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.

[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.

[Clinical, endocrinological and pathohistologic aspects of beta-HCG positive seminoma]. / Klinische, endokrinologische und pathohistologische Aspekte zum Beta-HCG-positiven Seminom.

The most important aspects of the clinical findings, endocrinology and course of the disease in 14 patients with the histological diagnosis of pure seminoma of the testis and positive serum beta-HCG levels are presented. In addition to routine investigations, immunohistochemical examination of the formalin-fixed specimen by the immunoperoxidase technique was also carried out. Serum alpha-feto-protein levels remained normal in all 14 patients. There was no correlation between serum beta-HCG level and tumour stage. The longest period of observation was 76 months and the shortest 8 months. Patients with no evidence of metastatic disease (5 patients, N0M0) or patients with low-stage disease (5 patients, N1 or N2M0) respond very well to radiotherapy. 4 patients (N3-N4M0) with large retroperitoneal metastases or distant lymph node metastases underwent different combinations of treatment.

[Accuracy of computed tomography in urological tumour diagnosis (author's transl)]. / Treffsicherheit der Computertomographie in der urologischen Tumordiagnostik.

The value of CT in comparison with other partly invasive diagnostic measures was assessed in 127 urological patients with the diagnosis "expansive process of the kidney" or "tumour" (bladder, prostate and testicles). The significance, the margin of error and correspondence with surgical and medical findings are described. Computed tomography represents a valuable supplement to tumour diagnosis in urology. It is accurate, offers basic information for radiation planning and polychemotherapy, is useful in control check-ups of patients with tumours of the kidney or testicles and should be employed in spite of the relatively high expense if a tumour is suspected.

[Chemical castration using a depot LHRH-agonist as a palliative therapy concept in prostatic carcinoma--clinical, endocrinological and experimental studies]. / Chemische Kastration mit einem Depot LHRH-Agonisten als palliatives Therapiekonzept beim Prostatakarzinom--klinische, endokrinologische und experimentelle Untersuchungen.

79 patients with locally advanced and/or metastatic prostate cancer were treated by means of a biodegradeable depot formulation of the luteinizing hormone releasing hormone analogue Goserelin (Zoladex). All patients received 3.6 mg depot Goserelin (Zoladex 3.6 mg implantate) subcutaneously into the anterior abdominal wall at 4 weekly intervals. The average time of observation was 24.2 months. The best objective response rate was found in 62%. Serum testosterone levels initially increased after the first depot injection and then decreased ultimately to castrate range (less than 0.6 ng/ml) between day 15 and day 27 (median 21) in the majority of patients. Castrate testosterone levels were still found 48 months after the start of treatment with depot Goserelin. 6 months after institution of treatment in 66.7% of cases evident signs of histological regression were found in the primary tumour tissue. Adenocarcinoma presented with a highly significantly better response pattern than anaplastic carcinoma. In animal experiments a single dose of 1 mg depot Goserelin was administered to adult male rats and the effect on serum testosterone levels and target organs (testes and ventral prostate) were investigated. Mean testosterone levels (mean = 0.31 ng/ml) decreased to castrate range (less than 0.3 ng/ml). 4 weeks after depot injection weight of the testes and prostate weight were significantly reduced. However 8 weeks after administration of 1 mg depot Goserelin there was no significant between the control group and the treated group. We conclude that the depot formulation of Goserelin (Zoladex) is effective, simple, practicable and safe in the treatment of advanced prostatic cancer. Current clinical studies are confirming the importance of reversible medical castration by LHRH agonists before radical prostatectomy.

[Clinical and diagnostic value of computed tomography in retroperitoneal space-occupying extrarenal and extrapancreatic lesions (author's transl)]. / Klinische Bedeutung und Wertigkeit der Computer-tomographie des Retroperitoneums im Nachweis extrarenaler und extrapankreatischer Raumforderungen.

In order to determine the diagnostic accuracy and clinical value of CT in the detection of retroperitoneal tumours and tumour-like conditions an evaluation was conducted of 397 CT examinations in 287 patients. Staging, monitoring of therapy and detection of relapse of the disease are the main indications for CT examination. CT should be used in the first place in the course of diagnostic staging procedures of patients with malignant tumours and tumour recurrence. This is justified by an overall diagnostic accuracy of 90% and the ability of CT to show up the exact localization and extent of tumours and the different patterns of lymph node involvement.

[Late result following successful penis replantation with spontaneous closure of a urethral fistula]. / Spätergebnis nach erfolgreicher Penisreplantation mit spontanem Urethrafistelverschluss.

We report about the postoperative course and late result in a case of successful reimplantation of a totally amputated penis. A small urethral fistula closed spontaneously during the postoperative. Follow-up at five years shows a satisfactory cosmetical and functional result.

[Radioisotope lymphadenectomy in testicular tumors (author's transl)]. / Radioisotopenlymphonodektomie bei malignen Hodentumoren.

This paper presents a preliminary report of the first eleven patients with testicular cancer who underwent lymphadenectomy assisted by radioisotope techniques with a special designed gamma surgical camera. In cases of only partial carcinomatous infiltration the lymph nodes are well marked with the radioisotope. Additionally colour television gives the surgeon an objective continuous control of the actually dissected lymphatic tissue during all phases of surgery. In our experience the use of radioisotope-techniques and a gamma surgical camera seem to be of great value in improving lymph node extirpation in cases of testicular cancer.

[Hydatid torsion as a cause of acute scrotum--clinical, sonographic and anatomic aspects]. / Hydatidentorsion als Ursache des akuten Skrotums--klinische, sonographische und anatomische Aspekte.

Out of 82 patients with acute swelling of the scrotum, 25 (30.5%) had hydatid torsion. Hydatid torsion was the second most common cause of acute scrotal swelling in the entire patient group. In the group of patients up to 14 years of age (n = 36), hydatid torsion was found in 47.2% and was the most common cause of acute scrotal swelling, followed by torsion of the spermatic cord. Only 3 patients had torsion of an appendage of the epididymis. All other patients (n = 22) had torsion of the hydatid of Morgagni (appendage of the testicle). A difference in anatomical structure and vascularization during childhood seems to be the most important aspect regarding hydatid torsion and hemorrhagic infarction. Ultrasonographic examination of the scrotum and checking to see if the typical physical signs are present can help in making the exact diagnosis. In 13 patients with hydatid torsion, the scrotum was examined with ultrasound high-frequency transducers (7.5, 10 and 12 MHz). In 4 patients, the diagnosis was hydatid torsion, as determined by ultrasonography. Two patients were treated conservatively with a daily follow-up including a clinical examination and investigation of the scrotum with ultrasound. The patients recovered very quickly and the acute symptoms resolved within a few days in virtually all instances. Thus, in cases where the diagnosis is proven and the course of the disease is reasonably mild and painless, conservative management of intrascrotal hydatid torsion is possible and can be an effective means of treatment in lien of surgical intervention.

[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.

Testicular tumor and crytoptorchidism.

71 (7.2%) of 990 patients with testicular tumors were either clinically cryptorchid or had a history of maldescendent testis. 3.4% of the tumors arose in untreated or unsuccessfully treated testicular nondescent. Ipsilateral and contralateral development of malignancy were equally common. Neoplastic changes were even observed in patients who had undergone corrective surgery prior to their 5th year of life. There was no predominating histologic type of tumor.

[Drug prevention of recurrence in bladder tumors. Intravesical adriblastin instillation following transurethral resection of non-infiltrating bladder tumors]. / Medikamentöse Rezidivprophylaxe bei Blasentumoren. Intravesikale Adriblastin-Instillation nach transurethraler Resektion nicht-infiltrierender Blasentumoren.

29 patients were treated with intravesical adriamycin-instillations after transurethral resection of non-infiltrating bladder tumor. 50 mg Adriblastin were administered every four weeks during one year. In no case there were severe side-effects. Endoscopic controls were performed every three months. 12-28 months after beginning of therapy 6 recurrences (20,7%) were noted.

[Pyelonephrostomy as a life-extending measure in terminal cancer]. / Pyelonephrostomie als lebensverlängernde Massnahme bei terminaler Karzinomkrankheit.

Between 1975 and 1980 35 patients with incurable carcinomas and bilateral ureteral obstruction who had been fitted with pull-through pyelonephrostomies were retrospectively studied with particular reference to the post-operative quality of their lives. 30 patients who died of the primary diseased had survived for periods of between 14 days and 30 months; the average was 7.5 months. There was no significant correlation between pre-operative kidney function and survival time. The post-operative quality of the lives of the patients who had shown good kidney function before the nephrostomy was fitted was significantly better than that of the patients with bad kidney function.

[The value of exfoliative cytology of the urine in the diagnosis of bladder tumors]. / Wertigkeit der Exfoliativzytologie des Harns bei der Diagnostik von Blasentumoren.

It is reported on the cytological and histological results of 253 bladder tumors. There was an exact correspondence of the results in 80.3%; in 11.4% it was not possible to prove the existence of the bladder tumor cytologically. Most of these were low-grade malignant tumors. In 8.3% of the cases the results were obtained through PAP III according to the scheme of Papanicolaou.

[Therapy of urinary tract infections with dibekacin]. / Therapie des Harnwegsinfekts mit Dibekacin.

The use of a new aminoglycosid antibiotic (dibekacin = Orbicin) in the treatment of severe urinary tract infections in a urological clinic is presented. After having given their written informed consent, 50 patients were treated with a dosage of 150-225 mg dibekacin, administered in three single daily doses. From a total of 41 mono-infections, asepsis could be attained in 70,7%, in 17,1% no effect could be observed and in 12,2% it came to a change of bacteria. From a total of 9 mixed infections, asepsis was observed only twice after the end of therapy. 87,5% of the patients reported about a far-reaching improvement or complete disappearance of clinical symptoms. In 2 cases allergic exanthema was observed. The local toleration was good. Disturbances of the otovestibular function were not registered.

[Value of beta-HCG blood levels in patients with malignant tumors of the testis]. / Wertigkeit der Serum-beta-HCG-Bestimmung bei Patienten mit malignen Hodentumoren.

In 24 of 43 patients (56%) with malignant germ cell tumors of the testis, the serum was positive for HCG prior to ablation of the testis. We give a detailed account of the course of HCG levels in the serum of 7 patients with seminoma of the testis. Positive serum-HCG-findings 8 to 10 days after semi-castration and prior to retroperitoneal lymphadenectomy indicate tumor metastases. In two thirds of our patients, we observed a correlation between regression of metastases under chemotherapy and the pattern of serum-HCG-levels.

Effects of the duration of therapy with the LHRH agonist D-ser (BUT)6 Azgly10-LHRH (ICI 118-630) on the steroid hormone content and the morphology of human testicular tissue in the treatment of patients with advanced prostate cancer.

In 20 patients with locally advanced or metastatic prostate cancer, testicular tissue obtained by bilateral subcapsular orchidectomy was examined for steroid hormone content and morphological changes. Eight patients (group I) had not received previous treatment. Twelve patients had been treated with monthly subcutaneous doses of the depot luteinizing hormone-releasing hormone (LHRH) agonist D-ser (BUT)6 Azgly10-LHRH (ICI 118-630). Six patients (group II) had been treated for less than 6 months and 6 patients (group III) for more than 6 months. The longest duration of treatment with depot LHRH was 36 months. After 2 months of treatment (group II), maximum hormone suppression was achieved and remained unchanged even if treatment was continued for 3 years. The mean serum testosterone levels were decreased in group II (means = 0.586 mg/ml) and in group III (means = 0.575 mg/ml) and were found to be in the range of castration; a statistically significant reduction in luteinizing hormone (P less than 0.000001) and follicle-stimulating hormone (P less than 0.05) was observed in the treated patient groups. The content of the steroid hormones dihydroepiandrosterone sulfate (DHEA)-S, testosterone, androstenedione, oestradiol, progesterone and 17-alpha-hydroxyprogesterone/g testicular tissue was significantly lower in patients on LHRH agonists. The differences in concentration were particularly pronounced for DHEA-S, T and A. As in the case of serum concentrations, the testicular tissues showed no differences between groups II and III. In the treated groups a significant reduction in weight was seen, depending on the duration of therapy. Similarly, the structural changes visible by the aid of light and electron microscopes increased with the duration of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of routine sonography in the diagnosis and conservative management of renal angiomyolipoma.

A prospective study was undertaken to assess the value of ultrasonography in the clinical monitoring of angiomyolipomas. 26 patients with angiomyolipomas as diagnosed by sonography and verified by computerized tomography (CT) were followed up by sonographic monitoring over a mean period of 45 months. One case was associated with tuberous sclerosis. Inclusion criteria for conservative management had been clinically asymptomatic angiomyolipomas smaller than 5 cm. Significant tumor growth and a change of the sonographic pattern during follow-up was seen in 2 patients. After renewed follow-up CT scanning failed to reveal negative density values, both patients were nephrectomized. Histologic examination showed hemorrhage in the tumor. The remaining 24 patients (92%) showed no changes in the sonographic patterns. Minor tumor growth of 0.5 cm on average was seen in 6 patients over a mean follow-up period of 52 months. Surgical intervention was refrained from in these 24 patients due to the consistent sonographic pattern and the absence of clinical symptoms. Once the angiomyolipoma is verified by CT, sonographic monitoring suffices if the sonostructure remains unchanged. Minor asymptomatic angiomyolipomas today no longer require surgical intervention as this benign tumor has a pathognomonic sonographic appearance.

The gonadotropin response to synthetic gonadotropin releasing factor in patients with testicular cancer.

The response of LH and FSH to synthetic gonadotropin releasing factor (GRF) was investigated in 19 patients with malignant germ cell cancers of the testicle prior to radical orchiectomy. The study showed: 1. Patients with circulating beta-HCG presented with increased plasma levels of oestradiol. Base line FSH and response to GRF were significantly decreased. 2. In patients without detectable beta-HCG plasma concentrations of oestradiol and testosterone were within the normal ranges as compared to healthy age matched controls. Base line levels of FSH and LH were increased and an exaggerated response to GRF was observed. From the results of this study it can be concluded that hypergonadotropic dysfunction of pituitary-gonadal axis exists in patients with testicular cancer of germ cell origin. Beta-HCG production by tumour tissue results in hyperoestrogenism and interferes with the pituitary-gonadal axis in terms of inhibition of pituitary gonadotropin release.