Konstantinos Katsanos

Stenting of the Upper Gastrointestinal Tract: Current Status

Minimally invasive image-guided insertion of self-expanding metal stents in the upper gastrointestinal tract is the current treatment of choice for palliation of malignant esophageal or gastroduodenal outlet obstructions. A concise review is presented of contemporary stenting practice of the upper gastrointestinal tract, and the procedures in terms of appropriate patient evaluation, indications, and contraindications for treatment are analyzed, along with available stent designs, procedural steps, clinical outcomes, inadvertent complications, and future technology. Latest developments include biodegradable polymeric stents for benign disease and radioactive or drug-eluting stents for malignant obstructions.

Bayesian network meta-analysis of nitinol stents, covered stents, drug-eluting stents, and drug-coated balloons in the femoropopliteal artery

OBJECTIVE Several randomized controlled trials (RCTs) have shown the superiority of some of these technologies over balloon angioplasty, but direct comparisons between these treatment options are lacking. The authors conducted a network meta-analysis of RCTs comparing bare nitinol stents, covered nitinol stents, paclitaxel- or sirolimus-eluting stents (PES or SES), and paclitaxel-coated balloons (PCB) with plain balloon angioplasty or with each other in the femoropopliteal artery (PROSPERO registry: CRD42013004845). METHODS Sixteen RCTs comprising 2532 patients with 4227 person-years of follow-up were analyzed on an intention-to-treat basis. Bayesian random effects Poisson and binomial models were used for mixed treatment comparisons (WinBUGS). Clinical heterogeneity was accounted for by incorporating a meta-regression model on trial-specific baseline risk. End points included technical success, vascular restenosis, target lesion revascularization, and major amputations. Pairwise odds ratios and rate ratios (ORs and RRs) of absolute treatment effects were calculated, and the probabilities of each treatment being best are reported. Summary estimates are reported as the posterior median and associated credible intervals (CrIs) that serve the same purpose as confidence intervals in the context of the Bayesian framework. Extensive sensitivity, meta-regression, and network consistency analyses were performed to evaluate heterogeneity. RESULTS Technical success was highest with covered stents (pooled OR, 13.6; 95% CrI, 3.3-31.1, probability best 82%) followed by uncovered stents (pooled OR, 7.0; 95% CrI, 2.6-129, probability best 18%) when compared with balloon angioplasty (reference treatment). Vascular restenosis was lowest with PES (RR, 0.43; 95% CrI, 0.16-1.18, probability best 45%) followed by PCB (RR, 0.43; 95% CrI, 0.26-0.67, probability best 42%). Target lesion revascularization was lowest with PCB (RR, 0.36; 95% CrI, 0.23-0.55, probability best 56%) followed by PES (RR, 0.42; 95% CrI, 0.16-1.06, probability best 33%). Major amputations were rare in all treatment and control groups (pooled amputation rate of 0.7 events per 100 person-years). CONCLUSIONS Immediate technical success is better with the use of covered stents, whereas paclitaxel-eluting stents and paclitaxel-coated balloons offer the best long-term results in the femoropopliteal artery.

Systematic Review and Meta-analysis of Randomized Controlled Trials of Paclitaxel-Coated Balloon Angioplasty in the Femoropopliteal Arteries: Role of Paclitaxel Dose and Bioavailability

Purpose: To provide a qualitative analysis and quantitative synthesis of randomized controlled trials (RCTs) investigating paclitaxel-coated balloons (PCBs) in the femoropopliteal artery. Methods: PubMed, EMBASE, AMED, Scopus, CENTRAL, online content, and abstracts from international meetings were last screened in April 2015 for eligible RCTs using the PRISMA selection process. Risk of bias was assessed using the Cochrane Collaboration’s tool, and quality of evidence was evaluated with the GRADE system. Outcome measures included late lumen loss (LLL) at 6 months and event rates of major limb amputations, binary lesion restenosis, and target lesion revascularization (TLR). Pooled treatment effects were analyzed in a random effects model to account for clinical heterogeneity; the outcomes are presented as the rate ratios (RRs) and their 95% confidence intervals (CIs). Extensive meta-regression was performed to analyze potential confounders. The review was registered in the PROSPERO database (CRD42015023938; www.crd.york.ac.uk/PROSPERO ). Results: Eleven RCTs with 1609 subjects (1403 claudicants and 206 patients with critical limb ischemia) with medium-length femoropopliteal lesions (mean range 5.1–11.9 cm) were included. There was consistently high-quality evidence supporting the clear superiority of PCBs in terms of reduced LLL (mean difference −0.89 mm, 95% CI −1.14 to −0.64, p<0.001), less binary restenosis (RR 0.47, 95% CI 0.37 to 0.61, p<0.001), and fewer TLR events (RR 0.33, 95% CI 0.22 to 0.49, p<0.001). Major amputations were rare in both active and control arms (pooled event rate: 0.7%, 95% CI 0.3% to 1.2%). Results were stable across all potential risk modifiers and in the presence of stents as well. There was high-quality evidence that the dose of paclitaxel was related to the magnitude of the treatment effect; standard dose (3.0-μg and 3.5-μg) PCBs were significantly more effective compared with low-dose 2-μg PCB in reducing both restenosis (RR 2.1, 95% CI 1.2 to 3.4, p<0.001) and TLR (RR 2.5, 95% CI 1.9 to 3.8, p<0.001). Conclusion: PCBs reduce by more than half the rates of restenosis and TLR in the femoropopliteal artery regardless of stent placement. Biologic effect size may vary according to paclitaxel bioavailability.

Drug-eluting versus plain balloon angioplasty for the treatment of failing dialysis access: Final results and cost-effectiveness analysis from a prospective randomized controlled trial (NCT01174472)

OBJECTIVE To report the final results and cost-effectiveness analysis of a prospective randomized controlled trial investigating drug-eluting balloon (DEB) versus plain balloon angioplasty (BA) for the treatment of failing dialysis access (NCT01174472). METHODS 40 patients were randomized to angioplasty with either DEB (n=20) or BA (n=20) for treatment of significant venous stenosis causing a failing dialysis access. Both arteriovenous fistulas (AVF) and synthetic arteriovenous grafts (AVG) were included. Angiographic follow up was scheduled every two months. Primary endpoints were technical success and target lesion primary patency at 1 year. Cumulative and survival analysis was performed. Incremental net benefit (INB) and incremental cost effectiveness ratio (ICER) were calculated and the cost-effectiveness acceptability curve (CEAC) was drawn. RESULTS Baseline variables were equally distributed between the two groups. At 1 year, cumulative target lesion primary patency was significantly higher after DEB application (35% vs. 5% after BA, p<0.001). Overall, median primary patency was 0.64 years in case of DEB vs. 0.36 years in case of BA (p=0.0007; unadjusted HR=0.27 [95%CI: 0.13-0.58]; Cox adjusted HR=0.23 [95%CI: 0.10-0.50]). ICER was 2198 Euros (€) per primary patency year of dialysis access gained. INB was 1068€ (95%CI: 31-2105€) for a willingness-to-pay (WTP) threshold of 5000€ (corresponding acceptability probability >97%). CONCLUSION DEB angioplasty may be a cost-effective option that significantly improves patency after angioplasty of venous stenoses of failing vascular dialysis access. Further large-scale randomized trials are warranted.

Economic analysis of endovascular drug-eluting treatments for femoropopliteal artery disease in the UK

Objectives To estimate the clinical and economic impact of drug-eluting endovascular treatment strategies for femoropopliteal artery disease compared with current standard of care. Design Systematic literature search to pool target lesion revascularisations (TLR). Model-based per-patient cost impact and quasi-cost-effectiveness projection over 24 months based on pooled TLRs and current reimbursement. Setting The UKs National Health Service (NHS). Participants Patients presenting with symptomatic femoropopliteal disease eligible for endovascular treatment. Interventions Current National Institute for Health and Care Excellence (NICE) guideline-recommended treatment with percutaneous transluminal balloon angioplasty (PTA) and bailout bare metal stenting (BMS) versus primary BMS placement, or drug-coated balloon (DCB), or drug-eluting stent (DES) treatment. Primary and secondary outcome measures 24-month per-patient cost impact to NHS (primary outcome). Secondary outcomes: pooled 24-month TLR rates; numbers needed to treat (NNTs); cost per TLR avoided and estimated incremental cost-effectiveness ratio (ICER) in £ per quality-adjusted life year (QALY). Results N=28 studies were identified, reporting on 5167 femoropopliteal lesions. Over 24 months, DCB, DES and BMS reduced TLRs of de novo lesions from 36.2% to 17.6%, 19.4% and 26.9%, respectively, at an increased cost of £43, £44 and £112. NNTs to avoid 1 TLR in 24 months were 5.4, 6.0 and 10.8, resulting in cost per TLR avoided of £231, £264 and £1204. DCB was estimated to add 0.011 QALYs, DES 0.010 QALYs and BMS 0.005 QALYs, resulting in estimated ICERs of £3983, £4534 and £20 719 per QALY gained. A subset analysis revealed more favourable clinical and economic outcomes for a 3.5 µg/mm2 DCB with urea excipient, compared with the rest of DCBs. A modest reduction of 10% in DCB and DES prices made drug-eluting treatments dominant. Conclusions Widespread adoption of drug-eluting endovascular therapies for femoropopliteal disease would add meaningful clinical benefit at reasonable additional costs to the NHS. Based on currently available data, DCBs offer the highest clinical and economic value.

Standards of Practice for Superficial Femoral and Popliteal Artery Angioplasty and Stenting

This is a Standards of Practice document endorsed by CIRSE. The authors performed a literature review and provide recommendations and quality improvement guidelines based on the most recent and highest level of evidence available to date on the field of Superficial Femoral and Popliteal Artery Angioplasty and Stenting. Standards for the use of basic and more advanced endovascular techniques in the femoropopliteal arteries are reported and relevant aspects of case selection, imaging, follow-up, and overall patient management are presented to guide endovascular practice in Europe.

Comparative Efficacy and Safety of Different Antiplatelet Agents for Prevention of Major Cardiovascular Events and Leg Amputations in Patients with Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis.

There is a lack of consensus regarding which type of antiplatelet agent should be used in patients with peripheral arterial disease (PAD) and little is known on the advantages and disadvantages of dual antiplatelet therapy. We conducted a systematic review and network meta-analysis of available randomized controlled trials (RCT) comparing different antiplatelet drugs (Aspirin, Ticlopidine, Clopidogrel, Ticagrelor, Cilostazol, Picotamide and Vorapaxar as monotherapies or in combination with aspirin) in PAD patients (PROSPERO public database; CRD42014010299).We collated evidence from previous relevant meta-analyses and searched online databases. Primary efficacy endpoints were: (1) the composite rate of major adverse cardiovascular events (MACE; including vascular deaths, non-fatal myocardial infarction and non-fatal stroke), and (2) the rate of major leg amputations. The primary safety endpoint was the rate of severe bleeding events. Bayesian models were employed for multiple treatment comparisons and risk-stratified hierarchies of comparative efficacy were produced to aid medical decision making. Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH) are reported in case of significant results. We analyzed 49 RCTs comprising 34,518 patients with 88,358 person-years of follow-up with placebo as reference treatment. Aspirin, Cilostazol, Vorapaxar and Picotamide were ineffective in reducing MACE. A significant MACE reduction was noted with Ticagrelor plus aspirin (RR: 0.67; 95%CrI: 0.46–0.96, NNT = 66), Clopidogrel (RR: 0.72; 95%CrI: 0.58–0.91, NNT = 80), Ticlopidine (RR: 0.75; 95%CrI: 0.58–0.96, NNT = 87), and Clopidogrel plus aspirin (RR: 0.78; 95%CrI: 0.61–0.99, NNT = 98). Dual antiplatelet therapy with Clopidogrel plus aspirin significantly reduced major amputations following leg revascularization (RR: 0.68; 95%CrI: 0.46–0.99 compared to aspirin, NNT = 94). The risk of severe bleeding was significantly higher with Ticlopidine (RR: 5.03; 95%CrI: 1.23–39.6, NNH = 25), Vorapaxar (RR: 1.80; 95%CrI: 1.22–2.69, NNH = 130), and Clopidogrel plus aspirin (RR: 1.48; 95%CrI: 1.05–2.10, NNH = 215). Clopidogrel monotherapy showed the most favourable benefit-harm profile (79% cumulative rank probability best and 77% cumulative rank probability safest). In conclusion, Clopidogrel should be the indicated antiplatelet agent in PAD patients. Dual antiplatelet therapy with aspirin and Clopidogrel can reduce the rate of major leg amputations following revascularization, but carries a slightly higher risk of severe bleeding.

Emerging technologies for image guidance and device navigation in interventional radiology.

Recent developments in image-guidance and device navigation, along with emerging robotic technologies, are rapidly transforming the landscape of interventional radiology (IR). Future state-of-the-art IR procedures may include real-time three-dimensional imaging that is capable of visualizing the target organ, interventional tools, and surrounding anatomy with high spatial and temporal resolution. Remote device actuation is becoming a reality with the introduction of novel magnetic-field enabled instruments and remote robotic steering systems. Robots offer several degrees of freedom and unprecedented accuracy, stability, and dexterity during device navigation, propulsion, and actuation. Optimization of tracking and navigation of interventional tools inside the human body will be critical in converting IR suites into the minimally invasive operating theaters of the future with increased safety and unsurpassed therapeutic efficacy. In the not too distant future, individual image guidance modalities and device tracking methods could merge into autonomous, multimodality, multiparametric platforms that offer real-time data of anatomy, morphology, function, and metabolism along with on-the-fly computational modeling and remote robotic actuation. The authors provide a concise overview of the latest developments in image guidance and device navigation, while critically envisioning what the future might hold for 2020 IR procedures.

Onyx Embolization of Sporadic Angiomyolipoma

Percutaneous embolization is the currently preferred treatment of symptomatic or ruptured renal angiomyolipomas (AMLs). Alcohol, microparticles, and coils are usually used. We present what is to our knowledge the first case of successful embolization of a solitary sporadic AML with the use of a new nonadhesive liquid embolic agent (ethylene vinyl alcohol copolymer; Onyx). Onyx injection was slow and controllable and achieved complete tumor devascularization, producing a characteristic appearance like a vascular cast. Short-term follow-up magnetic resonance imaging showed complete tumor necrosis without any recurrent pathologic vessels. The specific features, potential advantages in AML treatment, and technical limitations of this new liquid embolic agent are discussed.

Targeted True Lumen Re-Entry With the Outback Catheter Accuracy, Success, and Complications in 100 Peripheral Chronic Total Occlusions and Systematic Review of the Literature

Purpose: To report a single-center experience with the Outback re-entry device for targeted distal true lumen re-entry during subintimal recanalization of chronic total occlusions (CTOs) and compare the results with a systematic review of the literature. Methods: Between February 2011 and July 2013, 104 Outback devices were employed in 91 patients (mean age 64±9 years; 57 men) for subintimal recanalization of 100 vessels with CTOs after initial failure of spontaneous reentry. Fifty-two cases involved a retrograde approach to aortoiliac occlusions and 48 were re-entry attempts in infrainguinal CTOs. Outcome measures included complications and technical success, defined as successful targeted re-entry at the preplanned site of the distal true lumen. To evaluate device accuracy, the re-entry distance (between the point of true vessel reconstitution and the eventual re-entry point) was measured. Results: Outback success was 93% (93/100); only 7 cases failed owing to heavy calcification (5/52 aortoiliac vs 2/48 infrainguinal, p=0.44). Re-entry was highly accurate, with a re-entry distance of ~1 cm in both subgroups (1.2±0.1 cm in aortoiliac vs 1.3±0.1 cm in infrainguinal, p=0.40). There were no major and 17 minor complications (9/52 aortoiliac vs 8/48 infrainguinal, p=0.93). Results are in line with the systematic review that identified 11 studies (only 1 randomized trial) involving mostly the femoropopliteal segment (119 aortoiliac and 464 infrainguinal segments). The pooled Outback success rate was 90% (95% confidence interval 85% to 94%) and the pooled complication rate was 4.3% (95% confidence interval 1.6% to 8.3%). Conclusion: The Outback device is safe and has a very high rate of achieving targeted true lumen re-entry, which minimizes the sacrifice of healthy vessel in the aortoiliac and infrainguinal arteries.