Xiang Ming Lao

Effects of antiviral therapy on hepatitis B virus reactivation and liver function after resection or chemoembolization for hepatocellular carcinoma

How hepatitis B virus (HBV) infection react to hepatocellular carcinoma (HCC) treatment remains unclear, and the roles of anti‐HBV therapy were seldom reported in HCC.

Transforming growth factor-β1-induced epithelial–mesenchymal transition generates ALDH-positive cells with stem cell properties in cholangiocarcinoma

Epithelial-mesenchymal transition (EMT) is a major factor that facilitates the invasiveness and metastasis of cancer. Recent studies have demonstrated that EMT plays a key role in generating cancer stem cells (CSCs). This study aimed to investigate the effect of EMT on CSCs that were identified as positive for aldehyde dehydrogenase (ALDH) in cholangiocarcinoma (CCA). We demonstrated that transforming growth factor-β1 (TGF-β1)-induced EMT in the human cholangiocarcinoma (CCA) cell line, TFK-1, resulted in the acquisition of mesenchymal traits, as well as the expression of ALDH, which was accompanied by decreased sensitivity to the chemotherapeutic agent, 5-fluorouracil. ALDH-positive cells isolated from TFK-1 cells had higher proliferation potential in vitro and tumourigenic ability in vivo. They also expressed mesenchymal markers. Moreover, the expression levels of TGF-β1 and ALDH1 were correlated with poor prognosis in patients. We conclude that ALDH acts as a marker for CSCs in CCA, and TGF-β1-induced EMT is involved in the generation of CSCs. These findings offer a new tool for the study of CCA stem cells and illustrate a direct link between EMT and the gain of stem-cell properties.

A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma.

ABSTRACT Background & Aims: There is no generally accepted adjuvant therapy for hepatocellular carcinoma (HCC) after curative resection. Autologous cytokine-induced killer (CIK) cells therapy has been reported to improve outcomes of patients with HCC, but its role as an adjuvant therapy remains unclear. This study aimed to evaluate the efficacy and safety of CIK as an adjuvant therapy for HCC after curative resection. Methods: This is a single center, phase 3, open label, randomized controlled trial (RCT). Two hundred patients who were initially diagnosed with HCC of Barcelona Clinic Liver Cancer (BCLC) stage A or B, and underwent curative hepatectomy were randomly assigned to receive four cycles of CIK treatment (the CIK group, n = 100) or no treatment (the control group, n = 100). The primary outcome was time to recurrence. The secondary outcomes included disease-free survival (DFS), overall survival (OS) and adverse events. Results: All patients in the CIK group finished the treatment by protocol. The median time to recurrence (TTR) was 13.6 (IQR 6.5–25.2) mo in the CIK group and 7.8 (IQR 2.7–17.0) mo in the control group (p = 0.01). There were no significant differences between the groups in DFS and OS. All adverse events were grade 1 or 2. There were no significant differences in incidence between the two groups. Conclusions: Four cycles of CIK therapy were safe and effective to prolong the median TTR in patients with HCC after curative resection, but the treatment did not improve the DFS and OS.

Identification of a novel microRNA signature associated with intrahepatic cholangiocarcinoma (ICC) patient prognosis

BackgroundThe clinical significance of microRNAs (miRNAs) in intrahepatic cholangiocarcinoma (ICC) is unclear. The objective of this study is to examine the miRNA expression profiles and identify a miRNA signature for the prognosis of ICC.MethodsUsing a custom microarray containing 1,094 probes, the miRNA expression profiles of 63 human ICCs and nine normal intrahepatic bile ducts (NIBD) were assessed. The miRNA signatures were established and their clinical significances in ICC were analyzed. The expression levels of some miRNAs were verified by quantitative real-time RT-PCR (qRT-PCR).ResultsExpression profile analysis showed 158 differentially expressed miRNAs between ICC and NIBD, with 77 up-regulated and 81 down-regulated miRNAs. From the 158 differentially expressed miRNAs, a 30-miRNA signature consisting of 10 up-regulated and 20 down-regulated miRNAs in ICC was established for distinguishing ICC from NIBD with 100% accuracy. A separate 3-miRNA signature was identified for predicting prognosis in ICC. Based on the 3-miRNA signature, a formula was constructed to compute a risk score for each patient. The patients with high-risk had significantly lower overall survival and disease-free survival than those with low-risk. The expression level of these three miRNAs detected by microarray was verified by qRT-PCR. Multivariate analysis indicated that the 3-miRNA signature was an independent prognostic predictor.ConclusionsIn this study, a 30-miRNA signature for distinguishing ICC from NIBD, and a 3-miRNA signature for evaluating prognosis of ICC were established, which might be able to serve as biomarkers for prognosis of ICC. Further studies focusing on these miRNAs may shed light on the mechanisms associated with ICC pathogenesis and progression.

Adjuvant cytokine-induced killer cell therapy improves disease-free and overall survival in solitary and nonmicrovascular invasive hepatocellular carcinoma after curative resection

Abstract Cytokine-induced killer (CIK) cell therapy has recently been used as an adjuvant setting following resection of hepatocellular carcinoma (HCC), while its benefit remains unclear. This study aimed to evaluate the efficacy of adjuvant CIK application in solitary HCC patients undergoing curative resection with stratification of microvascular invasion (MVI). In total, specimens and data from 307 solitary HCC patients undergoing curative resection between January 2007 and December 2010 were included. Of these, 102 patients received CIK treatment after surgery (CIK group), whereas 205 patients did not (control group). Pathological evaluation was used to retrospectively determine MVI status. The CIK group had 60 MVI-negative and 42 MVI-positive patients, while the numbers in control group were 124 and 81. Kaplan-Meier and Cox regression analyses were used to validate possible effects of CIK treatment on disease free survival (DFS) and overall survival (OS) as appropriate. For all patients, the CIK group exhibited significantly higher OS than the control group (log-rank test; P DFS = 0.055, P OS  = 0.020). Further analysis based on MVI stratification showed that for patients with MVI, DFS and OS did not differ between the 2 groups (P DFS  = 0.439, P OS  = 0.374). For patients without MVI, the CIK group exhibited better DFS and OS than the control group (P DFS  = 0.042, P OS  = 0.007), and multivariate analyses demonstrated that CIK treatment was an independent prognostic factor both for DFS and OS. For solitary HCC, CIK cell therapy after curative resection improves DFS and OS for patients without MVI, but has no statistically significant survival benefit for patients with MVI.

Changes of HBV DNA After Chemoembolization for Hepatocellular Carcinoma and the Efficacy of Antiviral Treatment.

Unlike systemic chemotherapy for hematological malignancies with hepatitis B virus (HBV) infection, transarterial chemoembolization (TACE) for HBV-related hepatocellular carcinoma (HCC) has only recently been reported to cause HBV reactivation and subsequent hepatitis. Most patients with HBV-related HCC have an underlying disease with liver fibrosis or cirrhosis, and TACE may potentially induce HBV reactivation and liver decompensation. Currently, there are no clinical guidelines for managing TACE-caused HBV reactivation. In this review, we summarize the changes of HBV status and liver function after TACE and the effect of antiviral treatment before, during, or after TACE.

Hepatocellular carcinoma with en bloc diaphragmatic resection: A single-center experience over 14 years

BACKGROUND Diaphragmatic resection is not common in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). This study aims to evaluate retrospectively the clinical characteristics and surgical results of HCC patients undergoing hepatectomy plus diaphragmatic resection. METHODS Between January 2000 and December 2013, 52 HCC patients underwent curative resections combined with diaphragmatic resection, with 11 patients had pathological diaphragmatic invasion (DI), 41 patients had diaphragmatic fibrous adhesion (DFA). The clinicopathological features and results were compared between the two groups. RESULTS 86.5% of the patients had HBV infection. Diameter of tumors was 8.6 ± 3.4 cm, and 34.6% had multiple tumors. In addition, 28.8% had microvascular invasion, 3.8% had macrovascular invasion, but none of the patients had lymph node metastasis or distant metastasis. Moreover, 21.2% had tumor rupture before surgical resection. The DI group exhibited similar clinicopathological features with the DFA group. There were no treatment-related deaths, and major complication was postoperative pleural effusion (46.2%). Other clinical pulmonary issues, such as pneumothorax (5.8%) and pneumonia (3.8%), were also detected. OS at 1, 3 and 5 years was 82.0%, 41.2% and 35.7%, respectively. There was no significant difference in OS and DFS between the DI and DFA groups (P = 0.499 and P = 0.956, respectively). CONCLUSIONS En bloc resection of diaphragm was associated with acceptable morbidity and mortality, and there was no difference in OS and DFS between HCC patients with DI or DFA. Therefore, it would be advisable to perform en bloc diaphragmatic resection when HCC patients present with gross diaphragmatic involvement.