The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification.

BACKGROUND: There is currently no standard adjuvant treatment proven to prevent hepatocellular carcinoma (HCC) recurrence. Recent studies suggest that postoperative adjuvant transarterial chemoembolization (PA-TACE) is beneficial for patients at high risk of tumor recurrence. However, it is difficult to select the patients. The present study aimed to develop an easy-to-use score to identify these patients. METHODS: A total of 4530 patients undergoing liver resection were recruited. Independent risk factors were identified by Cox regression model in the training cohort and the Primary liver cancer big data transarterial chemoembolization (PDTE) scoring system was established. RESULTS: The scoring system was composed of ten risk factors including alpha-fetoprotein (AFP), albumin-bilirubin (ALBI) grade, operative bleeding loss, resection margin, tumor capsular, satellite nodules, tumor size and number, and microvascular and macrovascular invasion. Using 5 points as risk stratification, the patients with PA-TACE had higher recurrence-free survival (RFS) compared with non-TACE in > 5 points group (P < 0.001), whereas PA-TACE patients had lower RFS compared with non-TACE in ≤ 5 points group (P = 0.013). In the training and validation cohorts, the C-indexes of PDTE scoring system were 0.714 [standard errors (SE) = 0.010] and 0.716 (SE = 0.018), respectively. CONCLUSIONS: The model is a simple tool to identify PA-TACE for HCC patients after liver resection with a favorable performance. Patients with > 5 points may benefit from PA-TACE.

A proteomic analysis of transplanted liver in a rat model of chronic rejection.

BACKGROUND: Chronic rejection (CR) is an important cause of liver allograft failure. In the latter condition, re-transplantation of the liver (ReLT) is the only option for survival. Unfortunately, with the current state of knowledge, it is difficult to diagnose and treat early CR. OBJECTIVE: To explore the biomarkers of the chronic rejection in orthotopic liver transplantation (OLT). METHODS: A rat model of chronic liver allograft rejection was established, and the differential protein expression in chronic allograft rejection (CR) was analyzed by iTRAQ-MALDI-TOF/TOF. RESULTS: Expression of sixty-two proteins was found to be significantly changed in CR rats. In the present study, CLU, Lcn2 and Krt19 were identified and quantified as early and reliable biomarkers for chronic rejection. CONCLUSION: Analysis of differential protein expression by iTRAQ-MALDI-TOF/TOF is a potentially effective method to help understand the mechanism of CR in orthotopic liver transplantation. The proteins CLU, Lcn2 and Krt19 might be potential prognostic markers for predicting chronic rejection after liver transplantation.

[The effect of different hepatic vascular exclusion for massive hemorrhage in hepatectomy].

OBJECTIVE: To analyze the effect of different hepatic vascular exclusions for massive hemorrhage in hepatectomy. METHODS: The clinical data of 2238 cases with hepatectomy treated from January 1995 to August 2009 was analyzed retrospectively in the cause of massive hemorrhage (blood loss ≥ 1000 ml), blood loss during liver resection and massive hemorrhage incidence with different methods of hepatic vascular exclusion. RESULTS: Among 2238 cases received hepatectomy, 215 cases (9.6%) had massive hemorrhage because of portal vein tumor thrombus extraction (26.0%), extensive adhesions around the tumor (24.7%), section of liver hemorrhage (23.7%), hepatic vascular injury (15.8%), and tumor rupture (9.8%). Among 2182 cases received hepatectomy without portal vein tumor thrombus extraction, 159 cases (7.3%) had massive hemorrhage, 1257 cases (57.6%) which blood loss were less than 400 ml. Hepatectomy with different hepatic vascular exclusion methods had different blood loss and massive hemorrhage incidence. CONCLUSION: Pringle combined with clamping infrahepatic vena cava method and the liver double-hanging maneuver through the retrohepatic avascular tunnel on the right of the inferior vena cava method can reduce blood loss and massive hemorrhage incidence in hepatectomy more effectively, especially for huge liver tumor resection.

[Study on virtual liver surgery planning applied to hepatic resection].

OBJECTIVE: To evaluate the impact of preoperative three-dimensional visualization and virtual liver surgery planning on hepatic resection. METHODS: All relevant structures (livers, portal vein, hepatic veins, and tumors) were extracted from multislice CT scans of 142 cases treated from May 2007 to May 2009. By the liver surgery planning system software Liv 1.0, reconstruction and image analysis of the relevant structures was performed and virtual resections of liver were carried out. Data were correlated to intraoperative findings. RESULTS: (1) Three-dimensional visualization revealed the spatial relationship of tumors to the intrahepatic vascular system, thus giving impressions how the neoplasms were situated. Virtual tumor resections corresponded to the intraoperative findings. (2) With the planning, an intended resection could be performed virtually and optimal identification of resection margins could be achieved. The ischemia and congestion territory within the remaining liver parenchyma could be calculated. Simulation resections could avoid liver parenchyma over resection and maintain a sufficient amount of liver tissue to sustain hepatic function. Virtual simulations of tumor resection were used successfully to plan of surgical procedures in the hepatic tumors. Hepatectomy was performed in 29 cases after virtual tumor resections but seemed impossible with conventional CT scan. Resection plans of 92 cases were optimized after virtual resections. (3) The mean liver volume of patients with primary hepatocellular carcinoma measured by the software and the real resected was (477 +/- 223) ml and (451 +/- 209) ml respectively. Comparison by means of linear regression analysis between volume measurement on the software and the real resected showed a nearly ideal correlation coefficient (R = 0.922, P < 0.01). The mean error was 6.1%. CONCLUSIONS: The three-dimensional tumor visualization and virtual simulation of tumor resections of the software Liv 1.0 provide an important reference for a valuable planning of complex hepatic resections. It is not only benefit to improve the predictability and security of hepatectomy but also helpful to improve the success rate of complex hepatic resections.

Antisense RhoC gene suppresses proliferation and invasion capacity of human QBC939 cholangiocarcinoma cells.

BACKGROUND: Cholangiocarcinoma is a highly aggressive, fatal malignancy, which is resistant to all current therapeutic approaches. The recent elevation in the incidence of cholangiocarcinoma has highlighted the need for novel approaches targeting the molecular basis of its invasiveness. Previously we reconstructed a RhoC antisense eukaryotic expression vector and transfected it into a cholangiocarcinoma cell line (QBC939) by the lipofectamine method. This study was undertaken to determine the effect of the antisense RhoC gene on the proliferation and invasion capacity of QBC939. METHODS: Antisense RhoC cDNA was transfected into QBC939 with lipofectin 2000. The cell growth curve was constructed to determine the proliferation rate of cells; flow cytometry was used to analyze cell cycle changes of the tumor cells; and a Boyden chamber was used to assess the invasive ability of the cells before and after gene transfection. RESULTS: After the antisense RhoC cDNA was transfected, the number of colonies formed was significantly lower than that in the other two groups (54+/-8 vs. 91+/-11 vs. 90+/-9, P<0. 05) so was the number of the cells which crossed to the lower surface of the matrigel-coater filters (36+/-6 vs. 96+/-12 vs. 95+/-7, P<0.05). There was also a higher percentage of transfected cells in G1 phase than in the other two groups (52.5% vs. 43.4% vs. 43.7%). CONCLUSION: The antisense RhoC gene can suppress the capacities of proliferation and invasion in a cholangiocarcinoma cell line in vitro.

Down-regulation of the gax gene in smooth muscle cells of the splenic vein of portal hypertension patients.

BACKGROUND: The expression of gax, an anti-proliferative homeobox gene, is rapidly down-regulated in vascular smooth muscle cells (VSMCs) following arterial injury. Whether the down-regulation of gax is involved in modulating the proliferation of smooth muscle cells of the splenic vein in patients with portal hypertension has not yet been elucidated. The aim of this study was to investigate the expression of the mRNA of the gax gene in smooth muscle cells of the splenic vein in patients with portal hypertension. METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of gax mRNA and immunohistochemistry staining was performed to demonstrate the expression of PCNA protein in the splenic veins of 28 patients with portal hypertension and those of 12 normal controls. This study was approved by the Institutional Ethics Committee and informed consent was obtained from all participants. RESULTS: RT-PCR showed that the expression of gax mRNA was PCNA-positive and negative in the splenic vein of patients with portal hypertension (1.08+/-0.04 and 1.39+/-0.27, respectively). There was a significant difference in the 28 patients compared with the 12 normal controls (P<0.01). The relative expression of PCNA protein in the vascular tissues was significantly higher in the experimental group than in the control group. CONCLUSIONS: Down-regulation of gax mRNA and the overexpression of PCNA protein were seen in smooth muscle cells of the splenic vein in patients with portal hypertension, regulating the proliferation, migration and phenotypic change and resulting in remodelling of the splenic vein, which may play an important role in the pathogenesis and maintenance of portal hypertension.

[The study on correlation of c-myc gene expression with vascular smooth muscle cell proliferation in patients with portal hypertension].

OBJECTIVE: To investigate c-myc proto-oncogene expression and the relationship of PCNA protein expression of extrahepatic vascular smooth muscle cell in patients with portal hypertension and normal vessels. METHODS: RT-PCR was used to demonstrate the expression of c-myc mRNA and immuno-chemistry strain was performed to detect the expression of PCNA protein in splenic veins of 28 patients with portal hypertension and 12 normal vessels. RESULTS: The straining of PCNA protein was (29.8 +/- 4.7)% in splenic veins with portal hypertension, Normal vessels did not detect PCNA protein expression (P < 0.01); RT-PCR showed that the expression of c-myc mRNA in PCNA-positive control and in negative control of splenic veins with portal hypertension were (7.61 +/- 1.04)% and (3.82 +/- 0.92)%, respectively. There ws different between two groups (P < 0.01) and significant different (P < 0.01) when compared with (1.01 +/- 0.21)% in normal vessels. CONCLUSIONS: The c-myc was immediate-early gene when it modulated proliferation of vascular smooth muscle cell. Hemodynamic disturbance of portal vein system activate the proto-oncogene of smooth muscle cells in splenic vein of patients with portal hypertension, promoting the proliferation, migrating and phenotypic change and resulting in vascular remodelling of splenic veins.