Testes Of Patients Research Articles

Physiologic Testicular Uptake of 18-F Fluorodeoxyglucose in the Indian Population.

Objective:The objective of the study is to assess the physiologic uptake of testes in patients undergoing 18F-fluoro-2-deoxyglucose (FDG) position emission tomography/computed tomography (PET/CT) scans for various malignancies other than testicular malignancy.Materials and Methods:The testicular uptake of 18F-FDG expressed as the standardized uptake value (T) was measured on PET/CT images in 320 men with no known testicular pathology from July 2019 to March 2020 at Tata Main Hospital, Jamshedpur. The ratio of maximum standardized uptake value (SUVmax) of the testis (T) to SUVmax of muscle (M) T/M ratio and to SUVmax of the liver (L) T/L ratio was calculated using SUVmax of right adductor muscle and liver, respectively. Testicular volume was calculated with the measurements taken from the axial, coronal, and sagittal slices of CT images. The correlation of testicular uptake with age, blood serum glucose level, and testicular volume was also analyzed.Results:The mean age of 320 men was 57 ± 15 years (range: 10–94) and the mean blood glucose level was 107.7 ± 23.5 mg/dl (range: 64–175). Mean testicular SUVmax in 320 men was 2.48 ± 0.80 (range: 0.67–5.5). The mean testicular volume of 640 testes of 320 men was 18.80 ± 4.83 cm3 (range: 3.85–33.56 cm3). The mean values of (T/M) and (T/L) ratios in the studied population were 3.64 ± 1.21 (range: 1.08–5.58) and 0.97 ± 0.251 (range: 0.34–1.88), respectively. The laterality index (L − R/(L + R) ×2) in 320 men was 0.074 ± 0.050 (0.000–0.308). There was a minimal negative correlation between testicular SUVmax and age (r = −0.136, P = 0.15). Mild negative correlation was noted between T/M ratio and age (r = −0.291, P < 0.0001) and between T/L ratio and age (r = −0.182, P = 0.001) in the studied population.Conclusion:The physiological testicular FDG uptake (SUVmax) of testes was 2.48 ± 0.80 (0.67–5.5) among the Indian population in this study, which has a mild negative correlation with age.

COVID-19 disrupts spermatogenesis through the oxidative stress pathway following induction of apoptosis.

To evaluate the incidence of apoptosis within the testes of patients who died from severe acute respiratory syndrome coronavirus 2 (COVID-19) complications, testis tissue was collected from autopsies of COVID-19 positive (n = 6) and negative men (n = 6). They were then taken for histopathological experiments, and RNA extraction, to examine the expression of angiotensin-converting enzyme 2 (ACE2), transmembrane protease, serine 2 (TMPRSS2), BAX, BCL2 and Caspase3 genes. Reactive oxygen species (ROS) production and glutathione disulfide (GSH) activity were also thoroughly examined. Autopsied testicular specimens of COVID-19 showed that COVID-19 infection significantly decreased the seminiferous tubule length, interstitial tissue and seminiferous tubule volume, as well as the number of testicular cells. An analysis of the results showed that the Johnsen expressed a reduction in the COVID-19 group when compared to the control group. Our data showed that the expression of ACE2, BAX and Caspase3 were remarkably increased as well as a decrease in the expression of BCL2 in COVID-19 cases. Although, no significant difference was found for TMPRSS2. Furthermore, the results signified an increase in the formation of ROS and suppression of the GSH activity as oxidative stress biomarkers. The results of immunohistochemistry and TUNEL assay showed that the expression of ACE2 and the number of apoptotic cells significantly increased in the COVID-19 group. Overall, this study suggests that COVID-19 infection causes spermatogenesis disruption, probably through the oxidative stress pathway and subsequently induces apoptosis.

Testicular Adrenal Rest Tumors or Bilateral Leydig Cell Tumors?

Testicular Adrenal Rest Tumors, also known as Testicular Tumors of the Androgenital Syndrome, are benign tumors found in the testes of patients with congenital adrenal hyperplasia. While considered benign, they are significant in that they can proliferate within the rete testis and cause infertility. We present a patient who appeared to have findings consistent with testicular adrenal rest tumors and is in the process of malignancy rule out.

Comparison of testicular vascularity via superb microvascular imaging in varicocele patients with contralateral normal testis and healthy volunteers.

In this study, we aimed to determine vascular changes in the testes in patients with varicocele using the two-dimensional color superb microvascular imaging vascular index (2DcSMIVI) and compared them with those of the normal contralateral testes of the same patients as well as the normal testes of control subjects without varicocele. A total of 114 participants and 228 testes were included in the study. 63 patients with varicocele and 51 asymptomatic volunteers were included. In total, 70 testes with varicocele (group A), 56 normal contralateral testes (Group B), and 102 bilateral normal testes were classified (Group C). Participants' testicular volume and 2DcSMIVI values were obtained via superb microvascular imaging. Testes with varicocele were graded according to Sarteschi classification. Statistically significant differences in mean testicular volume were observed among the three groups. The volume and 2DcSMIVI values of the varicocele side testes were significantly lower than those of groups B and C. Significant differences were also observed between Sarteschi grade and 2DcSMIVI values in group A. We can determine impaired microcirculation of varicocele side testes quantitatively with the 2DcSMIVI technique, and obtained VI values can be used effectively in diagnosis and follow-up of the damage in testes. Our results show that 2DcSMIVI values can play a significant role in the evaluation of testicular blood flow as a predictive sign of testicular damage.

The Comparison of Resistance Index of Testicular Artery Using Color Doppler Ultrasound in Infertile Men Undergoing Varicocelectomy.

Background:Varicocele is one of the leading causes of infertility in men. Resistance index (RI) in testis is a parameter indicating parenchymal perfusion and microvascular functions. Increased RI in the testis of patients with varicocele might be a sign of impairments in microvascularization and a significant decrease in testicular perfusion. In the present study, RI in capsular and intraparenchymal testicular arteries was evaluated in patients with varicocele who underwent varicocelectomy.Methods:This prospective cohort study was performed in 2019–2020 in Guilan, Iran. Sixty-six patients were included. Semen analysis was also done before surgeries. Patients with at least one disorder in semen analysis entered the study. RI in testicular arteries was measured by an experienced radiologist before surgeries. Six months after varicocelectomy, all patients underwent the same semen analysis and ultrasound imaging. Data were analyzed using SPSS software. The tests for analysis included McNemar Test and Wilcoxon and p<0.005 was considered as the significance level.Results:According to the results, 42 patients (63.6%) had positive changes in sperm analysis after surgeries. Sperm analysis showed a significant increase in number, concentration, morphology, and motility of sperm after surgeries (p<0.001). Further measurements of capsular and intratesticular RI in all patients also indicated a significant decrease (p<0.001).Conclusion:Increased RI might be associated with impaired microperfusion in testis followed by impairments in semen. Moreover, mean capsular and intratesticular RI in patients decreased after surgeries and this decrease was significantly more in patients who had improvement in their semen parameters.

Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections on Testis.

PurposeTo evaluate the presence and analyze the pathological changes within the testes of patients who died or recovered from severe acute respiratory syndrome coronavirus 2 (COVID-19) complications.Materials and MethodsTestis tissue was collected from autopsies of COVID-19 positive (n=6) and negative men (n=3). Formalin-fixed paraffin-embedded tissues were stained with hematoxylin and eosin (H&E) and subjected to immunofluorescence for angiotensin-converting enzyme 2 (ACE-2) expression. Fluorescent-labeled tissue slides were imaged on a quantitative pathology scope with various zoom levels allowing for qualitative and quantitative interpretation. Tissue from four COVID-19 positive autopsy cases and a live seroconverted patient was imaged with transmission electron microscopy (TEM).ResultsH&E histomorphology showed three of the six COVID-19 biopsies had normal spermatogenesis while the remaining three had impaired spermatogenesis. TEM showed the COVID-19 virus in testis tissue of one COVID-19 positive autopsy case and the live biopsy, H&E stain on the same autopsy case demonstrated interstitial macrophage and leukocyte infiltration. Immunofluorescent stained slides from six COVID-19 positive men demonstrated a direct association between increased quantitative ACE-2 levels and impairment of spermatogenesis.ConclusionsThe novel COVID-19 has an affinity for ACE-2 receptors. Since ACE-2 receptor expression is high in the testes, we hypothesized that COVID-19 is prevalent in testes tissue of infected patients. This study suggests the male reproductive tract, specifically the testes, may be targets of COVID-19 infection. We found an inverse association between ACE-2 receptor levels and spermatogenesis, suggesting a possible mechanism of how COVID-19 can cause infertility.

Possible Potential Outcomes from COVID-19 Complications on Testes: Lesson from SARS Infection.

Coronavirus infection disease-2019 (COVID-19) gained worldwide fame after deadly outbreak in China and its subsequent spread to many countries. So far, COVID-19 is not fully contained, and new cases are arising on daily bases in various countries. Due to zoonotic nature and human-to-human spread, COVID-19 is considered pandemic with more causalities in developing countries. Full genome analysis revealed its resemblance with severe acute respiratory syndrome (SARS) virus with minor variation in non-structural proteins. Both viruses use the common angiotensin converting enzyme (ACE2) receptor to attach to the epithelial cells of the target organs. Currently, COVID-19 patients are treated with drugs that are used for lungs infections. However, ACE2 has high expression in other human organs such as kidney and testes. Thus, it is assumed that, like SARS, it may have adverse effects on other vital organs, which have dominant expression of ACE2. In testis, SARS affected patients displayed peritubular fibrosis, extensive germ cell disruption, damage of blood-testis barrier integrity and more frequent occurrence of apoptosis. Here, we critically discuss the possible adverse effects of COVID-19 on the testes of patients along with future precautions to overcome the complications of reproductive organs. Key Words: COVID-19; SARS; ACE2, Testes.

Sentinel nubbin: A potential pitfall in the management of undescended testis secondary to epididymo-testicular nonunion

Epididymal anomalies are common in boys with undescended testis. Epididymo-testicular non-union with a nubbin in the scrotum is a rare anomaly and may be confusing during management of cryptorchidism. The non-fused epididymis and vas deferens which are descended to the scrotum, may be regarded as nubbin tissue secondary to testicular atrophy and proximal testis may be overlooked. To evaluate a relatively rare anomaly of epididymo-testicular non-union in which vas deferens and epididymis are descended to the scrotum resembling a nubbin tissue, while a separate testis remains in a proximal peritoneal fold (hernia or processus vaginalis)which could potentially be missed during the management of patients with undescended testis. The charts of the fourteen patients with epididymo-testicular non-union and a scrotal nubbin are retrospectively evaluated. Median age of the patiens was 1.5 years (0.5-12), 11 were left and 3 were right. No connection could be demonstrated between the testis and vaso-epididymal unit in any of the patients. Orchidopexy was performed in 13 patients while orchidectomy in1 patient. The scrotal nubbin tissue is excised in 4 patients and histological examination revealed sections of vas deferens and epididymis. One of the patients underwent inguinal exploration and orchidectomy for assumed testicular atrophy elsewhere but histological examination revealed vas deferens and epididymis without any sign suggesting an atrophic testis. An intrabdominal testis was found incidentally in this patient and he underwent 2 additional procedures for orchidopexy. Although epididymo-testicular anomalies are common in boys with undescended testis, nonunion is the rarest type of this anomaly. Similar cases are reported in the literature as simple fusion anomalies with indefinite clinical significance or even polyorchidism although no accessory testis could be demonstrated. However, the scrotal nubbin tissue which actually contains epididymis and vas is a potential decoy and may result in missing of the proximal testis if regarded as a sign of testicular atrophy and further evaluation is obviated. As this is retrospective study, actual incidence of the condition is yet to be determined. A scrotal nubbin tissue may be secondary to epididymo-testicular nonunion as well as testicular atrophy. As feasibility of radiological imaging studies are limited, a laparoscopic exploration may be considered to confirm or to exclude a separate testis in patients with scrotal nubbin. Prospective studies are needed to evaluate the actual incidence of the condition and gain-loss analysis of laparoscopic exploration.

Expression profile of microRNAs in the testes of patients with Klinefelter syndrome

Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy. A distinctive characteristic of KS is oligozoospermia. Despite multiple studies that have described the natural history of the degenerative process of germ cells in patients with KS, the molecular mechanisms that initiate this process are not well characterized. MicroRNA (miRNA)-mediated post-transcriptional control mechanisms have been increasingly recognized as important regulators of spermatogenesis; however, only a few studies have evaluated the role of miRNAs in the gonadal failure of these patients. Here, we describe a differential expression profile for the miRNAs in testicular tissue samples taken from KS patients. We analysed testicular tissue samples from 4 KS patients and 5 control patients (obstructive azoospermia) through next-generation sequencing, which can provide information about the mechanisms involved in the degeneration of germ cells. A distinctive differential expression profile was identified for 166 miRNAs in the KS patients: 66 were upregulated, and 100 were downregulated. An interactome analysis was performed for 7 of the upregulated and the 20 downregulated miRNAs. The results showed that the target genes are involved in the development, proliferation, and differentiation processes of spermatogenesis, which may explain their role in the development of infertility. This is the first report of a miRNA expression profile generated from testicular tissue samples of KS patients.

Incidental Testicular Pathologies in Patients With Idiopathic Hydrocele Testis: Is Preoperative Scrotal Ultrasound Justified?

Hydrocele testis is a common disease with a prevalence of 1% in adults. Although it can be diagnosed by physical examination, scrotal ultrasound represents a standard diagnostic tool, to exclude underlying pathologies among them testicular or scrotal malignancies. We conducted a retrospective analysis of 156 patients aged between 20 and 60 years who underwent surgical hydrocelectomy between 2003 and 2018. Pre-surgical ultrasound, histological results, complications and patients' characteristics were analysed. Malignancies were found in 0% of patients in the pre-surgical ultrasound. Interestingly, we found a higher incidence of hydrocele testis in patients with increasing age and 27% presented with symptoms other than painless enlargement of the scrotum. Among them recurrent pain was the most common. Surgical complications occurred in only 3.2%. Testicular cancer is an important differential diagnosis of hydrocele testis. However, in our study no case of incidental testicular cancer or scrotal malignancy was found in the pre-surgical ultrasound.

MP38-18 POTENTIAL ROLE OF EEF1A1 AND TPT1 GENES EXPRESSED IN THE SPERMATOGONIAL STEM CELLS AS A PREDICTIVE FACTOR OF SUBSEQUENT TESTICULAR GROWTH

You have accessJournal of UrologyInfertility: Basic Research & Pathophysiology (MP38)1 Apr 2020MP38-18 POTENTIAL ROLE OF EEF1A1 AND TPT1 GENES EXPRESSED IN THE SPERMATOGONIAL STEM CELLS AS A PREDICTIVE FACTOR OF SUBSEQUENT TESTICULAR GROWTH Kentaro Mizuno*, Hidenori Nishio, Taiki Kato, Hideyuki Kamisawa, Yoshinobu Moritoki, Satoshi Kurokawa, Akihiro Nakane, Tetsuji Maruyama, Takahiro Yasui, and Yutaro Hayashi Kentaro Mizuno*Kentaro Mizuno* More articles by this author , Hidenori NishioHidenori Nishio More articles by this author , Taiki KatoTaiki Kato More articles by this author , Hideyuki KamisawaHideyuki Kamisawa More articles by this author , Yoshinobu MoritokiYoshinobu Moritoki More articles by this author , Satoshi KurokawaSatoshi Kurokawa More articles by this author , Akihiro NakaneAkihiro Nakane More articles by this author , Tetsuji MaruyamaTetsuji Maruyama More articles by this author , Takahiro YasuiTakahiro Yasui More articles by this author , and Yutaro HayashiYutaro Hayashi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000887.018AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We previously detected differentially expressed genes (EEF1A1 and TPT1) in the testis of cryptorchidism (Mizuno K, et al., J Urol. 2009). Although these proteins were specifically expressed in the spermatogonia, the clinical significance of these genes remains unclear. Thus, we investigated the relationship between the expression of these genes in immature testes and subsequent testicular growth using the testes of patients with cryptorchidism. METHODS: For patients with cryptorchidism (n = 129) and hydrocele testes (n = 19) who underwent surgeries from April 2003 to September 2009, we used the specimens derived from testicular biopsies for morphological assessments. Total RNA of testicular tissues were also extracted and cDNAs were prepared. To quantify the expression value of EEF1A1 and TPT1 genes, real-time RT-PCR were performed with specific primers. After the surgeries, we checked the location and volume of their testes until August 2019. This study was performed after approval of the institutional review board of our hospital (IRB # 083). RESULTS: Of 129 boys with cryptorchidism, we selected 14 patients of whose cases were unilateral and whose age at surgery was < 2 years. The mean age at surgery was 15.2 ± 4.6 months, and the mean follow-up period was 114.4 ± 16.9 months. The relative expression values of EEF1A1 and TPT1 in the testicular tissue at orchiopexy were 1.33 ± 0.43 and 1.16 ± 0.44, respectively. The correlation coefficient between the EEF1A1 gene expression and subsequent testicular growth rate was -0.355 (figure), and the TPT1 was -0.326. CONCLUSIONS: We could detect a weak association between EEF1A1 and TPT1 expressions and testicular growth in patients with cryptorchidism 15 years after surgery. Because these genes were associated with the differentiation of spermatogonia and maintenance of pluripotency, it is likely that cell differentiation and proliferation was impaired in the cryptorchid testes, which highly expressed these genes, even if an orchiopexy had been performed at the recommended time. While subsequent long-term prospective surveillance will be required, EEF1A1 and TPT1 might be available as novel predictive factors of testicular growth. Source of Funding: None. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e576-e576 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kentaro Mizuno* More articles by this author Hidenori Nishio More articles by this author Taiki Kato More articles by this author Hideyuki Kamisawa More articles by this author Yoshinobu Moritoki More articles by this author Satoshi Kurokawa More articles by this author Akihiro Nakane More articles by this author Tetsuji Maruyama More articles by this author Takahiro Yasui More articles by this author Yutaro Hayashi More articles by this author Expand All Advertisement PDF downloadLoading ...

Testicular stiffness in varicocele: evaluation with shear wave elastography.

PurposeThis study was conducted to evaluate the potential role of shear wave elastography (SWE) in the evaluation of testes in patients with varicocele.MethodsA total of 116 testes of 58 patients with left-sided varicocele and 58 testes of 29 age-matched healthy controls were included in the study. The patients' testes were classified into groups A (normospermic) and B (oligospermic) based on the presence of oligospermia. The mean SWE values and volume of the testes with varicocele were compared with the contralateral normal testes of the patients and the testes of healthy controls.ResultsThe mean SWE value of the left testes in groups A (4.77±1.16 kPa) and B (6.15±1.96 kPa) exceeded that of the healthy controls (3.79±0.94 kPa) (P<0.001). The mean SWE value of the left testes in group B (6.15±1.96 kPa) exceeded that of group A (4.77±1.16 kPa) (P=0.002). No correlation was observed between testicular stiffness and the grade of varicocele (r=0.102, P=0.423)ConclusionThe testes with varicocele were stiffer than the contralateral testes and the testes of healthy controls, and SWE might play an auxiliary role to conventional ultrasonography in assessing pathologic alterations in the testis owing to varicocele.

Shear Wave Elastography Evaluation of Testes in Patients With Varicocele.

We aimed to determine histological damage in patients with varicocele by comparing the elasticity of their affected testes with that of their normal contralateral testes as well as normal testes of control subjects without varicocele using shear wave elastography (SWE). In total, 48 patients with varicocele (96 testes) and 52 control subjects (104 testes) were included in this study. Shear wave elastography values were measured in the longitudinal plane using an oval region of interest that covered as much of the testicular contours as possible. Fifty testes with varicocele were classified as group A, 46 normal contralateral testes of the same patients as group B, and 104 normal testes of control subjects as group C. The normal group C testes were randomly chosen from patients who had applied for ultrasonography for any reason and agreed to participate in the study. The testicular volume and SWE values were compared between these 3 groups. The average age of the patients was 28.45 years, and no significant difference in age was found between the 3 groups (P = 0.665). A significant difference in the testicular volume was found between groups A and C (P = 0.014). The SWE values were significantly higher in group A than in groups B and C (P < 0.001). No significant correlation was observed between the testicular volume and SWE values in any of the groups. Our results showed that SWE can be used as an effective technique to assess testicular stiffness in patients with varicocele to predict interstitial fibrosis and the severity of histological damage.

Morphological changes of the testes in patients operated on cryptorchidism

Purpose: to study the morphological changes of testis in patients who had cryptorchidism in childhood.Methods. The examination results of 9 patients who underwent treatment for cryptorchidism and presented with infertility within marriage when they were 24–30 y. o. were studied. Clinical examination, ultrasound imaging of the scrotum, complete spermograms, hormonal studies, open biopsy of the testis with subsequent pathomorphological assessment of biopsy specimens were carried out.Results: observation of 9 patients with azoospermia who had undergone a course of conservative and surgical treatment for cryptorchidism when they were 4–14 years, resulted in testicular atrophy leading to the decrease in the tissue mass of the organ and high level of FSH.Conclusion: hormonal tests, ultrasound examinations and pathomorphological studies enable to estimate the extent of epitheliospermatogenic layer involvement.

β-adrenergic receptors in the up-regulation of COX2 expression and prostaglandin production in testicular macrophages: Possible relevance to male idiopathic infertility

Catecholaminergic neuronal elements (CNE) and macrophages (MACs) are increased in testes of patients with idiopathic infertility. Now, we describe an anatomical proximity between CNE and MACs, expression of specific α- and β-adrenergic receptors (ADRs) subtypes in MACs, and a positive correlation between the number of MACs and cyclooxygenase (COX2) expression - key enzyme in prostaglandin (PG) synthesis and an inflammatory marker - in testes of infertile men. To examine a potential effect of adrenergic input on COX2 expression, we used two additional experimental models: non-testicular human MACs (THP1 cell line) and non-human testicular MACs purified from adult Syrian hamsters. We found that epinephrine and norepinephrine up-regulate COX2 expression and PGD2 production through β1-and β2-ADRs.Our results demonstrate the existence of a yet unknown link between CNE and MACs in the human testis that could trigger inflammation and tissue homeostatic dysregulation associated with pathogenesis or maintenance of infertility states.

Genes located in Y-chromosomal regions important for male fertility show altered transcript levels in cryptorchidism and respond to curative hormone treatment

BackgroundUndescended (cryptorchid) testes in patients with defective mini-puberty and low testosterone levels contain gonocytes that fail to differentiate normally, which impairs the development of Ad spermatogonia and ultimately leads to adult infertility. Treatment with the gonadotropin-releasing hormone agonist GnRHa increases luteinizing hormone and testosterone and rescues fertility in the majority of pathological cryptorchid testes. Several Y-chromosomal genes in the male-specific Y region (MSY) are essential for spermatogenesis, testis development and function, and are associated with azoospermia, infertility and cryptorchidism. In this study, we analyzed the expression of MSY genes in testes with Ad spermatogonia (low infertility risk patients) as compared to testes lacking Ad spermatogonia (high infertility risk) before and after curative GnRHa treatment, and in correlation to their location on the Y-chromosome.ResultsTwenty genes that are up- or down-regulated in the Ad- group are in the X-degenerate or the ampliconic region, respectively. GnRHa treatment increases mRNA levels of 14 genes in the ampliconic region and decreases mRNA levels of 10 genes in the X-degenerate region.ConclusionOur findings implicate Y-chromosomal genes, including USP9Y, UTY, TXLNGY, RBMY1B, RBMY1E, RBMY1J and TSPY4, some of which are known to be important for spermatogenesis, in the curative hormonal treatment of cryptorchidism-induced infertility.

Intravenous but not intrathecal central nervous system–directed chemotherapy improves survival in patients with testicular diffuse large B-cell lymphoma

BackgroundTesticular lymphoma is a rare malignancy affecting mainly elderly men, the majority representing diffuse large B-cell lymphoma (DLBCL). Its relapse rate is higher than that of nodal DLBCL, often affecting the central nervous system (CNS) with dismal prognosis. Patients and methodsWe searched for patients with testicular DLBCL (T-DLBCL) involvement from the pathology databases of Southern Finland University Hospitals and the Danish Lymphoma Registry. Clinical information was collected, and outcomes between treatment modalities were evaluated. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were assessed using Kaplan–Meier and Cox proportional hazards methods. ResultsWe identified 235 patients; of whom, 192 were treated with curative anthracycline-based chemotherapy. Full survival data were available for 189 patients. In univariate analysis, intravenous CNS-directed chemotherapy, and irradiation or orchiectomy of the contralateral testis translated into favourable PFS, DSS and OS, particularly among the elderly patients (each p ≤ 0.023). Intrathecal chemotherapy had no impact outcome. In multivariate analyses, the advantage of intravenous CNS-directed chemotherapy (hazard ration [HR] for OS, 0.419; 95% confidence interval [CI], 0.256–0.686; p = 0.001) and prophylactic treatment of contralateral testis (HR for OS, 0.514; 95% CI, 0.338–0.782; p = 0.002) was maintained. Rituximab improved survival only among high-risk patients (International Prognostic Index≥3, p = 0.019). The cumulative risk of CNS progression was 8.4% and did not differ between treatment modalities. ConclusionThe results support the use of CNS-directed chemotherapy and prophylactic treatment of the contralateral testis in patients with T-DLBCL involvement. Survival benefit appears resulting from better control of systemic disease rather than prevention of CNS progression.

567 - Risk factors of concomitant undescended testis in patients with hypospadias

567 - Risk factors of concomitant undescended testis in patients with hypospadias

Corrigendum to: Decreased expression of DNA methyltransferases in the testes of patients with non-obstructive azoospermia leads to changes in global DNA methylation levels.

DNA methylation plays key roles in epigenetic regulation during mammalian spermatogenesis. DNA methyltransferases (DNMTs) function in de novo and maintenance methylation processes by adding a methyl group to the fifth carbon atom of the cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites. Azoospermia is one of the main causes of male infertility, and is classified as obstructive (OA) or non-obstructive (NOA) azoospermia based on histopathological characteristics. The molecular background of NOA is still largely unknown. DNA methylation performed by DNMTs is implicated in the transcriptional regulation of spermatogenesis-related genes. The aim of the present study was to evaluate the cellular localisation and expression levels of the DNMT1, DNMT3A and DNMT3B proteins, as well as global DNA methylation profiles in testicular biopsy samples obtained from men with various types of NOA, including hypospermatogenesis (hyposperm), round spermatid (RS) arrest, spermatocyte (SC) arrest and Sertoli cell-only (SCO) syndrome. In the testicular biopsy samples, DNMT1 expression and global DNA methylation levels decreased gradually from the hyposperm to SCO groups (P P P <0.05). Although both DNMT1 and DNMT3A were localised in the cytoplasm and nucleus of the spermatogenic cells, staining for DNMT3B was more intensive in the nucleus of spermatogenic cells. In conclusion, the findings suggest that significant changes in DNMT expression and global DNA methylation levels in spermatogenic cells may contribute to development of male infertility in the NOA groups. Further studies are needed to determine the molecular biological effects of the altered DNMT expression and DNA methylation levels on development of male infertility.

Decreased expression of DNA methyltransferases in the testes of patients with non-obstructive azoospermia leads to changes in global DNA methylation levels.

DNA methylation plays key roles in epigenetic regulation during mammalian spermatogenesis. DNA methyltransferases (DNMTs) function in de novo and maintenance methylation processes by adding a methyl group to the fifth carbon atom of the cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites. Azoospermia is one of the main causes of male infertility, and is classified as obstructive (OA) or non-obstructive (NOA) azoospermia based on histopathological characteristics. The molecular background of NOA is still largely unknown. DNA methylation performed by DNMTs is implicated in the transcriptional regulation of spermatogenesis-related genes. The aim of the present study was to evaluate the cellular localisation and expression levels of the DNMT1, DNMT3A and DNMT3B proteins, as well as global DNA methylation profiles in testicular biopsy samples obtained from men with various types of NOA, including hypospermatogenesis (hyposperm), round spermatid (RS) arrest, spermatocyte (SC) arrest and Sertoli cell-only (SCO) syndrome. In the testicular biopsy samples, DNMT1 expression and global DNA methylation levels decreased gradually from the hyposperm to SCO groups (P P P <0.05). Although both DNMT1 and DNMT3A were localised in the cytoplasm and nucleus of the spermatogenic cells, staining for DNMT3B was more intensive in the nucleus of spermatogenic cells. In conclusion, the findings suggest that significant changes in DNMT expression and global DNA methylation levels in spermatogenic cells may contribute to development of male infertility in the NOA groups. Further studies are needed to determine the molecular biological effects of the altered DNMT expression and DNA methylation levels on development of male infertility.