Stem cell factor (SCF) and its receptor, c-Kit, constitute an important signal transduction system with proliferative and anti-apoptotic functions. Besides regulating hemopoietic stem cell proliferation and liver regeneration, it has been implicated in the regulation of human malignancies. However, the cellular expression of the SCF-c-Kit gene system in the liver during cholangiocarcinogenesis has not been studied to date. The protein-and mRNA-expression levels of SCF and c-Kit genes were examined in normal rat liver, in isolated normal rat liver cells and in a thioacetamide-induced rat model of intrahepatic cholangiocarcinoma (CC). Immunohistochemical analysis of the normal liver showed that SCF is expressed in the wall of the hepatic artery and in some cells, which were located along the sinusoids, although it was absent from hepatocytes and biliary epithelial cells. The mRNA analysis of isolated normal liver cell populations revealed a co-expression of SCF-and c-Kit-mRNA in sinusoidal endothelial cells and in Kupffer cells, whereas passaged and cultured liver myofibroblasts (MFs) expressed only SCF. Low levels of the SCF-and c-Kit-mRNA expression could be detected in isolated hepatocytes of the normal liver. Immunohistochemical analysis of the CC tissue showed SCF positivity in proliferating biliary cells (CK-19 þ ), in macrophages (ED-1 þ ) and in MFs (a-smooth-muscle-actin, a-SMA þ ) of the tumoral microenvironment. c-Kit-positivity could be detected on hepatocytes of the regenerating nodules and on the proliferating bile ducts of CC. Compared with the normal liver tissue, SCF-mRNA from the CC tissue was upregulated up to 20-fold, whereas c-Kit-mRNA was upregulated up to fivefold. These data indicate that several cell populations may become able to express SCF and/or c-Kit during cholangiocarcinogenesis. Therefore, the SCF-c-Kit system may contribute to tumor development, for instance, by inducing proliferation of hepatocytes and of biliary cells and by acting as a surviving factor for CC cells.
Background: A major disadvantage of current spacers for two-stage revision total knee arthroplasty (R-TKA) is the risk of (sub-) luxation during mobilization in the prosthesis-free interval, limiting their clinical success with detrimental consequences for the patient. The present study introduces a novel inverse spacer, which prevents major complications, such as spacer (sub-) luxations and/or fractures of spacer or bone. Methods: The hand-made inverse spacer consisted of convex tibial and concave femoral components of polymethylmethacrylate bone cement and was intra-operatively molded under maximum longitudinal tension in 5° flexion and 5° valgus position. Both components were equipped with a stem for rotational stability. This spacer was implanted during an R-TKA in 110 knees with diagnosed or suspected periprosthetic infection. Postoperative therapy included a straight leg brace and physiotherapist-guided, crutch-supported mobilization with full sole contact. X-rays were taken before and after prosthesis removal and re-implantation. Results: None of the patients experienced (sub-) luxations/fractures of the spacer, periprosthetic fractures, or soft tissue compromise requiring reoperation. All patients were successfully re-implanted after a prosthesis-free interval of 8 weeks, except for three patients requiring an early exchange of the spacer due to persisting infection. In these cases, the prosthetic-free interval was prolonged for one week. Conclusion: The inverse spacer in conjunction with our routine procedure is a safe and cost-effective alternative to other articulating or static spacers, and allows crutch-supported sole contact mobilization without major post-operative complications. Maximum longitudinal intra-operative tension in 5° flexion and 5° valgus position appears crucial for the success of surgery.
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