Treatment of locally advanced prostatic carcinoma with LHRH analogues: cytological, DNA-cytophotometrical, and clinical results.

From June 1, 1981 to December 31, 1985, 122 patients aged 54 to 83 years, with locally advanced prostatic carcinoma, were treated with buserelin. Nineteen of the patients received combined therapy with buserelin and androcur for the first 3 months. To control the response of the primary tumor to therapy, fine-needle aspiration biopsy of the prostate was made in all patients at 3-month intervals. Fifty-eight (76.3%) of 76 patients with locally advanced prostatic carcinoma, with or without bone metastases, who underwent buserelin therapy for periods of 12-54 months showed good to satisfactory regression grades in the primary tumor. Eighteen patients (23.7%) showed poor regression or none, established by cytological findings and the measure of DNA by means of single cell-scanning cytophotometry. In three of the 58 patients, tumor progression or bone metastases occurred despite favorable regression grade; these were the only cases in which there was a discrepancy between the clinical course of the disease and the grade of regression in the primary tumor. According to TNM classification, 68 of the 78 patients treated for 12-54 months were in stage T3 NX M0; eight were in stage T3/T4 NX M1. On the basis of our long-term studies, it can be stated that buserelin therapy induces positive therapy response in more than 75% of locally advanced, inoperable, primary prostatic carcinoma. The clinical castration caused by buserelin through selective suppression of gonadotrophic secretion in the pituitary gland is, as the term implies, no more effective than surgical castration. However, the gonadotrophin suppression induced by buserelin is reversible and spares the patient the psychic stress of orchiectomy. This is a decisive advantage in light of the fact that in 20-40% of patients with locally advanced primary prostatic carcinoma, the primary tumor is hormone-refractory, and surgical castration would prove unnecessary after all.

Urolithiasis in childhood. A study of 181 cases.

181 of 2,606 patients hospitalized for urolithiasis in 12 years were younger than 15 years (6.9%). In accordance with the data given by other authors, we found the incidence of urolithiasis in children to be 1-5%, which, at least in Central Europe, corresponds approximately with that in adults. The causative factors or cofactors we established were malformation of the kidneys and urinary tract in 35.9%, and infections of the urinary tract in 80.7%. Defined metabolic disorders were found in only 5.5% of patients. Stone analysis showed a predominance of phosphate-containing calculi. Control examinations were done in 154 children over periods of 6 months to 11 years. "Recurrent lithiasis' was seen in 32 patients, however, the exact comparison of pre- and postoperative X-ray films showed that in 17 cases the calculi had not been completely removed during surgery (11%). Consequently, a real recurrent lithiasis was present in 15 children only (9.9%). Since the West Berlin population includes a high percentage of Turkish people, we can conclude from our case material that even those Turkish children who were born in West Berlin suffer from urolithiasis 2-2.5 times as often as German children of the same age-groups.

Results of ofloxacin therapy in andrologic patients suffering from therapy-requiring asymptomatic infections.

In 1990, microbiological ejaculate analyses were carried out on a routine basis on 125 andrological patients, in addition to the determination of the concentration, motility and morphology of the spermatozoa. Fourteen patients (11.2%) with therapy-requiring asymptomatic infections (TAI) > 10(4) CFU (colony-forming units) ml-1 were effectively treated with Ofloxacin (Tarivid) at 2 x 200 mg d-1 for a period of 20 d. Concentration, motility and morphology of the spermatozoa were determined before the Ofloxacin treatment and controlled 1, 3, and 6 months later and correlated to the values obtained before the treatment. Over the entire period of observation, the morphology did not change significantly, whilst initially 1 month after the treatment the concentration and the motility decreased significantly (P < 0.05). Three months later they again reached the starting values. After 6 months, a significant improvement occurred with regard to the motility, as compared to the starting values (P < 0.01), whilst the concentration remained at the level of the starting values. By this, Ofloxacin has been proved to be an effective medication for the treatment of TAI. In the end, it still remains an open question whether the improvement in sperm motility is primarily related to the Ofloxacin therapy.

Prognostic relevance of DNA ploidy and proliferative activity in urothelial carcinoma of the renal pelvis and ureter. A study on a follow-up period of 6 years.

In 55 patients with urothelial carcinoma of the renal pelvis or ureter, the ploidy, the DNA heterogeneity and the counts of cell cycle phases in the tumor were examined by means of single-cell DNA cytophotometry in order to find more prognostic factors than those already known (stage and grade). Follow-up periods ranged from 1 to 6 years. At the time of first diagnosis, 42 (76%) of the patients had tumors of the renal pelvis, 13 (24%) of them had ureteral tumors. 23 (42%) patients were in stage pT 1 N 0, 15 (27%) in stage pT 2 N 0, 12 (22%) in stage pT 3 N 0, and 5 (9%) were in stage pT 3 N+. The histological malignancy grade most frequently seen in the patients examined--i.e. in 51% of cases--was malignancy grade II. 25% of the patients had grade III tumors whereas only 24% had grade I tumors. With malignancy grade I, DNA cytophotometry showed DNA frequency peaks to be in the diploid range while tumors with malignancy grade II showed heterogenous DNA patterns. 71% of the patients with malignancy grade III showed aneuploid DNA values; 29% of them had polyploid DNA values. For malignancy grades II and III, the proliferation rate of the tumor cells was statistically significantly higher than for malignancy grade I. The determination of tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry gives valuable clues regarding prognosis.

Effect of different local and systemic therapy upon urinary bladder cytology.

1,900 cytological analyses of urine and bladder washings were made in 127 patients with urothelial bladder carcinomas before, during and after therapy. Following transurethral resection, all patients were treated by intravesical instillation of mitomycin C or thiotepa. Because of a locally advanced bladder carcinoma, 26 patients who were not candidates for radical cystectomy were given an integrated treatment of radiotherapy and chemotherapy. Intravesical administration of mitomycin C and thiotepa as well as integrated radiotherapy and chemotherapy induce a variety of cytological effects (toxic and/or metabolical) which may lead to cytological misinterpretations in the follow-up. DNA measurements by means of single-cell spectrocytophotometry show that the cytological effects induced by the above-mentioned therapies are not accompanied by an increase in the nuclear DNA content. It is concluded that the knowledge of these induced effects is mandatory for a correct interpretation of urinary cytology in the follow-up. Considering these effects and the clinical history, bladder carcinoma recurrences during and after intravesical chemotherapy or integrated radiotherapy and chemotherapy may be detected early by urinary cytology in the hands of an experienced cytopathologist or urologist. Furthermore, alterations of the urinary cytology occur after systemic application of cyclophosphamide and under immunosuppressive therapy.

[CEA, HCG-beta and alpha fetoproteins - clinical significance as tumor markers]. / CEA, HCG-beta and alpha-Fetoprotein - klinische Bedeutung des Tumormarker.

Representation of the clinical significance of the tumor markers CEA, HCG-beta and alpha 1-fetoprotein (AFP) of the basis of the relevant literature and of own studies. As a marker for tumors of the urogenital tract, CEA is at present of very little value as it is too unspecific. HCG-beta and AFP, on the other hand, are important new parameters for both the demonstration of so-called subclinical metastases (staging) and clinical case control, particularly with malignant nonseminomatous tumors of the testicles. Over a period of four years we found in 62 out of 85 patients with nonseminomatous testicle tumors that -- in accordance with the literature -- simultaneous determination by the two markers (85% positive) is decidedly superior to the determination by one marker only. Out of 23 patients with a histologically classified seminoma, one patient (i.e. 4.4%) was HCG-beta positive. So far, the prognostic significance of such findings has generally not been clarified. It is shown here that exclusively "marker-oriented" therapy planning and case control without the clinical examination methods used so far are not yet justified because of the inadequate specificity and sensitivity of these two markers as well as of more recent ones (SP-1, TPA). Nevertheless, HCG-beta and AFP are at present important new methods in the areas of diagnosis (staging), therapy planning and case control as primarily increased marker values, or marker values increased during or after therapy clearly indicate metastasizing or renewed tumor activity, respectively.

[Primary hyperparathyroidism: studies of 4,000 urinary calculi patients treated with extracorporeal shockwave lithotripsy]. / Primärer Hyperparathyreoidismus: Untersuchungen bei 4000 mit der ESWL behandelten Harnsteinpatienten.

The incidence of primary hyperparathyroidism was determined in 4000 renal stone formers treated by ESWL at our institution from 1983 to 1990. Based on repeated measurements of serum calcium and serum parathyroid hormone an incidence of 2.8% was found. In 60% of patients with primary hyperparathyroidism stone disease occurred for the first time. The majority of patients (68%) were more than 50 years of age. 56% of patients were men, 44% were women.

[1st clinical results of the treatment of locally advanced prostatic cancer with a powerful LH-RH analog: buserelin acetate]. / Premiers résultats cliniques concernant le traitement du cancer de la prostate à un stade local avancé au moyen d'un puissant analogue de la LH-RH: l'acétate de buséréline.

From a series of 39 patients presenting with a locally advanced cancer of the prostate (Stage C), 26 were treated with an LH-RH analogue, Buserelin, for a period ranging between 7 and 22 months. After an initial period of subcutaneous injections, the treatment was administered by intranasal spray (400 mcg three times a day). This resulted in levels of testosterone similar to those of castrated men. In order to evaluate the effects of buserelin on the primary tumour, a degree of cytological regression was established for all of the patients, using fine-needle aspiration biopsy which was performed every three months. The cytological results correspond with the DNA analyses performed by cytophotometry of isolated cells and reveal a statistically significant reduction in the degree of anaploidy or polyploidy in the cases in which the prostatic cancer had responded favourably to treatment with buserelin. 21 of the 26 patients treated with this potent LH-RH analogue showed a good therapeutic response. 5 patients who did not show any signs of cytological regression were secondarily treated with estramustine phosphate because of their resistance to hormones. One patient received cyclophosphamide as a tertiary treatment because of progression of his symptoms after 15 months. No appreciable side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of prostatic cancer with LH-RH analogues.

Twenty-one of 32 patients with locally advanced prostatic cancer (stage C) were treated with the LH-RH analogue Buserelin for 7-19 months. After an initial sequence of subcutaneous injections, treatment was continued with intranasal spray application (three daily doses of 400 micrograms each) which ensured maintenance of serum testosterone within the range seen in castrated men. To evaluate the response of the primary tumor to Buserelin, cytological regression was established for all patients by fine-needle aspiration biopsy every 3 months. The cytological results corresponded with those of DNA analyses of single-cell cytophotometry showing a statistically significant drop of the grade of aneuploidy or polyploidy when the prostatic carcinoma responded positively to Buserelin therapy. Seventeen of 21 patients treated with the potent LH-RH analogue showed good therapy response. Four patients with no cytological signs of tumor regression received secondary treatment with estramustine phosphate because of hormone resistence. One patient had to be crossed over to cyclophosphamide, the third drug, for clinical progression after 15 months. Essential side effects have not been observed. Continuous treatment of locally advanced prostatic cancer with Buserelin, combined with close control of the patient, offers not only a real alternative to surgical castration--as the patient is spared the psychical stress of orchiectomy--but also to estrogen therapy with its risk of cardiovascular side effects.

Sustained suppression of testosterone production by the luteinising-hormone releasing-hormone agonist buserelin in patients with advanced prostate carcinoma. A new therapeutic approach?

Nine patients with advanced carcinoma of the prostate were treated with the luteinising-hormone-releasing-hormone agonist buserelin (2 mg/day subcutaneously for 3 days then 0.4-1.2 mg/day intranasally for up to 24 weeks). There was a rise in luteinising-hormone levels during the first few days of treatment, but levels fell after 3 weeks and remained lower than normal after 24 weeks' treatment. In patients receiving 0.6-1.2 mg buserelin per day testosterone levels fell to less than 1 ng/ml within 3 weeks and were still as low as those found in surgically castrated men after 24 weeks. Histology showed regressive changes in some tumours after 3-6 months' buserelin treatment similar to those seen in surgically castrated men. Buserelin treatment may be an alternative to surgery in patients with advanced carcinoma of the prostate.

DNA ploidy is a valuable predictor for prognosis of patients with resected renal cell carcinoma.

BACKGROUND: Renal cell carcinomas (RCCs) are heterogeneous and include several distinct entities with a range of biologic and clinical behaviors from relatively favorable to extremely aggressive. The heterogeneity leads to unpredictable outcome and survival. DNA ploidy is a relatively new predictor differentiating diploid from aneuploid tumor cells according to regular or irregular DNA content. The authors evaluated the predictive value of DNA ploidy in patients who underwent resection because of RCC. METHODS: In a prospective study, 180 patients who underwent resection because of RCC were investigated. DNA cytometry was conducted on each resected tumor to determine DNA ploidy. Patients were completely followed up until death or up to 12 years. RESULTS: Survival analysis showed that patients who underwent resection because of RCC in tumor classifications pT1, pT2, and pT3 survived 10 years in 85%, 53%, and 8% of cases, respectively. Patients suffering from small tumors (pT1 and pT2, n = 44) with diploid nuclei survived 10 years in 94% but only in 8% if the tumor was aneuploid (n = 55). In addition, 91% of patients who underwent resection of large tumors (pT3, n = 12) with diploid nuclei survived 10 years, but no patient with large and aneuploid tumor (n = 51) survived more than 3 years. Furthermore, 92% of all patients afflicted from diploid RCC survived 10 years. This finding was independent of tumor stage. CONCLUSIONS: The results of this study suggest that DNA ploidy is a significant and independent predictor for survival of patients afflicted from RCC and superior to tumor classification and grade. DNA ploidy is a reliable prognostic factor for RCC and yields considerable information for patient management and predicting clinical outcome.