St. H. Flüchter

Local Microwave Hyperthermia of Benign Prostatic Hyperplasia

Recently, hyperthermia has been used for treatment of benign prostatic hyperplasia. The preliminary results reported were promising. However, apart from patients with total urinary retention, objective voiding parameters have not been reported in detail for patients with prostatism. In a phase II study we treated 30 patients with benign prostatic hyperplasia by local microwave hyperthermia (915 MHz.). The prostate was heated transrectally to 42 to 43C, with the treatment consisting of 8 sessions of 60 minutes each given twice a week. To assess the results of treatment several parameters were determined before and 4 weeks after hyperthermia therapy, including transrectal ultrasound of the prostate with volumetry, urinary flow rate and residual volume. Of the patients 28 could be evaluated and only 2 showed a relevant improvement. Neither the voiding parameters nor the size of the prostate could be changed significantly by hyperthermia. The success rate of 7.1% is even lower than the spontaneous temporary regression rate of benign prostatic hyperplasia. Thus, we believe that hyperthermia cannot be regarded as an effective treatment for benign prostatic hyperplasia comparable to transurethral resection.

Histological effects of local microwave hyperthermia in prostatic cancer

Recent investigations have shown that hyperthermia can reduce the volume of the prostate and improve local symptoms in patients with carcinoma of the prostate. Histological examinations of the effect of hyperthermia on prostatic cancer tissue, however, have not been performed systematically until now. Thus, we initiated a study to investigate the effects of heat on prostatic cancer as a prerequisite for further clinical trials on hyperthermia as treatment for prostatic cancer. Twenty patients with untreated prostatic cancer underwent local hyperthermia (915 MHz), each receiving four sessions of 60 min each. The intraprostatic temperature was 42-43 degrees C. Histological specimens of the prostate were taken before the treatment and 1-2 weeks after the last hyperthermia session. Hyperthermia produced hyperaemic alterations of the prostatic stroma and a diffuse oedema with interstitial lymphoplasmacellular infiltration. Definite signs of tumour cell necrosis, however, could not be seen in any of the patients. Hence the shrinkage of prostatic tumours described earlier cannot be explained by histologically proven tumour cell destruction. Thus hyperthermia is not adequate as a single treatment for prostatic cancer. Hyperthermia may, however, be useful as part of integrated therapy regimens together with cytostatic or hormonal agents and radiotherapy because of hyperaemic, chemo- and radiosensitizing effects.

Combination of Hyperthermia and Cytostatics in the Treatment of Bladder Cancer

The intravenous administration of cytostatics in cases of locally extended carcinomas of the bladder seems to promise success. As concomitant disadvantage however we have to mention that the drugs in high concentrations needed for this treatment give rise to systemic toxic effects limiting the rational use of the drug. A further rise of cytostatic tissue concentration seems possible by performing a synchronous tumor injection of cytostatics and microspheres. An additional anticancer effect and the synergistic activation of cytostatic effectivity must be assumed by a following local transurethral high-frequency hyperthermia of the bladder. Our first urological experiences with this integrated therapy in six locoregional (T3-4N0M0) and six advanced metastasizing (T3-4N1M0-1) bladder cancers are presented consisting of a combined intraarterial cytostatic microspheres carcinoma infusion (CMCI) and scheduled adjunctive transurethral high-frequency hyperthermia (TUHH). In the case of locoregional tumor the aim was cancer destruction or debulking and in the case of metastasizing tumor palliation of local disease. Mechanisms of action, methodical procedures, indications, results as well as side effects of the intraarterial CMCI and TUHH treatment as developed by our department are presented and discussed.

Serum- und Gewebe-Mitomycin-C-Spiegel nach intravesikaler Instillation

Local mitomycin C (MMC) bladder instillation immediately after transurethral resection of superficial transitional cell carcinoma of the bladder caused an MMC serum concentration up to 24.5 ng/ml of a

Influence of Transrectal Hyperthermia on Prostate-Specific Antigen in Prostatic Cancer and Benign Prostatic Hyperplasia

The prostate-specific antigen (PSA) is a glycoprotein synthesized exclusively by the prostate. Since manipulations on the prostate can increase PSA serum levels, we investigated the effects of transrectal hyperthermia on PSA levels in prostate cancer (PC) and benign prostatic hyperplasia (BPH). Patients and treatments were the following: group 1a, PC St.D (n = 12): 8 hyperthermia sessions (twice a week) and LHRH-agonists plus flutamide; group 1b, PC St.D (hormone resistant; n = 10): 8 hyperthermia sessions (once a week) and epirubicin (50 mg intravenously, once a week); group 1c, PC St.C (n = 5): 6 hyperthermia sessions (once a week) and radiotherapy (60 Gy); group 2, BPH (n = 10): 8 sessions (twice a week). PSA levels were determined before, during (immediately before each hyperthermia session) and 1 week after therapy. Apart from hormone-/hyperthermia-treated patients, who showed a continuous decrease in PSA during therapy, all the other groups revealed a transient increase in PSA during the hyperthermia treatment. This effect is attributed to manipulations on the prostate and hyperthermia-specific effects on prostatic cells. The decrease in PSA on hormone/hyperthermia therapy can be explained by the tremendous effect of androgen deprivation on PSA levels overshadowing the hyperthermia effect.

Klinische Erfahrungen mit der lokalen Mitomycin-Therapie oberflächlicher Urothelkarzinome der Harnblase

105 Patienten mit Harnblasenkarzinom Tis, TA und Ti wurden nach transurethraler Elektroresektion der Blase (TUR) adjunktiv einer topischen Zytostatikatherapie mit Mitomycin C (MMC) unter folgender Zielsetzung unterzogen: 1 Zur kurativen Beeinflussung des carcinoma in situ 2. Zur Vermeidung von Tumorzellimplantationen. Nach einer jetzt durchschnittlichen Beobachtungszeit von 22,3 Monaten hatten nur 12,4% der Patienten ein Tumorrezidiv. Die Therapie-nebenwirkungen sind gering. MMC-Serumresorptionsstudien bei 19 Patienten zeigten, das 20 mg MMC, unmittelbar nach der TUR in die Blase instilliert, nicht zu toxisch systemischen Konzentrationen im Serum fuhrt.

Clinical Value of Different Methods for Determination of Acid Phosphatase in Prostatic Cancer

The availability of a radioimmunoassay (RIA) and an enzyme immunoassay (EIA) for the prostate specific acid phosphatase required a study to compare these techniques with the conventional colorimetric assay. Our study is based on examinations of 188 normal persons and 136 patients with carcinoma of the prostate. The advantage of the immunologic methods - RIA and EIA - lies in their stable immunologic activity and their high specificity. However, RIA and EIA are not screening methods for incidental carcinoma because of their low sensitivity for stage-A tumors. Their good sensitivity at lower ranges of concentration makes them suitable for checking the course of a prostatic carcinoma during therapy. The level of prostatic acid phosphatase may allow conclusions about intra-or extracapsular growth of the prostatic carcinoma.

Experimental data on the application of a stoma prothesis in cutaneous ureterostomy

SummaryThe main problem with urinary diversion via cutaneous ureterostomy is stomal stenosis. Results with experimental and clinical implants of carbon polymer stoma prostheses (max. clinical observation period: 31 months) for vesicostomies have encouraged us to find out whether implants of this material would be suitable for cutaneous ureterostomies as well. The first step was dilatation of the ureters in 16 mongrel dogs, 4 mini pigs and 4 sheep. This was done by knotting a thread over a splint which had been introduced into the ureter. After 7 days the ureter was ligated prevesically and a carbon polymer stoma was implanted into the ureter.37 of the 48 stoma implants were well tolerated and provided water tight urinary drainage; slight encrustation occurred but, radiologically, a smooth flow of contrast medium was seen. Ten of these 37 cases had transient urinary leakage. Eleven of the 48 stoma implants were unsuccessful because of insufficient healing, urinary extravasation, parastomal inflammation or severe encrustations.The results of these experiments on animals would seem to justify initial clinical use. It is conceiveable that in this way stomal stenosis of the cutaneous ureterostomy can be avoided.

Combined Treatment of Advanced Bladder Carcinoma

Extended carcinomas of the bladder mostly run an unfavorable course. As a rule these tumors are resistent to radiation therapy. Intravenous administration of cytostatics promises success as described recently (Cant et al. 1985; Jakse et al. 1985). A concomitant disadvantage, however, is that the drugs in the high concentrations needed for treatment give rise to systemic toxic effects. Attempts to increase tissue concentration of cytostatics by performing a transarterial perfusion of carcinoma gave encouraging results (Aigner 1985). A further rise of cytostatic tissue concentration seems possible if a cytostatic microspheres (Spherex; Pharmacia, Freiburg) carcinoma infusion (CMCI) is performed synchronously. Injected intraarterially, the 45-jim microspheres of starch occlude tumor vessels and cause (a) an accumulation of cytostatics in the center of the tumor, but with low concentrations in the periphery, and (b) transient ischemia in the tumor, the starch molecules being degraded by the body’s amylase (Davis et al. 1984; Fliichter et al. 1986, 1987). An additional activation of cytostatic effectivity must be assumed if adjunctive transurethral high-frequency hyperthermia (TUHH) of the bladder is employed (Fig. 1). This technique when used alone has a damaging effect on transitional cell carcinoma of the bladder (Bichler et al. 1982; Harzmann 1980). This paper describes first experiences of this combined treatment schedule in the field of urology.

Initial Experience with the Second-Generation Lithotripter, Dornier HM-4

In addition to the widely-used first-generation lithotripter (Dornier HM-3), an increasing number of second-generation devices are now in clinical use. We are currently reporting our initial experience with the Dornier HM-4. The main improvements over the previous device with this model are the coupling of the shock waves by means of a water cushion, a modified shockwave generation with an enlarged ellipsoid and decreased generator energy, and computer-assisted handling. Additionally, a system for respirational triggering is installed. Treatment-related technical data are printed out by a small computer. The modification of shock-wave delivery with less energy through a larger-diameter ellipsoid is believed conducive in decreasing the need for anesthesia. However, an increasing number of secondary treatments are being reported from other centers.