Comparison of AngioJet Thrombectomy System Versus Suction Catheter with the Adjunct of Catheter-Directed Thrombolysis for Lower Extremity Deep Venous Thrombosis.

BACKGROUND: This study aims to investigate the value of the AngioJet thrombectomy system with adjunct of catheter-directed thrombolysis (CDT) in treating lower extremity deep venous thrombosis (LEDVT). METHODS: 48 patients who were clinically confirmed LEDVT and treated by percutaneous mechanical thrombectomy (PMT) combined with CDT, were included in this retrospective study (AJ-CDT, n = 33; Suction-CDT, n = 15). Baseline characteristics, clinical outcomes and surveillance data were reviewed and analyzed. RESULTS: The overall clot reduction rate of AJ-CDT group was significantly higher than that of Suction-CDT group (77.86% vs 64.47%, P = .027). The CDT therapeutic time (5.75 ± 3.04 vs 7.67 ± 2.82 days, P = .045) and urokinase dosage (3.63 ± 2.16 vs 5.76 ± 2.12 million IU, P = .003) were lower in AJ-CDT group, respectively. There was statistical significance in the transient hemoglobinuria between 2 groups (72.73% vs 6.67%, P < .001). At postoperative 48 hours, the serum creatinine (Scr) value was higher in AJ-CDT group compared to Suction-CDT group statistically (78.56 ± 32.16 vs 60.21 ± 15.72 µmol/l, P = .049). However, the incidence of acute kidney injury (AKI) and uric acid (UA) concentration at postoperative 48 hours between these 2 groups were no statistical difference. There was no statistical significance in the Villalta score and post-thrombosis syndrome (PTS) incidence during postoperative follow-up. CONCLUSIONS: AngioJet thrombectomy system is more effective for the treatment of LEDVT by providing a higher clot reduction rate with shorter thrombolytic time and lower thrombolytic drug dosage. However, the device-related potential risk of renal function injury should be taken appropriate precautions.

Generation of functional hepatocyte-like cells from human bone marrow mesenchymal stem cells by overexpression of transcription factor HNF4α and FOXA2.

BACKGROUND: Our previous study showed that overexpression of hepatocyte nuclear factor 4α (HNF4α) could directly promote mesenchymal stem cells (MSCs) to differentiate into hepatocyte-like cells. However, the efficiency of hepatic differentiation remains low. The purpose of our study was to establish an MSC cell line that overexpressed HNF4α and FOXA2 genes to obtain an increased hepatic differentiation efficiency and hepatocyte-like cells with more mature hepatocyte functions. METHODS: Successful establishment of high-level HNF4α and FOXA2 co-overexpression in human induced hepatocyte-like cells (hiHep cells) was verified by flow cytometry, immunofluorescence and RT-PCR. Measurements of albumin (ALB), urea, glucose, indocyanine green (ICG) uptake and release, cytochrome P450 (CYP) activity and gene expression were used to analyze mature hepatic functions of hiHep cells. RESULTS: hiHep cells efficiently express HNF4α and FOXA2 genes and proteins, exhibit typical epithelial morphology and acquire mature hepatocyte-like cell functions, including ALB secretion, urea production, ICG uptake and release, and glycogen storage. hiHep cells can be activated by CYP inducers. The percentage of both ALB and α-1-antitrypsin (AAT)-positive cells was approximately 72.6%. The expression levels of hepatocyte-specific genes (ALB, AAT, and CYP1A1) and liver drug transport-related genes (ABCB1, ABCG2, and SLC22A18) in hiHep cells were significantly higher than those in MSCs-Vector cells. The hiHep cells did not form tumors after subcutaneous xenograft in BALB/c nude mice after 2 months. CONCLUSION: This study provides an accessible, feasible and efficient strategy to generate hiHep cells from MSCs.

MiR-199a-5p suppresses tumorigenesis by targeting clathrin heavy chain in hepatocellular carcinoma.

The deregulation of microRNA (miRNA) is frequently associated with a variety of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the expression and possible role of miR-199a-5p in HCC. The expression of miR-199a-5p was measured by quantitative RT-PCR in HCC. The effect of miR-199a-5p was evaluated by cell viability and colony formation assays in HCC cell lines and tumor cell growth assay in xenograft nude mice. Quantitative real time PCR results showed that miR-199a-5p was down-regulated in 77.9 % (67/86) of HCC tissues compared with adjacent nontumor tissues. MiR-199a-5p mimic reduced cell viability and colony formation by induction of cell arrest in HCC cell lines and inhibited tumor cell growth in xenograft nude mice, but miR-199a-5p inhibitor increased cell viability and colony formation in HCC cell lines and tumor cell growth in xenograft nude mice. Furthermore, CLTC was defined as a potential direct target of miR-199a-5p by MiRanda and TargetScan predictions. The dual-luciferase reporter gene assay results showed that CLTC was a direct target of miR-199a-5p. The use of miR-199a-5p mimic or inhibitor could decrease or increase CLTC protein levels in HCC cell lines. We conclude that the frequently down-regulated miR-199a-5p can regulate CLTC and might function as a tumor suppressor in HCC. Therefore, miR-199a-5p may serve as a useful therapeutic agent for miRNA-based HCC therapy.

Comparison of endovenous microwave ablation versus radiofrequency ablation for lower limb varicose veins.

OBJECTIVE: Endovenous microwave ablation (EMA) is a recently developed thermal ablation technique used in the treatment of lower limb varicose veins. However, its efficacy and safety have been largely understudied. In the present study, we sought to explore the clinical results of EMA and radiofrequency ablation (RFA) in treating lower limb varicose veins. METHODS: Patients who underwent EMA (n = 65) or RFA (n = 46) at our institute from September 2018 to September 2020 were included in this retrospective investigation. The clinical results and complications were evaluated at 1, 3, 6, and 12 months after the procedure. The effects on disease severity and quality of life were evaluated using the venous clinical severity score and chronic venous insufficiency questionnaire (CIVIQ). RESULTS: The technical success rate was 100% for both experimental groups. Although the operative time between the two groups was comparable, the EMA technique was associated with lower direct costs (P < .001), although also with prolonged hospitalization (P < .001). We found that the use of EMA correlated with more pain at 48 hours postoperatively. Except for the visual analog scale scores, no statistically significant variations were observed in the occurrence of postoperative complications within the first 48 hours postoperatively between the EMA and RFA groups, including paresthesia, ecchymosis, induration, and phlebitis (P > .05). At 4 weeks postoperatively, significantly less pigmentation was observed in the RFA group than in the EMA group (13.04% vs 32.31%; P = .020). However, the pigmentation had resolved in all patients by 12 months postoperatively. The two groups had a reduction in the venous clinical severity scores and an increase in the CIVIQ scores after the procedure. However, the CIVIQ scores within the RFA group had increased more than had those within the EMA group (P < .05). No significant differences were found in recurrence between the two groups (EMA group, 1.54%; RFA group, 2.17%; P = .804). CONCLUSIONS: Both ablation techniques are safe and effective. RFA is associated with relatively higher treatment costs but shorter hospitalization and better quality of life improvement.

[Clinical observation of transcatheter arterial chemoembolization plus sorafenib in the treatment of advanced hepatocellular carcinoma with different types of portal vein tumor thrombosis].

OBJECTIVE: To explore the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus sorafenib in the treatment of advanced hepatocellular carcinoma with different types of portal vein tumor thrombosis. METHODS: A total of 32 patients of advanced hepatocellular carcinoma with tumor thrombosis in portal vein were retrospectively analyzed. All of them took oral sorafenib after TACE. They were divided into 3 groups according to imaging examinations of tumor thrombosis in portal vein. Tumor thrombosis in main portal vein was group A, tumor thrombosis in right/left portal branch group B and tumor thrombosis in the second branch of portal vein group C. Tumor response rate, disease control rate (DCR), overall survival (OS) and time to tumor progression (TTP) was followed up. Liver functions were compared with the pre-treatment level. The occurrences of adverse events were recorded. RESULTS: DCR was 20.0% (Group A), 70.0% (Group B) and 91.7 % (Group C) at 2 months post-treatment. DCR in groups B and C had significant differences with group A (P < 0.05). The median OS was 3 (Group A), 9 (Group B) and 14 months (Group C) and the median TTP 0 (Group A), 3 (Group B) and 6 months (Group C) respectively. The median OS and median TTP were significantly longer in Groups B and C than those in Group A (P < 0.05). Liver function at 2 months post-treatment had no statistical difference with the baseline. The most common adverse effects included hand foot skin reaction (n = 23, 3 cases of grade 3), hypertension (n = 3), diarrhea (n = 25, 3 cases of grade 3), hair loss (n = 12), oral ulcers (n = 1) and gastrointestinal bleeding (n = 2). CONCLUSION: The combined use of TACE and sorafenib is both safe and efficacious in the treatment of advanced hepatocellular carcinoma with tumor thrombosis in portal vein. And it may prolong OS and TTP in hepatocellular carcinoma with tumor thrombosis in right/left portal vein and second branch of portal vein.

[Diagnosis and treatment of carotid-cavernous fistula: analysis of 28 patients].

OBJECTIVE: To evaluate the feasibility and efficacy of endovascular treatment for different types of carotid cavernous fistula (CCF) via the approach of internal carotid artery (ICA) or inferior petrosal sinus (IPS). METHODS: From April 2005 to June 2010, 28 CCF patients underwent endovascular treatment at our institution. There were 13 males and 15 females with a mean age of 39 years (range: 21 - 71). According to the Barrow's classification, they were classified into type A (n = 21), type B (n = 2) and type D (n = 5). Patients of type A underwent detachable balloon embolization of ipsilateral cavernous sinus or stent-graft placement via the ICA approach. Patients of types B and D received detachable coil plus n-BCA (n-butyl-2-cyanoacrylate) embolization of ipsilateral cavernous sinus via the IPS approach. The technical results, complications and therapeutic outcomes were reviewed. RESULTS: Detachable balloons (number: 1 - 4) were used in 16 patients of type A. Angiography at immediate postembolization showed a complete occlusion of fistula in 15 patients and a small residual fistula (< 20%) in 1 patient. Five patients of type A received stent-graft placement. One stent was placed in 4 patients and 2 stents in 1 patient. Complete fistula closures with preserved ICA were documented on immediate angiogram in 3 patients whereas a large residual flow (> 50%) persisted in 1. The fistula was completely occluded after 3 detachable balloons were deployed in affected cavernous sinus through a gap between stent and vascular wall. Both fistula and ICA were occluded in 1 patient after stenting. No cerebral infarction was observed due to the adequate collateral blood flow from contralateral ICA. Complete closures of affected cavernous sinus were achieved in 6 patients of types B and D while residual flow (< 50%) persisted in 1. The number of detachable coils for each embolization ranged from 3 to 8 (mean: 6.0). The volume of n-BCA mixture varied from 1.0 to 2.1 ml (mean: 1.3). The mean duration of n-BCA injection was 65 s (range: 45 - 90). Clinical symptoms were completely relieved in 26 patients. During the mean follow-up period of 30 months (range: 12 - 60), no recurrence of clinical symptoms was observed. No thrombosis or stenosis was found in the lumina of stents. CONCLUSION: Detachable balloon embolization is the preferential treatment for direct CCF. Detachable coil plus n-BCA embolization of cavernous sinus via the IPS approach is an efficient and safe treatment for indirect CCF.

[Labeling of liver cancer cell for fluorescence imaging study by far-red fluorescence protein reporter gene mKate2].

OBJECTIVE: To create far-red fluorescence protein reporter gene mKate2 lentivirus, label human liver cancer cell line HepG2 with lentivirus and explore the feasibility of in vitro fluorescence imaging of labeled tumor cells so as to provide experimental rationales for in vivo fluorescence tumor imaging. METHODS: mKate2 gene was amplified from pmKate2-N plasmid. Then the fragment was inserted into the lentivirus expression vector pLenti6.3/V5-DEST. The expression plasmids pLenti6.3-mKate2 and the packaging plasmids were cotransfected into 293T cells. The biological titer of lentivirus was determined. HepG2 cells were infected with mKate2 lentivirus at a MOI (virus multiplicity of infection) of 6 for 96 hours. The infection efficiency was assayed through fluorescence microscope and fluorescent-activated cell scanning (FACS). And 2 × 10(6) mKate2-HepG2 cells were collected for fluorescence imaging through an optical imaging system. And the optimal imaging parameters were determined. RESULTS: DNA sequencing analysis confirmed that mKate2 gene sequence was correct and there was no mutation or deletion. The biological titer of produced mKate2 lentivirus was 1.6 × 10(6) TU/ml. At 96 hours after mKate2 lentivirus infection, fluorescence microscope showed that mKate2 was expressed in a large percentage of cells. FACS assay showed that the mKate2 positive rate was 93.8% ± 0.4%. Excitation light 530 ± 15 nm and emission light 710 ± 28 nm were the optimal imaging parameters for mKate2-HepG2 cells. CONCLUSION: Lentivirus can mediate efficiently the mKate2 reporter gene labeling of human liver cancer cell line HepG2. The mKate2-labeled HepG2 cells can be detected through in vitro fluorescence imaging. Further tracing studies of in vivo tumor fluorescence imaging are technically feasible.

Systemic Inflammation Response Index is a Prognostic Risk Factor in Patients with Hepatocellular Carcinoma Undergoing TACE.

BACKGROUND: Mounting evidence has shown that systemic inflammation response index (SIRI), a novel prognostic biomarker based on peripheral lymphocyte, neutrophil and monocyte counts, is associated with poor prognosis for several tumors. However, the prognostic value of SIRI in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is elusive. Herein, we aimed to evaluate the correlation between SIRI and clinical outcomes in these patients. METHODS: A total of 194 consecutive patients who underwent TACE were included in this study. Patients were stratified into high and low SIRI groups based on the cut-off value using receiver operating characteristic (ROC) analysis. Independent risk factors for tumor response were analyzed using forward stepwise logistic regression. A one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) and overall survival (OS) between low and high SIRI patients. The discriminatory power of the combination of number of tumors and SIRI in predicting initial TACE response was evaluated by ROC analysis. RESULTS: Patients were divided into high SIRI (> 0.88) and low SIRI (≤ 0.88) groups. High SIRI (p = 0.003) and more than three tumors (p = 0.002) were significantly related to poorer tumor response. Moreover, the low SIRI group had longer PFS and OS than the high SIRI group (both P < 0.05) before and after PSM. Combination of SIRI and number of tumors can improve the predictive ability to predict initial TACE response with an area under the curve (AUC) of 0.678. CONCLUSION: Pretreatment peripheral blood SIRI was found to be an independent predictor of tumor response and clinical outcomes in patients with HCC undergoing TACE. Patients with high SIRI may have a poor prognosis.

[Multimodality interventional treatments for biliary complications after orthotopic liver transplantation: a preliminary study].

OBJECTIVE: To describe the technique, efficacy, and safety of multimodality interventional treatments for biliary complications after orthotopic liver transplantation (OLT). The core of multimodality interventional treatments is percutaneous transhepatic biliary drainage (PTBD). METHODS: From January 2006 to May 2008, seventy-two patients with biliary complications afte OLT were closed in our study. On the basis of the cholangiographic appearance, patients were classified into 4 groups: anastomotic biliary strictures (n = 19), hilar biliary strictures (n = 16), multifocal/diffuse biliary strictures (n = 31), and anastomotic biliary fistulae (n = 6). All patients were treated in our hospital, including PTBD only in 6 patients, PTBD combined with balloon dilation in 50 patients, balloon dilation and plastic stent implantation in 10 patients, balloon dilation and metallic stent implantation in 6 patients. Their data were analyzed retrospectively, including serum hemobilirubin, cholangiographic appearance and complications. RESULTS: PTBD were successful in all cases. The clinical symptoms improved or eliminated were observed in 66 cases, the effective rate was 91.7% (66/72). Among 72 patients, 26 patients were free of drainage tube, 8 patients underwent second PTBD for the obstruction of biliary stents, and 38 patients maintained drainage tube for long-term. In 66 patients with biliary obstruction, the direct bilirubin was (145 +/- 106) micromol/L before treatments and 76 micromol/L +/- 59 micromol/L one month after PTBD (t = 3.78, P < 0.001). The rate of biliary tract infection was 14.3% and 43.8% respectively with the tip of drainage tube placed in biliary duct and in duodenum. There was a significantly statistical difference between these two items (chi(2) = 4.886, P = 0.027). CONCLUSION: PTBD combined with balloon dilation and biliary stent implantation is a effective therapeutic modality for biliary complications after OLT, which can improve patients' clinical symptoms, elevate patients' quality of life. The tip of drainage tube being placed in biliary duct can decrease the rate of biliary tract infection significantly.

[Transportal variceal sclerotherapy with n-butyl-2-cyanoacrylate for gastric fundal varices].

OBJECTIVE: To evaluate the technique, safety and clinical efficacy of transportal variceal sclerotherapy with n-butyl-2-cyanoacrylate (NBCA) for gastric fundal varices. METHODS: Twenty-one patients with gastric fundal varices confirmed by endoscopy were enrolled in this study. The causes of the gastric varices were cirrhosis caused by hepatitis virus B or C (n = 16) and hepatocellular carcinoma with portal venous obstruction (n = 5). Percutaneous transhepatic or transplenic portography were performed on all 21 patients. The gastric varices were treated with NBCA-lipiodol mixture injected via a microcatheter introduced into the varices. For 8 patients who had large gastrorenal shunts (GRS), a balloon-occluded catheter was introduced into the GRS via the right femoral and left renal veins before injecting the NBCA-lipiodol. During the NBCA-lipiodol injection, the balloon was inflated to block the flow of GRS. Follow-up evaluations included findings of the laboratory liver function tests, upper intestinal endoscopies, and the occurrences of rebleeding. RESULTS: In 20 patients (95.2%), the gastric varices were successfully obliterated with 2-8 ml of NBCA-lipiodol. In one patient with a large GRS, sclerotherapy was not successfully performed because a balloon-occluded catheter was not available during the procedure. In five patients, small amounts of NBCA-lipiodol entered into the distal pulmonary artery branches. Two of them suffered from transient irritable coughs; no patient developed severe pulmonary embolism. Embolization of portal venous branches occurred in two patients, which were not treated specifically. In comparison with the findings before the treatments, the serum alanine aminotransferase levels decreased at both 3 and 6 months after treatments (P less than 0.05); serum albumin levels increased at 6 months (P less than 0.05); the prothrombin times decreased at 6 months (P less than 0.05); but no significant changes were seen in the serum bilirubin levels. Fifteen patients were followed-up endoscopically for 3 months after the treatment. Gastric varices were completely resolved in 10 patients (66.7%) and were markedly smaller in 4 patients (26.6%). Worsening of the esophageal varices occurred in 3 patients (20%). All the patients were followed-up from 1 to 30 months [(16.7+/-8.8) months]. Rebleeding was observed in 4 patients, and the cumulative rebleeding rate at 1 year was 9.52%. CONCLUSION: Transportal variceal sclerotherapy with NBCA is a safe and effective method for treating gastric varices. Microcatheter technique and occlusion of the large gastrorenal shunt with a balloon-occluded catheter are necessary to ensure obliteration of gastric varices and prevent pulmonary embolism.

[The role of multi-detector row CT in the diagnosis and hemodynamic studies of gastric varices in portal hypertension].

OBJECTIVE: To evaluate the value of multi-detector row CT (MDCT) in the diagnosis and hemodynamic studies of gastric varices (GV) in portal hypertension by comparison with endoscopy and DSA direct portography. METHODS: Thirty-six consecutive cirrhotic patients with GV confirmed by endoscopy underwent tri-phase contrast-enhanced CT scans and CT portography (CTP) within 2 weeks after endoscopy examination. Three independent experienced radiologists, who were blinded to the patients' clinical data, analyzed the CT images, including the size and location of GV as well as afferent and efferent veins of GV, separately. Interobserver agreement among the 3 radiologists with regard to the diagnosis of submucosal and perigastric GV was determined by Kappa (k) values. The findings of endoscopy were used as standards. RESULTS: Sub mucosal GV was diagnosed in 34 of the 36 patients (94.4%) and perigastric GV in all 36 patients (100%) by the observation of the 3 radiologists. MDCT showed an excellent interobserver reliability with regard to the diagnosis of submucosal GV (kappa = 0.85) and perigastric GV (kappa = 1.0). Agreement between MDCT and endoscopy with regard to the opacification of variceal size and location were 86.1% and 88.9% respectively. The sensitivity, specificity, accuracy, and positive predictive value of CTP in the opacification of afferent and efferent veins of GV were all more than 80%. The frequencies of participation of posterior gastric vein and short gastric vein in blood supply to gastric fundal varices in the isolated gastric varices and gastroesophageal varices type 2 (GEV2) were 94.1% and 70.6% respectively, both significantly higher than those in the gastroesophageal varices type 1 (GEV1, 52.6% and 31.6%, respectively, both P < 0.05). The main blood drainage route of GEV1 was via azygous system into the super vena cava (100%), whereas in the gastric fundal varices the main blood drainage route was via the gastrorenal shunts into the inferior vena cava (82.4%). CONCLUSION: MDCT can be used as an important tool for detecting submucosal and perigastric GV, and can clearly reveal the size, location, and hemodynamics of GV.