Comparison of liver resection and radiofrequency ablation in long-term survival among patients with early-stage hepatocellular carcinoma: a meta-analysis of randomized trials and high-quality propensity score-matched studies.

BACKGROUND: Whether radiofrequency ablation (RFA) and liver resection (LR) are comparable treatments for early-stage hepatocellular carcinoma (HCC) is controversial. We conducted this study to provide ample clinical evidence for the argument. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify randomized controlled trials (RCTs) and propensity score-matched (PSM) studies that compared long-term outcomes of both RFA and LR for patients with early-stage HCC. The hazard ratios (HRs) with 95% confidence intervals (95% CI) of overall survival (OS) and disease-free survival (DFS) were calculated. RESULTS: Thirty-six studies consisting of six RCTs and 30 PSM studies were included in this study, and a total of 7384 patients were involved, with 3694 patients being treated with LR and 3690 patients with RFA. Meta-analysis showed that LR provided better OS and DFS than RFA (HR: 1.22, 95% CI: 1.13-1.31; HR: 1.56, 95% CI: 1.39-1.74, respectively). A sensitivity analysis indicated that the results were stable. For the subgroup of patients with BCLC 0 stage, RFA and LR resulted in similar OS and DFS. For the subgroup of patients with single tumor sizes less than 3 cm, RFA reached similar OS (HR: 1.19, 95% CI: 0.90-1.58) but worse DFS compared with LR (HR: 1.45, 95% CI: 1.11-1.90). For the subgroup of ablation margin larger than 0.5 cm, LR still resulted in better OS than RFA (HR: 1.29, 95% CI: 1.09-1.53); while the ablation margin was larger than 1 cm, both RFA and LR resulted in similar OS. The modality of RFA was also a factor that affected results. Subgroup analysis showed that patients receiving ultrasound-guided RFA had worse OS and DFS than LR (HR: 1.24, 95% CI: 1.14-1.36; HR: 1.44, 95% CI: 1.25-1.66, respectively). CONCLUSIONS: Meta-analysis showed that LR provided better OS and DFS for patients with early-stage HCC. However, RFA and LR had similar effects on long-term survival in patients with BCLC 0 stage HCC. RFA and LR probably had similar effects on OS in patients with solitary HCC less than 3 cm or when the ablation margin was larger than 1 cm which need more studies to confirm. The effects of different modalities of RFA on long-term survival are needed for further assessment.

Efficacy of transarterial therapy combined with first-line tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a network meta-analysis.

BACKGROUND: Transarterial therapies, including transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and selective internal radiation therapy, combined with first-line tyrosine kinase inhibitors (TKIs) are considered the standard therapy for unresectable hepatocellular carcinoma. However, inconsistent results have been reported in various studies assessing different combinations of targeted agents. METHODS: A network meta-analysis (NMA) was performed by including 23 randomized controlled trials (RCTs) with 6175 patients to investigate the efficiency of transarterial therapies in combination with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), time to progression (TTP), and tumor objective response rate (ORR). A random-effects consistency model was used in this Bayesian NMA. Hazard ratio and odd risks with a 95% credible interval were calculated and agents were ranked based on ranking probability. RESULTS: HAIC showed maximal OS and TTP and TACE plus lenvatinib showed maximal PFS, ORR, and disease control rate (DCR). HAIC and TACE plus lenvatinib were ranked highest based on their respective parameters, which were OS for HAIC and PFS, ORR, and DCR for TACE plus lenvatinib. CONCLUSION: HAIC and TACE plus lenvatinib were relatively better choice for unresectable hepatocellular carcinoma. However, owing to the lack of statistically significant OS benefits among most agents, other agents should be considered as potential alternatives for unresectable hepatocellular carcinoma.

Does adjuvant hepatic artery infusion chemotherapy improve patient outcomes for hepatocellular carcinoma following liver resection? A meta-analysis.

BACKGROUND: Adjuvant hepatic artery infusion chemotherapy (HAIC) has been shown to be beneficial to the patient outcomes in hepatocellular carcinoma (HCC). METHODS: Randomized controlled trials (RCTs) and non-RCTs were identified from six databases up to January 26, 2023. Patient outcomes were assessed using overall survival (OS) and disease-free survival (DFS). Data were presented as hazard ratios (HR, 95% confidence intervals, or CIs). RESULTS: The present systematic review included 2 RCTs and 9 non-RCTs with a total of 1290 cases. Adjuvant HAIC improved OS (HR of 0.69; 95% CI of 0.56-0.84; p < 0.01) and DFS (HR of 0.64; 95% CI of 0.49-0.83; p < 0.01). Subgroup analysis showed that HCC patients with portal vein invasion (PVI) or microvascular invasion (MVI) benefit from adjuvant HAIC in terms of OS ((HR of 0.43; 95% CI of 0.19-0.95; p < 0.01) and (HR of 0.43; 95% CI of 0.19-0.95; p = 0.0373), respectively) and DFS ((HR of 0.38; 95% CI of 0.21-0.69; p < 0.01) and (HR of 0.73; 95% CI of 0.60-0.88; p = 0.0125), respectively). Adjuvant HAIC with the oxaliplatin-based approach significantly improved OS (HR of 0.60; 95% CI of 0.36-0.84; p = 0.02) and (HR of 0.59; 95% CI of 0.43-0.75; p < 0.01), respectively). CONCLUSION: This meta-analysis demonstrated that postoperative adjuvant HAIC was beneficial in HCC patients with PVI and MVI. It remains unclear whether HAIC can improve the survival outcome in all HCC patients after hepatic resection.

Comparison of the effects of lenvatinib and sorafenib on survival in patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND AIM: The first-line systemic therapy for advanced hepatocellular carcinoma (HCC) involves the use of sorafenib and lenvatinib. The present meta-analysis attempted to compare the therapeutic safety and effectiveness of the two drugs in advanced HCC. METHODS: The library databases of Cochrane, Embase, PubMed, and Web of Science were systematically searched to identify eligible studies comparing the long-term outcomes of sorafenib and lenvatinib use in advanced HCC patients. Overall survival (OS) was considered the primary endpoint, whereas the progression-free survival (PFS), severe adverse events (AEs), objective response rate (ORR), and disease control rate (DCR) were considered the secondary endpoints. RESULTS: The present systematic review included 8 nonrandomized studies and 1 randomized controlled trial, comprising a total of 1, 914 cases. OS in patients receiving lenvatinib was better than that in patients receiving sorafenib [hazard ratio (HR): 1.23; 95% confidence interval (CI): 1.04-1.45]. Additionally, patients who received lenvatinib exhibited better PFS, ORR, and DCR (HR: 0.89, 95% CI: 0.79-0.99), [odds ratio (OR: 7.50, 95% CI: 4.43-12.69)], (OR: 7.50, 95% CI: 4.43-12.69), but higher incidences of AEs than those receiving sorafenib (OR: 1.28, 95% CI: 1.08-1.53). CONCLUSION: Lenvatinib is superior to sorafenib in treating unresectable HCC patients.

Short-term clinical outcomes and five-year survival analysis of laparoscopic-assisted transanal natural orifice specimen extraction versus conventional laparoscopic surgery for sigmoid and rectal cancer: a single-center retrospective study.

Background: The cosmetic benefits of natural orifice specimen extraction (NOSE) are easily noticeable, but its principles of aseptic and tumor-free procedure have caused controversy. Methods: We conducted a retrospective analysis of the clinical data of patients who underwent laparoscopic-assisted transanal NOSE or conventional laparoscopic surgery (CLS) for sigmoid and rectal cancer at our hospital between January 2018 and December 2018. The study aimed to compare the general characteristics, perioperative indicators, postoperative complications, and five-year follow-up results between the two groups. Results: A total of 121 eligible patients were enrolled, with 52 underwent laparoscopic-assisted transanal NOSE and 69 underwent CLS. There were no significant differences observed between the two groups in terms of gender, age, body mass index (BMI), TNM stage, etc. (P > 0.05). However, the NOSE group exhibited significantly shorter total incision length and longer operation time compared to the CLS group (P < 0.05). There were no statistically significant differences observed between the two groups in terms of positive rate of bacterial culture, incidence rates of intraabdominal infections or anastomotic leakage (P > 0.05). Furthermore, during follow-up period there was no statistically significant difference observed between these two groups concerning overall survival rate and disease-free survival outcomes (P > 0.05). Conclusions: The management of surgical complications in CLS is exemplary, with NOSE presenting a sole advantage in terms of incision length albeit at the cost of prolonged operative time. Therefore, NOSE may be deemed appropriate for patients who place high emphasis on postoperative cosmetic outcomes.

Comparison of different time intervals between laparoscopic cholecystectomy to endoscopic retrograde cholangiopancreatography for patients with cholecystolithiasis complicated by choledocholithiasis.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) is a common strategy for treatment of patients with gallstones with co-existing stones in the common bile duct (CBD). We conducted this study to compare the effect of different time intervals between ERCP and LC. Methods: A total of 214 patients who underwent elective LC after ERCP for gallstones and CBD stones between January 2015 and May 2021 were retrospectively reviewed. We compared the hospital stay, operation time, perioperative morbidity, and conversion rate to open cholecystectomy, according to the interval between ERCP and ERCP and LC, namely, one day, 2-3 days, and 4 days or more. A generalized linear model was used to analyze the differences among the groups for outcomes. Results: There were a total of 214 patients with 52, 80, and 82 patients in group 1, group 2, and group 3 respectively. These groups did not differ significantly in terms of major complications or conversion to open surgery (p = 0.503 and p = 0.358, respectively). The generalized linear model showed that operation times in group 1 and group 2 were similar (odds ratio (OR) 0.144, 95% confidence interval (CI) 12.597, 8.511, p = 0.704), while operation time was significantly longer in group 3 than in group 1 (OR 4.005, 95% CI, 0.217, 20.837, p = 0.045). Post-cholecystectomy hospital stay was similar among the three groups, while post-ERCP hospital stay was significantly longer in group 3 compared with group 1. Conclusion: We recommend that LC be performed within three days after ERCP to reduce operating time and hospital stay.

Design, synthesis, and biological evaluation of 2,6,7-substituted pyrrolo[2,3-d]pyrimidines as cyclin dependent kinase inhibitor in pancreatic cancer cells.

Pancreatic cancer is a highly malignant tumor, and more effective treatment is urgently needed to lengthen the life of patients. In this paper a class of new 2,6,7-substituted pyrrolo[2,3-d]pyrimidine derivatives of CDK 4/6 inhibitor ribociclib (1) was designed and synthesized to investigate their effect on the proliferation of pancreatic cancer cells. The structure-activity relationship (SAR) of synthetic compounds was analyzed based on both their in vitro anti-proliferative activity and the CDK4 inhibitory activity. A series of 6-anilinocarbonyl-substituted pyrrolo[2,3-d]pyrimidine derivatives (25, 41-48) showed the significantly increased potency against two proliferating cancer cell lines (MIA PaCa-2 and BxPC-3) in MTT assay though their CDK4 inhibitory activity were lower in a varying range compared to 1. The most potent compound 41 was identified as a highly selective and potent CDK 4/6 inhibitor in the human kinases profiling assay, it also exhibited the favorable in vitro pharmacokinetic properties for further in vivo evaluation. Meanwhile, 41 exhibited the potential as a combination partner with mTOR inhibitor to treat pancreatic cancer. Alternatively, introducing of sulfonamide fragment into C2-substituent of pyrrolo[2,3-d]pyrimidine provided the clue for future optimization to afford new CDK9 inhibitors.

Design, synthesis, and evaluation of novel 4-amino-2-(4-benzylpiperazin-1-yl)methylbenzonitrile compounds as Zika inhibitors.

The prevalence of Zika virus (ZIKV) has become widespread in recent years. ZIKV infection is associated with severe congenital CNS malformations in both newborns and adults. However, neither vaccines nor therapeutics are available to control ZIKV infection until now. We started by hit screening our in-house small molecule library, then designed, synthesized, and evaluated a new class of 1, 4-bibenzylsubstituted piperazine derivatives for their cytopathic effect (CPE) protection effect in a ZIKV-infected Vero E6 cellular assay. A preliminary structure-activity relationship study identified five novel 4-amino-2-(4-benzylpiperazin-1-yl)methylbenzonitrile analogs with obvious CPE reduction effects against ZIKV at micromolar concentrations. Moreover, compound 3p exerted a significant antiviral effect on both Zika RNA replication and virus protein expression in a dose-dependent manner at low micromolar concentrations. This study demonstrated the potential of a novel 4-amino-2-(4-benzylpiperazin-1-yl)methylbenzonitrile scaffold for the development of anti-ZIKV candidates.

Tamoxifen promotes apoptosis and inhibits invasion in estrogen­positive breast cancer MCF­7 cells.

Tamoxifen (TAM) is the earliest non-steroidal antiestrogen drug, which has been widely used in endocrine therapy targeting breast cancer. The aim of the present study was to investigate the effect of TAM on the proliferation, apoptosis, migration and invasion of the estrogen­positive (ER+) breast cancer cell line MCF­7 in vitro, and elucidate its mechanisms. It was demonstrated that TAM suppressed proliferation, migration and invasion, and induced apoptosis in MCF­7 cells. Further investigation revealed that the mitochondrial membrane potential and the amount of ATP were significantly decreased following the treatment of MCF­7 cells with TAM. Mitochondria are an important source of reactive oxygen species (ROS) and they are also the target of ROS as well. In the present study, TAM promoted the formation of ROS in MCF­7 cells. In conclusion, these results reveal the underlying mechanism by which TAM induces ER+ breast cancer cell apoptosis and inhibits invasion, thereby supporting the use of TAM in breast cancer treatment.