[Treatment of colorectal and non-colorectal liver metastases: rationale for neoadjuvant therapeutic concepts]. / Therapie kolorektaler und nichtkolorektaler Lebermetastasen: Sinnhaftigkeit neoadjuvanter Therapiekonzepte.

BACKGROUND: Liver metastases represent the most common secondary malignant liver disease. Data regarding the incidence of colorectal and non-colorectal liver metastases are rare due to insufficient documentation in a register. Results regarding neoadjuvant therapy are limited and mostly from retrospective analyses. OBJECTIVE: A summary and rating of the rationale for neoadjuvant therapeutic concepts for colorectal and non-colorectal liver metastases were performed. MATERIAL UND METHODS: The analysis was based on European and American guidelines and included publications in both German and English languages. The results and recommendations were summarized and a review based on the literature is given. RESULTS: Neoadjuvant treatment of liver metastases is performed with heterogeneous intentions. The selection of biologically favorable tumors as well as the conversion of primarily non-operable into resectable metastases of the liver are classical reasons for neoadjuvant treatment. The rationale for neoadjuvant treatment of colorectal and especially for non-colorectal liver metastases cannot be answered in a consistently coherent way with respect to the current status quo of the literature and guidelines. The creation of treatment strategies in clinical settings follows criteria, such as patterns of metastases, complexity of the resection and biological factors (metachronous/synchronous metastases, prognostic factors). CONCLUSION: Neoadjuvant treatment in the context of conversion therapy is the standard procedure for metastasized colorectal cancer. The biological selection of favorable tumors as the basis for neoadjuvant treatment of resectable lesions is not a consistently used standard for colorectal cancer. Non-colorectal liver metastases are resected only as part of individual concepts.

Hepatocyte Transplantation to the Liver via the Splenic Artery in a Juvenile Large Animal Model.

Hepatocyte transplantation (HcTx) is a promising approach for the treatment of metabolic diseases in newborns and children. The most common application route is the portal vein, which is difficult to access in the newborn. Transfemoral access to the splenic artery for HcTx has been evaluated in adults, with trials suggesting hepatocyte translocation from the spleen to the liver with a reduced risk for thromboembolic complications. Using juvenile Göttingen minipigs, we aimed to evaluate feasibility of hepatocyte transplantation by transfemoral splenic artery catheterization, while providing insight on engraftment, translocation, viability, and thromboembolic complications. Four Göttingen Minipigs weighing 5.6 kg to 12.6 kg were infused with human hepatocytes (two infusions per cycle, 1.00E08 cells per kg body weight). Immunosuppression consisted of tacrolimus and prednisolone. The animals were sacrificed directly after cell infusion (n=2), 2 days (n=1), or 14 days after infusion (n=1). The splenic and portal venous blood flow was controlled via color-coded Doppler sonography. Computed tomography was performed on days 6 and 18 after the first infusion. Tissue samples were stained in search of human hepatocytes. Catheter placement was feasible in all cases without procedure-associated complications. Repetitive cell transplantations were possible without serious adverse effects associated with hepatocyte transplantation. Immunohistochemical staining has proven cell relocation to the portal venous system and liver parenchyma. However, cells were neither present in the liver nor the spleen 18 days after HcTx. Immunological analyses showed a response of the adaptive immune system to the human cells. We show that interventional cell application via the femoral artery is feasible in a juvenile large animal model of HcTx. Moreover, cells are able to pass through the spleen to relocate in the liver after splenic artery infusion. Further studies are necessary to compare this approach with umbilical or transhepatic hepatocyte administration.

[Surgical treatment of peritoneal metastases of gastric cancer]. / Chirurgische Therapie beim peritoneal metastasierten Magenkarzinom.

BACKGROUND: Up to 17% of all patients with gastric cancer are diagnosed with the presence of peritoneal metastases, which is associated with a poor prognosis. The most promising results were shown with multimodal treatment regimens including systemic chemotherapy and cytoreductive surgery (CRS). A subsequent hyperthermic intraperitoneal chemotherapy (HIPEC).possibly has a positive effect and is currently being tested. OBJECTIVES: This manuscript highlights the key role of CRS and HIPEC in patients with peritoneal metastases of gastric cancer and illustrates which patients benefit from this intensive therapy. METHODS: We performed a comprehensive review of the literature to demonstrate relevant aspects in the treatment of peritoneal metastases in gastric cancer. RESULTS: The use of CRS and HIPEC improves the overall survival to 11 months compared to best supportive care in selected patients. Patients who present with low volume peritoneal disease (peritoneal cancer index ≤6) have the best prognosis. This intensive treatment is associated with a relatively high morbidity (15-50%) and mortality (1-10%). Complete cytoreduction, i.e. a complete macroscopic absence of tumor tissue after resection is the most important prognostic factor. CONCLUSION: The CRS and HIPEC procedures have a proven survival benefit in selected patients. Due to the relatively high morbidity and mortality, the evaluation should be performed by an experienced team including a surgical oncologist, medical oncologist and intensive care physician, to achieve the highest rate of complete cytoreduction in combination with low morbidity; however, the effect of HIPEC has to be proven and the results of the randomized GASTRIPEC trial are awaited.