Proteinase-activated receptor-1 (PAR(1)), a thrombin receptor and the prototype of a newly discovered G-protein-coupled receptor subfamily, plays an important role in tumor development and progression. In this study, we documented the expression of the thrombin receptors PAR(1), PAR(3), and PAR(4) in permanent hepatocellular carcinoma (HCC) cell lines and primary HCC cell cultures. Stimulation of HCC cells with thrombin and the PAR(1)-selective activating peptide, TFLLRN-NH(2), increased transmembrane migration across a collagen barrier. This effect was blocked by the PAR(1) antagonist SCH 79797, confirming that the PAR(1) thrombin receptor subtype is involved in regulating hepatoma cell migration. In addition, the PAR(4)-selective agonist, AYPGKF-NH(2), also stimulated HCC cell migration whilst the PAR(4) antagonist, trans-cinnamoyl-YPGKF-NH(2), attenuated the effect of thrombin on HCC cell migration. PAR(1)- and PAR(4)-triggered HCC cell migration was blocked by inhibiting a number of key mediators of signal transduction, including G proteins of the G(i)/G(o) family, matrix metalloproteinases, ERK/MAPKinase, cyclic AMP-dependent protein kinase, Src tyrosine kinase, and the EGF receptor kinase. Our data point to a cooperative PAR(1)/PAR(4) signaling network that contributes to thrombin-mediated tumor cell migration. We suggest that a combined inhibition of coagulation cascade serine proteinases, the two PARs and their complex signaling pathways may provide a new strategy for treating hepatocellular carcinoma.

Primary non-curative gastric resection can reduce the incidence of severe tumor-related complications and can prolong overall survival in selected subgroups. In particular, younger patients with no more than two tumor locations should be considered for this procedure.

BPMN and t.BPM are sufficiently suitable for the planned modelling and imaging of CP. The application in medicine is new, and transfer from the industrial process management is in principle possible. BPMN-CP may be used for teaching and training, patient information and quality management. The graphical image is clearly structured and appealing. Even though the efficiency in the creation of BPMN-CP increases markedly after the training phase, high amounts of manpower and time are required. The most sensible and consequent application of a BPMN-CP would be the direct integration into the hospital computer system. The integration of a modelling language, such as BPMN, into the hospital computer systems could be a very sensible approach for the development of new hospital information systems in the future.

Breast cancer patients younger than 50 years with technically resectable hepatic metastases, minimal extrahepatic tumour and positive HER2 expression appear to be suitable candidates for liver resection with curative intent. An aggressive multi-disciplinary management of those patients including surgical treatment may improve long-term survival.

Background Although up to 9% of patients with gastric cancer develop liver metastases, liver resection is rarely performed because of co-existing non-curative factors. Furthermore, the benefit of liver resection is still controversially discussed. Our goal was to investigate the outcome of patients who underwent liver resection or radiofrequency ablation (RFA) for hepatic metastasized gastric cancer. Methods Retrospectively collected data from a prospectively maintained database were analyzed from 15 patients who underwent liver resection or RFA for liver metastases from gastric cancer. Results Overall 5-year survival and median survival were 27% and 48 months for resected/RFA patients. The perioperative complication rate was low. One patient has been tumor-free for 90 months now. Conclusions Liver resection in patients with hepatic metastasized gastric cancer is beneficial and safe if an R0 situation can be achieved. RFA might be a useful alternative in those patients where surgery is not feasible.

From these data, we have developed a simple score for the risk stratification which may be useful for future studies on interdisciplinary management of colorectal liver metastases.

Patients with resectable liver and lung metastases of the colorectal primary should be considered for surgery after multidisciplinary evaluation regardless of the number or size of the metastases or the disease-free intervals. Clear resection margins are the strongest prognostic parameter.

Multimodal treatment and individual follow-up might be beneficial in patients with higher risk of recurrence after R0 resection of node-negative gastric cancer.