Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression.

OBJECTIVE: Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed. PATIENTS AND METHODS: Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time. RESULTS: In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022). CONCLUSIONS: During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.

In vitro fertilization with spermatozoa from alloplastic spermatocele.

This case report describes successful IVF of oocytes of a 22-year-old female with epididymal spermatozoa aspirated from alloplastic spermatocele of the husband presenting with bilateral congenital absence of the vas deferens. Motile spermatozoa were aspirated from the reservoir 3 months after implantation. Abortion occurred 22 days after embryo replacement.

An LH-RH analogue (Zoladex) in the management of carcinoma of the prostate: a preliminary report comparing daily subcutaneous injections with monthly depot injections.

The luteinizing hormone releasing hormone, Zoladex, has been used in three centres, Pontefract, Antwerp and Mistelbach, to treat carcinoma of the prostate. An initial protocol using a soluble daily injection has been followed by a second study employing a monthly administered depot preparation. After an initial stimulation it has been shown that both daily and monthly injections reduce plasma testosterone to castrate levels. Circulating luteinizing hormone levels are also initially stimulated and then suppressed. Treatment toxicity has been minimal and in these short term studies reduction of acid phosphatase and subjective and objective tumour responses have been similar to those expected from effective hormonal therapy of prostatic cancer.

[The effect of kallikrein on sperm motility (author's transl)]. / Spermienmotilität unter Kallikrein

The effect of kallikrein (240 KE/week i.m. or 600 KE/day orally) on the sperm count, sperm motility and morphology was investigated in 27 patients with pathological ejaculate findings. Kallikrein was administered over a period of 9 to 12 weeks. A significant increase in sperm motility was observed in patients with asthenospermia. No influence was noted on the ejaculate findings in patients with oligospermia. Interference between the kallikrein-kinin system and sperm motility is postulated.

PIP: The effect of kallikrein (240 KE/weekly im or 600 KE/daily orally) on the sperm count, sperm motility, and sperm morphology was investigated in 27 patients with pathological ejaculate findings. Kallikrein was administered over a period of 9-12 weeks. A significant increase in sperm motility was observed in patients with awthenospermia. No influence was noted on the ejaculate findings in patients with oligospermia. Interference between the kallikrein-kinin system and sperm motility is postulated.

[Spermatological changes after ligature of the spermatic vein for idiopathic varicocele]. / Spermatologische Veränderungen nach Ligatur der Vena spermatica bei idiopathischer Varikozele.

Spermatological examinations were performed on 61 patients before and after varicocelectomy. Sperm morphology remained unchanged, but the sperm density increased in 67.2% cases and in 54.1% the sperm motility rose over a period of up to 18 months following the treatment. In 72.1% of the cases an improvement in at least one ejaculate parameter was noted. Of 52 patients who underwent the operation because of infertile marriage, the patient's wife became pregnant in 23.1% following varicocelectomy. Pathogenesis of the varicocele and the problems involved in ligaturing the spermatic vein for male subfertility are discussed.

[Serum prolactin levels during therapy of prostatic cancer with oestradiol-17 beta-undecylate and cyproterone acetate (author's transl)]. / Prolaktinserumspiegel während der Behandlung des Prostatakarzinoms mit Ostradiol-17 beta-undezylat und Cyproteronacetat.

Sixteen patients aged from 50 to 79 years with inoperable prostatic cancer were allocated at random to treatment either with 300 mg cyproterone acetate at weekly intervals or with 100 mg oestradiol-17 beta-undecylate every month. Blood samples were taken before treatment and at monthly intervals during the 6-month period of treatment. Serum prolactin levels were determined by a double-antibody radioimmunoassay. Basal serum levels of prolactin were 7.76 +/- 4.84 ng/ml and 9.50 +/- 4.32 ng/ml in the two groups of patients before therapy with oestradiol-17 beta-undecylate or cyproterone acetate, respectively. These pretreatment serum prolactin levels were statistically indistinguishable. Serum prolactin levels did not rise significantly during the first 5 months of treatment with cyproterone acetate, although an increase in prolactin was found in the sixth months of therapy with the antiandrogen. On the other hand, oestradiol-17 beta-undecylate raised serum prolactin levels significantly already after one month of treatment and the mean values were significantly higher than in the antiandrogen-treated group. These data combine to suggest cyproterone acetate as a suitable alternative to oestrogens in the therapy of inoperable prostatic cancer.

[Effect of pathologic changes in the urinary epithelium on the absorption of ethoglucide (Epodyl) from the bladder]. / Einfluss pathologischer Urothelveränderungen auf die Resorption von Ethoglucid (Epodyl) aus der Harnblase.

Studies on the absorption of Ethoglucid from human urinary bladder, utilizing a photometric method to determine Ethoglucid in biological fluids, gave the following results: The intact uroepithelium prevents absorption of interluminal Ethoglucid as well as no significant increase of absorption was seen in the presence of superficial, highly differentiated cancers or inflammatory alterations of the bladder. Urothelial lesions after transurethral resection or infiltrating cancers permit an intercellular diffusion of Ethoglucid from the bladder cavity into the systemic circulation, due to a loss of intercellular gaps between the urothelial elements.

[Leydig cell function in idiopathic oligozoospermia]. / Leydig-Zell-Funktion bei idiopathischer Oligozoospermie.

Repeated blood sampling at 10-minute intervals over a 4-hour period (15.00 until 19.00) for simultaneous determination of FSH, LH and testosterone was carried out in 7 normospermic men and 8 patients presenting with idiopathic oligozoospermia. Fluctuations of LH and testosterone were observed within the 4-hour sampling period. Only minor alterations of FSH were found. Planimetric assessment of the areas under the curves of FSH, LH and testosterone did not show any significant difference in FSH. Testosterone was found to be significantly decreased in the oligospermic group (p less than 0.025), while LH showed a tendency to be increased (p less than 0.1). These results point out that single determinations of LH and testosterone do not provide exact information, due to the wide range of hormone fluctuation. Serial sampling of the hormones demonstrates Leydig cell dysfunction in patients with moderate idiopathic oligozoospermia.

[Anastomosis of the vas deferens employing concentrated fibrinogen: an experimental study in rabbits (authors transl)]. / Vaso-Vasoanastomose unter Verwendung von Fibrinogenkonzentraten: Versuche an Kaninchen

Bilateral vaso-vasostomy was carried out in 30 rabbits using highly concentrated fibrinogen in combination with thrombin and clotting Factor XIII for tissue adhesion. The patency of the anastomoses was confirmed radiologically and by the injection of a dye, as well as histologically in paraffin-embedded and Goldner-stained serial sections. The overall patency amounted to 58% in animals investigated 4--6 weeks postoperatively (i.e. 17 out of 30 anastomoses). Stenosis of the junction was observed in all patent anastomoses investigated. The results of vaso-vasostomy employing a biological tissue adhesive were markedly superior to those with cyanoacylate.

[Androgen therapy of impotentia coeundi in elderly men. Psychological and endocrinological investigations (author's transl)]. / Androgenbehandlung der Impotentia coeundi alternder Männer. Psychologische und Endokrinologische Studien.

The aim of the present investigation was to assess impotence in elderly men by clinical, endocrinological and psychological examinations. Altogether 17 patients were treated in a double-blind study with placebo or 75 mg mesterolone per day over 8 weeks. The subjects were aged between 45 and 60 years and suffered from impotentia coeundi. No differences in serum LH and testosterone levels were noted between the start and end of therapy. Similarly, serum LH and testosterone levels in these patients did not differ from those in a control group. These results suggest that the "male climacteric" need not necessarily the associated with alterations in hormone parameters. On the other hand, mesterolone therapy resulted in an improvement in potency and other psychosomatic parameters.

[Endocrine interrelationships in patients with malignant testicular tumours (author's transl)]. / Endokrine Wechselbeziehungen bei Patienten mit malignen germinalen Hodentumoren.

Testicular function was investigated in 40 patients with malignant testicular tumours of different histology and tumour stage, by spermatological and endocrinological analyses. In patients without ectopic production of beta-HCG in the tumour tissue a hypergonadotropic tubular disfunction of the testis was present, resulting in elevated plasma FSH concentrations and moderate to severe oligozoospermia. Ectopic production of beta-HCG in the tumour stimulates the secretion of 17 beta-oestradiol, particularly in the Leydig cells, which suppresses pituitary gonadotropin secretion via negative testicular pituitary feedback. Spermatological analyses showed severe spermatogenetic disorders. Prolactin levels, however, were not altered in patients with testicular cancer.

[Treatment of infertile couples--an interdisciplinary task (author's transl)]. / Behandlung der sterilen Ehe--Eine interdisziplinäre Aufgabe.

The results obtained by closest cooperation between gynaecologist and andrologist in the treatment of sterile marriages are reported. 127 couples were treated over a period of 20 months. Almost 100% of the males and 60% of the females were sub- or infertile. Treatment of both partners was meticulously coordinated in order to increase the success ratio. Interdisciplinary cooperation seemed to be advantageous particularly in homologous insemination. 23 pregnancies were achieved, i.e. 18.1%, despite the unpromising nature of this negatively selected material.

Pituitary-gonadal feedback in testicular disorders.

Stimulation response of the pituitary to LHRH and testicular biopsy were investigated in 17 infertile men in comparison to 10 healthy controls. A significant elevation of basal FSH and LHRH-stimulated FSH serum levels was observed in Sertoli cell only syndrome and spermatogenetic arrest, while LH and testosterone remained normal. The LHRH test seems to be of value for differentiation of pretesticular, testicular and posttesticular infertility.

[Fertility in patients with testicular seminoma (author's transl)]. / Fertilität bei Patienten mit Seminom des Hodens.

In view of the excellent prognosis and the desire for children frequently expressed after post-operative healing, fertility studies were performed in 234 patients with seminoma of the tests. There already was a reduced sperm count before therapy in 39 out of 46 patients. The damage to spermatogenesis induced by radiotherapy can lead to azoospermia, cryptozoospermia and severe oligozoospermia in the first two years. The different irradiation techniques with the resulting burden on the residual testis are described. By appropriate irradiation adapted to the stage of the disease as well as by application of a testis guard, the damage to the residual testis can be reduced to the extent that restitution can be expected after two years. Four fathers produced healthy children within three to five years after the end of treatment.