Correlation between preoperative Doppler ultrasonography-assessed specific accessory cephalic vein diameter-cephalic vein diameter ratio (r) and early dysfunction of Radial artery-Cephalic vein arteriovenous fistula: a single-center cross-sectional study.

Background: Accessory cephalic vein (ACV) ligation can circumvent immature arteriovenous fistula (AVF). However, no consensus has been reached on the definite timing of ACV ligation. This study aimed to retrospectively analyze the correlation between preoperative Doppler ultrasonography (DUS)-assessed specific ACV diameter-cephalic vein diameter ratio (r) and early dysfunction of Radial artery-Cephalic vein (RC)-AVF in order to improve the early maturity rate of RC-AVF. Methods: A total of 258 patients who underwent RC-AVF at The Third Affiliated Hospital, Sun Yat-sen University from 1 June 2018 to 31 March 2022 were included in this study. The inclusion criteria were as follows: (I) cephalic vein ≥2.0 mm and radial artery ≥1.5 mm, suitable for RC-AVF establishment; (II) presence of an ACV. As per the specific r determined using preoperative DUS assessment, all patients were classified into two groups: Group A (r<0.8) and Group B (r≥0.8). Furthermore, patients in each group were divided into intervention and non-intervention subgroups based on the presence or absence of intraoperative ACV ligation, respectively. Patient data including age, sex, underlying disease, AVF side, and radial diameter were compared. The difference of maturity rate between participants in the intervention group and non-intervention group with different r values was analyzed, so as to obtain the relationship between different r values and maturity rate. Results: No statistical differences were observed between the intervention and non-intervention subgroups in the two groups in terms of sex, age, comorbidities, complications, AVF side, radial artery, cephalic vein, and ACV diameters (P>0.05). When r<0.8, the maturity rates of the intervention group and the non-intervention group were 80% and 92.98%, respectively, χ2=4.561. The difference in maturation rate between the intervention and non-intervention subgroups was insignificant (P=0.075) when r<0.8. When r≥0.8, the maturity rates of the intervention group and the non-intervention group were 89.83% and 45.45%, respectively, χ2=25.943. The difference in maturation rates between the intervention and non-intervention subgroups was significant when r≥0.8 (P<0.001). Conclusions: Preoperative DUS suggested a correlation between r≥0.8 and early immaturity of RC-AVF. Therefore, concurrent intraoperative ACV ligation should be carried out when preoperative r is ≥0.8, as it may reduce the early power dysfunction of RC-AVF.

Stent placement with iodine-125 seeds strand effectively extends the duration of stent patency and survival in patients with unresectable malignant obstructive jaundice.

Background: This study aimed to compare the treatment outcomes and safety between stent placement with or without Iodine-125 (125I) seeds strand for patients with unresectable malignant obstructive jaundice (MOJ).Methods: A total of 84 patients with unresectable MOJ treated in our hospital were retrospectively included and divided into the stent group (n = 54) undergoing biliary stent placement and the stent + seeds group (n = 30) receiving stent placement with 125I seeds strand. The therapeutic outcome, postoperative complications, duration of patient survival and stent patency were compared between groups. Kaplan-Meier survival analysis was performed to compare the duration of patient survival and stent patency between groups. Cox-regression analysis was performed to investigate predictive factors for disease-free survival and overall survival.Results: The stent + seeds group had significantly longer duration of patency (231.57 ± 256.54 vs. 110.37 ± 120.52) and overall survival (310.57 ± 330.54 vs. 173.15 ± 219.40) than the stent group (both p < .05). In addition, Kaplan-Meier survival analysis confirmed that the stent + seeds group had longer duration of patency (log-rank test, p = .001) and higher overall survival rate (log-rank test, p = .020) than the stent group. Furthermore, Cox-regression analysis demonstrated that treatment methods was an independent factor associated with disease-free survival (HR: 0.36, 95% CI: 0.19-0.70; p = .003) and overall survival (HR: 1.01, 95% CI: 1.00-1.01; p < .001).Conclusion: The stent placement with 125I seeds strand can significantly improve the primary patency rate and overall survival time in MOJ patients.

Chiral ruthenium(II) complex Δ-[Ru(bpy)2(o-FMPIP)] (bpy = bipyridine, o-FMPIP = 2-(2'-trifluoromethyphenyl) imidazo[4,5-f][1,10]phenanthroline) as potential apoptosis inducer via DNA damage.

Chiral ruthenium(II) complexes have long been considered as potential anticancer agents. Herein, in vivo inhibitory activity of a chiral ruthenium(II) complex coordinated by ligand 2-(2'-trifluoromethyphenyl) imidazo [4,5-f][1,10]phenanthroline, Δ-[Ru(bpy)2(o-FMPIP)] (D0402) on Kunming(KM) mice bearing tumor (H22 hepatic cancer) has been evaluated, and the results showed that the tumor weight of mice treated with 0.22 mg/(kg·day) D0402 via i.v. administration for 7 days decreased about 31.79% compared to the control group, while the body weight, as well as the thymus, spleen, liver, lung, and kidney indices of mice treated with D0402 observed almost no loss compared to the control group. Furthermore, the mechanism studies on anti-angiogenic showed that D0402 could inhibit the formation of angiogenesis in the transgenic Tg(fli1a: EGFP) zebrafish. After treated with D0402, the sub-intestinal vessels(SIVs) of the zebrafish became disordered and chaotic, and was dosage dependent. Moreover, the TUNEL analysis and comet assays revealed that D0402 can induce apoptosis of HepG2 cell through DNA damage, and this was further demonstrated by immunofluorescence analysis with the number of γ-H2AX increased following the increasing amount of D0402. Besides, in vivo toxicity of D0402 has also been investigated on the development of zebrafish embryo, and the results showed that there were no death or development delay occurred for zebrafish embryo treated with D0402 up to concentration of 60 µM. All in together, this study suggested that D0402 can be developed as a potential inhibitor against liver cancer through co-junction of anti-angiogenesis and apoptosis-inducing via DNA damage in the near future.

DDX24 Mutations Associated With Malformations of Major Vessels to the Viscera.

Vascular malformations present diagnostic and treatment challenges. In particular, malformations of vessels to the viscera are often diagnosed late or incorrectly due to the insidious onset and deep location of the disease. Therefore, a better knowledge of the genetic mutations underlying such diseases is needed. Here, we evaluated a four-generation family carrying vascular malformations of major vessels that affect multiple organs, which we named "multiorgan venous and lymphatic defect" (MOVLD) syndrome. Genetic analyses identified an association between a mutation in DEAD-box helicase 24 (DDX24), a gene for which the function is largely unknown, and MOVLD. Next, we screened 161 patients with sporadic vascular malformations of similar phenotype to our MOVLD family and found the same mutation or one of the two additional DDX24 mutations in 26 cases. Structural modeling revealed that two of the mutations are located within the adenosine triphosphate-binding domain of DDX24. Knockdown of DDX24 expression in endothelial cells resulted in elevated migration and tube formation. Transcriptomic analysis linked DDX24 to vascular system-related functions. Conclusion: Our results provide a link between DDX24 and vascular malformation and indicate a crucial role for DDX24 in endothelial cell functions; these findings create an opportunity for genetic diagnosis and therapeutic targeting of malformations of vessels to the viscera.

Inhibition of Orai1 Store-Operated Calcium Channel Prevents Foam Cell Formation and Atherosclerosis.

OBJECTIVE: To determine the role of orai1 store-operated Ca(2+) entry in foam cell formation and atherogenesis. APPROACH AND RESULTS: Acute administration of oxidized low-density lipoprotein (oxLDL) activates an orai1-dependent Ca(2+) entry in macrophages. Chelation of intracellular Ca(2+), inhibition of orai1 store-operated Ca(2+) entry, or knockdown of orai1 dramatically inhibited oxLDL-induced upregulation of scavenger receptor A, uptake of modified LDL, and foam cell formation. Orai1-dependent Ca(2+) entry induces scavenger receptor A expression and foam cell formation through activation of calcineurin but not calmodulin kinase II. Activation of nuclear factor of activated T cells is not involved in calcineurin signaling to foam cell formation. However, oxLDL dephosohorylates and activates apoptosis signal-regulating kinase 1 in macrophages. Orai1 knockdown prevents oxLDL-induced apoptosis signal-regulating kinase 1 activation. Knockdown of apoptosis signal-regulating kinase 1, or inhibition of its downstream effectors, JNK and p38 mitogen-activated protein kinase, reduces scavenger receptor A expression and foam cell formation. Notably, orai1 expression is increased in atherosclerotic plaques of apolipoprotein E(-/-) mice fed with high-cholesterol diet. Knockdown of orai1 with adenovirus harboring orai1 siRNA or inhibition of orai1 Ca(2+) entry with SKF96365 for 4 weeks dramatically inhibits atherosclerotic plaque development in high-cholesterol diet feeding apolipoprotein E(-/-) mice. In addition, inhibition of orai1 Ca(2+) entry prevents macrophage apoptosis in atherosclerotic plaque. Moreover, the expression of inflammatory genes in atherosclerotic lesions and the infiltration of myeloid cells into the aortic sinus plaques are decreased after blocking orai1 signaling. CONCLUSIONS: Orai1-dependent Ca(2+) entry promotes atherogenesis possibly by promoting foam cell formation and vascular inflammation, rendering orai1 Ca(2+) channel a potential therapeutic target against atherosclerosis.

Survival benefit of chemoembolization plus Iodine125 seed implantation in unresectable hepatitis B-related hepatocellular carcinoma with PVTT: a retrospective matched cohort study.

OBJECTIVES: To investigate the survival benefit of transarterial chemoembolization (TACE) plus Iodine125 seed implantation (TACE-Iodine125) in hepatitis B-related HCC patients with portal vein tumour thrombus (PVTT) and the underlying prognostic factors. METHODS: A retrospective matched cohort study was performed on consecutive HCC patients with PVTT from January 2011 to June 2014. Seventy patients (TACE-Iodine125 group) who underwent TACE-Iodine125 were compared with a historical case-matched control group of 140 patients (TACE group) who received TACE alone. The survival of patients and the underlying prognostic factors were analysed. RESULTS: The median survival times of the TACE-Iodine125 and TACE groups were 11.0 and 7.5 months, respectively (p < 0.001). The survival probability at 12, 24, and 36 months was 50 %, 14.5 %, and 14.5 % vs. 25 %, 9 %, and 5 % in the TACE-Iodine125 and TACE groups, respectively (p < 0.001). The PVTT responders had better survival than the PVTT non-responders (p < 0.001). For the PVTT non-responders, there were no differences in the survival curves between the groups (p = 0.353). Multivariate analysis showed that type III PVTT (p < 0.001) and APS (p < 0.001) were independent predictors of poor prognosis. In contrast, the treatment modality of TACE-Iodine125 (p < 0.001) and PVTT response (p = 0.001) were favourable prognostic features. CONCLUSIONS: TACE combined with Iodine125 seed implantation may be a good choice for selected HB-HCC patients with PVTT. KEY POINTS: • TACE-Iodine125 was more effective than TACE for patients with HCC-PVTT. • The TACE-Iodine125 procedure was safe. • TACE-Iodine125 was conditional for patients with HCC-PVTT. • TACE-Iodine125 resulted in a better PVTT response compared to TACE alone. • A good PVTT response is a favourable prognostic factor.

MR tracking of SPIO-labeled mesenchymal stem cells in rats with liver fibrosis could not monitor the cells accurately.

Our previous study showed that in vivo magnetic resonance (MR) imaging is effective in tracking superparamagnetic iron oxide (SPIO)-labeled bone marrow mesenchymal stem cells (BMSCs) in rats with liver fibrosis. SPIO-labeling-induced signal reduction on MR images was completely reversed within 15 days after transplantation. It is still unclear whether the signal changes in MR imaging could reflect the number of transplanted cells in the liver. In the present study, BMSCs of male rats were doubly labeled with enhanced green fluorescent protein (EGFP) and SPIO and injected intravascularly into female rats with liver fibrosis. At different time points after injection, MR imaging was performed. The distribution of SPIO particles and EGFP-positive cells was determined by Prussian blue staining and EGFP immunohistochemistry, respectively. The distribution of transplanted BMSCs in various organs was assessed by detection of the SRY gene using real-time quantitative PCR. At 15 days post transplantation, the numbers of transplanted cells were significantly decreased in the lung, kidney, spleen and muscle, but not liver and heart, in comparison with those at 7 days after transplantation. EGFP staining-positive cells were observed in the liver intralobular parenchyma, while Prussian blue staining was negative at 42 days after transplantation. Taken together, SPIO particles and EGFP-labeled BMSCs show a different tissue distribution pattern in rats with liver fibrosis after a long-term period of monitoring. SPIO-based MR imaging may not be suitable for long-term tracking of transplanted BMSCs in vivo.

[Transarterial chemoembolization plus computed tomography-guided percutaneous radiofrequency ablation for small hepatocellular carcinoma in special locations].

OBJECTIVE: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC) in special locations. METHODS: From June 2008 to December 2011, a total of 36 patients with small HCC (39 lesions) received TACE plus CT-guided percutaneous RFA at our hospital. The follow-up period was over 6 months. They were divided into 2 groups according to the locations of HCC: special location (located at hepatic subcapsular, portal area, next to large blood vessels or other organs) and non-special location groups. All patients underwent TACE at one month pre-RFA.Follow-up imaging with enhanced computed tomography (CT) or magnetic resonance imaging (MRI) was performed one month after combined treatment to evaluate the complete ablation rate in two groups.If a complete ablation was achieved, enhanced CT or MRI was performed every 1-3 months to evaluate the local tumor progression. The occurrence rate of complications, complete ablation rate, local tumor progression and time to tumor progression (TTP) were compared between two groups. RESULTS: In the special location group, a total of 24 TACE and 26 ablations were performed in 20 patients with 22 lesions while there were 18 TACE and 17 ablations in 16 patients with 17 lesions in the non-special location group.In the special location group, 12 patients (46.2%) suffered procedure-related complications, including a major complication (n = 1, left ventricular failure) and a minor complication (n = 11) of vascular injury (n = 6), subcapsular hemorrhage (n = 3) and arterial-portal vein fistula (n = 2); whereas only 3 patients (17.6%) suffered a minor complication of subcapsular hemorrhage (n = 1) and arterial-portal vein fistula (n = 2) in the special location group. The occurrence rate of complications was similar between two groups (P = 0.101). The complete ablation rate after one month was 68.2% (15/22) in the special location group and it was significantly higher than that of the non-special location group (100%, P = 0.012).In the special location group, the 6-month, 1-, 2-, 3-year local tumor progression rates were 31.8%, 40.9%, 45.5%, 45.5% versus 0,0,0, 5.9% in the non-special location group respectively. The mean TTP of 14.4 months in the special location group was markedly shorter than that in the non-special location group (31.5 months, P = 0.001). CONCLUSION: The combined regimen of TACE and percutaneous RFA is both safe and feasible for small HCC in special location. And the rate of local tumor progression is significantly higher than that of non-special location tumor. Postoperative close imaging follow-up is needed for tumor residue or recurrence.

Effects of percutaneous transhepatic interventional treatment for symptomatic Budd-Chiari syndrome secondary to hepatic venous obstruction.

OBJECTIVE: Budd-Chiari syndrome (BCS) is a rare and life-threatening disorder characterized by hepatic venous outflow obstruction. The management of BCS includes anticoagulation and thrombolysis, percutaneous transhepatic stent angioplasty (PTSA), and transjugular intrahepatic portosystemic shunt (TIPS), but the effect of these approaches varies greatly. The aim of our study was to retrospectively evaluate the medium-term effects of PTSA and TIPS of BCS secondary to hepatic venous outflow obstruction and to determine the critical factors affecting the efficacy. METHODS: From June 2007 to June 2012, 18 patients (15 males and 3 females; mean age, 36 ± 9 years) with BCS (obstruction of the hepatic veins) treated by PTSA (n = 15) and TIPS (n = 3) were studied retrospectively. Clinical records were analyzed with respect to underlying disease, therapeutic interventions, complications, quality of life, and overall outcome. RESULTS: Percutaneous transhepatic interventional treatment was technically successful in all patients. In PTSA group, the primary and secondary stent patency rates were 80% and 86.7%, respectively. In the TIPS group, ascites resolved completely, and liver congestion and function were relieved greatly in all three patients. Hemodynamic features and clinical symptoms in patients with successful treatment improved significantly. Physical aspects evaluated by SF-36 were improved greatly at the end of follow-up. CONCLUSIONS: For segmental stenosis or occlusion of hepatic vein caused by thrombosis or membranous webs, PTSA should be recommended as the first choice. TIPS should be applied for diffuse stenosis or occlusion in all the hepatic veins and branches. Standard anticoagulation may promote stent patency. Quality of life after interventional treatment was improved partially, and the mental aspects need to be further investigated.

MR tracking of magnetically labeled mesenchymal stem cells in rats with liver fibrosis.

PURPOSE: In vivo magnetic resonance (MR) tracking of magnetically labeled bone marrow mesenchymal stem cells (BMSCs) administered via the mesenteric vein to rats with liver fibrosis. MATERIALS AND METHODS: Rat BMSCs were labeled with superparamagnetic iron oxide (SPIO) and the characteristics of the BMSCs after labeling were investigated. Eighteen rats with CCL4-induced liver fibrosis were randomized to three groups to receive SPIO-labeled BMSCs (BMSC-labeled group), cell-free SPIO (SPIO group), or unlabeled BMSCs (control group). MR imaging of the liver was performed at different time points, and signal-to-noise ratio (SNR) of the liver was measured. In vivo distribution of delivered BMSCs was assessed by histological analysis. RESULTS: Labeling of BMSCs with SPIO did not significantly alter cell viability and proliferation activity. In BMSC-labeled group, the liver SNR immediately decreased from 8.56+/-0.26 to 3.53+/-0.41 at 1 h post injection and remained at a significantly lower level till 12 days (P<.05 versus the level before). By contrast, the liver SNR of the SPIO group almost recovered to the preinjection level (P=.125) at 3 days after a transient decrease. In control group, the liver SNR demonstrated no significant difference at the tested time points. Additionally, Prussian blue-positive cells were mainly distributed in the liver parenchyma, especially in injured areas. CONCLUSION: The magnetically labeled BMSCs infused through the mesenteric vein can be detected in the fibrotic liver of rats using in vivo MR imaging up to 12 days after injection.

Gastric varices in patients with portal hypertension: evaluation with multidetector row CT.

BACKGROUND: Gastric varices (GVs) are a major cause of gastrointestinal bleeding in patients with portal hypertension. Few studies have evaluated GVs with multidetector row computed tomography (MDCT). GOALS: To assess the diagnostic performance of MDCT in detecting GVs and revealing variceal hemodynamic changes in patients with cirrhosis. STUDY: A total of 127 consecutive cirrhotic patients who underwent both liver MDCT and esophagogastroduodenoscopy (EGD) were analyzed retrospectively. Two independent radiologists reviewed MDCT images for the detection of GVs. The variceal hemodynamic changes were assessed by the 2 radiologists in consensus on MDCT portography. RESULTS: On the basis of EGD, of the 127 patients, 36 had GVs (28.4%), including small GVs in 15 patients and large GVs (>or=5 mm) in 21 patients. In detecting and grading GVs, there were moderate agreements (kappa value: 0.514 to 0.563) between MDCT and EGD, but in differentiating large varices requiring prophylactic therapy, a substantial agreement (kappa value: 0.804 for radiologist 1 and 0.796 for radiologist 2) was found. For radiologist 1, the sensitivity, specificity, accuracy, and positive and negative predictive values of MDCT for the identification of large GVs were 85.7%, 96.2%, 94.5%, 81.8%, and 97.1%, respectively; whereas for radiologist 2, they were 81.0%, 97.2%, 94.5%, 85.0%, and 96.3%, respectively. In evaluating the afferent and efferent veins of varices, the sensitivity, specificity, accuracy, and positive predictive value of MDCT portography were more than 80.0%. CONCLUSIONS: MDCT is an effective screening tool for differentiating large GVs and revealing the afferent and efferent veins of varices in patients with cirrhosis.

[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.

[Radiofrequency ablation with or without transcather arterial chemoembolization for management of hepatocellular carcinoma].

OBJECTIVE: To evaluate the efficacy and complications of radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) for management of hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was conducted for 62 small HCC cases undergoing RFA with or without TACE, and in each case, the tumors were not more than 3 with a diameter below 5 cm. Nineteen cases were managed with RFA alone (RFA group) while the other 27 underwent RFA combined with TACE (TACE+RFA group). Percutaneous RFA (RITA 1500) procedure was performed under CT guidance 1-3 weeks after TACE in TACE+RFA group. RESULTS: The complete tumor necrosis rate was 77.8% (21/27) in TACE+RFA group, significantly higher than that in RFA group [57.9% (11/19), P<0.01], and the former group had a significantly lower local recurrence rate than the latter [22.2% (6/27) vs 42.1% (8/19), P<0.01]. Postoperative fever, local pain and temporary hepatic function abnormality were the common complications that were relieved after proper interventions, and mortality did not occur in these cases. CONCLUSION: The combination of TACE and RFA significantly increases the complete tumor necrosis rate and decreases the recurrence rate of small HCC. CT-guided percutaneous RFA can be a safe and effective therapy for small HCC.