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The invasion and metastasis of malignant tumors are the main factors affecting the prognosis of patients. Tumor parenchymal cells are significantly heterogeneous and their biological characteristics are very different. The tumor cells of the tumor invasive front (TIF) often play a decisive role in invasion and metastasis. It was found that the cells in this region may have more stem cell characteristics, more invasiveness and therapeutic resistance, which can better predict the progression of tumors and provide a reference for the formulation of personalized treatment schemes. This article summarizes the clinical significance of the TIF from three aspects: pathology, biological characteristics, imaging, especially molecular imaging. DOI: 10.11855/j.issn.0577-7402.2019.01.13

Background & Aims Radical resection is the best treatment for patients with advanced hepatic alveolar echinococcosis (AE). Liver transplantation is considered for selected advanced cases; however, a shortage of organ donors and the risk of postoperative recurrence are major challenges. The aim of this study was to assess the clinical outcomes of ex vivo liver resection and autotransplantation for end-stage AE. Methods In this prospective study, 69 consecutive patients with end-stage hepatic AE were treated with ex vivo resection and liver autotransplantation between January 2010 and February 2017. The feasibility, safety and long-term clinical outcome of this technique were assessed. Results Ex vivo extended hepatectomy with autotransplantation was successful in all patients without intraoperative mortality. The median weight of the graft and AE lesion were 850 (370–1,600) g and 1,650 (375–5,000) g, respectively. The median duration of the operation and anhepatic phase were 15.9 (8–24) h and 360 (104–879) min, respectively. Six patients did not need any blood transfusion. Complications higher than IIIa according to Clavien classification were observed in 10 patients. The 30-day-mortality and overall mortality (>90 days) were 7.24% (5/69) and 11.5% (8/69), respectively. The mean hospital stay was 34.5 (12–128) days. Patients were followed-up systematically for a median of 22.5 months (14–89) without recurrence. Conclusion This is the largest series assessing ex vivo liver resection and autotransplantation in end-stage hepatic AE. This technique could be an effective alternative to liver transplantation in patients with end-stage hepatic AE, with the advantage that it does not require an organ nor immunosuppressive agents. Lay summary Ex vivo liver resection and autotransplantation were performed in a large series of patients with end-stage hepatic alveolar echinococcosis. The results showed that this surgical option was feasible, with acceptable postoperative mortality, but 100% disease-free survival in survivors. Careful patient selection, as well as precise assessment for size and quality of the remnant liver are key to successful surgery.

In certain cases, major hepatectomy is essential and inevitable in patients with hilar cholangiocarcinoma and obstructive jaundice (OJ). The current study was designed to evaluate effects of a novel method of portal blood occlusion, where the portal vein was occluded (OPV) and the hepatic artery flow was preserved in rats with OJ that underwent partial hepatectomy. OJ was induced in rats by ligation of the common bile duct for 7 days. Subsequently, OJ rats underwent hepatectomy removing 76% of the liver following occlusion of the portal triad (OPT), OPV or without portal blood occlusion. Liver blood flow (LBF), liver damage and regeneration were assessed. The safety limit for the duration of liver ischemia was 20 min for OPT and 40 min for OPV in rats with OJ. OPT and OPV methods resulted in significantly decreased microvascular LBF in rats with OJ from 529.53±91.55 laser speckle perfusion units (LSPU) in the control to 136.89±32.32 and 183.99±49.25 LSPU, respectively. Liver damage was assessed analyzing levels of serum alanine transaminase and direct bilirubin, determining interleukin-1β and tumor necrosis factor-α expression and histological examination. It was demonstrated that liver damage and caspase-3 and -9 expression in the liver were substantially reduced in the OPV group compared with the OPT group. In addition, the OPV method significantly improved liver regeneration in OJ rats, as indicated by increased rates of liver regeneration and expression of proliferating cell nuclear antigen and Ki-67 compared with the OPT group. Therefore, the OPV method may prolong the duration of portal blood occlusion, reduce liver injury and improve liver regeneration by preserving hepatic arterial flow during portal blood control in rats with OJ undergoing partial hepatectomy. The current study describes a novel technique, which may be applied in liver surgery in patients with complex jaundice.

Background: Hepatocellular carcinoma (HCC) (about 85–90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. Summary: This guideline presents official recommendations of the National Health and Family Planning Commission of the People’s Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. Key Messages: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Background The incidence of biliary complications after living donor adult liver transplantation (LDALT) is still high due to the bile duct variation and necessity reconstruction of multiple small bile ducts. The current surgical management of the biliary variants is unsatisfactory. We evaluated the role of a new surgical approach in a complicated hilar bile duct variant (Nakamura type IV and Nakamura type II) under emergent right lobe LDALT for high model for end-stage liver disease score patients. Methods The common hepatic duct (CHD) and the left hepatic duct (LHD) of the donor were transected in a right-graft including short common trunks with right posterior and anterior bile ducts, whereas the LHD of the donor was anastomosed to the CHD and the common trunks of a right-graft bile duct and the recipient CHD was end-to-end anastomosed. Results Ten of 13 grafts (Nakamura types II, III, and IV) had two or more biliary orifices after right graft lobectomy; seven patients had biliary complications (53.8%). Later, the surgical innovation was carried out in five donors with variant bile duct (four Nakamura type IV and one type II), and, consequently, no biliary or other complications were observed in donors and recipients during 47–53 months of follow-up; significant differences ( P Conclusion Our initial experience suggests that, in the urgent condition of LDALT when an alternative live donor was unavailable, a surgical innovation of cutting part of the CHD trunks including variant right hepatic ducts in a complicated donor bile duct variant may facilitate biliary reconstruction and reduce long-term biliary complications.

We aimed to compare laparoscopic cholecystectomy (LC) and simultaneous laparoscopic transcystic common bile duct exploration (LTCBDE) using an ultrathin choledochoscope with LC followed by endoscopic retrograde cholangiopancreatography (ERC) and endoscopic sphincterotomy (ES) when indicated.We retrospectively reviewed the records of patients seen between 2004 and 2014 and treated with LC+LTCBDE or LC for gallstones and suspected choledocholithiasis. Postoperative complications and surgical outcomes were compared using t-test, Mann-Whitney U test, or chi-square test.115 patients underwent successful LC+LTCBDE and 112 LC; follow-up data was available for 103 and 106 patients, respectively. Seventeen patients (16.5%) in the LC+LTCBDE group and 10 (28.6%) in the LC+ERC+ES group developed complications (P = 0.114). The LC+LTCBDE group had a significantly higher rate of satisfactory biliary function outcomes than the LC+ERC+ES group (98.1% vs. 85.7%, respectively) (P = 0.017).Single-step LC+LTCBDE using an ultrathin choledochoscope may provide better outcomes in patients with gallstones and suspected choledocholithiasis.

Objective To evaluate the safety and feasibility of radiofrequency ablation (RFA) for hepatic pedicle lesioning in combination with hepatic artery clamping for precise liver resection by establishing a model of precise liver resection in animals. Methods Six healthy Guangxi Bama miniature pigs were selected for this study, and S3, S5 and S6 used as target hepatic segments. The hepatic pedicles were lesioned by radioablation under ultrasound guidance. The hepatic artery was clamped temporarily at the time of radioablation. Three segments (S3, S5 and S6) were resected on each pig. The main outcome measures included the local and general tolerance, the change of blood flow parameters of each segmental arterial and portal branches, and the microscopic appearance of the segmental arterial, portal and biliary tract branches. Results There was no any complication or death following RFA application, and the liver function was restored to normal 14 days after the operation in all animals. Demarcation areas were clear in all target hepatic segments. The blood flow velocity of the portal branches was 0cm/s in all the target hepatic segments after RFA. The arterial blood flow velocity was 15.1±15.4cm/s, which was significantly lower compared with that before RFA (P>0.000). There was no difference in the flow rate of the unaffected segmental vessels following RFA. The mean ablated length of segmental portal, arterial and biliary tract branches was 1.7±0.5cm, 1.4±0.4cm, 1.6±0.4cm, respectively. Conclusions The technique is expedient, safe and effective. Simultaneous temporary occlusion of the hepatic artery adds further benefit. The probe needs to be at least 1.5cm away from non targeted structures to avoid unintended thermal injury. DOI: 10.11855/j.issn.0577-7402.2016.08.05

Background Posthepatectomy liver failure and its transplant counterpart, small-for-size syndrome, remain significant limitations for liver resections and segmental liver transplantation. Partial hepatectomy in mice is one of the most commonly used models to study liver regeneration, but blood and tissue sampling necessary to collect data can affect outcomes or even require euthanasia. We therefore developed a quantitative observational system to predict death from hepatectomy during the first 24 postoperative hours. Materials and methods A total of 100 female, 10 to 12-week-old C57BL/6 mice underwent two-thirds hepatectomy and were monitored for up to 7 d. Our scoring system was based on five categories, each assigned 0-2 points: activity level, body posture, fur condition, respiratory status, and eye appearance. Seventy-five mice were scored 6 h, 12 h, 24 h, 2 d, 3 d, 5 d, and 7 d after surgery. The remaining 25 mice were scored similarly, but underwent, in addition, blood sampling for serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, or euthanasia with liver sampling for conventional hematoxylin-eosin and Ki-67 staining. Results Retrospective analysis indicated that body condition scores ≤5 on two consecutive time points within the first 24 postoperative hours accurately predicted eventual death. Animals in the low scoring group also had significantly higher serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, more hepatocyte necrosis in hematoxylin-eosin, and fewer Ki-67 positive hepatocytes. Conclusions Our scoring system accurately predicts survival, hepatocyte damage, liver regeneration, and systemic inflammation in a mouse hepatectomy model, within the first 24 hours of surgery. This could be useful in evaluating posthepatectomy interventions for their effect on survival and liver regeneration.

Hepatic venous anatomy is a significant component of liver segmental anatomy, and its high variability is a challenge for hepatobiliary surgeons. This was a retrospective study of 98 consecutive patients with no cirrhosis or malignant tumors. IQQA-Liver software was used to display and analyze three-dimensional (3D) images of the hepatic veins and their branches and variations. The average liver volume was 1272.65 ± 322.04 mL; the left hepatic veins drained the smallest parts (21.13 ± 5.41%) of the liver compared with the right (35.58 ± 12.41%) and middle hepatic veins (34.64 ± 8.76%). The most common pattern was that the left hepatic veins shared a common trunk with the middle hepatic veins in 51cases (52.0%). The visualization rate of the inferior right hepatic vein (IRHV) was 43.9%, and its drainage volume was 179.27 ± 128.79 mL. In 11.2% of patients, the drainage volume for the IRHV was larger than for the right hepatic vein (RHV). The patterns of the left hepatic and middle hepatic veins were also observed and classified. Umbilical hepatic veins appeared in 75 cases (76.5%), and anterior fissure hepatic veins appeared in 74 cases (75.5%).The rate of the presence of a separate segment 4 vein was 15.3%, and 77 patients had obvious superficial veins. There was a statistically significant correlation between the diameter of the IRHVs and the drainage volume of the IRHVs and RHVs. More detailed information about the anatomical features and variations of hepatic venous veins in Chinese people was provided using 3D reconstructions, and this will assist in more precise liver surgeries.

We aimed to elucidate the effects of hepatoma-derived growth factor (HDGF) on growth and metastasis of hepatocellular carcinoma (HCC) cells. Tissue microarrays with 236 HCC specimens and 18 extrahepatic metastases were utilized to detect the HDGF expression by immunohistochemistry. Meanwhile, HDGF expressions in HCC cell lines with different metastatic potentials were examined using immunofluorescence staining, real-time PCR and western blotting. After HDGF silencing, the growth and metastatic potentials of HCC cells were evaluated by soft agar assay, invasion assay, together with tumorigenicity assay in nude mice. The gelatin zymography was performed by detecting MMP-2 and MMP-9 levels. Additionally, western blotting was conducted to determine the levels of total and phosphorylated ERK1/2, JNK, p38 and Akt. The results showed that HDGF was overexpressed in HCC metastasis tumour, and the expression increased with the differentiation degree of tumours (Grade I 44.0%, Grade II 48.4% and Grade III 65.6%). Consistently, HDGF levels were positively associated with the metastatic capability of HCC cells (MHCC97L

Long non-coding RNAs (lncRNAs) had been proved to be pivotal regulators in carcinogenesis. On the basis of competitive endogenous RNAs (ceRNAs) system, lncRNAs significantly expanded their regulating networks. In our research, we aimed to figure out the exact role of lncRNA HNF1A-AS1 in the pathogenesis of hepatocellular carcinoma (HCC), in a ceRNA-dependent way. First, we revealed: HNF1A-AS1 was frequently overexpressed in HCC tissues and cell lines and its relative high expression was closely related to larger tumor size, multiple tumor lesions, poor differentiation and advanced TNM stage. Then we found: HNF1A-AS1 functioned as an oncogene in tumor growth and apoptosis through sponging tumor-suppressive hsa-miR-30b-5p (miR-30b) and de-repressing Bcl-2. Further experiments identified: HNF1A-AS1-miR-30b axis significantly promoted autophagy under starvation and ATG5 was first proved to be a target of miR-30b. In summary, we identified HNF1A-AS1-miR-30b axis as a key regulator in hepatocarcinogenesis, which may be promising biomarkers and therapeutic targets in the future.

Massive hepatectomy often leads to fatal liver failure because of a small remnant liver volume. The aim of this study was to investigate the potential mechanisms leading to liver failure. Sprague–Dawley rats had performed a sham operation, 85 % partial hepatectomy (PH) or 90 % PH, and all had free access to water with or without supplemented glucose. Liver function and survival were evaluated. Liver parenchymal injury was assessed by evaluating hepatic pathology, blood biochemistry, and apoptotic and necrotic alterations. The regeneration response was assessed by the weight gain of the remnant liver, hepatocyte proliferation markers, and regeneration-related molecules. The 90 % hepatectomy resulted in a significantly lower survival rate and impaired liver function; however, no significant more serious liver parenchymal injuries were detected. TNF-α, HGF, myc and IL-6 were either similarly expressed or overexpressed; however, the increase in remnant liver weight, mitotic index, and the presence of Ki-67 and PCNA were significantly lower in the 90 %-hepatectomized rats. mTOR, p70S6K and 4EBP1 were not activated in the remnant liver after a 90 % hepatectomy as obviously as those after an 85 % hepatectomy, which was concomitant with the higher expression of phospho-AMPK and a lower intrahepatic ATP level. Glucose treatment significantly improved the survival rate of 90 %-hepatectomized rats. Suppression of remnant liver regeneration was observed in the 90 % PH and contributed to fatal liver failure. This suppressed liver regenerative capacity was related to the inhibited activation of mTOR signaling.

Clinically, hepatectomy is a clean procedure performed without routine antimicrobial prophylaxis, regardless of the extent of liver loss. Translocation of endotoxin has been recognized as a fatal complication leading to liver failure. After extended hepatectomy, the portal hypertension, mucosal damage, intrahepatic bile acid retention, inhibited enterokinesia, and so forth are likely to contribute to enhanced endotoxin absorption. The effect of selective bowel decontamination (SBD) on the prognosis of hepatectomy were investigated.We adopted rat models of partial hepatectomy (70%, PHx) and subtotal hepatectomy (90%, SHx), gentamicin or saline of the same amount was administrated preoperatively. Liver damage makers, portal and systemic lipopolysaccharide, mucosal damage, signaling pathways, liver regeneration, and bile canalicular networks reconstruction were investigated.We found that SHx but not PHx resulted in significantly enhanced portal and systemic endotoxin. Inhibition of gastrointestinal gram-negative bacteria by gentamicin significantly reduced lipopolysaccharide levels and improved survival after SHx (56% with gentamicin, 24% with saline, P0.05). We also found SBD with gentamicin protected intestinal mucosa barrier, alleviated liver parenchymal damage, and promoted liver regeneration and bile canalicular networks reconstruction after extended liver resection.We conclude that SBD is beneficial and necessary for extended hepatectomy.

Liver failure remains as the most common complication and cause of death after hepatectomy, and continues to be a challenge for doctors. t test and χ2 test were used for single factor analysis of data-related variables, then results were introduced into the model to undergo the multiple factors logistic regression analysis. Pearson correlation analysis was performed for related postoperative indexes, and a diagnostic evaluation was performed using the receiver operating characteristic (ROC) of postoperative indexes. Differences in age, body mass index (BMI), portal vein hypertension, bile duct cancer, total bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), operation time, cumulative portal vein occlusion time, intraoperative blood volume, residual liver volume (RLV)/entire live rvolume, ascites volume at postoperative day (POD)3, supplemental albumin amount at POD3, hospitalization time after operation, and the prothrombin activity (PTA) were statistically significant. Furthermore, there were significant differences in total bilirubin and the supplemental albumin amount at POD3. ROC analysis of the average PTA, albumin amounts, ascites volume at POD3, and their combined diagnosis were performed, which had diagnostic value for postoperative liver failure (area under the curve (AUC): 0.895, AUC: 0.798, AUC: 0.775, and AUC: 0.903). Preoperative total bilirubin level and the supplemental albumin amount at POD3 were independent risk factors. PTA can be used as the index of postoperative liver failure, and the combined diagnosis of the indexes can improve the early prediction of postoperative liver failure.

Despite advances in the detection and treatment of hepatocellular carcinoma (HCC), the prognosis remains poor partly due to recurrence or extra/intrahepatic metastasis. Stem‑like cancer cells are considered the source of malignant phenotypes including metastasis in various types of cancer. HCC side population (SP), considered as stem‑like cancer cells, plays an important role in the migration and invasion in HCC, while the mechanisms involved remain unknown. In the present study, high levels of STAT3 and phospho‑STAT3 were observed in MHCC97H SP cells compared with the main population (MP) cells. Inhibition of phospho‑STAT3 led to a reduction of miR‑21 expression, an increase of PTEN, RECK, and programmed cell death 4 (PDCD4) expression as well as the migration and invasion of SP cells. A set of rescue experiments was performed using different combinations of STAT3 inhibitor, miR‑21 mimics and siRNAs to observe the expression of miR‑21 targets, cell migration and invasion alterations. Data indicated that the alterations induced by STAT3 inhibition were partly reversed by the upregulation of miR‑21. Additionally, the cells migration and invasion when silencing the targets of miR‑21 were also reversed by STAT3 inhibition. In conclusion, the present study revealed the aberrant expression of STAT3 and miR‑21 in HCC SP cells. Targeting STAT3 may limit HCC migration and invasion, which is likely to involve the regulation of miR‑21 and its targets PTEN, RECK and PDCD4. Strategies directed towards STAT3 may therefore be a novel approach for the treatment of HCC.

We conducted a hospital-based case-control study to assess the association between IL-10-592 A/C, IL-10-819 C/T, and IL-10-1082 A/G polymorphisms and the risk of liver cirrhosis in a Chinese population. This 1:1-matched case-control study included 192 patients from the Chinese PLA General Hospital. Genotypes of IL-10-592 A/C, IL-10-819 C/T, and IL-10-1082 A/G were detected by polymerase chain reaction amplification-restriction fragment length polymorphism analysis. Conditional regression analysis showed that individuals carrying the IL-10-1082 G allele had an only slightly increased risk of liver cirrhosis, with an adjusted odds ratio (95% confidence interval) of 2.14 (0.97-1.68). However, we did not identify a significant association between polymorphisms in IL-10-592 A/C and IL-10-819 C/T and the risk of liver cirrhosis. These findings may provide important clues for future studies of early detection screening of liver cirrhosis.

This paper was designed to evaluate a novel surgical procedure of using a gastroduodenal artery graft for reconstruction of the hepatic artery during radical resection of hilar cholangiocarcinoma, which is citation-free and self-contained. In this paper we retrospectively analyzed the clinical data, surgical procedure, and follow-up results in nine patients who underwent hepatic artery reconstruction using a gastroduodenal artery graft during their radical resection of hilar cholangiocarcinoma and no artery thrombosis or other surgical complications were found after operation with minimum follow-up duration of three months. We recommended that a gastroduodenal artery graft was shown to be a good choice for hepatic artery resection after radical resection of hilar cholangiocarcinoma.

Our purpose was to evaluate the reasons for reoperations and outcomes in patients with choledochal cysts (CCs). The records of patients with CCs who underwent reoperations from 1995 to 2012 were retrospectively reviewed. Of 165 patients with a mean age of 42.54 ± 14.05 years, 62 had Todani type I (37.6 %), 84 type IV-A (50.9 %), and 19 had unknown type CCs (11.5 %). Previous surgery was internal or external drainage alone in 66.1 % of patients with type I and 23.8 % of patients with type IV-A CCs. Partial cyst excision and Roux-en-Y cyst-jejunostomy or cyst excision and choledochoplasty by jejunal interposition were performed in 16.1 and 11.3 % of patients with type I and IV-A CCs, respectively. Reoperations at our hospital were maximal cyst excision and Roux-en-Y hepaticojejunostomy. Radical cyst excision was achieved in 93.5 % of patients with type I and 44.0 % of patients with type IV-A CCs. With an average follow-up of 48.23 ± 12.30 months, recurrent cholangitis and biliary-enteric anastomotic stenosis occurred in 18 (13.2 %) and 9 patients (6.6 %), respectively. Long-term biliary function was excellent or good in 83.8 % of patients. Radical cyst excision and Roux-en-Y hepaticojejunostomy provide good outcomes in patients with CCs.

Post-pancreaticoduodenectomy (PD) hemorrhage (PPH) is an uncommon but serious complication. This retrospective study analyzed the risk factors, managements and outcomes of the patients with PPH.A total of 840 patients with PD between 2000 and 2010 were retrospectively analyzed. Among them, 73 patients had PPH: 19 patients had early PPH and 54 had late PPH. The assessment included the preoperative history of disease, pancreatic status and surgical techniques. Other postoperative complications were also evaluated.The incidence of PPH was 8.7% (73/840). There were no independent risk factors for early PPH. Male gender (OR=4.40, P=0.02), diameter of pancreatic duct (OR=0.64, P=0.01), end-to-side invagination pancreaticojejunostomy (OR=5.65, P=0.01), pancreatic fistula (OR=2.33, P=0.04) and intra-abdominal abscess (OR=12.19, P0.01) were the independent risk factors for late PPH. Four patients with early PPH received conservative treatment and 12 were treated surgically. As for patients with late PPH, the success rate of medical therapy was 27.8% (15/54). Initial endoscopy was operated in 12 patients (22.2%), initial angiography in 19 (35.2%), and relaparotomy in 15 (27.8%). Eventually, PPH resulted in 19 deaths. The main causes of death were multiple organ failure, hemorrhagic shock, sepsis and uncontrolled rebleeding.Careful and ongoing observation of hemorrhagic signs, especially within the first 24 hours after PD or within the course of pancreatic fistula or intra-abdominal abscess, is recommended for patients with PD and a prompt management is necessary. Although endoscopy and angiography are the standard procedures for the management of PPH, surgical approach is still irreplaceable. Aggressive prevention of hemorrhagic shock and re-hemorrhage is the key to treat PPH.

Background and Aim To compare percutaneous transhepatic biliary drainage (PTBD) and endoscopic biliary drainage (EBD) for management of malignant biliary tract obstruction (MBTO). Methods PubMed, Google Scholar, and the Cochrane database were searched to 31 December 2013. Main outcome measurements were therapeutic success rate, 30-day mortality rate, overall complications, cholangitis, and pancreatitis. Results Eight studies (five retrospective and three randomized controlled trials) were included in the meta-analysis with a total of 692 participants. Combined odds ratio (OR) = 2.18 revealed no significant difference in therapeutic success between PTBD and EBD (95% confidence interval [CI] = 0.73–6.47, P = 0.162). However, after excluding two studies that appeared to be outliers, PTBD exhibited a better therapeutic success rate than EBD (pooled OR = 4.45, 95% CI = 2.68–7.40, P

Previously known as a first-response protein upon viral infection and other stress signals, double-stranded RNA-dependent protein kinase (PKR, also termed EIF2AK2) has been found to be differentially expressed in multiple types of tumor, including hepatocellular carcinoma, suggesting that PKR may be involved in tumor initiation and development. However, whether and how PKR promotes or suppresses the development of hepatocellular carcinoma remains controversial. In the present study, PKR expression was investigated using qPCR and western blot analysis, which revealed that PKR expression was upregulated in liver tumor tissues, when compared to that of adjacent normal tissues, which were obtained from four primary liver cancer patients. Furthermore, in vitro cellular assays revealed that PKR exerts a key role in maintaining the proliferation and migration of HepG2 human hepatocellular carcinoma cells. Mouse models with xenograft transplantations also confirmed a tumorigenic role of PKR in HepG2 cells. Furthermore, a transcription factor, signal transducer and activator of transcription 3 (STAT3), was revealed to mediate the tumor-promoting function of PKR in HepG2 cells, as shown by in vitro cellular proliferation and migration assays. In conclusion, the results suggested a tumorigenic role of PKR in liver cancer and a detailed mechanism involving an oncogenic transcription factor, STAT3, is described. Therefore, PKR may present a potential novel therapeutic target for the treatment of liver cancer.

Background Transarterial chemoembolization (TACE) is commonly used to treat advanced hepatocellular carcinoma (HCC), but less is known regarding safety and efficacy of TACE in patients with HCC and portal vein tumour thrombosis (PVTT). The objective of this study was to evaluate the effect of TACE treatment on 1-year survival in patients with HCC and PVTT. Methods Medline, EMBASE, CENTRAL databases (until July 2013) were searched for studies that evaluated the efficacy of TACE with regard to survival in patients with HCC and PVTT. One-year survival rate, the primary end point, was compared between patients who received TACE and those who received control treatment. Results Five prospective studies were identified that assessed the efficacy of TACE on survival. These studies included 600 patients: 335 received TACE therapy and 226 received control treatments. Three of the five studies reported 1-year survival data and were used in the meta-analysis. The combined odds ratio (3.079, 95% confidence interval = 1.094–8.662) indicated that patients who received TACE had a significantly better 1-year survival rate compared with patients in the control group (P = 0.033). Conclusions There are several limitations to this analysis that should be considered when interpreting the findings. The studies used different treatment regimens as controls or with TACE. These differences across the studies may have altered the 1-year survival outcomes in each study and confounded our analysis. This meta-analysis showed that TACE improves the 1-year survival of patients with HCC and PVTT. However, additional prospective controlled trials are required to further substantiate these findings.

BACKGROUND Juxtahepatic vena cava (JHC) injury is difficult to handle because of JHC injury's specific position and liver obstruction. The traditional shunt method initially appeared to be useful but ultimately failed. Simple and effective methods are needed to solve it. METHODS Firstly, the clinical data, including the computed tomography images, of 120 patients were collected. In addition, a JHC digital model was constructed based on computed tomography images. According to the digital model data, a circulation loop simulating the blood flow in the JHC was established. Secondly, we analyzed the hemodynamics of a JHC shunt with pig blood. Finally, the new shunt was designed based on the data obtained. The shunt consists of a covered stent and transfer device and was tested. RESULTS The JHC has a three-dimensional cylindrical structure. The mean (SD) length of the retrohepatic vena cava is 78.21 (9.83) mm, which shows correlations with the patient's age and weight (r = -0.343 and 0.271, respectively, p < 0.05). An equation is obtained as follows: retrohepatic vena cava (millimeter) = 71.23 - 0.293 × age (year) + 0.32 × weight (kilogram). The shunt diameters must be 10 mm and 12 mm to maintain the blood pressure difference Point a and Point b at approximately 3.75 mm Hg (5 cm H2O), when the flow rate is 3,000 mL/min and 5,000 mL/min, respectively. The stent graft showed effective hemostasis in tests. However, it failed when the inferior vena cava was pulled harder. CONCLUSION A temporary stent graft as a new shunt for JHC injury has not been previously reported. It is a combination of both a traditional operation and a simple endovascular technique, which showed effective hemostasis in tests.

Objective Radiofrequency ablation (RFA) is effective in treating hepatocellular carcinoma (HCC) and less invasive than surgical resection. However, ‘one-off' complete tumor ablation on liver function has not been reported. Methods We retrospectively reviewed 36 HCCs which met the criteria of ‘one-off' complete tumor ablation: (1) tumor was completed covered by the ablated zone (confirmed by postoperative enhanced CT) with a single RFA and, (2) no sign of recurrence for at least 6 months. We categorized tumors into two groups: near vascular tumor (NVT) if the distance was less than 5 mm, and far vascular tumor (FVT) otherwise. Results Thirteen HCCs met the criteria of NVTs, and 23 HCCs met that of FVTs. The Average tumor size was 2.6 ± 0.3 cm in FVTs and 2.5 ± 0.3 cm in NVTs. Although restored to normal range by postoperative day (POD) 7, ALT, AST, total bilirubin (TB), albumin and prothrombin time showed more significant fluctuation in NVTs compared to those in FVTs on POD1 through POD5. Moreover, 53.9% (7/13) patients in NVT group and 26.1% (6/23) in FVT group developed post-RFA transient ascites (OR = 5.1, 95% CI = 1.1–24.4). Incidence of post-RFA pleural effusion were 61.5% (8/13) in NVT but only 17.4% (4/23) in FVTs (OR = 7.6, 95% CI = 1.6–35.9). Conclusion ‘One-off' complete tumor ablation may impair liver function and led to more postoperative complication if a tumor is within 5 mm away from a large blood vessel (≥3 mm). Particular caution should be made in preoperative assessment on the anatomic relation between tumor and large blood vessel for patients.

Objective To explore a rational method of placing appropriate pancreatic drainage after pancreaticoduodenectomy, and evaluate its safety and feasibility. Methods Classic Bernoulli's flowing mechanics energy equation (Bernoulli's equation) was used to calculate the dynamics of pancreatic juice flowing inside of the drainage tube. With given constant flowing velocity and density of pancreatic juice, four related factors on ΔP(pressure difference between entrance and exit planes of drainage tube) were investigated viarehearsing the formula. Effects on draining velocity by diameter and length of the tube were further verified by use of self-made pancreas drainage simulator, as well as the impact of liquid level difference on ΔP. Results Data obtained from calculation elucidated that the rank of 4 related factors was as follows: inner diameter﹥liquid level difference﹥liquid viscosity﹥tube length. The experiment also verified that the influence of draining velocity depended more on diameter rather than length. Liquid level difference was identified as major independent impact factor on ΔP. Conclusions Tube calibre ranging 1.5-2.0mm to allow a continuity of liquid flow is an essential factor to promise a fluent drainage. A 1.4m-length drainage tube is recommended for external draining, however, intraintestinal drainage of the pancreatic duct may be the best option. DOI: 10.11855/j.issn.0577-7402.2014.03.03

Objective To explore the relative physical factors influencing tumor burst during radiofrequency ablation (RFA) treatment of hepatocellular carcinoma (HCC). Methods Watertight globes of different size filled with water were used to simulate tumor mass of HCC, and then they were heated to a balanced gradient inner temperature similar to that occurring during RFA treatment. The changes in inner pressure of the wall of globes were then recorded according to gradient balanced temperature. Results Responding to a gradually elevation of inner temperature, the inner pressure against the watertight globe wall increased exponentially from 7.38kPa at 40℃ to 70.14kPa at 90℃, i.e. there was a about 9.5-fold increase at 40℃. The inner pressure could reach a pressure of 101.33kPa at 100℃. Continued heating to above 100℃, the vaporized water expanded the globe, the inner pressure would reach to 198.64kPa when the temperature reached 120℃, and the inner pressure would reach 476.24kPa when thetemperature reached 150℃. Conclusions The inner pressure of tumor increases exponentially along with rise of temperature, especially so when heated above 100℃. The vaporization of liquid inside of the tumor could exceed the inner pressure, and it is considered as the major factor in producing tumor burst during RFA treatment. DOI: 10.11855/j.issn.0577-7402.2014.02.03

Tumor biomarkers commonly used for the detection of hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombosis (PVTT) do not show satisfactory sensitivity and specificity. This study assesses the diagnostic value of the tumor biomarkers for the diagnosis of HCC with PVTT. A retrospective study was conducted on 475 patients diagnosed as HCC with PVTT and 977 patients diagnosed with HCC by imaging and requiring surgery at our hospital from January 1993 to January 2011. Serum alpha-fetoprotein AFP, carcinoembryonic antigen, and cancer antigen 125 (Ca125) of the patients were studied. No significant differences were observed in the patients’ general characteristics. The receiver operating characteristic (ROC) analysis showed that the cut-off of AFP and Ca125 was 32.91 ng/ml and 113.65 U/ml, respectively (AUC = 0.814 and 0.783). The parallel testing with AFP and Ca125 has a sensitivity of 0.909 and a specificity of 0.410; the serial testing has a sensitivity of 0.520 and a specificity of 0.97. The condition of AFP ≥ 20,000 ng/ml can detect HCC with PVTT with a sensitivity of 0.24, a specificity of 0.96, and an accuracy of 0.73 and positive screening of 0.76. The standard of both AFP > 32.91 ng/ml and Ca125 > 113.65 U/ml or AFP ≥ 20,000 ng/ml can detect HCC with PVTT with a specificity of 0.97 and 0.96, respectively, providing important guidance for clinical practice.

The treatment of type IV-A choledochal cyst is particularly difficult and remains a challenge because of the rareness and the various presentations of the disease involving not only the extrahepatic but also the intrahepatic biliary tract. The purpose of this study is to analyze our clinical experience for surgical treatment of type IV-A choledochal cyst, and compare between children and adults.During a 10-year period of time (2000-2010), clinical data of 81 consecutive patients with type IV-A choledochal cyst were retrospectively analyzed. We divided these patients into two groups, the child group (age ≤ 18 years) and the adult group (age18 years). According to whether the patient received additional liver resection, patients were divided into a extrahepatic cystectomy (EHC) group and an additional liver resection (LR) group. The long-term outcomes after surgery were evaluated in two groups.Of all 81 patients, there were 17 children and 64 adults; 16 children and 35 adults belonged to EHC group, one child and 29 adults belonged to LR group. The morbidity of biliary stricture and/or lithiasis in the adults was significantly higher than that in the children (p = 0.0410.05). In the EHC group, the reoperation rate of adults was significantly higher than that of children (p = 0.0190.05). For adult patients, the morbidity of biliary stricture and/or lithiasis and the reoperation rate in EHC group was significantly higher than that in LR group (p = 0.0370.05 and p = 0.0260.05 respectively). Five adults were found to have cholangiocarcinoma within a follow-up period, while no child was found to. However, for adult patients, no significant discrepancy was observed between EHC group and LR group (p = 0.3660.05).The present study suggests that the children have better outcomes than adults for patients with type IV-A choledochal cyst after EHC, while LR brings better outcomes than EHC for adult patients.

Aim To investigate the effect of different hepatic vascular occlusion maneuvers on the growth of hepatocarcinoma after liver ischemia–reperfusion (I/R) injury. Methods A mice hepatocarcinoma model was established by portal vein injection of H22 hepatoma cells. After 3 days, the mice underwent sham operation, occlusion of portal triad (OPT), portal vein (OPV), or intermittent clamping (INT) operation. The hepatic I/R injury, pathological changes, hepatic replacement area, proliferative cell nuclear antigen expression, and extracellular signal-regulated kinase (ERK) 1/2 activation were assessed 5 days after reperfusion. Results Alanine aminotransferase and aspartate aminotransferase levels in the OPV group were significantly lower than those in the OPT and INT groups at 24 h after reperfusion. The hepatic injury of clamped liver lobes in the OPV group, represented by histopathological alterations and myeloperoxidase activity, was much slighter than that in the OPT and INT groups. The values of hepatic replacement area in the sham operation, OPT, OPV, and INT groups were 7.661 2.55%, 35.61 1 4.23%, 9.02 1 3.01%, and 19.95 1 4.10%, respectively. Proliferative cell nuclear antigen expression and ERK1/2 activation of tumor cells were the highest in the OPT group, and the lowest in the OPV and INT groups. Conclusion Preserving hepatic artery flow during portal triad blood inflow occlusion substantially inhibits the outgrowth of hepatocarcinoma via attenuating hepatic I/R injury in a murine liver tumor model. These results suggest a better prevention of hepatic tumor outgrowth after hepatectomy by using the selective portal vein clamping method in liver cancer patients.

The main objective of this study is to assess the feasibility and safety of treating hepatocellular carcinoma (HCC) proximal to the gallbladder using laparoscopic radiofrequency ablation (RFA). Surgical ablation of tumor located adjacent to the gallbladder may damage the gallbladder wall, even with a laparoscope and this ablation method is not precise and incomplete and is frequently combined with alcohol injections with need for further RFA treatment. Four patients were included in this study, with typical HCC where the tumor was present on the left, right, or bed side surrounding the gallbladder. The gallbladder was not separated or removed during larascopic inspection. In the RFA treatment procedure, the tumor lesion was pre-heated for 10 min, and heating was continued for 20 min. The integrity of the gallbladder wall was properly maintained. A follow-up to check for possible local recurrence was carried out 1 year after the RFA. The goal of "one-off" tumor complete RFA is to achieve thorough ablation of the tumor in a single treatment and limiting the possibility of recurrence within 6 months. Seven days after RFA, liver functions of all the patients returned to near-preoperative levels. The patients experienced slight pain in the upper right abdomen, which disappeared in 2-3 days. Results of B ultrasound on days 3-5 showed thickening of the periphery of the ablation area, without significant effusion. Enhanced CT on day 3 showed that RFA low-density area completely covered the lesions. No significant abnormality was observed in the gallbladder and its vicinity. One month after the surgery, B ultrasound and CT examination revealed no significant abnormalities. All patients had an intact gallbladder, and no extrahepatic or intrahepatic bile duct dilatation occurred. There was no evidence of damage to the bile duct or the vessels. Follow-up for 18-32 months found that all patients were in good condition. "One-off" complete RFA can be safely implemented to ablate HCC close to the gallbladder with the assistance of a laparoscope while maintaining integrity and continuity of the gallbladder, and without the need for secondary treatments.

Continuous theoretical and technological progress in the face of increasing expectations for quality health care has transformed the surgical paradigm. The authors systematically review these historical trends and propose the novel paradigm of "precision surgery," featuring certainty-based practice to ensure the best result for each patient with multiobjective optimization of therapeutic effectiveness, surgical safety, and minimal invasiveness. The main characteristics of precision surgery may be summarized as determinacy, predictability, controllability, integration, standardization, and individualization. The strategy of precision in liver surgery is to seek a balance of maximizing the removal of the target lesion, while maximizing the functional liver remnant and minimizing surgical invasiveness. In this article, the authors demonstrate the application of precision approaches in specific settings in complex liver surgery. They propose that the concept of precision surgery should be considered for wider application in liver surgery and other fields as a step toward the ultimate goal of perfect surgery.

Objective To explore the heat conduction effect (HCE) and effective extent in liver tissue produced by radiofrequency ablation (RFA). Methods To simulate the HCE produced by RFA, isolated swine livers were heated to different temperature for a range of different heating time with RFA. The temperature of liver in different distance away from the center and the changes in color and morphology of liver tissue after radiofrequency treatment were recorded to explore the attenuation pattern of different heating center temperature and duration of treatment. Results When the temperature of heating center reached 70℃, 5mm in radius of liver tissue was ablated in 10min. To expand the range to 10mm, central temperature should be maintained above 80℃ or 90℃, and the heating time should be maintained for 40min and 25min, respectively. Conclusion To complete ablation of an area of liver tissue with 10mm in diameter with HCE, the temperature of heating center should be maintained at higher than 8090℃ and the ablation time should be maintained for 25-40min.

Objective To assess the feasibility and safety of laparoscopic one-off complete radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) in caudate lobe. Methods Ten patients (9 males and 1 female) with caudate lobe HCC were treated by laparoscopic RFA in the General Hospital of PLA from Dec. 2009 to Dec. 2010. The mean age of the patients was 48 years (ranged from 32 to 65). Nine cases were Child-Pugh A, and one was Child-Pugh B. The mean diameter of tumors was 2.6cm (1.8-3.2cm). The mean follow-up period for focal recurrence was 6 months to evaluate the result of one-off tumor complete ablation. Results The monitored mean temperature of ablation area was about 86.4℃ (83-97℃), and the elevation of body temperature as measured in nose was 1.5℃ (1.1-2.0℃) just after the procedure of ablation was terminated. No additional therapy was needed after RFA, no single focal recurrence appeared 6 months after the procedure of ablation, and the survival condition was satisfactory during 24-36 months of follow-up period. Conclusion The laparoscopic one-off complete RFA for HCC situated in caudate lobe is safe and feasible.

Objective To evaluate the feasibility and safety of laparoscopy-assisted one-off complete radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) adjoining gallbladder. Methods Five cases of HCC adjacent to different location of gallbladder were involved in present study. The tumor diameter ranged from 2.5 to 4.2cm. Laparoscopy-assisted radiofrequency ablation was performed without isolation or resection of gallbladder so as to maintain its anatomical integrity. The patients were followed up with the aid of ultrasonography and computed tomography postoperatively, at the same time the surviving quality was assessed. Results Three days after the operation, ultrasound examination showed that the gallbladder wall close to the ablated area was increased by 0.3-0.4cm, and the CT images showed that the density of gallbladder wall was increased. Six months after the operation, the contrast enhanced CT images showed that the gallbladder was intact and no high density area was observed in every patient, implying that the tumor was one-off ablated completely. All the patients lived a life with good quality during the follow-up period of 18-36 months. Conclusion Laparoscopy-assisted one stage radiofrequency ablation for hepatocellular carcinoma adjoining gallbladder with maintenance of the anatomical integrity of gallbladder is technically safe and feasible.

Objective To establish the animal model of radiofrequency ablation (RFA) on living swine liver, and observe the pathologic changes caused by the "river effect (RE)"of RFA on relevant regional hepatocytes. Methods Three target segments of liver of each of 6 Guangxi BA-MA mini pigs were selected for ablation. Under the guidance of sonography, the tip of RFA electrode was inserted into the liver close to segmental outflow vessel, and every ablated point was heated for 6 minutes. Pathological changes of relevant downstream region along portal vein and hepatic artery were observed under microscope after RFA. Results The ablated region of the liver was oblong in shape with outer diameter of 2.2±1.1cm on gross inspection. Thermal damage (e.g. obvious dilated blood sinuses, with abundant inflammatory cell infiltration in portal vein region and necrosis of hepatocytes, etc.) was observed in downstream region of the relevant portal vein under microscope after RFA. However, liver tissue in adjacent area around the vessel was intact, and no obvious thermal damage was found. Conclusion The "river effect" during RFA for liver tissue may lead to thermal damage to hepatocytes along the downstream region of the regional portal vein, and this effect decreases gradually toward the surface of liver segment.

Summary Backgrounds and aim Microglial cells as an important part of central nervous system (CNS) have generally believed to play significant role in the process leading to a number of neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, prion diseases, multiple sclerosis, HIV-dementia, and stroke. Although different diseases have quite different pathogenesis, the activation of microglia was shared with all of them. Recently, the resolvin D1 (RvD1) as an endogenous antiinflammatory lipid mediator has been confirmed to be involved in the treatment of inflammation-related neuronal injury in neurodegenerative diseases. Therefore, the inhibition of microglia-activated inflammation has been considered as a major treatment strategy in neurodegenerative disease therapy. However, the molecular mechanisms of RvD1 in microglial cells remain unknown and still do not be reported. Methods We taken murine microglia as the experimental sample, and Western blotting, ELISA, reverse-transcriptase PCR, real-time PCR, and electrophoretic mobility shift assay were used to study whether the RvD1 inhibit inflammation of microglial cells. The tumor necrosis factor α (TNF-α), IL-1β, inducible nitric oxide synthase (iNOS) expression, nuclear factor-κB (NF-κB) activation, and mitogen-activated protein kinase (MAPK) pathways were investigated in lipopolysaccharide (LPS)-activated primary microglia. Results Our data suggested that RvD1 inhibited the production of LPS-induced microglia inflammatory mediators and TNF-α, IL-1β, and iNOS expression. In addition, according to the study of related signaling pathways, RvD1 attenuated LPS-induced microglia NF-κB activation,MAPK phosphorylation, and activator protein-1 transcriptional activity. Conclusion This is the first study to demonstrate that RvD1 effects on the reduction of pro-inflammatory responses in LPS-induced microglial cells. The mechanisms underlying these effects may include its potent intracellular NF-κB down-regulation and subsequent pro-inflammatory cytokines release in LPS-activated microglia.

Liver-directed gene therapy has become a promising treatment for many liver diseases. In this study, we constructed a multi-functional targeting molecule, which maintains targeting, endosome-escaping, and DNA-binding abilities for gene delivery. Two single oligonucleotide chains of Melittin (M) were synthesized. The full-length cDNA encoding anti-hepatic asialoglycoprotein receptor scFv C1 (C1) was purified from C1/pIT2. The GAL4 (G) gene was amplified from pSW50-Gal4 by polymerase chain reaction. M, C1 and G were inserted into plasmid pGC4C26H to product the recombinant plasmid pGC-C1MG. The fused gene C1MG was subsequently subcloned into plasmid pET32c to product the recombinant plasmid C1MG/pET32c and expressed in Escherichia coli BL21. The scFv-Mel-Gal4 triple fusion protein (C1MG) was purified with a Ni2+ chelating HiTrap HP column. The fusion protein C1MG of roughly 64 kD was expressed in inclusion bodies; 4.5 mg/ml C1MG was prepared with Ni2+ column purification. Western blot and immunohistochemistry showed the antigen-binding ability of C1MG to the cell surface of the liver-derived cell line and liver tissue slices. Hemolysis testing showed that C1MG maintained membrane-disrupting activity. DNA-binding capacity was substantiated by luciferase assay, suggesting that C1MG could deliver the DNA into cells efficiently on the basis of C1MG. Successful expression of C1MG was achieved in E. coli, and C1MG recombinant protein confers targeting, endosome-escaping and DNA-binding capacity, which makes it probable to further study its liver-specific DNA delivery efficacy in vivo. Copyright © 2013 John Wiley & Sons, Ltd.

Reperfusion is the key strategy in acute ST-segment elevation myocardial infarction (STEMI) care, and it is time-dependent. Shortening the time from symptom to reperfusion and choosing the optimal reperfusion strategy for STEMI patients are great challenges in practice. We need to improve upon the problems of low reperfusion rate, non-standardized treatment, and economic burden in STEMI care. This article briefly reviews the current status of reperfusion strategy in STEMI care, and also introduces what we will do to bridge the gap between the guidelines and implementation in the clinical setting through the upcoming China STEMI early reperfusion program.