Management of undescended testis

The term cryptorchidism indicates a testis, which has failed to descend to the scrotum and is located at any point along the normal path of descent or at an ectopic site. Hormones play a pivotal role in testicular descent except during the migration to the level of internal inguinal ring. Cryptorchidism is present in about 4.5% of newborns with a higher incidence in preterms. The incidence decreases to 1.2% by the first year. It is classified as palpable and impalpable. The most common site of an ectopic testis is superficial inguinal pouch. Retractile testis is often bilateral and most common in boys between 5 and 6 years of age. Hypospadias and inguinal hernias are the most common associated anomalies seen with undescended testis. A thorough clinical examination helps in arriving at the etiology. A short hCG stimulation test helps to exclude anorchia. Different imaging techniques are of little help in diagnosis and require the help of an experienced radiologist. Laparoscopy has an important role in the diagnosis and management of undescended testis. The common complications include torsion and atrophy of testis. Infertility is seen in about 40% of unilateral and 70% of bilateral cryptorchidism. Undescended testis is 20 to 40 times more likely to undergo malignant transformation than normal testis. Both hCG and GnRH have been used with limited success in these children. All boys with cryptorchidism should be referred to a pediatric surgeon before 2 years of age. These children should be followed up every year after surgery to identify testicular tumors.     

不同日龄隐睾复位大鼠睾丸组织结构观察

目的 观察不同13龄隐睾复位大鼠睾丸组织结构的变化.方法 72只21 d雄性SD大鼠随机分为单侧隐睾组、双侧隐睾组、假手术对照组各24只.建立单、双侧隐睾动物模型.2周后行隐睾大鼠睾丸下降固定术,于日龄40、60 d处死取睾丸,采用苏木素.伊红染色光镜下观察各组大鼠精曲小管生育力指数(TFI)和平均精曲小管直径(MTD);生物素-dUTP/酶标亲和素法(TUNEL法)检测睾丸生殖细胞凋亡情况.结果 隐睾侧睾丸MTD、TFI显著低于阴囊内睾丸,而隐睾生殖细胞凋亡指数(AI)明显增高于阴囊内睾丸(P＜0.05);单侧隐睾组阴囊内睾丸TFI低于相应日龄的假手术对照组,但无统计学意义(P＞0.05).40 d时单侧隐睾组隐睾侧睾丸生殖细胞AI较双侧隐睾组低(P＜0.05),日龄60 d,各组隐睾侧睾丸AI较40 d时明显降低(P＜0.05),但单侧隐睾和双侧隐睾AI比较无统计学差异(P＞0.05).结论 实验隐睾复位大鼠睾丸AI升高,同时单侧隐睾鼠对侧睾丸组织存在不同程度的损害.随着复位时间的延长,隐睾组织的病理损害有恢复的趋势.     

Testicular histology related to fertility outcome and postpubertal hormone status in cryptorchidism

BACKGROUND: Early surgical correction of an undescended testis is performed to prevent the development of male infertility. However, in boys with cryptorchidism early successful surgery cannot prevent infertility if they lack Ad spermatogonia. In this study, sperm concentrations and postpubertal hormone levels were correlated to bilateral testicular histology. The aim was to define the risk of future infertility via a testis biopsy program for boys with cryptorchidism. METHODS: Eighty-nine boys who had an orchidopexy were subjected to bilateral testicular biopsy. Histological analysis of 178 biopsies indicated three groups of high, intermediate, and low risk of infertility according to the presence of Ad spermatogonia. After puberty, sperm concentrations were analysed and correlated with plasma gonadotropin and testosterone levels. FINDINGS: In patients with unilateral cryptorchidism 70% of scrotal testes had an impaired transformation of Ad spermatogonia, indicating that cryptorchidism is a bilateral disease. Sperm concentrations correlated to the number of Ad spermatogonia found at the time of orchidopexy (p<0.001). All males in the high risk of infertility group were oligospermic (mean: 8.9x10 (6) sperm/ejaculate) and 20% were azoospermic. These patients had 25 times less sperm compared to the group with presence of Ad spermatogonia in both testes (p<0.001). Correlations between testicular histology and postpubertal hormone levels confirmed a relative gonadotropin deficiency in the majority of males with cryptorchidism. INTERPRETATIONS: Ad spermatogonia proved to be a discriminating factor for the fertility outcome in cryptorchidism. Gonadotropin treatment following orchidopexy should be considered in cryptorchidism when no Ad spermatogonia are found in undescended gonads and scrotal testis have Ad germ cell counts <0.005 per tubule.     

Evaluation of low-dose hCG treatment for cryptorchidism

The aim of this study was to evaluate the efficiency of low-dose hCG (human chorionic gonadotropin) (500 IU/week for 3 weeks) in the treatment of cryptorchidism and in the assessment of Leydig cell functions. We include 35 male patients who had been diagnosed with cryptorchidism by the pediatric endocrinology specialist in the study. Twenty-one cases (Group I) received 500 IU/week of hCG while 14 patients (Group II) received 1500 IU/m2 three times a week, both for three weeks. The percentage of testis descent was calculated for both groups for the right and left testes. Leydig cell functions were evaluated by the pre- and post-treatment measurement of plasma testosterone level in all cases. A delta testosterone greater than 100 was considered to be a sufficient response. Among our patients, 77% had unilateral and 23% bilateral cryptorchidism. Unilateral cryptorchidism was detected in 80.9% of Group I patients and 71.4% of Group II patients. The pre-treatment percentages for Group I of right- and left-sided cryptorchidism were 81% and 38.1%, respectively, which decreased to 23.8% and 9.5% after treatment. The pre-treatment percentages for Group II of right- and left-sided cryptorchidism were 57.1% and 71.4%, respectively, which decreased to 14.3% and 35.7% after treatment. The success rate of hCG treatment, as defined by the testis descending into the scrotum, was 66.7% for Group I and 57.1% for Group II (p > 0.05). There was no significant difference between the two groups when Leydig cell functions were assessed. In conclusion, it is possible to use low-dose hCG for the treatment of cryptorchidism and the assessment of Leydig cell functions.     

Cryptorchidism: isolated and associated with other genitourinary defects

Cryptorchidism is the most common disorder of sexual differentiation in male children, with an incidence of 3.4 per cent in the term newborn, decreasing to 0.8 per cent at 1 year of age. The mechanisms of normal testicular descent are multifactorial and include an intact hypothalamic-pituitary-testicular axis, as well as a normal gubernaculum and epididymis. In boys with cryptorchidism, the testes demonstrate degenerative changes histologically as early as 1 to 2 years of age. Both testes may be affected, even with a unilateral undescended testis. The most important long-term complications of cryptorchidism include infertility and testicular cancer. The risk of malignancy is approximately 40 times higher in male subjects with cryptorchidism than in normal men, and is highest in male subjects who have had an intra-abdominal testis and in certain intersex conditions. Orchiopexy does not appear to lessen this risk. Hormonal therapy with HCG or LH-RH has remained unproven in clinical trials in the United States; therefore, orchiopexy remains standard treatment. HCG is recommended if the clinician suspects that a testis is retractile, however. Orchiopexy should be performed between 12 and 18 months of age to prevent the degenerative changes that are demonstrable by 2 years.     

小儿隐睾扭转的诊治体会

目的：探讨小儿隐睾合并扭转的临床诊治经验。方法回顾性分析2008年7月至2013年12月我们收治的14例小儿隐睾合并睾丸扭转病例的临床资料,其中左侧9例,右侧5例;左侧9例中,2例为双侧隐睾;右侧5例中,1例术中及术后病理检查证实为隐睾合并睾丸成熟畸胎瘤。14例均为单侧隐睾扭转。患儿年龄4岁至11岁5个月,平均3．1岁。结果14例患儿中,11例行扭转坏死睾丸切除术,3例行扭转睾丸复位＋下降固定术,患儿均同期行健侧睾丸固定术或健侧睾丸下降固定术。术后经2个月至5年随访,11例睾丸切除患儿健侧睾丸发育良好,血清睾酮水平正常;3例睾丸下降固定术患儿中,2例睾丸发育良好,1例合并睾丸畸胎瘤患儿经保睾手术后患侧睾丸发育较小,无肿瘤复发。结论早期诊断和及时手术治疗是提高隐睾并扭转患儿睾丸存活率的关键。     

单侧隐睾大鼠对侧睾丸组织中SCF/c-kit基因表达变化及意义

目的 研究单侧隐睾大鼠对侧睾丸病理变化及SCF/c-kit基因表达,探讨单侧隐睾致对侧睾丸损害的机制.方法 30只SD大鼠随机分为对照组和实验组,实验组复制单侧(左侧)腹腔隐睾模型.3个月后分别取两组右侧睾丸组织进行real-time RT-PCR、Western blot及免疫组化检测干细胞生长因子(SCF)和其受体c-kit基因及其蛋白表达变化,TUNEL法检测细胞凋亡.结果 所有动物均存活,与对照组相比实验组对侧睾丸明显缩小,光镜下观察其曲细精管发生退化,生精上皮变薄,管腔较空,生殖细胞明显减少,细胞凋亡增加.两组凋亡指数分别为14.4±0.63和4.45±0.37,差异有统计学意义(P＜0.05).荧光实时定量PT-PCR检测SCF、c-kit基因mRNA含量,实验组对侧睾丸明显降低,两组相比差异有统计学意义(P＜0.05).Western blot检测SCF及c-kit蛋白表达含量,实验组对侧睾丸同样明显降低,两组相比差异有统计学意义(P＜0.05).免疫组化染色显示各级生精细胞膜均有c-kit表达,SCF主要表达于支持细胞膜表面,但实验组两者的表达均较对照组减弱.相关性检验SCF与AI相关系数r=-0.941,P＜0.01;c-kit与AI相关系数r=-0.908,P＜0.01;SCF与c-kit相关系数r=0.956,P＜0.01,均有统计学意义.结论 单侧隐睾可致对侧睾丸SCF/c-kit基因表达减弱,生精细胞凋亡增加引起不育.     

The influence of patency of the vaginal process on the efficacy of hormonal treatment of cryptorchidism

To investigate the effects of patency of the vaginal process (processus vaginalis testis) on the efficacy of hormonal treatment of cryptorchidism, we carried out a blind, controlled, prospective study in which all patients underwent inguinal herniography. The sample comprised 310 boys with true cryptorchidism (244 unilateral, 66 bilateral) and without symptomatic hernia/hydrocele or other pathologies. Patient age ranged from 8 months to 11 years 5 months. All patients were treated with human chorionic gonadotropin (twice-weekly intramuscular injections for 5 weeks; total dose 2500 lU for patients less than 1-year-old, 5000 IU for 1- to 6-year-olds, 10000 IU for 6- to 11-year-olds). Following treatment, 37% (139/376) of the testes descended. The incidence of descent was highest for testes initially in caudal positions. Considering only non patent (i.e., normal) vaginal processes, the incidence of testis descent was 49.5% (139/281); none of the 95 testes associated with a patent vaginal process descended in response to hormone treatment.     

隐睾儿童血清苗勒管抑制物质的研究

目的探讨苗勒管抑制物质(MIS)在隐睾的诊断以及睾丸发育评价中的作用。方法选择54例单纯性隐睾患儿为观察组,36例无生殖器病变的儿童为对照组,分别检测两组儿童血清MIS水平,并比较两者之间的差异。结果观察组与对照组按年龄分组,各组间年龄比较,差异无统计学意义(P>0.05)。观察组血清MIS为48.1±26.2 ng/ml,对照组为76.3±22.8 ng/ml,两组比较,差异有统计学意义(P<0.05)。双侧隐睾患儿血清MIS为39.2±28.3 ng/ml,单侧隐睾患儿为56.5±30.1 ng/ ml,两者比较,差异有统计学意义(P<0.05)。MIS水平与睾丸发育情况呈正相关(r=0.35,P<0.05),与治疗年龄相关(r=0.19,P<0.05)。结论MIS可作为反映隐睾患儿睾丸发育状况的一项重要指标。     

胚胎期不同药物诱导大鼠隐睾模型的比较

目的 比较氟他胺(flutamide,Flu)、邻苯二甲酸二丁酯(dibutyl phthalate,DBP)、己烯雌酚(diethylstilbestrol,DES)诱导建立隐睾大鼠模型的病理表现,选择适宜研究隐睾生殖母细胞发育缺陷的动物模型.方法 SD孕鼠于妊娠12～21 d分别给予Flu(25 mg·kg-1·d-1)、DES(1.5μg·kg-1·d-1)皮下注射,DBP(500 mg·kg-1·d-1)灌胃建立隐睾模型,设立空白无干预组及玉米油皮下注射组为对照组,共5组.出生后(postnatal day,PD)20、80天获取睾丸组织,比较各药物诱导后隐睾发生率、睾丸形态学、组织学的差异.结果 Flu及DBP诱导隐睾睾丸体积PD20分别为(123.27±7.09)mm3、(117.39±8.00)mm3,PD80为(0.96±0.26)cm3、(0.79±0.28)cm3.隐睾睾丸脏器系数PD20分别为(2.27±0.09)‰、(2.26±0.09)‰,PD80分别为(1.94±0.62)‰、(2.20±0.87)‰.隐睾平均曲细精管直径(MSTD)PD20分别为(91.50±6.29)μm、(94.74±6.75)μm,PD80分别为(161.26±33.80)μm、(122.20±12.55)μm.隐睾平均曲细精管面积(MSTA)PD20分别为(6.62±0.90)×103μm2、(7.14±1.03)×103μm2,PD80分别为(2.00±1.00)×104μm2、(1.19±0.24)×104μm2.隐睾体积、脏器系数、MSTD及MSTA较对照组有明显差异(P＜0.01).Flu诱导隐睾管腔化延迟,PD20、PD80管腔中央仍可见生殖母细胞(Gonocyte,Go)残留.DES未诱导出SD大鼠隐睾,DBP组睾丸均无Go残留.结论 Flu诱导的隐睾组织中存在Go迁移障碍,曲细精管发育延迟,该模型更适宜于研究临床隐睾Go发育障碍.     

Cryptorchidism--current opinions

Cryptorchidism is the most common developmental disorder of endocrine organs in boys. Incidence depends on the age of the child--is the highest in the premature infants (30%), in term infants 2-5%, in adults 0.3%. Aetiology is still unclear and it is thought to be multifactorial including: dysgenesis of the testis, endocrine abnormalities and anatomical block on the way of the descent of the testis. In 90% of cases the pathology is unilateral. Abnormal localisation of the testis leads to the histomorphological changes which may be the causes of complications. The most dangerous are: infertility and neoplasms. The author presents also the diagnostic methods and therapeutic management in cryptorchidism.     

What a hidden testicle can hide?...or the clinical traps of cryptorchidism]

Although cryptorchidism is probably the most frequent genital anomaly encountered in boys, this pathology remains largely unexplained and its long-term prognosis is still uncertain. Despite the relative easiness of this diagnosis, attention should be paid to some clinical traps, which can mislead the sexual identity. Indeed, beside the isolated common cryptorchidism, many troubles of the testicular migration can be associated with various malformative syndromes and can be named as "cryptorchidism symptoms". Most of these syndromes are obvious, but some can be suspected only by the way of an abnormal descent of testis. Cryptorchidism, which is systematically screened out during any pediatric consultation, should play the role of clinical marker for various endocrine or genetic disorders. Among them, the intersex states should be underlined to avoid the harmful effects of misdiagnosis. We dealt with this subject through a clinical and practical approach.     

Epididymal and vasal abnormalities in undescended testes and azoospermia

Epididymal and vasal abnormalities (EVA) have long been known to be associated with cryptorchidism. In order to provide data concerning the incidence of EVA in undescended testicles, we operatively examined the anatomic relationship of the epididymis, vas, and testis in 456 cryptorchid patients (390 unilateral and 66 bilateral, over-all 522 undescended testes). As a control group we examined 50 adults postmortem and 96 pediatric patients operated upon for inguinal hernia or hydrocele. We divided the operative findings into two groups: simple variants of normal, and forms of complete anatomic disconnection of the spermatic ducts.We were unable to find any anatomic disconnection in either control group. In contrast, in 99 of the 522 maldescended testes operated upon (19%) we found some form of anatomic disconnection along the proximal spermatic ducts. The incidence was 17% in unilateral cryptorchidism and 26% in bilateral cases, in 16% of whom the EVA was bilateral. According to the literature and our previous study, azoospermia is present in about 18%–20% of adults operated upon for bilateral cryptorchidism. Our present study may suggest that in bilateral cryptorchid patients who were operated upon in the pediatric age range, the azoospermia in adulthood could be partially related to some form of bilateral occlusion or interruption of the spermatic ducts. Correspondence to: G. Belloli     

Is there an optimal contralateral testicular cut-off size that predicts monorchism in boys with nonpalpable testicles?

ObjectiveTo identify a contralateral testicular cut-off size that would predict monorchism (intra-abdominal vanishing testis or inguinal/scrotal nubbin) in boys with unilateral nonpalpable testis (NPT).Materials and methodsBoys with cryptorchidism, treated by a single surgeon at a tertiary care center from 2009 to 2013, were grouped based on intra-operative findings: boys with a solitary gonad (monorchism group, M) and two control groups: intra-abdominal testis (IAT) and palpable undescended testis (pUDT). Immediately before the procedures, the contralateral descended testes were measured using callipers. Boys with NPT underwent diagnostic laparoscopy. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and receiver operating characteristic (ROC) curves were calculated.ResultsOut of the 324 boys with cryptorchidism, 58 were found to have pUDT and 85 had NPT. Of these 85 boys with NPT, 50 had an IAT and 35 had monorchism. Mean ages at surgery for groups M, IAT and pUDT were similar (28.0, 31.3 and 30.4 months, respectively; P = 0.4). Mean length of the contralateral descended testes in groups M, IAT and pUDT was 24.3, 16.5 and 18.8 mm, respectively. Contralateral testicular cut-off lengths of 18, 19 and 20 mm had positive likelihood ratios (LR+) of 6.5, 7.4 and 10.1, respectively. The area under the ROC curve was 95% (95% CI: 91–100%).ConclusionA contralateral testicular cut-off length of 19–20 mm had the best accuracy in predicting monorchism in boys aged 11–30 months with unilateral NPT.     

Inguinal approach for the management of unilateral non-palpable testis: Is diagnostic laparoscopy necessary?

ObjectiveDuring the last decade laparoscopy has increasingly been advocated as the primary investigative procedure for the management of the non-palpable testis. We reviewed the medical records in a consecutive series of boys with non-palpable testis to examine the contribution of the initial inguinal approach in the management of unilateral non-palpable testis.Materials and methodsAmong the 183 consecutive patients with cryptorchidism from 2003 to 2012, there were 21 patients with unilateral and three with bilateral non-palpable testes. All unilateral patients then underwent inguinal and scrotal exploration through an inguinal incision. For those patients with an intra-abdominal peeping testis, the gonad was placed into the scrotum after meticulous cranial mobilization of the spermatic cord.ResultsPatient age ranged from 11 months to 144 months (mean age: 23 months). Among the 21 unilateral cases, testicular absence or atrophy was confirmed in seven patients with a scrotal nubbin in six, and blind-ending vas and vessels at the external inguinal ring in one patient. Among the remaining 14 patients with sizeable testes, 12 testes were intra-abdominal peeping testes and two testicles were seen within the distal inguinal canal, which may be missed on physical examination owing to patient obesity. The intra-abdominal peeping testicle had the opened processus vaginalis entering the internal ring in which testicle was found. These were fixed into the scrotum successfully by cranial mobilization of spermatic vessel sometimes cutting the internal oblique muscle and by Prentiss and Fowler-Stephen's maneuver. Diagnostic laparoscopy was done on three patients with bilateral cases.ConclusionsGiven the result that most of nubbins are within the scrotum and testes with intra-abdominal peeping testes are fixed down safely into the scrotum, the inguinal approach may suffice for the management of unilateral non-palpable testis. Laparoscopy should be reserved for patients with bilateral non-palpable undescended testes.     

Spigelian-cryptorchidism syndrome: a case report and discussion of the basic elements in a possibly new congenital syndrome

Pediatric cases of Spigelian hernias are rare. Only a few reports on this condition, in combination with ipsilateral cryptorchidism and testis in the hernia sac, have been published. We report on Spigelian hernia in a 3-week-old boy containing both the ipsilateral testis, without a gubernaculum and an incarcerated loop of the small intestine. It has been suggested that the combination of Spigelian hernia and ipsilateral cryptorchidism is part of a new syndrome. We discuss whether the lack of a gubernaculum and an inguinal canal reported in other similar cases may be additional elements of this new syndrome. We present a comprehensive overview of pediatric patients with Spigelian-cryptorchidism syndrome reported in the English language literature. In 75% of male infants with Spigelian hernia, there is an associated ipsilateral cryptorchidism, and in 87% of these patients, the testis is found inside the hernia sac. Thus, the surgeon dealing with a congenital Spigelian hernia should look for an undescended testis and be prepared to find it in the hernia sac.     

Combination of hypospadias and maldescended testis as cardinal symptoms in gonosomal chromosome aberrations.

Intersexual genitals or distinct hypospadias in combination with maldescended testis can be caused by endocrinological as well as chromosomal abnormalities. Even in early childhood such clinical findings require specific diagnostic procedures and subsequent treatment which is often invasive but has special importance as regards the early diagnosis of gonadal tumors. We present a child with cryptorchidism on the right, inguinal testis on the left and penoscrotal hypospadias. Cytogenetic analyses revealed a mosaic karyotype 45, X/46, X, idic (Yp) with unequal distribution of the mosaic in different tissues. In consequence of this chromosomal aberration the patient had mixed gonadal dysgenesis which is associated with an increased risk of tumor development in the aberrant gonads. The principles of pediatric, urological, cytogenetic and endocrinological diagnostics and the mode of data collection in the presented case are described and discussed. Furthermore, a protocol for preventive screening is presented, which combines urological and endocrinological investigations in males with malformations of the genito-urinary tract to minimize the risk of tumor development in the aberrant gonads.     

Hormonal treatment of cryptorchidism—hCG or GnRH—a multicentre study

In a modified, double-blind controlled study, 163 prepubertal boys (aged 1.8-13.0 years) with bilateral and 94 (aged 1.5-13.1 years) with unilateral cryptorchidism were allocated to treatment with either human chorionic gonadotrophin (im), gonadotrophin releasing hormone (intranasally) or placebo (intranasally). In individuals with the bilateral condition treatment with human chorionic gonadotrophin resulted in complete descent of both testes in 23% of patients. Treatment with human chorionic gonadotrophin in unilateral cryptorchidism resulted in complete descent in 19% of patients; all results were significantly better than those obtained with gonadotrophin releasing hormone or placebo. Linear and logistic regression analysis of the results obtained by treatment of bilateral disease showed that all treatments were more successful the younger the age of the boys. The data indicated that bilateral and unilateral cryptorchidism respond differently to hormonal treatment. We suggest that human chorionic gonadotrophin should be the first choice of treatment for prepubertal boys older than one year.     

Is the ascending testis actually ‘stationary’? Normal elongation of the spermatic cord is prevented by a fibrous remnant of the processus vaginalis

The processus vaginalis (PV) forms as a peritoneal diverticulum within the gubernaculum testis to allow the testis to exit from the abdominal cavity. Failure of its closure leads to inguinal hernias and hydroceles. Ascending testis, which is likely to be an acquired form of undescended testis, may also be part of the spectrum of failure of regression of the PV At orchidopexy for cryptorchidism in older boys with a history of a scrotal testis in infancy, we find that the PV persists as a fibrous string, preventing normal elongation of the vas deferens and gonadal vessels with increasing size of the boy. We propose that the ascending testis is actually stationary, and is caused by persistence of a fibrous remnant of the PV Seen in this light, ascending testes are directly related to inguinal hernias.