We did not include serial measurements of the evaluated cytokines in our study and therefore we are not able to display how cytokine levels respond to surgical treatment. Further studies involving larger patient series are needed before serum cytokine levels can be established as an unequivocally reliable parameter in clinical practice. However, our results provide insights for further investigations. The identification of clinical relevant inflammatory markers is crucial to make progress from bench to daily clinical practice. Longitudinal monitoring of IL-6, IL-8, and IL-10 could reveal a distinct cytokine pattern in dependence of disease severity. We assume that cytokine profiles obtained at the time when NEC is first diagnosed might be capable of distinguishing infants in need for surgery from prospective responders to medical treatment. Despite advances in our understanding of the biology and natural history of HCC and marked improvements in diagnostic techniques, the prognosis for HCC patients remains discouraging because of the high recurrence rate and frequent incidence of intrahepatic metastasis. HCC patients have a high mortality rate due to high intrahepatic recurrence. Various forms of postoperative therapies have been reported, such as interferon, transarterial chemoembolization, and adoptive immunotherapy. Adjuvant interferon has a significant beneficial effect after curative surgery for HCC. However, interferon is frequently associated with adverse effects. Postoperative transarterial chemoembolization seems promising only for HCC patients at high risk of recurrence. Adoptive immunotherapy, while associated with lower recurrence after HCC surgery, does not appear to increase overall survival. Therefore, a more effective and safer postoperative therapy is needed. A vitamin K2 analog, marketed under the name menatetrenone, which is already in use as a novel and safe therapy for osteoporosis, was shown in 2004 to prevent recurrence of HCC in women with viral cirrhosis. Since then, several clinical studies have investigated the efficacy of postoperative therapy with VK2 analog in HCC patients. A systematic review based on four randomized controlled trials involving 209 patients showed that the analog significantly improved tumor recurrence-free survival. However, a recent double-blind, randomized, placebo-controlled study involving 548 patients failed to find an association between postoperative use of the VK2 analog and lower HCC recurrence. In addition to these contradictory findings, this recent RCT failed to address the longterm efficacy of the VK2 analog. To help resolve these questions about the efficacy of VK2 analog therapy, we performed a meta-analysis based on the same studies as in the previous systematic review as well as the most recent large-scale RCT, and we focused on not only short-term but also long-term outcomes. A manual search of the relevant references and review articles was performed to identify additional relevant studies. RCTs, quasi-randomized studies and cohort studies were included. Studies identified by the search were screened independently by two reviewers. Any disagreements were arbitrated by a third reviewer. Two reviewers independently evaluated all the included RCTs in terms of randomization by sequence generation, allocation concealment, blinding of outcome assessors and reporting of intention-to-treat analysis.
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