Prostate cancer detection with two sets of ten-core compared with two sets of sextant biopsies.

OBJECTIVES: To compare the cancer detection of two consecutive sets of prostate biopsies using either the sextant or the 10-core technique. METHODS: Ninety-one specimens after radical prostatectomy were used and consecutive sets of biopsies were performed ex vivo on each prostate after the operation. The sextant biopsies were taken paramedian and midlobular, three per side. For the 10-core biopsies, two cores per side from the lateral areas of the prostate were added. We developed a realistic simulation of a transrectal sonographic biopsy procedure. RESULTS: In the first set of sextant biopsies, 55 prostate cancers (60.4%) were found; in the second set, 13 additional tumors were detected. Two consecutive sets of sextant biopsies thus found 68 tumors (74.7%). Using one 10-core biopsy led to cancer detection in 71 of the prostates (78%). A second 10-core biopsy revealed 11 additional tumors, for a cumulative cancer detection rate of 90.1%. We found that 9 (9.9%) of all the cancers were not diagnosed by two consecutive sets of this extended biopsy protocol. Eight of these cancers (88.9%) were clinically significant as determined by a tumor volume larger than 0.5 cm(3). CONCLUSIONS: Although the 10-core protocol is far superior to the commonly used sextant protocol, a significant number of prostate cancers can still be found on a second similar set of prostate biopsies. Even after two consecutive sets of 10-core biopsies, approximately 10% of the prostate tumors remained undetected. Most of them were clinically significant.

Early clinical experience with 5-aminolevulinic acid for the photodynamic therapy of superficial bladder cancer.

OBJECTIVE: To report clinical experience with intravesical instillations of 5-aminolevulinic acid (ALA) for the photodynamic therapy of superficial bladder cancer and to assess any side-effects of the treatment. PATIENTS AND METHODS: Ten patients (six men and four women, mean age 62.3 years, range 42-73) with refractory superficial bladder cancer were treated with photodynamic therapy using 5 g of ALA dissolved in 30 mL sodium bicarbonate instilled intravesically. After a mean retention of 5.1 h, the bladder interior was illuminated transurethrally at radiation integrals of 15, 30 or 60 J/cm2. At integrals of 15 or 30 J/cm2 red light (635 nm) was used and at 60 J/cm2, green light (514 nm, 40 J/cm2) was combined with a subsequent application of red light (635 nm, 20 J/cm2). RESULTS: After 10-12 weeks, four patients had a complete remission, two a partial remission, there was no change in three and one had progressive disease. Of those patients responding, the bladder was preserved in five after a mean follow-up of 15 months (range 6-27). There were no photodermatoses or bladder shrinkage in any patient. CONCLUSIONS: Photodynamic therapy with intravesically applied ALA is effective in destroying superficial urothelial carcinomas of the bladder. There were no serious side-effects which could preclude further clinical testing.

Integral photodynamic treatment of refractory superficial bladder cancer.

PURPOSE: Cystectomy is indicated after unsuccessful transurethral resection and intravesical treatment of superficial bladder cancer. As an alternative, whole bladder photodynamic therapy was done. MATERIALS AND METHODS: In 21 patients the bladder was irradiated with laser light at a wavelength of 630 nm. after intravenous injection of a synthetic porphyrin mixture. RESULTS: Of the 21 patients 12 attained complete remission with a mean disease-free interval of 18.0 months (range 3 to 42), 3 with partial remission were rendered disease-free with transurethral resection or neodymium:YAG laser coagulation and 6 underwent cystectomy. CONCLUSIONS: In patients with refractory superficial bladder cancer the bladder can be preserved by use of photodynamic therapy.

Fluorescence cystoscopy following intravesical instillation of 5-aminolevulinic acid: a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias.

Methods have been sought for the in vivo marking of tiny papillary tumors of the bladder and flat urothelial lesions such as dysplasia or carcinoma in situ, which can easily be missed during conventional endoscopy under white light. A new procedure is reported for the fluorescence detection of urothelial dysplasia and early bladder cancer. The method is based on intravesical application of 5-aminolevulinic acid (ALA). ALA if applied exogenously induces accumulation of protoporphyrin IX (PPIX) in the urothelium of the bladder. PPIX is an intensively red fluorescing agent. The mean ratio of fluorescence intensity between urothelial cancer and normal epithelium was found to be 17:1. Fluorescence excitation was achieved by violet light from a krypton ion laser (lambda = 406.7 nm) or from a xenon arc lamp with a bandpass filter system (lambda = 375-440 nm). Both light sources proved to be of equal suitability for fluorescence excitation. Fluorescence microscopy revealed that the PPIX fluorescence is strictly limited to the urothelium. It could not be detected from the submucosa or muscle of the bladder. Bladder wall biopsies were taken from 90 patients with suspicion of bladder cancer under fluorescence view. The fluorescence detection proved to be of high sensitivity (98%). No serious side effects which would preclude further clinical testing, especially no cutaneous photoreaction, were observed. Tumor-associated fluorescence induced by topical ALA application offers new perspectives in the diagnosis and treatment of bladder cancer. In case of suspicious or positive urine cytologic findings, ALA fluorescence cystoscopy may be useful for detecting the precise site of the malignancy. The procedure might be helpful in complete resection or coagulation of urothelial neoplasms. Due to this, diminishing recurrence rates are expected. However, this hypothesis has to be studied in prospective clinical trials.

Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid.

OBJECTIVES: Tiny papillary tumors and flat urothelial lesions such as dysplasia or carcinoma in situ can easily be missed during routine cystoscopy. Various methods for in vivo detection of fluorescing agents (preferentially localized in malignant tissue) have been developed. Most of them are based on systemically administered synthetic porphyrin compounds and require sensitive detection devices and image processing units for fluorescence visualization. The usefulness of intracellularly accumulated endogenous protoporphyrin IX (PPIX), induced by 5-aminolevulinic acid (ALA), for diagnosis of early bladder cancer and the correlation with cystoscopic, microscopic, and fluorescence findings was investigated. METHODS: ALA was instilled intravesically in 68 patients, followed by fluorescence cystoscopy with violet light from a krypton ion laser that produced fluorescence excitation. There were 299 biopsies obtained from fluorescing and nonfluorescing areas of the bladder. RESULTS: ALA-induced fluorescence could be easily observed with the naked eye during cystoscopy under violet light illumination. All tumor lesions were sharply marked with brightly shining red fluorescence. Correlation of fluorescence and microscopic findings gave a sensitivity of 100% and a specificity of 68.5%. There were 26 malignant or precancerous lesions that were missed during routine cystoscopy but were detected only by ALA-induced fluorescence. CONCLUSIONS: Labeling of urothelial lesions by PPIX fluorescence induced by intravesically instilled ALA seems to be a promising diagnostic procedure for malignant lesions that are difficult to visualize with standard cystoscopy.

[Photodynamic diagnosis of urothelial neoplasms after intravesicular instillation of 5-aminolevulinic acid]. / Photodynamische Diagnose urothelialer Neoplasien nach intravesikaler Instillation von 5-Aminolävulinsäure.

Following transurethral resection of bladder cancer, the fate of patients is clearly related to the presence or absence of precancerous or malignant lesions in the remaining mucosa. We report on a new procedure for in situ diagnosis of these flat, hardly visible urothelial lesions. The method is based on tumor-selective accumulation of endogenous protoporphyrin IX following intravesical instillation of 5-aminolevulinic acid. On excitation with violet light even tiny papillary tumors, dysplastic lesions and carcinoma in situ are bright fluorescing red. In 15 patients 26 neoplastic lesions had been diagnosed only by protoporphyrin IX fluorescence. False-negative results have not yet been observed. In 84% of 285 evaluable specimens the fluorescence findings corresponded correctly with the microscopic findings. It is expected that photodynamic diagnosis will become a matter of routine in detection of bladder cancer.

[Photodynamic therapy of superficial bladder cancer. An alternative to radical cystectomy?]. / Die photodynamische Therapie (PDT) des oberflächlichen Harnblasenkarzinoms. Eine Alternative zur radikalen Zystektomie?

If transurethral resection and intravesical treatment with BCG or chemotherapeutic agents are unsuccessful in recurrent flat multifocal superficial bladder cancer, cystectomy is considered to be indicated. A whole-bladder photodynamic therapy (PDT) was carried out in 23 patients in this worst-case situation, in 19 of whom minimum follow-up of 3 months has been possible. In 5 patients with carcinoma in situ and in 14 patients with flat papillary tumors covering nearly the whole bladder, Photofrin or Photosan-3 was applied intravesically. Irradiation of the bladder followed about 48 h, later with a light dose of 15 J/cm2 or 30 J/cm2 at a wave length of 630 nm. In 12 patients complete remission was achieved; 7 patients showed no evidence of disease over a follow-up period of 3-31 months (median 16.3 months). One patient was lost to follow-up. In 7 patients recurrent disease or residual tumor was observed following PDT, but these were easily managed by transurethral resection or Nd:YAG laser coagulation. In 4 patients PDT failed and cystectomy was carried out. Systemic progression was not observed. PDT has to be regarded as an alternative to cystectomy in the treatment of refractory superficial bladder cancer.

Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster.

In this study the localisation of porphyrinoid photosensitizers in tumours was investigated. To determine if tumour selectivity results from a preferential uptake or prolonged retention of photosensitizers, intravital fluorescence microscopy and chemical extraction were used. Amelanotic melanoma (A-Mel-3) were implanted in a skin fold chamber in Syrian Golden hamsters. Distribution of the porphyrin mixture Photofrin and three porphycenes, pure porphyrinoid model compounds, was studied quantitatively by intravital fluorescence microscopy. Extraction of tissue and blood samples was performed to verify and supplement intravital microscopic results. Photofrin accumulated in melanomas reaching a maximum tumour:skin tissue ratio of 1.7:1. Localisation of the different porphycenes was found to be highly tumour selective (3.2:1), anti-tumour selective (0.2:1), and non-selective (1:1) with increasing polarity of the porphycenes. The two non-tumour selective porphycenes had distinctly accelerated serum and tissue kinetics; serum halflife times being as short as 1 min. The specific localisation of the slowly distributed, tumour selective photosensitizers, occurred exclusively during the distribution from serum and uptake into tissues. For the most selective porphycene, the tumour selection process had a halflife of 260 +/- 150 min and led to a strongly fluorescent tumour edge edema. Accumulation of porphyrines by the amelanotic melanoma (A-Mel-3) can be attributed to an enhanced uptake rate for lipophilic molecules in this subcutaneously growing neoplasm. The slow distribution of the two tumour specific photosensitizers and the strong fluorescence of these hydrophobic molecules in the tumour compartment with a high water content indicate a carrier role of serum proteins in the selection process. Enhanced permeability of the tumour vasculature to macromolecules appears to be the most probable reason for the tumour selectivity of these two sensitisers.

Acute effects of shock waves on tumors assessed by magnetic resonance imaging. Possible role of blood flow reduction.

RATIONALE AND OBJECTIVES: The effects of shock waves on experimental tumors in vivo by gadolinium(+)-DTPA-enhanced magnetic resonance imaging (MRI) are assessed. METHODS: Two amelanotic hamster melanomas were implanted in the dorsal skin of 19 hamsters. In experiment 1 (n = 7), MRI of untreated tumors was performed before, and 5 and 15 minutes after intravenous injection of Gd(+)-DTPA. In experiment 2 (n = 12), 200 shock waves were applied on one of the implanted tumors. Magnetic resonance imaging was performed 15 minutes after treatment before, and 5 and 15 minutes after injection of Gd(+)-DTPA. RESULTS: In experiment 1, signal intensities (SI) of untreated tumors increased after injection of Gd(+)-DTPA. In experiment 2, enhancement was significantly delayed in shock-wave-treated tumors as compared with controls. Histology of the treated tumors revealed vascular damage. CONCLUSION: Differences in enhancement between shock-wave-treated and control tumors after injection of Gd(+)-DTPA are interpreted as the consequence of reduced and delayed accumulation of Gd(+)-DTPA in treated tumors due to shock wave induced vascular damage and reduced tumor perfusion.

[Magnetic resonance tomography of scaphoid pseudarthrosis: clinical and x-ray aspects]. / Kernspintomographie der Skaphoidpseudarthrose: Klinische und röntgenologische Gesichtspunkte.

37 patients with non-unions of fractures of the carpal scaphoid were examined with MRI and the results compared with conventional radiographs. Advantages of MRI are the documentation of concomitant soft tissue changes in the region of the pseudarthrosis, and the early detection of osteonecrosis of one of the fragments. Advantages of conventional radiographs are the exact documentation of cancellous bone morphology and the position of the fragments.

[Photodynamic laser tumor therapy with a hematoporphyrin derivative in spinocellular carcinoma of the external ear]. / Photodynamische Lasertumortherapie mit Hämatoporphyrin-Derivat (HpD) eines Spinozellulären Karzinomes der Ohrmuschel.

Haematoporphyrine-derivative (hpd) selectively photosensitises malignant tumours following intravenous application. 48 hours after injection of hpd an integral laser-light application of the tumour and the surrounding normal tissue was performed. We report on the successful administration of this photodynamic therapy in a patient with a spinocellular carcinoma of the auricle. 16 days after therapy the tumour showed a complete response without damage of the also irradiated surrounding normal tissue. Apart from a temporary sensitivity to light no side effects of the therapy were seen.

[Gd-DTPA-supported magnetic resonance tomographic perfusion follow-up of shockwave-treated tumors]. / Gd-DTPA-gestützte kernspintomographische Perfusionskontrolle von stosswellentherapierten Tumoren.

The signal characteristics of 14 shockwave-treated and 14 solid control tumors were studied before and after injection of Gd-DTPA in an animal model. T1-weighted images of shockwave-treated tumors documented no significant signal intensity increase after contrast media injection in comparison with the untreated control tumors. The reduction of perfusion in shockwave-treated tumors can be documented in vivo by the signal intensity changes of the tumors after contrast media injection.