[Computed tomography and magnetic resonance imaging of colonic diseases]. / Dickdarmerkrankungen in Computertomographie und Magnetresonanztomographie.

BACKGROUND: Early diagnosis of a luminal colonic disease is of essential clinical importance to start timely optimised therapy and detect complications early. OBJECTIVES: This paper aims to provide an overview of the use of radiological methods in diagnosing neoplastic and inflammatory luminal diseases of the colon. Characteristic morphological features are discussed and compared. MATERIALS AND METHODS: Based on an extensive literature review, the current state of knowledge regarding the imaging diagnosis of luminal pathologies of the colon and their importance in patient management is presented. RESULTS: Technological advances in imaging have made the diagnosis of neoplastic and inflammatory colonic diseases using abdominal computed tomography and magnetic resonance imaging the established standard. Imaging is performed as part of the initial diagnosis in clinically symptomatic patients, to exclude complications, as a follow-up assessment under therapy and as an optional screening method in asymptomatic individuals. CONCLUSIONS: Accurate knowledge of the radiological manifestations of the numerous luminal disease patterns, the typical distribution pattern and characteristic bowel wall changes are essential to improve diagnostic decision-making.

[Influence of smoking on the gastrointestinal tract : Range of findings]. / Einfluss des Rauchens auf den Gastrointestinaltrakt : Spektrum der Befunde.

BACKGROUND: Nicotine is a highly addictive drug that, if consumed regularly, can result in chronic or incurable diseases and a reduced quality of life. OBJECTIVES: The aim of this review is to describe the possible health consequences of smoking on the gastrointestinal tract and to provide an overview of related neoplastic and nonneoplastic gastrointestinal diseases. MATERIALS AND METHODS: Based on an extensive literature review, the current knowledge about smoker-associated diseases of the gastrointestinal tract is summarized. RESULTS: Smoking is a significant risk factor for the development of neoplastic and nonneoplastic diseases within the entire gastrointestinal tract. However, they are not associated with specific, smoking-associated radiologic imaging features. CONCLUSION: Knowledge of a smoker's history and possible consequences of nicotine on the gastrointestinal tract can help in the interpretation of radiological images and improve diagnostic decision-making skills and accuracy.

Inhibition of T-antigen expression promoting glycogen synthase kinase 3 impairs merkel cell carcinoma cell growth.

Merkel cell carcinoma is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV). Since proliferation of MCPyV-positive MCC tumor cells strictly depends on expression of the virus-encoded T antigens (TA), these proteins theoretically represent ideal targets for different kinds of therapeutic approaches. Here we developed a cell-based assay to identify compounds which specifically inhibit growth of MCC cells by repressing TA expression. Applying this technique we screened a kinase inhibitor library and identified six compounds targeting glycogen synthase kinase 3 (GSK3) such as CHIR99021 as suppressors of TA transcription in MCC cells. Involvement of GSK3α and -ß in the regulation of TA-expression was confirmed by combining GSK3A knockout with inducible GSK3B shRNA knockdown since double knockouts could not be generated. Finally, we demonstrate that CHIR99021 exhibits in vivo antitumor activity in an MCC xenograft mouse model suggesting GSK3 inhibitors as potential therapeutics for the treatment of MCC in the future.

Association of Platelet Count and Mean Platelet Volume with Overall Survival in Patients with Cirrhosis and Unresectable Hepatocellular Carcinoma.

BACKGROUND: Platelets have been reported to influence tumor biology and may promote metastasis. Traditionally, thrombocytopenia, a hallmark of cirrhosis, was associated with hepatocellular carcinoma (HCC) development. However, the impact of platelet count on outcome in patients with established HCC is not well studied. METHODS: Outcomes of patients with cirrhosis diagnosed with HCC between 1995 and 2013 (derivation cohort) and 2000-2016 (validation cohort) who were not eligible for surgical treatment and did not receive antiplatelet therapy were retrospectively studied. Thrombocytopenia was defined as platelet count < 150 g/L. High mean platelet volume (MPV) was defined as ≥median value of the respective cohort (derivation cohort: ≥11 fL; validation cohort: ≥10.6 fL). RESULTS: Among 626 patients with unresectable HCC, thrombocytopenia was present in 378 (60.4%) and was associated with favorable baseline tumor characteristics: lower diameter of the largest nodule (5.6 ± 3.2 vs. 7.6 ± 4.2 cm), less extrahepatic spread (9.5 vs. 20.2%, both p < 0.001), less macrovascular invasion (21.2 vs. 31.0%, p = 0.005), and lower BCLC stages (63.0 vs. 73.4% BCLC C/D; p = 0.007) as compared to patients with normal platelet count. On univariate analysis, thrombocytopenia and larger MPV were associated with longer overall survival (OS) (thrombocytopenia: median OS [95% CI], 11.5 [9.3-13.8] vs. 5.5 [3.8-7.1] months; p = 0.001; MPV ≥11 fL: 11.7 [9.1-14.2] vs. 6.0 [4.4-7.6] months; p < 0.001). In multivariate analysis, the combined variable of thrombocytopenia and larger MPV was independently associated with longer OS (HR [95% CI], 0.80 [0.65-0.98]; p = 0.029). These results were confirmed in an independent external validation cohort of 525 patients with cirrhosis and HCC. Again, patients with thrombocytopenia and high MPV had significantly longer OS (15.3 [11.7-18.9] vs. 9.3 [7.4-11.2] months; p < 0.001). CONCLUSIONS: Thrombocytopenia and higher MPV are associated with better outcome in patients with advanced HCC. These findings may prompt further clinical research on additive antiplatelet therapy in the prevention and management of HCC.