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Sommer C.M.,University of Heidelberg | Kauczor H.U.,University of Heidelberg | Pereira P.L.,SLK Kliniken Heilbronn GmbH
Visceral Medicine | Year: 2016

Background: Cholangiocarcinoma (CC) is the second most primary liver malignancy with increasing incidence in Western countries. Currently, surgical R0 resection is regarded as the only potentially curative treatment. The results of systemic chemotherapy and best supportive care (BSC) in patients with metastatic disease are often disappointing in regard to toxicity, oncologic efficacy, and overall survival. In current practice, the use of different locoregional therapies is increasingly more accepted. Methods: A review of the literature on locoregional therapies for intrahepatic cholangiocarcinoma (ICC) was undertaken. Results: There are no prospective randomized controlled trials. For localized ICC, either primary or recurrent, radiofrequency ablation (RFA) is by far the most commonly used thermal ablation modality. Thereby, a systematic review and meta-analysis reports major complication in 3.8% as well as 1-, 3-, and 5-year overall survival rates of 82, 47, and 24%, respectively. In selected patients (e.g. with a tumor diameter of ≤3 cm), oncologic efficacy and survival after RFA are comparable with surgical resection. For diffuse ICC, different transarterial therapies, either chemotherapy-based (hepatic artery infusion (HAI), transarterial chemoembolization (TACE)) or radiotherapy-based (transarterial radioembolization (TARE)), show extremely promising results. With regard to controlled trials (transarterial therapy versus systemic chemotherapy, BSC or no treatment), tumor control is virtually always better for transarterial therapies and very often accompanied by a dramatic survival benefit and improvement of quality of life. Of note, the latter is the case not only for patients without extrahepatic metastatic disease but also for those with liver-dominant extrahepatic metastatic disease. There are other locoregional therapies such as microwave ablation, irreversible electroporation, and chemosaturation; however, the current data support their use only in controlled trials or as last-line therapy. Conclusion: Dedicated locoregional therapies are commonly used for primary and recurrent ICC as well as liver-only and liver-dominant extrahepatic metastatic disease. Currently, the best evidence and most promising results are available for RFA, HAI, TACE, and TARE. In cohort studies, the overall survival rates are similar to those obtained with surgery or systemic therapies. Prospective randomized controlled trials are warranted to compare safety and efficacy between different surgical, interventional, and systemic therapies, as well as their combinations. © 2016 S. Karger GmbH, Freiburg.


Akkad J.,SLK Kliniken Heilbronn GmbH | Bochum S.,SLK Kliniken Heilbronn GmbH | Martens U.M.,SLK Kliniken Heilbronn GmbH | Martens U.M.,University of Heidelberg
Langenbeck's Archives of Surgery | Year: 2015

Background: Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and continues to be a major healthcare concern. Molecular heterogeneity of CRC is believed to be one of the main factors responsible for the considerable variability in treatment response. With the recent development of powerful genomic technologies, novel insights in tumor biology of CRC have now been provided, facilitating the recognition of new molecular subtypes with prognostic and predictive implications.Purpose: The purpose of this review article is to summarize current knowledge about genomic, epigenomic, and proteomic characteristics of CRC, as well as their implications for biomarker identification and individualized targeted therapy.Conclusion: Supplementing the findings from several previous studies, the Cancer Genome Atlas (TCGA) project recently finalized the systematic characterization of CRC resulting in the first tumor dataset with complete molecular measurements at DNA, RNA, and protein levels. The challenge now is to translate these findings into a robust and reproducible CRC classification system linking molecular features of the tumor to precision medicine. © 2015, Springer-Verlag Berlin Heidelberg.


Hoffmann R.,University of Tübingen | Thomas C.,University of Tübingen | Rempp H.,University of Tübingen | Schmidt D.,University of Tübingen | And 3 more authors.
European Radiology | Year: 2012

Objective: To assess the accuracy, the duration and factors that influence the duration of MRI-guided liver or soft-tissue biopsies. Methods: Nineteen liver biopsies and 19 soft-tissue biopsies performed using 1.5T-MRI guidance were retrospectively analysed. Diagnostic performance and complications were assessed. Intervention time was subdivided into preparation period, puncture period and control period. Correlation between procedure time and target size, skin-to-target-distance, used sequences and interventionalists' experience were analysed. Results: Overall sensitivity, specificity and accuracy were 0.86, 1.0 and 0.92, respectively. Two minor complications occurred. Overall median procedure time was 103.5 min. Liver biopsies lasted longer than soft-tissue biopsies (mean [soft-tissue]: 73.0 min, mean [liver]: 134.1 min, P < 0.001). The most time consuming part was the preparation period in both, soft-tissue and liver biopsies corresponding to 59.6% and 47.4% of the total intervention time, respectively. Total procedure time in liver biopsies (P = 0.027) and puncture period in liver and soft-tissue biopsies (P [liver] = 0.048, P [soft-tissue] = 0.005) was significantly prolonged for longer skin-to-target-distances. Lower numbers of image acquisitions (P [liver] = 0.0007, P [soft-tissue] = 0.0012) and interventionalists' experience reduces the procedure duration significantly (P < 0.05), besides all false-negative results appeared during the first five biopsies of each individual radiologist. Conclusion: The interventionalists' experience, skin-to-target-distances and number of image acquisition influence the procedure time significantly. Key Points : •Appropriate training and supervision is essential for inexperienced interventionalists. •Two perpendicular image orientations should confirm the correct biopsy needle position. •Communication between interventionalist and technician is essential for a fluent biopsy procedure. •To shorten intervention time appropriate previous imaging is essential. © 2011 European Society of Radiology.


Hoffmann R.,University of Tübingen | Rempp H.,University of Tübingen | Schmidt D.,University of Tübingen | Pereira P.L.,SLK Kliniken Heilbronn GmbH | And 2 more authors.
Journal of Vascular and Interventional Radiology | Year: 2012

Purpose: To reduce risk of development of a hepatic abscess in patients with preexisting bilioenteric anastomosis (BEA) undergoing radiofrequency (RF) ablation of hepatic tumors by use of prolonged antibiotic prophylaxis over at least 10 days. Materials and Methods: Between April 2003 and June 2011, 184 patients underwent 206 percutaneous RF ablation procedures for hepatic malignancies. Eight patients presented with BEA and were treated in 10 sessions at 14 tumor locations. These 8 patients were male and ranged in age from 5573 years. Median follow-up was 34 months. Antibiotic prophylaxis was given before the intervention (n = 9, piperacillin/tazobactam; n = 1, ciprofloxacin). Oral antibiotic prophylaxis after the intervention was continued with ciprofloxacin for at least 10 days. In four cases, prophylaxis after the intervention was extended with additional antibiotics. Results: A liver abscess occurred 22 days after 1 of 10 RF ablation sessions in patients with preexisting BEA. The patient who developed an abscess presented with a large hepatocellular carcinoma (59 mm × 54 mm) and underwent transarterial chemoembolization 8 days before RF ablation. No hepatic abscess occurred after 196 RF ablation sessions in 176 patients without BEA. Conclusions: Preexisting BEA is a risk factor for formation of hepatic abscesses after RF ablation. An antibiotic prophylaxis regimen before the intervention and for a prolonged period after the intervention that covers anaerobic bacteria for at least 10 days is presented. Combined therapy of transarterial chemoembolization and RF ablation increases the risk for complications in patients with known BEA. © 2012 SIR.


Sopova K.,University of Tübingen | Sopova K.,SLK Kliniken Heilbronn GmbH | Gatsiou K.,Goethe University Frankfurt | Stellos K.,Goethe University Frankfurt | And 3 more authors.
Current Alzheimer Research | Year: 2014

Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Growth factors have been demonstrated to act in a synergistic way in angiogenesis and neurogenesis contributing to self-healing powers of the adult human brain. A growing body of evidence demonstrates that levels of many growth factors (neurotrophins and hematopoietins) are altered in cerebrospinal fluid and peripheral blood from AD patients and in animal models of AD. The present review summarizes the role of several neurotrophic growth factors (e.g., BDNF, SCF, NGF, GDNF) and haematopoietic growth factors (e.g., G-CSF, VEGF, SDF-1) in AD. Moreover, we summarize recent studies evaluating the diagnostic and prognostic value of growth factor levels in blood and cerebrospinal fluid in patients with AD and discuss the potential role of these growth factors as a promising new therapeutic approach in AD. © 2014 Bentham Science Publishers.


Medical providers have become subject to predatory competition in recent years which was deliberately created in the public policy process. However, this competition lacks a comprehensive set of rules. This brought up adverse economic incentives to carry out non-indicated treatments and disregard costly safety standards. Therefore, justice and medical experts must act as allies, define clear minimum standards and enforce them against all decision makers in hospitals and doctor's practices. In the event of damage, it is useful to review 11 medical case groups in which criminal investigations should be directed not only against direct practitioners but also against the responsible heads whether they are doctors or not. © Springer-Verlag 2012.


Ruef P.,SLK Kliniken Heilbronn GmbH | Mangatter A.,SLK Kliniken Heilbronn GmbH
Phlebologie | Year: 2016

Aim: Complicated infantile hemangioma need early, safe and effective treatment. The aim of this study was to provide greater insight into systemic and topical propranolol treatment efficacy and side effects. Methods: We report our retrospective experiences of 207 paediatric patients treated with systemic propranolol and of 148 paediatric patients treated with propranolol gel topically photographed and analysed with a specific hemangioma score. Results: Propranolol treatment was successful in >99 % of the patients. The hemangioma score showed a significant decrease during systemic treatment (8.3 ± 3.3 at beginning and 1.5± 1.4 after 6 months) and during topical treatment (4.2 ± 1,6 at beginning and 2.2 ± 1.3 after three months). Systemic treatment did not show any differences when distributed according to different localizations or to the patient's ages. During topical propranolol treatment relevant serum levels were not determined. Relevant side effects that may have made it necessary to discontinue the treatment were not observed. However, there was a statistically significant reduction in heart rate but not in mean arterial blood pressure during the first six in-hospital systemic drug applications. Conclusion: Systemic propranolol treatment is highly effective and nearly always safe. Topical treatment with propranolol gel (off-label) is suitable for specific hemangioma in addition to cryotherapy and systemic treatment with propranolol. These findings provide highly valuable information on this drug treatment for complicated infantile hemangioma in infants. © Schattauer 2016.


Since 1996 acute subretinal hemorrhages have been treated by intravitreal injections. Large proteins injected into the vitreous cavity can cross the retina as well as the underlying retinal pigment epithelium. After intravitreal injection of tissue plasminogen activator (TPA), plasminogen, which is part of a subretinal clot, is converted to plasmin in the presence of fibrin. Plasmin is a relatively unspecific protease that liquefies a formed fibrin clot. Simultaneous intravitreal injection causes an inferior displacement of the liquefied hemorrhage. Beside mechanical effects on subretinal clots plasmin inhibits choroidal neovascularization by hydrolysis of the extracellular matrix as well as growth factors. After successful displacement of a subretinal hemorrhage an additional anti-VEGF (vascular endothelial growth factor) therapy is required. © 2012 Springer-Verlag.


Sommer C.M.,Abteilung Radiologie | Stampfl U.,Abteilung Radiologie | Kauczor H.U.,Abteilung Radiologie | Pereira P.L.,SLK Kliniken Heilbronn GmbH
Radiologe | Year: 2014

Clinical/methodical issue: Evidence-based therapeutic and diagnostic algorithm for hepatocellular carcinoma. Standard radiological methods: Ultrasound, computed tomography, magnetic resonance imaging, image-guided percutaneous biopsy, percutaneous thermal ablation and transarterial chemoembolization. Methodical innovations: Diagnostic and therapy of hepatocellular carcinoma according to the official German interdisciplinary guidelines. Performance: The formulation of the German S3 guidelines on diagnosis and therapy of hepatocellular carcinoma was performed under special consideration of quality indicators and standardized quality improvement methods. Achievements: In 2013 the German S3 guidelines on diagnosis and therapy of hepatocellular carcinoma were published and clinically implemented as part of the nationwide guideline program in oncology of the Deutsche Krebsgesellschaft (German Cancer Society). Practical recommendations: The German S3 guidelines on diagnosis and therapy of hepatocellular carcinoma have to be considered as the national gold standard with the goal of optimization of patient care. © 2014 Springer-Verlag Berlin Heidelberg.


Lummel N.,Ludwig Maximilians University of Munich | Wollenweber F.A.,Ludwig Maximilians University of Munich | Demaerel P.,University Hospital uven | Bochmann K.,Ludwig Maximilians University of Munich | And 4 more authors.
Journal of Neurology | Year: 2015

Cortical superficial siderosis (cSS) is an increasingly recognized MR-imaging marker most probably caused by focal convexity subarachnoid hemorrhage (SAH). There is accumulating evidence that cSS represents an important risk factor for subsequent intracranial hemorrhages. Here, we aimed to determine clinical symptoms, underlying etiologies, and radiological characteristics of cSS in a large patient cohort. We performed an electronic database search on all patients who presented between 2002 and 2013 to the university hospital Munich with non-traumatic and non-aneurysmal cSS. T2*-weighted gradient-echo sequences were analyzed regarding localization and extent of cSS as well as of acute SAH, intracerebral hemorrhages (ICH) and microbleeds. Besides, all available clinical, laboratory, imaging and histological data were analyzed. 113 subjects matched the inclusion criteria. The following etiologies for cSS were identified: definite (n = 6; 5 %), probable (n = 75; 66 %), and possible (n = 28; 25 %) cerebral amyloid angiopathy (CAA); reversible cerebral vasoconstriction syndrome: 2 (2 %); central nervous system vasculitis: 1; and hyperperfusion syndrome: 1. Acute ICH was evident in 55 (49 %) cases. Other clinical manifestations were: transient focal neurological episodes (TFNE): 38 (34 %); cognitive impairment: 14 (12 %); generalized seizure: 4 (4 %); and headache: 2 (2 %). Adjusting for age and gender, cognitive impairment was more frequent in disseminated cSS, while TFNE was more often found in focal cSS (p = 0.042). Our data indicate CAA to be the most common etiology of cSS. In absence of symptomatic ICH, patients with focal cSS frequently present with TFNE, while those with disseminated cSS commonly manifest with cognitive impairment. © 2015, Springer-Verlag Berlin Heidelberg.

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