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Hirche C.,University of Heidelberg | Hirche C.,Helios Hospital Berlin Buch | Mohr Z.,Helios Hospital Berlin Buch | Kneif S.,Helios Hospital Berlin Buch | And 2 more authors.
Journal of Surgical Oncology | Year: 2012

Background The lymph node status was shown to be an important prognostic factor for breast cancer, but controversial issues remain. There has been increased focus on optimizing the visualization of lymph nodes for an accurate and selective approach to axillary lymph nodes. Fluorescence-guided lymphatic imaging is a potential candidate for further research on remaining controversies. Methods Forty-seven patients were subject to injection of indocyanine green for navigation to the SLN based on fluorescent dye retention detection. In two groups, patients either received intended axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) for superstaging or isolated SLNB for minimal-invasive staging. The prospective study was designed to evaluate the technical feasibility with focus on solitary positive SLN. Results Visualization of lymphatic vessels with bright fluorescence of the SLN was feasible in 46 of 47 patients. Eighteen of 19 nodal positive patients were correctly identified with a sensitivity of 94.7% in all patients after ALND. After immunohistochemistry, in 19 of 25 overall nodal positive patients (76%) the SLN was the only positive lymph node. Conclusion Fluorescence-guided imaging using fluorescence retention detection allows transcutaneous navigation with a high rate of solitary positive SLN identification as an alternative technique for further research. Copyright © 2011 Wiley Periodicals, Inc.


Xiong L.,University of Heidelberg | Gazyakan E.,University of Heidelberg | Yang W.,University of Tübingen | Engel H.,University of Heidelberg | And 3 more authors.
European Journal of Surgical Oncology | Year: 2014

Background Indocyanine green (ICG) fluorescence-guided sentinel node biopsy (SLNB) has been successfully employed in various kinds of tumors. Clinical results of previous studies on this technique are at different levels of evidence. This Meta-analysis was conducted to provide a more precise estimation on its clinical performance. Methods Eligible studies were identified from systematical PubMed and EMBASE searches; data were extracted. A Meta-analysis was performed to generate pooled detection rate, sensitivity, specificity, diagnostic odds ratio (DOR) and summary receiver operator characteristic curves. Results Fifteen published articles were included. Clinical data of 513 patients were obtained. The pooled detection rate, the pooled sensitivity, the pooled specificity, the pooled DOR and their 95% confidence intervals (95% CI) were 0.96 (0.91-0.99), 0.87 (0.79-0.92), 1.00 (0.99-1.00) and 150.13 (57.42-392.56), respectively. Significant heterogeneities existed among studies. Significant publication bias was found in detection rate. The concentration < 5 mg/ml subgroup and the injected volume ≤2 ml subgroup had higher DORs, sensitivities and detection rates than the concentration ≤ 5 mg/ml subgroup and the injected volume <2 ml subgroup, respectively. Conclusion Based on this Meta-analysis, this technique could be valued promising for detecting the presence of LN metastases. ICG injection with reduced concentration and larger volume may provide improved performance. © 2014 Elsevier Ltd. All rights reserved.


Hirche C.,Helios Hospital Berlin Buch | Hirche C.,University of Heidelberg | Mohr Z.,Helios Hospital Berlin Buch | Kneif S.,Helios Hospital Berlin Buch | And 4 more authors.
International Journal of Colorectal Disease | Year: 2012

Purpose Lymph node status is the most important prognostic factor in colon cancer, but the role of sentinel lymph node biopsy (SLNB) as a tool for identification of micro-metastatic disease and extraanatomical lymph nodes for adjuvant strategies and a tailored approach still remains unclear. Indocyanine green (ICG) fluorescence detection is a new method for SLNB allowing real-time lymphography and lymph node detection. This study was designed to evaluate the feasibility of fluorescence-guided sentinel lymph node detection in colon carcinoma. Methods Twenty six patients with colon adenocarcinoma were prospectively included in this study. Intraoperatively, a peri-tumorous injection with a mean of 2.0 ml ICG was performed, followed by lymphatic mapping and SLNB. Clinical feasibility, detection rate, and sensitivity of the method were analyzed. Results No adverse reactions occurred due to the injection of ICG. Overall, ICG fluorescence imaging identified 1.7 sentinel lymph node (SLN) in average in 25 out of 26 patients (detection rate, 96%). Metastatic involvement of the SLN was found in nine out of 11 nodal positive patients by conventional histopathology. The sensitivity of the method was 82% for colon carcinoma, respectively. Conclusion ICG fluorescence imaging is a new, feasible method for SLNB of colon carcinoma and enables ultra-staging with improved accuracy but with limited validity due to the small number of cases. One advantage of this technique is real-time visualization of lymphatic vessels and SLNB without radiation exposure. Further, larger series are necessary to analyze the role of fluorescence-guided SLNB for colon cancer. © 2011 CARS.


Keller T.,University of Hamburg | Zeller T.,University of Hamburg | Ojeda F.,University of Hamburg | Tzikas S.,Johannes Gutenberg University Mainz | And 13 more authors.
JAMA - Journal of the American Medical Association | Year: 2011

Context: Introduction of highly sensitive troponin assays into clinical practice has substantially improved the evaluation of patients with chest pain. Objective: To evaluate the diagnostic performance of a highly sensitive troponin I (hsTnI) assay compared with a contemporary troponin I (cTnI) assay and their serial changes in the diagnosis of acute myocardial infarction (AMI). Design, Setting, and Patients: A total of 1818 patients with suspected acute coronary syndrome were consecutively enrolled at the chest pain units of the University Heart Center Hamburg, the University Medical Center Mainz, and the Federal Armed Forces Hospital Koblenz, all in Germany, from 2007 to 2008. Twelve biomarkers including hsTnI (level of detection, 3.4 pg/mL) and cTnI (level of detection, 10 pg/mL) were measured on admission and after 3 and 6 hours. Main Outcome Measures: Diagnostic performance for AMI of baseline and serial changes in hsTnI and cTnI results at 3 hours after admission to the emergency department. Results: Of the 1818 patients, 413 (22.7%) were diagnosed as having AMI. For discrimination of AMI, the area under the receiver operating characteristic (ROC) curve was 0.96 (95% CI, 0.95-0.97) for hsTnI on admission and 0.92 (95% CI, 0.90-0.94) for cTnI on admission. Both were superior to the other evaluated diagnostic biomarkers. The use of hsTnI at admission (with the diagnostic cutoff value at the 99th percentile of 30 pg/mL) had a sensitivity of 82.3% and a negative predictive value (for ruling out AMI) of 94.7%. The use of cTnI (with the diagnostic cutoff value at the 99th percentile of 32 pg/mL) at admission had a sensitivity of 79.4% and a negative predictive value of 94.0%. Using levels obtained at 3 hours after admission, the sensitivity was 98.2% and the negative predictive value was 99.4% for both hsTnI and cTnI assays. Combining the 99th percentile cutoff at admission with the serial change in troponin concentration within 3 hours, the positive predictive value (for ruling in AMI) for hsTnI increased from 75.1% at admission to 95.8% after 3 hours, and for cTnI increased from 80.9% at admission to 96.1% after 3 hours. Conclusions: Among patients with suspected acute coronary syndrome, hsTnI or cTnI determination 3 hours after admission may facilitate early rule-out of AMI. A serial change in hsTnI or cTnI levels from admission (using the 99th percentile diagnostic cutoff value) to 3 hours after admission may facilitate an early diagnosis of AMI. ©2011 American Medical Association. All rights reserved.


Marko L.,Max Delbrück Center for Molecular Medicine | Kvakan H.,Max Delbrück Center for Molecular Medicine | Kvakan H.,HELIOS Hospital Berlin Buch | Park J.-K.,Hannover Medical School | And 10 more authors.
Hypertension | Year: 2012

Angiotensin (Ang) II induces vascular injury in part by activating innate and adaptive immunity; however, the mechanisms are unclear. We investigated the role of interferon (IFN)-γ and interleukin (IL)-23 signaling. We infused Ang II into IFN-γ receptor (IFN-γR) knockout mice and wild-type controls, as well as into mice treated with neutralizing antibodies against IL-23 receptor and IL-17A. Ang II-treated IFN-γR knockout mice exhibited reduced cardiac hypertrophy, reduced cardiac macrophage and T-cell infiltration, less fibrosis, and less arrhythmogenic electric remodeling independent of blood pressure changes. In contrast, IL-23 receptor antibody treatment did not reduce cardiac hypertrophy, fibrosis, or electric remodeling despite mildly reduced inflammation. IL-17A antibody treatment behaved similarly. In the kidney, IFN-γR deficiency reduced inflammation and tubulointerstitial damage and improved glomerular filtration rate. Nonetheless, albuminuria was increased compared with Ang II-treated wild-type controls. The glomeruli of Ang II-treated IFN-γR knockout mice exhibited fewer podocytes, less nephrin and synaptopodin staining, and impaired podocyte autophagy. Thus, IFN-γ blockade, but not IL-23 receptor antibody treatment, protects from Ang II-induced cardiac damage and electric remodeling. In the kidney, IFN-γ signaling acts in a cell type-specific manner. Glomerular filtration rate is preserved in the absence of the IFN-γR, whereas podocytes may require the IFN-γR in the presence of Ang II for normal integrity and function. © 2012 American Heart Association, Inc.


Barthel H.,University of Leipzig | Gertz H.-J.,University of Leipzig | Dresel S.,Helios Hospital Berlin Buch | Peters O.,Charité - Medical University of Berlin | And 7 more authors.
The Lancet Neurology | Year: 2011

Background: Imaging with amyloid-β PET can potentially aid the early and accurate diagnosis of Alzheimer's disease. Florbetaben ( 18F) is a promising 18F-labelled amyloid-β-targeted PET tracer in clinical development. We aimed to assess the sensitivity and specificity of florbetaben ( 18F) PET in discriminating between patients with probable Alzheimer's disease and elderly healthy controls. Methods: We did a multicentre, open-label, non-randomised phase 2 study in 18 centres in Australia, Germany, Switzerland, and the USA. Imaging with florbetaben ( 18F) PET was done on patients with probable Alzheimer's disease (age 55 years or older, mini-mental state examination [MMSE] score=18-26, clinical dementia rating [CDR]=0·5-2·0) and age-matched healthy controls (MMSE ≥28, CDR=0). Our primary objective was to establish the diagnostic efficacy of the scans in differentiating between patients with probable disease and age-matched healthy controls on the basis of neocortical tracer uptake pattern 90-110 min post-injection. PET images were assessed visually by three readers masked to the clinical diagnosis and all other clinical findings, and quantitatively by use of pre-established brain volumes of interest to obtain standard uptake value ratios (SUVRs), taking the cerebellar cortex as the reference region. This study is registered with ClinicalTrials.gov, number NCT00750282. Findings: 81 participants with probable Alzheimer's disease and 69 healthy controls were assessed. Independent visual assessment of the PET scans showed a sensitivity of 80% (95% CI 71-89) and a specificity of 91% (84-98) for discriminating participants with Alzheimer's disease from healthy controls. The SUVRs in all neocortical grey-matter regions in participants with Alzheimer's disease were significantly higher (p<0·0001) compared with the healthy controls, with the posterior cingulate being the best discriminator. Linear discriminant analysis of regional SUVRs yielded a sensitivity of 85% and a specificity of 91%. Regional SUVRs also correlated well with scores of cognitive impairment such as the MMSE and the word-list memory and word-list recall scores (r -0·27 to -0·33, p≤0·021). APOE e{open}4 was more common in participants with positive PET images compared with those with negative scans (65% vs 22% [p=0·027] in patients with Alzheimer's disease; 50% vs 16% [p=0·074] in healthy controls). No safety concerns were noted. Interpretation: We provide verification of the efficacy, safety, and biological relevance of florbetaben ( 18F) amyloid-β PET and suggest its potential as a visual adjunct in the diagnostic algorithm of dementia. Funding: Bayer Schering Pharma AG. © 2011 Elsevier Ltd.


Goubergrits L.,Charité - Medical University of Berlin | Schaller J.,Charité - Medical University of Berlin | Kertzscher U.,Charité - Medical University of Berlin | Van Den Bruck N.,Zuse Institute Berlin | And 4 more authors.
Journal of the Royal Society Interface | Year: 2012

Haemodynamics and morphology play an important role in the genesis, growth and rupture of cerebral aneurysms. The goal of this study was to generate and analyse statistical wall shear stress (WSS) distributions and shapes in middle cerebral artery (MCA) saccular aneurysms. Unsteady flow was simulated in seven ruptured and 15 unruptured MCA aneurysms. In order to compare these results, all geometries must be brought in a uniform coordinate system. For this, aneurysms with corresponding WSS data were transformed into a uniform spherical shape; then, all geometries were uniformly aligned in three-dimensional space. Subsequently, we compared statistical WSS maps and surfaces of ruptured and unruptured aneurysms. No significant (p > 0.05) differences exist between ruptured and unruptured aneurysms regarding radius and mean WSS. In unruptured aneurysms, statistical WSS map relates regions with high (greater than 3 Pa) WSS to the neck region. In ruptured aneurysms, additional areas with high WSS contiguous to regions of low (less than 1 Pa) WSS are found in the dome region. In ruptured aneurysms, we found significantly lower WSS. The averaged aneurysm surface of unruptured aneurysms is round shaped, whereas the averaged surface of ruptured cases is multi-lobular. Our results confirm the hypothesis of low WSS and irregular shape as the essential rupture risk parameters. © 2011 The Royal Society.


Chopra S.S.,University Medicine | Mrak K.,Helios Hospital Berlin Buch | Warnick P.,University Medicine | Huenerbein M.,Helios Hospital Berlin Buch
Hepato-Gastroenterology | Year: 2012

Background/Aims: Natural orifice endoscopic surgery (NOTES) is an emerging technique that has been postulated as a promising alternative to laparoscopy in the field of minimal invasive surgery. Until now appropriate indications, safe access routes and general feasibility of this approach have not been defined exactly in surgical oncology. Methodology: A total of 474 patients undergoing cancer surgery were analyzed regarding possible applications of transluminal endoscopic surgery. Patient with potential indications underwent intraoperative endoscopy to evaluate technical aspects, indications and intraoperative feasibility. Results: A potential indication for transluminal surgery was found in 54 of 474 patients (11%) undergoing abdominal cancer surgery. Staging of gastrointestinal tumors was considered the main indication (45%) followed by splenectomy (11%) and diagnostic excision (11%). As a potential access route the transgastric approach was considered in 42 patients (66%) and the transcolonic approach in 18 patients (28 %). Of these 42 patients, 19 (30%) presented with significant intra-abdominal adhesions which would have resulted in a more complicated procedure. Accurate transluminal orientation was considered impossible in 13 cases (20%). Conclusions: Although some indications for NOTES procedures in surgical oncology have been identified in this study these techniques have to be assessed cautiously. Implementation of NOTES in surgical oncology is currently difficult because of technical problems, lack of intraoperative orientation and abdominal adhesions. © H.G.E. Update Medical Publishing S.A.


Hirche C.,Helios Hospital Berlin Buch | Murawa D.,Helios Hospital Berlin Buch | Mohr Z.,Helios Hospital Berlin Buch | Kneif S.,Helios Hospital Berlin Buch | Hunerbein M.,Helios Hospital Berlin Buch
Breast Cancer Research and Treatment | Year: 2010

Background: Sentinel lymph node (SLN) biopsy is a selective approach to axillary staging of breast cancer with reduced morbidity. Current detection methods including radioisotope and blue dye show good results but some drawbacks are remaining. Indocyanine green (ICG) fluorescence detection was evaluated as a new method for SLN biopsy in breast cancer allowing both transcutaneous visualization of lymphatic vessels and intraoperative identification of SLN. Methods: Forty-three women with clinically node negative breast cancer received subareolar injection of ICG for fluorescence detection of SLN. All patients underwent either planned axillary lymph node dissection (ALND) with SLN biopsy or selective SLN biopsy to determine need for ALND. Clinical feasibility, detection rate, sensitivity, and axillary recurrence after isolated SLN biopsy were analyzed. Results: Overall ICG fluorescence imaging identified 2.0 SLN in average in 42 of 43 patients (detection rate: 97.7%). Metastatic involvement of the SLN was found in 17 of 18 nodal positive patients by conventional histopathology (sensitivity: 94.4%). Immunohistochemistry revealed isolated tumor cells in five further cases. There was only one false-negative case in 43 patients (5.6%). In 17 of 23 overall nodal positive patients, the SLN was the only positive lymph node. After a median follow-up of 4.7 years none of the patients presented with axillary recurrence. Conclusion: ICG fluorescence imaging is a new method for SLN biopsy in breast cancer with acceptable sensitivity and specificity comparable to conventional methods. One advantage of this technique is that it allows transcutaneous visualization of lymphatic vessels and intraoperative lymph node detection without radioisotope. © Springer Science+Business Media, LLC. 2010.


Dai Y.,Helios Hospital Berlin Buch | Chopra S.S.,Helios Hospital Berlin Buch | Wysocki W.M.,Helios Hospital Berlin Buch | Hunerbein M.,Helios Hospital Berlin Buch
International Journal of Colorectal Disease | Year: 2010

Background: The application of stents in benign colorectal strictures is considered controversial. The aim of the present study was to assess effectiveness and complications associated with colorectal stent placement in benign colorectal disease. Patients and methods: Fourteen patients with benign colorectal strictures who had undergone previous surgery (colorectal anastomotic stenosis, 13; neosphincter scar stenosis, one) were treated with covered self-expanding metal stent or plastic stent. Placement of the stent was performed with combined endoscopy and contrast enhanced fluoroscopy. Results: Self-expanding stents were successful implanted in all 14 patients without acute procedure-related complications. All patients experienced immediate decompression after stent placement with expansion and patency of the stent. Relief of bowel obstruction for at least 12 months was achieved in seven of 14 patients (50%). Anastomotic fistula healed in four of six patients (67%). Despite the initial success of stenting, re-operations had to be performed in two of seven patients because of late recurrence of the stricture after a mean follow-up of 37 months. Conclusions: Temporary insertion of self-expanding stents is a safe procedure that may be effective in selected cases of benign colorectal stricture. However, repeat surgery will be necessary in a considerable number of patients due to primary or secondary failure of stenting. © 2010 Springer-Verlag.

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