Mesenchymal stem cells together with mycophenolate mofetil inhibit antigen presenting cell and T cell infiltration into allogeneic heart grafts

Donor-derived mesenchymal stem cells (MSC) can induce long-term acceptance in a rat heart transplantation model when injected prior to transplantation in combination with mycophenolate mofetil (MMF). In contrast, MSC alone cause accelerated graft rejection. To better understand these conflicting data we studied the effects of MSC and MMF on lymphocyte populations in heart allografts and secondary lymphatic organs. Allogeneic MSC injected prior to transplantation are immunogenic in this model because activated CD4+ and CD8+ cells emerged earlier in secondary lymphatic organs of MSC- and MSC/MMF-treated animals, compared to animals not treated with MSC. Consequently T cells infiltrated the grafts of MSC-only treated animals promptly causing accelerated graft rejection. However, few T cells or antigen-presenting cells (APC) infiltrated the grafts of animals treated with MSC and MMF. Consistent with this finding, intercellular adhesion molecule 1 (ICAM-1) and E-selectin was down-regulated exclusively in MSC/MMF-treated grafts, indicating that MSC together with MMF interfere with endothelial activation. Additionally, the presence of interferon-gamma (IFN-γ) enhanced MSC capabilities to suppress T cell proliferation in vitro. Interestingly, MMF did not influence serum IFN-γ levels in vivo. Together, our data indicate that MSC pre-activate T cells, but co-treatment with MMF eliminates these T cells, decreases intragraft APC and T cell trafficking by inhibiting endothelial activation, and allows IFN-γ stimulation of suppressive MSC.     

A population-based analysis on the rate and surgical management of colorectal liver metastases in Southern Germany

Purpose  

Early detection and multidisciplinary treatment of colorectal liver metastases (CLM), preferably resection, can significantly prolong the survival of colorectal cancer patients. The purpose of this study was to analyze the incidence, management and long-term clinical outcome of CLM patients using data from a regional German tumour registry.     

Peri-operative anaesthetic management of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is a long and complex procedure with significant blood and fluid loss during debulking and important pathophysiological alterations during the HIPEC phase. We performed a retrospective analysis of 78 consecutive patients undergoing cytoreductive surgery with HIPEC at a university hospital. Our data demonstrate large intra-operative fluid turnover, with 51% of patients requiring a blood transfusion. During HIPEC, airway pressure and central venous pressure increased with a lower oxygenation ratio as a result of increased intra-abdominal pressure with the closed abdomen technique. As a consequence of the raised body temperature, heart rate, end tidal carbon dioxide and arterial lactate levels increased with a slight metabolic acidosis. Peri-operative analysis of routine clotting parameters revealed disturbances of the coagulation status. For pain management, 72% of patients received supplementary thoracic epidural analgesia with consequential peri-operative opioid sparing and a reduced duration of postoperative ventilation.     

Decision support in vaccination policies

Background

Looking across boarders reveals that the national immunization programs of various countries differ in their vaccination schedules and decisions regarding the implementation and funding of new vaccines. The aim of this review is to identify decision aids and crucial criteria for a rational decision-making process on vaccine introduction and to develop a theoretical framework for decision-making based on available literature.

Methods

Systematic literature search supplemented by hand-search.

Results

We identified five published decision aids for vaccine introduction and program planning in industrialized countries. Their comparison revealed an overall similarity with some differences in the approach as well as criteria. Burden of disease and vaccine characteristics play a key role in all decision aids, but authors vary in their views on the significance of cost-effectiveness analyses. Other relevant factors that should be considered before vaccine introduction are discussed to highly differing extents. These factors include the immunization program itself as well as its conformity with other programs, its feasibility, acceptability, and equity, as well as ethical, legal and political considerations. Assuming that the most comprehensive framework possible will not provide a feasible tool for decision-makers, we suggest a stepwise procedure.

Conclusions

Though even the best rational approach and most comprehensive evaluation is limited by remaining uncertainties, frameworks provide at least a structured approach to evaluate the various aspects of vaccine implementation decision-making. This process is essential in making consistently sound decisions and will facilitate the public's confidence in the decision and its realization.     

Surgical therapy of gastric stump carcinoma--a retrospective analysis of 109 patients.

BACKGROUND/AIMS: Although gastric stump carcinoma has been described as early as 1922, knowledge regarding best treatment is still insufficient. Therefore, we analyzed our results of the surgical therapy of gastric stump carcinoma. METHODOLOGY: Between May 1968 and November 1996, 109 patients were operated upon because of gastric stump carcinoma, and the data of these cases were retrospectively analyzed. Survival rates were calculated with the Kaplan-Meier method (Log-rank-test; p < 0.05). RESULTS: A distal Billroth II gastrectomy was the most frequent type of prior operation in 95.4% of the patients. Resectability was 67% (n = 73), and in 64 cases total gastrectomy with systematic lymphadenectomy was performed. Overall post-operative morbidity and mortality were 33.9% and 13.8% respectively. These figures were significantly reduced to 13.8% and 2.8% in the last decade. The 5-year survival rate after radical resection was 40.7%, and prognosis was influenced by R-classification and tumor stage. CONCLUSIONS: Improvements of surgical technique and intensive care management enable resections of gastric stump carcinoma with a low peri-operative morbidity and mortality. Total gastrectomy with systematic lymphadenectomy should be the goal of surgical therapy to obtain a curative resection. Long-term prognosis is similar to that of primary gastric carcinomas.