Si-yuan Fu

A prospective, randomized, controlled trial of preoperative transarterial chemoembolization for resectable large hepatocellular carcinoma.

Objective:To evaluate the effect of preoperative transarterial chemoembolization (TACE) for resectable large hepatocellular carcinoma (HCC). Summary Background Data:Resection of HCC is potentially curative, but local recurrence is very common. There is currently no effective neoadjuvant or adjuvant therapy. Methods:From July 2001 to December 2003, 108 patients (hepatitis B carrier = 98.1%) with resectable HCC (≥5 cm) was randomly assigned to preoperative TACE treatment (n = 52) or no preoperative treatment (control group) (n = 56). Results:Five patients (9.6%) in the preoperative TACE group did not receive surgical therapy because of extrahepatic metastasis or liver failure. The preoperative TACE group had a lower resection rate (n = 47, 90.4% vs. n = 56, 100%; P= 0.017), and longer operative time (mean, 176.5 minutes vs. 149.3 minutes; P= 0.042). No significant difference was found between the 2 groups in operative blood loss, surgical morbidity, and hospital mortality. At a median follow-up of 57 months, 41 (78.8%) of 52 patients in the preoperative TACE group and 51 (91.1%) of 56 patients in the control group had recurrent disease (P= 0.087). The 1-, 3-, and 5-year disease-free survival rates were 48.9%, 25.5%, and 12.8%, respectively, for the preoperative TACE group and 39.2%, 21.4%, and 8.9%, respectively, for the control group (P= 0.372). The 1-, 3-, and 5-year overall survival rates were 73.1%, 40.4%, and 30.7%, respectively, for the preoperative TACE group and 69.6%, 32.1%, and 21.1%, respectively, for the control group (P= 0.679). Conclusions:Preoperative TACE did not improve surgical outcome. It resulted in drop-out from definitive surgery because of progression of disease and liver failure.

Roles of Chemokine Receptor 4 (CXCR4) and Chemokine Ligand 12 (CXCL12) in Metastasis of Hepatocellular Carcinoma Cells

Chemokines are involved in human hepatocellular carcinoma (HCC) carcinogenesis. However, the exact mechanism of chemokines in HCC carcinogenesis remains unknown. Here we investigated the roles of chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) in the metastasis of HCC. We found that the expression levels of CXCR4 mRNA in HCC tissues, MHCC97 cells, and HUVEC cells were 2.52 ± 1.13, 2.34 ± 1.16 and 1.63 ± 1.26, respectively and that the CXCR4 protein levels were 1.38 ± 0.13, 1.96 ± 0.32 and 1.86 ± 0.21, respectively. In contrast, CXCR4 was not detected in normal hepatic tissues. In 78 HCC patients, we also found that the concentration of CXCL12 in cancerous ascitic fluid was 783-8,364 pg/ml and that CXCL12 mRNA level in HCC metastasis portal lymph nodes was 1.21 ± 0.87 but undetectable in normal hepatic tissues. Finally we discovered that recombinant human CXCL12 could induce MHCC97 cells and HUVEC cells to migrate with chemotactic indexes (CI) of 3.9 ± 1.1 and 4.1 ± 1.6, respectively. Cancerous ascetic fluid could also induce the migration of MHCC97 cells with a CI of 1.9 ± 0.8. Thus, our data suggest that CXCR4 and CXCL12 may play an important role in the metastasis of HCC by promoting the migration of tumor cells.

Posthepatectomy HBV reactivation in hepatitis B-related hepatocellular carcinoma influences postoperative survival in patients with preoperative low HBV-DNA levels.

Objective: This study aimed to clarify the incidence of hepatitis B virus (HBV) reactivation and its significance on long-term survival after partial hepatectomy in patients with HBV-related hepatocellular carcinoma (HCC), who had preoperative low HBV-DNA level of less than 2000 IU/mL. Background: HBV reactivation is a frequent complication of systemic chemotherapy in hepatitis B surface antigen–positive patients. Surgery and anesthesia result in a generalized state of immunosuppression in the immediate postoperative period. Data on HBV reactivation and its significance after partial hepatectomy are unclear. Patients and Methods: Consecutive patients from January 2006 to December 2007 were retrospectively studied. Results: HBV reactivation happened in 19.1% of patients in 1 year. There were 28 patients whose HBV reactivation was detected after the diagnosis of HCC recurrence. On multivariate analysis, hepatitis B e antigen (HBeAg) positivity, preoperative HBV-DNA above the lower limit of quantification (≥200 IU/mL), Ishak inflammation score of greater than 3, preoperative transarterial chemoembolization (TACE), operation time of more than 180 minutes, blood transfusion, and without prophylactic antiviral therapy were significantly associated with an increased risk of HBV reactivation. HBV reactivation negatively influenced postoperative hepatic functions. The posthepatectomy liver failure rate in patients with HBV reactivation was significantly higher than in those without reactivation (11.8% vs 6.4%; P = 0.002). The 3-year disease-free survival (DFS) rate and overall survival (OS) rates after resection in patients with HBV reactivation were significantly lower than those without reactivation (34.1% vs 46.0%; P = 0.009, and 51.6% vs 67.2%; P < 0.001, respectively). HBeAg positivity, detectable preoperative HBV-DNA level, high Ishak inflammation score, preoperative TACE, long operation time, and blood transfusion were independent risk factors for HBV reactivation, whereas prophylactic antiviral therapy was a protective factor. HBV reactivation, HBeAg positivity, HBV-DNA level of 200 IU/mL or more, tumor diameter greater than 5 cm, presence of satellite nodules, presence of portal vein tumor thrombus, blood transfusion, and resection margin less than 1.0 cm were independent risk factors for DFS. A HBV-DNA level of 200 IU/mL or more, an Ishak fibrosis score of 4 or greater, a tumor diameter greater than 5 cm, the presence of satellite nodules, the presence of portal vein tumor thrombus, a resection margin less than 1.0 cm, no prophylactic antiviral therapy, and HBV reactivation were independent risk factors for OS. Conclusions: HBV reactivation was common after partial hepatectomy for HBV-related HCC with a preoperative low HBV-DNA level of less than 2000 IU/mL. Routine prophylactic antiviral treatment should be given before partial hepatectomy.

Randomized clinical trial of chemoembolization plus radiofrequency ablation versus partial hepatectomy for hepatocellular carcinoma within the Milan criteria

This study aimed to compare sequential treatment by transcatheter arterial chemoembolization (TACE) and percutaneous radiofrequency ablation (RFA) with partial hepatectomy for hepatocellular carcinoma (HCC) within the Milan criteria.

Liver resection under total vascular exclusion with or without preceding Pringle manoeuvre

Adequate control of bleeding is crucial during liver resection. This study analysed the safety and efficacy of hepatectomy under total hepatic vascular exclusion (THVE) in patients with tumours encroaching or infiltrating the hepatic veins and/or the inferior vena cava (IVC).

Liver resection with selective hepatic vascular exclusion: a cohort study.

Objective:To report our experience on the safety and efficacy of hepatic resection under selective hepatic vascular exclusion (SHVE). Methods:SHVE was used in 246 consecutive patients undergoing major or complex liver resection in our center. Preoperative demographic and clinical data, details of the surgical procedure, pathologic diagnosis, postoperative course, and complications were collected prospectively. Results:From January 2000 to July 2007, liver resections were performed under SHVE in 246 patients; total SHVE, right partial SHVE, and left partial SHVE in 145, 54, and 47 patients, respectively. SHVE was converted to total hepatic vascular exclusion in 3 patients because the tumor invaded the wall of the inferior vena cava. Hemodynamic tolerance to SHVE was excellent, with only a slight increase in systemic and pulmonary vascular resistance during clamping. There were no deaths and the morbidity rate was 24.8%. The mean hospital stay was 9.6 days (range, 8–18). Conclusion:Our study showed that SHVE was safe, efficacious, and it was applicable to liver tumors which were near, but had not invaded into the inferior vena cava.

A prospective randomized controlled trial to compare two methods of selective hepatic vascular exclusion in partial hepatectomy

BACKGROUND AND AIM Selective hepatic vascular exclusion (SHVE) has not been widely used because of difficulty in extrahepatic isolation of hepatic veins. This study aims to compare the results of SHVE using tourniquets or Satinsky clamps on major hepatic veins in partial hepatectomy for liver tumors involving the roots of hepatic veins. METHODS Between June 2008 and March 2012, a randomized controlled trial was performed on patients undergoing liver resection to compare selective hepatic vascular exclusion using tourniquets or Satinsky clamps in partial hepatectomy. In the tourniquet group, the hepatic veins were completely isolated and occluded with tourniquets. In the Satinsky clamp group, the hepatic veins were dissected on the anterior and side walls only and they were clamped directly by Satinsky clamps. RESULTS The time for dissecting hepatic veins was significantly shorter in the Satinsky clamp group (7.5 ± 6.6 min vs 21.3 ± 7.4 min) than the tourniquet group. In the tourniquet group, 5 hepatic veins could not be completely isolated and encircled. In 4 additional patients the hepatic vein was slightly torn during dissection. These 9 patients received successful occlusion using Satinsky clamps. In the Satinsky group, all occlusion of the hepatic vein was successful. There was a significant difference in the success rate in hepatic vein occlusion using the Satinsky and the tourniquet groups 60/60 vs 51/60, P = 0.0018. CONCLUSIONS Both techniques of hepatic vein occlusion were safe and efficacious. As the use of Satinsky clamps is safer, easier and took less time, it is recommended.

Selective hepatic vascular exclusion versus Pringle manoeuvre in liver resection for tumours encroaching on major hepatic veins.

Control of bleeding is crucial during liver resection, and several techniques have been developed to achieve this. This study compared the safety and efficacy of selective hepatic vascular exclusion (SHVE) and Pringle manoeuvre in partial hepatectomy for liver tumours compressing or involving major hepatic veins.

Diagnostic difficulties and treatment strategy of hepatic angiomyolipoma.

OBJECTIVE Based on a large series of histopathologically confirmed hepatic angiomyolipomas, we retrospectively studied the typical diagnostic features of hepatic angiomyolipoma and proposed a treatment strategy for this disease. MATERIALS AND METHODS From December 1997 to December 2007, 74 consecutive patients who received definitive treatment for hepatic angiomyolipoma, at a single tertiary center, were studied. RESULTS There was a marked female predominance (54 females vs. 20 males) and the mean age was 42 years. Forty patients had no symptoms and the tumors were detected incidentally during a medical check-up. From this study, we proposed the typical diagnostic features of hepatic angiomyolipoma to be the absence of risk factors for malignancy, normal tumor marker levels, and typical imaging features on ultrasound (USG), abdominal contrast computed tomography (CT), or magnetic resonance imaging (MRI). Only 23% of patients could have been diagnosed before surgery using these features. One patient (1.4%) had a malignant angiomyolipoma, and died with distant metastases 14 months after surgery. After a median follow-up of 64 months, there was no recurrence in the other 73 patients. CONCLUSION Patients with typical diagnostic features suggestive of hepatic angiomyolipoma could be observed with regular surveillance. Definitive treatment should be performed when the tumor has symptoms/complications, when the tumor is enlarging, or when a malignant lesion cannot be ruled out.

eIF5B increases ASAP1 expression to promote HCC proliferation and invasion

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Despite the therapeutic advances that have been achieved during the past decade, the molecular pathogenesis underlying HCC remains poorly understood. In this study, we discovered that increased expression eukaryotic translation initiation factor 5B (eIF5B) was significantly correlated with aggressive characteristics and associated with shorter recurrence-free survival (RFS) and overall survival (OS) in a large cohort. We also found that eIF5B promoted HCC cell proliferation and migration in vitro and in vivo partly through increasing ASAP1 expression. Our findings strongly suggested that eIF5B could promote HCC progression and be considered a prognostic biomarker for HCC.