Dieter Jocham

First Clinical Experience With Extracorporeally Induced Destruction of Kidney Stones by Shock Waves

&NA; We performed extracorporeally induced destruction of kidney stones on 72 patients. No complications have resulted from the tissue exposure to high energy shock waves. Clearance studies before and after the shock wave treatment indicate no changes in renal function. The method was used successfully in all patients with stones in the renal pelvis. In none of these patients was an open operation required. Two patients with ureteral stones also were treated with shock waves but had to be operated upon because of insufficient destruction of the stone.

Extracorporeal shock wave lithotripsy

Urolithiasis represents the symptomatic manifestation of various metabolic disturbances which persist after elimination of the immediate problem, i.e., urinary stones, and may lead to the development of recurrent stones. Invasive surgical removal of recurrent stones is sometimes associated with considerable problems. Against this backdrop it is not surprising that after development (1974-1980) and clinical testing (1980-1982) at the Department of Urology of the Ludwig Maximilian University in Munich, a meanwhile clinically proven method of totally noninvasive extracorporeal lithotripsy (ESWL) has disseminated within a relatively short time (from October 1983), first in West Germany (April 1986: 20 ESWL centers) and later all over the world (April 1986: 133 ESWL centers). With the advent of ESWL and semiinvasive techniques of stone extraction (percutaneous lithotripsy, ureterorenoscopy) a transformation of the therapeutic strategy for urolithiasis has been ushered in.

Extracorporeal shock-wave lithotripsy (ESWL) for treatment of urolithiasis

We present our experience with extracorporeal shock wave lithotripsy (ESWL) and the new therapeutic aspects it has generated. The current state of technology also will be discussed.

Transurethral Resection For Bladder Cancer Using 5-Aminolevulinic Acid Induced Fluorescence Endoscopy Versus White Light Endoscopy

PURPOSE Endoscopy done under fluorescence induced by 5-aminolevulinic acid has proved to be a procedure with high sensitivity for detecting transitional cell carcinoma of the bladder. In this multicenter, parallel group, phase III study we compared 5-aminolevulinic acid fluorescence endoscopy guided transurethral bladder resection with transurethral bladder resection done using only white light endoscopy. The proportion of tumor-free resected cases in the 2 groups was evaluated. MATERIALS AND METHODS After patient stratification according to participating centers and European Organization for the Research and Treatment of Cancer risk score 65 and 64 were randomized to the 5-aminolevulinic acid fluorescence and white light endoscopy groups, respectively. Residual tumor was evaluated in the 2 groups by repeat transurethral resection 10 to 14 days later. Analysis was performed according to the intent to treat principle with all patients randomized, followed by per protocol analysis. RESULTS Intent to treat analysis revealed that in the white light endoscopy group 40.6% of cases were resected tumor-free at primary resection, whereas with 5-aminolevulinic acid fluorescence endoscopy guided transurethral resection 61.5% were resected tumor-free (p <0014). On protocol analysis 46.9% patients in the white light and 67.3% in the 5-aminolevulinic acid fluorescence endoscopy groups were resected tumor-free (p <0.031). No difference was noted in the 2 groups in regard to side effects or laboratory findings. CONCLUSIONS The risk of residual tumor after transurethral resection of transitional cell carcinoma is significantly decreased by 5-aminolevulinic acid fluorescence endoscopy.

Clinical experience with the integral photodynamic theraphy of bladder carcinoma

Photodynamic therapy (PDT) was given to 20 patients who had recurring superficial tumours after unsuccessful application of other treatments. The phototherapeutic results were evaluated by check-ups at 3 month intervals (endoscopy, cytology, bladder mapping, renal ultrasonography) and computed tomography (CT) examination at 8-13 month intervals. In six patients treated with PDT no tumour recurrence was found over the whole observation period up to nearly 5 years. Four patients remained free of tumour (12 and 14 months) after repeated transurethral resection (TUR) and Nd:YAG laser therapy following PDT. Due to an initial application of insufficient irradiation, four patients required a second photodynamic treatment. In one of these cases a circumscribed dysplasia which appeared at the left ostium 26 months following PDT was treated successfully using the Nd:YAG laser following TUR. In six patients slight mucosal atypia persisted for a period of at least 2.5 years. One cystectomy had to be performed because of bladder shrinkage. The dissected bladder was free of tumour. According to these preliminary results, PDT with strict patient selection (worst case situation with recommended cystectomy) is justified in the case of recurrent superficial TIS bladder carcinoma.

Quantitative and comparative study of haematoporphyrin-derived photosensitizers on a murine tumour model

Eight commercially available HPD-photosensitizers intended for photodynamic therapy were tested in a murine tumour model with regard to their therapeutic efficacy. The regrowth delay of the fibrosarcoma SSK-2 on the mouse C3H, Neuherberg-line, was determined 3, 24, 48 and 72 h after injection of the drugs (dose: 9 mg kg−1 body weight). The corresponding pharmacodynamics, as measured by regrowth delay, were approximated by an exponential function and the characterizing coefficients derived. These coefficients served to quantify the photodynamic properties of the drugs.The pharmacodynamics of five substances were compared with those obtained fluorometrically. The latter showed shorter decay constants than the therapy-correlated substances which indicates different metabolic behaviour of the therapeutic and diagnostically useful fluorescent components of haematoporphyrin-derived photosensitizers.

Fluorescence detection and photodynamic treatment of photosensitized tumours in special consideration of urology

Most methods of modern laser tumour therapy are physically based on the conversion of light to heat. Recently tumours have also been treated using ionizing processes for tissue ablation. Photodynamic laser therapy (PDT), however, involves light-induced non-thermal biochemical processes and the use of a photosensitizer.Several drugs are known to be stored selectively in tumours after systemic application. This transient marking can be used for diagnostic and therapeutic procedures. The marker most commonly used is dihaematoporphyrin ether/ester (DHE) intravenously injected at doses of 0.2–3.0 mg/kg bodyweight for diagnosis and therapy, respectively. The corresponding clearance intervals after injection of DHE range from 3–48 h to 25–75 h.Detection of photosensitized tumours might offer great advantages. The highly sensitive two-wavelength laser excitation method with computerized fluorescence imaging recently has been transferred to the hospital for clinical tests.Photoinduced production of singlet oxygen is claimed to be the initial process which leads to later tumour destruction and therapy. PDT has been applied to 20 patients suffering from superficial tumours (TIS GII–III) recurred after application of other treatments. The results after PDT were evaluated by three-monthly check-ups (endoscopy, cytology, bladder mapping, renal ultrasonography) as well as by computed tomography (CT) examination at 8–13 month intervals. In six patients treated by PDT no tumour recurrence has been found over the whole observation period of up to 5 years. Four patients have remained free of tumour (12 and 14 months) after repeated transurethral resection (TUR) and Nd-YAG laser therapy following PDT. Due to an initial application of insufficient irradiation four patients required a second PDT. In one patient a circumscribed dysplasia appeared at the left ostium 26 months following PDT and was treated successfully by means of thermal Nd-YAG laser irradiation following TUR. In six patients slight mucosal atypia persisted for a period of at least 2.5 years. One cystectomy had to be performed because of bladder shrinkage. The dissected bladder, however, was free of tumour.These preliminary results suggest that PDT is justified in patients who are in a worst-case situation with cystectomy recommended in case of recurrent superficial TIS bladder carcinoma and indicate the future potential of photodynamic therapy of tumours.Homogeneous irradiation of the area to be treated and a reliable light dosimetry are prerequisites for an effective tumour therapy. Standard instruments for a routine application do not exist, but are under development.

Laser-assisted detection of endogenous porphyrins in malignant diseases

Visualization of earlystagecancer turnsout to be a keypoint in dinical oncology. Ruorescence detection of systemicallyadministered dyes provento accumulate in tumors is one type of diagnostic procedure. The occurrence of endogenous chromophores in malignant tissue has been observed through laserinduced fluorescence in the red spectral range between 550nm and 750nm. Following lumination aftemating between violet and blue lines from a Kr-laser, an optkal mu1tkhanne1 analyser has detected fluorescence in defined areas wfthin chemically induced bladder tumors in rats. The same technique has also been used for the quantitative comparison of fluorescence in human gastrointestinal tumors in nude mice in-vivo. Results show that endogenous porphynns are present in rat bladder tumors as well as in gastrointestinal tumors in nude mice. A correlation between the porphyrin-related fluorescence signal and the histopathological examination indicates that the porphyrin content is dependent upon the tumor grading.

Uniform light distribution in hollow organs by means of backscattering layers

The uniform distribution of light over the area to be photodynamically treated is one of the prerequisites for a successful tumor therapy. For homogenization of laser light distributions especially in hollow organs a new method has been developed. It applies fiber coupled emitters in combination with a highly backscattering layer deposited on the inner wall of the organ to be irradiated. The effect of homogenization by means of this layer has been calculated for spherical and cylindrical hollow organs and compared with experimental results. This method also seems to be applicable for organs with irregular geometry. Laser light applications for different medical fields will be described. Applying the same method, isotropic light detectors with diameters of less than 1 mm have been developed for irradiation control during photodynamic treatment or for determination of light distributions in tissue.

Comparison of Fluorescing and Photosensitizing Properties of Different Porphyrin - Derivative - Preparations

Several substances are known to demonstrate a temporary difference in concentration between normal and tumorous tissue after systemic application. This difference is due to the different metabolic rates in both tissues and enables the marking of tumors for fluorescence detection1,2and for treatment by means of photodynamic methods3,4.