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We demonstrated that postoperative mesenchymal circulating tumor cell (mCTC) in peripheral blood were independent risk factors for the recurrence of hepatocellular carcinoma (HCC) after radical resection. However, few studies have been conducted on the efficacy and survival benefit of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) for patients with mCTC-positive HCC. We evaluated the effect of PA-TACE on the prognosis of mCTC-positive/mCTC-negative HCC patients. A total of 261 HCC patients from February 2014 to December 2017 undergoing curative hepatectomy were included in this study. Recurrence-free survival (RFS) rates, overall survival (OS) rates, and prognostic factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazard model. The results showed that 57.8% (59/102) mCTC-positive and 43.4% (69/159) mCTC-negative patients underwent PA-TACE. Multivariate analyses demonstrated that PVTT (HR 2.370; 95% CI, 1.535–3.660; P

BACKGROUND/AIMS: Autophagy plays a positive role in the prevention of liver damage after hepatic ischemia-reperfusion injury (HIRI); however, the molecular mechanism is still a mystery. Understanding the molecular events behind this injury may have important implications for devising proper strategies for managing liver injury. This study investigated the effects of Frizzled-2 expression on autophagy as well as Ca(2+) concentration and apoptosis in BRL-3A cells. MATERIALS AND METHODS: BRL-3A cells exposed to the hypoxia/reoxygenation (H/R) condition were used as an in vitro HIRI hepatic cell model. The transfection of Frizzled-2 small interfering RNA (siRNA) or expression vector was performed to silence or overexpress Frizzled-2 in BRL-3A cells. The intracellular Ca(2+) concentration was monitored by the fluorescence of Ca(+). Western blot was used to detect autophagy-related proteins and apoptotic marker Caspase-3. The cellular autophagosome was observed by a transmission electron microscope. RESULTS: Beclin-1 and Atg7 expressions were considerably induced by H/R treatment, and this induction was attenuated by Frizzled-2 siRNA in BRL-3A cells. The LC3B-II/I ratio was inhibited by H/R treatment, although it was considerably induced by Frizzled-2 siRNA. The overexpression of Frizzled-2 induced intracellular Ca(2+) concentration and expressed autophagy-related proteins and Caspase-3 except for the suppression of LC3B-II/I ratio in BRL-3A cells in the normoxia condition. CONCLUSION: The overexpression of Frizzled-2 mimicked H/R treatment and suppressed autophagy activity, whereas Frizzled-2 siRNA induced cellular autophagy and attenuated the H/R-induced hepatic injury in BRL-3A cells. These developments suggest that Frizzled-2 siRNA protects hepatic BRL-3A cells from the injury of H/R via autophagy modulation.

Frizzled-2 plays an important role in maintaining normal hepatic cell functionality. This study aimed to investigate the role of inhibition of Frizzled-2 in protecting rat liver BRL-3A cells from Hypoxia/Reoxygenation (H/R). In vitro H/R hepatic cell model was established by culturing BRL-3A cells under H/R condition. Frizzled-2 siRNA was transfected into BRL-3A cells to inhibit Frizzled-2 signaling. Wnt5a and Frizzled-2 were significantly increased in BRL-3A cells upon H/R treatment. H/R treatment induced cell cytotoxicity, the early apoptosis rate and the intracellular Ca2+ level in BRL-3A cells while silencing frizzled-2 gene decreased the H/R induced cell cytotoxicity, apoptosis and intracellular Ca2+ level. In vivo mice study further showed the up-regulation of Frizzled-2/Wnt 5 pathway and cleaved Caspase-3 expression in liver tissues under ischemia and reperfusion injury (IRI). In summary, inhibition of Frizzled-2 by its siRNA may protects BRL-3A cells by attenuating the H/R induced cell cytotoxicity and apoptosis.

Background Circulating tumour cells (CTCs), especially mesenchymal CTCs, are important determinants of metastasis, which leads to most recurrence and mortality in hepatocellular carcinoma (HCC). However, little is known about the underlying mechanisms of CTC colonisation in pre-metastatic niches. Methods Detection and classification of CTCs in patients were performed using the CanPatrol™ system. A lentiviral vector expressing Prrx1-targeting shRNA was constructed to generate a stable HCC cell line with low expression of Prrx1. The effect of Prrx1 knockdown on stemness, migration, and drug resistance of the cell line was assessed, including involvement of SDF-1/CXCR4 signalling. Promising clinical applications of an inhibitor of STAT3 tyrosine phosphorylation, C188–9, and specific blockade with CXCR4 antibody were explored. Results The number of mesenchymal CTCs in blood was closely associated with tumour recurrence or metastasis. Pre-metastatic niche-derived SDF-1 could downregulate Prrx1, which induced the stemness, drug resistance, and increased expression of CXCR4 in HCC cells through the STAT3 pathway in vitro. In vivo, mice bearing tumours of Prrx1 low-expressing cells had significantly shorter survival. In xenograft tumours and clinical samples, loss of Prrx1 was negatively correlated with increased expression of CXCR4 in lung metastatic sites compared with that in the primary foci. Conclusions These findings demonstrate that decreased expression of Prrx1 stimulates SDF-1/CXCR4 signalling and contributes to organ colonisation with blood CTCs in HCC. STAT3 inhibition and specific blockade of CXCR4 have clinical potential as therapeutics for eliminating organ metastasis in advanced HCC.

Metastasis is a complex process that requires the interaction between tumor cells and their microenvironment. As an important regulator of intestinal microenvironment, gut microbiota plays a significant role in the initiation and progression of colorectal cancer (CRC), but the underlying mechanisms remain elusive. In this study, a metastasis-related secretory protein cathepsin K (CTSK) was identified as a vital mediator between the imbalance of intestinal microbiota and CRC metastasis. We implanted MC38 cells into the cecal mesentry of antibiotic-treated mice with intragastrically administration of E. coli to mimic gut microbiota imbalance. The bigger primary tumors and more liver metastatic foci were detected in the E. coli group accompanied with high LPS secretion and CTSK overexpression compared with that in the control group. CTSK contributes to the aggressive phenotype of CRC cells both in vitro and in vivo. Silencing CTSK or administration of Odanacatib, a CTSK-specific inhibitor, totally abolished the CTSK-enhanced migration and motility of CRC cells. Interestingly, the tumor-secreted CTSK could bind to toll-like receptor 4 (TLR4) to stimulate the M2 polarization of tumor-associated macrophages (TAMs) via an mTOR-dependent pathway. Recombinant CTSK could neither stimulate CRC growth and metastasis, nor induce M2 macrophage polarization in TRL4(−/−) mice. Meanwhile, CTSK could stimulate the secretion of cytokines by M2 TAMs including IL10 and IL17, which, in turn, promote the invasion and metastasis of CRC cells through NFκB pathway. Clinically, overexpression of CTSK in human CRC tissues is always accompanied with high M2 TAMs in the stroma, and correlated with CRC metastasis and poor prognosis. Our current research identified CTSK as a mediator between the imbalance of gut microbiota and CRC metastasis. More importantly, we illustrated a CTSK-mediated-positive feedback loop between CRC cells and TAMs during metastasis, prompting CTSK as a novel predictive biomarker and feasible therapeutic target for CRC.

A growing body of research indicates that the monitoring of circulating tumor cells (CTCs) may have great significance to the diagnosis of malignant tumors, assessment of condition, selection of treatment methods, and evaluation of prognosis and has a broad range of potential applications. However, the value of CTCs with different phenotypes in the diagnosis of hepatocellular carcinoma (HCC) and assessment of patient condition remains unclear. We collected 5 ml of peripheral blood from 176 patients who were found to have space-occupying lesions in the liver via B-ultrasound diagnosis at Zhujiang Hospital affiliated with Southern Medical University between August 2015 and October 2017 and used CanPatrol™ CTCs assay technology to isolate and count CTCs with different phenotypes in the patients’ peripheral blood. This allowed analysis of the value of CTCs with different phenotypes in the diagnosis of HCC and assessment of BCLC stage. We used CanPatrol™ CTCs assay technology to isolate different types of CTCs: epithelial CTCs (only stained for epithelial markers), mesenchymal CTCs (only stained for mesenchymal markers), mixed CTCs (stained for epithelial markers and mesenchymal markers), and total CTCs (all of the foregoing CTC phenotypes). Of 176 observed patients, 6 patients were finally diagnosed as other malignant tumor liver metastasis, 113 were diagnosed as having hepatocellular carcinoma, and 57 were diagnosed as having nonmalignant liver diseases. Furthermore, we intend to evaluate the diagnostic value of different phenotype CTCs count in discrimination between hepatocellular carcinoma and nonmalignant liver diseases. We found that CTCs of all types were significantly more numerous in the peripheral blood of the HCC group patients than in the NLD group patients (P

Aim: Circulating tumor cells (CTC) are a precursor to metastasis in several types of cancer and are occasionally found in the bloodstream in association with immune cells, such as white blood cells (WBCs). CTC-associated WBC (CTC-WBC) clusters can promote CTC appreciation and metastasis, suggesting that patients with CTC-WBC clusters found in the peripheral blood may have a worse prognosis. However, it is unclear whether CTC-WBC clusters are present in the peripheral blood of patients with hepatocellular carcinoma (HCC) and suggest a poor prognosis for HCC.Methods: We collected peripheral blood from 214 patients with HCC from January 2014 to December 2016. CanPatrol™ CTC analysis technology was used to isolate and count CTCs and CTC-WBC clusters in the patients' peripheral blood. Chi-squared analysis was used to calculate the correlation between the CTC-WBC clusters and clinicopathological characteristics. Kaplan–Meier survival analysis and Cox regression analysis were used to assess patient prognosis.Results: We used CanPatrol™ CTC analysis technology to count different types of CTCs and CTC-WBC clusters. The results showed that CTC-WBC clusters and tumor size (P = 0.001), tumor number (P = 0.005), portal vein tumor thrombus (P = 0.026), BCLC stage (P < 0.001), AFP level (P = 0.002), and total number of CTCs (P < 0.001) were statistically related. Cox regression analysis revealed that CTC-WBC clusters are an independent prognostic indicator of DFS (HR = 1.951, 95%CI:1.348–2.824, P < 0.001) and OS (HR = 3.026, 95%CI:1.906–4.802, P < 0.001) in HCC patients. Using Kaplan–Meier analysis, we found that positive CTC-WBC cluster patients had significantly shorter DFS and OS than patients with negative CTC-WBC (P < 0.001 and P < 0.001, respectively).Conclusions: CTC-WBC clusters in the peripheral blood are an independent predictor of DFS and OS, and their presence indicates poor prognosis in patients with HCC.

Background. Liver allograft preservation frequently involves static cold storage (CS) and machine perfusion (MP). With its increasing popularity, we investigated whether MP was superior to CS in terms of beneficial outcomes. Methods. Human studies and large animal studies that optimized livers for transplantation using MP versus CS were assessed (PubMed/Medline/EMBASE). Meta-analyses were conducted for comparisons. Study quality was assessed according to the Newcastle-Ottawa quality assessment scale and SYRCLE’s risk of bias tool. Results. Nineteen studies were included. Among the large animal studies, lower levels of lactate dehydrogenase (SMD -3.16, 95% CI -5.14 to -1.18), alanine transferase (SMD -2.46, 95% CI -4.03 to -0.90), and hyaluronic acid (SMD -2.48, 95% CI -4.21 to -0.74) were observed in SNMP-preserved compared to CS-preserved livers. NMP-preserved livers showing lower level of hyaluronic acid (SMD -3.97, 95% CI -5.46 to -2.47) compared to CS-preserved livers. Biliary complications (RR 0.45, 95% CI 0.28 to 0.73) and early graft dysfunction (RR 0.56, 95% CI 0.34 to 0.92) also significantly reduced with HMP preservation in human studies. No evidence of publication bias was found. Conclusions. MP preservation could improve short-term outcomes after transplantation compared to CS preservation. Additional randomized controlled trials (RCTs) are needed to develop clinical applications of MP preservation.

Background Circulating tumor cells (CTCs) have been actively studied for their functions in hepatocellular carcinoma (HCC) recurrence. However, the relationship between circulating tumor cells subtypes and hepatocellular carcinoma recurrence is still unclear. Methods CTCs were collected from the peripheral blood of 62 postoperative HCC patients. The CTCs were isolated with a filtration-based method. Multiplex fluorescence in situ hybridization was used to characterize the CTCs based on mRNA expression levels of epithelial and mesenchymal markers. Results Of the 62 HCC patients, 26 were diagnosed with early recurrence (ER) and 36 did not experience recurrence. Comparison between the recurrence group and the non-recurrence group showed the total number of CTCs, mesenchymal CTCs, and mixed CTCs in the recurrence group was significantly higher than in the non-recurrence group. Receiver operator characteristic (ROC) curve analysis was performed to define the positive cutoff values as follows: total number of CTCs ≥ 4, mesenchymal CTCs ≥ 1, and mixed CTCs ≥ 3. Analysis showed that portal vein tumor thrombus (hazard ratio [HR] = 2.905, P = 0.023) and mesenchymal CTC positivity (HR = 3.453, P = 0.007) were independent risk factors for ER. The correlation between the presence of mesenchymal CTCs and time to recurrence was further examined, and the results showed significantly shortened postoperative disease-free survival in patients positive for mesenchymal CTCs (P

AIM To establish a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure having an appropriate treatment window. METHODS Sixteen cynomolgus monkeys were randomly divided into four groups (A, B, C and D) after intracranial pressure (ICP) sensor implantation. D-galactosamine at 0.3, 0.25, 0.20 + 0.05 (24 h interval), and 0.20 g/kg body weight, respectively, was injected via the small saphenous vein. Vital signs, ICP, biochemical indices, and inflammatory factors were recorded at 0, 12, 24, 36, 48, 72, 96, and 120 h after D-galactosamine administration. Progression of clinical manifestations, survival times, and results of H&E staining, TUNEL, and Masson staining were recorded. RESULTS Cynomolgus monkeys developed different degrees of debilitation, loss of appetite, and jaundice after D-galactosamine administration. Survival times of groups A, B, and C were 56 ± 8.7 h, 95 ± 5.5 h, and 99 ± 2.2 h, respectively, and in group D all monkeys survived the 144-h observation period except for one, which died at 136 h. Blood levels of ALT, AST, CK, LDH, TBiL, Cr, BUN, and ammonia, prothrombin time, ICP, endotoxin, and inflammatory markers [(tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6)] significantly increased compared with baseline values in different groups (P < 0.05). Pathological results showed obvious liver cell necrosis that was positively correlated with the dose of D-galactosamine. CONCLUSION We successfully established a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure, and the single or divided dosage of 0.25 g/kg is optimal for creating this model.

// Peng Zhang 1, * , Peihua Cao 1, * , Xiaofeng Zhu 2 , Mingxin Pan 1 , Kebo Zhong 1 , Rui He 2 , Yang Li 1, 3 , Xingyuan Jiao 2 , Yi Gao 1, 3, 4 1 Department of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong, P. R. China 2 Organ Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P. R. China 3 Guangdong Provincial Research Center of Artificial Organ and Tissue Engineering, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong, P. R. China 4 State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, Guangdong, P. R. China * These authors contributed equally to this work Correspondence to: Yi Gao, email: gaoyi6146@163.com Xingyuan Jiao, email: jiaoxingyuan@hotmail.com Keywords: HOXA-AS2, LncRNA, GBC, metastasis, EMT Received: January 19, 2017 Accepted: March 09, 2017 Published: March 25, 2017 ABSTRACT Gallbladder carcinoma (GBC) is the most common malignancy of the bile duct and patients with GBC have extremely poor prognoses. Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, including cell growth, differentiation, apoptosis, and cancer progression. However, the function of lncRNAs in the progression of GBC remains largely unknown. Here, we reported that HOXA cluster antisense RNA2 (HOXA-AS2) was upregulated in GBC. In vitro experiments revealed that HOXA-AS2 knockdown significantly inhibited GBC cells proliferation by causing G1 arrest and promoting apoptosis, whereas HOXA-AS2 overexpression promoted cell growth. Further functional assays indicated that HOXA-AS2 overexpression significantly promoted GBC cell migration and invasion by promoting EMT. Taken together, our study demonstrates that HOXA-AS2 could act as a functional oncogene in GBC, as well as a potential therapeutic target to inhibit GBC metastasis.

Spheroid culture is a widely used three-dimensional culture technology that simulates the three-dimensional structure of tumors in vivo and has been considered a good model for tumor research. However, current commercialized spheroid culture tools have the shortcomings of high cost or relatively poor spheroid-forming results for some special cells. To solve such problems, we designed a 3D printed, reusable, stamp-like resin mold that could shape microstructures for spheroid culture of tumor cells on the surface of agarose substrate in a 96-well plate. We applied this homemade three-dimensional culture tool in spheroid formation for hepatocellular carcinoma cells. The experimental data show that the effect of spheroid culture on four hepatocellular carcinoma cell lines in our homemade spheroid culture plate is better than that of the commercialized ultralow attachment spheroid culture plate, and compared to two-dimensional culture, three-dimensional culture improves cell functions. In addition, the drug-sensitive test based on patient-derived hepatocellular carcinoma cells showed a different pattern between spheroid and two-dimensional cultures. In conclusion, our spheroid culture tool is characterized by its low cost, reusability, low cell consumption, convenience in medium exchange, and good effect of spheroid formation, suggesting that this technique could be widely used in individual treatment and high-throughput drug screening.

Background and Objectives. The feasibility and safety of single-port laparoscopic surgery for left lateral liver lobectomy are largely unknown. This study is aimed at comparing the effectiveness and safety between single-port laparoscopic (SPL) and conventional multiport laparoscopic (CL) surgeries for hepatic left lateral sectionectomy. Methods. A total of 65 patients receiving laparoscopic hepatic left lateral sectionectomy between January 2008 and July 2015 were included and divided into the SPL group (n=40) and the CL group (n=25). Results. There was no significant difference in the operative time, estimated intraoperative blood loss, length of hospital stay, and incidences of postoperative complications (biliary leakage, hemorrhage, and contusion at incision) between groups (all P>0.05). However, the SPL group had a significantly lower VAS pain score (at 24 h but not 7 days postoperation) and higher cosmetic satisfaction scores (at both 2 months and 6 months postoperation) than the CL group (all P<0.01). Moreover, multivariate linear regression analysis further confirmed the superior pain score and cosmetic outcome in the SPL group. Conclusions. Single-port laparoscopic hepatic left lateral sectionectomy is a safe and feasible treatment for patients with lesions in the left hepatic lobe. Patients with benign lesions in the left hepatic lobe are more suitable to receive single-port laparoscopic hepatic left lateral sectionectomy than those with malignancies.

Background As novel biomarkers for various cancers, microRNAs negatively regulate genes expression via promoting mRNA degradation and suppressing mRNA translation. miR-589 has been reported to be deregulated in several human cancer types. However, its biological role has not been functionally characterized in gastric cancer. Here, we aim to investigate the biological effect of miR-589 on gastric cancer and to reveal the possible mechanism. Methods Real-time PCR was performed to evaluate the expression of miR-589 in 34 paired normal and stomach tumor specimens, as well as gastric cell lines. Functional assays, such as wound healing, transwell assays and in vivo assays, were used to detect the biological effect of miR-589 and LIFR. We determined the role of miR-589 in gastric cancer tumorigenesis in vivo using xenograft nude models. Dual-luciferase report assays and Chromatin immunoprecipitation (ChIP) assay were performed for target evaluation, and the relationships were confirmed by western blot assay. Result MiR-589 expression was significantly higher in tumor tissues and gastric cancer cells than those in matched normal tissues and gastric epithelial cells, respectively. Clinically, overexpression of miR-589 is associated with tumor metastasis, invasion and poor prognosis of GC patients. Gain- and loss-of function experiments showed that miR-589 promoted cell migration, metastasis and invasion in vitro and lung metastasis in vivo. Mechanistically, we found that miR-589 directly targeted LIFR to activate PI3K/AKT/c-Jun signaling. Meanwhile, c-Jun bound to the promoter region of miR-589 and activated its transcription. Thus miR-589 regulated its expression in a feedback loop that promoted cell migration, metastasis and invasion. Conclusion Our study identified miR-589, as an oncogene, markedly induced cell metastasis and invasion via an atypical miR-589-LIFR-PI3K/AKT-c-Jun feedback loop, which suggested miR-589 as a potential biomarker and/or therapeutic target for the gastric cancer management. Electronic supplementary material The online version of this article (10.1186/s13046-018-0821-4) contains supplementary material, which is available to authorized users.

e15654 Background: China accounts for over 50% of global liver cancer burden and most patients have advanced disease at the time of diagnosis. Currently, very little is known about the mutational landscape of Chinese HCC patients because it is risky to perform tissue biopsy on late-stage patients. In this study, this problem was overcome by genetic profiling using circulating tumor DNA (ctDNA) and frequently mutated loci were evaluated as biomarkers for prognosis prediction. Methods: Targeted next generation sequencing (NGS) was performed on ctDNA obtained from patients with advanced HCC using a 150-gene panel. The relationship between overall survival (OS) and genetic alterations was analyzed using Kaplan-Meier method. The predictive value of frequently mutated genes was then validated using 607 western HCC cases of the cBioPortal (http://www.cbioportal.org,including TCGA and other two studies). Impact of 8q24 amplification on transcription of other genes was analyzed using mRNA data from TCGA database. Results: Fifty-eight Chinese advanced HCC patients were enrolled and ctDNA was detected in 89.7% of them. The most frequently mutated genes were TP53 (57.7%) and TERT (30.8%) and amplification of chromosome 8q24 occurred at a higher frequency (20.0%) than previously reported for western HCC patients. The 8q24 amplified patients showed significantly shorter OS compared to those without 8q24 amplification (4.9 months vs. Not Reached, p = 0.008). This was confirmed by the cBioPortal database, where 8q24 amplification, which was identified in 10.1% of the HCC cases, was also associated with decreased OS (55.6 months vs.102.7 months, p < 0.001). Gene expression analysis using TCGA mRNA data revealed that upon 8q24 amplification, transcription of 56 genes was upregulated and 169 genes were downregulated, among which ABC transporters, RAS signaling and Hippo signaling pathways were significantly enriched in 8q24 amplified population (p = 0.001, 0.015, 0.027, respectively) as suggested by KEGG analysis. Conclusions: Amplification of chromosome 8q24 ocurred at a higher frequency in Chinese HCC patients and showed promise as a biomarker for prognosis prediction.

Gastric cancer is the third leading type of cancer and has the third leading cancer‑associated mortality in China. The mechanism of thermo‑chemotherapy in gastric cancer cells remains to be elucidated. The present study aimed to investigate the role of autophagic cell death in the thermo‑chemotherapy of gastric cancer. The current study included four groups: An empty control group, a hyperthermia group, a chemotherapy (oxaliplatin) group, and a thermo‑chemotherapy group. Cell viability was analyzed by the MTS assay. Production of intracellular reactive oxygen species (ROS) was quantified by flow cytometry. Autophagy‑associated proteins, Beclin 1, microtubule‑associated protein 1A/1B‑light chain (LC3B) and mammalian target of rapamycin (mTOR), were determined by western blot analysis. The results indicated that thermo‑chemotherapy markedly increased intracellular ROS production, and decreased mitochondrial membrane potential. The transmission electron microscopy results indicated that thermo‑chemotherapy induced production of autophagic bodies. In addition, thermo‑chemotherapy‑induced cell damage at the cellular and animal levels indicated a notable increase in the expression of the autophagy‑associated genes, LC3B and Beclin 1. A negative correlation between mTOR expression and autophagy was also identified, which demonstrates that thermo‑chemotherapy induces autophagic cell death by activating the autophagy‑associated signaling pathways. The results of the present study demonstrated that the ROS level is important in autophagic death of the gastric carcinoma cells, and the increased ROS level, induced by thermo‑chemotherapy treatment, induced autophagy in gastric carcinoma cells.

AIM To establish a reversible porcine model of acute liver failure (ALF) and treat it with an artificial liver system. METHODS Sixteen pigs weighing 30-35 kg were chosen and administered with acetaminophen (APAP) to induce ALF. ALF pigs were then randomly assigned to either an experimental group (n = 11), in which a treatment procedure was performed, or a control group (n = 5). Treatment was started 20 h after APAP administration and continued for 8 h. Clinical manifestations of all animals, including liver and kidney functions, serum biochemical parameters and survival times were analyzed. RESULTS Twenty hours after APAP administration, the levels of serum aspartate aminotransferase, total bilirubin, creatinine and ammonia were significantly increased, while albumin levels were decreased (P < 0.05). Prothrombin time was found to be extended with progression of ALF. After continuous treatment for 8 h (at 28 h), aspartate aminotransferase, total bilirubin, creatinine, and ammonia showed a decrease in comparison with the control group (P < 0.05). A cross-section of livers revealed signs of vacuolar degeneration, nuclear fragmentation and dissolution. Concerning survival, porcine models in the treatment group survived for longer times with artificial liver system treatment (P < 0.05). CONCLUSION This model is reproducible and allows for quantitative evaluation of new liver systems, such as a bioartificial liver. The artificial liver system (ZHJ-3) is safe and effective for the APAP-induced porcine ALF model.

Yinbing Wu,1,2 Mingxin Pan,1 Shuzhong Cui,2 Mingchen Ba,2 Zulong Chen,2 Qiang Ruan2 1Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, 2Treatment Center of Body Cavitary Thermo-Perfusion, Cancer Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China Background: This study aimed to evaluate the efficacy and safety of ultrasound-guided continuous hyperthermic intraperitoneal perfusion chemotherapy (CHIPC) for the treatment of malignant ascites (MA). Methods: Between July 2011 and June 2013, 36 MA patients were prospectively and consecutively hospitalized for three cycles of elective CHIPC under ultrasound guidance, maintained at a constant flow rate of 400–600mL/min normal saline containing 5-fluorouracil plus mitomycin or carboplatin and at a constant temperature of 43°C±0.2°C, for 90minutes. Main outcome measures were ascites resolution, Karnofsky performance status (KPS), and serum tumor biomarkers at 2weeks after the last cycle of CHIPC. All the patients underwent uneventful CHIPC as scheduled, and vital signs remained stable over CHIPC. Results: At 2weeks after the last cycle of CHIPC, MA completely and partially resolved in 26 (72.2%) patients and eight (22.2%) patients, respectively; mean KPS score increased from pretreatment 61±9 to posttreatment 76±9 (P