and proximal (43). Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression. RESULTSLow birth weight, being a twin or triplet, mother being a diethylstilbestrol-daughter, fertility treatments, paternal subfertility, obesity, prescriptive drug use, and familial occurrence of hypospadias or testicular cancer were associated with hypospadias in general. For familial occurrence of hypospadias, there were high risk estimates for the distal and middle phenotypes with an OR (95%CI) of 10.4 (4.5-24.1) and 9.0 (3.1-26.0), but not for the proximal type at 1.8 (0.2-14.9). By contrast, the association with low birth weight (a proxy for placental dysfunction) seemed much stronger for proximal hypospadias with an OR (95%CI) of 9.1 (3.4-24.2) compared with distal and middle hypospadias at 2.6 (1.4-5.0) and 2.3 (0.8-6.5). There were similar estimates for pre-eclampsia. CONCLUSIONThese findings indicate aetiological heterogeneity of hypospadias and provide indications for the possible mechanisms through which specific risk factors may interfere with penile development. KEYWORDShypospadias, risk factors, endocrine disruptors, phenotype, severity Study Type -Aetiologic (case-referent) Level of Evidence 2a OBJECTIVETo obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case-referent study in which a distinction was made between different phenotypes. PATIENTS AND METHODSCases and referents were 305 boys with hypospadias and 629 boys with middle ear effusion whose parents completed postal questionnaires. Hypospadias phenotype was classified as distal (195 boys), middle (67),

The histological complete response rate after 6 consecutive instillations of apaziquone in patients with superficial bladder cancer was 67% (95% CI 51 to 80). Local side effects were comparable to side effects due to other chemotherapy instillations.

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A pure triphasic testicular Wilms' tumor, without teratomatous elements, was studied using multiple techniques. Carcinoma in situ (CIS), the characteristic precursor of testicular germ cell tumors of adults (TGCTs), was found in the adjacent parenchyma. Flow cytometric analysis showed a single hypotriploid tumor stem line. Karyotyping of the tumor revealed some numerical and structural abnormalities, including an i(12p), the chromosomal marker of TGCTs. In situ hybridization supported the karyotypic findings, and showed a similar numerical distribution in CIS and the tumor. Molecular analysis of the tumor illustrated that all short arms of chromosome 12, including i(12p), were of maternal origin. No 12q deletions were detected. In spite of complete loss of the paternal 11p13 band, the zinc finger regions and exons 2 and 6 of the WT1 gene contained no aberrations. Therefore, this tumor suppressor gene is not inactivated due to aberrations in the studied regions. In addition, all four WT1 alternative transcripts were expressed in the tumor. No aberrations were found in chromosomal bands 11p15.5, 16q22.1, and 16q24. Both parental alleles of the human imprinted genes H19 and IGF2 were expressed in the tumor. This is the first report on the chromosomal and molecular characterization of an extrarenal Wilms' tumor. Its germ cell origin was unequivocally demonstrated.

Since the development of surgery, the possibility of testis transplantation has fascinated man for centuries. Hunter and Berthold are considered to be the most important investigators in this field and, in addition, to be the founders of modern endocrinology. The association of testis transplantation with rejuvenation led to widespread popularity for this treatment in the first three decades of the twentieth century. At the same time, controversies concerning the aim of the treatment have coloured the early years of endocrinology. In the 1960s renewed interest in the subject arose for experimental reasons, leading to the development of microsurgical techniques for autotransplantation of high-lying undescended testes in children. Homologous testis transplantation has never become a subject of great interest, probably for ethical reasons. This possible treatment for hypogonadism, however, has been developed experimentally and has been performed in man only in Russia and China, evidently with success. The details of these studies and their outcomes are discussed.