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Biomedical subjects

M Kriegmair

Publications and source records attributed to M Kriegmair.

At least 37 records · Page 2Linked to original sources
PubMed1996

Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence.

PURPOSE: We determined whether the sensitivity of detecting dysplasia or early bladder cancer can be improved by 5-aminolevulinic acid induced porphyrin fluorescence. MATERIALS AND METHODS: A 3% 5-aminolevulinic acid solution was instilled intravesically before cystoscopy in 104 patients. The 5-aminolevulinic acid induced porphyrin fluorescence was excited by violet light from a krypton ion laser (wavelength 406.7 nm.). RESULTS: The sensitivity of the fluorescence cystoscopy (96.9%) was significantly (p < 0.0001) greater than that of white light cystoscopy (72.7%). There was no impact on specificity. CONCLUSIONS: Due to the high sensitivity of the procedure fluorescence guided biopsies are recommended instead of random biopsies.

Administration, Intravesical↗
PubMed1995

Paraureteral calculi caused by ureteroscopic perforation.

OBJECTIVES: Ureteroscopy has become an effective and safe procedure for treatment of ureteral calculi. Formation of strictures are considered long-term complications with a low incidence. This report focuses on the incidence of strictures in cases of calculi pushed or flushed retroperitoneally alongside the ureter because of iatrogenic ureteral perforation. METHODS: Fifteen consecutive patients with paraureteral calculi caused by ureteroscopic perforation were observed. An excretory urogram was performed after a mean of 22.5 months, with a range of 9 to 54 months. In all patients, a stent was placed for 3 to 41 days (mean, 13.5 days) and antibiotics were administered between 3 and 5 days postoperatively. RESULTS: Only 1 patient of 15 with a short stricture of the distal ureter was observed. The stricture was successfully treated by endoscopic ureterotomy, balloon dilation, and transient placement of a ureteral stent. CONCLUSIONS: Paraureteral calculi caused by ureteral perforation are a minor complication of ureteroscopy, which rarely lead to formation of strictures. Removal of paraureteral calculi by enhanced endoscopic procedures or open surgery is not required.

Adult↗
PubMed1995

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.

Actuarial Analysis↗
PubMed1995

Outcome analysis after post-chemotherapy surgery in patients with non-seminomatous germ cell tumours.

BACKGROUND: The goal of the study was to analyse long-term outcome after post-chemotherapy surgery in male patients with non-seminomatous germ cell tumours (NSGCT). PATIENTS AND METHODS: We reviewed the charts of 111 patients with metastatic NSGCT treated at a single institution from 1979 to 1993 who underwent post-chemotherapy resection of residual masses after normalisation of tumour markers. The prognostic relevance of the extent of tumour residuals, the comprehensiveness of surgery and the histology at resection was analysed. RESULTS: Thirteen patients (12%) harboured viable cancer, and 46 patients (41%) mature teratoma at post-chemotherapy surgery. Only seven (54%) of the 13 patients with viable cancer remained continuously disease-free. Incomplete surgery predicted an impaired outcome (62% vs. 86% survival), although only one recurrence was observed at a site of an incompletely resected mass. Moreover, a progression-free interval < or = 3 months after post-chemotherapy surgery was correlated with worse subsequent survival (p = 0.0001). CONCLUSIONS: Post-chemotherapy surgery remains an essential part of the treatment for metastatic NSGCT. Resection of viable cancer and mature teratoma is of therapeutic benefit. Viable cancer at surgery defines the need for further chemotherapy.

Adolescent↗
PubMed1995

Cellular fluorescence of the endogenous photosensitizer protoporphyrin IX following exposure to 5-aminolevulinic acid.

Supplying 5-aminolevulinic acid (ALA), a precursor in the biosynthetic pathway to heme from an external source leads to an accumulation of the endogenous fluorescent photosensitizer protoporphyrin IX (PPIX). Following instillation of ALA in the urinary bladder neoplastic tissue can be discerned by fluorescence cystoscopy or treated by illumination with light of an appropriate wavelength. In order to provide a biological rationale for the clinical findings, we have analyzed the capacity of three different cell lines to accumulate PPIX by flow cytometry. Three different urothelial cell lines, normal fibroblasts and endothelial cells were exposed to ALA under varying conditions. Urothelial cell lines J82 and RT4, derived from malignancies of the bladder displayed fluorescence intensities 9- and 16-fold, respectively, above the fluorescence level of the normal urothelial cell line HCV29. Human umbilical cord endothelial cells fluoresced moderately while the fibroblast cell line N1 exhibited a fluorescence level comparable to those of the cancer cells. Fluorescence increased with increasing cell density and was also dependent on the growth of cells as monolayers or multicellular spheroids. Increasing ALA concentrations led to saturation of fluorescence after 4 h of incubation at cell type-specific fluorescence levels obtained at different ALA concentrations. Continuous incubation in medium containing serum resulted in a linear rise of fluorescence during the first 4 h, which was followed by a saturation period (8-24 h) and a renewed rise. In the case of serum depletion, fluorescence intensities were significantly higher and increased linearly during the entire 48 h incubation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminolevulinic Acid↗
PubMed1995

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.

Administration, Intravesical↗
PubMed1995

[Tumor cell vaccination for treatment of renal cell carcinoma].

Vaccination, mostly with inactivated autologous tumour, has been carried out for the treatment of renal cell cancer since 1976. Attempts to enhance immunogenicity have involved the use of different modifications and added adjuvants for preparation of the vaccines. In metastatic renal cell cancer vaccination has proved to be ineffective, apart from remissions observed in isolated cases. In principle, however, it does seem that vaccination might be valuable as an adjuvant treatment for renal cell cancer. Following resection of the primary tumour, the blood and lymphatic system should be sterilized by cytotoxic T cells and antitumour antibodies induced by vaccination. The effectiveness of such therapeutic procedures cannot be proven except in prospective randomized trials with untreated patients as controls. Clinical trials of autologous tumour vaccines modified by bacillus Calmette Guérin have failed to demonstrate increased disease-free survival. New prospects for future vaccine preparations are opened up by the recent detection of MHC-restricted tumour-specific T cells and by the possibility of genetically modified vaccines.

Adjuvants, Immunologic↗
PubMed1995

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.

Aged↗
PubMed1994

Immunocytochemical detection and phenotypic characterization of micrometastatic tumour cells in bone marrow of patients with prostate cancer.

Monoclonal antibodies (mAbs) specific for cytokeratins are potent probes for the identification of disseminated individual epithelial tumour cells in mesenchymal organs such as bone marrow. We have used a monoclonal antibody (mAB) against cytokeratin 18 (CK18) for the detection of individual metastatic tumour cells in bone marrow aspirates from 84 patients with carcinoma of the prostate. CK18+ cells were detected in a sensitivity of 1 per 8 x 10(5) marrow cells using the alkaline phosphatase anti-alkaline phosphatase (APAAP) system for staining. We were able to detect CK18+ tumour cells in the marrow of 33% of patients with stage N0M0 prostate cancers. The incidence of CK18+ cells showed a significant correlation with established risk factors, such as local tumour extent, distant metastases and tumour differentiation. For further characterization of such cells in patients with prostate cancer, we developed an immunocytochemical procedure for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate-specific antigen (PSA). In a first step, cells were incubated with a murine mAb against PSA, followed by gold-conjugated goat anti-mouse antibodies. In a second step, a biotinylated mAb to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 14 patients with carcinomas of the prostate. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hyperplasia (BPH).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Diseases↗
PubMed1994

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.

Administration, Intravesical↗
PubMed1994

Intravesical instillation of 5-aminolevulinic acid: the fluorescent metabolite is limited to urothelial cells.

OBJECTIVES: For photodynamic therapy 5-aminolevulinic acid is an attractive compound, since it is a physiologic endogenous substance, and its application in excess results in the accumulation of the metabolite protoporphyrin IX, a very effective photosensitizer. The topical application of 5-aminolevulinic acid in the urinary bladder led to pronounced fluorescence in neoplasias when excited with violet laser light during cystoscopy. The aim of this study was the determination of the transmural distribution of protoporphyrin IX in order to estimate potential efficacy and side effects of a therapeutic application of 5-aminolevulinic acid. METHODS: 5-Aminolevulinic acid was instilled prior to cystoscopy and biopsies were taken of lesions that were either fluorescing or nonfluorescing. Fluorescence distribution was analyzed by fluorescence microscopy on cryostat sections prepared from 72 biopsy specimens. In addition, multicellular spheroids grown from tumor cells and fibroblasts were exposed to 5-aminolevulinic acid and analyzed accordingly. RESULTS: Biopsy preparations showed that the fluorescence of protoporphyrin IX was limited to normal and neoplastic urothelial cells. Clinical findings were supported by the in vitro data, which showed negative protoporphyrin IX fluorescence in fibroblasts. CONCLUSIONS: Thus, 5-aminolevulinic acid might be superior in selective accumulation to conventional sensitizers known to localize also in endothelial cells of the tumor stroma. The data appear to hold great promise for 5-aminolevulinic acid in photodynamic diagnosis and therapy in bladder cancer, as phototoxicity will be limited to mucosal lesions. Bladder shrinkage due to photodamage of subepithelial structures even in case of high light doses is not expected.

Administration, Intravesical↗
PubMed1994

Sequential resection of residual abdominal and thoracic masses after chemotherapy for metastatic non-seminomatous germ cell tumours.

Thirty-eight patients with advanced non-seminomatous germ cell tumours (NSGCTs) underwent multiple surgical interventions (two in 33 patients, three in four patients, four in one patient) after cisplatin-based chemotherapy. All patients had normal serum tumour markers but persistent radiographic masses. The larger mass was routinely resected first. Fifteen patients (39%) had dissimilar histological findings at sequential surgical procedures, 12 of whom demonstrated less favourable pathological features during the first operation and three at the second. Patients who underwent both retroperitoneal lymph node dissection (RPLND) and lung resection showed less favourable histological features in the retroperitoneum in nine cases and in the lung in three cases. Eight of 16 patients (50%) without mature teratoma in their primary tumours showed complete necrosis/fibrosis at all surgical interventions, whereas all patients whose primary tumour was classified as malignant teratoma intermediate demonstrated mature teratoma at least at one anatomical site. As histology of post-chemotherapy residual masses cannot be extrapolated from one anatomical site to another, patients usually are properly managed by excision of all residual masses. In particular, in patients with necrosis/fibrosis at lung resection omission of RPLND is not advised.

Abdominal Neoplasms↗
PubMed1994

[Photodynamic diagnosis of urothelial neoplasms after intravesicular instillation of 5-aminolevulinic acid].

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.

Administration, Intravesical↗
PubMed1994

[Photodynamic therapy of superficial bladder cancer. An alternative to radical cystectomy?].

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.

Aged↗
PubMed1994

[Laser treatment of urethral strictures].

Since the late 1970s different laser systems have been applied for the treatment of urethral strictures. Thermal effects adjacent on tissue have made the long term results of Nd:-YAG and Ar+ laser application discouraging. New laser systems (KTP, Excimer, Ho: YAG) still have to prove their efficacy in randomized clinical trials against cold knife urethrotomy.

Adult↗
PubMed1994

[Laser coagulation treatment of urothelial tumors of the upper urogenital tract with the Nd:-YAG laser].

Six patients with upper urinary tract tumors were treated in our department with the Nd:-YAG laser between 1989 and 1993. The average follow-up was 23.8 months. The mean age of the patients was 65.7 years. The patients were selected for organ-conserving treatment because of bilateral synchronous tumors (2 cases), a solitary renal unit (2 cases), renal insufficiency with high surgical risk (1 case) and high surgical risk alone (1 case). Two patients were treated with open tumor excision and laser, two patients with ureteroscopic and percutaneous procedures one patient with percutaneous treatment and one patient with ureteroscopy. Two patients underwent nephroureterectomy; one of them died of metastatic bladder cancer 9 months later. Local relapses were observed in one patient who had been treated endoscopically. In a follow-up period of 6-36 months there were three patients who had no relapses. Three patients received intracavitary therapy. Kidney conserving procedures with the Nd:-YAG laser in patients with upper urinary tract tumors should be reserved for highly selected cases.

Aged↗
PubMed1994

[Laser lithotripsy of ureteral calculi].

A total of 149 patients with 152 ureteral stones were treated with intraureteral lithotripsy by Dye-laser (83.55%), Alexandrite-laser (41.27%), electrohydraulic lithotripsy adapted for use in the ureter (25.16%) or neodymium: YAG laser with optomechanic coupling (3.2%). The Dye-laser has an automatic pulse shut-off mechanism with spectral analysis of the reflected laser beam, so that effective laser pulses can only be released by contact with a stone. Most (127 of 83.5%) of the stones could be completely fragmented, so that no further treatment was necessary. In 16 cases (10.5%) the stone was too hard for fragmentation and had to be removed by alternative techniques. Intraureteral lithotripsy is a save and effective method of treating ureteral stones that cannot be reached or have not been treated successfully by shockwave lithotripsy. No significant differences in outcome were found between the different lasers or electrohydraulic lithotripsy. In selected cases endoscopic treatment may be recommended as treatment of first choice.

Adolescent↗