Maoheng Zu

Comparison osteopontin vs AFP for the diagnosis of HCC: A meta-analysis

BACKGROUNDS Osteopontin (OPN) has been reported as one of the most promising markers for hepatocellular carcinoma (HCC). The goal of this meta-analysis was to evaluate the clinical value of the plasma OPN versus alpha-fetoprotein (AFP) in the diagnosis of HCC. METHODS A comprehensive literature search of PubMed, Foreign Medical Journal Service, Chinese Science Journals Database, and Google Scholar was conducted on articles published before 1st October 2013. The sensitivity, specificity, and other measures of accuracy of OPN in the diagnosis of HCC were pooled using random effects models. The methodological quality of each study was assessed by QUADAS (quality assessment for studies of diagnostic accuracy). Statistical analysis was performed by employing Meta-Disc 1.4 and Stata, version 12. Summary receiver operating characteristic curves were used to summarize overall test performance. RESULTS Seven studies were included in our meta-analysis. The summary estimates for OPN and AFP in the diagnosis of HCC in these studies as follows: sensitivity, 0.86 (0.79-0.91) vs 0.66 (0.53-0.76), specificity, 0.86 (0.69-0.94) vs 0.95 (0.87-0.98), positive likelihood ratio (PLR), 6.10 (2.43-15.32) vs 13.25 (4.69-37.49), negative likelihood ratio (NLR), 0.16 (0.09-0.28) vs 0.36 (0.26-0.51), diagnostic odds ratio (DOR), 38.52 (8.99-165.08) vs 36.75 (11.04-122.32), and the area under the curve (AUC), 0.92 vs 0.87. CONCLUSION Our study demonstrates that OPN has a comparable accuracy to AFP for the diagnosis of HCC, while the value of OPN in combination with AFP for HCC detection deserves further investigation.

Strategy and long-term outcomes of endovascular treatment for Budd-Chiari syndrome complicated by inferior vena caval thrombosis.

OBJECTIVES The aim of this study was to evaluate the strategy and long-term outcomes of endovascular treatment of Budd-Chiari syndrome (BCS) complicated by inferior vena cava (IVC) thrombosis. METHODS The treatment strategy and outcomes of BCS complicated by IVC thrombosis were retrospectively evaluated in a single-center study. The treatment was aimed at the IVC thrombus, not hepatic vein occlusion. All 133 patients with BCS complicated by IVC thrombosis from February 2003 to March 2013 underwent endovascular treatment. For the fresh thrombus group (n=75) recanalization was performed after transcatheter thrombolysis with urokinase. For the mixed thrombus group (n=19) a small balloon pre-dilation of the IVC was performed first, followed by transcatheter thrombolysis using urokinase and a large balloon dilation of the IVC. For the old thrombus group (n=39) a large balloon dilation or/and stent placement was performed directly. Pre- and post-treatment follow-ups were recorded. RESULTS The endovascular treatment was successful in 131 out of 133 patients (98.5%). Thirty seven patients had synchronous hepatic vein occlusion. The incidence of serious complications was 4.5% (6/133). Symptomatic pulmonary embolism occurred in three cases, cerebral hemorrhage in two, and cardiac tamponade in one. The cumulative 1-, 5-, and 10-year primary patency rate was 96.3%, 84.0%, and 64.6%, respectively. The cumulative 1-, 5-, and 10-year secondary patency rate was 99.0%, 96.1% and 91.3%, respectively. Segmental occlusion of the IVC and duration of anticoagulant therapy less than 6 months were independent risk factors for reocclusion. CONCLUSIONS For patients with BCS complicated by IVC thrombosis, an individualized treatment strategy based on the property of the thrombus can result in excellent long-term patency.

Clinical outcomes of warfarin anticoagulation after balloon dilation alone for the treatment of Budd-Chiari syndrome complicated by old inferior vena cava thrombosis.

BACKGROUND To evaluate the safety and clinical efficacy of warfarin anticoagulation after balloon dilation alone for the treatment of Budd-Chiari syndrome (BCS) complicated by old inferior vena cava (IVC) thrombosis. METHODS From January 2008 to November 2013, 19 BCS patients complicated with old IVC thrombosis were treated with balloon dilation followed by oral administration of anticoagulant warfarin. Follow-up was performed at 1 week, then 1, 2, 3, 6, and 12 months after balloon dilation, and then annually thereafter. IVC patency and morphologic changes of the old thrombus were examined by ultrasound, and clinical symptoms and signs were determined by clinical examinations during follow-up. RESULTS Successful IVC balloon dilation was achieved in the 19 patients (100%). Inferior vena cavography demonstrated the patency of IVC lumen, and the size of the old thrombus was not altered. The mean pressure gradient between IVC and the right atrium was reduced from 27.5 ± 3.0 cm H2O (range, 22-35) before treatment to 5.4 ± 1.3 cm H2O (range: 2-7) after treatment (t = 41.6, P < 0.05; 1 cm H2O = 0.098 kPa). Patients were followed up as outpatients for an average of 15.9 ± 14.4 months (range, 3-66). Anticoagulation with warfarin was well tolerated in all patients after balloon dilation alone. Of the 19 patients, complete resolution of the old thrombus was achieved in 12 patients and partial resolution was achieved in 7 patients. Color Doppler ultrasound showed that 17 patients had IVC lumen patency, and 2 patients had IVC reocclusion. None of the patients had recurrence of thrombosis, symptomatic pulmonary embolism, and bleeding complications throughout the follow-up period. CONCLUSIONS Our results indicate that warfarin anticoagulation after balloon dilation alone is a safe and effective therapy for BCS patients with old IVC thrombosis.

Comparison of Long-Term Outcomes of Endovascular Management for Membranous and Segmental Inferior Vena Cava Obstruction in Patients With Primary Budd–Chiari Syndrome

Background—Endovascular management is important for the treatment of primary Budd–Chiari syndrome, which is caused by inferior vena cava (IVC) obstruction. The aims of this study were to compare long-term outcomes of endovascular management for primary Budd–Chiari syndrome patients with membranous obstruction of IVC (MOVC) and segmental obstruction of IVC (SOVC) and explore the optimal endovascular strategy for these conditions. Methods and Results—Clinical data of 265 patients with Budd–Chiari syndrome who received endovascular management (MOVC group, n=136; SOVC group, n = 129) were retrospectively reviewed. Cumulative IVC patency rates were generated by the Kaplan–Meier method and compared by log-rank test. In total, 245 patients were followed up from 3 to 72 months after treatment. The difference of long-term outcomes of balloon dilation alone versus stent placement was not significant in each group. The overall cumulative 1-, 3-, and 5-year primary IVC patency rates were 98.3%, 90.7%, and 83.8% in the MOVC group and 88.3%, 79.1%, and 67.9% in the SOVC group (P=0.007), respectively. The long-term IVC patency rates were lower in the SOVC group than in the MOVC group for patients who underwent balloon dilation alone (P=0.001) and did not significantly differ for patients who underwent stent placement between both the groups (P=0.687). Conclusions—The long-term treatment outcome of endovascular management was better for primary Budd–Chiari syndrome patients with MOVC than for those with SOVC. Balloon dilation alone could be the optimal treatment for patients with MOVC. However, stent placement should be more strongly recommended for patients with SOVC.

Risk factors of recurrence among 471 Chinese patients with Budd-Chiari syndrome

BACKGROUND AND AIM Budd-Chiari syndrome (BCS) is a rare form of vascular disease. There is limited literature available regarding the prognosis of this disease. The aim of this study was to characterize the cumulative recurrence rates and to investigate the risk factors of recurrence in Chinese patients with BCS. METHODS Four hundred and seventy-one patients were diagnosed as having BCS in the Affiliated Hospital of Xuzhou Medical College (Jiangsu, China) between January 2008 and December 2012. Follow-ups were conducted by phone calls or correspondence. Cumulative recurrence rates were assessed with the Kaplan-Meier curves. Independent risk factors of recurrence were calculated with the Coxs proportional hazards regression model. RESULTS Four hundred and twenty-five patients with BCS had complete follow-up data, in which 24 patients died, 98 patients had recurrence, with the median duration of follow-up being 19.3 months (range 3 to 61.4). The cumulative 1-, 2-, 3-, 4- and 5-year recurrence rates were 12%, 22%, 27%, 35% and 42%, respectively. Univariable and multivariable Coxs proportional hazards regression models showed that the risk factors of recurrence include: age ≤ 30 years (HR=2.261, 95% CI: 1.412-3.621), differentiated typology (hepatic vein type: HR=1.885, 95% CI: 1.045-3.402; combined type: HR=2.088, 95% CI: 1.233-3.536), elevated lactate dehydrogenase (LDH) levels (HR=1.125, 95% CI: 1.101-1.212) and the Child-Pugh class B/C (B: HR=1.758, 95% CI: 1.057-2.926; C: HR=2.626, 95% CI: 1.396-4.940). CONCLUSIONS Regardless of thrombophilia and haematological causes, exceptionally found in Chinese patients, the 5-year recurrence rate of BCS was as high as 42%. Age ≤ 30 years, hepatic vein type, combined type, increased LDH levels and the Child-Pugh class B/C were independent predictors of BCS recurrence.

Inhibition of mammalian target of rapamycin by rapamycin increases the radiosensitivity of esophageal carcinoma Eca109 cells

The aim of the present study was to investigate whether radiation induces the mammalian target of rapamycin (Rap) (mTOR) signaling pathway in esophageal carcinoma Eca109 cells, and whether mTOR inhibition by rapamycin increases Eca109 cell radiosensitivity. Changes in the levels of mTOR signaling pathway and DNA damage-repair proteins in Eca109 cells prior to and following radiation were determined. The Eca109 cells were treated with Rap (0, 100, 200 and 400 nmol/l) in combination with radiation (0, 2, 4 and 6 Gy). The cell proliferation inhibition rate was determined by MTT assay. The optimum Rap concentration and radiation dose, which appropriately inhibited cell proliferation, were then selected for further study. An appropriate combination of Rap and radiation for the Eca109 cells was also selected and changes in the mTOR signaling pathway, apoptosis and DNA damage-repair proteins, as well as in cell clone formation, survival curves, the apoptosis rate and radiation-induced DNA damage were determined. The expression of the mTOR signaling pathway and DNA damage-repair proteins were found to increase following the irradiation of the Eca109 cells. In addition, Rap was found to inhibit the mTOR signaling pathway and the expression of the DNA damage-repair proteins. At the same radiation dose, with increasing Rap concentration, the proliferation inhibition rates of the Eca109 cells were found to improve. The clone formation and survival curves of the experimental group were less than those of the control groups. Furthermore, the cell apoptosis rate and expression of cleaved caspase-3 and bax in the experimental group were higher than those of the control groups, whereas the expression of bcl-2 was less than that of the control groups. The radiation-induced DNA damage of the experimental group was greater than that of the control group. The inhibition of mTOR by Rap was found to effectively inhibit the proliferation, survival and radiation-induced DNA damage repair of the Eca109 cells following irradiation, as well as promoting radiation-induced apoptosis, thereby increasing the radiosensitivity of the esophageal carcinoma Eca109 cells.

Catheter-directed thrombolytic therapy combined with angioplasty for hepatic vein obstruction in Budd-Chiari syndrome complicated by thrombosis

The aim of this study was to assess the efficacy and safety of catheter-directed thrombolysis combined with angioplasty in the treatment of hepatic vein obstruction in Budd-Chiari syndrome (BCS) complicated by thrombosis. In 14 cases of BCS, the patients with hepatic vein obstruction complicated by thrombosis who underwent catheter-directed urokinase thrombolysis, balloon dilatation and/or stent placement were followed up with an ultrasound examination of the liver. Among the 13 cases of successful treatment, one hepatic vein was recanalized in 12 patients (right hepatic vein, seven cases; left hepatic vein, three cases; middle hepatic vein, one case and accessory hepatic vein, one case) and two hepatic veins (right and left) were recanalized in one patient without serious complications, such as bleeding and pulmonary embolism. There was one patient in whom the treatment was unsuccessful. During an average follow-up period of 24.8±19.6 months, hepatic vein restenosis was observed in one patient in the sixth month after opperation; however, a successful result was obtained following a second balloon dilatation. The remaining 12 patients did not demonstrate any recurrence of restenosis or thrombosis. Catheter-directed thrombolysis combined with angioplasty was observed to be an effective and safe method for the treatment of hepatic vein obstruction in BCS complicated by thrombosis.

Number and function of circulating endothelial progenitor cells in patients with primary Budd-Chiari syndrome

BACKGROUND AND AIM Primary Budd-Chiari syndrome (BCS) is associated with vascular endothelial injury. Circulating endothelial progenitor cells (EPCs) provide an endogenous mechanism to repair endothelial injury. This study investigated the levels and functionality of EPCs in patients with primary BCS. METHODS EPCs (CD34+/CD133+/KDR+) were quantified in 82 patients with primary BCS (inferior vena cava type: n=19; hepatic vein type: n=22; and mixed type: n=41), 10 cirrhosis controls (CC group) and 10 age-matched healthy controls (HC group), using flow cytometry. EPCs proliferation was detected by MTT assay, adhesion by adhesion activity assay, and migration capacity by Transwell assay. RESULTS EPCs levels were significantly lower in the BCS group (0.020±0.005%) than in the CC and HC groups (0.260±0.201%, 0.038±0.007%; P<0.001 for each). EPCs cultured in vitro from BCS and CC groups had, respectively, lower proliferation activity (0.20±0.04, 0.23±0.06 vs 0.58±0.07, each P<0.001), adhesion activity (15.8±1.7, 18.2±4.3 vs 35.0±2.5 cells/random microscopic field (RMF), each P<0.001) and migration activity (16.1±1.5, 16.7±3.0 vs 23.9±2.0 cells/RMF, each P<0.001) than in the HC group. EPCs functionality did not significantly differ between the BCS and CC groups. The numbers and functions of EPCs did not significantly differ among patients with inferior vena cava type, hepatic vein type and mixed type of BCS. CONCLUSION Patients with primary BCS had lower EPCs levels, with less proliferation, adhesion and migration activities. These findings suggest that lower levels of less functional EPCs may be associated with venous occlusion in primary BCS patients.