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M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 55 records · Page 3Linked to original sources

[Immunotherapy for advanced renal cell carcinoma].

Significant advances have been achieved in the surgical treatment of localized renal cell carcinoma over recent years. However, despite significant research efforts, the prognosis is still dismal in the majority of patients with advanced disease. Treatment with IFN-ac leads to moderately increased survival. In addition, survival can be prolonged by tu-mor nephrectomy in patients with synchronous metastases. Combined treatment with IFN-a, IL-2 and 5-FU has demonstrated a survival benefit in a single randomized controlled trial. High dose IL-2 causes long-term regression in a small fraction of patients. All of these treatments, however, frequently cause significant morbidity and therefore the potential benefit has to be weighed carefully against toxicity in each individual patient. Although, in general, the results of immunotherapeutic approaches have been dis-appointing, studies using allogeneic stem cells, allogeneic mononuclear cells and vaccines clearly demonstrate, that tumor control can be achieved by means of immunological intervention. Future research will hopefully lead to the development of strategies helpful for a greater proportion of patients with this disease.

Antineoplastic Agents↗

Anti-fetal immune response mechanisms may be involved in the pathogenesis of placental abruption.

Placental abruption is an unpredictable severe complication in pregnancy. In order to investigate the possibility that the activation of the fetal nonadaptive immune system may be involved in the pathogenesis of this disease, IL-6 release from cord blood monocytes was examined by intracellular cytokine staining and flow cytometric analysis. Our results demonstrate that preterm placental abruption (n = 15) in contrast to uncontrollable preterm labor (n = 33) is associated with significantly (P < 0.001) increased release of IL-6 from the fetal monocytes. The same holds true for rhesus disease (n = 9, P < 0.001) that is characterized by a maternal production of antibodies against the rhesus-D antigen expressed by the fetal erythrocytes. This suggests that during rhesus disease, IL-6 release of monocytes is induced by antibody-mediated cross-linking of these cells to the erythrocytes in the fetal circulation. Hence, this assumption favors the idea that also in case of placental abruption, an increased maternal antibody production against paternal antigens leads to an elevated IL-6 release by the fetal monocytes. To elucidate this potential mechanism, the presence of anti-HLA-antibodies was assessed in the maternal circulation of patients with placental abruption (n = 17) and patients with uncontrollable preterm labor (n = 29). The percentage of women producing anti-paternal HLA-antibodies was significantly (P < 0.01) increased in the group of women with preterm placental abruption (47%) in comparison to women with uncontrollable preterm labor (14%). Therefore, our results suggest that an increased humoral immune response of the mother against the fetus may be decisively involved in the pathogenesis of placental abruption.

Abruptio Placentae↗

[Uterine adenomyosis in infertile patients: MR imaging findings and clinical conclusions].

PURPOSE: To evaluate the clinical value of magnetic resonance imaging (MRI) of the uterus and the pelvis in infertile female with symptomatic endometriosis for the assessment of uterine morphology and function. MATERIALS AND METHODS: Forty-one infertile women (mean age: 33.2 years) with symptomatic endometriosis documented by laparoscopy were evaluated with high-field MRI (Sonata, Siemens) using T2- and T1-weighted sequences. In addition, the patients underwent hysterosalpingoscintigraphy (HSSG) for evaluation of the uterotubal transport capacity. Pathologic findings of the uterine junction zone were correlated with the laparoscopic results, clinical symptoms and uterotubal transport capacity. RESULTS: Adenomyosis was diagnosed on T2-weigthed MR-images in 35 (85.4 %) patients (focal adenomatosis in 26 patients and diffuse adenomatosis in 9). Patients showing signs of adenomyosis tended to be older than patients without adenomyosis (mean age 34.1 years vs. 30.1 years) and showed a longer history of symptomatic endometriosis. A positive transport capacity in HSSG was observed in 73.1 % (19/26) of the patients with focal adenomyosis and in only 22.2 % (2/9) of patients with diffuse adenomyosis. In 83.3 % (5/6) of the patients without signs of adenomyosis, a positive uterotubal transport was documented. CONCLUSION: MRI of the uterus is a helpful diagnostic tool for the diagnosis of adenomyosis and for planning further therapies. Patients with the diagnosis of adenomyosis showed a reduced uterotubal transport capacity that depended on the severity of adenomyotic changes and might be a possible cause of infertility.

Adult↗

[New aspects in diagnosis and therapy of endometriosis].

Endometriosis and adenomyosis show a high prevalence and can be regarded as different symptoms of a unique disease - the dislocation of basal endometrium. Diagnostic methods for detecting adenomyosis are transvaginal sonography (TVS) or T-2-weighed magnetic resonance imaging (MRI). Patients with endometriosis show a significant impairment of utero-tubal sperm transport capacity, which is even increased the stronger the adenomyotic component of the disease is. Adenomyosis can be regarded as a cause for infertility especially in minor and mild forms of endometriosis and is therefore often followed by IVF/ICSI-treatment. Infertility patients with endometriosis should be counselled for intensive infertility treatment. Without a current wish for conception, fertility potential should be preserved by hormonal suppression of uterine peristalsis in order to avoid progression of the disease.

Endometriosis↗

[Management of breast cancer treatment -- a multidisciplinary approach].

The management of breast cancer care poses very high expectations on implementing the treatment recommendations and guidelines for diagnostic procedures into routine treatment. Most recently a majority of these tasks has been transferred to the responsibilities of the breast centers being established all over Germany these days. Guidelines on treatment and diagnostic procedures and minimal invasive techniques have therefore been discussed among 1 300 colleagues and experts at the Duesseldorfer Symposium in June 2004.

Breast Neoplasms↗

Rituximab consolidation after high-dose chemotherapy and autologous blood stem cell transplantation in follicular and mantle cell lymphoma: a prospective, multicenter phase II study.

BACKGROUND: Patients with follicular (FL) or mantle cell lymphoma (MCL) are incurable with conventional therapy. We investigated the safety and efficacy of rituximab consolidation after autologous stem cell transplantation (ASCT) in order to prevent relapse by clearance of minimal residual disease (MRD). METHODS: Rituximab was given approximately 8 weeks after CD34+ cell enriched ASCT at 375 mg/m2, weekly for 4 weeks. Monitoring of MRD was performed by repetitive PCR analyses. RESULTS: Thirty-one patients were included; one died early after ASCT before rituximab administration. Thirty patients (20 FL, 10 MCL) were evaluable after rituximab consolidation, and 27 of these were assessable for MRD detection. Rituximab consolidation post-ASCT was safe, the most common toxicity being infection. At a median follow-up of 42 months (range 13-96) after ASCT, 25 patients were censored with an actuarial event-free survival (EFS) of 81% at 4 and 5 years. Four patients (two FL, two MCL) relapsed, and one additional MCL patient died unexpectedly in complete remission. PCR-negativity was observed in 22% of the patients before ASCT, 53% post-ASCT (P=0.0547), 72% after rituximab (P=0.0018) and 100% at 6 months post-transplant (P < 0.001). CONCLUSIONS: One single course of rituximab consolidation given after ASCT is safe, may help to eliminate MRD and may translate into improved EFS in both FL and MCL patients.

Adult↗

Mitomycin C, 5-fluorouracil and folinic acid (Mi-Fu-Fo) as salvage chemotherapy in breast cancer patients with liver metastases and impaired hepatic function: a phase II study.

Patients with measurable liver metastases due to breast cancer and elevated liver enzymes were enrolled into the study. The planned schedule was mitomycin C 8 mg/m2 on day 1, 5-fluorouracil 750 mg/m2 and folinic acid 300 mg/m2 on day 1 and 2 every 4 weeks (Mi-Fu-Fo). Between May 1998 and December 2002, 30 patients with a median age of 51 years (range 33-74) were enrolled. All of them suffered from extensive metastases of the liver resulting in liver dysfunction. Myelosuppression was the most frequent toxicity. Six patients had a partial remission, 12 patients had stable disease and 12 patients progressed during treatment. The median time to progression was 4.5 months in all patients and 7.0 months in patients who responded to the therapy. The median overall survival for the total population was 6.0 months and in the group of responding patients 12.0 months. Mi-Fu-Fo, therefore, provides a valid option for breast cancer patients with liver dysfunction due to liver metastases.

Adult↗

Quality of life in goserelin-treated versus cyclophosphamide + methotrexate + fluorouracil-treated premenopausal and perimenopausal patients with node-positive, early breast cancer: the Zoladex Early Breast Cancer Research Association Trialists Group.

PURPOSE: To compare quality of life (QoL) in premenopausal and perimenopausal patients with node-positive, early breast cancer treated with the endocrine agent goserelin (Zoladex; AstraZeneca Pharmaceuticals LP, Wilmington, DE) or cyclophosphamide + methotrexate + fluorouracil (CMF). PATIENTS AND METHODS: Patients from 86 centers worldwide were randomly assigned to receive either goserelin (3.6 mg every 28 days for 2 years; n = 514) or CMF (six 28-day cycles; n = 496), and were included in the QoL study. QoL was assessed using a self-administered patient questionnaire that consisted of 39 items from the Rotterdam Symptom Checklist, including dimensions evaluating physical and psychological symptom distress, activities of daily living, hormonal effects, and an assessment of overall QoL. RESULTS: Early benefits were noted during months 3 to 6 of treatment, for goserelin compared with CMF. Significant differences were found for changes in overall QoL (eg, 6.96 +/- 0.88 v 0.69 +/- 0.92 at 6 months; P <.0001) and for physical symptom distress, activity levels, and "effort to cope with illness" dimensions. At 1, 2, and 3 years, there were no significant differences in overall QoL or specific QoL dimensions. Scores for hormonal symptoms were worse with goserelin during the 2-year goserelin treatment period; however, this trend was reversed at 3 years. CONCLUSION: Goserelin offers improved overall QoL during the first 6 months of therapy compared with CMF chemotherapy in premenopausal and perimenopausal patients with early breast cancer. Coupled with equivalent efficacy in estrogen receptor-positive patients, these data support the use of goserelin as an alternative to CMF in premenopausal and perimenopausal patients with estrogen receptor-positive, node-positive early breast cancer.

Adult↗

[Anesthetic regimen for HIV positive parturients undergoing elective cesarean section].

OBJECTIVE: Worldwide, 50 million people are infected with the human immunodeficiency virus (HIV), and 43% are women. Perinatal vertical transmission of HIV accounts for most new pediatric cases. Elective Cesarean delivery, combined antiretroviral therapy perioperatively and abandonment of breast-feeding postoperatively reduces vertical HIV transmission. However, the incidence of maternal and neonatal morbidity perioperatively is relatively unknown. The goal of the present study was to prospectively record perioperative maternal and neonatal complications in the largest HIV positive collective undergoing elective Cesarean section with spinal anesthesia published to date. METHODS: From 1999-2001, 54 HIV positive parturients were enrolled in this study. All parturients received IV zidovudine therapy (2 mg/kg body weight) perioperatively. Spinal anesthesia was performed using 60 mg of 4% hyperbaric mepivacaine plus 5 microg sufentanil intrathecally. Sensory, analgesic and motor block characteristics, the incidence of maternal hypotension, postoperative maternal complications as well as neonatal outcome were recorded. RESULTS: Short-term hypotension occurred in 65% of the parturients. Intraoperatively, one parturient died following amniotic fluid embolism. In 17% of the parturients, postoperative complications headed by wound healing impairment, bronchitis and pneumonia requiring prolonged antibiotic therapy were observed. To date, after a minimum observation period of 8 months, only one infant (1.8%) is HIV positive. CONCLUSION: Intrathecal mepivacaine combined with sufentanil in HIV positive parturients undergoing elective Cesarean section is an appropriate anesthetic option. Postoperative maternal morbidity was 17%. Neonatal outcome showed no evidence of neonatal depression.

Adult↗

Survival analyses from the ZEBRA study. goserelin (Zoladex) versus CMF in premenopausal women with node-positive breast cancer.

The Zoladex Early Breast Cancer Research Association (ZEBRA) trial compared the efficacy and tolerability of goserelin (Zoladex) with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy in pre-/perimenopausal women with node-positive early breast cancer. The results of disease-free survival (DFS) analyses have already been published. Here we present an update including data on overall survival (OS) from the ZEBRA trial at a median follow-up of 7.3 years. In patients with oestrogen receptor (ER)-positive tumours, non-inferiority of goserelin versus CMF for OS was shown; goserelin was again shown to be equivalent to CMF for DFS. This updated analysis has demonstrated that the two treatments are also equivalent for distant disease-free survival (DDFS). In patients with ER-negative disease, goserelin was inferior to CMF for DFS, DDFS and OS. This follow-up analysis confirms the previously reported outcomes from the ZEBRA trial and demonstrates that goserelin offers an effective alternative to CMF chemotherapy for adjuvant therapy of premenopausal patients with ER-positive, node-positive early breast cancer.

Aged↗

[The role of stereotactic 11G vacuum biopsy for clarification of BI-RADS IV findings in mammography].

PURPOSE: To evaluate the potential of stereotactic vacuum breast biopsy in the histologic evaluation of suspicious mammographic findings ( BI-RADS IV). MATERIALS AND METHODS: In 221 patients with 227 probable mammographic lesions categorized as ( BI-RADS -IV), stereotactic biopsies were performed with an 11-gauge vacuum-assisted biopsy device (Mammotome). The evaluation included the histology of the specimens obtained with the Mammotome or with surgery, the time for the biopsy, the amount of bleeding, number of rotations and procured specimens, the extent of the resection and the complications. RESULTS: The biopsies were technically successful in 214 of the 227 probable mammographic lesions, with 176 lesions mostly resected and 34 lesions removed more than 50 %. No representative tissue was obtained from 4 lesions. All biopsies were performed without any clinically relevant complications and terminated after adequate material was obtained (O 28 specimens, 2.58 rotations). The mean time needed for performing the biopsy was 40.2 minutes. The histologic findings were DCIS (42 lesions), ADH (7 lesions), LCIS (3 lesions), ID-Ca (14 lesions, IL-Ca (3 lesions), and IDL-Ca (1 lesion). In 28 of 42 lesions with the initial DCIS histology, the surgical histology was also DCIS (n=28) or no residual tumor (n=10). In 4 lesions with an initial DCIS-histology, the surgical histology was invasive ductal cancer (9.5 %). The late follow-up examinations (up to 3 years) did not find any evidence of a false negative biopsy. CONCLUSION: Stereotactic vacuum breast biopsy ideally complements existing breast biopsy methods. The method is minimal invasive with a low rate of mostly minor complications.

Artifacts↗

[Chemoprevention of breast cancer: a literature review and report on the current status in Germany].

The prevention of breast cancer is increasingly of focus in health-politics policies and has gained a valid position in the area of medical intervention. Data from a current meta-analysis of all four randomised Tamoxifen prevention studies illustrate a reduction of 38 % (Odds ratio 0.62; 95 % CI 0.42-0.89) in the incidence of breast cancer. This observation lead to registration of this drug in the USA for the prevention of breast cancer in women with a calculated 5-year risk of > 1.66 %. In addition to Tamoxifen, further substances are currently being tested with the aim of improving the therapeutic index whilst reducing incidence and mortality rates. These are primarily substances which have proven efficacy in the treatment of breast cancer (other antioestrogens, aromatase inhibitors and GnRH-analogues) or those whose mechanism of action predict a preventative effect (retinoids, phytooestrogens, substitution preparations e. g. Tibolone). In Germany, chemoprevention is currently only to be recommended within study protocols, as to date no substance is approved in the indication 'prevention of breast cancer'. A essential contribution to the accrual of valid data is the conduct of breast cancer prevention trials. The participation of women with high risk of breast cancer in Germany is, in contrast to comparable international studies, problematic. Data on the current knowledge and attitude of the female population towards such trials (gathered via a questionnaire of the DACH in 7 000 women) show that only 19.5 % of the women questioned during a consultation with a gynaecologist were aware of the possibility of active chemoprevention. However, 55.3 % stated that they would be prepared to take such a substance, were chemoprevention possible. Studies for both pre- and post-menopausal women with increased risk of breast cancer are currently active in Germany (GISS and IBIS-II of the study group GABG - German Adjuvant Breast cancer Group). An intensive information campaign to raise public awareness of breast cancer risk amongst women and their physicians is planned in conjunction with the IBIS-II study (www.brustkrebsvorbeugen.de). Latest literature recommendations for prevention of breast cancer (Chlebowski et al.) have been assessed.

Anticarcinogenic Agents↗

[New aspects of carcinoma of the breast therapy and of gynaecological carcinoma treatment].

Dose-dense chemotherapy and high dose chemotherapy have been issued in the adjuvant and primary therapy of breast cancer. Should we use GnRH analogues after chemotherapy in premenopausal women who have not become amenorrheic through chemotherapy? How important are the taxanes in the primary and adjuvant treatment of breast cancer? The optimal screening method for women at high-risk for breast cancer was addressed as one of the most important topics. Primary and recurrent ovarian cancer therapy needs to be improved further. The optimal primary therapy for endometrial cancer and cervical cancer with radiotherapy and/or chemotherapy was another addressed issue.

Breast Neoplasms↗

Mepivacaine for spinal anesthesia in parturients undergoing elective cesarean delivery: maternal and neonatal plasma concentrations and neonatal outcome.

OBJECTIVE: Worldwide, long-acting bupivacaine is most commonly used for spinal anesthesia in parturients undergoing elective Cesarean delivery. However, advances in surgical technique and shorter duration of surgery make short-acting local anesthetic like mepivacaine appropriate, particularly if combined with opioids to enhance postoperative maternal pain relief. MATERIAL AND METHODS: We assessed the effect of 4% hyperbaric mepivacaine (60 mg) plus 10 microg fentanyl for spinal anesthesia in 11 parturients undergoing elective Cesarean delivery. Sensory, motor and analgesic block characteristics, neonatal outcome (Apgar scores, umbilical cord blood analysis, neurologic and adaptive capacity score) as well as fetal and maternal mepivacaine plasma concentrations at delivery were determined (HPLC/UV). RESULTS: Motor block (Induction-Bromage 0) duration lasted 113 +/- 20 min. Effective analgesia (VAS < or = 40) was 128 +/- 35 min. Maternal and fetal mepivacaine free plasma concentration were 0.18 +/- 0.05 microg/ml and 0.10 +/- 0.03 microg/ml, respectively. The fetal to maternal (UV/MV)-ratio for mepivacaine free plasma concentration was 0.56. Apgar scores, NACScores and the umbilical blood analysis showed no evidence of neonatal depression. CONCLUSIONS: Particularly with short duration of surgery (21 +/- 5 min) intrathecal mepivacaine combined with fentanyl offers a favorable clinical alternative in parturients undergoing elective Cesarean delivery.

Anesthesia, Spinal↗

Multicenter phase II study of oral capecitabine (Xeloda(")) in patients with metastatic breast cancer relapsing after treatment with a taxane-containing therapy.

BACKGROUND: Capecitabine is a rationally designed oral, tumor-activated fluoropyrimidine carbamate with high activity in metastatic breast cancer. This multicenter phase II study was designed to evaluate further the efficacy and safety of capecitabine in patients with metastatic breast cancer previously treated with a taxane-containing regimen. PATIENTS AND METHODS: All patients had to have documented progression after paclitaxel- or docetaxel-containing chemotherapy. Treatment comprised 3-week cycles of oral capecitabine 1250 mg/m(2) twice-daily for 14 days followed by a 7-day rest period. RESULTS: One hundred and thirty-six patients were enrolled. Disease stabilization occurred in 63 patients (46%) and the overall response rate was 15% (95% confidence interval 10% to 23%), providing an overall tumor control rate of 62%. Median time to progression was 3.5 months, median duration of response was 7.5 months and median overall survival was 10.1 months. Capecitabine was generally well-tolerated: most treatment-related adverse events were grade 1/2 in intensity; grade 3/4 treatment-related adverse events were hand-foot syndrome (13%), diarrhea (8%), vomiting (4%) and nausea (3%). There were no treatment-related deaths. CONCLUSIONS: This study confirms that capecitabine achieves a high tumor control rate in heavily pretreated patients with metastatic breast cancer. Due to its favorable safety profile and convenient oral administration, capecitabine can be given as an outpatient therapy. Capecitabine should be considered the reference treatment in this setting based on consistently high efficacy and good tolerability.

Administration, Oral↗

Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study.

PURPOSE: Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause. PATIENTS AND METHODS: The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer. RESULTS: Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P =.0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, 1.76; 95% CI, 1.27 to 2.44). Amenorrhea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhea was generally permanent in CMF patients (22.6% v 76.9% amenorrheic at 3 years). Chemotherapy-related side effects such as nausea/vomiting, alopecia, and infection were higher with CMF than with goserelin during CMF treatment. Side effects related to estrogen suppression were initially higher with goserelin, but when goserelin treatment stopped, reduced to a level below that observed in the CMF group. CONCLUSION: Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer.

Amenorrhea↗

Factors influencing the prognostic role of oestrogen and progesterone receptor levels in breast cancer--results of the analysis of 670 patients with 11 years of follow-up.

In the last two decades, the prognostic role of the steroid hormone receptors has been the subject of a myriad of publications. Nevertheless, its relevance after long-term follow-up is still not clear. The confusion about the prognostic value is mainly due to the difficulty in comparing analyses. Despite different study-designs and statistical approaches, oestrogen (ER) and progesterone (PR) receptors are widely accepted as prognostic factors. Data from 670 breast cancer patients with a median follow-up of 11.4 years were analysed retrospectively. ER and PR were measured by the dextran-coated charcoal (DCC) assay. To investigate the time dependence of the prognostic relevance of ER and PR, separate analyses were done for follow-up shorter and longer than 5 years. Special focus was directed at patients < or =50 and >50 years, node-negative women, in particular those without adjuvant therapy. Univariate and multivariate analyses were performed. In univariate analysis, ER and PR were associated with a significantly longer overall survival at the cut-off levels 10, 20 or 100 fmol/mg protein. The significant survival benefit occurred in the first 5 years of follow-up and remained unchanged in the following period. In the multivariate analyses, only the PR was of significant prognostic value (for PR> or =20 fmol/mg P=0.036, for PR> or =100 P=0.01, Cox analysis). In patients younger than 51 years, only PR was an independent prognosticator at the cut-off level of 100 fmol/mg protein, while in patients >50 years both hormone receptors were not significant. In N0 patients, only the PR reached long-term prognostic independence at a cut-off point of > or =100 fmol/mg (P=0.018). In addition, in the group of node-negative women < or =50 years without adjuvant therapy the PR level reached prognostic significance. The hormone receptor status was a prognostic factor only during the first 5 years of follow-up. Our data suggest that age, lymph node status, length of follow-up and probably the ER/PR assay are important for the evaluation of ER and PR as prognostic variables. In most analyses, PR appeared to be superior to ER in predicting the prognosis of primary breast cancer patients.

Adult↗