115 research outputs found
Die Wirkung von Ausfallrisiko und Insolvenzkosten auf die Kapitalkosten von Unternehmen
Die Bestimmung der Kapitalkosten von verschuldeten Unternehmen ist ein in der Literatur vielfach behandeltes und diskutiertes Forschungsgebiet. Dies ist insoweit kaum verwunderlich, da spätestens seit der weithin gebräuchlichen Anwendung von DCF-Verfahren zur Unternehmensbewertung die Kapitalkosten als Diskontsatz in den Fokus gerückt sind. Während hierbei die Berücksichtigung der steuerlichen Abzugsfähigkeit von Fremdkapitalzinsen etabliert ist, finden Friktionen wie Ausfallrisiko oder Insolvenzkosten im Allgemeinen deutlich weniger Beachtung. An dieser Stelle setzt die vorliegende Dissertation an:
Der wissenschaftliche Beitrag dieser Arbeit liegt in der Neuentwicklung eines Modellrahmens zur Bestimmung der Kapitalkosten unter Einfluss der Friktionen Steuern, Ausfallrisiko und Insolvenzkosten. Ausgehend von einem bereits durch Miles/Ezzell (1980) dargestellten Modellrahmen ohne Ausfallrisiko und Insolvenzkosten, werden Ausfallrisiko und Insolvenzkosten ergänzt. Im Ergebnis resultieren in Abhängigkeit von exogenen Faktoren geschlossene Bewertungsgleichungen für verschuldete Kapitalkosten, Marktwerte von Eigen- und Fremdkapital sowie Fremdkapitalzins. Darauf aufbauend wird das vorgelegte Modell anhand von real existierenden Unternehmen kalibriert. In Abhängigkeit der Höhe der Insolvenzkosten können dabei selbst bei Unternehmen mit guten Rating-Noten hohe Bewertungsunterschiede nachgewiesen werden
Postoperative Veränderungen der distalen Aortenwandarchitektur bei Patienten nach chirurgischer Behandlung einer akuten Aortendissektion Typ A
Die Arbeit handelt von postoperativen Veränderungen der distalen Aortenwandarchitektur bei Patienten nach chirurgischer Behandlung einer akuten Aortendissektion Typ A.:Abkürzungsverzeichnis I
Inhaltsverzeichnis II
1. Einleitung 1
1.1 Historischer Exkurs zur Leipziger Herzchirurgie 1
1.2 Anatomie der Aorta 2
1.3 Erkrankungen der thorakalen Aorta 4
1.4 Die akute Aortendissektion 4
1.5 Klassifikation 4
1.6 Ätiologie und Pathophysiologie 7
1.7 Klinik 9
2. Diagnostik 10
3. Operative Versorgung 13
3.1 Operationsindikation 13
3.2 Operationsverfahren 14
3.2.1 Aorta ascendens 14
3.2.2 Operationserweiterung in den Aortenbogen 17
3.2.3 Operationserweiterung in die Aorta descendens 17
Zielstellung 19
4. Originalpublikation 20
5. Zusammenfassung der Arbeit 30
Literaturverzeichnis III
Tabellenverzeichnis VII
Abbildungsverzeichnis VIII
Darstellung des wissenschaftlichen Beitrags IX
Erklärung über die eigenständige Abfassung der Arbeit X
Lebenslauf XI
Danksagung XII
Randomized controlled trial of S-1 maintenance therapy in metastatic esophagogastric cancer – the multinational MATEO study
Background: The optimal duration of firstline chemotherapy in metastatic esophagogastric cancer is unknown. In most clinical trials therapy was given until tumour progression or limiting toxicity. Maintenance concepts aiming to prolong the duration of response and maintain quality of life have been established in other tumour types but not in esophagogastric cancer. S-1 is an oral fluoropyrimidine with proven efficacy in metastatic esophagogastric cancer. Methods: The Maintenance Teysuno® (S-1) in esophagogastric cancer (MATEO) trial is a multinational, randomized phase II study that explores the role of S-1 maintenance therapy in Her-2 negative, advanced esophagogastric adenocarcinoma. After a 12-week firstline platinum-fluoropyrimidine-based chemotherapy patients without tumour progression are randomized in a 2:1 allocation to receive S-1 alone or continue with the same regimen as during the primary period. The primary endpoint is overall survival. Secondary endpoints include safety and toxicity, progression-free survival and quality of life. Correlative biomarker analyses focus on the identification of a subgroup of patients with a prolonged benefit from S-1 based maintenance therapy. Discussion: MATEO will be the first trial to define the role of a S-1 based maintenance therapy in patients having received a platinum-based firstline chemotherapy. Trial registration: NCT02128243 (date of registration: 29–04-2014)
Palliative chemotherapy for pancreatic adenocarcinoma: a retrospective cohort analysis of efficacy and toxicity of the FOLFIRINOX regimen focusing on the older patient
Background: Pancreatic cancer occurs more frequently in older patients, but these are underrepresented in the phase III clinical studies that established the current treatment standards. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens like FOLFIRINOX.
Methods: We conducted a retrospective analysis of patients treated according to the FOLFIRINOX protocol at our institution between 2010 and 2014 with a focus on older patients.
Results: Overall survival in our cohort was 10.2 months. Only 43% of patients did not need dose adaptations, but dose reductions did not lead to an inferior survival. We did not find evidence that patients aged 65 years and older deemed fit enough for palliative treatment had more toxicities or a worse outcome than younger patients.
Conclusion: We conclude that treatment with the FOLFIRINOX protocol in patients with pancreatic cancer should not be withhold from patients solely based on their chronological age but rather be based on the patient’s performance status and comorbidities
Outcomes and risk factors for cancer patients undergoing endoscopic intervention of malignant biliary obstruction
Background: Malignant bile duct obstruction is a common problem among cancer patients with hepatic or lymphatic metastases. Endoscopic retrograde cholangiography (ERC) with the placement of a stent is the method of choice to improve biliary flow. Only little data exist concerning the outcome of patients with malignant biliary obstruction in relationship to microbial isolates from bile. Methods: Bile samples were taken during the ERC procedure in tumor patients with biliary obstruction. Clinical data including laboratory values, tumor-specific treatment and outcome data were prospectively collected. Results: 206 ERC interventions in 163 patients were recorded. In 43 % of the patients, systemic treatment was (re-) initiated after successful biliary drainage. A variety of bacteria and fungi was detected in the bile samples. One-year survival was significantly worse in patients from whom multiresistant pathogens were isolated than in patients, in whom other species were detected. Increased levels of inflammatory markers were associated with a poor one-year survival. The negative impact of these two factors was confirmed in multivariate analysis. In patients with pancreatic cancer, univariate analysis showed a negative impact on one-year survival in case of detection of Candida species in the bile. Multivariate analysis confirmed the negative prognostic impact of Candida in the bile in pancreatic cancer patients. Conclusion: Outcome in tumor patients with malignant bile obstruction is associated with the type of microbial biliary colonization. The proof of multiresistant pathogens or Candida, as well as the level of inflammation markers, have an impact on the prognosis of the underlying tumor disease
Immunotherapy of Colorectal Cancer
It is known that the immune response, reflected by high T cell infiltrates in primary tumors and metastases, influences the clinical course of colorectal cancer (CRC). Therefore, immunotherapy concepts have been adapted from other tumor entities, which typically rely on the activation of T cells in the tumor microenvironment (e.g. blockade of the immune checkpoint molecules PD-1 and CTLA-4). However, most of the strategies using the approved checkpoint inhibitors and/or combination strategies have more or less failed to produce impressive results in early phase trials in CRC. Therefore, a number of novel targets for checkpoint inhibition are currently in early phase clinical testing (TIM-3, Lag-3, OX40, GITR, 4-1BB, CD40, CD70). A simple activation of infiltrating T cells will not, however, lead to a meaningful anti-tumor response without modulating the environmental factors in CRC. Thus, it is absolutely necessary to improve our understanding of the complex regulation of the tumor microenvironment in CRC to design individual combination treatments leading to effective immune control
Immediate tumor resection in patients with locally advanced gastroesophageal adenocarcinoma with nonresponse to chemotherapy after 4 weeks of treatment versus resection after completion of chemotherapy (OPTITREAT trial, DRKS00004668): study protocol for a randomized controlled pilot trial
Background: Neoadjuvant chemotherapy is a standard of care for patients with adenocarcinoma of the esophagus and stomach in Europe, but still only 20–40 % respond to therapy and the critical issue; how to treat nonresponding patients is still unclear. So far, there is no randomized trial evaluating the impact of early termination of neoadjuvant chemotherapy and immediate tumor resection in nonresponding patients with locally advanced gastroesophageal cancer on postoperative outcome. With this exploratory pilot trial, we want to get first estimates about the effect of discontinuation of chemotherapy with the aim to plan and conduct a further definitive trial. Methods/design: OPTITREAT is designed as a single-center, randomized controlled pilot trial with two parallel study groups. Four weeks after starting neoadjuvant chemotherapy in all patients, clinical response will be assessed by endoscopy and endosonographic ultrasound. Then, nonresponding patients (n = 84) will be randomized in a 1:1 ratio to intervention group with stopping chemotherapy and immediate tumor resection or control group with completion of chemotherapy before surgery. Outcome measures are overall survival, R0 resection rate, perioperative morbidity and mortality, histopathological response, and quality of life. Statistical analysis will be based on the intention-to-treat population. Due to the study design as an explorative pilot trial, no formal sample size calculation was performed. The planned total sample size of 120 patients is considered ethical and large enough to show the feasibility and safety of the concept. First data on differences between the study groups in the defined endpoints will also be generated. Discussion: Individualized therapy is of utmost interest in the treatment of locally advanced gastroesophageal adenocarcinoma as less than half of the patients show objective response to current chemotherapy regimens. The findings of the OPTITREAT trial will help to get first data about clinical response evaluation followed by immediate tumor resection in nonresponding patients after 4 weeks of neoadjuvant chemotherapy. Based on the results of this pilot study, a future confirmatory trial will be planned to prove efficacy and evaluate significance. Trial registration: German Clinical Trial Register number: DRKS0000466
A phase II study for metabolic in vivo response monitoring with sequential 18FDG-PET-CT during treatment with the EGFR-monoclonal-antibody cetuximab in metastatic colorectal cancer: the Heidelberg REMOTUX trial
BACKGROUND: The epidermal growth factor receptor monoclonal antibody cetuximab has proven activity in metastatic colorectal cancer. To date, the mechanisms of action are not completely understood. Especially the impact on tumor glucose metabolism, or tumor vascularization remains largely unclear. The understanding of mechanisms such as early changes in tumor metabolism is of clinical importance since there may be a substantial influence on choice and sequence of drug combinations. Early signals of response to cetuximab may prove useful to identify patients having a relevant clinical treatment benefit. The objective of this trial is to evaluate the predictive relevance of the relative change in (18 )F-Fluorodeoxyglucose tumor uptake for early clinical response during short-term single agent treatment with cetuximab. Early clinical response will be routinely measured according to the response evaluation criteria in solid tumors. Accompanying research includes cytokine immune monitoring and analysis of tumor proteins and tumor genes. METHODS/DESIGN: The REMOTUX trial is an investigator-initiated, prospective, open-label, single-arm, single-center early exploratory predictive study. The first (18 )F-FDG PET-CT is conducted at baseline followed by the run-in phase with cetuximab at days 1 and 8. At day 14, the second (18 )F-FDG PET-CT is performed. Subsequently, patients are treated according to the Folfiri-cetuximab regimen as an active and approved first-line regimen for metastatic colorectal carcinoma. At day 56, clinical response is evaluated with a CT-scan compared to the baseline analysis. Tracer uptake is assessed using standardized uptake values (SUVs). The main hypothesis to be tested in the primary analysis is whether or not the relative change in the SUV from baseline to day 14 has any predictive relevance for early clinical response determined at day 56. Patients are followed until death from any cause or until 24 months after the last patient has ended trial treatment. DISCUSSION: The aim of this trial is to evaluate metabolic changes in metastatic colorectal cancer during short-term single agent treatment with cetuximab and to analyse their potential of predicting early clinical response. This could be helpful to answer the question if early identification of patients not responding to cetuximab is possible. TRIAL REGISTRATION: ClinicalTrials.gov NCT200811021020; EudraCT 20090132792
Beta-2-microglobulin Mutations Are Linked to a Distinct Metastatic Pattern and a Favorable Outcome in Microsatellite-Unstable Stage IV Gastrointestinal Cancers
Immune checkpoint blockade (ICB) shows remarkable clinical effects in patients with
metastatic microsatellite-unstable (MSI) cancer. However, markers identifying potential
non-responders are missing. We examined the prevalence of Beta-2-microglobulin (B2M)
mutations, a common immune evasion mechanism, in stage IV MSI gastrointestinal
cancer and its influence on metastatic pattern and patients’ survival under ICB. Twentyfive
patients with metastatic, MSI gastrointestinal adenocarcinoma were included.
Eighteen patients received ICB with pembrolizumab and one patient with nivolumab/
ipilimumab. Sequencing was performed to determine B2M mutation status. B2M
mutations and loss of B2M expression were detected in 6 out of 25 stage IV MSI
cancers. B2M mutations were strongly associated with exclusively peritoneal/peritoneal
and lymph node metastases (p=0.0055). However, no significant differences in therapy
response (25% vs. 46.6%, p>0.99) and survival (median PFS: 19.5 vs 33.0 months,
p=0.74; median OS 39 months vs. not reached, p>0.99) were observed between B2Mmutant
and B2M-wild type tumor patients. Among metastatic MSI GI cancers, B2Mmutant
tumors represent a biologically distinct disease with distinct metastatic patterns.
To assess ICB response in B2M-mutant MSI cancer patients, future studies need to
account for the fact that baseline survival of patients with B2M-mutant MSI cancer may be
longer than of patients with B2M-wild type MSI cancer
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