Background: Shortage of donor organs is one of the major problems for liver transplant programmes. Living liver donation is a possible alternative, which could increase the amount of donor organs available in the short term. Objective: To assess the attitude towards living organ donation in the general population to have an overview of the overall attitude within Germany. Methods: A representative quota of people was evaluated by a mail questionnaire (n = 250). This questionnaire had 24 questions assessing the willingness to be a living liver donor for different potential recipients. Factors for and against living liver donation were assessed. Results: Donating a part of the liver was almost as accepted as donating a kidney. The readiness to donate was highest when participants were asked to donate for children. In an urgent life-threatening situation the will to donate was especially high, whereas it was lower in the case of recipient substance misuse. More women than men expressed a higher disposition to donate for their children. Sex, religion, state of health and age of the donor, however, did not influence other questions on the readiness to consider living organ donation. The will for postmortem organ donation positively correlated with the will to be a living organ donor. Conclusions: The motivation in different demographic subgroups to participate in living liver transplantation is described. Differences in donation readiness resulting from the situation of every donor and recipient are thoroughly outlined. The acceptance for a living liver donation was found to be high – and comparable to that of living kidney donation.
Jaeger, Mark D.1; Tsui, Tung-Yu1; Lauth, Oliver S.1; Dahlke, Marc H.1; Deiwick, Andrea1; Neipp, Michael1; Wonigeit, Kurt1; Schlitt, Hans J.1 Author Information
Abstract The Ras/Raf/MEK pathway represents an important oncogenic signaling pathway in gastrointestinal malignancies, including pancreatic cancer. Although activating B-Raf mutations are infrequent in pancreatic cancer, we hypothesized that targeting Raf could be valuable for therapy of this cancer entity. Moreover, as vascular endothelial growth factor receptor 2 (VEGFR2) is involved in tumor angiogenesis, we sought to investigate the effects of dual inhibition of Raf and VEGFR2 on pancreatic tumor growth, vascularization, and metastasis. Effects of a Raf/VEGFR2 inhibitor (NVP-AAL881) on pancreatic cancer cells, endothelial cells, and vascular smooth muscle cells were determined by Western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis, and migration assays, respectively. Changes in the expression of VEGF-A or survivin were investigated by ELISA and/or real-time PCR. The growth-inhibitory effects of Raf/VEGFR2 inhibition were additionally evaluated in orthotopic tumor models. Results showed that various Raf isoforms were activated in pancreatic cancer cells and NVP-AAL881 diminished the activation of MEK, Akt, Erk, and also STAT3. Moreover, dual inhibition of Raf/VEGFR2 significantly reduced VEGF expression and impaired cancer cell migration. Importantly, besides blocking VEGF-induced Erk and SAPK phosphorylation in endothelial cells, the Raf inhibitor diminished STAT3 phosphorylation, independent of a VEGFR2 blockade, and reduced the expression of survivin. In addition, cell proliferation and migration of both endothelial cells and vascular smooth muscle cells were significantly reduced. In vivo, blocking Raf/VEGFR2 significantly inhibited orthotopic tumor growth and vascularization and reduced cancer metastasis. In conclusion, blocking Raf exerts growth-inhibitory effects on pancreatic tumor cells, endothelial cells, and pericytes and elicits antiangiogenic properties. Dual targeting of Raf and VEGFR2 appears to be a valid strategy for therapy of pancreatic cancer. [Mol Cancer Ther 2008;7(11):3509–18]
Objectives: PORTAS-3 was designed to compare the frequency of pneumothorax or haemothorax in a primary open versus closed strategy for port implantation. Background Data: The implantation strategy for totally implantable venous access ports with the optimal benefit/risk ratio remains unclear. Methods: PORTAS-3 was a multicentre, randomized, controlled, parallel-group superiority trial. Adult patients with oncological disease scheduled for elective port implantation were randomized to a primary open or closed strategy. Primary endpoint was the rate of pneumothorax or haemothorax. Assuming a difference of 2.5% between the 2 groups, a sample size of 1154 patients was needed to prove superiority of the open group. A logistic regression model after the intention-to-treat principle was applied for analysis of the primary endpoint. Results: Between November 9, 2014 and September 5, 2016, 1205 patients were randomized. Of these, 1159 (open n = 583; closed n = 576) were finally analyzed. The rate of pneumothorax or haemothorax was significantly reduced with the open strategy [odds ratio 0.27, 95% confidence interval (CI) 0.09–0.88; P = 0.029]. Operation time was shorter for the closed strategy. Primary success rates, tolerability, morbidity, dose rate of radiation, and 30-day mortality did not differ significantly between the groups. Conclusion: A primary open strategy by cut-down of the cephalic vein, if necessary enhanced by a modified Seldinger technique, reduces the frequency of pneumothorax or haemothorax after central venous port implantation significantly compared with a closed strategy by primary puncture of the subclavian vein without routine sonographic guidance. Therefore, open surgical cut-down should be the reference standard for port implantation in comparable cohorts. Trial Registration: German Clinical Trials Register DRKS 00004900.
Identifying immunosuppressive agents with antitumor effects could help address the problem of posttransplant malignancy. Here we tested for potential inhibitory effects of mycophenolate mofetil (MMF) on tumors in vitro and in vivo.Mouse CT26 colon adenocarcinoma, B16 melanoma, and human TMK1 gastric adenocarcinoma cells were tested for in vitro growth in the presence of MMF. In vitro angiogenesis was tested with a rat aortic-ring assay. Tumor cells were implanted into dorsal skinfold chambers (DSFC) to assess in vivo angiogenesis. Subcutaneous tumor growth was determined in mice receiving MMF.MMF caused a dose-dependent reduction in tumor cell numbers in vitro, starting between 0.1 to 1 microM. Vessel sprouting from aortic rings was markedly blocked by similar concentrations of MMF. In vivo, however, DSFC results showed a marginal reduction in CT26 tumor angiogenesis with MMF doses of 40 or 80 mg/kg/day, although MMF did inhibit TMK1 vascularity. Moreover, 80 mg/kg/day MMF did not reduce subcutaneous CT26 tumor volumes, but did slightly inhibit B16 and TMK1 expansion. Interestingly, the mycophenolic acid (MPA) blood level 2 hr after 80 mg/kg/day MMF bolus dosing was near 14 mg/L, but decreased dramatically thereafter, suggesting a drug availability issue. Indeed, intermittent 2-hr MMF pulses in tumor-cell cultures substantially reduced the antiproliferative effect of MPA.MMF strongly inhibits tumor cell growth and angiogenesis in vitro, but only marginally inhibits tumors in vivo. These contrasting results may relate to drug availability, where intermittent exposure of tumor cells to immunosuppressive doses of MMF substantially reduce its potential antitumor effects.
