Background: Treatment options for pancreatic ductal adenocarcinoma (PDAC) are limited. Histone deacetylase inhibitors are a new and promising drug family with strong anticancer activity. The aim of this study was to examine the efficacy of in vitro and in vivo treatment with the novel pan-HDAC inhibitor belinostat on the growth of human PDAC cells. Methods: The proliferation of tumour cell lines (T3M4, AsPC-1 and Panc-1) was determined using an MTT assay. Apoptosis was analysed using flow cytometry. Furthermore, p21^Cip1/Waf1 and acetylated histone H4 (acH4) expression were confirmed by immunoblot analysis. The in vivo effect of belinostat was studied in a chimeric mouse model. Antitumoural activity was assessed by immunohistochemistry for Ki-67. Results: Treatment with belinostat resulted in significant in vitro and in vivo growth inhibition of PDAC cells. This was associated with a dose-dependent induction of tumour cell apoptosis. The apoptotic effect of gemcitabine was further enhanced by belinostat. Moreover, treatment with belinostat increased expression of the cell cycle regulator p21^Cip1/Waf1 in Panc-1, and of acH4 in all cell lines tested. The reductions in xenograft tumour volumes were associated with inhibition of cell proliferation. Conclusion: Experimental treatment of human PDAC cells with belinostat is effective in vitro and in vivo and may enhance the efficacy of gemcitabine. A consecutive study of belinostat in pancreatic cancer patients alone, and in combination with gemcitabine, could further clarify these effects in the clinical setting.

Summary: Background: To determine the adherence to supervised exercise training and underlying reasons for non-adherence amongst patients with inpatient treatment of symptomatic lower extremity peripheral arterial disease (PAD). Patients and methods: This was a prospective questionnaire-based survey study of all consecutively treated inpatients with treatment for either intermittent claudication or chronic limb-threatening ischaemia (CLTI) surveyed at sixteen participating centres in Germany. Results: A total of 235 patients (median age 70 years) were included, thereof 29.4% females and 34.6% with CLTI. The median time from first PAD diagnosis was 4 years (IQR: 1–8). Only 11.4% have previously participated in any walking exercise programme before the index treatment, thereby 10.0% in the IC subgroup and 12.0% with CLTI. Amongst all patients, 35.6% responded they were appropriately informed about the necessity and benefits of walking exercise programmes by their hospital physicians (25.8% by general practitioners), and 65.3% agreed that adherence to supervised exercise may improve their pain-free walking distance. A total of 24.5% responded they had access to necessary information concerning local walking exercise programmes. Amongst 127 free text comments on the reasons for non-adherence to supervised exercise training, 64% of the comments contained lack of information or consent on such measures. Conclusions: Less than 12% of the patients enrolled in the current study have ever participated in a walking exercise programme during their life course. Although all practice guidelines contain corresponding class I recommendations, especially for patients suffering from IC, most patients responded that they were not appropriately informed about the necessity of exercise training along with the fact that 65% agreed that exercise may increase the pain-free walking distance. Taken all together, these results emphasise that we miss an important opportunity in the patient-physician communication. Efforts should be made to improve acceptance and application of structured walking-exercise for patients with PAD.

Purpose: Colonic ischaemia (CI) represents a serious complication after aortic surgery. This study aimed to analyse risk factors and outcome of patients suffering from postoperative CI. Methods: Data of 1404 patients who underwent aortic surgery were retrospectively analysed regarding CI occurrence. Co-morbidities, procedural parameters, colon blood supply, procedure-related morbidity and mortality as well as survival during follow-up (FU) were compared with patients without CI using matched-pair analysis (1:3). Results: Thirty-five patients (2.4%) with CI were identified. Cardiovascular, pulmonary and renal comorbidity were more common in CI patients. Operation time was longer (283 ± 22 vs. 188 ± 7 min, p < 0.0001) and blood loss was higher (2174 ± 396 vs. 1319 ± 108 ml, p = 0.0049) in the CI group. Patients with ruptured abdominal aortic aneurysm (AAA) showed a higher rate of CI compared to patients with intact AAA (5.4 vs. 1.9%, p = 0.0177). CI was predominantly diagnosed by endoscopy (26/35), generally within the first 4 postoperative days (20/35). Twenty-eight patients underwent surgery, all finalised with stoma creation. Postoperative bilateral occlusion and/or relevant stenosis of hypogastric arteries were more frequent in CI patients (57.8 vs. 20.8%, p = 0.0273). In-hospital mortality was increased in the CI group (26.7 vs. 2.9%, p < 0.0001). Survival was significantly reduced in CI patients (median: 28.2 months vs. 104.1 months, p < 0.0001). Conclusion: CI after aortic surgery is associated with considerable perioperative sequelae and reduced survival. Especially in patients at risk, such as those with rAAA, complicated intraoperative course, severe cardiovascular morbidity and/or perioperative deterioration of the hypogastric perfusion, vigilant postoperative multimodal monitoring is required in order to initiate diagnosis and treatment.

Zusammenfassung: Das Gehtraining gehört zu den wichtigsten Säulen der Behandlung der peripheren arteriellen Verschlusskrankheit (pAVK). Das Gehtraining in Gruppen unter Anleitung ist dabei besonders effektiv. In Deutschland ist ein flächendeckendes Angebot von Gehtrainingsgruppen nicht verfügbar. Von der Deutschen Gesellschaft für Gefäßchirurgie und Gefäßmedizin (DGG e. V.), vertreten durch die Kommission „pAVK und diabetischer Fuß“ wurde daher eine Kampagne zur bundesweiten Förderung des Aufbaus von lokalen Gehtrainingsgruppen gestartet. In diesem Artikel wird an Gefäßmediziner appelliert, bei sich vor Ort die Gehtrainingsgruppen auszubauen und mitzugestalten. Die Wege zum Ausbau solcher Gehtrainingsgruppen werden beschrieben.

Background and Aims: The variety of modern antithrombotic medications complicates the choice of individual perioperative therapy in vascular surgery, especially when more than one antithrombotic option is possible. The aim of this study was to determine the perioperative and periinterventional setting concerning antithrombotics in vascular surgery in Germany.Methods: This article is based on a survey from year 2018 of heads of German vascular surgical departments or units regarding their experience with different anticoagulants. The survey asked for the frequency and time of preoperative pausing of the antithrombotics before various vascular operations or interventions.Results: The evaluable response rate was 52% (169/324). Acetylsalicylic acid was discontinued before open aortic surgery in 9% (15/169) of respondents. Clopidogrel was paused in 65% (107/169) before open aortic surgery, in 25% (41/169) before vascular surgery (like carotid endarterectomy, endovascular aortic repair, or operations on peripheral arteries), and in 11% (18/169) before peripheral percutaneous interventions. Discontinuation of vitamin K antagonists or direct oral anticoagulants (took place before conventional operations in 99.4%; oral anticoagulation was continued for peripheral percutaneous interventions in only 6% (8/169). Management was heterogeneous with regard to the timing of the perioperative medication pause. Clopidogrel was not discontinued according to time specifications in 8%; ticagrelor in 75%; rivaroxaban in 23%; and dabigatran in 29%, compared to the recommendations of the industrial information sheets.Conclusion: The perioperative antithrombotic therapy in German vascular surgery clinics is not uniform and does not correspond to the current specialist recommendations in a notable proportion of clinics.