Sakari Wikström

Germ cell apoptosis after treatment of cryptorchidism with human chorionic gonadotropin is associated with impaired reproductive function in the adult.

Cryptorchidism results in impaired fertility. Reduced numbers of testicular germ cells can be shown histologically during the first years of life. The process causing germ cell loss in cryptorchid prepubertal boys is unknown, but it could be the result of a form of programmed cell death known as apoptosis. 25 adult men with a history of surgically treated cryptorchidism were studied, 15 of whom had received an unsuccessful human chorionic gonadotropin (hCG) therapy before orchidopexy. Apoptotic DNA fragmentation was assayed in testis biopsies taken during orchidopexy by end-labeling, both in extracted DNA and histochemically in situ. Only a few scattered apoptotic spermatogonias were seen by end-labeling of biopsies from patients not treated with hCG, whereas more extensive labeling of spermatogonia was seen after hCG treatment. As estimated by gel electrophoresis, the amount of low molecular weight DNA was 4.3-fold higher in the hCG-treated group when compared with the level in scrotal testis of non-hCG-treated patients (P < 0.001). About 20 yr after the biopsy, the low molecular weight DNA fragmentation correlated negatively with the testis volume (r = -0.84; P < 0.001) and positively with serum FSH levels (r = 0.73; P < 0.001). Findings in the semen analysis were similar between the groups. Apoptotic loss of spermatogonia after hCG treatment of cryptorchidism warrants reevaluation of the safety of this treatment.

Early Treatment of Cryptorchidism, Semen Quality and Testicular Endocrinology

PURPOSE We evaluated the effect of patient age at treatment of cryptorchidism in relation to subsequent semen quality. MATERIALS AND METHODS Semen analyses and hormonal evaluations were performed in 51 men who were treated for cryptorchidism at ages 10 months to 12 years. RESULTS Sperm concentration was normal in 90% of the patients with unilateral and 50% with bilateral cryptorchidism. No patient treated before age 4 years had severe sperm defects. Elevated follicle-stimulating hormone levels indicated severe testicular damage. CONCLUSIONS Fertility is better in patients with bilateral cryptorchidism if treated before age 4 years. Age at treatment did not have a significant effect on semen quality in patients with unilateral cryptorchidism.

Measurement of Testicular Volume: Comparison of 3 Different Methods

PURPOSE We compared 3 commonly used clinical methods to measure testicular volume. MATERIALS AND METHODS The volumes of 151 testes in 76 adults treated for cryptorchidism during childhood were measured with an ordinary ruler, an orchidometer and ultrasonography. RESULTS Mean testicular volume was 15 +/- 8 ml. (standard elevation) measured with a ruler, 16 +/- 7 ml. with an orchidometer and 17 +/- 8 ml. with ultrasonography. The correlation among methods was significant. CONCLUSIONS To measure testicular size use of an ordinary ruler is recommended for clinical purposes because of its simplicity, availability and low cost.

Risk of renal scarring in vesicoureteral reflux detected either antenatally or during the neonatal period

OBJECTIVES To evaluate both the demographic features and the renal outcome of fetal vesicoureteral reflux (VUR), two well-defined populations were analyzed: those with hydronephrosis detected by obstetric ultrasonography, and neonates diagnosed after developing their first urinary tract infection within the first 4 postnatal weeks. METHODS Twenty-one neonates with antenatally detected VUR were compared with 30 patients with neonatally detected symptomatic disease. The mode of presentation, fate of reflux, and renal outcome were analyzed. RESULTS Significantly more bilateral dilating VUR was found in postnatally versus antenatally diagnosed patients (53% versus 29%; P = 0.05). Fourteen percent presented with congenital renal dysplasia. No difference was found in the incidence of congenital dysplasia between the two groups. Focal renal scars developed during follow-up in 19% of renal units. New scars were observed in dilating VUR only, especially in grades 4 and 5 (P <0.05), and these were exclusively in the postnatal patient group (P <0.005). CONCLUSIONS Several demographic features of fetal VUR differ, depending on whether detected antenatally or postnatally. The incidence of bilateral dilating VUR was greater in postnatally detected cases, suggesting a more severe manifestation of the disease. Renal injury occurred in an appreciable number of renal units. The damage may be of congenital origin or may be acquired secondary to urinary tract infection. The risk of acquired renal scarring is particularly significant if dilating VUR is not detected until neonatally after the first urinary tract infection.

Predictive factors associated with significant urinary tract abnormalities in infants with pyelonephritis.

BACKGROUND Major urinary tract abnormalities are detected in 20 to 40% of infants with acute pyelonephritis (APN). Early detection of structural defects is essential for protecting the kidneys from reinfection and subsequent scarring. The purpose of this study was to investigate whether any factors present during the acute phase of infection could predict the presence of existing significant urinary tract abnormalities in infants. METHODS A prospective study of 180 infants, aged 1 to 24 months, with APN was conducted. Blood and urine samples were collected. Renal ultrasound (US) was performed within 0 to 6 days from admission. Final diagnosis of the urinary tract anatomy was elucidated using the results of two or more radiologic imaging studies. RESULTS Risk factors for the presence of significant urinary tract abnormalities in infants were pathogens other than Escherichia coli in urine [relative risk (RR) 3.4, 95% confidence interval (CI) 2.2 to 5.3; P = 0.001], positive blood culture (RR 2.3, 95% CI 1.3 to 4.0; P = 0.039), young age (1 to 6 months) (RR 2.2, 95% CI 1.3 to 3.9; P = 0.004), lack of papG adhesin genes of E. coli in urine (RR 2.1, 95% CI 1.2 to 3.9; P = 0.016) and abnormal renal US (RR 2.0, 95% CI 1.2 to 3.4; P = 0.008). CONCLUSIONS Infants 1 to 6 months of age with APN caused by bacteria other than E. coli or by papG-negative E. coli strain, positive blood culture and abnormal renal US carry an increased risk for significant urinary tract abnormalities and need enforced follow-up.

Effect of Age at Operation, Location of Testis and Preoperative Hormonal Treatment on Testicular Growth after Cryptorchidism

PURPOSE We evaluated the effect of patient age, primary location of the gonad and preoperative human chorionic gonadotropin administration on future testicular growth in patients treated for cryptorchidism. MATERIALS AND METHODS Testicular volume was measured in 75 adults treated for cryptorchidism when they were 10 months to 13 years old. RESULTS The mean volume of the cryptorchid testes plus or minus standard deviation, whether unilateral or bilateral, was 11 +/- 6 ml. compared to 20 +/- 7 ml. for the spontaneously descended testes in patients with unilateral cryptorchidism. The results showed no significant correlation between patient age at treatment or original testicular location and final testicular volume, although the 22 testes of 18 patients undergoing surgery after age 5 years were somewhat smaller (9 +/- 5 ml.) than the 66 testes of 55 younger patients (12 +/- 6 ml.). However, 26 patients who had received human chorionic gonadotropin treatment had a significantly smaller testis (9 +/- 5 ml.) than did 57 treated with surgery alone (12 +/- 6 ml., p < 0.05). CONCLUSIONS Early orchiopexy at age younger than 2 years is not necessarily essential. Adult testicular volume is slightly greater in patients with cryptorchidism if treated at ages up to 5 years. Preoperative location of the testis in otherwise healthy boys exerts no definite effect on final testicular volume. Preoperative human chorionic gonadotropin administration may have an adverse effect on future testicular growth.

Predominance of Class II papG Allele of Escherichia coli in Pyelonephritis in Infants with Normal Urinary Tract Anatomy

P-fimbrial genotypes of Escherichia coli strains and their possible association with urinary tract abnormalities were studied in infants with pyelonephritis. A total of 153 urinary E. coli strains were analyzed by polymerase chain reaction for class I, II, and III alleles of the pyelonephritis-associated adhesin gene papG. Strains with any class II papG alleles were found significantly more often in infants with normal anatomy and function or in infants with clinically insignificant abnormalities than they were in infants with significant abnormalities (90 of 119 vs. 14 of 34 infants; P<. 001). On the other hand, strains without any papG alleles were found significantly more often in infants with major urinary tract abnormalities (11 of 34 vs. 17 of 119 infants; P=.016). Our genotypic findings indicate that, especially in infants with a normal urinary tract, infection is caused by more-virulent E. coli than is present in infants without a normal urinary tract. This virulence could be due to expression of pyelonephritogenic P fimbriae by an infecting E. coli strain.

Outcome of patients with antenatally detected pelviureteric junction obstruction

We investigated the outcome of patients with antenatally detected pelviureteric junction (PUJ) obstruction treated either conservatively or surgically. The series comprised 68 such patients, 54 with unilateral obstruction. Of the unilateral cases, 22 units were treated conservatively, 21 underwent early and 11 late surgery. Of the bilateral cases, 18 units were treated conservatively, 9 underwent early pyeloplasty, whereas 1 underwent later surgery. Among the conservatively treated unilateral cases, none of the patients’ good renal function deteriorated during follow-up. In the group with early surgery, the primary good function remained unchanged in all. In some patients, moderate function improved after early pyeloplasty, but in patients with poor function no improvement occurred. Of patients who underwent late pyeloplasty, primary good renal function remained unchanged in all except 1, although it had deteriorated to moderate function in some before surgery. In all except 1 patient with bilateral obstruction treated conservatively, both the grade of hydronephrosis and split function remained unchanged. In most patients the outcome of antenatally detected unilateral PUJ obstruction with initially good renal function, whether treated conservatively or surgically, seems favorable. Some patients with moderate function might benefit from pyeloplasty. In kidneys with poor function, recovery may be minimal despite pyeloplasty.

Renal transplantation in children with emphasis on young patients.

We report the results of 41 consecutive renal transplantations performed on 39 children (median age 2.7 years). Twenty-six recipients were less than 5 years old. Twenty-one recipients (13 under the age of 5 years) received cadaver (CAD) grafts. All grafts except 2 were from adult donors and were placed extraperitoneally. Patients were on triple immunosuppression (cyclosporine plus azathioprine plus methylprednisolone). Mean followup time was 2.3 years. No vascular and only one ureteral complication was seen. Acute tubular necrosis occurred in 3 patients (7.3%). No grafts were lost due to acute rejection. Three-year patient survival and 1-year graft survival were 100%. The overall 3-year actuarial graft survival was 86%. Three-year survival of grafts from living-related donors (LRD) was 92% and that of CAD grafts 75%. In recipients younger than 5 years, 3-year LRD graft survival was 89% and CAD graft survival 73%. No significant differences in graft survival between recipients of different age groups or between LRD and CAD grafts were found. We conclude that results of renal transplantation in children under 5 years of age are comparable to those of older children, even using CAD grafts, when adult donors and triple immunosuppression are used.

Late urologic sequelae after surgery for congenital sacrococcygeal teratoma

Forty-five patients treated for congenital sacrococcygeal teratoma were examined for late urologic outcome. The follow-up ranged from 4 to 42 (median 22) years. Only 8 patients experienced subjective urinary complaints. Sonography of the urinary tract revealed unilateral hydronephrosis in 2 patients, an ectopic kidney in 1, and a severely scarred kidney in 1; 1 patient had asymptomatic bacteriuria. Urodynamic screening using uroflowmetry was abnormal in 35 patients (78%). The risk of significant postoperative complications and subsequent late sequelae was greatest among patients with intrapelvic extension of the primary tumor.