Laparoscopic hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: a systematic review and meta-analysis.

OBJECTIVE: To compare the effects of laparoscopic hepatectomy (LH) on the short-term and long-term outcomes in hepatocellular carcinoma (HCC) patients with and without clinically significant portal hypertension (CSPH). METHODS: A systematic literature search of the PubMed, EMBASE, and Cochrane databases was performed for articles published from inception to March 1, 2023. Meta-analysis of surgical and oncological outcomes was performed using a random effects model. Data were summarized as mean difference and risk ratio with 95% confidence intervals. RESULTS: Five cohort studies with a total of 310 HCC patients were included (CSPH 143; Non-CSPH 167). In terms of surgical outcomes, estimated blood loss and the length of hospital stay were significantly lower in the Non-CSPH group than in the CSPH group. There were no significant differences between the two groups regarding other surgical outcomes, including the operative time, ratio of conversion to open surgery, and overall complication rate. In addition, there were also no significant differences between the two groups regarding the oncological outcomes, such as 1-, 3-, and 5-year overall survival. CONCLUSIONS: HCC patients with and without CSPH who underwent LH had comparable surgical and oncological outcomes. LH is a safe and effective treatment for HCC patients with CSPH under the premise of rational screening of patients.

Robotic versus laparoscopic liver resection for liver malignancy: a systematic review and meta-analysis of propensity score-matched studies.

OBJECTIVE: How different surgical procedures, including the robotic-assisted liver resection (RLR) and laparoscopic liver resection (LLR), can affect the prognosis of patients with liver malignancies is unclear. Thus, in this study, we compared the effects of RLR and LLR on the surgical and oncological outcomes in patients with liver malignancies through propensity score-matched cohort studies. METHODS: The PubMed, Embase, and Cochrane databases were searched using Medical Subject Headings terms and keywords from inception until May 31, 2023. The quality of the included studies was assessed using the Newcastle-Ottawa quality assessment scale. The mean difference with 95% confidence interval (95% CI) was used for analysis of continuous variables; the risk ratio with 95% CI was used for dichotomous variables; and the hazard ratio with 95% CI was used for survival-related variables. Meta-analysis was performed using a random-effects model. RESULTS: Five high-quality cohort studies with 986 patients were included (370 and 616 cases for RLR and LLR, respectively). In terms of surgical outcomes, there were no significant differences in the operation time, conversion rate to open surgery, overall complication rate, major complication rate, and length of hospital stay between the RLR and LLR groups. In terms of oncological outcomes, there were no significant differences in the 5-year overall survival and disease-free survival between the two groups. CONCLUSION: Surgical and oncological outcomes are comparable between RLR and LLR on patients with liver malignancies. Therefore, the benefits of applying RLR in patients with liver malignancies need to be further explored.

Expression profiles of lncRNAs, miRNAs, and mRNAs during the proliferative phase of liver regeneration in mice with liver fibrosis.

The role of lncRNAs in the regeneration of fibrotic liver is unclear. To address this issue, we established a 70% hepatectomy model of liver fibrosis in mice, used high-throughput sequencing technology to obtain the expression profiles of lncRNAs, miRNAs, and mRNAs, and constructed a lncRNA-miRNA-mRNA regulatory network. A total of 1329 lncRNAs, 167 miRNAs, and 6458 mRNAs were differentially expressed. On this basis, a lncRNA-miRNA-mRNA ceRNA regulatory network consisting of 38 DE lncRNAs, 24 DE miRNAs, and 299 DE mRNAs was constructed, and a transcription factor (TF) - mRNA regulatory network composed of 20 TFs and 98 DE mRNAs was built. Through the protein network analysis, a core protein interaction network composed of 20 hub genes was derived. Furthermore, Xist/miR-144-3p/Cdc14b and Snhg3/miR-365-3p/Map3k14 axes in the ceRNA regulatory network were verified by Real-Time quantitative PCR. Therefore, we concluded that these new insights may further our understanding of liver regeneration.

Laparoscopic versus open repeat hepatectomy for recurrent hepatocellular carcinoma: a systematic review and meta-analysis of propensity score-matched cohort studies.

OBJECTIVE: The effectiveness of laparoscopic repeat hepatectomy (LRH) versus open repeat hepatectomy (ORH) on recurrent hepatocellular carcinoma (RHCC) is unclear. We compared the surgical and oncological outcomes of LRH and ORH in patients with RHCC with a meta-analysis of studies based on propensity score-matched cohorts. METHODS: A literature search was conducted on PubMed, Embase, and Cochrane Library with Medical Subject Headings terms and keywords until 30 September 2022. The quality of eligible studies was evaluated with the Newcastle-Ottawa Scale. Mean difference (MD) with a 95% CI was used for the analysis of continuous variables; odds ratio (OR) with 95% CI was used for binary variables; and hazard ratio with 95% CI was used for survival analysis. A random-effects model was used for meta-analysis. RESULTS: Five high-quality retrospective studies with 818 patients were included; 409 patients (50%) were treated with LRH and 409 (50%) with ORH. In most surgical outcomes, LRH was superior to ORH: less estimated blood loss, shorter operation time, lower major complication rate, and shorter length of hospital stay (MD=-225.9, 95% CI=[-360.8 to -91.06], P =0.001; MD=66.2, 95% CI=[5.28-127.1], P =0.03; OR=0.18, 95% CI=[0.05-0.57], P =0.004; MD=-6.22, 95% CI=[-9.78 to -2.67], P =0.0006). There were no significant differences in the remaining surgical outcomes: blood transfusion rate and overall complication rate. In oncological outcomes, LRH and ORH were not significantly different in 1-year, 3-year, and 5-year overall survival and disease-free survival. CONCLUSIONS: For patients with RHCC, most surgical outcomes with LRH were superior to those of ORH, but oncological outcomes with the two operations were similar. LRH may be a preferable option for the treatment of RHCC.

Laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma: Systematic review and meta-analysis of propensity score-matched studies.

OBJECTIVE: To compare the effects of laparoscopic hepatectomy (LH) versus open hepatectomy (OH) on the short-term and long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC) through a meta-analysis of studies using propensity score-matched cohorts. METHODS: The literature search was conducted in PubMed, Embase, and Cochrane Library databases until August 31, 2022. Meta-analysis of surgical (major morbidity, the length of hospital stay, 90-day postoperative mortality), oncological (R0 resection rate, lymph node dissection rate) and survival outcomes (1-, 3-, and 5-year overall survival and disease-free survival) was performed using a random effects model. Data were summarized as relative risks (RR), mean difference (MD) and hazard ratio (HR) with 95% confidence intervals (95% CI). RESULTS: Six case-matched studies with 1054 patients were included (LH 518; OH 536). Major morbidity was significantly lower (RR = 0.57, 95% CI = 0.37-0.88, P = 0.01) and the length of hospital stay was significantly shorter (MD = -2.44, 95% CI = -4.19 to -0.69, P = 0.006) in the LH group than in the OH group, but there was no significant difference in 90-day postoperative mortality between the 2 groups. There were no significant differences in R0 resection rate, lymph node dissection rate, 1-, 3-, and 5-year overall survival or disease-free survival between the LH and OH groups. CONCLUSIONS: LH has better surgical outcomes and comparable oncological outcomes and survival outcomes than does OH on ICC. Therefore, laparoscopy is at least not inferior to open surgery for intrahepatic cholangiocarcinoma.

Oncological outcomes of anatomic versus non-anatomic resections for small hepatocellular carcinoma: systematic review and meta-analysis of propensity-score matched studies.

BACKGROUND: Primary liver cancer is the second-most commonly occurring cancer and has resulted in numerous deaths worldwide. Hepatic resection is of two main types, i.e., anatomic resection (AR) and non-anatomic resection (NAR). The oncological outcomes of hepatocellular carcinoma (HCC) patients after AR and NAR are still considered controversial. Therefore, we aimed to compare the impact of AR and NAR on the oncological outcomes of HCC patients with tumor diameters ≤ 5 cm using the propensity score matching method and research-based evidence. METHOD: A systematic literature search was conducted. The main outcomes were disease-free survival (DFS), overall survival (OS), intrahepatic recurrence rate, and extrahepatic metastasis rate. Relative risk (RR) was calculated from forest plots and outcomes using random-effects model (REM). RESULT: AR significantly improved DFS at 1, 3. and 5 years after surgery, compared to NAR (RR = 1.09, 95% CI = 1.04-1.15, P = 0.0003; RR = 1.16, 95% CI = 1.07-1.27, P = 0.0005; RR = 1.29, 95% CI = 1.07-1.55, P = 0.008). However, both of the difference in DFS at 7 years and OS at 1 and 3 years after AR versus that after NAR were not statistically significant. Nevertheless, the long-term OS associated with AR (5, 7, and 10 years) was superior to that associated with NAR (RR = 1.12, 95% CI = 1.03-1.21, P = 0.01; RR = 1.19, 95% CI = 1.04-1.36, P = 0.01; RR = 1.18, 95% CI = 1.05-1.34, P = 0.008). The difference in the intrahepatic recurrence rate after AR versus that after NAR was not statistically significant, but the extrahepatic metastasis rate after AR was significantly lower than that observed after NAR (RR = 0.61, 95% CI = 0.40-0.94, P = 0.03). CONCLUSION: Therefore, AR should be the preferred surgical approach for HCC patients with tumor diameters ≤ 5 cm. TRIAL REGISTRATION: PROSPERO registration number CRD42022330596.

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: Systematic review and meta-analysis of propensity-score matched studies.

BACKGROUND: The outcomes of elderly (≥65 years) patients with hepatocellular carcinoma (HCC) after laparoscopic liver resection (LLR) vs open liver resection (OLR) are debated. We compared the surgical and oncological outcomes after LLR and OLR in elderly HCC patients based on matched cohort studies that performed propensity score matching (PSM). METHODS: A computer search of the PubMed, Embase, and Cochrane databases until January 31, 2022, was conducted using a combination of Medical Subject Heading (MeSH) terms and other terms. The Newcastle-Ottawa literature evaluation scale was used for quality assessment of the included studies that met the inclusion criteria and none of the exclusion criteria. The postoperative LLR and OLR markers after PSM were summarized. RESULTS: Seven matched cohort studies were included. There were 1346 patients after PSM, of which 673 (50%) underwent LLR and 673 (50%) underwent OLR. All studies were of high quality. For surgical outcomes, the length of surgery was longer in the LLR group than in the OLR group (RR = 29.47, 95% CI = 26.55-32.39, P < 0.00001), but the length of hospitalization was significantly shorter (RR = -1.05,95% CI = -1.24 to -0.86, P < 0.00001), and the incidence of total postoperative complications and severe complications were significantly fewer (RR = 0.69,95% CI = 0.60-0.79, P < 0.00001; RR = 0.49,95% CI = 0.35-0.71, P = 0.0001, respectively). There were no significant differences in overall survival or disease-free survival between the two groups (HR = 0.87, 95% CI = 0.63-1.21, P = 0.41; HR = 0.87, 95% CI = 0.69-1.08, P = 0.20, respectively). CONCLUSIONS: In elderly patients with HCC, LLR was associated with better surgical outcomes than OLR, but there was no significant difference in oncological outcomes. LLR should be the preferred surgical method for elderly patients with HCC.

[Effects of sub-micro emulsion composition on cellular disposition of incorporated lipophilic drug].

OBJECTIVE: To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug. METHODS: Sub-micro emulsions containing 10 % oil, 1.2 % lecithin and 2.25 % glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated. RESULTS: Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09 ± 1.98)ng/µg protein which had significant difference with control group [(38.54 ± 0.34)ng/µg protein]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73 ± 0.84)ng/µg protein, which was about 3 times of that in anionic emulsions [(15.71 ± 0.74)ng/µg protein], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug. CONCLUSION: Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination.