Phenotypic severity scoring system and categorisation for prune belly syndrome: application to a pilot cohort of 50 living patients.

OBJECTIVE: To design a novel system of scoring prune belly syndrome (PBS) phenotypic severity at any presenting age and apply it to a large pilot cohort. PATIENTS AND METHODS: From 2000 to 2017, patients with PBS were recruited to our prospective PBS study and medical records were cross-sectionally analysed, generating individualised RUBACE scores. We designed the pragmatic RUBACE-scoring system based on six sub-scores (R: renal, U: ureter, B: bladder/outlet, A: abdominal wall, C: cryptorchidism, E: extra-genitourinary, generating the acronym RUBACE), yielding a potential summed score of 0-31. The 'E' score was used to segregate syndromic PBS and PBS-plus variants. The cohort was scored per classic Woodard criteria and RUBACE scores compared to Woodard category. RESULTS: In all, 48 males and two females had a mean (range) RUBACE score of 13.8 (8-25) at a mean age of 7.3 years. Segregated by phenotypic categories, there were 39 isolated PBS (76%), six syndromic PBS (12%) and five PBS-plus (10%) cases. The mean RUBACE scores for Woodard categories 1, 2, and 3 were 20.5 (eight patients), 13.8 (25), and 10.6 (17), respectively (P < 0.001). CONCLUSIONS: RUBACE is a practical, organ/system level, phenotyping tool designed to grade PBS severity and categorise patients into isolated PBS, syndromic PBS, and PBS-plus groups. This standardised system will facilitate genotype-phenotype correlations and future prospective multicentre studies assessing medical and surgical treatment outcomes.

Hormonal Aspects of the Pathogenesis and Treatment of Cryptorchidism.

A normal functioning hypothalamic-pituitary-testicular axis is required for normal testicular descent. The percentage of cases that result from a disturbance in this axis remains controversial. Much has yet to be learnt about cryptorchidism, but is seems that the existence of A dark spermatogonia (Ad spermatogonia) is essential for later fertility. Bilateral cryptorchid patients have a high risk of later infertility, even though they undergo early surgery for cryptorchidism. It is possible today to distinguish-to a certain extent-between three different groups of cryptorchid patients based on testicular histology, gonadotropins, and inhibin B at the time of early surgery: Group 1, patients suspected of prepubertal transient hypothalamic-pituitary-testicular hypofunction and a high risk of later infertility; Group 2, patients with hypergonadotropic hypogonadism and a primary testicular dysfunction; and Group 3, patients with normal histology and normal serum levels of inhibin B and gonadotropins at the time of early surgery and a low risk of later infertility. Given the potential adverse effects of hormonal treatment, attention should be directed toward small doses of adjuvant gonadotropin-releasing hormone (GnRH) treatment for those who might benefit the most, that is, bilateral cryptorchid boys at early surgery without evidence of normal maturation of gonocytes into Ad spermatogonia. Optimally, gonadotropin levels in such patients should be measured to ensure that levels are not compensatory elevated, thereby supporting the suspicion of hypothalamic-pituitary-testicular hypofunction. Studies of GnRH-supplementary treatment should include testicular biopsy at surgery and at follow-up in childhood as well as examinations of fertility potential in adulthood.

[Diagnosis and management of the undescended testis--an update in the light of the current guidelines]. / Diagnostik und Therapie des Maldeszensus testis--ein Update unter Berücksichtigung der Leitlinien.

Cryptorchidism, or undescended testis (UDT), occurs in 1-3% of male term infant births. At least two-thirds of UDTs will descend spontaneously, typically during the first 6 months of life. UDTs are associated with loss of spermatogenic potential and testicular malignancy in the long term. Orchiopexy performed prior to puberty may significantly reduce the malignant potential by up to 4-fold. Neoadjuvant hormonal therapy starting at 6 months of life has been shown to potentially improve the testicle's fertility index and should be part of the therapeutic concept. However, the use of hormonal treatment and HCG beyond the first year of life is to be challenged given a potentially negative impact on testicular function. Laparoscopic exploration and therapy is the method of choice for non-palpable testes. Ideally, surgical repair of the UDT should be completed by the age of 1 year.

Epidemiology, classification and management of undescended testes: does medication have value in its treatment?

Genetic, hormonal, and anatomical factors are believed to be involved in the etiology of undescended testes. Due to increased risk of infertility, testicular cancer, torsion and/or accompanying inguinal hernia (>90%) as well as cosmetic concerns, all these patients require treatment. In this review paper, we aimed to evaluate the success rates of treatment modalities used in undescended testes, beginning from 1930 to the present, and to draw attention to the possible risks and benefits and also the efficacy of hormonal therapy in the management of the disorder, which is still a controversial issue. Hormonal therapy may lead to penile growth, painful erection, and behavioral changes while on treatment. In recent years, it has been reported that human chorionic gonadotropin (hCG) treatment was associated with interstitial edema due to increased vascular permeability, inflammation-like changes, and several adverse effects on germ cells by increasing pressure and apoptotic process. It has also been reported that LHRH analogues have positive effects on germ cells by increasing fertility in patients undergoing unilateral or bilateral orchiopexy. In some studies, the success rate of hCG treatment was reported to be higher following buserelin. In some other studies, hCG treatment was recommended before orchiopexy to reduce the risk for surgical ischemia. There are a limited number of randomized controlled studies, so evidence showing the efficacy of hormonal therapy is insufficient. According to the 2007 Consensus Report of Nordic countries, it is recommended that surgery is the first-line treatment modality in undescended testes and that it should be performed by pediatric surgeons and urologists at the age of 6-12 months.

Altered infant feeding patterns in boys with acquired nonsyndromic cryptorchidism.

BACKGROUND: Genetic and environmental factors likely influence susceptibility to nonsyndromic cryptorchidism, a common disease presenting at birth or in later childhood. We compared cases and controls to define differential risk factors for congenital versus acquired cryptorchidism. METHODS: We compared questionnaire and clinical data from cases of congenital cryptorchidism (n = 230), acquired cryptorchidism (n = 182) and hernia/hydrocele (n = 104) with a group of healthy male controls (n = 358). Potential predictor variables (p < 0.2 in univariable analysis) were included in stepwise multivariable logistic regression models. RESULTS: Temporary (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4-0.8) or exclusive (OR, 0.6; 95% CI, 0.4-0.9) breastfeeding was reduced and soy formula feeding increased (OR, 1.8; 95% CI, 1.2-2.9) in acquired but not congenital or hernia/hydrocele groups. The highest risk estimates were observed for primary soy formula feeding with limited or no breastfeeding (OR 2.5; 95% CI, 1.4-4.3; adjusted OR, 2.7; 95% CI, 1.4-5.4) in the acquired group. Primary feeding risk estimates were equivalent or strengthened when multivariable models were limited to age greater than 2 years, full-term or not small for gestational age, or Caucasian subjects. Pregnancy complications and increased maternal exposure to cosmetic or household chemicals were not consistently associated with either form of cryptorchidism in these models. CONCLUSIONS: Our data support reduced breastfeeding and soy formula feeding as potential risk factors for acquired cryptorchidism. Although additional studies are needed, hormonally active components of breast milk and soy formula could influence the establishment of normal testis position in the first months of life, leading to apparent ascent of testes in childhood. Birth Defects Research (Part A), 2012.

Bilateral undescended testes classified according to preoperative and postoperative status of gonadotropins and inhibin B in relation to testicular histopathology at bilateral orchiopexy in infant boys.

PURPOSE: In recent series of boys with cryptorchidism gonadotropin levels have been higher and serum inhibin B levels have been lower than normal. To some extent the serum values of inhibin B reflect the state of germinative epithelium in cryptorchid testes. We evaluated whether blood samples of gonadotropins and inhibin B as well as histopathology could be used to classify undescended testes. MATERIALS AND METHODS: A total of 69 boys (median age 2 years) who underwent surgery for bilateral cryptorchidism had blood samples taken preoperatively and 3 months to 2.1 years postoperatively. Testicular biopsies were performed bilaterally at orchiopexy. The average germ cell number per tubular transverse tubule was measured. RESULTS: Group 1 included 17 patients with increased follicle-stimulating hormone levels. Serum follicle-stimulating hormone and luteinizing hormone decreased significantly after surgery. In 77% of patients (13 of 17) follicle-stimulating hormone levels were normalized. Of these boys 35% (6 of 17) had a low postoperative serum inhibin B. Group 2 consisted of 27 patients with a decreased germ cell number and/or low preoperative inhibin B, but not increased serum follicle-stimulating hormone or luteinizing hormone. There were no significant postoperative changes in follicle-stimulating hormone and luteinizing hormone. Of these boys 22% (6 of 27) had a low serum inhibin B postoperatively. In group 3 there were 25 patients with a normal germ cell number, normal preoperative serum inhibin B and normal gonadotropins. There were no significant changes in luteinizing hormone and follicle-stimulating hormone postoperatively. Only 1 boy in this group had a low postoperative serum inhibin B. CONCLUSIONS: Patients with increased gonadotropin levels may have testicular dysgenesis and some may benefit from early surgery. Patients with normal gonadotropin levels and a decreased germ cell number have transient hypothalamus-pituitary-gonadal hypofunction and a poor fertility prognosis. These patients may benefit from gonadotropin treatment after orchiopexy. Patients with normal gonadotropins, inhibin B and germ cell number have a good fertility prognosis after surgery.

Retractile testes: a review of the current literature.

The current evidence for the management of retractile testes is discussed in this review. Issues such as clinical definitions, natural history, possible outcomes and evidence for surgical intervention are evaluated. After reviewing the literature, the authors summarize that currently there is not enough evidence to warrant surgery for retractile testes, but rather a strategy of surveillance should be adopted.

Undescended testis: how extensive should the work up be?

AIM: The aim of this study was to highlight various anomalies associated with undescended testis and to determine how much work up is necessary for this condition. MATERIAL AND METHODS: The study was conducted in the department of Pediatric Surgery SKIMS Srinagar, Kashmir. All patients between 0-14 years of age who attended out patient department (OPD) from January 2002 to December 2003 with maldescent of testes were included in the study. Detailed relevant history and physical examination findings were recorded in all the cases. Baseline investigations were performed along with ultrasonography of the abdomen. In relevant cases other investigations like intravenous urography, micturating cystourethrography, CT scan and laparoscopy were performed as and when indicated. RESULTS: A total of 250 cases of undescended testis were registered during this period. Maximum number of cases were in the age group of 5-10 years. In 130 (52%) cases the right testis was undescended while 75 (30%) had left sided undescended testis and 45 (18%) had bilateral undescended testis. Maldescended testis comprised 11% of the admissions. The majority of cases were having gestational age of 37 weeks or more. The associated anomalies picked up on investigations included duplication of upper urinary tract (3.2%), hydronephrosis and polycystic kidney (0.8% each), horseshoe kidney, ectopic kidney, crossed renal ectopia (0.4% each) Posterior urethral valves, Prune belly syndrome (0.4%) and spina bifida (0.4%). On detailed clinical examination of genitalia several abnormalities were picked which included hydrocele, hypospadias, hernia, chordee, micropenis and ambiguous genitalia. CONCLUSION: We recommend ultrasonography to be done in all cases of undescended testis in addition to a thorough history and physical examination. Intravenous pyelography, micturating cystourethrogram, CT scan and other investigations should be performed selectively based on history, physical examination or ultrasound findings.

Spermatogenesis after 1-stage fowler-stephens orchiopexy in experimental cryptorchid rat model.

PURPOSE: To evaluate the validity of 1-stage Fowler-Stephens orchiopexy, we performed this procedure for intra-abdominal testes in an experimental cryptorchid rat model and assessed postoperative spermatogenesis. MATERIALS AND METHODS: Cryptorchidism in rats was induced by injecting flutamide into the abdomen of pregnant Sprague Dawley rats for 7 days (days 14 to 20 of gestation). Four-week-old cryptorchid rats were divided into the 4 groups of sham operation (group 1, 7 rats), orchiopexy only (group 2, 7), spermatic vessel ligation only (group 3, 7), and spermatic vessel ligation and orchiopexy (1-stage Fowler-Stephens orchiopexy, group 4, 7). The testes were removed 12 weeks after birth in all groups, and testicular weight, testicular histopathological findings and presence of sperm in the epididymis were examined. RESULTS: All operated testes had reticulated vessels on the tunica albuginea. There were no statistically significant differences in the testicular weight between groups 1 (mean +/- SD 0.47 +/- 0.04 gm) and 4 (0.30 +/- 0.19), suggesting that Fowler-Stephens orchiopexy did not induce significant testicular atrophy. However, seminiferous tubule diameters in group 4 were significantly smaller than in group 1 (p <0.001), and no sperm was observed in the epididymis of group 4 rats, suggesting that Fowler-Stephens orchiopexy reduced seminiferous tubule diameters and did not improve spermatogenesis. CONCLUSIONS: Although Fowler-Stephens orchiopexy is a good procedure to maintain testicular size and correct cosmetic deformity of an absent scrotum, it may not significantly contribute to the improvement of spermatogenesis.

Laparoscopic management of impalpable testis in children, new classification, lessons learned, and rare anomalies.

INTRODUCTION: Cryptorchidism is the most common genitourinary anomaly in male children. About 20% of cryptorchid testicles are impalpable. Laparoscopy has become one of the important diagnostic modalities for the management of impalpable testes. The aim of the present study was in highlighting the lessons and rare anomalies encountered during the management of impalpable testes in children over a period of 10 years in a single pediatric surgery center and to establish a new classification that better describes the anomalies. MATERIALS AND METHODS: A retrospective review of 93 laparoscopic explorations for nonpalpable testes between 1998 and 2008 was conducted. Demographic data, intraoperative findings and management, associated anomalies, and postoperative follow-up were collected and analyzed. A new laparoscopic classification is described. RESULTS: Age range was 7 months to 8 years. Twenty bilateral versus 73 unilateral impalpable testes were operated on. Four groups were established with subgroups in each group. Group 1 (vanishing syndrome) had 44 cases, group 2 (peeping testes) had 21 cases, group 3 (intra-abdominal testes) had 38 cases, and group 4 (disorders of sex development) had 10 cases. Associated anomalies included 4 cases of Down syndrome, 7 cases of neurologic impairment, 3 of renal anomalies, 3 of cardiac anomalies, and 1 case of eye anomalies. Follow-up range was 1-6 years. CONCLUSIONS: A new laparoscopic classification is presented that better describes the anomalies and help-in planning the treatment of impalpable testes. Impalpable testes with Down syndrome are sometimes associated with bizarre anatomy. Parents should be well informed of all the possible findings, especially in bilateral cases.

Pliorquidismo / Polyorchidism

OBJETIVO: Presentamos un caso de teste supernumerario, rara entidad, de la que hay recogidos y fundamentados unos 100 casos.MÉTODOS: Se trata de un varón de 44 años, que consultó por descubrimiento casual de masa escrotal derecha. A la exploración física, ecográfica y tomográfica ya se sospechó el diagnóstico de poliorquidia, refrendándose posteriormente mediante exploración quirúrgica y biopsia. Dada la ausencia de patología y la completa normalidad de la línea seminal se optó por no actuar, no extirpando el teste supernumerario.RESULTADOS: Existen clasificaciones para una correcta evaluación de la poliorquidia, que relacionan la localización respecto a escroto, y la existencia o no de epidídimo y deferentes independientes para las dos gónadas.CONCLUSIONES: Aunque remota, existe la posibilidad de degeneración maligna en estos testes, por lo que se impone la exploración quirúrgica y la extirpación de los testes supernumerarios cuando la biopsia arroje dudas, en cuanto a displasia o presencia de carcinoma in situ, o cuando sean origen de dolor(AU)

OBJECTIVE: To report one case of supernumerary testicle, a rare entity with around 100 cases published.METHODS: 44-year-old male patient consulting for incidental discovering of a right scrotal mass. The diagnosis of polyorchidism was suspected after physical examination, ultrasound, and CT scan, and confirmed subsequently on surgical exploration and biopsy.Due to the absence of pathology and complete normal seminal lines decision was taken to not perform orchiectomy of the supernumerary testicle.RESULTS: There are classifications for proper evaluation of polyorchidism, which state the relation between site of the testicle in relation to scrotum, existence or absence of independent epididymis and vasa deferentia for both testicles.CONCLUSIONS: Although remotely, there is a possibility of malignant degeneration of these testicles, so that surgical exploration and excision of the supernumerary testicles when their biopsy is doubtful in terms of dysplasia or if they present carcinoma in situ or they are a source of pain(AU)

Polyorchidism: a case report and classification.

Polyorchidism is an uncommon congenital anomaly, defined as the presence of more than 2-histologically proven-testes. Approximately 90 cases are reported in the literature. It is found predominantly on the left side. We report a right-sided polyorchidism found during orchidopexy in a 6-year-old boy. The supernumerary testis had its own tunica vaginalis, epididymis, and deferent duct, but shared the blood supply with the ipsilateral distal testis. The diagnosis was confirmed histologically. Because of the shortness of its vessels, the supernumerary testis could not undergo orchidopexy and was removed. We review the classification systems proposed for polyorchidism. Most are based on embryologic considerations, but none is capable of including all cases described in the literature. Thus, we present an anatomical system for a more comprehensive taxonomy of polyorchidism according to its reproductive function.

Cryptorchidism: classification, prevalence and long-term consequences.

UNLABELLED: Undescended testis is a common finding in boys, and the majority of cases have no discernible aetiology. There are unexplained geographical differences and temporal trends in its prevalence. Cryptorchidism, especially bilateral, is associated with impaired spermatogenesis and endocrine function and increases the risk of testicular cancer. There is an urgent need to identify factors that adversely affect testicular development and optimize treatment. CONCLUSION: Cryptorchidism may reflect a primary testicular maldevelopment with long-term consequences.

Laparoscopy for impalpable testis: classification-based management.

BACKGROUND: The undescended testis represents one of the most common disorders of childhood. The authors evaluated the safety and efficacy of laparoscopy for the abdominal testis and present a classification of the laparoscopic diagnostic findings to facilitate decision making. METHODS: Between 2000 and 2005, 95 patients (22 bilateral and 73 unilateral testes, for a total of 117 impalpable testes) with a mean age of 5 years underwent laparoscopy. The testis was managed according to a special classification of the diagnostic findings. Testicular position, size, and viability according to technetium-99m ((99m)Tc) were assessed during the follow-up evaluation. RESULTS: The laparoscopic findings were classified into six types: type 0 (no testis or vanished testis proximal to the internal ring; 9 patients [7.5%]); type 1 (atrophic intracanalicular testis; 6 patients [5.4%], for whom no further intervention was administered); type 2 (testis at the internal ring with looping vas; 15 patients [14.5%], for whom laparoscopic orchiopexy was performed); type 3 (testis at the internal ring without looping of the vas; 29 patients [24.7%], for whom laparoscopic orchiopexy also was performed; type 4 (high abdominal testes; 49 patients [41.9%], with Staged Fowler-Stephens orchiopexy performed for 47 testes and laparoscopic orchidectomy for 2 testes; and type 5 (persistence of Müllerian duct structures [PMDS] or other abnormalities; 7 testes [6%]). After a mean follow-up period of 3 years, the laparoscopic orchiopexy testes were of good size and viable, but four testes (8.7%) were at the neck of the scrotum. The laparoscopically staged Fowler-Stephens orchiopexy group showed atrophy in two testes (4.3%), and all were in the bottom of the scrotum. CONCLUSIONS: Classification of the laparoscopic findings facilitates decision making. Laparoscopic orchiopexy is a natural extension of diagnostic laparoscopy for the intraabdominal testis at the internal ring or that seen peeping from it. Laparoscopically staged Fowler-Stephens orchiopexy is the procedure of choice for the high intraabdominal testis not amenable to the one-stage procedure.

Abnormalities of testicular descent.

Testicular descent occurs in two stages. The transabdominal phase (8-15 weeks) is controlled by enlargement of the caudal genito-inguinal ligament (gubernaculum) and regression of the cranial ligament. Insulin-like 3 from the Leydig cell appears to be the prime stimulator of gubernacular growth, augmented by Müllerian inhibiting substance/anti-Müllerian hormone. Testosterone causes regression of the cranial ligament. The inguinoscrotal phase (25-35 weeks) requires the migration of the gubernaculum from the groin to the scrotum; this migration is guided by the genito-femoral nerve releasing calcitonin gene-related peptide under the influence of androgen. The neonatal gonocyte transforms into a type A spermatogonium at 3-12 months of age, a step that is now known to be crucial for subsequent fertility, as the stem cells for spermatogenesis are created in this structure. This step is blocked in undescended testis and, hence, orchidopexy is currently recommended at 6-12 months of age. Congenital cryptorchidism is caused by the failure of gubernacular migration to the scrotum (1%-2%) but we now recognise that another 1%-2% of boys have acquired cryptorchidism, secondary to the failure of spermatic cord elongation with growth of the boy. These latter cases come to operation at 5-10 years of age. Surgery remains the mainstay of treatment, as hormonal therapy has not been proven to be effective, presumably because testicular descent is a complex anatomical mechanism.

Testicular descent and cryptorchidism: the state of the art in 2004.

The understanding of testicular descent has changed much in the 20 years since the authors' laboratory began studying the mechanism. The process is now known to occur in 2 steps with different anatomy and hormonal regulation but with many still unresolved controversies. Recent advances include the recognition of acquired cryptorchidism of critical early postnatal germ cell development and the recommendation for surgery at 6 months of age. The authors still await long-term outcome studies.

Retractile testes: an outcome analysis on 150 patients.

BACKGROUND/PURPOSE: Retractile testes are testicles that can be brought down into their normal position in the scrotum but then immediately retract upward and out of the scrotum. The purpose of this study is to provide data on the outcome of pediatric patients with retractile testes. METHODS: A retrospective analysis was conducted on prospectively collected data on the outcome of 150 consecutive patients with retractile testis examined and followed up by one pediatric surgeon from April 1982 to April 1999, inclusive. RESULTS: Age at presentation was 5.2 +/- 3.0 years, and follow-up duration was 3.8 +/- 3.0 years. The number of retractile testes was 205, right-sided for 58 patients (38.6%), left-sided for 37 (24.6%), and bilateral for 55 (36.7%). Family history of retractile testis was positive in 8 patients (5.3%). Thirty-four patients required surgery (22.7%); indication for surgery was given when retractile testes ascended and became cryptorchid or if testicular size decreased during follow-up. Orchidopexy was required more frequently (P <.001) in patients with an associated hernia (68.8% of cases) than in patients without hernias (9.2%). One patient with spontaneous testicular descent during follow-up had a testicular carcinoma. CONCLUSIONS: These findings suggest that the majority of patients (77.3%) with retractile testes have a spontaneously favorable evolution by 14 years of age and do not require surgical treatment. The authors report the first case of testicular carcinoma in a patient with retractile testis, and this indicates that these patients should be followed up even after testicular descent.

Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries.

BACKGROUND: Several investigators have shown striking differences in semen quality and testicular cancer rate between Denmark and Finland. Since maldescent of the testis is a shared risk factor for these conditions we undertook a joint prospective study for the prevalence of congenital cryptorchidism. METHODS: 1068 Danish (1997-2001) and 1494 Finnish boys (1997-99) were consecutively recruited prenatally. We also established prevalence data for all newborns at Turku University Central Hospital, Finland (1997-99, n=5798). Testicular position was assessed by a standardised technique. All subtypes of congenital cryptorchidism were included, but retractile testes were considered normal. FINDINGS: Prevalence of cryptorchidism at birth was 9.0% (95% CI 7.3-10.8) in Denmark and 2.4% (1.7-3.3) in Finland. At 3 months of age, prevalence rates were 1.9% (1.2-3.0) and 1.0% (0.5-1.7), respectively. Significant geographic differences were still present after adjustment for confounding factors (birthweight, gestational age, being small for gestational age, maternal age, parity, mode of delivery); odds ratio (Denmark vs Finland) was 4.4 (2.9-6.7, p<0.0001) at birth and 2.2 (1.0-4.5, p=0.039) at three months. The rate in Denmark was significantly higher than that reported 40 years ago. INTERPRETATION: Our findings of increasing and much higher prevalence of congenital cryptorchidism in Denmark than in Finland contribute evidence to the pattern of high frequency of reproductive problems such as testicular cancer and impaired semen quality in Danish men. Although genetic factors could account for the geographic difference, the increase in reproductive health problems in Denmark is more likely explained by environmental factors, including endocrine disrupters and lifestyle.