Risk of testicular cancer in cohort of boys with cryptorchidism.

OBJECTIVE: To determine the risk of testicular cancer in relation to undescended testis and its treatment based on recorded details of the maldescent, treatment, and biopsy from case notes. DESIGN: Cohort study. SETTING: Hospital for Sick Children, Great Ormond Street, London. SUBJECTS: 1075 boys with cryptorchidism treated by orchidopexy or hormones at the hospital during 1951-64. MAIN OUTCOME MEASURES: Relative risk of testicular cancer in the cohort compared with men in the general population. RESULTS: 12 testicular cancers occurred in 11 of the patients during follow up to mid-1990 (relative risk of cancer in males with cryptorchidism = 7.5 (95% confidence interval 3.9 to 12.8)). The relative risk fell significantly beyond 15 years after orchidopexy but did not decrease with younger age at orchidopexy. Risk was significantly raised in testes that had had biopsy samples removed during orchidopexy (relative risk = 66.7 (23.9 to 143.3) compared with a testis in a man in the general population) and was significantly greater in these testes than in undescended testes that had not had biopsy samples taken at orchidopexy (6.7 (2.7 to 13.5)). No reasons for biopsy or distinguishing clinical aspects of the testes that had had biopsy samples taken and later developed malignancies were evident in the case notes. No histological abnormalities were evident at initial biopsy except in one testis that had features of dysgenesis. CONCLUSIONS: Biopsy seems to be a stronger risk factor for testicular cancer than any factor previously identified. The trauma of open biopsy may contribute substantially to risk of malignancy or the testes may have been selected for biopsy on the basis of clinical factors predictive of malignancy but not mentioned in the case notes.     

Intérêt de l’abaissement du testicule non descendu chez l’adulte. Etude à propos de 259 patients

Introduction

Undescended testis is a frequent congenital disease, more often diagnosed and treated during childhood. However, due to ignorance or negligence, this disease can be seen even after puberty, when it raises a therapeutic problem: is orchidopexy still useful? This study was designed to evaluate the outcome of orchidopexy at adulthood in terms of improvement of fertility and prevention of malignant degeneration.

Material and methods

Retrospective study performed over a 23-year period (1983–2005). We have found 259 patients with undescended testis diagnosed and treated after the age of 18 years.

Results

The mean age of patients was 24 years (range: 18–63). In the majority of cases, undescended testis was diagnosed at a systemic medical examination in 199 patients (77% of cases), and in a context of infertility in 33 patients, testicular malignancy in 8 patients, testicular torsion in 2 patients and, in 17 cases, undescended testis had been known since birth but was neglected by the parents. Undescended testis was unilateral in 209 cases and bilateral in 50 cases. Out of 37 couples, only 4 gave birth to children (10.8% paternity rate). Sperm analysis was abnormal in all infertile patients. All patients were treated by orchidopexy, except for 36 patients in whom orchidectomy was performed due to testicular atrophy (27 cases), malignancy (8 cases) or necrosis (1 case). Biopsy of the intrascrotal testis was performed in 3 patients with unilateral cryptorchidism. Histological examination was normal in two cases and abnormal in one case. The long-term outcome was characterized by:

1. Testicular atrophy in 6 patients (2.7% of cases).
2. Progression to malignancy in 3 patients (1.3% of cases).
3. Improvement of sperm parameters in 16 of 33 infertile patients (48.5%); 4 patients fathered children after treatment.

Conclusion

Orchidopexy at adulthood can lead to improvement of infertility. It can also decrease the incidence of malignancy and facilitate clinical examination looking for possible malignancy. However, the best treatment remains preventive, based on early diagnosis and orchidopexy.     

Azoospermia and cryptorchidism in a male with a de novo reciprocal t(Y;16) translocation

An apparently balanced reciprocal translocation between the long arm of the Y chromosome and the long arm of the chromosome 16 t(Y;16)(q12;q13) is described in an infertile man with azoospermia and cryptorchidism. The patient was phenotypically normal and had bilateral inguinal hernia repair with orchidopexy at the age of 8 years. Histological examination of testicular biopsies revealed maturation arrest. Y/autosome translocations in the literature are relatively rare and mostly associated with infertility. To our knowledge, this is the sixth report about the reciprocal t(Y;16) translocation in the literature but the first presenting with cryptorchidism.     

Aspects cliniques, biologiques et thérapeutiques de la cryptorchidie diagnostiquée à l’âge adulte: analyse d’une série de 69 cas

Objective

To report the clinical, biological and therapeutic features of adult cryptorchidism and to determine whether orchidopexy at adulthood may improve male fertility.

Material and methods

We retrospectively studied the clinical pattern, biological and therapeutic features of 69 men aged of more than 18 years admitted for cryptorchidism at the urological department of Aristide-Le-Dantec teaching hospital between January 1999 and December 2007.

Results

The mean age of our patients was 31.04 ± 8.4 years. In the majority of cases, cryptorchidism was diagnosed in a context of infertility (38 cases), scrotum vacancy (21 cases) and testicular cancer (six cases). Cryptorchidism was unilateral in 69.5% and bilateral in 30.4% of cases. Semen analyses were done for 60 patients and showed azoospermia in 46.6%, oligozoospermia in 38.3% and a normal sperm count in 15% of cases. In all bilateral cryptorchidism cases, semen analyses showed azoospermia. At surgery, the undescended testis was found in 66 cases (95.6%) and orchidopexy was the most done surgical procedure. Seven patients (without testicular cancer) underwent unilateral orchiectomy and histology of specimens showed sertoli-cell-only syndrome with no spermatogenesis in all cases. The histological type of testicular cancer was seminoma (three cases) and embryonic carcinoma (three cases). In azoospermic men (28 cases) no induction of spermatogenesis was achieved after orchidopexy. In infertile patients, the improvement of sperm count was seen in three patients with unilateral cryptorchidism. Three patients with unilateral crytorchidism achieved pregnancy (pregnancy rate of 7.8%).

Conclusion

Orchidopexy for adult cryptorcidism had little impact in male fertility. Because of the risk of testicular cancer, orchidectomy was recommended as treatment of unilateral cryptorchidism. But with the recent development of TESE, orchidopexy appears as a reasonable treatment of adult cryptorchidism.     

Ectopie testiculaire croisée: à propos d’un cas

Crossed testicular ectopia, also called transverse testicular ectopia, is an uncommon congenital anomaly in which both testes migrate through a single inguinal canal toward the same hemiscrotum. More than 100 cases have been reported in the literature. This rare syndrome is commonly associated with abnormalities of genitourinary development, especially inguinal hernia and defective Müllerian regression. A conservative approach is recommended, now performed via laparoscopy. Long-term follow-up is required for assessment of fertility and early detection of testicular malignancy. The authors report a new case of crossed testicular ectopia in a 4-year-old boy who presented with right inguinal hernia and impalpable left testis.     

Incidence of disease after vasectomy: a record linkage retrospective cohort study.

OBJECTIVE--To determine whether vasectomy is associated with an increased risk of several diseases, and in particular testicular cancer, after operation. DESIGN--Retrospective cohort study using linked medical record abstracts. SETTING--Six health districts in Oxford region. SUBJECTS--13,246 men aged 25-49 years who had undergone vasectomy between 1970 and 1986, and 22,196 comparison subjects who had been admitted during the same period for one of three specified elective operations, appendicitis, or injuries. MAIN OUTCOME MEASURES--Hospital admission and death after vasectomy or comparison event. RESULTS--The mean durations of follow up were 6.6 years for men with a vasectomy and 7.5 years for men with a comparison condition. The relative risk of cancer of the testis in the vasectomy cohort (4 cases) compared with that in the other cohorts (17 cases) was 0.46 (95% confidence interval 0.1 to 1.4), that of cancer of the prostate (1 v 5 cases) 0.44 (0.1 to 4.0), and that of myocardial infarction (97 v 226 cases) 1.00 (0.8 to 1.3). There was no evidence of an increase associated with vasectomy in the incidence of a range of other diseases. CONCLUSIONS--Vasectomy was not associated with an increased risk of testicular cancer or the other diseases studied. With respect to prostatic cancer, while we found no cause for concern, longer periods of observation on large numbers of men are required.     

Sarco(endo)plasmic reticulum and plasmalemmal Ca(2+)-ATPase activities in cremaster muscles and sacs differ according to the associated inguinal pathology

Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and plasmalemmal Ca(2+)-ATPase (PMCA) activities in cremaster muscles and sacs, which have been subjected to different autonomic tonuses, were determined and compared. Samples of cremaster muscles and sacs associated with male or female inguinal hernia, hydrocele or undescended testis were obtained from children during operations and activities of SERCA and PMCA were determined. While highest SERCA and PMCA activities were encountered among cremaster muscles and sacs associated with undescended testis, least activities were encountered among structures associated with hydrocele. The alterations in SERCA and PMCA activities in cremaster muscles associated with undescended testis appear to reflect the attempts at maintaining the levels of cytosolic calcium. Despite similar total calcium contents, lower SERCA and PMCA activities were found in sacs associated with hydrocele compared to those associated with undescended testis suggest a difference among the levels of cytosolic calcium.     

Cryptorchidie: influence sur la fertilité de l’âge au moment de l’orchidopexie, du siège et de la taille du testicule et de l’existence d’anomalies épididymaires

Despite surgical treatment, cryptorchidism is the most common cause of infertility. Through a literature review, the authors report current data on the influence of age at the time of orchidopexy, testicular size, the position of the testis, and the existence of epididymal anomalies on fertility.     

Abus et danger du traitement au citrate de clomiphène dans l’infertilité masculine

Obiective

To describe a case of seminoma occurring in a patient with a past history of cryptorchidism, infertility and clomiphene citrate (CC) treatment. To review the literature of seminoma in association with these risk factors.

Case report

A 33 year old man developed typical seminoma in the right testis. A bilateral cryptorchidism was lately diagnosed and treated by orchidopexy at the age of 17. Primary infertility due to oligoasthenospermia was diagnosed at the age of 29. Treatment was initiated with CC at the dose of 25 mG/day. Semen quality improved gradually. After failure of various assisted reproductive techniques, a spontaneous pregnancy was achieved and a healthy baby delivered. Shortly after delivery the seminoma was diagnosed, after a totla of three years of treatment. Six cases of testicular tumors have been reported in the literature in which patients had been pretreated with fertility drugs for various priods of time before tumors was diagnosed. Cryptorchidism is a well-known risk factor for testicular malignancy, as is the infertil state. Clomiphene citrate may promote malignant transformation by activation of estrogen receptors, by raising gonadotropin and/or testosterone concentrations, or by other mechanisms.

Conclusion

Clomiphene citrate may have a previously unappreciated malignancy-promoting effect in infertile men, especially those with other risk factors. Clinicians treating similar patients should take this into account and the literature monitored for other associated cases.     

Abnormal germ cell development in cryptorchidism.

BACKGROUND: Previous studies suggest that two fundamental, probably androgen-dependent, steps in maturation of germ cells normally occur in the prepubertal testis: the disappearance of gonocytes (the fetal stem cell pool) and the appearance of adult dark spermatogonia (the adult stem cell pool) at 2-3 months of age and the appearance of primary spermatocytes (the onset of meiosis) at 4-5 years. Previous studies of small series of cryptorchid boys suggest that both steps are defective in undescended testes and to a lesser degree in descended testes contralateral to unilaterally undescended testes. The purpose of this study is to confirm the previous findings of defective germ cell maturation in a large series of boys with unilateral undescended testes. PATIENTS: Seven hundred and sixty-seven boys with unilateral cryptorchidism who had orchidopexy and bilateral testicular biopsies between birth and 9 years of age were studied. MATERIALS AND METHODS: Total and differential germ cell counts were performed on semithin histologic sections of the biopsies. The results from the undescended and contralateral descended testes were compared using the Wilcoxon signed-rank test and the Wilcoxon-Whitney-Mann U test. RESULTS: Gonocytes failed to disappear and adult dark spermatogonia failed to appear in undescended testes under 1 year of age indicating a defect in the first step in maturation at 2-3 months resulting in failure to establish an adequate adult stem cell pool. Primary spermatocytes failed to appear in undescended testes and appeared in only 19% of contralateral descended testes at 4-5 years of age indicating a defect in the onset of meiosis. CONCLUSION: Unilaterally undescended testes fail to establish an adequate adult stem cell pool which normally occurs at 2-3 months of age and fail to establish adequate meiosis which normally occurs at 4-5 years of age. Similar but less severe changes are seen in the contralateral descended testes. Defects in the two pubertal steps in germ cell maturation are associated with reduced total germ cell counts.     

Risk of testicular cancer after vasectomy: cohort study of over 73,000 men.

OBJECTIVE--To confirm or refute reports that vasectomy may increase the risk of cancers of the testis and prostate. DESIGN--Computerised record linkage study of cohort of men with vasectomy and comparison of cancer rates with those in the whole Danish population; manual check of all records of patients with testicular and prostate cancer diagnosed within the first year of follow up. SETTING--Denmark 1977-89. SUBJECTS--Cohort of 73,917 men identified in hospital discharge and pathology registers as having had a vasectomy for any reason during 1977-89. MAIN OUTCOME MEASURES--Observed incidences of testicular, prostate, and other cancers up to the end of 1989. RESULTS--The overall pattern of cancer incidence in the study cohort was similar to that expected nationally. No increased incidence in testicular cancer was observed (70 cases; standardised morbidity ratio 1.01 (95% confidence interval 0.79 to 1.28)). The incidence during the first year of follow up was also close to that expected (nine cases; standardised morbidity ratio 0.80 (0.36 to 1.51)). The incidence of prostate cancer was not increased (165 cases; standardised morbidity ratio 0.98 (0.84 to 1.14)). CONCLUSIONS--The incidence of testicular cancer in men with vasectomy is no higher than in other men. Vasectomy does not cause testicular cancer and does not accelerate the growth or diagnosis of pre-existing testicular neoplasms. Data concerning a causal relation between vasectomy and prostate cancer were inconclusive.     

Absent spermatogenesis despite early bilateral orchidopexy in 17-ketoreductase deficiency

We describe a 26-year-old patient with 17-ketoreductase deficiency who was raised as a male from 8 months and whose left testis was brought down at the age of 2.5 years and the right testis at the age of 4. Despite the early orchidopexy and not significantly decreased serum testosterone, he was sterile, and biopsy of the testes at the age of 26 revealed absence of spermatogenesis. This case indicates that the absence of spermatogonia in previously reported patients whose testes remained undescended until a later age could not be attributed solely to cryptorchidism. We suggest that decreased intratesticular testosterone due to steroidogenic defect in the developing testis mainly contributes to the arrest of spermatogenesis.     

The long-term effect of mesh bioprosthesis in inguinal hernia repair on testicular nitric oxide metabolism and apoptosis in rat testis

Polypropylene mesh is the most widely used material in inguinal hernia repair. Although polypropylene mesh is known as an inert material, it is experimentally proven that mesh generates a chronic inflammatory tissue reaction. The aim of the present study was to investigate the long-term effects of polypropylene mesh material used in inguinal hernia operations on testicular function, testicular nitric oxide (NO) metabolism and germ cell-specific apoptosis in rats. The study comprised 40 male rats that were randomly allocated into two groups. In group 1, the left spermatic cord was elevated and a 0.5 x 1 cm polypropylene mesh was placed behind the left inguinal spermatic cord and group 2 consisted of the sham-operated controls. Blood samples were taken at 6 months preoperatively and postoperatively after to assess luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels for hormonal evaluation. Testicular NO was evaluated by the Griess method, apoptosis by a TUNEL method and inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) expressions by immunohistochemical staining. Mild (+) eNOS expression was observed in all specimens. Mild (+) iNOS expression was only detected in ipsilateral testis of the mesh-implanted study group. Apoptotic cells were not detected in any samples. We are of the opinion that long-term polypropylene mesh implantation has no effect on testicular hormonal function and only a limited effect on nitric oxide levels and this effect is not sufficient to cause apoptosis in testis that could lead to infertility. It seems that mesh implantation is a reliable method in inguinal hernia repair; however, further work is required by more sensitive methods to fully elucidate the potential testicular damage.     

The treatment of cryptorchidism

Medical opinion is quite confused about the age for and the method of treatment of the undescended organ. Histologic studies reveal that the spermatogenic cells of the undescended testis show definite injury by the age of four or five years. It therefore seems necessary to see that the testis is in the bottom of the scrotum before that age. Chorionic gonadotropins or testosterone should be tried first. If medical treatment fails, orchidopexy should be done without delay.     

Maldescendus testis

Maldescendus testis is a common congenital abnormality occurring in 2-5% of full-term boys at birth in the Western countries. By 3 months of age, the incidence rate spontaneously reduces to 1-2% in this group. The etiology of the disorder is not known, but normal hypothalamo-pituitary-gonadal axis is usually a prerequisite for normal descent of the testes. Abnormal sexual differentiation is associated with maldescent. However, the majority of boys with maldescended testes show no endocrine abnormalities after birth. Several defects in developmental genes, such as homeobox genes and Insl3, have been described to cause cryptorchidism in mice, and disturbances in the regulation of these genes or their mutations may explain etiology of a large part of human testicular maldescent in the future. Increased degeneration of germ cells can be observed in undescended testes after the first year, and therefore early treatment is recommended. Surgical treatment is the most effective and reliable method to bring testes into the scrotum, but hormone treatment with either hCG or GnRH analogues can be considered, particularly in cases where testes can be palpated in high scrotal position. The efficacy of hormone treatment is less than 20% and depends on the initial location of the testis. Nonpalpable testes rarely descend with hormone treatment. Both surgery and hormone treatment can have untoward effects. Treatment with hCG has been associated with an inflammation-like reaction in the testes and an increased rate of apoptosis of germ cells leading to a reduced adult size of the testes. Vascular complications can occur during surgery, particularly in staged orchidopexies. Men with a history of undescended testis have an increased risk of testicular cancer. Impaired fertility is another long-term risk associated to maldescended testes. Fertility potential may be improved by early treatment. Although our knowledge on cryptorchidism has increased considerably during the last decades, many questions remain to be answered: Is the incidence rate increasing? What is causing maldescent? Do hormones have any role in the treatment?     

Le cancer à cellules germinales du testicule, élément constitutif du Syndrome de Dysgénésie Testiculaire: rôle des facteurs environnementaux et de la susceptibilité génétique

The incidence of testicular germ cell cancer has been increasing over recent decades in many countries of the world. Many studies over recent years have reported adverse trends in other aspects of male reproductive health, such as high and possibly increasing frequencies of undescended testis and hypospadias, declining semen quality, and an apparently growing demand for assisted reproduction due to male infertility. This article summarises the available evidence supporting a new concept that these male reproductive abnormalities may be signs of a single underlying entity: testicular dysgenesis syndrome (TDS). This syndrome, caused by nonspecific delays and aberrations of early testicular development, may be increasingly common because of deteriorating environmental and life-style factors that impair gonadal development. Geographical and ethnic differences in the incidence of various forms of TDS could be explained either by differences in exposure to adverse factors or by differences in genetic susceptibility to these factors.     

Cryptorchidie de l’enfant: syndrome ou symptôme?

Cryptorchidism is a frequent disease of children whose management remains controversial. Clinical diagnosis of cryptorchidism must assess the permanent location of the testis outside scrotum and must look for associated malformations. Endocrine investigation should include an evaluation of basal plasma testosterone and after an HCG stimulation test. Development of cryptorchidism is due to anatomical, histological and endocrine abnormalities. Medical treatment should be realised as early as possible. If testis descent does not occur, orchidopexy must be performed. Long-term effects of cryptorchidism are defined by infertility and testis cancer.     

Cancer risk in mothers of men operated for undescended testis

Background

Undescended testis, or cryptorchidism, occurs in 2–5% of boys born at term, and by 12 months of age about 1% of all boys have manifest cryptorchidism. Several hormonal substances control this process and disruption of the foetal sex-hormones balance is a potential cause of undescended testis, however, to a great extent the aetiology of cryptorchidism is unclear.

Methodology

To study risk factors involved in the aetiology of undescended testis, we assessed cancer risk in 15,885 mothers of men operated for undescended testis in Sweden. Women were followed-up for a median period of 23 years during which 811 first primary malignancies occurred. Their cancer incidence was compared with that in the general population estimating standardized incidence ratio (SIR) and corresponding 95% confidence interval (CI).

Principal Findings

The overall cancer risk experienced by the mothers of cryptorchid men did not differ significantly from that of the general population (SIR = 0.94; 95% C.I. = 0.88–1.01). Specifically, there was a reduction in ovarian cancer risk (SIR = 0.72; 95% C.I. = 0.51–0.99), while the risk of lung (SIR = 1.38 95% C.I. 1.03–1.81) and biliary tract/liver cancer (SIR: 1.76, 95% CI: 1.03–2.82) were increased.

Conclusions

Although we cannot rule out the role of chance, our data suggest a positive association between undescended testis and maternal lung cancer and a negative association with ovarian cancer, where the first may be partly attributable to smoking and the second to an altered hormonal milieu during pregnancy and thus both exposures may be risk factors for cryptorchidism.     

Infertilité et hypogonadisme primaire acquis après herniorraphie inguinale bilatérale

Primary acquired hypogonadism due to ischemic testicular atrophy is infrequent among the causes of male infertility. The authors report a case of a 35-year-old man presenting with infertility secondary to bilateral inguinal hernia repair using Mac-Vay technique. The patient had atrophy of both testes, and endocrinal analyses were typical: high LH and FSH levels but low testosterone level. The high rate of testicular atrophy in classical inguinal repair compared with those of tension-free techniques is recalled. The current case has to be added to the rare cases of male infertility.