Characterization of hepatitis B virus infection and viral DNA integration in non-Hodgkin lymphoma

Hepatitis B virus (HBV) infection has been reported to be associated with non-Hodgkin lymphoma (NHL). However, the evidence is limited to the seroepidemiological study. There is a lack of evidence showing the HBV infection and integration in NHL cells. Here, we reported that in the Shanghai area, the positive rates of serum HBsAg (OR: 3.11; 95% CI: 2.20-4.41) and HBeAg (OR: 3.99; 95% CI: 1.73-9.91) were significantly higher in patients with NHL. HBsAg, HBcAg and HBV DNA were detected in 34.4%, 45.2% and 47.0% of the NHL tissues, respectively. Furthermore, by using a high-throughput viral integration detection approach (HIVID), integrated HBV DNA was identified from 50% (6/12) HBV-related NHL tissues. There were a total of 313 HBV integration sites isolated from the NHL tissues, among which four protein-coding genes (FAT2, SETX, ITGA10 and CD63) were interrupted by HBV DNA in their exons. Seven HBV preferential target genes (ANKS1B, HDAC4, EGFLAM, MAN1C1, XKR6, ZBTB38 and CCDC91) showed significantly altered expression levels in NHL, suggesting a potential role of these genes in NHL development. Taken together, HBV integration is a common phenomenon in NHL. This finding opens up a new direction of research into the mechanistic link between HBV infection and NHL.     

发育性髋脱位闭合复位术前磁共振预判因素分析

目的探讨2岁以内发育性髋关节脱位(developmental dislocation of the hip,DDH)患儿术前磁共振相关因素对手术方式的预判。方法回顾性分析2013年7月至2017年2月收治的57例(60髋)符合条件的发育性髋关节脱位患儿资料,其中男9例,女48例。术中根据Bowen造影标准将患儿分为3组,闭合复位成功为A组(26例),闭合复位失败为B组(24例),无法复位为C组(7例)。在磁共振上测量三组患儿术前关节囊前入口角(anterior access angle,AAA)、下入口角(inferior access angle,IAA)、冠状位最大入口直径(coronal maximal access diameter,CMAD)、轴位最大入口直径(axial maximal access diameter,AMAD)、轴位股骨头直径(axial femoral head diameter,AFHD)、冠状位股骨头直径(coronal femoral head diameter,CFHD)、冠状位口径比(CMAD/AFHD)及轴位口径比(AMAD/CFHD)等指标,比较三组数据的差异有无统计学意义。Logistic多因素回归分析性别、侧别、年龄、脱位程度、负重时间等和治疗方式的相关性,受试者工作特征曲线(Receiver operating characteristic curve,ROC曲线)评估闭合复位组指标的灵敏度、特异度及拐点。结果3组数据的AAA、CFHD、AFHD等方面的差异无统计学意义(P>0.05)。A组IAA角为(108.2±9.8)°,显著大于B组(98.8±11.2)°和C组(91.7±6.9)°,三组差异具有统计学意义(P<0.05);A组与B组,A组与C组在CMAD、AMAD、CMAD/AFHD等的差异具有统计学意义(P<0.05)。A、B两组AMAD/CFHD的差异有统计学意义,A、C两组差异无统计学意义。B、C两组CMAD、AMAD、CMAD/AFHD、AMAD/CFHD的差异均无统计学意义(P>0.05)。根据Logistic多因素回归分析结果,性别、侧别、脱位程度、负重时间等和治疗方式的差异无统计学意义(P>0.05),年龄有相关性。A、B两组差异具有统计学意义的5组数据ROC曲线下最大面积为AMAD/CFHD(0.848),确定AMAD/CFHD的敏感度(74.1%)、特异度(92.3%)及拐点(0.515)。结论术前磁共振指标IAA、CMAD、AMAD、CMAD/AFHD、AMAD/CFHD可作为术前预判因素。当AMAD/CFHD比值>0.515时,建议行闭合复位治疗。     

The Comprehensive Analysis of Efficacy and Safety of CalliSpheres^® Drug-Eluting Beads Transarterial Chemoembolization in 367 Liver Cancer Patients: A Multiple-Center,Cohort Study

This study aimed to investigate the efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization (DEB-TACE) in treating Chinese patients with liver cancer. A total of 367 liver cancer patients from 24 medical centers were consecutively enrolled in this multiple-center, prospective cohort study, including 275 hepatocellular carcinoma (HCC) cases, 37 intrahepatic cholangiocarcinoma (ICC) cases, and 55 secondary liver cancer cases. All the patients received CalliSpheres^® DEB-TACE treatment. Treatment response, overall survival (OS), change of liver function, and adverse events (AEs) were assessed. DEB-TACE treatment achieved 19.9% complete response (CR) and 79.6% objective response rate (ORR), with mean OS of 384 days [95% confidence interval (CI): 375–393 days]. CR and ORR were both higher in HCC patients compared with primary ICC patients and secondary liver cancer patients, while no difference was discovered in OS. Portal vein invasion was an independent risk factor for CR, while portal vein invasion, previous conventional TACE (cTACE) treatment, and abnormal blood creatinine (BCr) were independent risk factors for ORR. In addition, largest nodule size 5.0 cm, abnormal albumin (ALB), and abnormal total bilirubin (TBIL) independently correlated with unfavorable OS. Most liver function indexes were recovered to baseline levels at 1–3 months after DEB-TACE. Common AEs were pain, fever, vomiting, and nausea; most of them were at mild grade. CalliSpheres^® DEB-TACE is efficient and well tolerated in Chinese liver cancer patients. Portal vein invasion, previous cTACE treatment, largest nodule size, abnormal BCr, ALB, and TBIL correlate with worse prognosis independently.     

Endostar,an Antiangiogenesis Inhibitor,Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.