Conversely, all seven of the included studies suggested that VK2 analog had no significant effects on OS after hepatic resection or local ablation, and the previous systematic review that included four of these studies concluded that the beneficial effect of VK2 analog on OS was uncertain. Two of the RCTs included in the present meta-analysis reported that the VK2 analog reduced HCC recurrence; for example, Mizuta and coworkers reported a hazard ratio for HCC Therefore while creating an algorithm we sought to maximize the differences while minimizing variance recurrence following VK2 analog therapy of 0.27. However, Yoshida and coworkers found no difference in disease-free survival between treatment and control arms. Subgroup analysis based on type of recurrence and certain tumor-related factors also produced negative results. The discrepancies between individual studies and meta-analyses on this topic highlight the importance of using as large a sample as possible. All the studies in this meta-analysis were conducted in Japan. Most patients were also infected with hepatitis C virus. Therefore, the efficacy of VK2 analog therapy in other patient populations or in patients infected with hepatitis B virus is unknown. Nevertheless, studies conducted in China and Japan suggest that the VK2 analog may prevent formation of a secondary tumor in residual liver tissue by inhibiting or activating certain signaling pathways. Therefore, trials of VK2 analog therapy conducted outside Japan may give results similar to those in the present meta-analysis. This meta-analysis has a significant limitation in that data for 548 of the 930 patients came from the trial by Yoshida and coworkers. This trial was discontinued at the second interim analysis because investigators found that VK2 did not prevent short-term recurrence. Thus, survival data for most of the patients in our meta-analysis are limited to one year. The longterm efficacy of VK2 analog needs to be validated by more RCTs. In addition, almost no included studies particularly reported the treatment modality after recurrence. The beneficial effects of VK2 analog are shown in later period. Treatment of HCC after recurrence might affect the clinical prognosis. This meta-analysis has other limitations, due primarily to limitations of the included studies. In Hotta et al., the baseline level of serum des-c-carboxy prothrombin was significantly different between the two arms. Not all studies included here described the method of randomization or allocation concealment. As a result, risk of selection bias and performance bias cannot be excluded. Only one study reported the sample size calculation, and only two used the intention-to-treat principle. Therefore, the results and conclusions of this metaanalysis should be interpreted with caution. Future clinical trials should strive to avoid these limitations as much as possible. In conclusion, our meta-analysis suggests that VK2 analog therapy shows some benefit in reducing the recurrence rate and increasing OS in patients with HCC after hepatic resection or local ablation. In addition, the oral VK2 analog appears to be safe. However, our results should be interpreted with caution because only 1-year survival data were available for 59% of the patients in the meta-analysis. Future studies should analyze the possible benefits of combining two or more postoperative therapies. The transient left ventricular apical ballooning syndrome, also known as takotsubo cardiomyopathy, is an acute cardiac syndrome that has only recently been generally recognized.