Abstract:Objective: To investigate the application value of associating liver partition and portal vein ligation in staged hepatectomy (ALPPS) for hepatocellular carcinoma (HCC) with post-hepatitic cirrhosis. Methods: The clinical data of one patient with HCC associated with hepatitis B virus (HBV) cirrhosis admitted in March 2014 to Xiangya Hospital of Central South University and undergoing ALPPS were retrospectively analyzed. Results: Preoperative assessment showed that the patient’s future liver remnant (FLR) to standard liver volume ratio was 20.2%. The patient underwent first-stage operation of right portal vein ligation and in situ splitting of the liver parenchyma, and then underwent a second-stage operation of right hemihepatectomy for tumor resection, on postoperative day (POD) 9, when the patient’s FLR to standard liver volume ratio reached 38.8% after the first-stage operation. For the first- and second-stage operation, the operative time was 255 min and 297 min, and the blood loss was 260 mL and 350 mL, respectively. The patient was discharged from the hospital on POD 21; no metastasis or recurrence occurred, and his HBV-DNA and AFP levels were within normal range during the 2-month follow-up period. Conclusion: For HCC patients with non-active HBV cirrhosis, a proper expansion of the indications for the ALPPS procedure is safe and feasible.

Abstract:Objective: To assess the value of repeated hepatectomy for recurrent hepatocellular carcinoma (HCC) and analyze the associated factors affecting the prognosis. Methods: The clinical data of 26 patients undergoing repeated hepatectomy for recurrent HCC in the First Affiliated Hospital of Chongqing Medical University, between 2006 and 2013 were retrospectively analyzed. Results: The intraoperative blood loss and operative time between the first operation and second operation had no statistical difference (both P>0.05). For the first operation, the postoperative median tumor-free survival time was 21.0 (3-192) months and the postoperative 1-, 3- and 5-year tumor-free survival rate was 69.6%, 26.1% and 8.7%, respectively; for the second operation, the postoperative tumor-free survival time was 19.0 (3-35) months, the postoperative 1-, 3- and 5-year tumor-free survival rate was 68.4%, 0% and 0%, the postoperative median survival time was 40.0 months, and the postoperative 1-, 3- and 5-year accumulative survival rate was 83.5%, 55.7% and 13.0%, respectively. Of the 26 patients, the overall survival time was (87.8±19.3) months, overall median survival tine was 57.0 months, and the 1-, 3- and 5-year accumulative survival rate was 100%, 60.8% and 30.4%, respectively. The survival rate in patients undergoing second liver resection for early recurrence after first operation (within 2 years) was significantly lower than those undergoing second liver resection for late recurrence after first operation (more than 2 year later) (P=0.001). Univariate analysis showed that recurrence interval, surgical type, and pathological stage were associated with the postoperative survival of repeated hepatectomy, and the P value for the three factors in multivariate analysis was 0.089, 0.006 and 0.054, respectively. Conclusion: Repeated hepatectomy can improve the overall survival rate of recurrent HCC patients, but the indications and rational surgical type should be strictly chosen. Those with short recurrence interval and advanced pathological stage may have a poor outcome after repeated hepatectomy.

Abstract:

Objective: To investigate the feasibility and safety of Glissonean pedicle transection method for laparoscopic hepatectomy. Methods: The clinical data of 18 patients undergoing laparoscopic liver resection with Glissonean pedicle transection method between January 2011 and June 2013 were retrospectively analyzed. Results: All of the 18 patients successfully underwent laparoscopic left hemihepatectomy or left lateral lobectomy using Glissonean pedicle transection method, and without any open conversion. The operative time was 42-300 min with an average of (215.6±56.6) min, the intraoperative blood loss was 50-200 mL with an average of (118.6±50.5) mL and without a need for blood transfusion, the length of hospital stay was 8-16 d with an average of (11.4±3.1) d, and there was no occurrence or complications. The patients were followed-up for 3-24 months, all of them were alive and had a satisfactory quality of life, and no tumor recurrence occurred in the 6 cases with hepatocellular carcinoma. Conclusion: Glissonean pedicle transection method can effectively control bleeding, and the use of this method in laparoscopic anatomic left hemihepatectomy or left lateral lobectomy is safe and feasible.

Abstract:Objective: To evaluate the clinical efficacy of sorafenib administration combined with liver resection in treatment of intermediate/advanced stage hepatocellular carcinoma (HCC). Methods: Data of patients with intermediate/advanced stage HCC undergoing liver resection and postoperative sorafenib therapy (observational group) from January 2010 to June 2012, along with the data of patients with intermediate/advanced stage HCC receiving surgical resection only (control group) during the same period at West China Hospital of Sichuan University were collected, for 1-to-2 matched case-control study. The survival and tumor recurrence between the two groups were compared. Results: A total of 81 patients were included, with 27 cases in observational group and 54 cases in control group. In observational group and control group up to the end of follow-up (30 September 2013), the median survival time was 18.6 and 11.9 months, and the difference had statistical significance (P=0.014); the median time to recurrence was 7.4 and 5.0 months, and the difference had no statistical significance (P=0.291); the median survival time for BCLC-B patients was 22.3 and 12.5 months, and the difference had statistical significance (P=0.017), while for BCLC-C patients was 17.6 and 10.4 months, and the difference had no statistical significance (P=0.291). Conclusion: Surgical resection plus sorafenib therapy has good efficacy in patients with intermediate/advanced HCC, especially those in BCLC-B stage. So, it is a treatment method deserving consideration.

Abstract:Objective: To investigate the effects of using parecoxib sodium for analgesia on post-hepatectomy cognitive function in elderly patients. Methods: Eighty patients over 60 years of age undergoing elective hepatectomy for liver cancer were randomly assigned into observational group and control group, with 40 cases in each group. Patients in observational group received parecoxib sodium administration after surgery (40 mg, intravenous injection, and once per 12 h for 3 d) and those in control group were given normal saline as placebo, and additional tramadol was used in either group according to need for analgesia to maintain the pain visual analog scale (VAS) not more than a score of 3. The Wechsler Adult Intelligence Scale (WAIS) and Wechsler Memory Scale (WMS) were used to test the incidence of postoperative cognitive dysfunction (POCD) in both groups of patients, and the blood levels of S-100β protein, inflammatory cytokines, cortisol, and ammonia were detected before surgery and on several time points after surgery. Results: The perioperative data between the two groups of patients showed no statistical difference (all P>0.05). The incidence of POCD was significantly lower in observational group than that in control group (7.5% vs. 25%, P<0.05). The levels of cortisol, IL-4 and ammonia had no significant alteration in both group at any postoperative time points compared with their preoperative levels (all P>0.05); the levels of S-100β protein, IL-6, TNF-α, IL-1β and CRP in both groups were significantly increased in different time spans with varying degrees in both groups compared with their preoperative levels (all P<0.05), but the increasing degrees of S-100β protein and IL-6 in observational group were less than those in control group within postoperative 24 and 48 h, respectively (all P<0.05). Conclusion: Parecoxib sodium administration can help improve the post-hepatectomy cognitive function in elderly patients, and the mechanism may probably associated with its decreasing the S-100β and IL-6 levels.

Abstract:Objective: To evaluate the clinical efficacy of 125I radioactive seed implantation in treatment of primary liver cancer. Methods: The clinical data of 84 liver cancer patients undergoing 125I radioactive seed implantation from June 2009 to August 2012 were retrospectively analyzed. Results: A total of 3 630 seeds were implanted in the 84 patients, with an average of 17 seeds for tumor size equal to or less than 35 cm and an average of 46 seeds for tumor size larger than 35 cm, and all patients were successfully implanted in one session. After implantation, the pain of the patients was relieved or disappeared, complete response (CR) was achieved in 40 cases, partial response (PR) was obtained in 36 cases, stable disease (SD) was seen in 8 cases, and the overall effective rate (CR+PR) was 90.5%. Postoperative follow-up ranged from 3 to 45 months, the average survival time of the patients was 16.5 months, and their 1- and 2-year survival rate was 64.3% and 31.0%, respectively. Conclusion: Intratumoral 125I radioactive seed implantation has demonstrable efficacy, and can be used as an alternative treatment modality for refractory, recurrent or metastatic liver cancer.

Abstract:Objective: To investigate the clinical efficacy of the combination of entecavir and interventional therapy in treatment of hepatitis B virus (HBV)-related hepatocellular carcinoma (HBVR-HCC). Methods: From February 2007 to February 2011, 85 patients definitely diagnosed as HBVR-HCC and without indication for surgery were selected. Of the patients, 44 cases underwent entecavir plus transarterial chemoembolization (TACE) treatment (observational group), and 41 cases received TACE alone (control group). The HBV DNA level, liver function, AFP level, and Child-Pugh score of the two groups before treatment and at 4, 12, 24, and 48 weeks after treatment were analyzed, and the clinical efficacy, incidence of adverse effects, and survival status between the two groups were compared. Results: With prolongation of treatment time, the HBV-DNA level in observational group was gradually decreased, while in control group it was gradually increased, and the differences at each time point after treatment between the two groups had statistical significance (P<0.05); the alanine transaminase (ALT) and AFP levels were gradually decreased, but their decreasing degrees were greater than those in control group after 24-week treatment (all P<0.05); the Child-Pugh scores in both groups were gradually increased but the increasing degree in observational group was significantly lower than that in control group after 24-week treatment (P<0.05). The effective rate of treatment in observational group was significantly higher, while the incidence of complications and adverse reactions in observational group was significantly lower than those in control group (all P<0.05). No statistical difference was noted in 1-year survival rate between the two groups (P>0.05), but the 2-year survival rate and median survival time in observational group were better than those in control group (both P<0.05). Conclusion: TACE may motivate the activity of HBV replication, and the combination of antiviral and TACE treatment for HBVR-HCC can effectively control HBV replication, and improve liver function without increase of side effects.

Abstract:Objective: To assess the efficacy of radiofrequency ablation (RFA) in the treatment of small hepatocellular carcinoma (HCC) and analyze the prognostic factors. Methods: The clinical data of 98 patients with small HCC undergoing RFA from January 2006 to June 2013 in Xiangya Hospital of Central South University were reviewed. The rate of local tumor progression, recurrence, and survival, as well as the factors affecting prognosis were analyzed. Results: The 98 patients were followed-up for 2 to 29 months, and their 1-, 3- and 5-year cumulative local tumor progression rate was 17.3%, 27.4% and 30.9%, 1-, 3- and 5-year cumulative intrahepatic distant recurrence rate was 25.7%, 62.1% and 77.3%, 1-, 2-, 3-, 4- and 5-year cumulative survival rate was 95.4%, 85.4%, 65.9%, 54.7% and 39.9%, and 1-, 2-, 3-, 4- and 5-year cumulative tumor-free survival rate was 74.0%, 52.7%, 45.0%, 37.0% and 25.3%, respectively. Multivariate analysis revealed that serum albumin≤35 g/L (P=0.001), time to first recurrence ≤1 year (P=0.002), and the first recurrence located in a different distant hepatic segment (P=0.004) were risk factors for the overall survival of the patients. Conclusion: RFA is safe and effective in treatment of small HCC, and is of high repeatability for early intrahepatic HCC recurrence. Low preoperative serum albumin level, short time interval to first recurrence, and first recurrence located in a different distant hepatic segment are important factors affecting the prognosis of the patients.

Abstract:Objective: To assess the value of ASA score in risk estimation for liver cancer patients undergoing surgical treatment. Methods: The perioperative clinical data of 419 patients undergoing hepatectomy for primary liver cancer from January 2006 to December 2010 were reviewed. The relationship between ASA score and clinical factors of the patients was analyzed, and the factors associated with postoperative complications and intraoperative blood transfusion were determined by multivariate regression analysis after univariate analysis screen for the possible related factors. Results: Statistical analysis showed that ASA score was affected by preoperative complications and hemoglobin content in liver cancer patients, and the intraoperative blood loss, blood transfusion volume, postoperative complications, and length of postoperative hospital stay was increased with ASA score increase (all P<0.05). Multivariate regression analysis identified that ASA score, intraoperative blood loss, liver cirrhosis, age, and alanine aminotransferase (ALT) level were independent factors for the occurrence of postoperative complications (all P<0.05), and ASA score, operative time, and tumor diameter were independent factors for intraoperative blood transfusion (all P<0.05). Conclusion: ASA score is a better index for early estimation of the perioperative risk of liver cancer patients undergoing hepatectomy.

Abstract:Objective: To investigate the influence of hepatitis B virus X protein (HBx) on the clock gene expression in normal hepatic cells. Methods: Human normal hepatic L02 cells were transfected with the HBx expression plasmid (pcDNA3.1-HBx) or empty vector plasmid (pcDNA3.1), respectively, then the HBx mRNA and protein expression in L02 cells was determined by RT-PCR method and Western blot analysis, respectively, and the mRNA expression of the clock genes that included CLOCK, BMAL1, Per1, Per2, Per3, Cry1, Cry2 and CKIε in L02 cells were detected by real-time PCR. Results: Results of RT-PCR and Western blot showed that both HBx mRNA and protein were obviously expressed in the L02 cells transfected with HBx expression plasmid, which were not seen in the L02 cells transfected with empty vector plasmid. Compared with L02 cells transfected with empty vector plasmid, the CLOCK and Cry1 mRNA expressions were remarkably increased while the mRNA expressions of BMAL1, Per1, Per2, Per3, Cry2 and CKIε were remarkably decreased in L02 cells transfected with empty vector plasmid, and all the differences had statistical significance (all P<0.05). Conclusion: HBx can change the expressions of clock genes in normal hepatic cells, which may disrupt circadian rhythm of liver cells, and this may be one of the mechanisms for the pathogenesis of liver cancer.

Abstract:Objective: To observe the influence of aquaporin 9 (AQP9) on migratory ability in liver cancer HepG2 cells through induction of its expression by oleic acid. Methods: In HepG2 cells following different treatment (treatment of 0, 250, and 500 μmol/L oleic acid, or treatment of AgNO3+500 μmol/L oleic acid), the AQP9 protein expression was determined by Western blot analysis and cellular migratory ability was measured by scratch assay, respectively. Results: After oleic acid treatment, the AQP9 protein expression was significantly up-regulated in HepG2 cells, and their migratory ability was significantly increased, which all presented a concentration-dependent manner (all P<0.05), while, these effects of oleic acid were abolished by pretreatment of the aquaporin inhibitor AgNO3. Conclusion: The migratory ability of liver cancer HepG2 cells is associated with the AQP9 expression, which is the higher the AQP9 expression, the stronger the migratory ability of the HepG2 cells.

Abstract:Objective: To investigate the Period1 expression in hepatocellular carcinoma (HCC) tissue and its significance. Methods: The Period1 mRNA and protein expressions in the specimens of 30 HCC tissues along with their adjacent liver tissues and 5 normal liver tissues were detected by RT-PCR method and Western blot analysis, and the methylation level in the promoter sequences of Period1 in HCC tissues and their adjacent liver tissues was determined by methylation-specific PCR. Period1 protein expression in 67 paraffin-embedded HCC tissue and adjacent liver tissue samples were examined by immunohistochemical staining, and the relations of Period1 expression with the clinicopathologic characteristics and prognosis of the patients were analyzed. Results: Both the Period1 mRNA and protein expressions in HCC tissue were significantly lower than those in the adjacent liver tissue or normal liver tissue (all P<0.05), but there was no statistical difference between the adjacent liver tissue and normal liver tissue (both P>0.05); the methylation level in the promoter sequences of Period1 in HCC tissue was significantly higher than that in the adjacent liver tissue (P<0.05); Period1 positive expression rate was 47.8% for HCC tissue and 83.6% for adjacent tissues in the paraffin-embedded samples, and the difference had statistical significance (P<0.05); Period1 expression was related to the degree of differentiation of HCC, tumor number, and vascular invasion (all P<0.05); the median time to recurrence and median survival time in HCC patients with negative Period1 expression were significantly reduced compared with those with positive Period1 expression (both P<0.05). Conclusion: Down-regulated Period1 expression may be closely related to the occurrence and development as well as invasion and metastasis of HCC, and promoter methylation is possibly an important mechanism for Period1 down-regulation.

Abstract:Objective: To investigate the influence of brain-derived neurotrophic factor (BDNF) on the chemosensitivity of human hepatocellular carcinoma Bel-7402 cells to fluorouracil (5-FU). Methods: Bel-7402 cells were treated with 5-FU alone (5-FU group) or 5-FU plus BDNF (5-FU+BDNF group) respectively, and the Bel-7402 cells without treatment served as control group. The cell growth and apoptosis were determined by MTT assay, colony formation assay, and flow cytometry respectively, and the bcl-2 mRNA expression in the cells was measured by RT-PCR method. Results: The OD value and number of colonies were significantly decreased, apoptosis rate was significantly increased, and bcl-2 mRNA expression was markedly down-regulated in the cells of 5-FU group, and all the differences had statistical significance compared with those of control group (all P<0.05); the changes in all of the above variables in cells of 5-FU+BDNF group were not evident, and the differences showed no statistical significance compared with those of control group (all P>0.05). Conclusion: BDNF can reduce the chemosensitivity of hepatocellular carcinoma Bel-7402 cells to 5-FU, and this effect may be associated with BDNF up-regulating the bcl-2 expression and thereby inhibiting cell apoptosis.

Abstract:Objective: To compare the transfection efficiency and cytotoxicity among Lipo2000 reagent, calcium phosphate method, and Lonza electroporation in transfection of hepatitis B virus X (HBx) gene expression plasmid (pHA-HBx) into the HepG2 cells. Methods: Green fluorescent protein (GFP)-tagged pHA-HBx was transfected into the HepG2 cells by Lipo2000 reagent, calcium phosphate method, and Lonza electroporation-based delivery, respectively. Then, the transfection efficiency was determined by flow cytometry and fluorescence microscopy, the HBx gene integration into the genome of the HepG2 cells was identified by RT-PCR method, and the cell survival status was examined and analyzed by Annexin V/PI staining, respectively. Results: RT-PCR results indicated that exogenous HBx gene was integrated into the genome and expressed in the HepG2 cells after either of the three transfection methods. The transfection efficiency of Lipo2000 reagent and Lonza electroporation-based delivery were higher than that of calcium phosphate method (both P<0.05), but it had no statistical difference between the first two methods (P>0.05). The high-to-low order of cell survival rate was Lonza electroporation, Lipo2000 reagent and calcium phosphate method, respectively (all P<0.05). Conclusion: Lonza electroporation for pHA-HBx transfection into HepG2 cells has high transfection efficiency and less cytotoxicity, so it is a relatively satisfactory transfection method.

Abstract:Objective: To investigate the effect of warm saline peritoneal lavage on acute necrotizing pancreatitis (ANP) in rats and its mechanism. Methods: Seventy-five SD rats were equally randomized into sham operation group, ANP model group (model group), and warm saline peritoneal lavage pretreatment plus ANP model group (pretreatment group). Rats were sacrificed at 6 h after surgery, and then serum concentration of amylase and cytokines were measured, the HSP70 and p38MAPK mRNA expressions in the pancreatic tissues were determined by RT-PCR, and the NF-κB expression in the pancreatic tissues was examined by immunohistochemical staining, respectively. Results: Compared with sham operation group, the serum levels of amylase, TNF-α, IL-6, and IL-8 were markedly increased in both model group and pretreatment group, but the increasing degrees of all the above parameters in pretreatment group were less than those in model group; the HSP70 and p38MAPK mRNA expressions in both model group and pretreatment group were remarkably increased, but the HSP70 mRNA expression level was higher while the p38MAPK mRNA expression level was lower in pretreatment group than that in model group, and all the above differences had statistical significance (all P<0.05). The pancreatic NF-κB showed weak-positive expression in sham operation group, strong-positive expression in model group, and moderate-positive expression in pretreatment group. Conclusion: Warm saline peritoneal lavage can improve the pathophysiological process of ANP, and the mechanism may be attributed to its inducing HSP70 expression which may inhibit the p38MAPK and NF-κB activities and reduce the expression of inflammatory cytokines.

Abstract:Objective: To assess the safety and efficacy of the application of fast-track surgery (FTS) in perioperative management of laparoscopic liver resection. Methods: The randomized controlled trials (RCTs) or clinical controlled trials (CCTs) concerning application of FTS in perioperative management of laparoscopic liver resection were collected by computer-based search of literature published between January 1966 and June 2014 from national and international databases. Meta-analysis was performed by using RevMan 5.2 software. Results: Three RCTs and 2 CCTs were finally included involving 247 patients, of whom 134 cases received FTS treatment (FTS group) and 113 cases received traditional perioperative care (control group). Results of Meta-analysis showed that the length of hospital stay was shortened and incidence of postoperative complications was reduced in FTS group compared with control group (WMD=-2.19, 95% CI=-2.94--1.43, P<0.00001; RR=0.60, 95% CI=0.38-0.92, P=0.02), while no statistical difference was noted in operative time, open conversion rate and hospitalization costs between the two groups (all P>0.05). Conclusion: Application of FTS in perioperative management of laparoscopic hepatectomy can reduce the length of hospital stay and incidence of complications and thereby accelerate postoperative recovery of the patients. However, the above results require further verification by more well-designed RCTs with large sample size and good quality.

Abstract:Objective: To evaluate the efficacy of radiofrequency ablation (RFA)-assisted hepatectomy in treatment of colorectal cancer liver metastases (CLM). Methods: The clinical data of 17 CLM patients undergoing open RFA-assisted hepatectomy were reviewed. The operative time, intraoperative blood loss, blood transfusion, and incidence of postoperative complications as well as the alterations in liver function and coagulation function of the patients before and after operation were analyzed. Results: Operations in all patients were successfully performed. The operative time was 55-237 min with an average of (93±19) min, and the intraoperative blood loss was 235-650 mL with an average of (280±40) mL. No blood transfusion was required in any of the patients during and after operation, and the abdominal drainage volume was 170-370 mL. Bile leakage occurred in one case (5.9%). The alanine transaminase (ALT) and aspartate aminotransferase (AST) levels of the patients were significantly elevated on postoperative 24 h and 72 h compared with their preoperative levels (all P<0.05), but both returned to their preoperative levels on postoperative 120 h, while the total bilirubin (TBIL) level and prothrombin time (PT) of the patients showed no significant alteration before and after operation (all P>0.05). Conclusion: RFA-assisted hepatectomy is safe and feasible for CLM, and it can also decrease the risk of bleeding.

Abstract:Objective: To investigate the safety and efficacy of laparoscopic approach in radical resection of colon cancer and simultaneous resection of liver metastases. Methods: Fifty patients with colon cancer and synchronous liver metastases admitted from March 2009 to April 2011 were selected, of whom 25 cases underwent laparoscopic radical resection of colon cancer and simultaneous resection of liver metastases (laparoscopic group) and another 25 cases were subjected to the traditional open surgery (laparotomy group). The intraoperative conditions, postoperative recovery, and postoperative 1-, 2- and 3-year survival rate between the two groups were compared. Results: The intraoperative blood loss, duration of postoperative analgesia, time to first flatus, length of hospital stay, and incidence of postoperative complications were significantly decreased in laparoscopic group compared with laparotomy group (all P<0.05), but no statistical difference was seen in operative time between the two groups (P>0.05). The postoperative 1-, 2- and 3-year survival rate in the two groups of patients had no statistical difference (all P>0.05). Conclusion: Totally laparoscopic resection of colon cancer and synchronous liver metastases is safe and effective, and can achieve the same clinical efficacy as open surgery. Meanwhile, it has the advantages of minimal invasiveness, fast postoperative recovery, and reduced complications.

Abstract:Liver transplantation, as the only effective treatment for end-stage liver disease, has since been well recognized. However, the availability of liver donors is far not enough to meet the needs at present. Use of liver from elderly donors (≥ 60 years) can partially alleviate the shortage of liver donors, but it remains controversial. In this paper, the authors address the relevant issues from the aspects of changes in liver of the elderly, current research status, and feasibility of liver transplantation with elderly donors.

Abstract:Obstructive jaundice can trigger an apoptosis program in hepatic cells and many factors are involved in the process of the occurrence of hepatic cell apoptosis during obstructive jaundice, and research into the mechanism may have great importance in prevention and treatment of the liver injury in obstructive jaundice. In this paper, the authors address the mechanism responsible for the occurrence of hepatic cell apoptosis during obstructive jaundice.

Abstract:Portal hypertension in our country is mainly intrahepatic portal hypertension caused by posthepatitic cirrhosis, and the clinical manifestations of the patients are closely related to the degree of elevation of portal pressure. The conditions of these patients are complicated and most cases need surgical treatment. The surgical approaches include devascularization, shunting and combined procedures, but many factors should be considered in surgical approach selection. Portal pressure is one of the important indicators that reflect the portal venous hemodynamics, and according to the intraoperative portal pressure, the proper surgical approach can be selected, and this is of great importance for achieving satisfactory results.