Kuansheng Ma

A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma

BACKGROUND & AIMSnThe aim of this study was to compare the efficacy of radiofrequency ablation (RFA) with surgical resection (RES) in the treatment of small hepatocellular carcinoma (HCC).nnnMETHODSnA total of 168 patients with small HCC with nodular diameters of less than 4 cm and up to two nodules were randomly divided into RES (n=84) and RFA groups (n=84). Outcomes were carefully monitored and evaluated during the 3-year follow-up period.nnnRESULTSnThe 1-, 2-, and 3-year survival rates for the RES and RFA groups were 96.0%, 87.6%, 74.8% and 93.1%, 83.1%, 67.2%, respectively. The corresponding recurrence-free survival rates for the two groups were 90.6%, 76.7%, 61.1% and 86.2%, 66.6%, 49.6%, respectively. There were no statistically significant differences between the two groups in overall survival rate (p=0.342) or recurrence-free survival rate (p=0.122). Multivariate analysis demonstrated that the independent risk factors associated with survival were multiple occurrences of tumors at different hepatic locations (relative risk of 2.696; 95% CI: 1.189-6.117; p=0.018) and preoperative indocyanine green retention rate at 15 min (ICG-15) (relative risk of 3.853; 95% CI: 1.647-9.015; p=0.002).nnnCONCLUSIONSnIn patients with small hepatocellular carcinomas, percutaneous RFA may provide therapeutic effects similar to those of RES. However, percutaneous RFA is more likely to be incomplete for the treatment of small HCCs located at specific sites of the liver, and open or laparoscopic surgery may be the better choice.

Increased liver-infiltrating CD8+FoxP3+ regulatory T cells are associated with tumor stage in hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, and patients who are diagnosed with this tumor typically have a poor prognosis. The suppressive effects of CD4(+)FoxP3(+) regulatory T cells on antitumor immune response in HCC have been studied in great detail. CD8(+)FoxP3(+) regulatory T cells have recently been detected in tumors; however, the role of CD8(+)FoxP3(+) regulatory T cells in HCC is still unknown. Here, the frequency and phenotype of CD8(+)FoxP3(+) regulatory T cells were analyzed by multicolor flow cytometry in liver of HCC patients and healthy donors. We observed that the percentage of these cells in HCC patients was significantly higher than that observed in healthy control donors (p = 0.0155); their phenotype was close to that of CD4(+) regulatory T cells. Furthermore, we show that CD8(+)FoxP3(+) regulatory T cells are activated and act as effector memory cells (EM, CD45RA(-)CCR7(-)CD27(+/-)CD28(+)). Most importantly, a higher percentage of intrahepatic CD8(+)FoxP3(+) regulatory T cells was found in patients with advanced HCC than in those with early HCC in terms of tumor-node-metastasis (TNM) stage (stage I vs III, p = 0.0007). These data suggest that CD8(+)FoxP3(+) regulatory T cells may contribute to HCC immune escape and disease progression.

High Serum Hyaluronic Acid and HBV Viral Load are Main Prognostic Factors of Local Recurrence after Complete Radiofrequency Ablation of Hepatitis B-Related Small Hepatocellular Carcinoma

PurposeThe risk factors of local recurrence after complete radiofrequency ablation (RFA) of hepatitis B-related small hepatocellular carcinoma (HCC), ≤3xa0cm, remains to be clarified. In this study, we evaluated the potential prognostic factors that affect recurrence.MethodsA total of 152 consecutive patients with small HCC who had undergone complete RFA were retrospectively studied. The risk factors of local recurrence and their impact on survivals of patients were analyzed.ResultsAfter a median follow-up of 35xa0months, intrahepatic recurrence occurred in 67 patients (44.1%). On univariate analysis, HBV DNA, hyaluronic acid, AFP, MELD score, and precollagen III were independent risk factors for recurrence. On multivariate analysis, HBV DNA and hyaluronic acid were independent risk factors for recurrence. The cumulative 1-, 3-, and 5-year disease-free survival rates were 86.8%, 41.2%, and 22.8% in the high viral load group and 96.4%, 65.8%, and 36.7% in the low viral load group, respectively. The difference between the two groups was significant (Pxa0=xa00.003). The cumulative 1-, 3-, and 5-year disease-free survival rates were 87.2%, 42%, and 27.2% in the abnormal hyaluronic acid group and 94.9%, 63.5%, and 33.9% in the normal group, respectively. The difference between the two groups also was significant (Pxa0=xa00.011). Multivariate analysis identified MELD score as the only independent risk factor for overall survival of all patients.ConclusionsHigh serum hyaluronic acid and HBV viral load are main prognostic factors of local recurrence after complete radiofrequency ablation of hepatitis B-related small HCC.The risk factors of local recurrence after complete radiofrequency ablation (RFA) of hepatitis B-related small hepatocellular carcinoma (HCC), ≤3xa0cm, remains to be clarified. In this study, we evaluated the potential prognostic factors that affect recurrence. A total of 152 consecutive patients with small HCC who had undergone complete RFA were retrospectively studied. The risk factors of local recurrence and their impact on survivals of patients were analyzed. After a median follow-up of 35xa0months, intrahepatic recurrence occurred in 67 patients (44.1%). On univariate analysis, HBV DNA, hyaluronic acid, AFP, MELD score, and precollagen III were independent risk factors for recurrence. On multivariate analysis, HBV DNA and hyaluronic acid were independent risk factors for recurrence. The cumulative 1-, 3-, and 5-year disease-free survival rates were 86.8%, 41.2%, and 22.8% in the high viral load group and 96.4%, 65.8%, and 36.7% in the low viral load group, respectively. The difference between the two groups was significant (Pxa0=xa00.003). The cumulative 1-, 3-, and 5-year disease-free survival rates were 87.2%, 42%, and 27.2% in the abnormal hyaluronic acid group and 94.9%, 63.5%, and 33.9% in the normal group, respectively. The difference between the two groups also was significant (Pxa0=xa00.011). Multivariate analysis identified MELD score as the only independent risk factor for overall survival of all patients. High serum hyaluronic acid and HBV viral load are main prognostic factors of local recurrence after complete radiofrequency ablation of hepatitis B-related small HCC.

Dynamic enhancing vascular pattern of intrahepatic peripheral cholangiocarcinoma on contrast-enhanced ultrasound: the influence of chronic hepatitis and cirrhosis

PurposeTo analyse the dynamic enhancing features by real-time contrast-enhanced ultrasound (CEUS) of intrahepatic peripheral cholangiocarcinoma (ICC) in patients with chronic hepatitis and cirrhosis.Materials and methodsCEUS was performed by using contrast pulse sequencing (CPS) imaging with mechanical index of <0.2 after injection of 2.4xa0mL of contrast agent. CEUS images of histologically confirmed ICC in 54 patents (15 patents with chronic hepatitis B, 16 patents with cirrhosis, and 23 patents with normal underlying liver) were analyzed.ResultsHeterogeneous hyperenhancement was more frequently identified in ICC with chronic hepatitis (9 of 15, 60.0%, pxa0=xa00.000) and cirrhosis (8 of 16, 50.0%, pxa0=xa00.010) than in patients with normal liver (6 of 23, 26.1%) during arterial phase. The majority of ICC in patients with normal liver displayed peripheral hyperenhancement (13 of 23, 56.5%), than in patients with chronic hepatitis (4 of 15, 26.7%, pxa0=xa00.000) and cirrhosis (5 of 16, 31.3%, pxa0=xa00.001). Intense contrast uptake during the arterial phase (heterogeneous hyperenhancement or global hyperenhancement) followed by washout in venous phases was more frequently displayed in ICC patients with chronic hepatitis (11 of 15, 73.3%, pxa0=xa00.000) and in patients with cirrhosis (11 of 16, 68.8%, pxa0=xa00.000) than in ICC patients with normal underlying liver (8 of 23, 34.8%).ConclusionThe enhancing vascular pattern of ICC on CEUS in patients with chronic hepatitis and cirrhosis is different from that in ICC without underlying liver disease. The enhancing vascular pattern is indistinguishable from HCC on CEUS in most ICC patients with chronic hepatitis or cirrhosis.

Randomized clinical trial of splenic radiofrequency ablation versus splenectomy for severe hypersplenism

Radiofrequency ablation (RFA) is a relatively new treatment for hypersplenism. The results of a randomized clinical trial comparing RFA and splenectomy with 5 years of follow‐up are reported.

The Use of Saline-Linked Radiofrequency Dissecting Sealer for Liver Transection in Patients With Cirrhosis

BACKGROUNDnIn patients with cirrhosis excessive hemorrhage and the need for blood transfusion are associated with increased postoperative morbidity and mortality as well as a poor long-term outcome. Saline-linked radiofrequency dissecting sealer (TissueLink) is a recent advance in technology that improves hemostasis during difficult liver resections. Preliminary studies have shown that this technique reduces blood loss without inflow occlusion.nnnPATIENTS AND METHODSnA controlled study was performed on 122 consecutive patients with cirrhosis who underwent liver resection for hepatocytotic carcinoma. The outcomes of liver transection with clamp crushing and TissueLink were compared to evaluate which strategy is most beneficial to the patients.nnnRESULTSnBoth intraoperative blood loss and blood transfusion requirements were significantly higher in the crushing clamp group than in the TissueLink group (P = 0.047 and P = 0.031, respectively). In addition, a significantly higher number of patients required a blood transfusion in the crushing clamp group (P < 0.001). However, the transection time was significantly faster in the crushing clamp group than in the TissueLink group (P < 0.001). The number of patients that required Pringles maneuver was markedly higher in the crushing clamp group (P < 0.001). In addition, the hemostasis time was significantly longer in the crushing clamp group (P < 0.001). The serum aspartate aminotransferase levels 3 and 7 days after surgery were significantly higher in the crushing clamp group than in the TissueLink group (P = 0.035 and P = 0.003, respectively). Serum total bilirubin levels were markedly increased 3 days after surgery in the crushing clamp group than in the TissueLink group (P = 0.011). Biliary leakage occurred in a higher number of crushing clamp patients (six) than TissueLink patients (three), although this difference was not significant. The operative morbidity not including biliary leakage was higher in the crushing clamp group than the TissueLink group (nine patients versus five patients, respectively).nnnCONCLUSIONnThis study reveals that the TissueLink procedure has beneficial effects during liver transection under cirrhotic conditions in terms of blood loss and reperfusion-related liver injury. However, this procedure requires a significantly longer transection time of the parenchyma.

Surgical Treatment of Giant Liver Hemangiomas: Enucleation with Continuous Occlusion of Hepatic Artery Proper and Intermittent Pringle Maneuver

BackgroundThe present study was designed to investigate the efficacy and safety of continuous occlusion of the hepatic artery proper combined with intermittent use of the Pringle maneuver for reduction of blood loss during enucleation of giant liver hemangiomas.MethodsA retrospective study was performed on 115 patients who underwent enucleation of giant liver hemangiomas with or without continuous occlusion of the hepatic artery proper at a tertiary care university hospital. The characteristics of patients and perioperative parameters including intraoperative blood loss, the degree of ischemia–reperfusion injury, the incidence and severity of postoperative complications, and the length of hospital stay were summarized and compared in the two groups.ResultsSeventy-three and 42 patients underwent enucleation of hepatic hemangiomas with and without continuous occlusion of the hepatic artery proper, respectively. The Pringle maneuver was routinely used in all patients in cycles of 15/5xa0min of clamp/unclamp times. Patient characteristics were comparable between the two groups. Intraoperative blood loss and blood transfusion in the continuous occlusion group were significantly lower than in the non-occlusion group (Pxa0<xa00.001 and Pxa0=xa00.012, respectively). In a comparison of the two groups, there were no significant differences in the changes of the perioperative serum aspartate transaminase and total bilirubin levels (Pxa0=xa00.086, Pxa0=xa00.829, respectively), and in the postoperative hospital stay and surgical complications according to Clavien’s classification (Pxa0=xa00.378, Pxa0=xa00.227, respectively).ConclusionsContinuous occlusion of the hepatic artery proper when added to intermittent use of the Pringle maneuver significantly reduced intraoperative blood loss when compared with intermittent Pringle maneuver alone. Enucleation of giant hepatic hemangiomas using continuous occlusion of the hepatic artery proper in addition to intermittent application of the Pringle maneuver for up to 1xa0h was safe.

Differentiation of bland from neoplastic thrombus of the portal vein in patients with hepatocellular carcinoma: application of susceptibility-weighted MR imaging

BackgroundNeoplastic and bland portal vein thrombi (PVT) are both common in patients with hepatocellular carcinoma (HCC). The correct discrimination of them is essential for therapeutic strategies planning and survival predicting. The current study aims to investigate the value of susceptibility-weighted imaging (SWI) in differentiating bland from neoplastic PVT in HCC patients.Methods20 HCC patients with bland PVT and 22 HCC patients with neoplastic PVT were imaged with non-contrast SWI at 3.0 Tesla MRI. The signal intensity (SI) of the PVT and HCC lesions in the same patients was compared on SW images. The phase values of the PVT were compared between neoplastic and bland thrombi cohorts. Receiver operator characteristics (ROC) analysis was conducted to evaluate the diagnostic ability of the phase values for neoplastic and bland thrombi discrimination.Results20 of 22 neoplastic PVT were judged similar SI and 2 were judged lower SI than their HCC. For 20 bland PVT, 19 were judged lower SI and 1 was judged similar SI as their HCC (P<0.001). The average phase values (0.361u2009±u20090.224) of the bland PVT were significantly higher than those of the neoplastic PVT (−0.328u2009±u20090.127, P<0.001). The AUC for phase values in differentiating bland from neoplastic PVT was 0.989. The best cut-off value was −0.195, which gave a sensitivity of 95% and a specificity of 95.5%.ConclusionsSW imaging appears to be a promising new method for distinguishing neoplastic from bland PVT. The high sensitivity and specificity suggest its high value in clinical practice.

Continuous Occlusion of Hepatic Artery Proper for Prevention of Blood Loss in Partial Hepatectomy for Ruptured Hepatocellular Carcinoma: A Case-Matched Comparative Study

BackgroundTo investigate the efficacy and safety of adding continuous occlusion of hepatic artery proper to intermittent Pringle maneuver in partial hepatectomy for ruptured hepatocellular carcinoma.Materials and MethodsThis is a retrospective study on data that were prospectively collected and entered into a computer database. A total of 36 patients who underwent partial hepatectomy for ruptured HCC by adding continuous occlusion of hepatic artery proper to intermittent Pringle maneuver at a tertiary care university hospital were compared with a historical case-matched control group of 36 patients who received intermittent Pringle maneuver only.ResultsThe patient characteristics were comparable for the 2 groups of patients. The mean hepatic artery occlusion time was 58xa0min (range 36–98xa0min). Intraoperative blood loss and blood transfusion rate in the study group were significantly lower than the control group (Pxa0<xa0.001 and Pxa0=xa0.004, respectively). There were no significant differences in the postoperative serum aspartate transaminase and total bilirubin levels (Pxa0=xa0.087, Pxa0=xa0.135, respectively), and in the postoperative hospital stay and surgical complications according to Clavien’s classification between the two groups (Pxa0=xa00.213, Pxa0=xa01.000, respectively). The disease-free survival rates in the study group was significantly better than the control group (Pxa0=xa0.023). Overall, HCC patients with rupture had poor prognosis.ConclusionsThe addition of continuous occlusion of hepatic artery proper to intermittent Pringle maneuver significantly reduced intraoperative blood loss for partial hepatectomy in patients with ruptured HCC when compared with intermittent Pringle maneuver alone. The procedure was found to be safe even for patients with liver cirrhosis.To investigate the efficacy and safety of adding continuous occlusion of hepatic artery proper to intermittent Pringle maneuver in partial hepatectomy for ruptured hepatocellular carcinoma. This is a retrospective study on data that were prospectively collected and entered into a computer database. A total of 36 patients who underwent partial hepatectomy for ruptured HCC by adding continuous occlusion of hepatic artery proper to intermittent Pringle maneuver at a tertiary care university hospital were compared with a historical case-matched control group of 36 patients who received intermittent Pringle maneuver only. The patient characteristics were comparable for the 2 groups of patients. The mean hepatic artery occlusion time was 58xa0min (range 36–98xa0min). Intraoperative blood loss and blood transfusion rate in the study group were significantly lower than the control group (Pxa0<xa0.001 and Pxa0=xa0.004, respectively). There were no significant differences in the postoperative serum aspartate transaminase and total bilirubin levels (Pxa0=xa0.087, Pxa0=xa0.135, respectively), and in the postoperative hospital stay and surgical complications according to Clavien’s classification between the two groups (Pxa0=xa00.213, Pxa0=xa01.000, respectively). The disease-free survival rates in the study group was significantly better than the control group (Pxa0=xa0.023). Overall, HCC patients with rupture had poor prognosis. The addition of continuous occlusion of hepatic artery proper to intermittent Pringle maneuver significantly reduced intraoperative blood loss for partial hepatectomy in patients with ruptured HCC when compared with intermittent Pringle maneuver alone. The procedure was found to be safe even for patients with liver cirrhosis.

Hepatitis B virus X protein suppresses caveolin-1 expression in hepatocellular carcinoma by regulating DNA methylation

BackgroundTo understand the molecular mechanisms of caveolin-1 downregulation by hepatitis B virus X protein (HBx).MethodsThe DNA methylation status of the caveolin-1 promoter was examined by nested methylation-specific PCR of 33 hepatitis B virus (HBV)-infected hepatocellular carcinoma (HCC) samples. The SMMC-7721 hepatoma cell line was transfected with a recombinant HBx adenoviral vector, and the effects of HBx protein on caveolin-1 expression and promoter methylation were examined and confirmed by sequencing. A reporter gene containing the caveolin-1 promoter region was constructed, and the effects of HBx on the transcriptional activity of the promoter were also studied.ResultsMethylation of the caveolin-1 promoter was detected in 84.8% (28/33) of HBV-infected HCC samples. Expression of caveolin-1 was significantly downregulated (Pu2009=u20090.022), and multiple CpG sites in the promoter region of caveolin-1 were methylated in SMMC-7721 cells after HBx transfection. Transfected HBx significantly suppressed caveolin-1 promoter activity (Pu2009=u20090.001).ConclusionsHBx protein induces methylation of the caveolin-1 promoter region and suppresses its expression.