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Biomedical subjects

P Albers

Publications and source records attributed to P Albers.

At least 19 recordsLinked to original sources

[Systemic therapy of penile cancer].

Penile cancer is a rare tumor in Europe with an incidence of 0.1-0.9 per 100,000 men per year. The success of our therapy is mainly influenced by the presence of lymph node metastases. At first diagnosis 17-45% of patients already harbor lymph node metastases. Bilateral inguinal and pelvic lymphadenectomy is a curative measure in these patients. In cases of gross inguinal metastases neoadjuvant chemotherapy leads to a remission rate of 21-60% and improves the resectability. The influence on survival is not proven. The same holds true for adjuvant therapy following lymphadenectomy. Polychemotherapy rarely leads to long-lasting complete remission in patients with distant metastases. The protocols consist usually of cisplatin, bleomycin, methotrexate, and 5-fluorouracil. The overall remission rate is around 15-32%. Because of the low efficacy of the present chemotherapy regimens, one should follow new strategies, comparable to those initiated for squamous cell cancer of other organs.

Antineoplastic Agents↗

[Therapeutic options for hormone-refractory prostate cancer].

For a long time, hormone-refractory prostate cancer was regarded as a chemoresistant tumor. The introduction of taxanes has prompted a change in this opinion. For the first time treatment with 75 mg/m(2) docetaxel every 3 weeks has evidenced a survival benefit in a phase III trial (median survival of 18.9 months versus 16.5 months with mitoxantrone). Further advantages were improved pain reduction and quality of life. Neutropenia was foremost among the side effects. Docetaxel is currently the standard treatment for hormone-refractory prostate cancer. The morbidity of metastatic hormone-refractory prostate cancer is influenced by bone metastases. Pain is a prominent feature. Skeletal complications are frequent. Therapy with 4 mg zoledronic acid reduced skeletal complications significantly in comparison to placebo. The most pronounced effect is the reduction of pathological fractures. Side effects include flu-like symptoms, muscle pain, and edemas. Zoledronic acid also belongs to the standard treatment of hormone-refractory prostate cancer with bone metastases.

Androgen Antagonists↗

Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with transitional cell carcinoma (AUO Trial AB 20/99).

The objectives are to evaluate and compare the response and toxicity of a 3-weekly and a 2-weekly regimen of gemcitabine (Gem) and paclitaxel (Pac) second-line treatment in patients with transitional cell carcinoma (TCC). Between June 2000 and July 2001, 30 patients with progressive disease (PD) during first-line chemotherapy (n = 11) or relapse after adjuvant cisplatin-based chemotherapy of a metastatic or locally advanced TCC (n = 18) have been randomised to receive either six cycles (schedule A) of 3-weekly Gem (1000 mg/qm, days 1 and 8) and Pac (175 mg/qm, day 1) or 2-weekly treatment until disease progression (schedule B) with Gem (1250 mg/qm, day 1) and Pac (120 mg/qm, day 2). Restaging was performed after every 6 weeks by clinical imaging. Of 30 patients, one patient in schedule A and two patients in schedule B were not evaluable for response due to serious adverse events (SAEs) during the first cycle. The overall objective response (OR) was 44% (12 of 27) with eight complete remissions (CRs) and four partial remissions. Median time to progression (TTP) was 11 (3-41) months in schedule A and 6 (1-15+) months in schedule B. Median survival was 13 (5-46) months in schedule A and 9 (0-16) months in schedule B. Schedule A showed a significantly higher rate of CRs (7 vs. 1, p < 0.05). With a median number of six (1-6) cycles (A) and nine (1-23) cycles (B), TTP and survival were not significantly different. In schedule B, one patient had WHO grade IV anaemia and leucopenia. WHO grade III toxicities were seen in schedule A/B as follows: anaemia 3 (23%)/2 (16%) patients, leucopenia 5 (38%)/2 (16%), thrombocytopenia 0/2 (16%) and alopecia 10 (76%)/4 (32%). The combination of Gem and Pac is an effective second-line regimen in patients with mainly poor prognosis due to PD after cisplatin-based chemotherapy. Except for three SAEs (uncertainly therapy related), both regimens were tolerated well. The 3-weekly schedule with a nonsplit Pac dose showed a significantly higher complete response rate in our small study population and, thus, might be superior to the 2-weekly schedule.

Adult↗

Single agent carboplatin for CS IIA/B testicular seminoma. A phase II study of the German Testicular Cancer Study Group (GTCSG).

BACKGROUND: The aim was to investigate the use of single agent carboplatin in patients with seminoma stage IIA/B. PATIENTS AND METHODS: In a prospective phase II trial, single agent carboplatin at a dose of AUC 7 mg.min/ml every 4 weeks for three cycles in stage IIA (n=51) or four cycles in stage IIB (n=57) was given to 108 patients with previously untreated seminoma stage IIA/B. Patients with residual masses of >or=3 cm were scheduled to receive secondary surgery. RESULTS: A complete response (CR) was achieved by 88/108 (81%) patients, 17/108 (16%) achieved a partial response (PR), two of 108 (2%) showed no change, and one patient progressed. In all patients with PR the residual disease was <or=3 cm; yet in two of 17 patients with PR, in two of two patients with NC and in one patient with disease progression residual tumor resection was performed demonstrating vital seminoma. Toxicity was acceptable with grades 3 and 4 myelosuppression, nausea and vomiting in less than 10% of patients each. After a median follow-up of 28 months (range 1-68 months) 14/108 (13%) patients relapsed, all after having achieved a CR. All relapses occurred in the retroperitoneum. One patient died from an unrelated cause. The overall failure rate was 19/108 patients (18%). The overall and disease specific survival was 99% and 100%, respectively. CONCLUSIONS: Four cycles of single agent carboplatin AUC 7 do not safely eradicate retroperitoneal metastases in patients with stage IIA/B seminoma.

Adult↗

Surgical outcome following radical nephrectomy in cases with inferior vena cava tumour thrombus extension.

AIM: To report our experience with extensive surgery in patients with and without metastatic renal cell carcinoma and gross venous tumour thrombus. MATERIAL AND METHODS: Twenty-seven patients with unilateral renal cell carcinoma and tumour thrombus into the vena cava underwent radical nephrectomy and thrombectomy. Eight patients presented with metastatic disease at the time of surgery. Mean follow-up was 17 months (1-54 months, median 9 months). Follow-up was available for 26 patients (96%). RESULTS: Thirteen patients were alive at the time of the study; 11 without evidence of disease with a mean follow-up of 25 months and two (one with and one without metastasis at surgery) with distant metastasis at 16 and 36 months. Eleven patients have died of progressive disease. Mean survival in patients (19 patients) without metastatic disease at time of surgery was 15.2 months; patients (seven patients) with metastatic disease at surgery had a mean survival of 6.7 months. CONCLUSION: Radical nephrectomy and vena caval tumour thrombectomy can be performed in selected patients with an acceptable complication rate. Patients without metastatic disease have a better prognosis than patients with metastatic disease.

Adult↗

Gene expression profiling in seminoma and nonseminoma.

PURPOSE: Gene expression profiles of seminoma were compared with nonseminoma to get insights into tumorigenesis. MATERIALS AND METHODS: Eleven testicular tumor biopsies (five pure seminoma, six nonseminoma; pT1N0M0 to pT2N2M1) and biopsies from unaffected sites were analyzed once per patient using a macroarray (1,176 genes). On the same patients, six genes were validated using real-time quantitative (RTQ) polymerase chain reaction (PCR). Additionally, in a separate cohort of 19 patients, 24 genes selected from the macroarray were measured using RTQ-PCR. RESULTS: (1) The agreement in gene expression was 94% between the two methods and two different patient cohorts. (2) Two features in gene expression were independent of the tumor entity: Most changes of gene expression occurred in five functional groups like "cell cycle" and "apoptosis." Genes within these groups were almost similarly (> 80%) up- or downregulated. (3) Nonseminoma were characterized by downregulated genes (75%), but in seminoma, upregulated genes (64%) prevailed. Furthermore, 64.4% of those genes that were differentially expressed in both tumor entities were usually upregulated in seminoma but downregulated in nonseminoma. A reverse pattern was found in 24.4% of such genes. Eleven percent of these genes showed a similar up- or downregulation in gene expression in both tumor entities. CONCLUSION: Seminoma in this preliminary study can be differentiated from nonseminoma due to almost opposing gene expression profiles (89% of the significantly differentially expressed genes) and are in line with the histological discrimination of both tumor entities. Underlying mechanisms and implications regarding the origin and tumor progression of both entities are discussed.

Adolescent↗

Primary intratesticular sarcoma of the testis: a rare manifestation of testicular cancer.

A 57-year-old white male presented with a 5-month history of a painless right testicular mass. Physical examination revealed a right testicular tumor. The patient underwent a right inguinal orchiectomy. Histopathologic evaluation showed a primary spindle-cell sarcoma of the testis. A retroperitoneal lymph node dissection was performed and revealed no lymphatic metastases. There was no recurrence of the disease over a 2-year follow-up period.

Humans↗

Synthesis, testing, and characterization of a novel Nafion membrane with superior performance in photoassisted immobilized Fenton catalysis.

A new type of Nafion/Fe structured membrane ensuring faster kinetics, higher efficiency, and mechanical properties has been prepared and will be compared in its performance with the Fe-exchanged commercial Dupont 117 Nafion/Fe membrane during the abatement of model organic compounds. During the casting of the laboratory Nafion sample, the iron ions were introduced directly into the Nafion oligomer solution. This novel laboratory Nafion/Fe was tested as an immobilized catalyst in the degradation of several toxic pollutants showing a faster photoassisted degradation kinetics and a wider effective photocatalytic pH range compared to the Fe-exchanged commercial Dupont 117 Nafion/Fe membrane. When carrying out Ar ion sputtering of the 50 topmost catalyst layers, evidence is presented by X-ray photoelectron spectroscopy that Fe ions are found in the inner Nafion layers and seem to be responsible for the immobilized photoassisted Fenton processes leading to the degradation of 4-chorophenol (4-CP) taken as a model organic pollutant for the degradation process reported in this study. In the laboratory sample, the iron oxy/hydroxy Nafion moiety undergoes a transition to a more stable Nafion/Fe species during 4-CP degradation as determined by X-ray diffraction. This more stable form shows a higher iron dispersion and crystallinity compared to the fresh sample and is stabilized by the Nafion matrix avoiding the formation of separate iron phases. By infrared absorption (Fourier transform infrared), evidence is presented for the band of akaganeite-like species at 870 cm(-1) on the laboratory Nafion/Fe sample. This band disappears after 4-CP degradation because of the formation of the more highly dispersed iron species. Sputtering experiments show a decrease of F-containing groups in the laboratory Nafion/Fe samples closer to the catalyst upper layer while the amounts of Fe, C, and in particular O species increase in the topmost layer(s). In particular, the oxygenated species develop in the Nafion/Fe up to approximately 50 A below the catalyst surface. These species remain stable during the long-term Nafion/Fe degradation of 4-CP. Dynamo-mechanical analysis performed on laboratory Nafion/ Fe membrane samples revealed that these membranes possessed a greater mechanical modulus and resistance than the commercial Dupont 117 Nafion membrane.

Journal Article↗

[The modified ureterosigmoidostomy (Mainz pouch II) as a continent form of urinary diversion].

INTRODUCTION AND OBJECTIVES: The purpose of this study was to examine the outcome of the "Mainz Pouch II" urinary diversion at two different centers (the Klinik und Poliklinik für Urologie, Bonn and the Ospedale "San Salvadore", Pesaro, Italy) in terms of different techniques of ureteral implantation. MATERIALS AND METHODS: Between March 1995 and February 2003, the procedure was performed on 83 patients with 165 renal units (RU). Ureteral implantation with the Goodwin-Hohenfellner technique was performed in 57 RU, with the Abol-Enein modification in 23 RU and the Le-Duc procedure in 85 RU. Follow-up was available for 71 patients (85%) with a period of 1 to 82 months (mean 19.5 months, median 12 months). A non-validated questionnaire was used in the Bonn series to determine specific urinary diversion items. RESULTS: Early complications occurred in 12%, three requiring surgical intervention. Two patients died within the first 30 days after initial surgery. Pyelonephritis occurred in 12 RU (14% of the patients, 8.5% of the RU). Ureteral stenosis requiring reimplantation was found in two RU. The continence rate was 100% during daytime in the Bonn series; all but one patient had to get up for urination at night. A total of 63% of the patients were able to distinguish between stool and urine. CONCLUSION: Mainz pouch II is a quick, safe and easy to perform urinary diversion which serves as a satisfying alternative to other forms of continent diversion. Follow-up shows a low complication rate with good results in terms of continence; however, long term results have to be evaluated. There are no significant differences in complication rates for the different ureteral implantation techniques.

Colon, Sigmoid↗

[Urinary diversion after cystectomy].

Urinary diversions become necessary in cases of a tumor-bearing urinary bladder requiring cystectomy or a nonfunctioning urinary bladder, e.g., due to neurogenic disorders. In order to choose the ideal urinary diversion, long-term function as well as complication rates, quality of life issues, and patient's acceptance become matters of debate. In this regard, orthotopic diversions are usually the first choice. However, there are contraindications for an orthotopic bladder substitute and sometimes the decision has to be made intraoperatively. Therefore, urinary diversions should only be offered by uro-oncological centers that are capable of performing different kinds of diversions. For many decades incontinent diversions have been the standard of care and for 20 years different kinds of cutaneous and orthotopic continent reservoirs have been performed. Bladder substitutes by means of tissue engineering, however, are still experimental.

Cystectomy↗

Accelerated photobleaching of orange II on novel (H5FeW12O4010H2O)/silica structured fabrics.

This study addresses the photobleaching (discoloration) and total organic carbon (TOC) reduction of the non-biodegradable azo-dye Orange II with H(5)FeW(12)O(40) in homogeneous solution and on H(5)FeW(12)O(40)/silica-structured fabrics in heterogeneous processes. The H(5)FeW(12)O(40)/silica fabric is able to catalyze Orange II bleaching only under light irradiation. In the dark, long-lived intermediates produced in solution were observed to preclude further degradation. The most efficient polytungstate was selected based on the performance during Orange II photobleaching in the presence of H(2)O(2). The H(5)FeW(12)O(40)/silica fabric needed approximately 60 min to photobleach 85% of an Orange II (0.2mM) solution. The amount of H(2)O(2) and the pH was optimized for the photobleaching of Orange II on the H(5)FeW(12)O(40)/silica fabric. The photobleaching was more efficient as the intensity of the applied light was increased. Repetitive photobleaching cycles of Orange II (0.2mM) on the H(5)FeW(12)O(40)/silica-structured fabric proceeded with the same kinetics, showing the stability of this fabric against oxidative radical attack and the absence of Fe-ions leaching into the solution during Orange II discoloration. The photobleaching times were similar for different concentrations of Orange II suggesting that it is controlled by mass transfer and not by a diffusion-controlled processes. The loading of the silica fabric was determined by elemental analysis to be 7.1% for Fe and 27.2% for W. By electron diffuse spectrometry W-clusters were identified on the silica fabrics and by high-resolution electron microscopy the W-clusters of the catalyst were observed to have sizes between 1 and 2 nm. By X-ray photoelectron spectroscopy, it is observed that the W-oxidation state is higher for the unused catalysts than in the catalyst after Orange II photobleaching. This lends support to a photo-assisted Fenton-like mechanism taking place in the H(5)FeW(12)O(40)/ silica-structured fabrics during Orange II decomposition.

Azo Compounds↗

European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.

Europe↗

[Gemcitabine/cisplatin vs. MVAC. 5 year survival outcome of the phase III study of chemotherapy of advanced urothelial carcinoma in Germany].

Of 405 patients with stage IV transitional cell carcinoma from an international multicenter phase III trial, 70 were randomized in Germany to receive either gemcitabine/cisplatin or standard MVAC systemic chemotherapy for locally advanced or metastatic urothelial cancer. Overall survival as the primary endpoint of the study was similar in both arms (median survival GC 15.4 months vs MVAC 16.1 months), as were tumor-specific survival and time to progressive disease. In the intent-to-treat analysis, the 5-year overall survival rate was 10% for patients randomized to GC and 18% randomized to MVAC. Tumor overall response rates (GC 54%, MVAC 53%) were similar. The toxic death rate was 0% in the GC arm and 3% (one patient) in the MVAC arm. Significantly more GC than MVAC patients experienced grade 3/4 anemia (GC 52%, MVAC 20%) with significantly more red blood cell transfusions in the GC arm.Significantly more GC than MVAC patients had grade 3/4 thrombocytopenia (GC 54%, MVAC 17%) without grade 3/4 hemorrhage or hematuria in either arm. More MVAC patients experienced grade 3/4 neutropenia (GC 56%, MVAC 61%, p=1.000), neutropenic or leukopenic fever (GC 0%, MVAC 10%, p=0.237), mucositis (GC 0%, MVAC 7%, p=0.495), and alopecia (GC 6%, MVAC 36%, p=0.004). GC represents a reasonable alternative for the palliative treatment of patients with locally advanced and metastatic transitional cell carcinoma. Sustained long-term survival was only found for patients with locally advanced cancer, lymphatic metastases, or solitary distant metastasis but not for visceral metastatic disease.

Adult↗

Preclinical evaluation of a radiosensitizing effect of gemcitabine in p53 mutant and p53 wild type bladder cancer cells.

OBJECTIVES: Despite clinical use, the radiosensitizing effect of gemcitabine (2'2'-difluorodeoxycytidine) in human transitional cell carcinoma (TCC) has not been shown to date. We investigated gemcitabine as a radiosensitizer for human TCC cells. METHODS: Monolayer cultures of RT112 (G1, p53 wild type), RT4 (G1-G2, p53 wild type), T24 (G3, p53, mutant type), and SUP (G4, p53 mutant type) cells were incubated in medium with gemcitabine. Electron beam radiation was applied alone, simultaneous, or 3, 6, 12, and 24 hours after gemcitabine. Jurkat leukemia cells were used as controls for radiation toxicity. Cell survival was determined 6, 12, 24, 48, and 72 hours after radiation by microculture tetrazolium assay. DNA damage was evaluated by flow cytometric assessment of poly(ADP-ribose) polymerase, and apoptosis was determined by terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling and flow cytometric assessment after annexin-V and propidium iodide labeling. RESULTS: In all TCC cell lines, radiation alone caused only little and insignificant growth inhibitory effects at 10 Gy. Gemcitabine alone had a dose-dependent cytotoxic and apoptosis inducing effect on all TCC cell lines independent of p53 status. Assays combining radiation with gemcitabine in different dose and time schedules demonstrated no radiosensitizing effect in TCC cells. CONCLUSIONS: Gemcitabine is effective in TCC cell lines independent of p53 status. A radiosensitizing effect could not be demonstrated. Again, p53 status was not predictive of the radioresponse in the bladder cancer cell lines. Clinical studies with gemcitabine and radiotherapy might nevertheless yield different results but should be performed with utmost caution.

Animals↗