Previous studies have indicated that sirolimus (SRL) may be effective for HCC patients undergoing liver transplantation (LT). However, the following results are still contradictory and do not have a clear conclusion. Therefore, we conducted an updated meta-analysis by retrieving published data in EMBASE, PubMed, and the Cochrane Library up to October 2017. Both efficiency and safety of SRL were analyzed using pooled odds ratio (ORs) with 95% confidence interval (CIs). A total of 11 studies involving 7,695 HCC patients were included. Compared with control group, SRL prolonged 1-year (OR = 2.44; CI = 1.66-3.59), 3 year (OR = 1.67; CI = 1.08-2.58) and 5-year (OR = 1.68; CI = 1.21-2.33) overall survival, as well as 1-year (OR = 2.13; CI = 1.19-3.81) disease-free survival. Pooled results found that SRL-treated patients had lower recurrence (OR = 0.60; CI = 0.37-0.98), lower recurrence-related mortality (OR = 0.58; CI = 0.42-0.81) and lower overall mortality (OR = 0.62; CI = 0.44-0.89). Moreover, fewer SRL-treated patients suffered from portal vein thrombosis (OR = 0.29; CI, 0.09-0.91) and diabetes (OR = 0.23; CI = 0.12-0.47), while SRL-treated patients were more vulnerable to acne compared with the control group (OR = 4.44; CI = 1.56-12.60). No significant differences in other adverse effects were found between two groups. Taken together, SRL-based immunosuppression is safe and effective in improving survival, as well as reducing recurrence and mortality for HCC patients following LT.
Objective: This multicenter randomized controlled trial was designed to test the hypothesis that early drain removal (EDR) could decrease the incidence of grade 2 to 4 complications for patients undoing pancreaticoduodenectomy (PD) with low or intermediate risk of postoperative pancreatic fistula (POPF). Background: The safety and effects of EDR on postoperative complications after PD are still controversial. Methods: A multicenter randomized controlled trial at 6 tertiary referral hospitals was carried out (NCT03055676). Patients who met the inclusion criteria, including drain amylase level less than 5000 U/L on postoperative day (POD) 1 and POD 3, and drain output less than 300 mL per day within 3 days after surgery, were enrolled. Patients were then randomized to the EDR group or the routine drain removal (RDR) group. In the EDR group, all drainage tubes were removed on POD3. In the RDR group, drainage tubes were removed on POD 5 or beyond. Primary outcome was the incidence of Clavien-Dindo grade 2 to 4 complications. Secondary outcomes were comprehensive complication index, grade B/C POPF, total medical expenses and postoperative in-hospital stay etc, within 90 days after surgery. Results: A total of 692 patients were screened, and 312 patients were eligible for randomization. Baseline characteristics were well balanced between the 2 groups and 96.8% of these 312 patients had low or intermediate risk of POPF, according to the 10-point fistula risk score. A total of 20.5% of the patients in the EDR group suffered at least 1 grade 2 to 4 complication, versus 26.3% in the RDR group (P ¼ 0.229). Multi-variate analysis showed older age (>65 years old) and blood transfusion were independent risk factors for grade 2 to 4 complications. The rate of grade B/C POPF was low in either group (3.8% vs 6.4%, P ¼ 0.305). The comprehensive complication index of the 2 groups was also comparable (20.9 vs 20.9, P ¼ 0.253). Total medical expenses were not significantly different. Postoperative in-hospital stay was clinically similar (15 days vs 16 days, P ¼ 0.010). Conclusions: Nearly half of the patients undergoing PD met the inclusion criteria, predicting low incidence of grade B/C POPF and major complications. EDR was safe in these patients but did not significantly decrease major complications.
Background/Aims: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies. Methods: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools. Results: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59–0.93], and AUC: 0.84 [95% CI 0.73–0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region. Conclusion: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients.
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