The short-term results from the multicenter RAPID randomized controlled trial indicate that the Legflow PEB is safe and feasible for the treatment of intermediate to long SFA lesions. In this trial, at least 70% of the patients suffered an occlusion. The PEB group had higher rates of primary patency and freedom from CD-TLR, although there were no statistically significant differences vs controls.
BackgroundTreatment 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.MethodsThe proliferation of tumour cell lines (T3M4, AsPC-1 and Panc-1) was determined using an MTT assay. Apoptosis was analysed using flow cytometry. Furthermore, p21Cip1/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.ResultsTreatment 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 p21Cip1/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.ConclusionExperimental 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.
Histone deacetylase inhibitors are a new and promising drug family with a strong anticancer activity and potent modulation of connexin expression. The restoration of connexins in cancer cells has been suggested as a possible mechanism to control tumor progression. The aim of this study was to investigate the effects of 4-phenylbutyrate (4-PB) on the growth of human pancreatic cell lines in vitro and in vivo with a focus on connexin modulation. The proliferation of tumor cells was determined using an MTT assay, and the effect of 4-PB in vivo was studied in a chimeric mouse model. The expression and localization of connexin 43 (Cx43) were assessed by Western blot, immunofluorescence microscopy, and immunohistochemistry. Antitumoral activity was assessed by immunohistochemistry for Ki-67 and histone H4. Treatment with 4-PB resulted in the significant in vitro and in vivo growth inhibition of pancreatic tumor cells. The reduction of the xenograft tumor volume was associated with the inhibition of histone deacetylation and decrease in cell proliferation. Treatment with 4-PB caused a significant increase in the Cx43 expression in T3M4 cells (up to 2.8-fold). The newly synthesized Cx43 was localized in the cytoplasm but not on the cell membrane. Treatment with 4-PB inhibited the proliferation of human pancreatic tumor cells in vitro and in vivo and increased the expression of Cx43. Therefore, 4-PB might be useful in the therapy of pancreatic cancer.
Insufficiency of pancreatic anastomosis with leakage from the pancreatic stump and the development of fistulas account for the majority of surgical complications following pancreatic resection, which are often life threatening. The cause of pancreatic fistulas of the remnant tissue on a molecular level remains unclear. Thus, the aim of the present study was to investigate risk factors associated with postoperative pancreatic fistula (POPF) formation and to define parameters that may predict the resection outcome. Pancreatic resection margins were selected from 31 patients, including 16 individuals without and 15 patients with POPF, to analyze the degree of fibrosis, lipomatous atrophy, inflammatory activity and infiltration. Wound healing factors were assessed by luminex technology using tissue homogenates, while the distribution in situ was assessed using immunohistochemistry. Increased chronic inflammatory infiltration, a higher degree of fibrosis and a reduction in lipomatous atrophy were observed in the samples without anastomotic fistulas. Multiplex analysis of 38 wound healing factors demonstrated significantly higher levels of interleukin (IL)-6, -8 and -12, glucagon-like peptide-1 and matrix metalloproteinase (MMP)-1, -2, -3 and -12 in the group without fistulas, while lower concentrations of IL-10, IL-17 and gastric inhibitory polypeptide were observed. Therefore, the observations of the present study indicated that increased inflammatory infiltration and inflammatory activity, as well as higher concentrations of proinflammatory cytokines and higher MMP levels at the resection margins, predisposed individuals to a lower fistula incidence rate following pancreatic resection.
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.
PMI is a rare but severe complication after pancreatic operations, contributing significantly to in-hospital mortality. Clinical management mainly includes an anti-coagulant approach. This may be related with an increased risk for PPH. Therefore, the use of anti-coagulant drugs in the early postoperative period-especially in asymptomatic patients-should be critically evaluated.
ZusammenfassungDas 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.
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