Tranilast abrogates cisplatin-induced testicular and epididymal injuries: An insight into its modulatory impact on apoptosis/proliferation.

Cisplatin is a chemotherapeutic agent whose therapeutic use is greatly limited by the associated organs' toxicity and particularly, testicular toxicity. Cisplatin-induced testicular damage reported being mediated through mitochondria-mediated apoptosis, inflammation, and oxidative stress. Evidence showed that tranilast (TRN) has the ability to restore the oxidative status and modulate TRAIL/caspase-8 signaling. This led us to hypothesize that TRN could abrogate cisplatin-induced testicular and epididymal injuries via inhibiting oxidative stress and modulating proliferation and TRAIL/caspase-8/cJNK signaling. Cisplatin injection induced oligospermia and abnormalities in testicular and epididymal structure along with impaired oxidative status. TRN administration (100 or 300 mg/kg) for 7 days post-cisplatin injection preserved spermatogenesis and restored testicular and epididymal architecture, but restoration was more so in TRN300 than TRN100. This was in line with the restoration of balanced oxidative status as indicated by the increased total antioxidant capacity, glutathione and superoxide dismutase activity, and the decreased malondialdehyde content in testes (p < 0.05 vs. cisplatin). TRN increased the cell proliferation revealed by the increased expression of proliferating cell nuclear antigen in a dose-dependent manner (p < 0.05 vs. cisplatin) whereas only TRN300 decreased testicular cJNK, TRAIL, and caspase-8 expression (p < 0.05 vs. cisplatin). Moreover, TRN dose-dependently inhibited the pro-inflammatory transcription factor NF-kB and the cytokine TNF-α expressions in testes. In conclusion, TRN300 was more effective than TRN100 in alleviating cisplatin-induced testicular and epididymal injuries and in enhancing spermatogenesis. This curative effect of TRN might be mediated through its antioxidant and anti-inflammatory impacts along with its modulatory impact on cJNK/TRAIL/caspase-8 signaling favoring proliferation rather than apoptosis.

How common are traumatic injuries to the epididymis? A study of prevalence, imaging appearance, and management implications.

PURPOSE: To evaluate the prevalence of epididymal injuries with scrotal trauma, review imaging appearance, clinical management, and outcomes. METHODS: In this retrospective study, the radiology report database was queried for scrotal ultrasounds containing keywords pertaining to trauma, from 1998 to 2019. Exams with no clinically documented trauma, exams with trauma > 1 year ago, and duplicate exams were excluded. Chart review was conducted for age, trauma mechanism, time interval between trauma and ultrasound, signs of infection, and clinical management. Reports were reviewed to record the presence of scrotal injury, traumatic epididymitis, or epididymal hematoma. Cases with epididymal injury underwent image review. Descriptive statistics, Fisher's exact test, and Mann-Whitney's U test were performed to evaluate for associations between clinical parameters and epididymal injury. RESULTS: Initial search yielded 385 exams. A total of 103 exams met inclusion criteria. Trauma mechanisms included straddle injury (35%), blunt scrotal trauma by ball or other object (29%), assault (28%), penetrating injury (4%), and fall (3%). Sixty-eight patients (66%) had scrotal injury on imaging. Twenty-six (25%) had epididymal injury. Thirteen were isolated to the epididymis, and 13 had associated testicular or extra-testicular findings. There were 12 cases of traumatic epididymitis and 14 epididymal hematomas. All epididymal injuries were managed non-operatively. A total of 7 were prescribed antibiotics, including 1 subject who otherwise had no evidence of infection. CONCLUSION: Epididymal injury is encountered in 25% of scrotal ultrasounds for trauma evaluation. Traumatic epididymitis can be seen in 12%. It is important for radiologists to recognize this entity, as it can be mistaken for infection.

Proximally Directed Double-looped Epididymis and Vas Deferens Simulating Vas Duplication: The Importance of Precise Definition of Abnormal Ductal Anatomy in Cryptorchidism.

OBJECTIVE: Epididymal and vasal abnormalities are frequently recognized with undescended testes. The most common defect identified is the extended or elongated epididymis, an anomaly in which the epididymal tail extends distally beyond the testis before looping back upon itself, then following its normal course. Although the impact on fertility has not been established, the necessity of recognizing these vaso-epididymal abnormalities surgically is obvious as these frequently simulate a blind-ending spermatic cord leading to inadvertent excision or leaving the unseen testis more proximally in the abdomen. With this in mind, we describe a more complex vaso-epididymal structural abnormality with proximal extension of the epididymis and vas simulating duplication of these structures. METHODS: The varied surgical findings of a proximally directed double-looped abnormal epididymis and vas deferens associated with cryptorchid testes were identified in 15 children. In all instances, the epididymis extended proximally up the spermatic cord for at least 4 cm, simulating reduplication of the vas deferens and leading to bizarre ductal anatomy and confusing anatomical findings. RESULTS: In our practice, a number of abnormalities of the vaso-epididymal structures have been defined, but we isolated a number of situations in which identification of a proximally directed double-looped epididymis was noted during surgical exploration for cryptorchidism. Our review demonstrated several situations such as this where misidentification could have resulted in inadvertent transection of the vas deferens. CONCLUSION: The need for recognition of these unusual ductal abnormalities associated with cryptorchid testes is re-emphasized by these extreme examples to prevent surgical mishaps at orchidopexy.

Protective effect of Eruca sativa seed oil against oral nicotine induced testicular damage in rats.

Nicotine is a pharmacologically active component of the tobacco that adversely affects the male reproductive system and fertility. Nicotine administration in experimental animals was found to affect spermatogenesis, epididymal sperm count, motility and the fertilizing potential of sperms. The goal of this work is to assess the protective or ameliorative effect of Eruca Sativa seed oil against testicular damage induced by oral administration of nicotine in rats. Male adult Sprague-Dawley rats were used and divided into three groups; control, nicotine treated and nicotine and Eruca seed oil treated groups. After three weeks of treatment, the rats were weighed and sacrificed where testes were removed and weighed then calculating relative testis weights. The testes were processed for routine paraffin embedding and staining and the sections were examined for different morphometric and histopathological changes. The results show that nicotine administration had an effect on the body and testis weight and various morphometric parameters of the testis. It also induced varying degrees of structural damage to the seminiferous tubules, with shrinkage and absence of mature spermatids. Disorganized, vacuolization and loss of germinal cells were noticed in the basement membrane. The co-administration of Eruca Sativa seed oil led to improvement in the morphometric and histopathological changes of the seminiferous tubules. In conclusion, Eruca Sativa seed oil treatment in this study had a protective role by reversing, almost completely, all morphometric and histological changes in the testis induced by nicotine administration.

Diagnóstico y tratamiento de los tumores del epidídimo / Diagnosis and treatment of epididymal tumors

Los tumores del epidídimo son infrecuentes y la mayoría benignos, por lo que muchos no se informan en la literatura médica. En ocasiones, llegar al diagnóstico histológico de certeza, implica realizar múltiples exámenes al paciente y un reto al desempeño del médico. En el presente trabajo se hace un recuento anatómo-fisiológico del epidídimo, así como la actualización del tema de los tumores de dicho órgano, en lo referente al diagnóstico y tratamiento. Se efectuó una búsqueda bibliográfica, en las bases de datos de Hinari, PubMed, MEDLINE y en el motor de búsquedas de Google, en el periodo de 2009 a 2013. Se emplearon los términos del MeSH: tumores paratesticulares, tumores intraescrotales y tumores del epidídimo, en idioma español e inglés. También se revisaron libros de consulta y revistas especializadas. Se confirma el valor del interrogatorio y del examen físico minucioso, para establecer el diagnóstico topográfico y diferencial de estos tumores. Aunque el ultrasonido es el estudio imagenológico de elección para su valoración inicial, muchas veces no es concluyente, por lo que resulta necesario obtener imágenes por resonancia magnética nuclear para lograr información adicional. Cuando el cuadro clínico y los hallazgos de las imágenes suponen un tumor benigno, la citología aspirativa con aguja fina es una opción fiable para clasificarlos en benignos o malignos. No obstante, si esta no es definitoria, se recurre a la biopsia por congelación transoperatoria, la cual se obtiene mediante inguinotomía, y así se evita orquiectomías radicales innecesarias. Los tratamientos adyuvantes, para los tumores malignos, son muy particularizados según la edad del paciente, el tipo histológico y el estadio.

Epididymus tumors are rare and the majority of them are benign, so there is not much information about them in the medical literature. Reaching the final histological diagnosis implies multiple testing and represents a challenge for the physician's performance. The present paper made an anatomical and physiological review of the epididymus as well as provided updating on the tumors affecting this organ in terms of diagnosis and treatment. Literature search was made in databases Hinari, PubMed, Medline and in Goggle from 2009 to 2013. The MeSH terms were paratesticular tumors, intrascrotal tumors and epididymal tumors in Spanish and English. Reference books and specialized journals were also reviewed. This paper confirmed the value of questioning and of the detailed physical exam in order to set the topographic and differential diagnosis of these tumors. Although ultrasound is the imaging study of choice for initial assessment, it is often inconclusive; therefore, it is necessary to obtain nuclear magnetic resonance images so as to have additional information. When the clinical picture and the findings from images may indicate a benign tumor, then fine needle aspiration cytology is a reliable option to make the final classification. Nevertheless, if this technique is not conclusive, then there is the biopsy through transoperative freezing, which is taken with inguinotomy, thus avoiding unnecessary radical orchiectomies. The adjuvant treatments for malignant tumors are very customized since they depend on the patient's age, the histological type and the tumor staging.

Diagnóstico y tratamiento de los tumores del epidídimo / Diagnosis and treatment of epididymal tumors

Los tumores del epidídimo son infrecuentes y la mayoría benignos, por lo que muchos no se informan en la literatura médica. En ocasiones, llegar al diagnóstico histológico de certeza, implica realizar múltiples exámenes al paciente y un reto al desempeño del médico. En el presente trabajo se hace un recuento anatómo-fisiológico del epidídimo, así como la actualización del tema de los tumores de dicho órgano, en lo referente al diagnóstico y tratamiento. Se efectuó una búsqueda bibliográfica, en las bases de datos de Hinari, PubMed, MEDLINE y en el motor de búsquedas de Google, en el periodo de 2009 a 2013. Se emplearon los términos del MeSH: tumores paratesticulares, tumores intraescrotales y tumores del epidídimo, en idioma español e inglés. También se revisaron libros de consulta y revistas especializadas. Se confirma el valor del interrogatorio y del examen físico minucioso, para establecer el diagnóstico topográfico y diferencial de estos tumores. Aunque el ultrasonido es el estudio imagenológico de elección para su valoración inicial, muchas veces no es concluyente, por lo que resulta necesario obtener imágenes por resonancia magnética nuclear para lograr información adicional. Cuando el cuadro clínico y los hallazgos de las imágenes suponen un tumor benigno, la citología aspirativa con aguja fina es una opción fiable para clasificarlos en benignos o malignos. No obstante, si esta no es definitoria, se recurre a la biopsia por congelación transoperatoria, la cual se obtiene mediante inguinotomía, y así se evita orquiectomías radicales innecesarias. Los tratamientos adyuvantes, para los tumores malignos, son muy particularizados según la edad del paciente, el tipo histológico y el estadio(AU)

Epididymus tumors are rare and the majority of them are benign, so there is not much information about them in the medical literature. Reaching the final histological diagnosis implies multiple testing and represents a challenge for the physician's performance. The present paper made an anatomical and physiological review of the epididymus as well as provided updating on the tumors affecting this organ in terms of diagnosis and treatment. Literature search was made in databases Hinari, PubMed, Medline and in Goggle from 2009 to 2013. The MeSH terms were paratesticular tumors, intrascrotal tumors and epididymal tumors in Spanish and English. Reference books and specialized journals were also reviewed. This paper confirmed the value of questioning and of the detailed physical exam in order to set the topographic and differential diagnosis of these tumors. Although ultrasound is the imaging study of choice for initial assessment, it is often inconclusive; therefore, it is necessary to obtain nuclear magnetic resonance images so as to have additional information. When the clinical picture and the findings from images may indicate a benign tumor, then fine needle aspiration cytology is a reliable option to make the final classification. Nevertheless, if this technique is not conclusive, then there is the biopsy through transoperative freezing, which is taken with inguinotomy, thus avoiding unnecessary radical orchiectomies. The adjuvant treatments for malignant tumors are very customized since they depend on the patient's age, the histological type and the tumor staging(AU)

Effects of traction on the spermatic cord of rats.

PURPOSE: To determine whether tension in the spermatic cord of rats causes lesions in the testis, epididymis or vas deferens. METHODS: Forty Wistar rats were randomly allocated into four groups. A traction force of 1.6 Newton (N) in group I and 1 N in group II was applied to the right spermatic cord. Group III was the sham, and group IV served as the control. RESULTS: Testicular lesions occurred on the right side in 66.7% of the rats and on the left side in 46.1% of the rats. The testes showed a decreased number of Sertoli cells, necrosis and a decreased number of germ cells in the seminiferous tubules. Anatomopathological changes in the vas deferens were not identified. There was no decrease in the thickness of the muscle wall of the vas deferens. In the right epididymis, 71.8% of the animals showed a reduction and 5% showed an absence of intraluminal sperm. In the left epididymis, 37.5% of the rats showed a reduction. The volume and the final testicular weight of the right side in group IV was different from those in the other groups. CONCLUSIONS: Anatomopathological lesions were found in the testis and epididymis.

Effects of traction on the spermatic cord of rats

PURPOSE: To determine whether tension in the spermatic cord of rats causes lesions in the testis, epididymis or vas deferens. METHODS: Forty Wistar rats were randomly allocated into four groups. A traction force of 1.6 Newton (N) in group I and 1 N in group II was applied to the right spermatic cord. Group III was the sham, and group IV served as the control. RESULTS: Testicular lesions occurred on the right side in 66.7% of the rats and on the left side in 46.1% of the rats. The testes showed a decreased number of Sertoli cells, necrosis and a decreased number of germ cells in the seminiferous tubules. Anatomopathological changes in the vas deferens were not identified. There was no decrease in the thickness of the muscle wall of the vas deferens. In the right epididymis, 71.8% of the animals showed a reduction and 5% showed an absence of intraluminal sperm. In the left epididymis, 37.5% of the rats showed a reduction. The volume and the final testicular weight of the right side in group IV was different from those in the other groups. CONCLUSIONS: Anatomopathological lesions were found in the testis and epididymis. .

Improvement of mercuric chloride-induced testis injuries and sperm quality deteriorations by Spirulina platensis in rats.

The present study was undertaken to investigate the protective effect of the filamentous cyanobacterium Spirulina platensis (S. platensis) on mercury (II) chloride (HgCl(2))-induced oxidative damages and histopathological alterations in the testis of Wistar albino rats. The animals were divided into four equal groups, i) control, ii) HgCl(2), iii) S. platensis and iv) combination of HgCl(2)+S. platensis. Oxidative stress, induced by a single dose of HgCl(2) (5 mg/kg, bw; subcutaneously, s.c.), substantially decreased (P<0.01) the activity level of testicular key enzymatic antioxidant biomarkers (superoxide dismutase, SOD; catalase, CAT and glutathione peroxidase, GPx), oxidative stress makers (blood hydroperoxide; testicular reduced glutathione, GSH and malondialdehyde, MDA), and testicular mercury levels. Moreover, HgCl(2) administration resulted in a significant (P<0.01) increase in the number of sperms with abnormal morphology and decrease in epididymal sperm count, motility, plasma testosterone level and testicular cholesterol. Furthermore, HgCl(2) exposure induced histopathological changes to the testis including morphological alterations of the seminiferous tubules, and degeneration and dissociation of spermatogenic cells. Notably, oral pretreatment of animals with Spirulina (300 mg/kg, bw) lowered the extent of the observed HgCl(2)-mediated toxicity, whereby significantly reducing the resulting lipid peroxidation products, mercury accumulation in the testis, histopathological changes of the testes and spermatozoal abnormalities. In parallel, the pretreatment with Spirulina also completely reverted the observed Hg-Cl(2)-induced inhibition in enzymatic activities of antioxidant biomarkers (SOD, CAT and GPx) back to control levels. The pretreatment of rats with S. platensis significantly recovered the observed HgCl(2)-mediated decrease in the weight of accessory sex organs. Taken together, our findings clearly highlight the role of S. platensis as a protective modulator of HgCl(2)-induced testicular injuries and suggest some therapeutic potential in mammals. Further investigation of therapeutic strategies employing Spirulina against heavy metals toxicity in humans is therefore warranted.

[A case of solitary epididymis rupture after blunt scrotal trauma].

Blunt trauma of the scrotum is sometimes associated with severe injuries such as testis rupture. However, there are few reports of traumatic rupture of the epididymis with blunt scrotal trauma. In addition, severe epididymis injuries after scrotal trauma are always associated with severe testis trauma. We experienced a case of solitary rupture of the left epididymis that occurred in a traffic accident. We report herein such a case and review the literature. To our knowledge, this case is the 4th case of solitary epididymis rupture by blunt scrotal trauma.

Microsurgical reconstruction of iatrogenic injuries to the epididymis from hydrocelectomy.

PURPOSE: We determined the feasibility and outcome of microsurgical reconstruction of the excurrent ductal tract in men with obstruction secondary to iatrogenic injury to the epididymis from hydrocelectomy. MATERIALS AND METHODS: A retrospective chart review was done to identify men with iatrogenic injury to the epididymis or scrotal vas deferens and a history of hydrocelectomy. The outcome of microsurgical reconstruction was assessed by postoperative semen analysis. Pregnancy data were noted in patients actively attempting to conceive at a followup of 6 months or greater. RESULTS: Eight men were found to have iatrogenic injury to the epididymides (6) or scrotal vas deferens (2) due to previous hydrocelectomy. Injury was bilateral in 4 men and unilateral in 4 with contralateral testicular absence, dysfunction or obstruction resulting from different etiologies, rendering all patients azoospermic. The mean obstructive interval was 16 years (range 6 to 32). Bilateral and unilateral vasoepididymostomy was performed in 4 and 2 men each, and crossed vasovasostomy was performed in 2. Postoperative semen analysis data were available on 6 men. A patent microsurgical anastomosis was observed in 5 of 6 cases (83%). Four of the 5 men with patency had a followup of greater than 6 months, of whom 3 actively pursued conception. One pregnancy was achieved naturally and 1 was achieved by in vitro fertilization with intracytoplasmic sperm injection. CONCLUSIONS: Hydrocelectomy may result in inadvertent injury to the excurrent ductal tract, causing obstruction and infertility. Microsurgical reconstruction results in the restoration of spermatozoa to the ejaculate in 83% of cases. The return of spermatozoa to the ejaculate may provide the couple with an opportunity to conceive naturally or through assisted reproduction.

Evaluating the risk of epididymal injury during hydrocelectomy and spermatocelectomy.

PURPOSE: We evaluated the risk of epididymal injury in patients undergoing hydrocelectomy and spermatocelectomy, and determined risk factors that may increase the chance of epididymal injury. To our knowledge the incidences of epididymal injury during hydrocelectomy and spermatocelectomy have not previously been reported. MATERIALS AND METHODS: The pathology reports of all patients undergoing hydrocelectomy and spermatocelectomy at a single institution from 1990 to 2003 were retrospectively reviewed to determine if a portion of the epididymis was present in the pathology specimen. Patients with epididymis present then underwent a chart review to determine possible risk factors for epididymal injury. RESULTS: A total of 338 adults underwent unilateral or bilateral hydrocelectomy from 1990 to 2003. Another 111 patients underwent spermatocelectomy during this period. In 19 patients (5.62%) epididymal injuries were documented during hydrocelectomy and in 19 (17.12%) epididymal injuries were documented during spermatocelectomy. No specific risk factors could be identified. CONCLUSIONS: The risk of epididymal injury during hydrocelectomy and spermatocelectomy is significant. Patients must be informed of this risk since epididymal injury may lead to infertility. To our knowledge this is the first published report documenting the incidence and risk of epididymal injury during hydrocelectomy or spermatocelectomy.

A case of traumatic testicular torsion associated with a ruptured epididymis.

To salvage the testis, most urological surgeons advocate early exploration of enlarging scrotal masses or suspected testicular ruptures resulting from trauma. A case of testicular torsion within a hematoma, following blunt testicular trauma is presented, and we suggest that another indication for exploring a scrotal mass following blunt injury is to help establish an early diagnosis of torsion of the testicle.

Major differences between the testis and epididymis in the induction of granulomas in response to extravasated germ cells. I. A light microscopical study in mice.

A spermatic granuloma is a chronic inflammatory lesion which surrounds extravasated spermatozoa. Clinically, the lesion develops in the interstitial spaces of the epididymis and vas deferens, and only exceptionally in the testis itself. In the present study, murine testes and epididymides were injured using a needle and the histological appearances of these organs was then compared. Traumatic injury induced extravasation of germ cells in both testes and epididymides. A few days later, spermatic granulomas consistently formed in the epididymides, however, such lesions were not induced in the testes. To examine the possibility that epididymal spermatozoa have inherently greater ability to form spermatic granulomas than do testicular germ cells, isolated epididymal spermatozoa or testicular germ cells were locally injected into the testes and epididymides of recipient mice. Spermatic granulomas readily formed in the epididymides after local injection of either epididymal spermatozoa or testicular germ cells. In contrast, such lesions did not form in the testes even when epididymal spermatozoa were injected. Therefore, this study suggests that the microenvironment of the testicular interstitium, rather than the extravasated components from the ruptured seminiferous tubules, is the main factor determining the limited formation of spermatic granulomas in the testis.

The incidence of spermatic cord structures in inguinal hernia sacs from male children.

Inguinal herniorrhaphy is a common surgical procedure in children. Controversy exists regarding the usefulness of microscopic examination of hernia sacs, and changes in reimbursement schemes have heightened this controversy. We summarize our experience with histologic examination of these specimens to establish benchmarks for the number of spermatic cord structures in inguinal hernia sacs from male children. A 14 1/2 consecutive calendar year review of pathology reports and histologic sections of hernia sacs was conducted at a tertiary care children's hospital. Of 7,314 males (range newborn to 19 years old), 65% had bilateral and 29% had unilateral herniorrhaphy (6% unknown). Seventeen cases contained vas deferens (0.23%); 22 had epididymis (0.30%); and 30 had embryonal rests (0.41%). Either vas deferens or epididymis was found in 0.53% of patients. No cases contained bilateral vas deferens, bilateral epididymis, or vas deferens in one side with epididymis in the contralateral side. Three hernia sacs contained co-existing vas deferens and epididymis. Our study helps to provide surgeons with information for preoperative counseling regarding potential injury to the vas deferens or epididymis. This study provides baseline comparison data for quality improvement programs. We believe that each institution should weigh the costs, risks, and benefits of performing microscopic examinations on hernia sacs, depending on their own experience and data.

Sperm retrieval and fertilization in repeated percutaneous epididymal sperm aspiration.

Percutaneous epididymal sperm aspiration (PESA) for retrieval of spermatozoa for intracytoplasmic sperm injection (ICSI) is a new simplified technique in the treatment of men with obstructive azoospermia. There has been a fear that the PESA procedure, being blind, could cause damage to the epididymal duct system and make it impossible to retrieve spermatozoa if a repeated procedure is required. We report here on repeated PESA procedures from the same unilateral epididymis. Twenty-seven men with obstructive azoospermia were investigated retrospectively regarding sufficiency of the number of motile spermatozoa for ICSI, fertilization rate (FR) and possibility of collecting spermatozoa for cryopreservation in repeated PESA procedures. Sufficient motile spermatozoa for ICSI were found in a similar proportion of men at the first two attempts: 91 and 89% respectively. Fertilization rate and the possibility of collecting spermatozoa for cryopreservation were also similar at the first two PESA procedures: 62 versus 67% and 33 versus 33% respectively. At the third procedure, motile spermatozoa for ICSI were retrieved in 86% (6/7), FR was 47% and spermatozoa were cryopreserved in one case. Two men underwent a fourth PESA. In both cases, a sufficient number of motile spermatozoa for ICSI was found and FR was 62%. This study shows that in men with obstructive azoospermia, PESA can be repeated on the same unilateral epididymis up to three times, with good opportunity of retrieving sufficient motile spermatozoa for ICSI.

[Attempted classification of scrotal contusions]. / Essai de classification des contusions scrotales.

We present a review of the literature and results of a survey involving 50 closed scrotal traumas. Based on this analysis, we propose an anatomoclinical classification of scrotal contusions based on what we consider to be the most appropriate therapeutic management.

Azoospermia: a complication of hydrocele repair in a fertile population.

Although minor complications have been reported, hydrocelectomy generally is considered to be a safe procedure. We recently treated 3 patients who became azoospermic after hydrocele repair. Of the patients 2 underwent bilateral and 1 unilateral hydrocelectomy. All 3 patients had iatrogenic injury to the vas deferens or epididymis after hydrocele repair.