Eric S. Hager

Endothelial Differentiation of Adipose-Derived Stem Cells from Elderly Patients with Cardiovascular Disease

Adipose-derived stem cells (ASCs) possess significant therapeutic potential for tissue engineering and regeneration. This study investigates the endothelial differentiation and functional capacity of ASCs isolated from elderly patients. Isolation of ASCs from 53 patients (50-89 years) revealed that advanced age or comorbidity did not negatively impact stem cell harvest; rather, higher numbers were observed in older donors (>70 years) than in younger. ASCs cultured in endothelial growth medium-2 for up to 3 weeks formed cords upon Matrigel and demonstrated acetylated-low-density lipoprotein and lectin uptake. Further stimulation with vascular endothelial growth factor and shear stress upregulated endothelial cell-specific markers (CD31, von Willebrand factor, endothelial nitric oxide synthase, and VE-cadherin). Inhibition of the PI(3)K but not mitogen-activated protein kinase pathway blocked the observed endothelial differentiation. Shear stress promoted an anti-thrombogenic phenotype as demonstrated by production of tissue-plasminogen activator and nitric oxide, and inhibition of plasminogen activator inhibitor-1. Shear stress augmented integrin α(5)β(1) expression and subsequently increased attachment of differentiated ASCs to basement membrane components. Finally, ASCs seeded onto a decellularized vein graft resisted detachment despite application of shear force up to 9 dynes. These results suggest that (1) advanced age and comorbidity do not negatively impact isolation of ASCs, and (2) these stem cells retain significant capacity to acquire key endothelial cell traits throughout life. As such, adipose tissue is a practical source of autologous stem cells for vascular tissue engineering.

May-Thurner syndrome: case report and review of the literature involving modern endovascular therapy.

May-Thurner syndrome is a rare clinical entity involving venous obstruction of the left lower extremity. Obstruction occurs secondary to compression of the left common iliac vein between the right common iliac artery and the underlying vertebral body. Current management largely involves endovascular therapy. A review was conducted of six studies containing at least five patients with May-Thurner syndrome treated by endovascular therapy. We compiled data on 113 patients, analyzing patient demographics, treatment details, and outcome. An 18-year-old female presented 1 week after the onset of left lower extremity pain and swelling. Duplex ultrasonography revealed extensive left-sided deep venous thrombosis (DVT). Thrombolysis followed by iliac vein stent placement restored patency to the venous system, with subsequent resolution of symptoms. Review of 113 patients revealed that the majority were females (72%) presenting with DVT (77%), most of which was acute in onset (73%). Therapy consisted of catheter-directed thrombolysis and subsequent stent placement in the majority of patients, resulting in a mean technical success of 95% and a mean 1-year patency of 96%. Endovascular therapy is the current mainstay of treatment for May-Thurner syndrome. Review of the current literature supports treatment via catheter-directed thrombolysis followed by stent placement with good early results.

Metastatic disease to the pancreas and spleen

Isolated metastases to the pancreas and spleen are a rare occurrence. When they are diagnosed, pancreatic metastases are most often from renal cell carcinoma, lung cancer, and breast cancer. The most common source of splenic metastases is gynecological in origin; the overwhelming majority is ovarian. If extensive staging studies reveal these metastases to be isolated, then curative resection may be warranted. This review will demonstrate that long-term survival may be achieved in patients with isolated metastases and a prolonged disease-free interval.

Factors that influence perforator thrombosis and predict healing with perforator sclerotherapy for venous ulceration without axial reflux

OBJECTIVE Refluxing perforators contribute to venous ulceration. We sought to describe patient characteristics and procedural factors that (1) impact rates of incompetent perforator vein (IPV) thrombosis with ultrasound-guided sclerotherapy (UGS) and (2) impact the healing of venous ulcers (CEAP 6) without axial reflux. METHODS A retrospective review of UGS of IPV injections from January 2010 to November 2012 identified 73 treated venous ulcers in 62 patients. Patients had no other superficial or axial reflux and were treated with standard wound care and compression. Ultrasound imaging was used to screen for refluxing perforators near ulcer(s). These were injected with sodium tetradecyl sulfate or polidocanol foam and assessed for thrombosis at 2 weeks. Demographic data, comorbidities, treatment details, and outcomes were analyzed. Univariate and multivariable modeling was performed to determine covariates predicting IPV thrombosis and ulcer healing. RESULTS There were 62 patients (55% male; average age, 57.1 years) with active ulcers for an average of 28 months with compression therapy before perforator treatment, and 36% had a history of deep venous thrombosis and 30% had deep venous reflux. At a mean follow-up of 30.2 months, ulcers healed in 32 patients (52%) and did not heal in 30 patients (48%). Ulcers were treated with 189 injections, with an average thrombosis rate of 54%. Of 73 ulcers, 43 ulcers (59%) healed, and 30 (41%) did not heal. The IPV thrombosis rate was 69% in patients whose ulcers healed vs 38% in patients whose ulcers did not heal (P < .001). Multivariate models demonstrated male gender (P = .03) and warfarin use (P = .01) negatively predicted thrombosis of IPVs. A multivariate model for ulcer healing found complete IPV thrombosis was a positive predictor (P = .02), whereas a large initial ulcer area was a negative predictor (P = .08). Increased age was associated with fewer ulcer recurrences (P = .05). Predictors of increased ulcer recurrences were hypertension (P = .04) and increased follow-up time (P = .02). Calf vein thrombosis occurred after 3% (six of 189) of injections. CONCLUSIONS Thrombosis of IPVs with UGS increases venous ulcer healing in a difficult patient population. Complete closure of all IPVs in an ulcerated limb was the only predictor of ulcer healing. Men and patients taking warfarin have decreased rates of IPV thrombosis with UGS.

Coil-assisted false lumen thrombosis in complicated chronic type B dissection

Type B dissections complicated by pain, malperfusion, or aneurysm expansion mandate surgical intervention. Success of this therapy is predicated on exclusion and thrombosis of the false lumen of the aneurysm. We report a case where cessation of flow was achieved using covered stent grafts in conjunction with coil embolization of the false lumen. The introduction of coils into the false lumen is a novel approach and may provide a helpful adjunct in endovascular treatment of complicated type B aortic dissections.

Lower extremity vascular stenting for a post-traumatic pseudoaneurysm in a young trauma patient

Endovascular treatment of post-traumatic pseudoaneurysms has become a viable, less invasive option when compared to open repair. Due to the relative youth of this technology, studies have yet to be concluded on the long-term patency of stent grafts in this population. For this reason, concern exists with endovascular stent placement in the young trauma patient. In this study, we present a case and review the literature on a post-traumatic pseudoaneurysm of the posterior tibial artery in a 19-year-old man treated with an endovascular stent.

Diagnostic and treatment modalities for autoimmune pancreatitis

Since the recognition of autoimmune pancreatitis (AIP) as a clinical entity, many advances have been made in defining clinical, radiologic, histologie, and laboratory parameters to assist in a complete definition of the disease. Despite all these efforts, a preoperative diagnosis still remains a clinical challenge but is of paramount importance, as these cases have been reported to be steroid-responsive; therefore, early treatment may obviate the need for surgical resection. Although the utilization of recently proposed guidelines by the Japanese Pancreas Society and an Italian study group may further assist the clinician and prompt the initiation of steroid treatment, the response to therapy should be observed within 2 to 4 weeks and reflected in progressive resolution of the presenting radiologic and laboratory abnormalities. Should these fail to demonstrate improvement, the diagnosis of AIP should undergo re-evaluation, and consideration for surgical exploration should be made, as the patient may be harboring a malignancy. Surgical resection in the form of pylorus-preserving pancreaticoduodenectomy remains the optimal solution in the attempt to clarify the diagnosis and offer treatment with low complication rates.

Cephalic vein transposition is a durable approach to managing cephalic arch stenosis

INTRODUCTION The proximal cephalic vein that enters the axillary vein (cephalic arch) is a common site of stenosis in patients with upper extremity arteriovenous fistulas for hemodialysis (HD). In this study, we present the outcomes of a series of cephalic vein transposition, to determine its utility in the setting of refractory arch stenosis. METHODS We conducted a retrospective review of patients undergoing cephalic vein transposition to manage refractory cephalic arch stenosis from January 1, 2008 to August 31, 2015. Demographics, past medical history, access history of the patients as well as procedural details of the surgery to the stenotic segment, patency of the access, and the need for subsequent interventions were recorded. RESULTS Twenty-three patients underwent a cephalic vein transposition during the study period. The patients undergoing cephalic transposition had their current access for an average of 3.0 ± 2.6 years and had an average of 2.3 ± 0.9 interventions on the access prior to the surgery. Complications from the surgery were uncommon (8.7%) and no patient required a temporary tunneled dialysis catheter. The re-intervention rate was 0.2 ± 0.2 interventions per patient per year. At two years, primary patency was 70.9% and cumulative patency was 94.7% for the patients with cephalic transposition. CONCLUSIONS Cephalic vein transposition is safe and effective treatment for cephalic arch stenosis without interrupting utilization of the access. The surgical approach to stenosis of the proximal cephalic vein is effective, requires minimal re-interventions, and should be considered for isolated, refractory cephalic arch stenosis in mature arteriovenous fistulas.

The Treatment of Venous Disease in North America

During the past 15 years treatment of chronic venous insufficiency (CVI) has dramatically changed in North America. In the US, approximately 13 % of men and 22 % of women have venous insufficiency as determined by the San Diego Population Study (Robertson et al., Phlebology 23:103–111, 2008). The advent of minimally invasive vein procedures combined with reimbursement charges have created a paradigm shift in the treatment of CVI. Since 2008, there has been a significant increase in the number of office based procedures and now these represent the standard of care. The increase of office procedures is presumed to be due to an expanding number of non-surgical specialists performing vein procedures, changes in office based reimbursement patterns, industry sponsored advertising and the advancement of technology. The Society for Vascular Surgery (SVS), American Venous Forum (AVF) and American College of Phlebology (ACP) have published guidelines for the treatment of CVI, emphasizing the importance of initial conservative therapy followed by minimally invasive endovascular interventions for patients that have failed to respond favorably (Gloviczki et al., J Vasc Surg 53:2S–48S, 2011; Eklof et al., J Vasc Surg 40:1248–1252, 2004). Technology advancements appear to have increased patient satisfaction and improved the morbidity associated with vein procedures. It’s apparent that therapeutic treatment options should cater to the individual all the while establishing realistic expectations for each patient. Recently, the US Food and Drug Administration approved several new venous treatment methods that may complement or replace current vein treatments. Guidance for future treatment of CVI will require updated societal guidelines, site accreditation, physician certification and large-scale randomized control trials.

Current techniques to treat pathologic perforator veins

Pathologic perforating veins have become an interest to the venous specialist caring for patients with CEAP 4 to 6 disease. Historically, open perforator ligation and then subdermal endoscopic perforator ligation was described. These methods had clear shortcomings. More recently, thermal ablation techniques, including radiofrequency ablation and laser ablation, have been described. Ultrasound-guided sclerotherapy has also been used as a possible means to treat pathologic perforator veins. This report describes and summarizes the updated techniques to treat perforating veins in a challenging patient population.