Radiomic advances in the transarterial chemoembolization related therapy for hepatocellular carcinoma.

Radiomics is a hot topic in the research on customized oncology treatment, efficacy evaluation, and tumor prognosis prediction. To achieve the goal of mining the heterogeneity information within the tumor tissue, the image features concealed within the tumoral images are turned into quantifiable data features. This article primarily describes the research progress of radiomics and clinical-radiomics combined model in the prediction of efficacy, the choice of treatment modality, and survival in transarterial chemoembolization (TACE) and TACE combination therapy for hepatocellular carcinoma.

Efficacy of intra-arterial catheter-directed thrombolysis for popliteal and infrapopliteal acute limb ischemia.

OBJECTIVE: The purpose of this study was to examine the efficacy and safety of catheter-directed thrombolysis (CDT) for first-line treatment of popliteal and infrapopliteal acute limb ischemia. METHODS: A total of 28 consecutive patients (30 limbs) who underwent CDT for treatment of popliteal and infrapopliteal acute limb ischemia of thromboembolic origin between March 2012 and December 2017 were enrolled in this study. Per the Society for Vascular Surgery, limbs were classified into three runoff score groups: <5, good; 5 to 10, compromised; and >10, poor. The primary end points were primary patency and limb salvage assessed by Kaplan-Meier survival analysis. Secondary end points were technical success and clinical success. The Society for Vascular Surgery-recommended scale for gauging changes in clinical status was used to assess clinical success. Safety of the procedure was evaluated on the basis of periprocedural complications according to the Society of Interventional Radiology classification system. RESULTS: Technical success was achieved in 25 (83.33%) treated limbs. Improved clinical status (grade +3/+2) was achieved in 93.33% of limbs. Primary patency and limb salvage for the entire cohort were 76.67% and 90% at 6 months and 60.0% and 76.67% at 12 months, respectively. The patency rate at 6 months and 12 months was 91.67% and 83.33% for the good runoff group, 80% and 60% for the compromised runoff group, and 50% and 25% for the poor runoff group, respectively. The patency rate of the good runoff group was significantly higher compared with that of the poor runoff group (P = .004). Major amputation rate and mortality rate were 16.67% and 7.14%, respectively, at 12 months. The reintervention rate was 3.57% at 6 months and 21.42% at 12 months. CONCLUSIONS: CDT is safe and effective for revascularization of smaller vessel acute arterial thromboembolism as a primary therapy. However, more studies with a larger sample are warranted.

Irradiation stents vs. conventional metal stents for unresectable malignant biliary obstruction: A multicenter trial.

BACKGROUND & AIMS: Placement of an irradiation stent has been demonstrated to offer longer patency and survival than an uncovered self-expandable metallic stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO). We aim to further assess the efficacy of an irradiation stent compared to an uncovered SEMS in those patients. METHODS: We performed a randomized, open-label trial of participants with unresectable MBO at 20 centers in China. A total of 328 participants were allocated in parallel to the irradiation stent group (ISG) or the uncovered SEMS group (USG). Endpoints included stent patency (primary), technical success, relief of jaundice, overall survival, and complications. RESULTS: The first quartile stent patency time (when 25% of the patients experienced stent restenosis) was 212 days for the ISG and 104 days for the USG. Irradiation stents were significantly associated with a decrease in the rate of stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at 360 days; p = 0.010). Patients in the ISG obtained longer survival time (median 202 days vs. 140 days; p = 0.020). No significant results were observed in technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%; p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p = 0.841). CONCLUSIONS: Insertion of irradiation stents instead of uncovered SEMS could improve patency and overall survival in patients with unresectable MBO. LAY SUMMARY: For patients with unresectable malignant biliary obstruction (MBO), placement of a self-expandable metallic stent (SEMS) is a recommended palliative modality to relieve pruritus, cholangitis, pain, and jaundice. However, restenosis is a main pitfall after stent placement. Data from this first multicenter randomized controlled trial showed that insertion of an irradiation stent provided longer patency and better survival than a conventional metal stent. ClinicalTrials.gov ID: NCT02001779.

Predictors of delayed wound healing after successful isolated below-the-knee endovascular intervention in patients with ischemic foot ulcers.

OBJECTIVE: The purpose of this study was to explore the predictors of delayed wound healing and their use in risk stratification for endovascular treatment (EVT) of patients with critical limb ischemia (CLI) due to isolated below-the-knee lesions. METHODS: Wound healing rates were analyzed retrospectively in patients who underwent successful below-the-knee percutaneous transluminal balloon angioplasty for CLI with tissue loss between May 2008 and June 2013. We also analyzed the independent predictors of delayed wound healing and their use in risk stratification. RESULTS: The cumulative wound healing rates were 13.9%, 43.8%, 57.7%, and 65.7% at 3, 6, 9, and 12 months, respectively. Multivariate Cox proportional hazards analysis revealed the following as independent predictors of wound nonhealing after initial successful EVT: patients with end-stage renal disease receiving dialysis (hazard ratio [HR], 2.6; 95% confidence interval [CI], 1.0-6.3; P  = .04); albumin level <3.0 g/dL (HR, 2.0; 95% CI, 1.1-3.8; P  = .02); C-reactive protein level >5.0 mg/dL (HR, 3.9; 95% CI, 1.6-9.6; P = .003); major tissue loss (HR, 2.1; 95% CI, 1.3-3.4; P = .003); wound infection (HR, 1.9; 95% CI, 1.2-2.9; P = .005); gangrene (HR, 1.8; 95% CI, 1.2-2.8; P = .008); wound depth (University of Texas grade 3; HR, 3.4; 95% CI, 1.4-8.6; P = .009); duration of ulcer (≥2 months; HR, 2.9; 95% CI, 1.0-8.4; P = .048); insulin use (HR, 1.7; 95% CI, 1.0-2.8; P = .04); and lack of below-the-ankle runoff (HR, 1.9; 95% CI, 1.0-3.4; P = .04). CONCLUSIONS: The general status of the patient and the target limb's condition are important predictors of wound nonhealing. Regarding the limb's condition, information on wound depth and duration in addition to wound extent and infection would further enable the selection of suitable CLI patients for EVT. Such information would also enable optimal wound management, leading to successful wound healing and improved limb salvage and survival rates.

MicroRNA-130a regulates autophagy of endothelial progenitor cells through Runx3.

Dysfunction of endothelial progenitor cells (EPC) contribute to diabetic vascular disease. MicroRNAs (miRNAs) are key regulators of diverse cellular processes, including angiogenesis. We recently reported that downregulated miR-130a in patients with Type 2 diabetes mellitus (DM) results in EPC dysfunction, including increased apoptosis, likely via its target runt-related transcription factor 3 (Runx3). However, whether miR-130a affects the autophagy of EPC is unknown. The aim of the present study was to explore the effects of miR-130a on the autophagy and cell death of EPC, as well as their expression of Beclin 1 (BECN1; an initiator of autophagosome formation) and the anti-apoptotic protein Bcl2 (which binds to and inactivates BECN1), and the role of Runx3 in mediating these effects. The EPC were cultured from peripheral blood mononuclear cells of diabetic patients and non-diabetic controls. Cells were transfected with an miR-130a inhibitor, or mimic-miR-130a or mimic-miR-130a plus lentiviral vector expressing Runx3 to manipulate miR-130a and/or Runx3 levels. The number of autophagosomes was counted under transmission electron microscopy and cell death was examined by flow cytometry. The mRNA expression of Beclin1 was measured by real-time polymerase chain reaction and the protein expression of Beclin1 and Bcl2 was determined by western blotting. Both the number of autophagosomes and Beclin1 expression were increased in EPC from patients with DM. Inhibition of miR-130a increased the number of autophagosomes and Beclin1 expression, but attenuated Bcl2 expression. Overexpression of miR-130a decreased the number of autophagosomes, cell death and Beclin1 expression, but promoted Bcl2 expression; these effects were mediated by Runx3. In conclusion, miR-130a is important for maintaining normal autophagy levels and promoting the survival of EPC via regulation of Bcl-2 and Beclin1 expression, via Runx3. MiR-130a may be a regulator linking apoptosis and the autophagy of EPC.

IP-FCM platform detects the existence and regulator-caused dissociation of components in naturally assembled HSP90 complex.

Flow cytometry, in conjunction with immunoprecipitation (IP-FCM), is suggested to have some advantages to conventional IP-western blot technology in analyzing protein complexes. In this paper, to further examine its practicability, we test the use of IP-FCM in detecting the HSP90 complex, which has gained importance in drug research and development and involves more than a dozen components. We found that IP-FCM could effectively detect HSP70, p23, Cdc37, and Cdk6 components in the HSP90 complex naturally formed in U937 cells when this complex was captured by anti-HSP90 antibody-coated polystyrene microspheres. IP-FCM could also detect alteration in components caused by treating cells with HSP90 inhibitors. In a cell-free environment, IP-FCM could detect the direct effects of ATP and/or HSP90 inhibitors (17-N-allylamino-17-demethoxygeldanamycin or celastrol) in causing component dissociation and the time- and dose-effects of inhibitor-caused dissociation. IP-FCM is a practical and powerful platform for analyzing HSP90 complex components, and is thus a useful tool in studying HSP90 complex function and screening inhibitors.

An essential role for stromal interaction molecule 1 in neointima formation following arterial injury.

AIMS: There is evidence to suggest that stromal interaction molecule 1 (STIM1) functions as a Ca2+ sensor on the endoplasmic reticulum, leading to transduction of signals to the plasma membrane and opening of store-operated Ca2+ channels (SOC). SOC have been detected in vascular smooth muscle cells (VSMCs) and are thought to have an essential role in the regulation of contraction and cell proliferation. We hypothesized that knockdown of STIM1 inhibits VSMC proliferation and suppresses neointimal hyperplasia. METHODS AND RESULTS: We examined the effect of the knockdown of STIM1 using a rat balloon injury model and cultured rat aortic VSMCs. Interestingly, knockdown of rat STIM1 by adenovirus delivery of small interfering RNA (siRNA) significantly suppressed neointimal hyperplasia in a rat carotid artery balloon injury model at 14 days after injury. The re-expression of human STIM1 to smooth muscle reversed the effect of STIM1 knockdown on neointimal formation. Rat aortic VSMCs were used for the in vitro assays. Knockdown of endogenous STIM1 significantly inhibited proliferation and migration of VSMCs. Moreover, STIM1 knockdown induced cell-cycle arrest in G0/G1 and resulted in a marked decrease in SOC. Replenishment with recombinant human STIM1 reversed the effect of siRNA knockdown. These results suggest STIM1 has a critical role in neointimal formation in a rat model of vascular injury. CONCLUSION: STIM1 may represent a novel therapeutic target in the prevention of restenosis after vascular interventions.

[Long-term outcome of interventional therapy for malignant biliary obstruction: a retrospective analysis of 109 cases].

OBJECTIVE: To evaluate the long-term outcome and its relative influenced factors of interventional therapy in dealing malignant biliary obstruction (MBO). METHOD: 109 MBO patients, 54 males and 55 females, aged (71 +/- 12), underwent interventional therapy: 55 patients received percutaneous transhepatic cholangiography and drainage (PTCD), and 54 underwent bile duct stent implantation. One week later, total bilirubin (TB), direct bilirubin (DB), and alanine transaminase (ALT) were examined, and Child-Pugh scoring was conducted.38 of the patient underwent transcatheter arterial chemo-embolization (TACE). RESULTS: One week after drainage the levels of ALT, TB, and DB of the patients undergoing PTCD and stent implantation all decreased in comparison with those before the treatment, the levels of the stent implantation group being significantly lower than those of the PTCD group (P = 0.019, 0.002, and 0.002 respectively), but there was no significant difference in Child-Pugh scale between these 2 group (P = 0.396). One week after TACE the levels of TB, DB, and Child-Pugh scale of the TACE group were all significantly lower than those of the patients without TACE (P = 0.000, 0.002, and 0.002 respectively), however, there was no significant difference in ALT level between these 2 groups (P = 0.834). The cumulative mean survival time was 26.45 weeks [standard error (SE) 4.07], and the mean survival time of the PTCD group was 28.19 weeks (SE, 6.54), not significantly different from that of the stenting groups were [21.38 weeks (SE, 2.51), P = 0.713]. The mean survival time of the TACE group was 43.71 weeks (SE, 8.32), significantly longer than that of the patients without TACE [14.38 weeks (SE, 2.66), P = 0.000]. CONCLUSION: Stenting is more effective than PTCD on relieving jaundice when the decreasing extent of bilirubin level is concerned. TACE therapy following PTCD and stent implantation will significantly contribute to the survival time of MBO patients.

Stage II surgical resection of hepatocellular carcinoma after TAE:a report of 38 cases.

AIM:To evaluate the curative effect of stageII surgical resection of hepatocellular carcinoma after TAE.METHODS:Thirty-eight patients with unresectable hepatocellular carcinoma were treated by transcatheter arterial embolization (TAE).When the sizes of tumors were markedly reduced after TAE, stage II surgical resections were performed.RESULTS:Before TAE, the diameters of tumors were 12.84cm & plusmn; 4.87cm (x & plusmn;s), but reduced to 5.12 cm& plusmn; 1.82cm (x& plusmn; s) after TAE (P < 0.001). Pathologic examination of the resected specimens revealed obvious necrosis in most cases. After surgery, 26 patients were alive, with the longest survival of 96 months, twelve died and 10 had tumor recurrence.CONCLUSION:Patients in moderate and advanced stages of hepatocellular carcinoma after TAE should be treated surgically, but the indication must be controlled strictly.