A new classification for hepatocellular carcinoma with hepatic vein tumor thrombus

BackgroundHepatic vein tumor thrombus (HVTT) is a significant poor risk factor for survival outcomes in hepatocellular carcinoma (HCC) patients. Currently, the widely used international staging systems for HCC are not refined enough to evaluate prognosis for these patients. A new classification for macroscopic HVTT was established, aiming to better predict prognosis.MethodsThis study included 437 consecutive HCC patients with HVTT who underwent different treatments. Overall survival (OS) and time-dependent receiver operating characteristic (ROC) curve area analysis were used to determine the prognostic capacities of the new classification when compared with the different currently used staging systems.ResultsThe new HVTT classification was defined as: type I, tumor thrombosis involving hepatic vein (HV), including microvascular invasion; type II, tumor thrombosis involving the retrohepatic segment of inferior vena cava; and type III, tumor thrombosis involving the supradiaphragmatic segment of inferior vena cava. The numbers (percentages) of patients with types I, II, and III HVTT in the new classification were 146 (33.4%), 143 (32.7%), and 148 (33.9%), respectively. The 1-, 2-, and 3-year OS rates for types I to III HVTT were 79.5%, 58.6%, and 29.1%; 54.8%, 23.3%, and 13.8%; and 24.0%, 10.0%, and 2.1%, respectively. The time-dependent-ROC curve area analysis demonstrated that the predicting capacity of the new HVTT classification was significantly better than any other staging systems.ConclusionsA new HVTT classification was established to predict prognosis of HCC patients with HVTT who underwent different treatments. This classification was superior to, and it may serve as a supplement to, the commonly used staging systems.     

铁螯合剂对大鼠脑出血脑水肿的治疗作用

目的:探讨铁螯合剂对大鼠脑出血(intracerebralhemorrhage,ICH)后脑水肿的治疗作用。方法:利用大鼠自体血注入大脑一侧的尾状核建立脑出血实验动物模型,随机将动物分为3组:实验组、对照组和假手术组。观察各组大鼠给药前后神经缺失症状并进行动物行为学评分;处死大鼠,测定血肿周围脑组织的水含量、钠离子含量、铁离子含量及丙二醛(MDA)、超氧化物歧化酶(SOD)的含量。结果:去铁敏治疗后ICH大鼠的神经功能缺失症状得到明显改善,脑水含量和钠离子含量明显降低,血肿周围局部脑组织铁、MDA的含量明显降低,SOD的活性明显提高。结论:铁螯合剂———去铁敏通过螯合铁离子能明显改善ICH大鼠的神经功能缺失症状,减轻ICH脑水肿形成。铁螯合剂可能是治疗ICH脑水肿潜在的药物之一。     

Overexpression of PDZ1 domain prevents apoptosis of rat hippocampal neurons induced by kainic acid

In our previous studies, Tat-GluR6-9c (a glutamate receptor 6 C-terminus peptide fused the TAT protein transduction sequence) not only inhibited the activation of MLK3 (mixed lineage kinase 3) and JNK (c-Jun N-terminal kinase) via the GluR6·PSD-95 (postsynaptic density protein 95)·MLK3 signaling module but also diminished neuronal death induced by kainic acid or transient cerebral ischemia in rat hippocampus. Here, we investigate whether overexpression of the PDZ1 domain of PSD-95 protein could suppress the binding of GluR6 with PSD-95 and the activation of MLK3, MKK7 (mitogen-activated kinase kinase 7) and JNK1/2, and rescused neuronal cell death induced by kainic acid. Our results showed that overexpression of the PDZ1 domain of PSD-95 protein could prevent nuclear accumulation and abrogate neuronal cell death in SD (Sprague–Dawley) rat hippocampal neuronal cells. Further studies indicated that overexpression of PDZ1 could inhibit the enhancement of binding of GluR6 to PSD-95 and prevent the activation of MLK3, MKK7 and JNK1/2 induced by kainic acid. Taken together, the essential role of the PDZ1 domain of PSD-95 in apoptotic cell death in neurons provides an experimental foundation for gene therapy of neurodegenerative diseases with overexpression of the PDZ1 domain.     

The role of three-dimensional imaging in optimizing diagnosis,classification and surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus

Background

Accurate assessment of characteristics of tumor and portal vein tumor thrombus is crucial in the management of hepatocellular carcinoma.

Aims

Comparison of the three-dimensional imaging with multiple-slice computed tomography in the diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus.

Method

Patients eligible for surgical resection were divided into the three-dimensional imaging group or the multiple-slice computed tomography group according to the type of preoperative assessment. The clinical data were collected and compared.

Results

74 patients were enrolled into this study. The weighted κ values for comparison between the thrombus type based on preoperative evaluation and intraoperative findings were 0.87 for the three-dimensional reconstruction group (n = 31) and 0.78 for the control group (n = 43). Three-dimensional reconstruction was significantly associated with a higher rate of en-bloc resection of tumor and thrombus (P = 0.025). Using three-dimensional reconstruction, significant correlation existed between the predicted and actual volumes of the resected specimens (r = 0.82, P < 0.01), as well as the predicted and actual resection margins (r = 0.97, P < 0.01). Preoperative three-dimensional reconstruction significantly decreased tumor recurrence and tumor-related death, with hazard ratios of 0.49 (95% confidential interval, 0.27–0.90) and 0.41 (95% confidential interval, 0.21–0.78), respectively.

Conclusion

For hepatocellular carcinoma with portal vein tumor thrombus, three-dimensional imaging was efficient in facilitating surgical treatment and benefiting postoperative survivals.     

Safety and immunogenicity of a novel human Enterovirus 71 (EV71) vaccine: a randomized, placebo-controlled, double-blind, Phase I clinical trial

There is an urgent need for a novel vaccine that is effective against human Enterovirus 71 (EV71) outbreaks. A double-blind, randomized controlled study was to evaluate the safety and immunogenicity of a human EV71 vaccine in healthy adults, children and infants. The vaccine dosages were 200 U and 400 U for children and adults, and 100 U, 200 U and 400 U for infants. Subjects were randomized to receive different dosages of the vaccine or placebo. Adults received intramuscular injection on Days 0, 14 and 28. Children and Infants received on Days 0, 28 and 56. The novel human EV71 inactivated vaccine was well tolerated and highly immunogenic in healthy volunteers, especially in infant populations. For immune response, the seropositive rates (with titers ≥≥1:8) of neutralizing antibody [NTAb] increased to 100% for all dosage groups after the second vaccination. For NTAb seronegative infants before vaccination, after one dose, the NTAb GMTs were 29.7 (95% CI, 13.1-67.2), 10.1 (95% CI, 6.6-15.3), and 27.4 (95% CI, 14.3-52.2) in the 100 U, 200 U, and 400 U vaccine groups, respectively; after two doses, the GMTs were 114.1 (95% CI, 44.5-292.4), 159.5 (95% CI, 49.3-515.3), and 509.0 (95% CI, 181.3-1429.1), respectively. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT01273246 and NCT01273233.     

Primary hepatic malignant fibrous histiocytoma mimicking cystadenocarcinoma: a case report

Introduction Malignant fibrous histiocytoma (MFH) is one of the common soft tissue sarcomas in adults, involving the extremities and less commonly the retroperitoneal space or other sites of the body.[1-3] It is thought to be originated from undifferentiated mesenchymal cells capable of multidirectional differentiation.[4] This is why it can be found in all organs.[5] MFH of the liver is extremely rare, and only 28 cases have been reported to date.[6-14] In this report we present a case of …     

A serological scoring system to predict lymph node metastasis in patients with hepatocellular carcinoma

Background

Lymph node metastasis (LNM)has widely been recognized as a poor prognostic indicator for hepatocellular carcinoma (HCC) patients. Preoperative prediction of LNM is important for clinicians to decide on treatment. This study was designed to develop a simple and convenient system to predict LNM.

Oral feeding and nasal instillation immunization with Microtus brandti lactate dehydrogenase C epitope DNA vaccine reduces fertility in mice via specific antibody responses

The immune responses induced by Microtus brandti lactate dehydrogenase C4 DNA vaccine via oral feeding and nasal instillation in mouse were investigated. The number of newborns of the vaccinated mice was statistically significantly reduced compared with the control mice, but the vaccine failed to affect the birthrate, as all vaccinated mice gave birth.     

Apoptosis and tumor inhibition induced by human chorionic gonadotropin beta in mouse breast carcinoma

For many breast cancer patients, human chorionic gonadotropin beta (hCGβ), which is a subunit of a hormone produced by the trophoblast and is essential for maintaining pregnancy, is expressed in the breast cancer cells. However, the mechanism as to how the CGβ in cell affects the cancer development is not very clear. Mouse breast carcinoma 4T1 with stably hCGβ expression (4T1-hCGβ) was established and transplanted into the Balb/c mouse abdominal mammary gland. hCGβ suppressed breast cancer cell viability in vitro, and dramatically inhibited tumor growth and attenuated tumor vessel formation in vivo. An 86–88% reduction in tumor volume in animals injected with breast cancer expressing hCGβ, as opposed to those injected with breast cancer without hCGβ expression, was observed. The production of p21 was promoted by hCGβ, whereas the Cdk2 was decreasing. These indicate that p21 signal pathway is involved in this process. Significant apoptosis was also detected in hCGβ-expressing breast cancer cells as well as the enhancement of Bax protein expression. Moreover, hCGβ blocked the blood vessels formation by inhibiting the expression of MMP9 and VEGF. Further hormone secretion analyses show that the anti-tumor activity induced by hCGβ is not related to the endocrine function.     

A new staging system for hepatocellular carcinoma associated with portal vein tumor thrombus

BackgroundA new staging system for patients with hepatocellular carcinoma (HCC) associated with portal vein tumor thrombus (PVTT) was developed by incorporating the good points of the BCLC classification of HCC, and by improving on the currently existing classifications of HCC associated with PVTT.MethodsUnivariate and multivariate analysis with Wald χ² test were used to determinate the clinical prognostic factors for overall survival (OS) in patients with HCC and PVTT in the training cohort. Then the conditional inference trees analysis was applied to establish a new staging system.ResultsA training cohort of 2,179 patients from the Eastern Hepatobiliary Surgery Hospital and a validation cohort of 1,550 patients from four major liver centers in China were enrolled into establishing and validating a new staging system. The system was established by incorporating liver function, general health status, tumor resectability, extrahepatic metastasis and extent of PVTT. This staging system had a good discriminatory ability to separate patients into different stages and substages. The median OS for the two cohorts were 57.1 (37.2–76.9), 12.1 (11.0–13.2), 5.7 (5.1–6.2), 4.0 (3.3–4.6) and 2.5 (1.7–3.3) months for the stages 0 to IV, respectively (P<0.001) in the training cohort. The corresponding figures for the validation cohort were 6.4 (4.9–7.9), 2.8 (1.3–4.4), 10.8 (9.3–12.4), and 1.5 (1.3–1.7) months for the stages II to IV, respectively (P<0.001). The mean survival for stage 0 to 1 were 37.6 (35.9–39.2) and 30.4 (27.4–33.4), respectively (P<0.001).ConclusionsA new staging system was established which provided a good discriminatory ability to separate patients into different stages and substages after treatment. It can be used to supplement the other HCC staging systems.