Treatment of astrocytoma grade III with Photofrin II as a radiosensitizer. A case report.

INTRODUCTION: Astrocytomas are neoplasms that originate from glial cells. Anaplastic astrocytoma is classified as WHO III, with 27 % of the individuals with grade III astrocytoma living for at least 5 years even after treatment (radiation and chemotherapy). Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in both in vitro and in vivo tumor models. MATERIAL AND METHODS: This case report presents a woman suffering from an inoperable astrocytoma WHO III since 2004. The patient was treated with radiation therapy and Photofrin II as a radiosensitiser. The patient underwent irradiation with 40 + 20 Gy boost. The patient was given a single intravenous dose of 1 mg/kg Photofrin II 24 h prior to the initiation of radiation therapy. RESULTS: The patient is still alive without any significant side effect with a follow up of 106 months. MRI shows no evidence of disease. CONCLUSION: The follow-up results are encouraging regarding the application of Photofrin II as an effective radiosensitizing agent in the treatment of inoperable WHO III astrocytoma.

[The Department of Urology at the Medical Center of the University of Munich and its partners in Central and Eastern Europe in the period from 1969 to 2004 : An eyewitness account]. / Die Urologische Universitätsklinik München und ihre Partner in Mittel- und Osteuropa in der Zeit von 1969 bis 2004 : Ein Zeitzeugenbericht.

During the 1980s, the Ludwig Maximillian University Department of Urology under the direction of Professor Dr. Egbert Schmiedt developed a close cooperation with Bulgarian urologists. As the successor of Professor Schmiedt, I have tried to continue this cooperation, especially in the scientific field, and also to integrate Romanian urology. At the request of several leading urologists of eastern European countries, the Central European Association of Urology which should act under the umbrella of European Association of Urology was founded. Although misunderstandings obviously prevented this, our efforts do not seem to have been useless-at least as far as the idea of modern European urology is concerned.

[Transcriptome analyses in renal cell carcinoma. Combination of laser microdissection and microarrays]. / Transkriptomanalysen beim Nierenzellkarzinom. Kombination von Lasermikrodissektion und Microarrays.

BACKGROUND: The objective of this study was to test the feasibility of combined laser microdissection and microarray-based expression analysis in renal cell carcinoma (RCC) and to detect the most strongly deregulated genes. METHODS: Laser microdissection of tumor areas and subsequent gene expression analysis (47,000 transcripts) was performed on snap-frozen primary tumor samples from 15 patients with clear cell RCC. Four normal kidney samples served as controls. Validation was performed for one gene with quantitative RT-PCR on additional samples. RESULTS: Isolation of intact RNA from microdissected tissue was successful; 179 transcripts were significantly deregulated by a factor of 5 or more. Upregulation of FABP7 was confirmed by quantitative RT-PCR. CONCLUSION: In RCC the combination of laser microdissection and subsequent microarray analysis provides reliable data from precisely defined material. This is an optimal starting point for the development of novel therapeutic and diagnostic options.

The Application of Photofrin II as a sensitizing agent for ionizing radiation--a new approach in tumor therapy?

Radiosensitizers represent an enticing concept in tumor therapy. As ionizing radiation affects both neoplastic and normal tissues, its effects are generally non-specific. The aim of applying a radiosensitizing agent is to achieve a maximum effect on tumor tissue, while minimizing the damage to normal tissues. A variety of parameters such as the oxygen supply and the state in the cell cycle, need to be taken into account when evaluating a potential radiosensitizer. Most of the previously known radiosensitizers are neither selective nor tumor specific. In this article, we review the properties and radiosensitizing potential of Photofrin II. Photofrin II is well-known as a photosensitizing agent in photodynamic therapy. In recent years, a radiosensitizing potential of the substance has been demonstrated, specifically increasing the sensitivity of solid tumor tissues, especially of radio-resistant, hypoxic tumor cells, to radiation. This radiosensitizing effect has been demonstrated both by in vitro studies and by animal experiments. Several studies with tissue cultures have demonstrated a radiosensitizing effect of Photofrin II in glioblastoma (U-373MG) and bladder cancer cell lines (RT-4). No effect was noted in colon carcinoma cell lines (HT-29). Unpublished data of additional cell lines will be mentioned in the review. Animal experiments with Lewis sarcoma and with bladder cancer have moreover demonstrated an in vivo effect of Photofrin II as a radiosensitizer. The mechanism of this radiosensitizing effect is not completely understood. In vitro data, however, support the hypothesis that the radiosensitizing action involves OH-radicals in addition to a potential impairment of repair mechanisms after sublethal damage of ionizing radiation. Moreover, early results of a phase I trial are available and document the potential feasibility of the application of Phototofrin II as a radiosensitizing agent in clinical practice.

Cellular and molecular analyses of major histocompatibility complex (MHC) restricted and non-MHC-restricted effector cells recognizing renal cell carcinomas: problems and perspectives for immunotherapy.

Renal cell carcinomas belong to the small group of tumors that are able to induce antitumor responses. Here we describe two general types of cytotoxic effector lymphocytes that can eliminate autologous tumor cells and discuss the role that major histocompatibility complex encoded molecules play in governing their specificities. Improved understanding of the cellular and molecular basis of renal cell carcinoma recognition opens new avenues of research with the potential to develop better immunotherapies for patients with metastatic disease.

[Indwelling transurethral catheter]. / Probleme mit dem Dauerkatheter? So machen Sie ein notwendiges Ubel erträglich.

Apart from injuries occurring during catheter placement, the most important of the risks associated with indwelling transurethral catheters are incrustation of the catheter and infection, possibly leading on to urosepsis. Recommended countermeasures are the application of strict criteria when establishing the indication for catheterization, reversion to alternative measures, such as condom urinals, and the careful selection of catheter material.

Porphyrins as radiosensitizing agents for solid neoplasms.

The biological effects of radiation affect both neoplastic and normal tissues. The nature and extent of such effects, however, depend on selected biological parameters (e.g., oxygen supply, cell cycle) and can be modified by chemical agents such as radiosensitizers, radioprotectors and chemotherapeutic agents. A precise control of the mode of action of the radiation is important in order to achieve the maximum effect on tumor tissue, while minimizing the effect on normal tissues. Most of the known and routinely used radiosensitizers are neither selective nor tumor specific. This article reviews a new selective and specific modality that increases the sensitivity of solid tumor tissue, especially of radio resistant, hypoxic tumor cells, to radiation. This modality is currently under early clinical evaluation and encompasses the application of Photofrin II, which is already used as a photosensitizer in photodynamic therapy (PDT) at predetermined times prior to irradiation.

Large de novo renal cell carcinoma in a 10-year-old transplanted kidney: successful organ-preserving therapy.

BACKGROUND: A recent review of the Cincinnati Transplant Tumor Registry recorded 24 de novo renal cell carcinomas developing in renal allografts. However, late development of these tumors after transplantation is very rare. Only four reports exist regarding conservative surgery on kidney transplant tumors. METHODS: This is a report on a case of a large 6-cm de novo renal cell carcinoma in a 10-year-old transplanted kidney. Optimal therapy by transplant nephrectomy or tumor enucleation was discussed. RESULTS: Partial resections or enucleations of renal cell carcinoma are still less than ideal in carcinomas larger than 3 cm considering the higher risk of local recurrence. But the recipient in this case had done so well and had had such a high quality of life after transplantation that partial nephrectomy as therapy of choice was selected. Now the patient is 2 years tumor free. CONCLUSION: The case report demonstrates that in certain select cases of large tumors, organ-preserving surgery could be an alternative approach in combining complete tumor removal with preservation of graft function.

Allogeneic vaccination for renal cell carcinoma: development and monitoring.

An allogeneic tumor cell vaccine should display a natural immunogenicity that allows the stimulation of tumor-reactive effector cells in patients. Furthermore, the vaccine should express antigens that are shared by many tumors to which patients are not tolerant. A variety of tumor peptides should be presented by different HLA-molecules due to limited MHC matching with recipients and last but not least, the vaccine should have a strong growth potential in vitro to allow adequate amounts of vaccine to be generated for long-term usage. In vitro and in situ studies with the renal cell carcinoma cell line RCC-26 demonstrate: (1) RCC-26 can induce complex allospecific responses through direct priming; (2) RCC-26 can not only reactivate cytotoxic T lymphocytes (CTL) of a memory phenotype but they also can induce de novo tumor-antigen associated responses in normal donors; (3) these cells present epitopes restricted by several MHC molecules, allowing the vaccination of patients matched for different HLA alleles; and (4) they stimulate HLA-A*0201-restricted T cells bearing characteristic T cell receptors (TCR). Thus, in addition to using limiting dilution killer and ELISPOT assays, molecular tracking of a tumor-specific TCR can be used to judge the development of antitumor reactivity and vaccine efficiency.

Interferon alfa and vinblastine versus medroxyprogesterone acetate in the treatment of metastatic renal cell carcinoma.

OBJECTIVES: Since the beginning of the 1980s, when gene technology provided sufficient amounts of cytokines, numerous Phase II studies in metastatic renal cell carcinoma were carried out mostly with interferon alfa (IFN-alpha) and interleukin-2 (IL-2). So far, no randomized prospective trials including untreated control groups have been reported. We present a prospective study comparing IFN-alpha and vinblastine (VBL) versus medroxyprogesterone acetate (MPA). METHODS: Immunochemotherapy schedule consists of IFN-alpha 8 million U/day subcutaneously for 3 days per week and VBL 0.1 mg/kg body weight intravenously at 3-week intervals. MPA was administrated intramuscularly at a dosage of 500 mg/week. The response rates, toxicities, and actuarial overall survival were analyzed. RESULTS: The overall response rate in 41 patients receiving IFN-alpha and VBL treatment was 20.5% (95% confidence interval, 9% to 33%). Four patients reached a complete and 5 patients reached a partial remission. No remissions were observed in 35 patients of the control group. A statistically significant survival benefit for the IFN-alpha and VBL group could not be demonstrated. Excluding fever, mild to moderate toxicities were observed. About one third of patients refused the proposed schedule due to general malaise and fatigue. CONCLUSIONS: A survival benefit or a favorable outcome of patients with metastatic renal cell carcinoma, treated with IFN-alpha and VBL, could not be demonstrated. As judged from this analysis, IFN-alpha and VBL therapy does not sufficiently meet the requirements of a palliative treatment of renal cell carcinoma.

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.

Expression of plakoglobin in renal cell carcinoma.

Little is known about the role of molecules involved in cell-cell interactions during the progression of renal cell carcinoma (RCC). We investigated the expression of plakoglobin (a component of the cadherin-catenin adhesion system) in 94 samples of normal kidney tissue from patients with RCC, in 109 primary renal cell carcinomas and in 16 metastases by immunohistochemistry. Expression of plakoglobin was significantly diminished in tumor tissue, particularly in metastatic lesions, as compared to normal kidney tissue (p < 0.001). Follow-up data were available from 87 patients. Patients with a diffuse plakoglobin expression (91-100% positive cells) in primary tumor tissue had a significant better survival rate than patients with a disturbed plakoglobin expression (p < 0.05) as determined by the log rank test. These results indicate that loss of plakoglobin may play an important role in malignant transformation of renal cells. Plakoglobin expression status could give additional information about the individual prognosis.

Resection of hypernephromas with vena caval or right atrial tumor extension using extracorporeal circulation and deep hypothermic circulatory arrest: a multidisciplinary approach.

OBJECTIVE: Among retroperitoneal tumors, renal cell carcinoma most often invades the retrohepatic inferior vena cava or the right atrium. Even in these cases, radical nephrectomy may be performed with curative intention. The aim of this retrospective study was to elucidate the impact of cardiopulmonary bypass and hypothermic circulatory arrest on surgical complications, primary mortality, and long-term survival. PATIENTS AND METHODS: From Jan. 1981 till Aug. 1996, 44 patients were operated upon for renal cell carcinoma with advanced vena caval extension. The patients were divided into two groups. In 19 cases (Cardiopulmonary Bypass Group), extracorporeal circulation and deep hypothermic circulatory arrest was used. The Conventional Technique Group comprised 25 patients who had radical nephrectomy, paraaortic lymphadenectomy and extirpation of the intracaval tumor thrombus applying common principles in vascular surgery. The median age was 59 years with a range from 42 to 78 years in the Cardiopulmonary Bypass Group, and 60 years, ranging from 22 to 72 years, in the Conventional Technique Group. In addition, both groups did not differ in gender, UICC TNMG staging classification, and perioperative risk factors. A review of the patient charts was done and surveys were sent to survivors or nearest of kin. Wilcoxon test and log-rank test were used as appropriate. RESULTS: A lower intraoperative complication rate was found in patients who had surgery using cardiopulmonary bypass. This was especially true with embolization of the tumor thrombus into the pulmonary arteries: 0.0% in Cardiopulmonary Bypass Group and 16.0% in Conventional Technique Group (P < 0.05). Severe hemorrhage occurred in 10.5% (Cardiopulmonary Bypass Group) and 16.0% (Conventional Technique Group). This translated into a significantly lower perioperative mortality in the Cardiopulmonary Bypass Group when compared to the Conventional Technique Group (5.6 and 16.0%, respectively). In spite of these results, differences in long-term survival did not reach statistical significance. But, a trend to superior long-term survival was apparent. The mean survival was 1289 +/- 278 days in the Cardiopulmonary Bypass Group and 746 +/- 166 days in the Conventional Technique Group. CONCLUSIONS: Due to acceptable long-term results, the resection of hypernephromas showing extensive vena caval invasion seems to be justified. The use of cardiopulmonary bypass and hypothermic circulatory arrest is able to decrease primary morbidity and mortality. However, the influence on long-term survival remains to be proven.

Interstitial laser therapy outcomes in benign prostatic hyperplasia.

Two hundred thirty-nine patients with benign prostatic hyperplasia (BPH) were treated using interstitial laser coagulation (ILC or LITT; laser-induced interstitial thermotherapy), and the long-term results were determined. In this minimally invasive procedure, special laser light guides were inserted into the adenoma tissue in order to achieve primary large-volume coagulation necrosis and secondary shrinking, leaving the urethra intact. The AUA Symptom Scores improved markedly, from an average of 25 pretreatment to an average of 6 at 1 year. Peak urine flow rates improved commensurably, from 8 mL/sec pretreatment to 18 mL/sec at 1 year. Postoperative irritative symptoms occurred occasionally, affecting only 12% of patients. Significant complications were rare, with 4% of patients suffering strictures and 7% retrograde ejaculation. No patients suffered impotence or incontinence. Only 9.6% of patients required retreatment for BPH during 12 months of follow-up. Twelve patients were treated with subsequent transurethral laser incision of the bladder neck in order to shorten the time required for improvement of voiding function.

Photofrin as a specific radiosensitizing agent for tumors: studies in comparison to other porphyrins, in an experimental in vivo model.

The use of ionizing radiation for tumor treatment represents a well established therapeutic modality. The efficiency and selectivity of radiotherapeutic protocols can be often enhanced by the addition of specific chemical compounds that optimise the response of the tumor to the incident radiation as compared with peritumoral tissue districts. The results of this study showed that Photofrin, a porphyrin derivative which is presently used as a tumor-photosensitizing agent in photodynamic therapy (PDT), can also act as an efficient tumor radiosensitizer. To test this possibility, we used nude mice subcutaneously implanted with human bladder cancer RT4. The mice were injected with different porphyrin-type photosensitizing agents, including Photofrin, 5-aminolevulinic acid, chlorin e(6), haematoporphyrin, protoporphyrin, Zn-tetrasulphophtalocyanine, and irradiated with 5 and 15 Gy using a Siemens X-ray device. Even though all the porphyrins accumulated in significant amounts in the neoplastic lesion, only Photofrin significantly improved the response of the tumor to irradiation by increasing the doubling time of the tumor volume from 6.2 days in the untreated control group to 10.9 days in the 5 and 15 Gy-irradiated groups. The tumor response was maximal with injected Photofrin doses of 7.5 mg/kg, and was not further enhanced by injection of higher doses. Our hypothesis is, that the radiosensitizing effect of Photofrin seems to be due to some oligomeric constituents which could specifically react with radiogenerated-radicals thereby amplifying the effect of the X-ray radiation.

[Diagnosis in urinary tract infections]. / Diagnostik bei Harnwegsinfektionen.

For a rational diagnostic work-up of urinary tract infections (UTI), a detailed history and a standardised examination of smear material, prostatic fluid and urine are essential. Examination of the urine is simple, with test strips, microscopic examination of the sediment and determination of the bacterial count by the dipstick procedure having proved their worth in practice. Isolation and identification of pathogens and the preparation of an antibiogram require special knowledge of microbiological techniques. Accurate evaluation of the urine and its constituents requires a knowledge of how the urine has been collected; we recommend spontaneously passed urine in men and young children, and catheter urine in women. Acute complicated and chronic recurrent UTIs require radiological studies and sonography. Occasionally, nuclear-medical investigations and angiography or CT may be necessary for detailed classification. In cases of obstruction of the lower UT or neurogenic problems with urinary bladder, urodynamic investigation and endoscopy must be performed. This stepwise diagnostic evaluation allows both optimal classification of the UTI and a saving in costs.

[Applications for lasers in carcinoma of the urinary bladder]. / Laseranwendung beim Harnblasenkarzinom.

The poor prognosis of bladder cancer, multimorbidity after therapeutic management and the suspicion that tumor, cell seeding is made more probable by TUR justify the search for safe and more effective treatment procedures. In this connection different laser systems must be discussed, but the optimal indications for the different laser combinations need to be determined by randomized, prospective studies.

[Laser--science fiction or a new dimension in medicine?]. / Laser--Science Fiction oder eine neue Dimension in der Medizin?

Using the Nd: YAG laser, contact-free destruction of tumors is possible while closing the blood and lymphatic vessels at the same time. It is very uncommon for a tumor to seed during the operation. In contrast to established operative procedures, further advantages are: no bleeding, no general anesthesia, minimal sedation for endoscopic procedures, and short operation times. Furthermore, this method presents interesting possibilities for the diagnosis and treatment of tumors, as well as in endoscopic lithotripsy.

[Endoscopic obliteration of tumors of the bladder using laser (author's transl)]. / Endoskopische Zerstörung von Blasentumoren mit Laser.

In the period between June 1976 and August 1979 we treated 302 bladder tumors up to a tip of thumb-size by Neodymium-YAG-laser. 196 larger bladder tumors were removed by transurethral resection combined with laser irradiation one week later. All tumors were pTA to pT3a, NO, MO. Two months after treatment we found local recurrence in 9% following use of the rigid laser endoscopes. In contrast, the local recurrence rate was only 2, 1% using laser endoscope with modified Albarran insert. In cases of small, multiple and flat bladder tumors the Neodymium-YAG-laser application is an effective and gentle procedure.

[Human papillomaviruses (HPV) in urology. II: 10 years evaluation of differential HPV therapy]. / Humane Papillomviren (HPV) in der Urologie. Teil II: 10-Jahres-Bewertung differenzierter HPV-Therapie.

Human papillomaviruses can give rise to histoclinical changes in the epithelium of the anogenital region. These have to be considered and treated differentially on the basis of their morphology, size, number, location and oncogenic relevance. Up until now, no method of treatment has proved to be clearly superior to others or to be especially suitable for the comprehensive therapy of all varieties of HPV efflorescences. We will present and evaluate a comprehensive concept of HPV treatment that takes into consideration the medical aspects of HPV associated lesions, the treatment choice of the patient, drugs approval and the legal responsibility for the individual methods of HPV treatment. Our experience enables us to critically analyze the current HPV therapy guidelines of various specialist societies which do not adequately take specific urological aspects into consideration.