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  • 1
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    German Medical Science; Düsseldorf, Köln
    In:  123. Kongress der Deutschen Gesellschaft für Chirurgie; 20060502-20060505; Berlin; DOC06dgch4770 /20060502/
    Publication Date: 2006-05-09
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
    Keywords: EXPRESSION ; SURVIVAL ; COMBINATION ; Germany ; MODEL ; THERAPY ; RISK ; PATIENT ; IMPACT ; INDUCTION ; ACID ; NO ; DIFFERENCE ; AGE ; RATES ; chemotherapy ; leukemia ; MULTIVARIATE ; RISK GROUP ; COMPLETE REMISSION ; INITIATION ; COLONY-STIMULATING FACTOR ; Bcl-2 ; SOUTHWEST-ONCOLOGY-GROUP ; ACUTE MYELOGENOUS LEUKEMIA ; acute myeloid leukemia ; INDUCTION THERAPY ; ELDERLY-PATIENTS ; PHASE-III ; DEHYDROGENASE ; overall survival ; all-trans retinoic acid ; COUNCIL AML11 TRIAL ; CYTOSINE-ARABINOSIDE ; elderly patients ; IDARUBICIN
    Abstract: The purpose of our study was (i) to evaluate the impact of all-trans retinoic acid ( ATRA) given as adjunct to chemotherapy and (ii) to compare second consolidation vs maintenance therapy in elderly patients with acute myeloid leukemia (AML). A total of 242 patients aged greater than or equal to61 years (median, 66.6 years) with AML were randomly assigned to ATRA beginning on day +3 after the initiation of chemotherapy (ATRA-arm, n = 122) or no ATRA (standard-arm, n 120) in combination with induction and first consolidation therapy. A total of 61 patients in complete remission (CR) were randomly assigned to second intense consolidation (n = 31) or 1-year oral maintenance therapy ( n 30). After induction therapy the intention-to-treat analysis revealed a significant difference in CR rates between the ATRA- and the standard-arm (52 vs 39%; P = 0.05). Event-free (EFS) and overall survival ( OS) were significantly better in the ATRA- compared to the standard-arm (P = 0.03 and 0.01, respectively). OS after second randomization was significantly better for patients assigned to intensive consolidation therapy (P〈0.001). The multivariate model for survival revealed lactate dehydrogenase, cytogenetic risk group, age, and first and second randomization as prognostic variables. In conclusion, the addition of ATRA to induction and consolidation therapy may improve CR rate, EFS and OS in elderly patients with AML
    Type of Publication: Journal article published
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  • 3
    Keywords: CELLS ; BLOOD ; Germany ; DISEASE ; POPULATION ; HYBRIDIZATION ; PATIENT ; DONOR ; SEQUENCE ; FREQUENCY ; TRIAL ; LYMPHOMA ; HUMANS ; AGE ; PCR ; LYMPHOCYTES ; INDIVIDUALS ; sensitivity ; specificity ; VALIDITY ; PREVALENCE ; real-time PCR ; SEQUENCE-ANALYSIS ; FOLLICULAR LYMPHOMA ; MINIMAL RESIDUAL DISEASE ; REARRANGEMENT ; BREAKPOINTS ; GENDER ; healthy individuals ; CONTAMINATION ; BCL-2/J(H) TRANSLOCATION ; nested PCR ; T(14/18) ; t(14 ; 18)
    Abstract: This Study assessed prevalence, frequency, age and gender distribution and breakpoint locations. and detection method validity for the bcl-2/IgH rearrangement in 204 healthy individuals. For this purpose, both classic two-step, nested. semi-quantitative PCR as well as a newly established sequence-specific, hybridization probe-based real-time quantitative PCR (RQ-PCR) were employed and tested for their sensitivity and specificity for detecting t(14; 18) positive cells in healthy blood donors. Interestingly, almost a quarter (24%; 39/204) of all healthy individuals carried the translocation, confirming data of one large prior report [Summers KE, Goff LK, Wilson AG, Gupta RK, Lister TA, Fitzgibbon J. Frequency of the Bcl-2/IgH rearrangement in normal individuals: implications for the monitoring of disease in patients with follicular lymphoma. J Clin Oncol 2001; 19(2):420-4]. Regarding presence as well as frequency of the translocation, no correlation to age (mean frequency 2.0: 10(4), with a median of 〈 1: 10(4), for 〈 40 years, and mean frequency 1.9:10(4), with a median of 〈 1:10(4) for individuals 〉= 40 years) nor gender was detected. Comparing the two PCR approaches, a 95.1% concordance (194/204) regarding t(I 4; 18) detection was determined for nested and RQ-PCR, with nested PCR being slightly more sensitive (reproducible detection limit 1: 105 cells versus 1:10(4); maximum detection limit 1:10(6) versus 1:10(5)). Sequence analysis confirmed individual breakpoints for all samples analyzed (29/29), indicating detection validity for both PCR approaches and ruling out contamination. The break-point location distribution pattern appeared to be comparable to the pattern seen with follicular lymphoma (FL) patient collectives. In conclusion, clonal bcl-2/IgH rearrangements are indeed a very frequent observation in healthy individuals, and appear to be independent of age and gender in regard to presence and frequency. This represents a conflicting finding in context of potential biological significance, and presents a potential disruptive factor for minimal residual disease (MRD) monitoring in FL patients. Prospective future trials will have to clarify the biological significance of this important observation. (c) 2005 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16297448
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  • 4
    Keywords: CANCER ; CELLS ; BLOOD ; CELL ; Germany ; human ; COMMON ; DISEASE ; RISK ; GENE ; SAMPLE ; SAMPLES ; TISSUE ; TIME ; PATIENT ; CONTRAST ; cell cycle ; CELL-CYCLE ; CYCLE ; treatment ; antibodies ; antibody ; NO ; AMPLIFICATION ; MALIGNANCIES ; MUTATION ; leukemia ; ABERRATIONS ; LYMPHOCYTES ; PROGNOSTIC-FACTORS ; INSTABILITY ; B-CELLS ; PROGNOSTIC FACTORS ; REPLICATION ; INDIVIDUALS ; T-LYMPHOCYTES ; T lymphocyte ; PERIPHERAL-BLOOD ; PROGNOSTIC FACTOR ; CD38 EXPRESSION ; HUMAN BREAST-TUMORS ; T lymphocytes ; POSSIBLE MECHANISM ; ARREST ; MALIGNANCY ; ONCOLOGY ; ACUTE MYELOID-LEUKEMIA ; chronic lymphocytic leukemia ; CLL ; GENOMIC ABERRATIONS ; B-cell chronic lymphocytic leukemia ; PROGNOSTIC-FACTOR ; CHROMOSOMAL INSTABILITY ; PHASE ; CYCLE ARREST ; USA ; correlation ; PROLIFERATIVE ACTIVITY ; B-LYMPHOCYTES ; EXTENT ; genomic ; B-CELL ; ANEUPLOIDY ; aberration ; correlates ; B cells ; B-cell chronic lymphocytic ; centrosome aberrations ; DOUBLING TIME ; GENE MUTATIONAL STATUS
    Abstract: B-cell chronic lymphocytic leukemia (CLL) is characterized by a high rate of clonal genomic alterations and a low proliferative activity with cell cycle arrest in G(0)/G(1) phase. Recently, centrosome aberrations have been described as a possible cause of chromosomal instability and aneuploidy in many human malignancies. To investigate whether centrosome aberrations do occur in CLL and whether they correlate with common prognostic factors and disease activity, we examined peripheral blood mononuclear cells (PBMC) from 70 patients with previously untreated CLL using an antibody to gamma-tubulin. All 70 CLL samples displayed significantly more cells with centrosome aberrations (median: 26.0%, range 11.0-41.5%) as compared to peripheral blood B lymphocytes from 20 age-matched, healthy individuals (median: 2.0 %, range 0-6 % p 〈 0.001). The extent of centrosome aberrations correlated with the proliferative activity of the CLL cases as measured by lymphocyte doubling time (p = 0.02) as well as with time to first treatment (p = 0.05). Accordingly, more centrosome aberrations were found in PHA-stimulated T lymphocytes from healthy individuals as well as in B cells from surgically removed tonsil tissue of patients with acute tonsillitis as compared to the peripheral blood B lymphocytes from the control group. In contrast, no correlation was observed between centrosome aberrations and immunoglobulin VH gene mutation status or cytogenetically defined risk groups. These findings suggest that, despite the common observation of most CLL cells remaining in G(0)/G(1) phase, their centrosome replication process is deregulated and correlates to the proliferative activity of CLL cells. (C) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17417785
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  • 5
    Keywords: CELL ; COMBINATION ; THERAPY ; DISEASE ; EXPOSURE ; POPULATION ; MONOCLONAL-ANTIBODY ; PATIENT ; CYCLE ; TRIAL ; LYMPHOMA ; CYCLOPHOSPHAMIDE ; FOLLICULAR LYMPHOMA ; MANAGEMENT ; THERAPIES ; ELDERLY-PATIENTS ; fludarabine ; LIFE ; rituximab ; quality of life ; prospective ; MAINTENANCE ; CHOP CHEMOTHERAPY ; INVESTIGATE ; CHEMOTHERAPY PLUS RITUXIMAB ; RESPONSE DURATION ; SIGNIFICANTLY INCREASES
    Abstract: The introduction of rituximab into the primary treatment of malignant lymphomas of the B cell lineage has had a major impact on the management of these diseases. In addition, prolonged exposure to rituximab as maintenance therapy has been beneficial in patients with follicular lymphoma and mantle cell lymphoma. For the individual patient, the effect of any prolonged antitumor therapy on the quality of life (QoL) is a very important question. However, so far, the question whether rituximab maintenance therapy may impair QoL in patients with non-Hodgkin's lymphoma remains unanswered. To investigate this subject, we have performed a prospective randomized trial of rituximab maintenance therapy (8 cycles rituximab 375 mg/m(2) every 3 months) versus observation in patients with CD20+B cell non-Hodgkin's lymphoma in our institution. Between July 2002 and December 2005, 122 patients were included into the trial. QoL was assessed with the standardized questionnaires EORTC-QLQ-C30, EuroQol-5D, and EuroQol-5D (VAS) in 91 patients. After statistical analysis with the exact Wilcoxon rank sum test, we found no significant differences of the QoL between the rituximab treatment group and the observation group. We conclude that rituximab maintenance therapy seems to be safe and does not impair quality of life in this patient population
    Type of Publication: Journal article published
    PubMed ID: 18665360
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  • 6
    Keywords: SURVIVAL ; QUANTIFICATION ; TRIAL ; PROGRESSION ; CHRONIC LYMPHOCYTIC-LEUKEMIA
    Type of Publication: Journal article published
    PubMed ID: 23787395
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  • 7
    Keywords: THERAPY ; TRIAL ; GUIDELINES ; fludarabine ; rituximab ; TERM-FOLLOW-UP ; REGIMEN ; ALEMTUZUMAB ; 1ST COMPLETE REMISSION ; REFRACTORY CLL
    Abstract: BACKGROUND: In a single-center retrospective donor versus no-donor comparison, we investigated if allogeneic stem cell transplantation (alloSCT) can improve the dismal course of poor-risk chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: All patients with CLL who were referred for evaluation of alloSCT within a 7-year time frame and had a donor search indication according to the EBMT criteria or because of Richter's transformation were included. Patients for whom a matched donor could be found within 3 months (matches) were compared with patients without such a donor (controls). Primary end point was overall survival measured from the 3-month landmark after search initiation. RESULTS: Of 105 patients with donor search, 97 (matches 83; controls 14) were assessable at the 3-month landmark. Matches and controls were comparable for age, gender, time from diagnosis, number of previous regimens, and remission status. Disregarding if alloSCT was actually carried out or not, survival from the 3-month landmark was significantly better in matches versus controls [hazard ratio 0.38, 95% confidence interval (CI) 0.17-0.85; P = 0.014]. The survival benefit of matches remained significant on multivariate analysis. CONCLUSION: This study provides first comparative evidence that alloSCT may have the potential to improve the natural course of poor-risk CLL as defined by the EBMT criteria.
    Type of Publication: Journal article published
    PubMed ID: 24356631
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  • 8
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; VOL: 10; DOC147 /20140519/
    Publication Date: 2014-05-20
    Description: Einleitung: Bei der Pan-Endoskopie teilen sich Anästhesist und Operateur die oberen Atemwege. Die Intubation behindert auch mit einem kleinen Tubus die Operation. Bei der Jet-Ventilation kommt es zu unangenehmen Vibrationen. Kurze intermittierende Apnoen nach Maskenbeatmung führen zu erheblichen Verzögerungen der OP. In unseren Kliniken führen wir seit Jahren erfolgreich die apnoeische Oxigenierung als Alternative durch. In einer retrospektiven Untersuchung stellen wir das Verfahren dar.Methodik: Wir werteten retrospektiv 47 Narkoseprotokolle aus. Die Patienten erhalten eine konventionelle Narkoseeinleitung. Durch aktive und passive Präoxigenierung werden mindestens 90% des Stickstoffs aus der Lunge ausgewaschen (Kontrolle mittels FetO2). Danach wird ein 8F Absaugkatheter in die Trachea eingeführt und an Sauerstoff mit einem Fluss von 1l/min angeschlossen. Durch die behinderte CO2-Elimination kommt es nach kurzer Zeit zu einem in die Lunge gerichteten Gasstrom (aventilatorischer Massenfluss), der ungefähr dem Sauerstoffverbrauch entspricht (1). Theoretisch könnte damit die Oxigenierung über mehrere Stunden bis zum Limit der CO2-Speicher aufrechterhalten werden.Ergebnisse: Bei drei Patienten musste wegen mangelnder Oxigenierung interveniert werden.Ansonsten wurden Apnoezeiten bis zu 45 Minuten problemlos toleriert. Bei keinem der Patienten kam es zu ST-Strecken-Veränderungen, hypertonen Krisen oder auffälligem Verhalten nach der Narkose. Die Operationsverhältnisse wurden von allen Operateuren als "exzellent" beschrieben.Diskussion: Die apnoeische Oxigenation stellt sich uns als das überlegene Verfahren dar und kann auch über längere Zeiträume problemlos durchgeführt werden. Folgende Kontraindikationen sollten aber beachtet werden: Patienten mit massivem Übergewicht Patienten mit Hirndruck Diathermie und Laser dürfen wegen der hohen Sauerstoffkonzentration nicht angewendet werden Der Erstautor gibt keinen Interessenkonflikt an.
    Keywords: ddc: 610
    Language: German
    Type: article
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  • 9
    Keywords: APOPTOSIS ; CELLS ; EXPRESSION ; IN-VITRO ; BLOOD ; Germany ; MOLECULES ; PATIENT ; IFN-GAMMA ; INDUCTION ; T-CELLS ; UP-REGULATION ; ADHESION ; B-CELLS ; TARGETS ; ADHESION MOLECULE ; PERIPHERAL-BLOOD ; INTERFERON-GAMMA ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; FAS-MEDIATED APOPTOSIS ; EFFECTOR ; adoptive immunotherapy ; INCREASE ; secretion ; CLL ; SEVERE COMBINED IMMUNODEFICIENCY ; peripheral blood ; EXPANSION ; killer cells ; CD154 GENE-THERAPY ; COSTIMULATORY MOLECULES
    Abstract: Cvtokine-induced killer cells (CIK cells), coexpressing CD3 and cb56, can be expanded from peripheral blood mommuclear cells by the timed addition of interferon-gamma (IFN-gamma), IL-2 and OKT3. The effects of CIK cells on primary, autologous CLL cells are described. We used MACS to separate CD3(+) cells for expansion of CIK cell effectors and CD19(+) targets from peripheral blood of 16 CLL patients. Apoptosis was assessed by measuring annexinV staining in CLL cells. After incubation of autologous CIK with CLL, specific apoptosis in CLL cells was 15%. Coincubation with irradiated CIK cells for 48 hr before adding vital CIK cells resulted in an increased ICAM-1 expression on CLL cells and an increase in apoptosis of CLL targets (30%). These effects were mediated by IFN-gamma secretion of CIK cells. In addition to their direct cytotoxic effect, CIK cells secrete IFN-gamma that modulates the expression of adhesion molecules on CLL cells, and this enhances apoptosis induction by cytotoxic effector cells. (c) 2006 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 16642465
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  • 10
    Keywords: CELLS ; BLOOD ; CELL ; COMBINATION ; Germany ; THERAPY ; DISEASE ; RISK ; DRUG ; TIME ; PATIENT ; CYCLE ; treatment ; STAGE ; TRIAL ; TRIALS ; LYMPHOMA ; NUMBER ; REDUCED RISK ; RATES ; chemotherapy ; PCR ; PROBES ; CLEARANCE ; PERIPHERAL-BLOOD ; FOLLICULAR LYMPHOMA ; MINIMAL RESIDUAL DISEASE ; NON-HODGKINS-LYMPHOMA ; CAPACITY ; RESIDUAL DISEASE ; ANTI-CD20 MONOCLONAL-ANTIBODY ; rituximab ; REMISSION ; prospective ; COMBINATION THERAPY ; E ; B-CELL ; peripheral blood ; nested PCR ; t(14 ; 18) ; molecular monitoring ; RQ-PCR ; t(14 : 18)
    Abstract: Accurate monitoring of the t(14; 18) translocation is regarded as highly desirable in patients with follicular lymphoma (FL) as absence of bcl-2/IgH positive cells has been correlated with a reduced risk of recurrence and, more recently, pre-treatment t(14;18) load with response to rituximab (R: Blood 2004; 103:4416-23). With the arrival of R clinical and molecular remission rates for various lymphoma entities improved significantly, creating the need to carefully review and reassess the role of PCR negativity for clinical outcome, specifically when considering the prolonged presence of the drug as compared to chemotherapy. To determine the rate of molecular clearance achieved by the addition of different doses of R 16 newly diagnosed, t(14;18) positive patients with FL (Ann Arbor stages III/IV) were investigated before, during and after primary chemotherapy with six cycles of CHOP combined with varying (1, 3 or 6) cycle numbers of R (varR1-, varR3- or varR6-CHOP, respectively) regarding molecular remission status. For this purpose classic nested PCR as well as a newly established RQ-PCR employing juxtaposed hybridisation probes were employed to assess molecular remission prior, during and post therapy. Interestingly, administering just a single cycle of R (varR1-CHOP) in combination with a standard regimen of CHOP resulted in rapid and effective clearance of t(14;18) carrying cells from the peripheral blood of 4/5 patients in this treatment group. 6/8 (6/8) varR1-/varR3-CHOP patients were fully cleared and 8/8 (7/8) var6-CHOP patients as assessed by RQ- (nested) PCR. This indicates the high clearance capacity of this combination therapy approach even when adding a very low cycle number of R (1 and 3, respectively) to CHOP in primary therapy of FL. In summary, the relationship established between molecular clearance and minimal residual disease/risk of recurrence may have to be redefined in the times of R. Upcoming large prospective trials will have to elucidate to what degree the clearance of peripheral blood from t(14;18) positive cells can still be regarded as informative regarding absence of minimal residual disease, remission status and/or risk of recurrence. (c) 2006 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16530831
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