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.

A New Mouse Model of Whole Pancreas Transplant With Graft Blood Through the Portal Vein.

OBJECTIVES: Pancreas transplant is currently the most effective method for maintaining physiological blood sugar levels and reversing small blood vessel injuries. Our team developed a model of whole pancreas transplant based on microsurgical techniques following the investigation of more than 300 mice. MATERIALS AND METHODS: A mouse pancreatic transplant model is required to investigate the pathophysiological process of pancreas transplant and pancreatic preservation technologies. Recently, the segment-neck pancreas transplant has been the most utilized mouse pancreatic transplant model. The innovative mouse pancreatic transplant modelthat we developed in this study uses the whole pancreas and returns heart blood flow into the liver via the portal vein. RESULTS: With our mouse pancreatic transplant model, the survivalrate of mice aftertransplant was >80%, and the success rate of pancreatic transplant was >90%. CONCLUSIONS: The segment-neck and the whole pancreas model can guarantee that the transplanted pancreas functions effectively, and both have excellent postoperative outcomes, survivalrates and pancreatic active rates.

Is percutaneous drainage better than endoscopic drainage in the management of patients with malignant obstructive jaundice? A meta-analysis of RCTs.

To compare the safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangial drainage (PTCD) in the treatment of malignant obstructive jaundice, a systematic review and meta-analysis of published studies was undertaken to assess the differences between the two procedures in terms of efficacy and safety. From November 2000 to November 2022, the Embase, PubMed, MEDLINE, and Cochrane databases were searched for randomized controlled trials (RCTs) on the treatment of malignant obstructive jaundice with ERCP or PTCD. Two investigators independently assessed the quality of the included studies and extracted the data. Six RCTs, including 407 patients, were included. The results of the meta-analysis showed that the overall technical success rate in the ERCP group was significantly lower than that in the PTCD group (Z=3.19, P=0.001, OR=0.31 (95% CI: 0.15-0.64)), but with a higher overall procedure-related complication incidence rate (Z=2.57, P=0.01, OR=0.55 (95% CI: 0.34-0.87)). The incidence of procedure-related pancreatitis in the ERCP group was higher than that in the PTCD group (Z=2.80, P=0.005, OR=5.29 (95% CI: 1.65-16.97)), and the differences were statistically significant. No significant difference was observed between the two groups when the clinical efficacy, postoperative cholangitis, and bleeding rate were compared.Both treatments for malignant obstructive jaundice were efficacious and safe. However, the PTCD group had a greater technique success rate and a lower incidence of postoperative pancreatitis.The present meta-analysis has been registered in PROSPERO.

Prognostic factors in hepatocellular carcinoma patients with Child-Pugh A liver function after hepatectomy: Not related to the surgical approach.

INTRODUCTION AND OBJECTIVES: Improving the prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is critical. This article aims to investigate the risk factors affecting the prognosis of HCC patients with Child-Pugh A (CPA) liver function after hepatectomy and to compare the prognosis of patients with anatomical resection (AR) and nonanatomical resection (NAR). METHODS: In total, 186 patients diagnosed with HCC between 2013 and 2019 were retrospectively enrolled. Univariate and multivariate analyses were performed using a Cox proportional hazard regression model to explore the factors related to prognosis. Overall survival (OS) and progression-free survival (PFS) were analyzed by log-rank tests and are shown by Kaplan-Meier curves. Chi-square tests and Mann-Whitney U tests were used to compare the difference in clinical characteristics between AR and NAR patients. RESULTS: Among the 186 enrolled patients, only 73 were followed over 60 months. The 1-, 3-, and 5-year survival rates were 74.5%, 46.7% and 26.0%, respectively. Multivariate analyses demonstrated that portal vein invasion (PVI) and tumor size were independent risk factors for OS and PFS. Preoperative hepatitis B surface antigen (HBsAg) and a-fetoprotein (AFP) levels were identified as independent risk factors only for PFS. In univariate analysis, the NAR group had a better OS rate than the AR group (1-year: 80.4% vs. 63.6%, 3-year: 55.9% vs. 30.3%, 5-year: 34.8% vs. 11.1%), but this was not confirmed by multivariate analysis. CONCLUSIONS: PVI and tumor size > 5 cm are risk factors for the prognosis of CPA HCC patients after hepatectomy, but the surgical type is not.

Development of a novel necroptosis-associated miRNA risk signature to evaluate the prognosis of colon cancer patients.

BACKGROUND: Necroptosis is a recently discovered caspase-independent form of cell death which plays an important role in the occurrence and development of cancer. As an important regulatory factor in necroptosis, microRNAs (miRNAs) are important for the development of colon cancer. This study established a novel necroptosis-related miRNA risk signature to evaluate the prognosis of patients with colon adenocarcinoma (COAD). METHODS: The necroptosis-related miRNAs were selected by assessing the differential expression of miRNAs in 459 COAD patient samples and 8 control samples from The Cancer Genome Atlas (TCGA). Selection operator Cox analyses and survival analyses were used to establish the risk signature of 7 miRNAs related to necroptosis. Functional enrichment analysis and nomograms were used to explore the potential effects of necroptosis-related miRNAs on prognosis and metastasis. The target genes of the necroptosis-related miRNAs were predicted using online databases and the genes related to overall survival (OS) were screened. RESULTS: The risk signature was based on 7 necroptosis-related miRNAs. Nomograms showed that the risk signature was effective at predicting the prognosis and TNM stage of COAD patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that these miRNAs play an important role in cancer development, metastasis, and prognosis. A total of 38 target genes for these miRNAs were found to be associated with the OS in COAD patients. CONCLUSIONS: This study provided novel evidence that necroptosis-related miRNAs are associated with the prognosis of COAD patients. A risk signature established based on these miRNAs could effectively predict the prognosis and metastasis of COAD in patients.

Laparoscopic Liver Resection Ameliorates the Postoperative Liver Function Impairment for Hepatocellular Carcinoma Patients.

To study whether laparoscopic liver resection (LLR) is able to alleviate the postoperative liver function impairment for hepatocellular carcinoma patients, the clinical data of 103 patients were retrospectively analyzed, including 42 patients who underwent LLR and 61 patients who underwent open liver resection (OLR), during the period spanning from 2012 to 2017. The postoperative peak aspartate aminotransferase and alanine aminotransferase levels in the LLR group were significantly lower than those of the OLR group (209.76±189.516 vs. 262.55±181.19, P=0.046; 250.56±200.944 vs. 411.01±412.51, P=0.005, for aspartate aminotransferase and alanine aminotransferase, respectively). The recovering of postoperative total protein and albumin in the LLR group was faster than that in the OLR group, and the total protein and albumin levels on the postoperative day-5 were significantly higher in the LLR group than in the OLR group (62.528±9.427 vs. 57.87±6.101, P=0.019; 36.456±4.875 vs. 33.653±4.112, P=0.012, respectively). In conclusion, these data show that LLR alleviates postoperative liver function impairment and increases liver function recovery.

A series of terpyridine containing flexible amino diethylacetate derivatives with large two-photon action cross-sections for effective mitochondrial imaging in living liver cancerous cells.

Small molecules possess large two-photon action cross sections (Φσ) are highly demanded for biological purpose. Herein, three novel terpyridine containing flexible amino diethylacetate organic small molecules (A1, A2 and A3) were rationally designed and their photophysical properties were investigated both experimentally and theoretically. The results revealed that the three chromophores possess large Φσ and remarkable Stokes' shift in high polar solvents, which are particularly benefit for further biological imaging application. One chromophore (A1) displayed an effective intracellular uptake against lung cancerous living cells A549. Colocalization studies suggested the internalized subcellular compartment was mitochondria. Consequently, chromophore A1 provides a promising platform to directly monitor mitochondria in living cells under two-photon confocal laser scanning microscopy.

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.

Biliary epithelial cells proliferate during oxygenated ex situ liver culture.

Biliary complications remain a major source of morbidity in liver transplant patients. Among these complications, nonanastomotic biliary strictures (NAS) are especially common and they are frequently therapy resistant in part because biliary epithelial cells are more sensitive to warm ischemic injury than hepatocytes. It has been a challenge to maintain the physiological function of biliary epithelial cells during liver transplantation. In this work, we have examined the effect of oxygen on proliferation of biliary epithelial cells in the rat livers obtained from donation after circulatory death (DCD). Twelve rat livers from DCD were divided into two groups. Livers in the control group were isolated following a standard procedure without oxygen supply. Livers in the experimental group were isolated with a constant supply of oxygen. All livers were then connected to an ex situ liver culture system in the presence of bromodeoxyuridine (BrdU), a thymidine analogue and a marker for cell proliferation. After 6 hours of normothermic ex situ liver culture, morphology and DNA replication in hepatocytes and biliary epithelial cells were assessed and compared between the two groups. We found that about 4.5% of the biliary epithelial cells in the experimental group proliferated compared with only 0.4% of cells in the control based on BrdU staining. No significant change in cell morphology was observed in those cells between the two groups. Thus, our results indicate that oxygen supply is required for maintenance of the physiological function of biliary epithelial cells during liver transplant and suggest that a constant oxygen supply during liver isolation along with ex situ liver organ culture can enhance the repair of biliary epithelial cell injury during liver transplantation.

Growing a whole porcine liver organ ex situ for six hours without red blood cells or hemoglobin.

UNLABELLED: Liver transplantation is an effective approach to end-stage liver disease. Shortage of donor liver and increased waiting time for liver transplantation necessitate the development of an organ culture system by which livers can be cultured and maintained ex situ for a prolonged period of time. The aim of this work is to test whether cell culture condition in vitro could be used to culture whole livers ex situ without the use of erythrocytes. Twelve castrated male land race/farm young porcine livers were exposed to 30 min warm ischemia and 30 min cold perfusion. Livers were isolated and connected to an Ex situ liver culture system using a standard culture medium RPMI1640 supplied with 10% of fetal bovine serum and sufficient dissolved oxygen under a normothermic condition for 6 hours. Metabolic biomarkers, bile and urea production, hepatic cell viability and histology analysis of biopsies were examined and newly proliferated hepatic cells labeled by BrdU were analyzed after 6 hours ex situ culture. The results from biochemical assays and histology analysis indicate that livers after the organ culture still maintain the full function. CONCLUSIONS: Our data demonstrate that the liver culture system established in this work can be used to culture whole livers ex situ in the absence of erythrocytes.

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.

Synthesis and evaluation of 2,4-disubstituted quinazoline derivatives with potent anti-angiogenesis activities.

A series of 2,4-disubstituted quinazoline derivatives were designed and synthesized. The biological results showed that most of quinazoline derivatives exhibited potent antiproliferative activities against a panel of three tumor cell lines and a good inhibitory effect against the adhesion and migration of human umbilical vein endothelial cells (HUVECs). Among these compounds, 11d was the most potent agent, that also exhibited the highest anti-angiogenesis activities in the chick embryo chorioallantoic membrane (CAM) assay.

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.