Establishing peripheral PD-L1 as a prognostic marker in hepatocellular carcinoma patients: how long will it come true?

BACKGROUND: The prognostic role of intratumoral programmed cell death ligand 1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been investigated by several meta-analyses. However, the prognostic value of pretreatment peripheral PD-L1 (PPPD-L1) level in HCC remains undetermined. Thus, this systemic review aimed to establish PPPD-L1 as a new prognostic marker in HCC according to available evidence. METHODS: Case-control studies investigating the prognostic role of PPPD-L1 in HCC were systemically sought in the database of PubMed and Web of Science until March 25th, 2020. Our main concern is survival results, including overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The combined results were summarized in narrative form according to data extracted from each included study. RESULTS: Finally, nine studies published from 2011 to 2019, were incorporated into this systemic review. Among these, six studies evaluated the PD-L1 expression by enzyme-linked immunosorbent assay (ELISA) from blood serum, and three studies evaluated the PD-L1 expression by flow cytometric analysis from peripheral blood mononuclear cells (PBMC). According to the extracted evidence, high PPPD-L1 expression, measured in either blood serum or PBMC, is associated with poor OS, poor DFS, and poor PFS. Meanwhile, PPPD-L1 was also correlated with enlarged tumor size and more likely with advanced tumor stage as well as vascular invasion. CONCLUSION: High PPPD-L1 level is associated with increased mortality rate and increased recurrence rate in HCC. As a convenient serum marker, PPPD-L1 could be a promising marker of prognosis in HCC patients.

[miR-455 Inhibits HepG2 Cell Proliferation and Promotes Apoptosis by Targeting RhoC].

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor prognosis and high mortality. The aberrant expression or alteration of microRNAs (miRNAs) contributes to the development and progression of cancer. Studies have shown that miR-455 plays a regulatory role in the development of HCC. Therefore, in the present study, the role of miR-455 was analyzed in HepG2 cells proliferation and apoptosis using MTT and flow cytometry methods. Binding sites were predicted by bioinformatics and luciferase assay was used to verify the target relationship between miR-455 and RhoC-encoding gene RHOC. After that, the effects of miR-455 on RHOC and its product RhoC, were explored by qPCR and Western blotting. As PTEN is a key tumor suppressor gene in HCC, and Bcl-2 and Caspase 3 are important indication of apoptosis, expression levels of PTEN, Bcl2 and Caspase 3 proteins were determined in cells overexpressing RhoC. We show that miR-455 promotes HepG2 cells apoptosis and inhibits proliferation. Bioinformatics analysis and luciferase assay indicate that specific recognition sites for miR-455 are within the RhoC 3'-UTR. Luciferase activity was significantly lower in the cells co-transfected with miR-455 mimics and RhoC-WT (p < 0.01) as compared to that in control cells, pointing that RHOC gene is, indeed, targeted by miR-455. RHOC mRNA was significantly reduced after miR-455 transfection in HepG2 cells. In addition, we show that RhoC could activate the HCC cells proliferation ability and inhibit apoptosis rate (p < 0.01), and decrease expression of PTEN and Caspase 3 (p < 0.01), while upregulating levels of Bcl2. In conclusion, our study indicates that miR-455 plays a suppressive role in HCC development by targeting RhoC-encoding mRNA.

Preoperative plasma fibrinogen is associated with poor prognosis in esophageal carcinoma: a meta-analysis.

PURPOSE: The aim of this meta-analysis was to investigate preoperative plasma fibrinogen (PPF) as a prognostic marker in esophageal carcinoma (EC) by meta-analysis. METHODS: Relevant studies were sought in the databases including Pubmed, Web of Science, Cochrane library, and Wanfang databases up to Oct 10th, 2017. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were used as effective value, and pooled HRs were synthesized by STATA 14.0 to assess the prognostic impact of PPF on EC patients. RESULTS: A total of 8 studies with 2827 patients were collected in this meta-analysis. Our results revealed that high PPF was significantly associated with poor OS (HR = 1.90, 95% CI 1.56-2.33, P = 0.000; HR = 1.76, 95% CI 1.28-2.42, P = 0.000) and poor DFS (HR = 1.91, 95% CI 1.50-2.43, P = 0.000; HR = 1.51, 95% CI 1.16-1.97, P = 0.000) in EC patients from univariate and multivariate analysis results, respectively, which suggested that EC patients with high PPF will suffer from high postoperative mortality and recurrence rate. CONCLUSION: High PPF was significantly associated with poor OS and DFS in EC patients. Fibrinogen can serve as a prognostic marker and even a future targeting molecule during the treatment of EC patients.

Development of hepatolithiasis due to a celery stalk retained within the bile ducts of the liver.

INTRODUCTION: Commonly encountered foreign bodies are remnants from surgical procedures and ingested materials. Rarely, the latter cause stone formation in the biliary tract. CASE HISTORY: We describe a 51-year-old female who underwent choledoduodenostomy and who presented with abdominal distension caused by multiple stones in the bile ducts within the liver (hepatolithiasis) and an intact celery stalk. Hepatolithiasis was demonstrated by ultrasonography and computed tomography of the abdomen. The celery stalk was not confirmed until exploration of the biliary duct. CONCLUSIONS: Here, we describe, for the first time, an intact, undigested celery stalk in the biliary tract which induced hepatolithiasis. We believe that choledochojejunostomy favoured reflux of the celery stalk from the duodenum into the biliary tract.

The clinical efficacy of laparoscopy combined with choledochoscopy for cholelithiasis and choledocholithiasis.

OBJECTIVE: To compare and analyze the clinical efficacy of laparoscopy combined with choledochoscopy, and laparoscopy combined with duodenoscopy, for cholelithiasis and choledocholithiasis. PATIENTS AND METHODS: A total of 105 patients with cholelithiasis and choledocholithiasis from our hospital, from January 2014 to January 2015, were enrolled in this study. All patients weren given primary treatment. After obtaining consent from our hospital Ethics Committee and the patients, all 10529 cases were divided into two groups according to their time of admission. The observation group consisted of 59 cases and the control group consisted of 46 cases. The control group were treated by laparoscopy combined with duodenoscopy (cholecystectomy +ERCP+calculi extraction with an endoscope) and the observation group were treated by laparoscopy combined with choledochoscopy. We then compared the clinical efficacy between the two groups of patients. RESULTS: The success rate of the first surgery in the observation group, was higher than that in the control group. The time of surgery and intra-operative blood loss of the observation group were less than the control group. The differences had statistical significance p < 0.05). When compared the post-operative fasting and evacuation time, average hospital stay and hospitalization expenses for the observation group were less than those of the control group. The difference had statistical significance (p < 0.05). The prevalence of post-operative complications and recurrence rate in the observation group were statistically significantly (p < 0.05) less than the control group (p < 0.05). CONCLUSIONS: Laparoscopy combined with choledochoscopy was effective and safe for treating cholelithiasis and choledocholithiasis. Its treatment outcomes might be superior to laparoscopy combined with duodenoscopy.

The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury is a major cause of post-operative hepatic dysfunction and liver failure after transplantation. This review summarizes the mechanisms of ischemia-reperfusion injury and analyzes the protective strategies based on the recent developments in the field. Development of hepatic ischemia-reperfusion injury is associated with metabolic acidosis, calcium overloading, and changes of mitochondrial membrane permeability. Hypoxia-induced activation of Kupffer cells results in generation of reactive oxygen species (ROS). These processes lead to activation of inflammation and immune responses that involve multiple cells and signaling molecules and result in increased level of apoptosis and necrosis. Generation of ROS is one of the major risk factors in the hepatic ischemia-reperfusion injury. A number of methods aimed to reduce the oxidative stress have been investigated, and some of them have been applied clinically. The methods mainly rely on the activation of pro-survival genes and associated mechanisms capable of reducing the level of ROS and inflammation at pre-treatment and post-conditioning stages. Potential benefits of these clinical approaches have been discussed here.

The repair of critical-size defects with porous hydroxyapatite/polyamide nanocomposite: an experimental study in rabbit mandibles.

This study was conducted to evaluate the healing of critical-size surgical defects after implantation of porous nano-hydroxyapatite/polyamide composite (nHA/PA) blocks based on a bilateral mandible model using adult New Zealand white rabbits. 15 rabbits were divided randomly into three groups according to the observation period: 4, 12 and 24 weeks. The defects on one side were implanted with nHA/PA blocks and the contralateral defects were kept empty as blank controls. A combination of macroscopic, radiographic, histological and histomorphometric studies were performed up to 24 weeks postoperatively and compared with normal healing. Large amounts of callus and active osteoblasts were found in the pore structure after 4 weeks of implantation, and the defects were completely occupied by neo-bone with density comparable with that of host bone at 24 weeks. Significant difference was found between nHA/PA groups and blank controls regarding X-ray opacity over the whole period and bone parameters at 4 weeks postoperation (P<0.05). The porous nHA/PA composite promotes bone formation over the extension of the defect, particularly in the early stage. Porous nHA/PA offers interesting potential for maxillofacial reconstructive procedures in load-free areas.