Early results of an Asian prospective multicenter VenaSeal real-world postmarket evaluation to investigate the efficacy and safety of cyanoacrylate endovenous ablation for varicose veins.

OBJECTIVE: The aim of A Singapore VenaSeal Real-World Post-Market Evaluation Study (ASVS) was to evaluate the performance of cyanoacrylate closure (CAC) for varicose veins in a prospective multiracial Singaporean Asian cohort. We report early clinical and patient satisfaction outcomes at 3 months after intervention. METHODS: There were 100 patients (151 legs; 156 truncal veins) who underwent CAC between April and December 2018. Of the 151 legs, 49 (32.5%) were treated for great saphenous vein (GSV) incompetence, 96 (63.6%) for bilateral GSV incompetence, 1 (0.7%) for small saphenous vein (SSV) incompetence, and 5 (3.3%) for combined unilateral GSV and SSV reflux. At baseline, 68 legs (45.0%) had C4 to C6 disease, and 67 legs (44.4%) had concomitant multiple stab avulsions. Patients were reviewed at 2 and 12 weeks by duplex ultrasound to check for venous recanalization (defined as ≥5 cm in length), pain score, revised Venous Clinical Severity Score, EuroQol-5 Dimension questionnaire score, Aberdeen Varicose Vein Questionnaire score, 14-item Chronic Venous Insufficiency Questionnaire (CIVIQ-14) for quality of life measures, and patient satisfaction. Time to return to work and normal activities were also recorded. RESULTS: There were 59 female patients, and mean age was 60.1 ± 12.7 years. There was 100% technical success. Patients tolerated the procedure well and reported low periprocedural pain (mean pain score, 2.9 [range, 0-9]). Patient surveys at the 3-month interval showed high satisfaction rates, with 72 of 91 (79.1%) being extremely or very satisfied. By day 10, of 100 patients, 93 (93%) resumed daily activities, whereas 36 (36%) had returned to work. At 2 weeks, GSV and SSV were completely occluded in 150 of 150 (100%) and 6 of 6 (100%) veins, respectively. At 3 months, GSV and SSV occlusion rates were 140 of 141 (99.3%) and 6 of 6 (100%), respectively. Transient superficial phlebitis was reported in 27 of 151 (18 %) legs, which was self-limited. At 3 months, revised Venous Clinical Severity Score improved from 5.00 (range, 1.00-18.00) to 1.00 (0.00-10.00; P < .001); EuroQol-5 Dimension score, from 0.686 (-0.382 to 1.00) to 1.00 (0.12-1.00; P < .001); Aberdeen Varicose Vein Questionnaire score, from 17.14 (1.29-61.15) to 4.83 (0.00-57.12; P < .001); and 14-item Chronic Venous Insufficiency Questionnaire, from 19.64 (1.79-73.21) to 7.14 (0.00-51.79; P < .001). CONCLUSIONS: CAC has a high safety profile and is an effective way to block refluxing truncal veins in Asian patients at early follow-up. Patients are highly satisfied and report low postoperative pain. There is significant continued quality of life improvement at 3 months. Early results are encouraging, but we await further prospective long-term follow-up from the study.

Single Asian Center Experience Using the Flixene™ Early Cannulation Graft for Hemodialysis Access Creation.

BACKGROUND: The aim of this study was to review the efficacy of the Flixene™ (Atrium™, Hudson, NH, USA) hemodialysis arterio-venous graft (AVG) in a multiethnic Asian cohort of patients with end-stage renal failure (ESRF). Primary outcome was graft primary patency rate and secondary end points included graft usability, time to cannulation, reinterventions required for access salvage, complications, and patient mortality. METHODS: Single-center, single-arm, multi-investigator nonrandomized retrospective study. Patients with ESRF who underwent Flixene™ graft implantation over a two-year period (January 2017 - December 2018) were included to allow at least one-year follow-up. Demographics, procedural and follow-up data were collected from the hospital electronic medical records. RESULTS: About 48 patients (49 AVG) were included. There were 24 (50%) men; mean age 63.7 (IQR 58.2-71.3) years. Technical success rate was 45/49 (91.8%); 4/49 (8.2%) AVG created did not reach cannulation. 11/49 (22.4%) and 28/49 (57.1%) achieved cannulation within 1 and 2 weeks, respectively. 6- and 12- month primary patencies were 33.5% and 19.6%, respectively. Primary-assisted patency rates were 46.6% and 29.6% at the same time intervals. Secondary patency rate was 77.6% and 63.9% at 6 and 12 months, respectively. There were 6 (12.2%) graft infections requiring explant and one-year mortality was 14%. CONCLUSIONS: Our experience with the Flixene™ early cannulation graft is comparable with other AVGs in terms of patency and infection rates. However, early cannulation rates are lower than in other case series.

Exit site complications following cyanoacrylate glue endovenous ablation of incompetent truncal veins for chronic venous insufficiency.

In the last 5 years, the use of nonthermal, nontumescent endovenous ablation such as cyanoacrylate glue (CAG) for treatment of chronic venous insufficiency has gained global popularity. This case series discusses the presentation and management of delayed access sheath site infections in patients who have undergone CAG therapy. The authors believe such adverse effects are related to granuloma formation owing to a hypersensitivity reaction to CAG at the puncture exit site. The endovenous surgeon should be aware of preventing glue spillage into the subcutaneous space at the access site during treatment, to minimize the risk of this complication developing.

Early (6 months) results of a pilot prospective study to investigate the efficacy and safety of sirolimus coated balloon angioplasty for dysfunctional arterio-venous fistulas: MAgicTouch Intervention Leap for Dialysis Access (MATILDA) Trial.

BACKGROUND: The aim of this pilot study was to evaluate the safety and efficacy of the MagicTouch™ sirolimus-coated balloon (SCB) catheter (Concept Medical Inc., Tampa, FL, US) on improving the patency of failing arterio-venous fistulas (AVF) with de novo and recurrent stenoses. MATILDA reports early outcomes at 3- and 6 months post intervention. METHODS: Single-centre, single-arm prospective pilot study of 33 (18 males; mean age 64.7±11.6 years) end-stage renal failure Asian patients with a dysfunctional AVF, who underwent SCB angioplasty between May 2019-January 2020. All procedures were performed under local anaesthetic without sedation and as day surgery. All patients were prescribed dual antiplatelet therapy for 3 months and followed up with Duplex ultrasound at 3 and 6 months. RESULTS: 47 stenotic target lesions treated and 24/33 (72.7%) patients were for restenosis. Main indications for intervention was low/dropping access flow (21/33; 63.6%) and most common target lesion was in the juxta-anastomosis (19/47; 40.4%). There was 100% technical and procedural success. There were no peri-procedural complications related to the SCB. The target lesion primary patency rates at 3 and 6 months were 46/47 (97.9%) and 29/35 (82.9%) respectively. Circuit access patency rates at 3 and 6 months were 31/33 (93.9%) and 17/25 (68%) respectively. There was one (2.9%) death at 6 months and 4/33 (12.1%) overall to date, all from patients' underlying co-morbidities. CONCLUSIONS: SCB angioplasty for dysfunctional AVF circuits is a safe and efficacious modality in Asian haemodialysis patients at six months comparable if not better than the paclitaxel data reported to date in the literature.

The Modified Frailty Index Does Not Predict Mortality After Major Lower Extremity Amputation for Peripheral Arterial Disease in an Asian Population.

BACKGROUND: Patients with critical limb ischemia (CLI) who undergo major lower extremity amputation (LEA) have been associated with high one-year mortality rates. Previous western-based studies have identified risk factors that exponentiate these poor outcomes, including nonambulatory status and cardiovascular morbidity. We assessed the effect of frailty, using the modified frailty index (mFI) in a cohort undergoing major LEA for CLI to predict mortality, perioperative complications, and unplanned readmissions in a tertiary institution from Singapore. METHODS: Data on patients who had undergone major LEA from January 2016 to December 2017 were collected retrospectively. Inclusion criteria were below-knee amputations (BKAs) or above-knee amputations (AKAs) performed for peripheral arterial disease-related tissue loss or sepsis only. Patients were categorized into 3 risk groups based on the 11-variable mFI: low mFI, 0-0.27; moderate mFI, 0.36-0.54; and high mFI ≥0.63. Univariate and multivariate analysis was performed using logistic regression analysis. RESULTS: 211 patients underwent major LEA, of whom 133 (63.0%) had undergone BKA. The mean mFI was 0.41 (range 0-0.81). 84/211 (39.8%) died within 1 year after the procedure, with mortality rates of 25/65 (38.4%), 49/127 (38.6%), and 10/19 (52.6%) in the low-, moderate-, high-mFI categories, respectively. High and moderate mFI had failed to demonstrate an increased risk of mortality when compared with the low-mFI group (P > 0.05). 91/211 (43.1%) patients had perioperative complications, whereas 27/211 (12.8%) patients were readmitted within 30 days of discharge. Myocardial infarction, chronic kidney disease, and atrial fibrillation were found to be predictive of poor outcomes after major LEA. CONCLUSIONS: Frailty as measured with the mFI did not predict outcome after major LEA. This could be due to confounding effects such as high prevalence of renal dysfunction and the constancy of diabetes and peripheral vascular disease in this population that would reduce the differentiation of patients using the mFI.

A systematic review, meta-analysis, and meta-regression of the efficacy and safety of endovascular arteriovenous fistula creation.

OBJECTIVE: The percutaneous endovascular approach to arteriovenous fistula (AVF) creation is a minimally invasive alternative to surgical AVF creation. This systematic review and meta-analysis aimed to investigate the efficacy and safety of endovascular AVF creation in patients with end-stage renal disease. METHODS: This study conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An electronic search was performed on major databases to identify relevant articles. Meta-analysis of proportions and meta-regression were conducted. RESULTS: Seven studies totaling 300 patients were included, of which four evaluated the everlinQ (TVA Medical, Austin, Tex) and three employed the Ellipsys (Avenu Medical, San Juan Capistrano, Calif) systems. The overall technical success rate was 97.50% (95% confidence interval [CI], 94.98-99.31%; I2 = 0.00%; P = .487). The 90-day maturation rate was 89.27% (95% CI, 84.00-93.66%; I2 = 21.29%; P = .283), and the 6-month patency and 12-month patency were 91.99% (95% CI, 87.98-95.35%; I2 = 0.00%; P = .780) and 85.71% (95% CI, 79.90-90.71%; I2 = 0.00%; P = NS), respectively. The overall procedure-related complication rate was 5.46% (95% CI, 0.310-14.42%; I2 = 81.21%; P = .000). Meta-regression was conducted on the pooled rates of technical success and complication, showing that age, diabetes, white race, hypertension, on dialysis, and body mass index were not significant sources of heterogeneity. CONCLUSIONS: Current endovascular AVF systems appear to be effective and safe. However, given the lack of head-to-head comparative analyses with surgical AVF creation, superiority cannot be established.

Maximally Disfiguring Surgery for Forefoot Osteomyelitis: Time for a Rethink?

The treatment of choice for diabetic foot osteomyelitis is surgical debridement and targeted antibiotics with or without revascularization, depending on vascular status. In our society, debridement is done by either a vascular or orthopedic surgeon, and the common teaching is that generous amputation of bone with the accompanying soft tissue envelope is essential for adequate source control and to prevent recurrence (which remains as high as 30% even with this approach). Most of our patients undergo formal ray amputation through the metatarsal neck, while a few get digital amputations through the interphalangeal joints. Many of the resultant wounds cannot be closed and are left to heal by secondary intention. These amputations invariably alter the biomechanics of the foot and leave large and slow-healing open wounds, which have associated adverse psychosocial impacts. We describe 2 cases of patients who had osteomyelitis in the region of the forefoot who underwent complete bony resections of the osteomyelitis but with sparing of the soft tissue envelopes with good outcomes, and we challenge the dogma that maximal debridement of soft tissue must accompany debridement of necrotic and infected bone.

A systematic review and meta-analysis of drug-coated balloon versus conventional balloon angioplasty for dialysis access stenosis.

BACKGROUND: Arteriovenous fistulas for patients undergoing hemodialysis (HD) are at high risk of stenosis. Despite conventional balloon angioplasty (CBA), restenosis rates are high. The use of a drug-coated balloon (DCB) may offer an alternative to reduce restenosis. METHODS: This study has been performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An electronic search on MEDLINE, Embase, and the Cochrane Library was performed to identify articles evaluating DCB angioplasty for patients with HD access stenosis. Risk ratios (RRs) of primary patency were pooled, and relevant subgroup and sensitivity analyses were conducted. RESULTS: There were 17 studies (8 randomized controlled trials [RCTs], 9 cohort studies) included, comprising a total of 1113 stenotic dialysis accesses, of which 54.7% underwent DCB angioplasty and 45.3% underwent CBA. There was a significantly superior 6-month (RR, 0.57; 95% confidence interval [CI], 0.44-0.74; P < .00001; I2 = 62%) and 12-month (RR, 0.73; 95% CI, 0.63-0.84; P < .0001; I2 = 53%) primary patency in the DCB angioplasty group in comparison to the CBA group (71.0% vs 49.2% at 6 months; 44.2% vs 20.6% at 12 months). Subgroup analyses of study design (RCTs, cohort studies) showed similar trends. Sensitivity analyses by excluding one poor-quality RCT and those employing the crossover analysis design also showed similar results. Studies investigating central venous stenosis showed significantly better 6-month (RR, 0.57; 95% CI, 0.41-0.79; P = .0009; I2 = 67%) and 12-month (RR, 0.69; 95% CI, 0.56-0.85; P = .0004; I2 = 64%) primary patency in the DCB angioplasty group in comparison to the CBA group. The pooled rate of minor complications was low in both the DCB (1.1%) and CBA (0.9%) groups. CONCLUSIONS: DCB angioplasty appears to be a better and safe alternative to CBA in treating patients with HD stenosis in terms of 6- and 12-month primary patency. However, a larger trial is warranted to establish these findings.

Fenestrated Endovascular Repair of Zones 1 and 2 Aortic Arch Pathologies.

BACKGROUND: Surgical management of aortic arch pathologies is complex, and endovascular developments have now enabled total or hybrid endovascular aortic arch repair. We present our early experience with fenestrated aortic arch repairs in Ishimaru zones 1 and 2 pathologies. METHODS: In a single tertiary institution, all consecutive endovascular aortic arch repairs were reviewed. A preoperative computed tomography aortogram was performed to assess anatomic suitability, which we defined as having a proximal sealing zone with a maximum diameter of 38 mm and minimum length of 20 mm, absence of significant aortic tortuosity, and suitable sealing zones in target vessels. RESULTS: From September 2015 to February 2018, 5 cases of fenestrated aortic arch endovascular repairs were performed. There were 3 male patients. The patients were between 57 and 83 years old, all of whom were American Society of Anesthesiologists (ASA) class II or III. Indications for surgery included aortic arch aneurysms (n = 3), a symptomatic aortic dissection, and a left subclavian artery aneurysm. Three patients had a scallop to the innominate artery, and one patient had a scallop to the left common carotid artery. Fenestrations were made to 3 left common carotid arteries and 3 left subclavian arteries. In 2 patients, a left carotid-subclavian bypass was performed, and the left subclavian artery origin occluded with a vascular plug. Technical success was 100%. One patient developed a right occipital infarct and acute myocardial infarction. The mean duration of surgery was 164 min, and the mean length of stay was 4.2 days. The mean follow-up period was 14.4 months. CONCLUSIONS: The use of fenestrated grafts in the aortic arch is a feasible treatment option. However, certain limitations still exist, and preoperative planning is important in ensuring clinical success. Although this procedure appears feasible in the short term, long-term results and durability remain to be seen.

Metformin Inhibits Cellular Proliferation and Bioenergetics in Colorectal Cancer Patient-Derived Xenografts.

There is increasing preclinical evidence suggesting that metformin, an antidiabetic drug, has anticancer properties against various malignancies, including colorectal cancer. However, the majority of evidence, which was derived from cancer cell lines and xenografts, was likely to overestimate the benefit of metformin because these models are inadequate and require supraphysiologic levels of metformin. Here, we generated patient-derived xenograft (PDX) lines from 2 colorectal cancer patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for colorectal cancer. Metformin (150 mg/kg) as a single agent inhibits the growth of both PDX tumors by at least 50% (P < 0.05) when administered orally for 24 days. In one of the PDX models, metformin given concurrently with 5-FU (25 mg/kg) leads to an 85% (P = 0.054) growth inhibition. Ex vivo culture of organoids generated from PDX demonstrates that metformin inhibits growth by executing metabolic changes to decrease oxygen consumption and activating AMPK-mediated pathways. In addition, we also performed genetic characterizations of serial PDX samples with corresponding parental tissues from patients using next-generation sequencing (NGS). Our pilot NGS study demonstrates that PDX represents a useful platform for analysis in cancer research because it demonstrates high fidelity with parental tumor. Furthermore, NGS analysis of PDX may be useful to determine genetic identifiers of drug response. This is the first preclinical study using PDX and PDX-derived organoids to investigate the efficacy of metformin in colorectal cancer. Mol Cancer Ther; 16(9); 2035-44. ©2017 AACR.

The Singapore Liver Cancer Recurrence (SLICER) Score for relapse prediction in patients with surgically resected hepatocellular carcinoma.

BACKGROUND AND AIMS: Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC). Current prognostic models for HCC are developed on datasets of primarily patients with advanced cancer, and may be less relevant to resectable HCC. We developed a postoperative nomogram, the Singapore Liver Cancer Recurrence (SLICER) Score, to predict outcomes of HCC patients who have undergone surgical resection. METHODS: Records for 544 consecutive patients undergoing first-line curative surgery for HCC in one institution from 1992-2007 were reviewed, with 405 local patients selected for analysis. Freedom from relapse (FFR) was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation was used. We compared the performance of SLICER in estimating FFR with other HCC prognostic models using concordance-indices and likelihood analysis. RESULTS: A nomogram predicting FFR was developed, incorporating non-neoplastic liver cirrhosis, multifocality, preoperative alpha-fetoprotein level, Child-Pugh score, vascular invasion, tumor size, surgical margin and symptoms at presentation. Our nomogram outperformed other HCC prognostic models in predicting FFR by means of log-likelihood ratio statistics with good calibration demonstrated at 3 and 5 years post-resection and a concordance index of 0.69. Using decision curve analysis, SLICER also demonstrated superior net benefit at higher threshold probabilities. CONCLUSION: The SLICER score enables well-calibrated individualized predictions of relapse following curative HCC resection, and may represent a novel tool for biomarker research and individual counseling.

Rectal arterio-portal fistula: an unusual cause of persistent bleeding per rectum following a proximal spleno-renal shunt.

Gastrointestinal arterio-venous malformations are a known cause of gastrointestinal bleeding. We present a rare case of persistent rectal bleeding due to a rectal arterio-portal venous fistula in the setting of portal hypertension secondary to portal vein thrombosis. The portal hypertension was initially surgically treated with splenectomy and a proximal splenorenal shunt. However, rectal bleeding persisted even after surgery, presenting us with a diagnostic dilemma. The patient was re-evaluated with a computed tomography mesenteric angiogram which revealed a rectal arterio-portal fistula. Arterio-portal fistulas are a known but rare cause of portal hypertension, and possibly the underlying cause of continued rectal bleeding in this case. This was successfully treated using angiographic localization and super-selective embolization of the rectal arterio-portal venous fistula via the right internal iliac artery.The patient subsequently went on to have a full term pregnancy. Through this case report, we hope to highlight awareness of this unusual condition, discuss the diagnostic workup and our management approach.