Cryptorchidism and pesticides: Is there a connection?

INTRODUCTION: The aim of our study was to compare the level of the most common organophosphate metabolite, dimethyl phosphate, in urine of women giving birth to both boys with cryptorchidism (study group), and healthy boys (control group), as well as to compare the level of dimethyl phosphate in our population with the results obtained in other populations. MATERIAL AND METHODS: After the ethical approval we included thirty women in both study and control groups. All newborns were born between 38 and 42weeks' gestation. Urine samples were taken on 3rd postpartal day. Gas chromatography with flame photometric detection was used to analyze dimethyl phosphate in urine following the method of Wu et al. Statistical analysis was done using Mann-Whitney test to compare the results in the two groups. RESULTS: Geometric mean of dimethyl phosphate in the study group was 7.18±8.26µg/L and the creatinine-corrected level was 5.63±5.95µg/L, and in the control group, the values are 7.98±6.75µg/L and 6.15±7.01µg/L, respectively. There was not a statistically significant difference in levels of dimethyl phosphate between these two groups (p=0.72786). Dimethyl phosphate levels obtained in similar studies are: 14.4µg/L in Israel, 3.7µg/L in Palestine, 10.3µg/L in Jerusalem, 1.60µg/L in Caribbean islands and 2.60µg/L in Canada. CONCLUSIONS: Pregnant women in our country are exposed to organophosphate pesticides, but a correlation between the exposure to organophosphate pesticides and cryptorchidism was not found. LEVEL OF EVIDENCE: I. TYPE OF STUDY: Prognostic study, prospective study.

Regional differences in maturation of germ cells of cryptorchid testes: role of environment.

OBJECTIVE: To investigate differences in maturation of germ cells in cryptorchid testes in three different regions. PATIENTS AND METHODS: A total of 103 consecutive patients were operated for unilateral undescended testis in Vojvodina, from March 2006 until September 2007, and had a testicular biopsy performed. Germ cells were counted, and the presence of Ad spermatogonia was noted. Biopsies were compared to biopsies of similar patients from two different regions: Philadelphia, USA (130), and Liestal, Switzerland (55 patients). RESULTS: In Vojvodina, 84.5% of patients had Sertoli cells only, or some spermatogonia, but no Ad spermatogonia, and 15.5% had Ad spermatogonia. In Philadelphia, 59.3% of patients had poor testicular histology, and 40.7% had Ad spermatogonia. In Liestal, 61.8% of patients had no, or some, spermatogonia, but no Ad spermatogonia, and 38.2% had Ad spermatogonia. There was a difference (p = 0.000025) between the patients with normal testicular histology from Philadelphia and those from Vojvodina, as well as between the patients from Vojvodina and Liestal (p = 0.0027). CONCLUSION: The reduction in the number of germ cells in patients with cryptorchidism from Vojvodina is more pronounced than patients from either Switzerland or USA. This is a unique observation, since such a study has not been published yet.

Development of Sertoli cells during mini-puberty in normal and cryptorchid testes.

BACKGROUND: Only a few studies have dealt with quantitative changes of Sertoli cells during human development, and the results of these studies are conflicting. Our hypothesis is that the development of Sertoli cells during mini-puberty follows the same pattern as germ cells. METHODS: We examined the biopsies of cryptorchid and normal testes from patients aged 1-12 months. Fifty complete, rounded tubules were examined and the number of Sertoli cells per tubule was determined. We compared the numbers in cryptorchid and normal testes, as well as the average number of Sertoli cells in each age group separately. RESULTS: The number of Sertoli cells per tubule in the cryptorchid testes of patients aged 1-4 months was 22.38 +/- 1.01 compared to cryptorchid patients aged 5-12 months (23.20 +/- 1.41). This number in patients with spontaneously descended testes aged 1-4 months was 23.53 +/- 1.98, while this number in the same group of patients aged 5-12 months was 26.20 +/- 1.40. The difference between the two age groups was statistically significant (p < 0.001, two-tailed test). CONCLUSIONS: Our results suggest the number of Sertoli cells increases with the hormonal surge. In cryptorchid patients, the number of Sertoli cells is diminished compared to the normal testis.

Relationship between adult dark spermatogonia and secretory capacity of Leydig cells in cryptorchidism.

OBJECTIVE: To examine whether hormonal therapy before orchidopexy affects the histology of the testis and to assess the responsiveness of the Leydig cells, as it has been shown that although basal plasma testosterone levels are within the 'normal' range in cryptorchid boys there is an insufficient increase of testosterone after a human chorionic gonadotrophin (hCG) stimulation in approximately 30% of cryptorchid boys. PATIENTS AND METHODS: In all, 55 boys (aged 1-7 years) with a unilateral undescended testis were included in the study and divided into two groups. Group I (32 boys) received hormonal therapy before orchidopexy; 17 boys received a long-acting LHRH analogue (buserelin) administered as a nasal spray in doses of 20 microg/day for 28 days, followed by 1500 IU hCG intramuscularly (i.m.) once a week for 3 weeks, and the remaining 15 received 1500 IU hCG i.m. once a week for 3 weeks. Group II (33 boys) had orchidopexy alone. During orchidopexy biopsies were taken from the undescended and contralateral descended testes of the boys in both groups for histological analyses. Variations in the number of adult dark (Ad) spermatogonia per tubule (Ad/T) were assessed and testosterone levels were measured during the course of the hormonal therapy (before treatment, 14 days after initiation of buserelin administration, 24 h after each hCG injection, and 3 months after cessation of therapy). RESULTS: In group I, 17 boys (53%) had a 'normal' Ad/T after hormonal treatment vs only six (18%) in group II after orchidopexy alone (P = 0.019). In the hormonally treated boys (group I) we compared the testosterone values 24 h after the second injection of hCG (when the response was most pronounced). Those with a normal Ad/T had a mean (sd) testosterone level of 199.5 (97.6) ng/dL vs 99.6 (85) ng/dL in those with an inadequate Ad/T response to hormonal therapy (P < 0.003). CONCLUSION: We have confirmed that there are two subgroups of cryptorchid boys. Patients with a sufficient Leydig cell secretory capacity will have normal testicular histology and Ad spermatogonia count after hormonal treatment. While those with a suboptimal Leydig cell capacity will have a low Ad spermatogonia count and consequently poor prognosis for future fertility, despite successful surgery. As to whether different types and durations of the hormonal therapy in patients with impaired Leydig cell response could lead to improved testicular histology and consequently improved prognosis for future fertility, remains to be answered.

The importance of mini-puberty for fertility in cryptorchidism.

PURPOSE: Mini-puberty is the hormonal surge of gonadotropins and testosterone which occurs in early infancy. It induces the development and transformation of gonocytes into Ad spermatogonia, which is impaired in many cryptorchid testes. We examine the role of testosterone in the transformation and development of Ad spermatogonia. MATERIALS AND METHODS: A total of 32 patients 1 to 7 years old were treated with human chorionic gonadotropin (HCG) to achieve epididymo-testicular descent before orchiopexy (group 1), and 33 patients underwent orchiopexy without previous hormonal treatment (group 2). A testicular biopsy was obtained during surgery from all the patients. The number of Ad spermatogonia per tubular cross section (Ad/tbx) was assessed and compared between the 2 groups. The number of Ad spermatogonia per tubular cross section in group 1 was also correlated with the post-stimulatory testosterone plasma values. RESULTS: In group 1, 17 patients had greater than 0.1 Ad/tbx, and the remaining patients had 0.1 or less Ad/tbx. In group 2, 6 patients had greater than 0.1 Ad/tbx. Of the boys with cryptorchidism 35% responded inadequately to HCG stimulation, while 10% did not respond. Those patients with suboptimal Leydig cell capacity (and an inadequate response to HCG stimulation) had a defective Ad spermatogonia differentiation of 0.1 or less. CONCLUSIONS: Boys with cryptorchidism with an insufficient testosterone surge after HCG risk infertility despite early and successful surgery. The testicular biopsy assists in identifying those who might benefit from hormonal treatment following successful orchiopexy.

[Ureteral triplication--a case report].

INTRODUCTION: Of all children born with congenital anomalies, 30-40% have urogenital abnormalities. Most of them are asymptomatic, but if any symptoms occur, they are usually symptoms of urinary infections. CASE REPORT: A four-year old girl was admitted because of recurrent urinary infections and in order to perform a thorough clinical examination. Clinical examination showed an asymmetrical gluteus and presence of a fibroma in the same region. Detailed radiologic examinations (ultrasonography, plain X-ray, excretory urography, voiding urethrocystography) revealed a triplicate ureter on the right side with a vesicoureteral reflux of the fifth grade on the same side. Intraoperatively, type III ureteric triplication according to Smith's classification was established. Ureteral remodeling and reimplantation was done. The postoperative course was good, and follow-up voiding urethrocystography showed absence of reflux. DISCUSSION: Ureteral triplication is a consequence of either development of three buds on the mesonephric duct, or development of two buds, one of which further divided into two parts. Most common anomalies associated with ureteral triplication are: ureteral duplication on the other side (37%), ectopy of the ureteric orifice (28%) and kidney dysplasia (8%). Vesicoureteral reflux is very common on affected or on both sides. Symptomatology is the same as in ureteral duplication--dominated by signs of urinary infections. CONCLUSION: Diagnosis of ureteral duplication requires detailed imaging. Treatment of symptomatic abnormalities should be individual, regardless of the applied treatment (conservative or operative).

[Urogenital abnormalities and atresia of the gastrointestinal tract].

INTRODUCTION: The goal of the study was to ivestigate the frequency of urogenital congenital abnormalities among atresias of the digestive system and analyze fetal maldevelopment. The study also deals with gastrointestinal and urogenital embryology. MATERIAL AND METHODS: This retrospektive study analyzed the clinical status of 55 newborns admitted to the Pediatric Surgery Clinic in Novi Sad due to atresia of the gastrointestinal tract during 1995-2003. All atresias were classified at primordial gut levels (foregut, midgut and hindgut). The incidence of associated abnormalities, especially urogenital, was analyzed. Diagnostic procedures included standard methods: clinical investigation, ultrasound, native and contrast medium radiography, etc. RESULTS: Results showed that urogenital anomalies were present in 21 (38.18%) newborns with gastrointestinal atresia. Foregut atresia was diagnosed in 14 newborns and it was associated with urogenital congenital anomalies in 9 (64.28%) newborns. Midgut atresias were found in 15 patients and in 4 (22.22/%) they were associated with urogenital anomalies. Hindgut atresias were established in 23 and in 8 (34. 78%) cases they were associated with urogenital anomalies. DISCUSSION AND CONCLUSIONS: It was confirmed that foregut atresias ara commonly accompanied by associated abnormalities. That is why the fourth gestational week is important when both gastrointestinal and urogenital systems are developed. When midgut differentiates into its own derivates, the frequency of congenital anomalies decreases for a short period, and then increases again during foregut development (seventh and eighth gestational weeks). There were no information on environmental teratogenic factors in maternal history. These abnormalities may be explained by complex urorectal development and separation of two systems.

[Possibilities of endoscopic treatment of primary vesicoureteral reflux]. / Mogucnosti endoskopske korekcije primarnog vezikoureteralnog refluksa.

INTRODUCTION: Vesicoureteral reflux, urinary infection and pyelonephritic scarring represent a well known triad in pediatric practice that may lead to severe scarring of kidneys, and development of so called reflux nephropathy. Apart from standard therapeutic options (conservative treatment and surgical therapy), endoscopic correction of refluxing vesicoureteral junction has been introduced into clinical practice. MATERIAL AND METHODS: This study included endoscopically treated patients with primary vesicoureteral reflux over a 9-year period, as well as certain clinical parameters. RESULTS: Endoscopic correction of primary vesicoureteral reflux with teflon paste has been successful in up to 93.5% of patients. After one application vesicoureteral reflux disappeared in 58.8% of cases. After two applications 86.0% of ureters were cured, whereas the third application had no further effect on existing reflux. Improvement with spontaneous regression of reflux was established in 7.5% of treated ureters. DISCUSSION: Endoscopic correction should be performed in all patients with third grade vesicoureteral reflux, and in selected patients with second and fourth grade reflux. First grade reflux should be treated conservatively, and fifth grade reflux should be treated surgically. CONCLUSION: Endoscopic treatment of primary vesicoureteral reflux is an easy, simple, fast and safe procedure that prevents regurgitation of urine from bladder to upper parts of the urinary system in most of cases.

[Osteosynthesis with Kirschner pin fixation in treatment of fractures with dislocation of the lateral condyle of the humerus in a pediatric population]. / Osteosinteza kirsnerovim iglama u lecenju preloma lateralnog kondila humerusa sa disokacijom ulomka u decjem uzrastu.

INTRODUCTION: Fractures of lateral condyle represent 17% of all pediatric fractures of the distal humerus, and in current pediatric orthopedics there is still no agreement regarding optimal treatment modalities. We presented a treatment protocol for pediatric dislocated fractures of the lateral condyle of the humerus used at the Pediatric Surgery Clinic in Novi Sad. MATERIAL AND METHODS: Over the study period (1991-2000) a total of 48 patients with dislocated fractures of the lateral condyle of the humerus were hospitalized at the Pediatric Surgery Clinic. Orthopedic reduction and percutaneous pin fixation under radiological supervision was done in 15 patients, while 33 patients needed surgical reduction and pin fixation. RESULTS: Satisfactory results were obtained in 42 patients (91.3%), out of which 29 patients (63.1%) presented with excellent results. Good results were obtained in 8 patients (17.4%), and fair results in 5 patients (10.8%). Unsatisfactory results were present in 4 patients (8.7%). Two patients were lost to follow-up. DISCUSSION: Dislocation fractures of the lateral condyle represent high risk for development of complications. Adequate diagnosis and treatment represent basic conditions for successful postinterventional result. Orthopedic reduction with percutaneous pin fixation is recommended for fractures that may be anatomically reduced. In cases of unsatisfactory results of reduction, as well as in cases with completely dislocated and rotated fragments, surgical reduction and pin fixation is necessary. CONCLUSIONS: Satisfactory results in 91.3% of cases, and long-term experience suggest that the recommended therapeutic option is adequate in treatment of dislocated fractures of the lateral condyle of the humerus in pediatric population.