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Biomedical subjects

F Hering

Publications and source records attributed to F Hering.

At least 19 recordsLinked to original sources
PubMed2004

Capecitabine in hormone-resistant metastatic prostatic carcinoma - a phase II trial.

The objective of the trial is to evaluate the efficacy of capecitabine in patients with metastatic hormone-resistant prostate carcinoma (HRPC), in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score) and its safety profile. In all, 25 patients with HRPC were enrolled on a phase II trial of capecitabine (Xeloda) at a dose of 1250 mg m(-2) orally twice daily on days 1-14 every 21 days. The inclusion criteria were PSA serum levels >3 x upper limit of normal, a WHO performance status 0-2, age <85 years and adequate bone marrow, liver and renal function. In patients with grade 2 or higher haematological toxicity on day 1 of the treatment cycle, therapy was first delayed, and then continued at a lower dose. Trial end points were PSA response and clinical benefit defined by quality of life (QL) data and analgesic consumption. The median age of patients was 70 years (range 54-85 years). A median of three cycles of capecitabine was administered (range 1-8). PSA response was observed in three patients (12%, 95% CI 3-31%), with times to tumour progression of 18, 21 and 35 weeks, respectively. In these patients, the response durations were 12, 17 and 32 weeks, respectively. Minor PSA regression was also seen in two further patients. The median time to tumour progression of all patients was 12 weeks (95% CI 9-15 weeks). Haematological toxicity was minor, with leukopenia grade 3 observed in one patient. There were three deaths during trial treatment, respectively, due to sepsis following mucositis and leukopenia, presumed sepsis with mucositis induced by chemotherapy and concomitant radiotherapy and cerebral dysfunction progressing to coma. Hand-foot syndrome grades 2 and 3 were observed in four patients each. Clinical benefit was observed in five patients (20%, CI 7-41%). Based on toxicity data, we recommend a lower starting dose of 1000 mg x m(-2) orally twice daily. While capecitabine has some activity in HRPC, as suggested by observed PSA responses, we conclude that it is not worthwhile to investigate capecitabine monotherapy in a phase III trial. Combinations of capecitabine with other agents, such as vinorelbine or docetaxel, may prove to be more effective.

Aged↗
PubMed2004

Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients.

INTRODUCTION: Approximately 85% of patients who die from prostate cancer present the spread of bone metastases. Even though the radiological appearance of such metastases is osteoblastic, it is now known that these lesions coexist in their microenvironment with blastic and lytic lesions. The process always begins with bone lysis by osteoclast proliferation, paralleling nearby bone deposition. The treatment options are palliative and have poor clinical response with short-lived improvement. We have studied the clinical effect of bisphosphonates (clodronate) in the treatment of skeletal complications from prostate cancer. MATERIALS AND METHODS: In an open prospective study, 58 patients with hormone-refractory prostate cancer with bone metastases were assessed from November 2000 to September 2003. The mean age was 70.3 y (range: 51-87 y). Bone scintigraphy, plain X-ray, assaying of prostate-specific antigen (PSA) and biochemical tests were requested before and following treatment. Patients were previously and subsequently assessed using the visual pain scale (0-10) and Karnofsky's index after the first and second intravenous (i.v.) infusions (administration of i.v. clodronate every 28 days) and every 4-6 months thereafter. Student's t-test was used for statistical analysis. RESULTS: A total of 53 patients (91.4%) showed improvement after the first and/or second cycle, which persisted for at least 4 months (average 6.3 months). The averages on the visual pain scale improved from 7.4 (range: 2-8) to 2.4 (0-7) and on Karnofsky's index from 43 (32-58) to 73 (50-82). The radiological appearance of the metastases improved in 27 patients (46.5%) and there were few relapses (six patients; 10.3%). CONCLUSIONS: Clodronate was effective in the treatment of skeletal complications from prostate cancer. There was an objective response in 91.4% of treated patients, with a marked improvement in the subjective visual pain scale evaluation as well as on Karnofsky's index, with low side effects.

Aged↗
PubMed2002

Vinorelbine in androgen-independent metastatic prostatic carcinoma--a phase II study.

The purpose of this study was to evaluate the efficacy of vinorelbine treatment in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score for the subgroup of patients with pain), as well as its toxicity in patients with progressive metastatic androgen-independent prostatic carcinoma. 44 patients with prostatic carcinoma progressing after orchiectomy or during treatment with hormonal agents were treated with vinorelbine at a dose of 30 mg/m(2) intravenously (i.v.) on days 1 and 8 of a 21-day cycle. Inclusion criteria were metastatic progressive prostatic carcinoma with prostate-specific antigen (PSA) serum levels >/=3 x upper limit of normal, World Health Organization (WHO) performance status </=2, age <85 years and adequate bone marrow, liver and renal functions. Treatment was continued until progression or a maximum of 12 cycles. Treatment was delayed for a week if haematological toxicity grade >/=2 was observed on the day of scheduled vinorelbine administration. 9 patients received less than three cycles, 6 due to rapid tumour progression. Treatment at day 1 had to be delayed in 13.7% of 183 cycles. Treatment at day 8 had to be omitted in 19.7% of all cycles. Grade >/=3 granulocytopenia occurred in 18% of patients. 4 patients had severe constipation. In 7 patients (15.9%, Confidence Interval (CI) 6.6-30.1%), a PSA response (>/=50% reduction of PSA levels) was observed. Among 8 patients with measurable disease, 3 had partial remission and 1 no change. Median time to PSA progression in 43 assessable patients was 11.9 weeks (range 3-52 weeks). Median duration of PSA response was 14 weeks (9-30 weeks). Clinical benefit was seen in 7 of 31 cases (23%) with baseline pain, there was no association with PSA response. Vinorelbine is a fairly well tolerated drug with a moderate single agent activity in patients with androgen-refractory prostate cancer.

Aged↗
PubMed2002

Reduction of latex sensitisation in spina bifida patients by a primary prophylaxis programme (five years experience).

Spina bifida patients represent a group with the highest risk for latex sensitisation and allergy with life-threatening symptoms mostly during surgery. At the end of 1995 we initiated a primary latex prophylaxis around and during surgery and anaesthesia of all spina bifida patients. The aim of our study was to investigate the prevalence of latex sensitisation in the spina bifida patients born during the five years after establishing latex prophylaxis in the Cologne Children's Hospital in December 1995. We investigated 34 serum samples of 27 spina bifida patients (mean age 2.4 years) for specific IgE antibodies against latex allergens (CAP system) and compared these patients born after 1995 with 38 spina bifida patients up to 5 years of age (mean 3.1 years) born before. In the prophylaxis group two of 27 patients (7 %), one of them with two operations outside the Children's Hospital, had low specific IgE against latex (</= 0.9 kU/l, 3 and 5 operations). The other patients in this group were not sensitised despite up to 8 operations (min. 1, mean 3.1). In contrast, before introducing the prophylaxis, 16 of 38 patients (42 %) were latex IgE-positive after multiple operations (min. 2, max. 11, mean 4.7) with values of specific IgE up to > 100 kU/l (mean 22.6 kU/l, min 0.4 kU/l). Sera of 22 patients remained negative for latex IgE (min. 1, max. 19, mean 4.3 operations). By primary latex prophylaxis during surgery, anaesthesia and in paediatric wards the prevalence of latex sensitisation can be significantly reduced even in the high risk group of spina bifida patients. Problems can arise by the need for surgery in hospitals not experienced in the treatment of spina bifida patients, where latex prophylaxis is neglected.

Case-Control Studies↗
PubMed2001

High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the chromosomal regions 3p25 and 8p11-p12 are recurrently amplified in bladder cancer. To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities.

Chromosomes, Human, Pair 3↗
PubMed2001

Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade.

The number of genes suggested to play a role in cancer biology is rapidly increasing. To be able to test a large number of molecular parameters in sufficiently large series of primary tumours, a tissue microarray (TMA) approach has been developed where samples from up to 1000 tumours can be simultaneously analysed on one glass slide. Because of the small size of the individual arrayed tissue samples (diameter 0.6 mm), the question arises of whether these specimens are representative of their donor tumours. To investigate how representative are the results obtained on TMAs, a set of 2317 bladder tumours that had been previously analysed for histological grade and Ki67 labelling index (LI) was used to construct four replica TMAs from different areas of each tumour. Clinical follow-up information was available from 1092 patients. The histological grade and the Ki67 LI were determined for every arrayed tumour sample (4x2317 analyses each). Despite discrepancies in individual cases, the grade and Ki67 information obtained on minute arrayed samples were highly similar to the data obtained on large sections (p<0.0001). Most importantly, every individual association between grade or Ki67 LI and tumour stage or prognosis (recurrence, progression, tumour-specific survival) that was observed in large section analysis could be fully reproduced on all four replica TMAs. These results show that intra-tumour heterogeneity does not significantly affect the ability to detect clinico-pathological correlations on TMAs, probably because of the large number of tumours that can be included in TMA studies. TMAs are a powerful tool for rapid identification of the biological or clinical significance of molecular alterations in bladder cancer and other tumour types.

Adenocarcinoma↗
PubMed2000

High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the 19q13 chromosomal region is frequently amplified in bladder cancer. The cyclin E gene (CCNE), coding for a regulatory subunit of cyclin-dependent kinase 2, has been mapped to 19q13. To investigate the role of cyclin E alterations in bladder cancer, a tissue microarray of 2,317 specimens from 1,842 bladder cancer patients was constructed and analyzed for CCNE amplification by fluorescence in situ hybridization and for cyclin-E protein overexpression by immunohistochemistry. Fluorescence in situ hybridization analysis showed amplification in only 30 of the 1,561 evaluable tumors (1.9%). Amplification was significantly associated with stage and grade (P: < 0.0005 each). Immunohistochemically detectable cyclin E expression was strong in 233 (12.4%), weak in 354 (18.9%), and negative in 1, 286 of the 1,873 interpretable tumors. The majority (62.1%) of CCNE-amplified tumors were strongly immunohistochemistry-positive (P: < 0.0001). The frequency of protein expression increased from stage pTa (22.2%) to pT1 (45.5%; P: < 0.0001) but then decreased for stage pT2-4 (29.4%; P: < 0.0001 for pT1 versus pT2-4). Low cyclin E expression was associated with poor overall survival in all patients (P: < 0.0001), but had no prognostic impact independent of stage. It is concluded that cyclin E overexpression is characteristic to a subset of bladder carcinomas, especially at the stage of early invasion. This analysis of the prognostic impact of CCNE gene amplification and protein expression in >1,500 arrayed bladder cancers was accomplished in a period of 2 weeks, illustrating how the tissue microarray technology remarkably facilitates the evaluation of the clinical relevance of molecular alterations in cancer.

Adult↗
PubMed2000

Response and palliation in a phase II trial of gemcitabine in hormone-refractory metastatic prostatic carcinoma. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: In a phase II trial, 43 patients with hormone-refractory prostate cancer were treated with gemcitabine at a dose of 1,200 mg/m2 over 2 hours (later decreased to 1,000 mg/m2 due to hematological toxicity) on days 1, 8 and 15 of a 28 day cycle. PATIENTS AND METHODS: Inclusion criteria were proven tumor progression after hormonal treatment and increased PSA levels, a WHO PS < or = 2, adequate bone marrow reserve, liver and renal function and age < or =, 80 years. Response criteria were based on PSA levels (CR: normalization of PSA, PR: > 50% decrease). Quality of life (QL) was assessed with the EORTC QLQ-C30 on day 1 of each treatment cycle and on day 8 of the first cycle (range of scales 0-100). Physician-rated pain intensity and use of pain medication were assessed at the same timepoints. RESULTS: Hematological toxicity of gemcitabine led to a dose-reduction in 48% of all cycles. Three of forty-three patients (RR = 7%) showed a PSA response: one CR and three PR with time to treatment failure of 8.7, 6.6 and > or = 9.3 months. Seven patients (16%) had stable disease (NC) for a median duration of 7.1 months (range 6.1-11.7 months). There was one case with objective regression of lymph node metastases. Patients reported a considerably impaired health status/QL (n = 41, median = 50) and severe fatigue (n = 41, median = 55.6) at baseline, with no change under treatment. Pain (QLQ-C30) was also severe at baseline (N=41, median=50) but was improved at the end of cycles 1 (n = 33, median change = -16.7, P = 0.0002), 2 (n = 19, median change = -33.3, P = 0.0006), 3 (n = 14, median change = -16.7, P = 0.06) and 4 (n = 9, median change = -33.3, P = 0.04). Patient-rated pain and use of analgesics as combined endpoint yielded palliation for at least 8 weeks in 14 patients (32%). Nine of these patients showed at least stable disease (CR/PR or NC by PSA level), five indicated a benefit in spite of progressive disease. CONCLUSIONS: Gemcitabine in the dose and schedule indicated above has a significant beneficial impact on pain in patients with hormone-refractory prostatic carcinoma despite its limited activity in terms of PSA response and considerable, especially hematological, toxicity.

Adenocarcinoma↗
PubMed1998

Transitional cell carcinoma of the vagina with pagetoid spread pattern.

A distinctive variant of a papillary noninvasive transitional cell carcinoma (TCC) of the vagina removed from a postmenopausal woman is described. The neoplasm was evaluated by immunohistochemistry. The designation of this neoplasm as a TCC is supported by its morphological features and its coexpression for cytokeratin (CK) 7 and CK 20. Its main feature is pagetoid infiltration into adjacent vaginal epithelium. This is the second reported case involving a transitional cell metaplasia (TCM) of the vagina, a possible precursor lesion of the TCC.

Adult↗
PubMed1997

A phase II study of oral idarubicin as a treatment for metastatic hormone-refractory prostate carcinoma with special focus on prostate specific antigen doubling time. Swiss Group for Clinical Cancer Research, Berne, Switzerland.

BACKGROUND: Treatment of hormone-refractory prostate carcinoma with chemotherapy is purely palliative, and reported response rates have been low. At the time this study was conducted, there was an urgent need for a trial using potentially efficacious drugs, with quality of life (QL), and serial prostate specific antigen (PSA) behavior as endpoints. METHODS: In this Swiss multicenter Phase II study, 30 patients were enrolled to receive oral idarubicin. Patients were administered 35 mg idarubicin on Days 1 and 8 of each cycle, and treatment was repeated every 3 weeks. Assessment was based on response rates, sequential PSA measurements in serum, toxicity, and selected aspects of QL. RESULTS: Twenty-six of 30 patients were evaluable for response, and none of them achieved a response. Three patients had stable disease as their best response, and their PSA levels also remained stable. In all other patients, PSA increased exponentially over time; the median PSA doubling time was 2.1 months (mean, 2.6; range, 0.7-6.1). Toxicity was minimal and consisted mainly of myelosuppression and nausea/vomiting. QL did not change significantly during therapy with regard to general well-being, fatigue, or nausea/vomiting. However, there were improvements in patient-rated and physician-rated pain. CONCLUSIONS: At the dose and schedule used in this study, oral idarubicin showed only minimal efficacy against hormone-refractory prostate carcinoma. In patients who did not respond, PSA doubling times were similar to those in patients who relapsed while receiving only antiandrogen therapy. In future clinical trials, QL and serial PSA behavior should be included in analysis.

Administration, Oral↗
PubMed1997

Impact of minimal lymph node metastasis on long-term prognosis after radical prostatectomy.

OBJECTIVES: In the management of clinically localized prostate cancer, understanding is of major concern. There is a considerable therapeutic dilemma in those patients in whom staging lymphadenectomy prior to intended radical prostatectomy reveals lymph node metastases. METHODS: Pelvic lymph node dissection and radical retropubic prostatectomy were performed in 132 consecutive patients. Patients with extracapsular disease and/or positive lymph nodes received adjuvant radiotherapy. Median follow-up after surgery was 7 years and 2 months. To study the influence of minimal lymph node metastasis, category pN1 was further subdivided into pN1.1 and pN1.2. Involvement of the prostatic capsule was either classified as infiltration (pT3.1) or performation (pT3.2) of the capsule. RESULTS: Disease-free survival after 10 years was 58% in patients with negative nodes, 37% in category pN1.1, 25% in category pN1.2 and 10% in category pN2. Corrected overall survival was 83% for node-negative patients and 73% for category pN1.1, but it was only 33% for pN1.2 and 29% for pN2. Patients in category pT3.1 had a statistically significant better survival than those in pT3.2. CONCLUSIONS: We conclude that radical prostatectomy combined with adjuvant radiotherapy is a valuable option in prostate cancer patients with minimal lymph node metastasis. When compared to infiltration of the capsule, complete capsular perforation does adversely affect prognosis.

Adenocarcinoma↗
PubMed1996

Isoelectric focusing of Tamm-Horsfall glycoproteins: a simple tool for recognizing recurrent calcium oxalate renal stone formers.

Tamm-Horsfall glycoproteins (THPs) from healthy probands and a majority of recurrent calcium oxalate renal stone formers reveal different physicochemical properties when analyzed using isoelectric focusing (IEF). The pI values of THPs from healthy probands are approximately 3.5 while THPs from recurrent renal stone formers have pI values of between 4.5 and 6. The two groups of THPs exhibit completely different protein patterns. The differences in IEF analysis allow differentiation between THPs from healthy probands and recurrent calcium oxalate stone formers and may possibly be used as a simple diagnostic method for the recognition of recurrent calcium oxalate renal stone formers.

Adjuvants, Immunologic↗
PubMed1996

Intracytoplasmic sperm injection (ICSI) with testicular sperm extraction (TESE) in non-obstructive azoospermia--two case reports.

Intracytoplasmic sperm injection (ICSI) with microsurgical epididymal sperm extraction (MESA) or testicular sperm extraction (TESE) can be offered to azoospermic men. We report our initial experience of two cases with ICSI-TESE in non-obstructive azoospermia. Both couples had a successful ICSI with embryo transfer. An ongoing triplet pregnancy at 21 weeks is observed.

Adult↗
PubMed1994

Influence of microinvasion of the capsule and/or micrometastasis of regional lymph nodes on disease free survival after radical prostatectomy.

Since 1976, 126 patients with clinically localized carcinoma of the prostate have been managed by radical retropubic prostatectomy. All patients with tumour spread beyond the capsule or metastasis in lymph nodes received radiotherapy. Tumour category pT3 was divided into invasion of the capsule or infiltration of the seminal vesicle. The disease-free 10-year survival rate in patients with minimal invasion of the capsule was 72% and in patients with infiltration of the seminal vesicles it was 26%. Unilateral lymph node metastases were classified as microscopic disease or macroscopic infiltration. The disease-free 10-year survival rate in patients with metastasis in 1 lymph node (micro- and macro-metastasis) was 65% in contrast to 0% in patients with bilateral disease.

Aged↗
PubMed1994

Tamm-Horsfall glycoprotein: role in inhibition and promotion of renal calcium oxalate stone formation studied with Fourier-transform infrared spectroscopy.

Tamm-Horsfall glycoprotein (THP) from healthy probands inhibits the precipitation of calcium oxalate, whereas THP from individuals who repeatedly develop calcium oxalate stones has no effect or even promotes precipitation. Using Fourier-transform infrared spectroscopy, we found a structural differentiation between these functionally different THPs: a decisive difference in sialic acid content. Quantitative analysis for sialic acid showed the same results. THP from healthy probands had a high sialic acid content (51 +/- 9 g/kg), whereas THP from recurrent stone formers had a decreased sialic acid content (21 +/- 4 g/kg). This explains the dual role of THP in the precipitation of calcium oxalate and the formation of renal stones and shows the importance of glycosylation in the function of this glycoprotein.

Calcium Oxalate↗