ABSTRACT
BACKGROUND: There is a controversy as to whether laparoscopic surgery leads to a poor prognosis compared to the open approach for early gallbladder carcinoma (GBC). We hypothesized that the laparoscopic approach is an alternative for early GBC. AIM: To identify and evaluate the safety and feasibility of laparoscopic surgery in the treatment of early GBC. METHODS: A comprehensive search of online databases, including MEDLINE (PubMed), Cochrane libraries, and Web of Science, was performed to identify non-comparative studies reporting the outcomes of laparoscopic surgery and comparative studies involving laparoscopic surgery and open surgery in early GBC from January 2009 to October 2019. A fixed-effects meta-analysis was performed for 1- and 5-year overall survival and postoperative complications, while 3-year overall survival, operation time, blood loss, the number of lymph node dissected, and postoperative hospital stay were analyzed by random-effects models. RESULTS: The review identified 7 comparative studies and 8 non-comparative studies. 1068 patients (laparoscopic surgery: 613; open surgery: 455) were included in the meta-analysis of 1-, 3-, and 5-year overall survival with no significant differences observed [(HR = 0.54; 95%CI: 0.29-1.00; I 2 = 0.0%; P = 0.051), (HR = 0.75; 95%CI: 0.34-1.65; I 2 = 60.7%; P = 0.474), (HR = 0.71; 95%CI: 0.47-1.08; I 2 = 49.6%; P = 0.107), respectively]. There were no significant differences in operation time [weighted mean difference (WMD) = 18.69; 95%CI: -19.98-57.36; I 2 = 81.4%; P = 0.343], intraoperative blood loss (WMD = -169.14; 95%CI: -377.86-39.57; I 2 = 89.5%; P = 0.112), the number of lymph nodes resected (WMD = 0.12; 95%CI: -2.95-3.18; I 2 = 73.4%; P = 0.940), and the complication rate (OR = 0.69; 95%CI: 0.30-1.58; I 2 = 0.0%; P = 0.377 ) between the two groups, while patients who underwent laparoscopic surgery had a reduced length of hospital stay (WMD = -5.09; 95%CI: -8.74- -1.45; I 2 = 91.0%; P= 0.006). CONCLUSION: This systematic review and meta-analysis confirms that laparoscopic surgery is a safe and feasible alternative to open surgery with comparable survival and operation-related outcomes for early GBC.
ABSTRACT
Both caloric restriction (CR) and mitochondrial proteostasis are linked to longevity, but how CR maintains mitochondrial proteostasis in mammals remains elusive. MicroRNAs (miRNAs) are well known for gene silencing in cytoplasm and have recently been identified in mitochondria, but knowledge regarding their influence on mitochondrial function is limited. Here, we report that CR increases miRNAs, which are required for the CR-induced activation of mitochondrial translation, in mouse liver. The ablation of miR-122, the most abundant miRNA induced by CR, or the retardation of miRNA biogenesis via Drosha knockdown significantly reduces the CR-induced activation of mitochondrial translation. Importantly, CR-induced miRNAs cause the overproduction of mtDNA-encoded proteins, which induces the mitochondrial unfolded protein response (UPRmt), and consequently improves mitochondrial proteostasis and function. These findings establish a physiological role of miRNA-enhanced mitochondrial function during CR and reveal miRNAs as critical mediators of CR in inducing UPRmt to improve mitochondrial proteostasis.
