell tumor presented with chest pain radiating to back and left arm. It started this morning and intensity did not worsen with exertion. He denied any dyspnea, diaphoresis or palpitations. He was non-smoker and non-obese. He denied any family history of premature coronary artery disease. He had undergone unilateral orchiectomy a year ago, and was currently receiving chemotherapy with bleomycin, etoposide and cisplatin; the last dose of his 3 rd cycle was given the day before. EKG showed ST elevation in leads I, aVL, V4 and V5. Troponin I was high to 6.9 ng/ml (ULN 0.045 ng/ml). He received intravenous infusion of thrombolytic. An angiogram done the next day showed moderate mid-LAD disease with residual clot. A CT scan and an echocardiogram later showed left ventricular thrombus (LVT). He was kept on therapeutic enoxaparin along with aspirin. Follow up echocardiogram showed resolution of the thrombus. His chemotherapy was stopped, and he has been kept on active surveillance since then. Discussion: Most cases of CBCR-associated myocardial infarction that have been reported have been seen in the older population with other risk factors for coronary artery disease. Cases where angiographic data was available, coronary artery vasospasm appeared to be the culprit rather than a true plaque rupture. While the presence of LVT raises possibility of thromboembolism to coronaries causing MI, the angiographic findings support accelerated plaque formation to be the cause of infarction. In earlier reports, elevated pre-treatment level of von Willebrand factor has been postulated to have some role in the disease pathogenesis. Other possible mechanisms for pathogenesis include endothelial cell damage, platelet activation, and imbalance between thromboxane-prostacyclin levels. This case emphasizes the need to keep cardiac etiologies of chest pain in the differential when evaluating patients on CBCR as timely intervention is life saving and prevent morbidity.