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Untch M.,HELIOS Klinikum Berlin Buch | Jackisch C.,Sana Klinikum | Schneeweiss A.,University of Heidelberg | Conrad B.,St Elisabeth Krankenhaus | And 21 more authors.
The Lancet Oncology | Year: 2016

Background: In metastatic breast cancer, nab-paclitaxel has been shown to significantly increase progression-free survival compared with solvent-based paclitaxel. The GeparSepto (GBG 69) trial assessed whether weekly nab-paclitaxel could increase the proportion of patients achieving pathological complete response compared with weekly solvent-based paclitaxel, both followed by epirubicin plus cyclophosphamide as neoadjuvant treatment. Method: In a phase 3 randomised trial, we enrolled patients with previously untreated unilateral or bilateral primary invasive breast cancer and randomly assigned them in a 1:1 ratio using dynamic allocation and Pocock minimisation by breast cancer subtype, Ki67 and SPARC expression. Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m2 (after study amendment, 125 mg/m2) on days 1, 8, and 15 for four 3-week cycles, or solvent-based intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 for four 3-week cycles. Taxane treatment was followed in both groups by intravenous epirubicin 90 mg/m2 plus intravenous cyclophosphamide 600 mg/m2 on day 1 for four 3-week cycles. Patients with HER2-positive tumours received concurrent trastuzumab 6 mg/kg (loading dose 8 mg/kg) and pertuzumab 420 mg (loading dose 840 mg) on day 1 of every 3-week cycle. Trastuzumab and pertuzumab were given every 3 weeks concomitantly with chemotherapy for all cycles. This report is the final analysis of the primary endpoint, pathological complete response (ypT0 ypN0), analysed for all patients who started treatment (modified intention to treat). We used a closed test procedure to test for non-inferiority, with the nab-paclitaxel group calculated as non-inferior to the solvent-based paclitaxel group if the lower 95% CI for the OR was above 0·858 (OR equivalent to pathological complete response [33%] minus a 10% non-inferiority margin [3·3%]; 29·7%). We planned to test for superiority only in case of a positive non-inferiority test, using an α of 0·05. Safety was assessed in all patients who received study drug. The trial is registered with ClinicalTrials.gov, number NCT01583426. Findings: Between July 30, 2012, and Dec 23, 2013, we randomly assigned 1229 women, of whom 1206 started treatment (606 with nab-paclitaxel and 600 with solvent-based paclitaxel). The nab-paclitaxel dose was reduced after enrolment of 464 participants to 125 mg/m2 due to increased treatment discontinuation and sensory neuropathy in this group. Pathological complete response occurred more frequently in the nab-paclitaxel group (233 [38%, 95% CI 35-42] patients) than in the solvent-based paclitaxel group (174 [29%, 25-33] patients; OR 1·53, 95% CI 1·20-1·95; unadjusted p=0·00065). The incidence of grade 3-4 anaemia (13 [2%] of 605 patients in the nab-paclitaxel group vs four [1%] of patients in the solvent-based paclitaxel group; p=0·048) and peripheral sensory neuropathy grade 3-4 (63 [10%] patients receiving any nab-paclitaxel dose; 31 [8%] of patients starting with 125 mg/m2 and 32 [15%] of patients starting with 150 mg/m2; vs 16 [3%] in the solvent-based paclitaxel group, p<0·001) was significantly higher for nab-paclitaxel than for solvent-based paclitaxel. Overall, 283 (23%) patients were noted to have at least one serious adverse event (based on study drug received), 156 (26%) in the nab-paclitaxel group and 127 (21%) in the solvent-based paclitaxel group (p=0·057). There were three deaths (during epirubicin plus cyclophosphamide treatment) in the nab-paclitaxel group (due to sepsis, diarrhoea, and accident unrelated to the trial) versus one in the solvent-based paclitaxel group (during paclitaxel treatment; cardiac failure). Interpretation: Substituting solvent-based paclitaxel with nab-paclitaxel significantly increases the proportion of patients achieving a pathological complete response rate after anthracycline-based chemotherapy. These results might lead to an exchange of the preferred taxane, solvent-based paclitaxel, for nab-paclitaxel in therapy for primary breast cancer. Funding: Celgene, Roche. © 2016 Elsevier Ltd.


PubMed | Hamburger Zentrum fur Kinder und Jugendrheumatologie, Center for Paediatric Rheumatology, Heinrich Heine University Düsseldorf, Charite University Medicine and Epidemiology Unit and 2 more.
Type: Journal Article | Journal: Clinical and experimental rheumatology | Year: 2016

While tumour necrosis factor (TNF)--inhibitor treatment improved outcome of juvenile idiopathic arthritis (JIA) management markedly, concerns have been raised about an association of TNF--inhibitor treatment and an increased risk for malignancies especially lymphoma.Cases of suspected malignancies documented in the German Biker Registry are reviewed in detail.Until Dec 31, 2015, 3695 JIA patients were prospectively followed with a total of more than 13,198 observation years. 12 cases of suspected malignancies, including 7 lymphoid neoplasms, have been reported in patients treated with methotrexate (MTX) , and /or TNF- inhibitors. 11 patients had received MTX, two received cyclosporine A, single patients received sulfasalazine, azathioprine or leflunomide. 10 patients were exposed to biologics, 9 etanercept, two adalimumab, one infliximab and one case was consecutively treated with adalimumab, etanercept, infliximab and abatacept. A case of mild myelodysplasia, in which the patient recovered spontaneously, a case of lymphoproliferation without clonality and a case of cervical dysplasia were treated as suspected, but not confirmed malignancies. Cases in which a malignant disease was confirmed included two cases of Hodgkins lymphoma, one case of non-Hodgkins lymphoma, two cases of acute lymphatic leukaemia (ALL) and one patient with lymphoproliferative disorder, who recovered after discontinuation of immunosuppressive therapy. Single confirmed cases of thyroid carcinoma, yolk sac carcinoma and anaplastic ependymoma have also been described. One patient not exposed to biologics died of ALL, all other patients recovered.In this large cohort of JIA patients, the occurrence of malignancies was higher than in the general population. Whether JIA patients had an increased risk for malignancies, either through their rheumatic disease, or through treatment remains in debate. Treatment with etanercept seems not to further increase the malignancy risk. Long-term observation of JIA patients treated with TNF- inhibitors into adulthood remains an important task.


Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma, but has not yet been evaluated in the context of resectable patients. Here we report findings from the phase 2 part of the phase 2/3 FLOT4 trial, which compared histopathological regression in patients treated with a docetaxel-based triplet chemotherapy versus an anthracycline-based triplet chemotherapy before surgical resection.In this randomised, open-label, phase 2/3 study, eligible participants were recruited from 28 German oncology centres. Patients with resectable gastric or gastro-oesophageal junction cancer who had clinical stage cT2 or higher, nodal positive (cN+) disease, or both were randomly assigned (1:1) to either three preoperative and three postoperative 3-week cycles of intravenous epirubicin 50 mg/mBetween Aug 18, 2010, and Aug 10, 2012, 300 patients (152 patients in the ECF/ECX group; 148 patients in the FLOT group) were enrolled into the phase 2 part of the study, 265 of whom (137 in the ECF/ECX group; 128 in the FLOT group) were assessable on a modified intention-to-treat basis. 119 (93%) of 128 patients in the FLOT group and 126 (92%) of 137 patients in the ECF/ECX group were given all planned preoperative cycles of treatment. FLOT was associated with significantly higher proportions of patients achieving pathological complete regression than was ECF/ECX (20 [16%; 95% CI 10-23] of 128 patients vs eight [6%; 3-11] of 137 patients; p=002). 44 (40%) of 111 patients in the ECF/ECX group and 30 (25%) of 119 patients in the FLOT group had at least one serious adverse event involving a perioperative medical or surgical complication. The most common non-surgical grade 3-4 adverse events were neutropenia (52 [38%] of 137 patients in the ECF/ECX group vs 67 [52%] of 128 patients in the FLOT group), leucopenia (28 [20%] vs 36 [28%]), nausea (23 [17%] vs 12 [9%]), infection (16 [12%] vs 15 [12%]), fatigue (19 [14%] vs 11 [9%]), and vomiting (13 [10%] vs four [3%]).Perioperative FLOT was active and feasible to administer, and might represent an option for patients with locally advanced, resectable gastric or gastro-eosophageal junction adenocarcinoma.None.


PubMed | Interdisziplinares Brustzentrum an den Kliniken Essen Mitte, Sana Klinikum, Krankenhaus Eilenriede, Klinik fur Gynakologie am Campus Charite Mitte and 16 more.
Type: Clinical Trial, Phase III | Journal: The Lancet. Oncology | Year: 2016

In metastatic breast cancer, nab-paclitaxel has been shown to significantly increase progression-free survival compared with solvent-based paclitaxel. The GeparSepto (GBG 69) trial assessed whether weekly nab-paclitaxel could increase the proportion of patients achieving pathological complete response compared with weekly solvent-based paclitaxel, both followed by epirubicin plus cyclophosphamide as neoadjuvant treatment.In a phase 3 randomised trial, we enrolled patients with previously untreated unilateral or bilateral primary invasive breast cancer and randomly assigned them in a 1:1 ratio using dynamic allocation and Pocock minimisation by breast cancer subtype, Ki67 and SPARC expression. Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m(2) (after study amendment, 125 mg/m(2)) on days 1, 8, and 15 for four 3-week cycles, or solvent-based intravenous paclitaxel 80 mg/m(2) on days 1, 8, and 15 for four 3-week cycles. Taxane treatment was followed in both groups by intravenous epirubicin 90 mg/m(2) plus intravenous cyclophosphamide 600 mg/m(2) on day 1 for four 3-week cycles. Patients with HER2-positive tumours received concurrent trastuzumab 6 mg/kg (loading dose 8 mg/kg) and pertuzumab 420 mg (loading dose 840 mg) on day 1 of every 3-week cycle. Trastuzumab and pertuzumab were given every 3 weeks concomitantly with chemotherapy for all cycles. This report is the final analysis of the primary endpoint, pathological complete response (ypT0 ypN0), analysed for all patients who started treatment (modified intention to treat). We used a closed test procedure to test for non-inferiority, with the nab-paclitaxel group calculated as non-inferior to the solvent-based paclitaxel group if the lower 95% CI for the OR was above 0858 (OR equivalent to pathological complete response [33%] minus a 10% non-inferiority margin [33%]; 297%). We planned to test for superiority only in case of a positive non-inferiority test, using an of 005. Safety was assessed in all patients who received study drug. The trial is registered with ClinicalTrials.gov, number NCT01583426.Between July 30, 2012, and Dec 23, 2013, we randomly assigned 1229 women, of whom 1206 started treatment (606 with nab-paclitaxel and 600 with solvent-based paclitaxel). The nab-paclitaxel dose was reduced after enrolment of 464 participants to 125 mg/m(2) due to increased treatment discontinuation and sensory neuropathy in this group. Pathological complete response occurred more frequently in the nab-paclitaxel group (233 [38%, 95% CI 35-42] patients) than in the solvent-based paclitaxel group (174 [29%, 25-33] patients; OR 153, 95% CI 120-195; unadjusted p=000065). The incidence of grade 3-4 anaemia (13 [2%] of 605 patients in the nab-paclitaxel group vs four [1%] of patients in the solvent-based paclitaxel group; p=0048) and peripheral sensory neuropathy grade 3-4 (63 [10%] patients receiving any nab-paclitaxel dose; 31 [8%] of patients starting with 125 mg/m(2) and 32 [15%] of patients starting with 150 mg/m(2); vs 16 [3%] in the solvent-based paclitaxel group, p<0001) was significantly higher for nab-paclitaxel than for solvent-based paclitaxel. Overall, 283 (23%) patients were noted to have at least one serious adverse event (based on study drug received), 156 (26%) in the nab-paclitaxel group and 127 (21%) in the solvent-based paclitaxel group (p=0057). There were three deaths (during epirubicin plus cyclophosphamide treatment) in the nab-paclitaxel group (due to sepsis, diarrhoea, and accident unrelated to the trial) versus one in the solvent-based paclitaxel group (during paclitaxel treatment; cardiac failure).Substituting solvent-based paclitaxel with nab-paclitaxel significantly increases the proportion of patients achieving a pathological complete response rate after anthracycline-based chemotherapy. These results might lead to an exchange of the preferred taxane, solvent-based paclitaxel, for nab-paclitaxel in therapy for primary breast cancer.Celgene, Roche.


Murawski N.,Medical School Hamburg | Held G.,Medical School Hamburg | Ziepert M.,University of Leipzig | Kempf B.,Klinikum Landshut | And 11 more authors.
Blood | Year: 2014

To define the role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement (ECFI) of aggressive B-cell lymphoma, we analyzed 11 consecutive German High-Grade Non-Hodgkin Lymphoma Study Group trials. ECFI occurred in 290/4155 (7.0%) patients (orbita, 31; paranasal sinuses, 93; main nasal cavity, 38; tongue, 27; remaining oral cavity, 99; salivary glands, 54). In a multivariable analysis adjusted for International Prognostic Index rituximab improved event-free and overall survival both in patients with and without ECFI. Three-year event-free (79% vs 79%; P = .842) and overall survival (86% vs 88%; P = .351) rates were similar in 145 patients receiving and 57 not receiving radiotherapy. Without rituximab, the 2-year cumulative rate of central nervous system (CNS) disease was increased in 205 ECFI patients compared with 2586 non-ECFI patients (4.2% vs 2.8%; P = .038), whereas this was not observed with rituximab (1.6% in 83 ECFI vs 3.4% in 1252 non-E CFI patients; P = .682). In 88 ECFI patients who received intrathecal prophylaxis with methotrexate, the 2-year rate of CNS disease was 4.2% compared with 2.3% in 191 patientswho did not ( P = .981). In conclusion, rituximab eliminates the increased risk for CNS disease in patients with E CFI. This retrospective analysis does not support intrathecal prophylaxis or radiotherapy to ECFI patients in complete remission/unconfirmed complete remission. These findings should be confirmed in a prospective study. © 2014 by The American Society of Hematology.


Kress P.,Klinikum Mutterhaus der Borromaerinnen | Schafer P.,Klinikum Mutterhaus der Borromaerinnen | Schwerdtfeger F.P.,Klinikum Mutterhaus der Borromaerinnen | Rosler S.,Esslingen University of Applied Sciences
European Archives of Oto-Rhino-Laryngology | Year: 2014

The aim of the study was to compare device life of more recent indwelling voice prostheses Provox Vega and Blom-Singer Dual Valve to device life of wellknown standard devices (Provox 2, Blom-Singer Classic). In a prospective, non-randomised study, device life of Blom-Singer Classic, Blom-Singer Dual Valve, Provox2, Provox Vega and Provox ActiValve voice prostheses was recorded in a group of 102 laryngectomised patients. In total 749 voice prosthesis were included. Average overall life time was 108 days, median 74 days. The prosthesis with the longest dwell time was the Provox ActiValve (median 291 days). Provox Vega had longer device life compared with Provox2 (median 92 days vs 66 days; p = 0.006) and compared with Blom-Singer Classic (median 92 days vs 69 days; p = 0.004). In conclusion, device lifetimes of Provox Vega and ActiValve were better than those of Provox2 and the Blom-Singer Classic. New voice prostheses, with a defined valve opening pressure (Provox Vega, Provox ActiValve, Blom-Singer Dual Valve) had longer lifetimes than prostheses without a defined opening pressure (Blom-Singer Classic and Provox 2). © The Author(s) 2013.


Furderer S.,Klinikum Mutterhaus der Borromaerinnen | Scholten N.,University of Cologne | Coenen O.,University of Cologne | Koebke J.,University of Cologne | Eysel P.,University of Cologne
Journal of Spinal Disorders and Techniques | Year: 2011

Summary Of Background Data: Dvorak et al in 1993 and Husted et al in 2003 reported 2 different screw fixation techniques at the thoracic spine as alternatives to transpedicular screws. So far, there is no investigation comparing the pullout stability of all 3 possible screw fixation techniques. Objective: To evaluate the stability of possible alternatives for transpedicular screw fixation. Study Design: A biomechanical human cadaver investigation of the transpedicular and 2 different extrapedicular techniques was performed in the form of a comparative pullout test. Materials And Methods: Eighteen human vertebral bodies from Th7 to Th9 were harvested from 6 donors, dissected from surrounding tissue, and matched to 3 different fixation groups. As alternatives for transpedicular screw fixation, an extrapedicular supratransverse screw insertion from posterolateral and a tricortical screw fixation technique, penetrating the transverse process and reentering the vertebral body at the pedicle base were evaluated biomechanically. A unilateral screw fixation was performed in one of the described techniques. Axial pullout strength was measured using a Zwick Z50 servoelectric testing machine. Results: The average pullout strength of the pedicle screws was 400 N, whereas the supratransverse and the pertransverse screw fixation resisted 370 N pullout force on average. There was neither a statistic significant difference between the pullout forces of the 3 groups nor a significant correlation of pullout strength and bone mineral density measured by quantitative computed tomography. Conclusions: In-vitro pullout resistance of thoracic screw fixation does not differ significantly in intrapedicular and extrapedicular insertion techniques. Copyright © 2011 by Lippincott Williams & Wilkins.


Schulz-Stubner S.,Deutsches Beratungszentrum fur Hygiene BZH GmbH | Zimmer P.,Klinikum Mutterhaus der Borromaerinnen | Leonards P.,Klinikum Mutterhaus der Borromaerinnen | Weissgerber P.,Deutsches Beratungszentrum fur Hygiene BZH GmbH
Hygiene + Medizin | Year: 2014

A pooled skin swab from temple to toe was introduced in a tertiary care hospital to facilitate the MRSA-screening regimen in addition to the conventional naso-pharyngeal swab. All positive MRSA test results from January 2012 to July 2013 which were recorded according to the German infection control protection law (IfSG) were evaluated as a pilot study of efficiency. 19 % (51 of 266) of MRSA cases were only detected by the pooled skin swab. Compared to multi location skin swabs a pooled skin swab, including the axilla and femoral region is an easy to perform and effective means to increase the sensitivity of MRSA-screening.


Schulz-Stubner S.,Deutsches Beratungszentrum fur Hygiene BZH GmbH | Zimmer P.,Klinikum Mutterhaus Der Borromaerinnen | Leonards P.,Klinikum Mutterhaus Der Borromaerinnen | Schaumann R.,Deutsches Beratungszentrum fur Hygiene BZH GmbH
Hygiene + Medizin | Year: 2014

Background: Currently our alcoholic hand disinfection dispenser pumps are cleaned with warm water in case of visual contamination or residuals on the pump. Other recommendations suggest a higher reprocessing interval (fixed times or with every bottle change). Material and Methods: We studied hand disinfection dispenser pumps in 27 representative areas of the hospital by swabbing the interior of the pumps suction inlet and dispenser outlet and the outside nose of the dispenser with sterile, moist cotton swabs. The residual alcoholic disinfection fluid was analyzed in four cases. The lifetime of the dispenser was characterized in three groups (< 6 months, 2-5 years, > 5 years). Results: Relevant bacterial contamination was not detected, irrespectively of the dispenser's age. Conclusion: Based on our results the current practice of manual cleaning of the alcoholic hand disinfection dispenser pumps with warm water in case of visual contamination or residuals on the pump and not in a regular time interval or with every bottle change seems justified and safe.


Turial S.,University Hospital Freiburg | Enders J.,University Hospital Freiburg | Schier F.,University Hospital Freiburg | Santos M.,Klinikum Mutterhaus der Borromaerinnen
Journal of Gastrointestinal Surgery | Year: 2011

Introduction: The aim of this retrospective comparative study was to compare the surgical results and outcomes of the newly inaugurated approach of microlaparoscopic pyloromyotomy with open techniques. Methods: The surgical charts of 110 infants (85 boys and 25 girls, ages ranging from 10 to 98 (average 28) days) undergoing pyloromyotomy microlaparoscopically (28), through the circumbilical approach (56), or via the right upper quadrant access (26) were reviewed. The variables were compared between the three surgical approach groups, and the statistical analysis was performed. Results: There was a significant difference between Bianchi and microlaparoscopy in terms of operation time (average 38.5 vs. 20.5 min, p < 0.0001) and time to full enteral feed (average 48 vs. 32 h, p = 0.001). There was no significant difference in postoperative length of stay (75 vs. 82 h, p = 0.12). The operative time for the surgeons experienced in microlaparoscopy was in average of 14 min (range, from 9 to 18 min). When comparing the Weber-Ramstedt procedure and microlaparoscopy, microlaparoscopy required significantly less operative time (50 vs. 20 min, p < 0.0001), a shorter time to full enteral feed (70 vs. 32 h, p < 0.001), and a shorter postoperative length of stay (90 vs. 82 h, p = 0.04). There were no cases of mucosal perforation or incomplete pyloromyotomy. Conclusion: Despite the small sample size included in the present study, it seems that microlaparoscopic pyloromyotomy is safe and feasible with the lowest rate of complications and the shortest operative time. The Bianchi approach is a good alternative to achieve a small scar without laparoscopy. © 2011 The Society for Surgery of the Alimentary Tract.

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