KRAS und weitere Signalmoleküle für die Therapieentscheidung beim metastasierten Kolonkarzinom

In recent years targeted therapy has made an impact in all aspects of oncology but in particular in the treatment of colorectal cancer. This development is the result of increasing knowledge on signal cascades in tumors in vitro and in vivo which play an essential role in the regulation of cell survival, tumor growth and metastasis. This has led to the development of strategies to interrupt signal cascades relevant for tumors and ideally with targeted medications to affect only the tumor and not other organs or cell systems. In the field of colorectal cancer the implementation of targeted therapies has if nothing else brought a clear improvement in tumor response, progression-free survival and total survival; however, not for all patients treated with these medications. There is therefore an increasing demand for predictive markers for therapy with these, even cost-intensive, therapeutics which allow a prediction whether a patient will profit from a certain targeted therapy. In this article the current state of the art and value of predictive markers for targeted therapy strategies against epidermal growth factor receptor for metastasized colorectal cancer will be presented.     

Anamnestische Ergebnisse bei Mammacarcinomen mit besonderer Berücksichtigung ihrer Bedeutung für die Therapie

Ohne Zusammenfassung     

Orthesen für die rheumatische Hand

Treatment of rheumatic hand deformities is a very sensitive task, requiring profound knowledge of functional anatomy as well as extensive rheumatologic experience. Assistive devices such as orthoses in the therapy of typical deformities aim to prevent continuing loss of function. Furthermore reduction of pain, economization of movements and maintaining postoperative results are important. Contraindications for surgical interventions are also an indication. Static orthoses are to be distinguished from individually produced dynamic devices, which may protect anatomical structures while providing relatively free motion. The indication for this treatment must be agreed by the physician in charge, the patient and the occupational therapist together, assisting functional exercises are strongly recommended. The condition of the skin must be considered and regular follow-up has to be arranged. Each region of the hand and characteristic deformities require individual orthotic devices, according to the capabilities of the patient. The patient's possible improvement of daily activities in relation to the disadvantages of having to use orthoses determines the therapy. Given indications for surgical procedures are taken into consideration from the onset of the treatment plan.     

Neue Therapieoptionen für die Leberfibrose

Liver fibrosis, i.?e., excessive hepatic scarring, is a common result of chronic liver diseases and may progress to cirrhosis. Rapidly increasing knowledge on the pathomechanisms of liver inflammation and fibrosis have prompted novel antifibrotic treatment strategies. Promising approaches include the modulation of cell death or inflammatory signaling pathways. Moreover, inhibiting the recruitment inflammatory immune cells into the liver, e.?g., via the chemokine receptor CCR2 antagonist cenicriviroc, or inhibiting the inflammatory activation of macrophages, e.?g., via galectin-3 inhibitors, are currently being evaluated in preclinical and early clinical studies. Likewise, novel antibodies against LOXL2 (simtuzumab) directly target the extracellular matrix, which is mainly composed of collagen and is stabilized by cross-links. The synthetic bile acid derivate obeticholic acid showed promising results in a phase 2 study (FLINT trial) in patients with nonalcoholic steatohepatitis (NASH) and fibrosis, prompting a multicenter phase III trial with this drug. The gut–liver axis is of exceptional relevance for fibrosis progression, and its components including gut microbiota, intestinal barrier function, and scavenger role of the liver for intestinal endotoxins represent additional targets for therapeutic interventions. Although the rapid knowledge transfer from bench to bedside is impressive, many aspects such as application schedule, patient selection, and appropriate end-points are not conclusively defined. Final results from ongoing trials need to be awaited regarding the efficacy of the new antifibrotic therapies.     

Über die Reizempfindlichkeit des Centrosoms und ihre Bedeutung für die Organoplastik und für die anorganoplastischen Gewebswucherungen

Ohne Zusammenfassung     

Tumor Budding beim kolorektalen Karzinom: Konsensus für den klinischen Einsatz

Background

Tumor budding in colorectal cancer has been identified as a robust biomarker. This morphological phenomenon, namely single tumor cells and small clusters of tumor cells that detach from the main tumor body, can also be used in certain clinical scenarios to guide patient management; however, tumor budding has hardly been integrated in colorectal cancer reporting protocols, mainly due to the lack of a standardized scoring method. The International Tumor Budding Consensus Conference (ITBCC), held in 2016 in Bern, Switzerland, has established evidence-based guidelines for assessing and reporting tumor budding in colorectal cancer.

Objective

Presentation of the current understanding of tumor budding in colorectal cancer with emphasis on clinically relevant applications.

Material and methods

Evaluation and overview of the relevant literature and level of evidence as a basis for the ITBCC guidelines.

Results

Current findings support tumor budding as a morphological correlate of epithelial-mesenchymal transition. Strong associations with nodal metastases, poorer survival and higher recurrence rates mean tumor budding can be used to identify at-risk patients with endoscopically resected pT1 colorectal cancer and stage II colorectal cancer who may require segmental resection or be offered adjuvant chemotherapy, respectively. According to the ITBCC tumor budding should be reported in both of these scenarios.

Conclusion

The ITBCC provides a basis for tumor budding to be integrated into standard colorectal cancer protocols; therefore, it can be expected that this marker will be increasingly reported. The ITBCC recommends that tumor budding be considered as an additional risk factor in a multidisciplinary setting.

     

Hybridraumtechnologie als Voraussetzung f��r die moderne Therapie der Aortendissektion

With the establishment of a hybrid room 7 years ago, it was possible for the first time to unite a full range of diagnostics and surgical therapy under the sterile conditions of an operating theatre in life-threatening aortic dissection. Thus, the early phase associated with high mortality rates (3%-5% per hour) could be significantly reduced from 8 h to 4 h. Multidisciplinary teams consisting of a cardiac surgeon, a cardiologist and an anaesthetist enable competent and rapid life-saving measures. In the case of acute and persistent visceral and/or peripheral malperfusion over many hours, primary endovascular reconstitution of perfusion precedes delayed surgical replacement of the ascending aorta with or without the aortic arch. Additional strategic and technical surgical developments have helped reduce overall hospital mortality from 15%-20% to 10%-15%. Though expensive to build, a high-technology hybrid room enables interdisciplinary specialization and concentration, as demonstrated by the exponential growth in the development of transcatheter aortic valve implants or the endovascular treatment of aortic disease.     

Hat die Bendiensche Flockungsreaktion Wert für die Krebsdiagnose?

Zusammenfassung Die Bendiensche Vanadium-Essigsäure-Serumreaktion ist unspezifisch. Ihr positiver Ausfall beweist nicht, daß eine bösartige Neubildung vorliegt, ihr negativer Ausfall gestattet nicht, eine solche auszuschließen.Für die Carcinomfrühdiagnose ist deshalb das Verfahren nicht zu verwenden.     

Neue Biologika für die Behandlung chronisch-entzündlicher Darmerkrankungen

Background

The therapeutic options for chronic inflammatory bowel diseases have seen an enormous development over the last decades. However, there are several unmet needs which warrant the development of additional biologics for a better and complete control of the inflammatory process.

State of development

Novel biological therapies that will be approved in the near future include blockade of the adhesion molecule integrin alpha4beta7 and the cytokine interleukin 23. Large phase III trials have established the clinical efficacy in ulcerative colitis and Crohn’s disease, respectively. The development of biologic therapies in earlier stages includes additional antibodies that block adhesion molecules as well as biologics that intercept the interleukin 6 pathway.

Conclusion

The therapeutic landscape in inflammatory bowel disease will be enriched by additional biologic therapies. Clinical studies should investigate the interaction with existing therapies, e.g. anti-tumor necrosis factor (TNF) therapies and the development of new endpoints for a better disease control and for improved long-term outcome.     

Über die Bedeutung der Vitamine für die Krebstherapie

Ohne ZusammenfassungMit 18 Textabbildungen.     

Ueber Verwertung spezifischer Serumreaktionen für die Carcinomforschung

Ohne Zusammenfassung     

Ein Verbesserungsvorschlag für die Praxis der Retraktionsmessung

Ohne Zusammenfassung