Wu Mengchao

A prospective randomized controlled trial to compare Pringle maneuver, hemihepatic vascular inflow occlusion, and main portal vein inflow occlusion in partial hepatectomy

BACKGROUND blood loss during liver resection and the need for perioperative blood transfusions have negative impact on perioperative morbidity, mortality, and long-term outcomes. METHODS a randomized controlled trial was performed on patients undergoing liver resection comparing hemihepatic vascular inflow occlusion, main portal vein inflow occlusion, and Pringle maneuver. The primary endpoints were intraoperative blood loss and postoperative liver injury. The secondary outcomes were operating time, morbidity, and mortality. RESULTS a total of 180 patients were randomized into 3 groups according to the technique used for inflow occlusion during hepatectomy: the hemihepatic vascular inflow occlusion group (n = 60), the main portal vein inflow occlusion group (n = 60), and the Pringle maneuver group (n = 60). Only 1 patient in the hemihepatic vascular occlusion group required conversion to the Pringle maneuver because of technical difficulty. The Pringle maneuver group showed a significantly shorter operating time. There were no significant differences between the 3 groups in intraoperative blood loss and perioperative mortality. The degree of postoperative liver injury and complication rates were significantly higher in the Pringle maneuver group, resulting in a significantly longer hospital stay. CONCLUSIONS all 3 vascular inflow occlusion techniques were safe and efficacious in reducing blood loss. Patients subjected to hemihepatic vascular inflow occlusion, or main portal vein inflow occlusion responded better than those with Pringle maneuver in terms of earlier recovery of postoperative liver function. As hemihepatic vascular inflow occlusion was technically easier than main portal vein inflow occlusion, it is recommended.

Artemisinin inhibits in vitro and in vivo invasion and metastasis of human hepatocellular carcinoma cells

Artemisinin (ART) is isolated from the medicinal plant Artemisia annua L. To determine its effects on the invasion and metastasis of tumors, the human hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC-7721 were treated with different concentrations of ART. Starting at 12.5μM, ART had inhibitory effects in migration and invasion assays that increased at higher concentrations. The inhibitory effect also became stronger with time, from 24 to 72h. ART significantly inhibited the in vivo metastatic abilities of the HepG2 HCC cell line. ART inhibited the invasion and metastasis of HCC cells both in vitro and in vivo by reducing the level of the MMP2 metalloproteinase, and by inducing the TIMP2 protein. ART activated Cdc42, which enhanced E-cadherin activity, resulting in greater cell-cell adhesion, and significantly reduced metastasis.

The biopathologic characteristics of dna content of hepatocellular carcinomas

A gross morphologic classification of 66 small hepatocellular carcinomas (SHCC, ⩽3 cm in diameter) was made and DNA content of 30 SHCC and 26 large hepatocellular carcinomas (LHCC, >3 cm in diameter) was determined by image analysis technology. The three types of SHCC are as follows: type I, noncapsule type; type II, capsule type; and type III, infiltrative type. Of the SHCC, 73.3% had diploid DNA content, and 84.6% of LHCC had aneuploid DNA content. The postoperative 5‐year survival rate of patients with SHCC was 62.1%, which is higher than the rate of 27.7% of patients with LHCC. There was no correlation between tumor size and serum alpha‐fetoprotein (AFP) levels. The results suggest that the period when SHCC are 3 cm in size may be important as the changes of DNA stemlines and biological characteristics would occur then. The SHCC of <3 cm reflect relatively benign biological behavior of early hepatocellular carcinoma and this period is the best opportunity for the clinician to get the best prognosis. Currently determination of serum AFP is still one of the possible and effective methods to early finding SHCC.

Primary hepatocellular carcinoma in women of mainland china a clinicopathologic analysis of 104 patients

The clinicopathologic characteristics of 104 hepatectomy samples from female patients with primary hepatocellular carcinoma (PHC) were compared with similar samples from 900 male patients with primary hepatocellular carcinoma; results of this comparison were studied. The male‐to‐female ratio was 8.7:1. The mean age of female patients with PHC was 46.2 years, which was approximately 3 years younger (49.1 years) than that of male patients with PHC. The frequency of associated liver cirrhosis (LC) was 49% in women with PHC and 68.2% in men with PHC (P < 0.01). The mean age of the female patients without LC was 43.2 years, more than 4 years younger (47.9 years) than that of the male patients. The mean ages of female and male patients with LC were 49.1 years and 49.8 years, 6 and 2 years older than that of their corresponding groups without LC, respectively. The positive rates of serum hepatitis B surface antigen (HBsAg) were 70.8% in the men and 59.7% in the women. The 5‐year postoperative survival rates were 50% in the women and 25.7% in the men (P < 0.01). It is suggested that the development of PHC in women appears at a younger age than that of PHC in men in China and usually is associated with a lower frequency of LC and a more satisfactory postoperative prognosis.

Independent Factors and Predictive Score for Extrahepatic Metastasis of Hepatocellular Carcinoma Following Curative Hepatectomy

BACKGROUND Postoperative extrahepatic metastasis (EHM) contributes to a poor prognosis in patients with hepatocellular carcinoma (HCC) after hepatectomy. This study was aimed to develop a practical method that can be used to predict postoperative EHM. METHODS In total, 578 patients were enrolled. We analyzed the clinicopathological features of the tumors and did a long-term follow-up to observe HCC recurrence. Postoperative EHM was detected in 136 patients, and multivariate analysis was used to confirm independent risk factors for postoperative EHM. After the factors were identified, a predictive scoring system was constructed as a weighted sum of these factors. The cutoff value that determines a high risk for EHM was defined by maximizing the Youdens index of the receiver operating characteristic curve. RESULTS Microvascular invasion, incomplete capsule, and larger tumor diameter were the three independent factors predictive for a high risk for EHM. The scoring system was derived with an area under the curve (AUC) of 0.81 for postoperative 10-year EHM prediction. A cutoff value of 43 was derived and validated with a sensitivity >90% and specificity >60% to predict the development of EHM. This system was further verified in a subgroup of Barcelona Clinic Liver Cancer stage 0-A patients with an AUC of 0.82. When the cutoff value was set at 43, the sensitivity and specificity were 90.38% and 64.88%, respectively. CONCLUSIONS Our predictive scoring system may be used to identify HCC patients who have a high risk for EHM following curative hepatectomy.

Enucleation of liver hemangiomas: is there a difference in surgical outcomes for centrally or peripherally located lesions?

BACKGROUND Partial hepatectomy for centrally located liver lesions is technically more challenging than that for peripheral lesions. Enucleation of liver hemangiomas is easier and safer than partial hepatectomy. Whether enucleation gives the same surgical outcomes for both centrally and peripherally located hemangiomas is unknown. This study aimed to evaluate the difference in surgical outcomes of enucleation of centrally and peripherally located liver hemangiomas. METHODS This study used a prospectively maintained database consisting of a consecutive series of patients who underwent enucleation of liver hemangiomas in a tertiary referral center from January 2004 to December 2006. Surgical variables, length of hospital stay, and postsurgical complications were compared between centrally and peripherally located liver hemangiomas. RESULTS During the study period, 172 patients underwent enucleation of hepatic hemangiomas. The lesions were centrally located in 76 patients (44.2%) and peripherally located in 96 patients (55.8%). The 2 groups were comparable in demographic data and lesion characteristics. There was no hospital mortality. The major complication rates were low in both groups (2.6% vs. 3.1%; P = .848). Enucleation of centrally located liver hemangiomas required significantly longer vascular inflow occlusion time (P <.001), longer operating time (P <.001), and more blood transfusion (P = .001). This group also had a higher volume of blood loss (P = .004) and longer hospital stay (P = .024) than the group with peripherally located liver hemangiomas. CONCLUSIONS Enucleation is a safe surgery for hemangiomas in any part of the liver, although it is technically more demanding for centrally than peripherally located hemangiomas.

Knockdown of HBV surface antigen gene expression by a lentiviral microRNA-based system inhibits HBV replication and HCC growth.

Summary.  Current options for the treatment of hepatitis B virus (HBV) infections, a common liver cancer risk factor, are limited. While RNA interference (RNAi) technologies have been shown to inhibit HBV replication, the consequent effects on hepatocellular carcinoma (HCC) cell growth are not fully understood. The aim of this study was to evaluate the effect of RNAi‐mediated decrease in the HBV surface antigen (HBsAg) gene on HBV replication and HCC growth. A lentiviral microRNA‐based system expressing siRNAs targeting the HBsAg gene (LVshHBS) was developed and transfected into HepG2.2.15 cells (HBV stably expressing line). We found that LVshHBS significantly inhibited the HBsAg mRNA and protein levels in the HepG2.2.15 cells, while HBsAg secretion into the culture supernatant decreased by 70%. BALB/c (nu/nu) mice were injected with HepG2.2.15 cells transduced with LVshHBS or control vectors to investigate the effect of inhibiting the HBsAg on the development of tumour growth in a human HCC nude mice model. Compared with the control, the tumour growth in nude mice was significantly decreased after injection with LVshHBS. Microarray analysis of tumour‐related genes in LVshHBS‐transduced HepG2.2.15 cells showed that the expressions of genes involved in cell cycle, differentiation and oncogenesis such as ACP2, BHLHB2, CLK3, CTSC, FOS, NR1D1, PIM1 and SEPT6 genes were downregulated, while that of the E2F3 gene was upregulated. In conclusion, lentiviral microRNA‐based RNAi against the HBsAg gene not only inhibits HBV replication but also inhibits the growth of HCC. Downregulation of growth‐related genes is implicated in this mechanism of inhibition.

An in vivo rat model for assessment of extrahepatic metabolism

INTRODUCTION Xenobiotic metabolism in extrahepatic tissues has been extensively studied in vitro, but it is difficult to estimate in vivo the share of xenobiotic transformation in extrahepatic tissues for lack of a suitable approach. In this paper an in vivo rat model for assessment of extrahepatic metabolism is described, and the model was investigated using the conversion of lidocaine to monoethylglycinexylidide (MEGX). METHODS The rats were anesthetized with ethyl ether inhalation. The liver was exposed, the liver artery ligated, and the portal vein was clamped at its distal end. The left hepatic lobe was partly excised along its inferior margin, and a heparinized silicone catheter, diameter 0.2 cm, was inserted into the portal and left hepatic veins to allow the recirculation of portal vein blood. A sham operation was performed in the control group. RESULTS Phenol red test showed that hepatic blood supply was absolutely blocked in model rats. At 30 min after establishing the portal-cavum bypass, the renal function and electrolytes did not change, but serum glucose decreased by 64.4 +/- 30.4%; 30 min after intravenous administration of 1.0% lidocaine 2 mg x kg(-1), serum MEGX in model rats was 32.0 +/- 7.14% of that in the control group, which mostly existed in a free form and was not induced by phenobarbital pretreatment. DISCUSSION The model is easy to establish and provides an in vivo method to study the extrahepatic metabolism of xenobiotics.

Pringle manoeuvre versus selective hepatic vascular exclusion in partial hepatectomy for tumours adjacent to the hepatocaval junction: a randomized comparative study.

OBJECTIVE To compare the efficacy of selective hepatic vascular exclusion versus Pringle manoeuvre in partial hepatectomy for tumours adjacent to the hepatocaval junction. METHODS A randomized comparative trial was carried out. The primary endpoint was intraoperative blood loss. The secondary endpoints were operation time, blood transfusion, postoperative liver function recovery, procedure-related morbidity and in-hospital mortality. RESULTS 160 patients were randomized into 2 groups: the Pringle manoeuvre group (n = 80) and the selective hepatic vascular exclusion (SHVE) group (n = 80). Intraoperative blood loss and transfusion requirements were significantly less in the SHVE group. In the SHVE group, laceration of hepatic veins happened in 18 patients. Profuse intraoperative blood loss of over 2 L happened in 2 patients but no patient suffered from air embolism because the hepatic veins were controlled. In the Pringle group, the hepatic veins were lacerated in 20 patients, with profuse blood loss of over 2 L in 7 patients and air embolism in 3 patients. The rates of postoperative bleeding, reoperation, liver failure and mortality were significantly higher and the ICU stay and hospital stay were significantly longer in the Pringle group. CONCLUSIONS SHVE was more efficacious than Pringle manoeuvre for partial hepatectomy in patients with tumours adjacent to the hepatocaval junction.

Role of Antivirus Therapy in Treatment of Hepatocellular Carcinoma with Chronic Hepatitis B Infection

AbstractObjective: To observe the recurrence and prognosis of hepatocellular carcinoma (HCC) patients coexisting with chronic hepatitis B infection with active virus replication after receiving antivirus therapy using lamivudine and thymosin α1 (Tα1) postoperatively. Methods: From Jan. 2000 to Dec. 2003, 70 patients with HCC coexisting chronic hepatitis B infection with active virus replication were prospectively divided into two groups: control group (n=35) received hepatectomy only; treatment group (n=35) received hepatectomy and lamivudine plus Tα1 therapy postoperatively. The suppression of HBV-DNA, HBeAg seroconverted rate, tumor recurrent rate and the median survival for the two groups were observed and calculated. Results: In treatment group and control group, the 2-year HBV-DNA suppression rate was 100% vs. 4% (P=0.0000); HBeAg seroconverted rate was 73.0% vs. 7.5% (P<0.05); the recurrent rate was 10.0 vs 6.5 months (P=0.0032); the median survival time was 12.5 vs. 6.0 months (P=0.0023), respectively. Conclusion: Antivirus therapy using lamivudine and Tα1 postoperatively may suppress the HBV reaction, delay the recurrent time and prolong the survival for HCC patients coexisting chronic HBV infection with active virus replication.