Total laparoscopic partial hepatectomy versus open partial hepatectomy for primary left-sided hepatolithiasis: study protocol for a randomized controlled trial.

BACKGROUND: The advantages of laparoscopic left-sided hepatectomy (LLH) for treating hepatolithiasis in terms of the time to postoperative length of hospital stay (LOS), morbidity, long-term abdominal wall hernias, hospital costs, residual stone rate, and recurrence of calculus have not been confirmed by a randomized controlled trial. The aim of this trial is to compare the safety and effectiveness of LLH with open left-sided hepatectomy (OLH) for the treatment of hepatolithiasis. METHODS: Patients with hepatolithiasis eligible for left-sided hepatectomy will be recruited. The experimental design will produce two randomized arms (laparoscopic and open hepatectomy) at a 1:1 ratio and a prospective registry. All patients will undergo surgery in the setting of an enhanced recovery after surgery (ERAS) programme. The prospective registry will be based on patients who cannot be randomized because of the explicit treatment preference of the patient or surgeon or because of ineligibility (not meeting the inclusion and exclusion criteria) for randomization in this trial. The primary outcome is the LOS. The secondary outcomes are percentage readmission, morbidity, mortality, hospital costs, long-term incidence of incisional hernias, residual stone rate, and recurrence of calculus. It will be assumed that, in patients undergoing LLH, the length of hospital stay will be reduced by 1 day. A sample size of 86 patients in each randomization arm has been calculated as sufficient to detect a 1-day reduction in LOS [90% power and α = 0.05 (two-tailed)]. The trial is a randomized controlled trial that will provide evidence for the merits of laparoscopic surgery in patients undergoing liver resection within an ERAS programme. CONCLUSIONS: Although the outcomes of LLH have been proven to be comparable to those of OLH in retrospective studies, the use of LLH remains restricted, partly due to the lack of short- and long-term informative RCTs pertaining to patients with hepatolithiasis in ERAS programmes. To evaluate the surgical and long-term outcomes of LLH, we will perform a prospective RCT to compare LLH with OLH for hepatolithiasis within an ERAS programme. TRIAL REGISTRATION: ClinicalTrials.gov NCT03958825. Registered on 21 May 2019.

Intratumoral and peritumoral expression of CD68 and CD206 in hepatocellular carcinoma and their prognostic value.

The aims of the present study were to determine whether the changes in density and location of CD68-positive and CD206-positive macrophages contribute to progression of hepatocellular carcinoma (HCC) and to evaluate prognostic values of these cells in post-surgical patients. A retrospective study involving 268 HCC patients was conducted. CD68-positive and CD206-positive macrophage infiltration in HCC tissues and adjacent tissues was examined by immunohistochemistry (IHC) and the relationship between the clinicopathological features and prognosis was analyzed. Receiver operating characteristics (ROC) curve was used to calculate diagnostic accuracy. There was an increase in CD68-positive and CD206-positive macrophage infiltration in adjacent tumor tissues compared with tumor tissues. ROC curve identified their optimal diagnostic cut-off values. The survival analysis showed that increased CD68 expression in adjacent tissues conferred superior overall survival (OS) and disease-free survival (DFS), while increase of CD206 in tumor yielded inferior OS and DFS. Cox regression analysis suggested both CD68-positive macrophages in adjacent area and intratumor CD206-positive macrophages as independent prognostic biomarkers for post-surgical HCC patients. Finally, a combination of CD68/CD206 and HBV-positive further improved prognostic stratification, especially in DFS. These results provide the first evidence for region- and subset-dependent involvement of CD68 and CD206 cells in HCC progression. A combination of CD68/CD206 density and HBV-positivity improves further predictive value for post-operative recurrence of HCC. Quantification of CD68/CD206 macrophages and their distribution can be exploited for better postsurgical management of HCC patients. These findings provide a basis for developing novel treatment strategies aimed at re-educating macrophages in tumor microenvironment.

A facile ultrasonication assisted method for Fe3O4@SiO2-Ag nanospheres with excellent antibacterial activity.

To increase the monodispersity of magnetic hybrid nanocomposites, a novel ultrasonic method was introduced to synthesize uniform Fe3O4@SiO2-Ag nanospheres. The immobilized Ag nanocrystals were tunable by varying the experimental conditions. An antibacterial assay indicated that the Fe3O4@SiO2-Ag nanospheres exhibited excellent antibacterial activities against Staphylococcus aureus and Escherichia coli, in which the minimum inhibition concentrations (MIC) were 40 µg mL(-1) and 20 µg mL(-1), respectively. The live/dead bacterial cell fluorescence stain assay agreed well with the antibacterial assay. The CCK-8 results indicated these nanospheres were bio-compatible for human normal cells and presented relative cytotoxicity against HepG2 tumor cells. These nanospheres could be easily uptaken by the cells and they could affect bacterial cells both inside and outside the cell membrane, which enable them to be promisingly applied in future biomedical areas.

Talin1, a valuable marker for diagnosis and prognostic assessment of human hepatocelluar carcinomas.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in the human population. Despite its significance, there is only limited understanding of pathological mechanisms and therapeutic options. Talin1, a focal adhesion complex protein that is required for cell adhesion and motility, regulates integrin interactions with extracellular matrix (ECM). In the present study, we aimed to study the possible role of Talin1 in diagnosis and prognosis of HCC. METHODS: Expression of Talin1 protein was detected in normal liver tissues (n=10), HCC tissues (n=32) and adjacent non-cancerous tissues (n=32) by immunohistochemistry and real time PCR. RESULTS: While Talin1 was observed in all tissues, the protein and mRNA expression of Talin1 in HCC tissues was significantly lower than that in the adjacent non-cancerous tissues and normal liver tissues(P<0.05). In addition, the expression of Talin1 in HCCs was significantly correlated with pathological differentiation, integrity of the tumor capsule, portal vein tumor thrombus and tumor size (P<0.05). CONCLUSIONS: Talin1 is possibly involved in the process of the carcinogenesis, infiltration and metastasis of HCC and has potential as a marker for diagnosis and prognostic assessment.

Promoter methylation and mRNA expression of DKK-3 and WIF-1 in hepatocellular carcinoma.

AIM: To investigate the promoter methylation status and mRNA expression of DKK-3 and WIF-1 gene in hepatocellular carcinoma (HCC). METHODS: DKK-3 and WIF-1 acted as Wnt-antagonists and tumor suppressors, but hypermethylation of the gene promoter and low mRNA expression activated Wnt signaling aberrantly and induced the development of HCC. Methylation status of the DKK-3 and WIF-1 gene promoter was investigated using methylation specific polymerase chain reaction (PCR) in tumor and adjacent non-cancerous tissues from 33 HCC patients and 20 normal liver tissues served as control. The expression of DKK-3 and WIF-1 mRNA was also determined by real-time quantitative reverse transcriptase PCR. The relationship between methylation, mRNA expression, and clinical data, as well as methylation and mRNA expression of the two genes were analyzed. RESULTS: The methylation of DKK-3 and WIF-1 genes in HCC increased significantly compared with adjacent non-cancerous tissues and normal control tissues (chi(2) =7.79, P < 0.05; chi(2) = 4.89, P < 0.05), and no significant difference in methylation between adjacent non-cancerous tissues and normal control tissues was observed. In HCC tissues, significant differences in the DKK-3 promoter methylation were observed in age and cirrhosis, and significant differences of the WIF-1 promoter methylation were observed in HBsAg and cirrhosis. The average expression of DKK-3 mRNA in HCC and adjacent non-cancerous tissues was increased significantly compared with normal control tissues. The average expression of WIF-1 mRNA showed no significant difference among the three tissues. The mRNA expression of DKK-3 gene in HCC was decreased as the pathological grade increased. CONCLUSION: The aberrant promoter methylation and decreased expression of DKK-3 and WIF-1 may be an important mechanism in HCC, and may be a far-reaching significance in early diagnosis and therapy of HCC.

[Clinicopathological significance of aberrant methylation of the fragile histidine triad gene in patients with hepatocellular carcinoma].

OBJECTIVE: To investigate the aberrant methylation of fragile histidine triad (FHIT) gene and to explore possible relationship between the aberrant methylation of FHIT and clinicopathological features in hepatocellular carcinoma (HCC). METHODS: The hypermethylation of FHIT was detected by the methylation specific PCR (MSP) method in 45 patients with HCC (tumoral and nontumoral tissue), 14 cases of normal livers and 4 HCC cell lines (SK-Hep-1, Hep-G2, Hep-3B and Huh7). The correlation of FHIT methylation and clinicopathological features was analyzed. RESULTS: The frequencies of hypermethylation of FHIT in tumoral and nontumoral tissue, normal liver and cell lines were 71.1%, 64.4%, 14.3% and 75.0%, respectively. A significant relation between hypermethylation of FHIT and poor survival was present (P = 0.0430). CONCLUSIONS: Hypermethylation of FHIT is a frequent and early event in HCC, it might relate to a poor prognosis for patients with HCC.

[Stability of patient bile and study on its influential factors].

The patient bile and its centrifugate were studied by FTIR spectra, UV-Vis spectra, particle size analysis, and zeta potential determination. The result showed that the patient bile was in a heterogenetic and unstable state, and some of the ultramicrons in the patient bile assembled to form precipitate after centrifugalized at different speeds. According to FTIR and UV-Vis spectra, the authors found that the composition of the precipitates was mainly cholesterol, bilirubin, calcium bilirubinate, protein, phospholipid and so on, which was much close to that of the core of patient gallstone. The change in the properties of cholesterol/phospholipid vesicles, and the production of the undissolvable calcium salt in the patient bile had crucial influence on the stability of the patient bile, which played important roles in the core-formation and initial growth of gallstone that were induced by the matrixes such as proteins, phospholipids etc.