Refinement of anatomic indications for the Nellix System for endovascular aneurysm sealing based on 2-year outcomes from the EVAS FORWARD IDE trial.

BACKGROUND: The Nellix System (Endologix, Inc, Irvine, Calif) for endovascular aneurysm sealing (EVAS) is a novel approach to abdominal aortic aneurysm treatment and conceptually different from endovascular aneurysm repair, whereby polymer is employed to fill and actively manage the abdominal aortic aneurysm sac. One-year safety and effectiveness results of the Nellix pivotal trial demonstrated encouraging outcomes with very low morbidity and mortality and high procedural and treatment success. Two-year imaging revealed a signal of migration, leading to a field safety notification issued by the manufacturer on October 21, 2016, and a dedicated root cause analysis, resulting in refinements to the instructions for use (IFU). We report the 2-year results of the investigational device exemption pivotal trial stratified according to the new and original criteria for selection of patients. METHODS: Comprehensive engineering evaluations, statistical analyses, and clinical assessments were conducted looking at patients enrolled in the pivotal trial (N = 150), roll-in cohort (N = 29), and continued access program (N = 154). All patients in all cohorts were treated on-IFU at the time of enrollment. Logistic regression models supported the mechanism that migration with Nellix is associated with a small aortic flow lumen relative to a large aneurysm thrombus burden and large aortic neck diameters. Based on these findings, refinements to the IFU criteria were applied, excluding patients with a thrombus index (maximum aneurysm sac/maximum flow lumen diameter) >1.4, aortic neck diameter >28 mm, and aortic neck conicity (>10% diameter change along the infrarenal neck) and requiring a 10-mm distal seal zone in the iliac artery. RESULTS: Freedom from all-cause mortality at 2 years was 94%. Patient outcomes were then stratified on the refined morphologic criteria and analyzed retrospectively. Two-year freedom from composite endoleak was high among both cohorts (95% on-IFU vs 92% off-IFU). Freedom from migration was 97.7% on-IFU vs 93.2% off-IFU (P = .0125). Freedom from aneurysm enlargement was 98.1% on-IFU vs 93.5% off-IFU (P value is not available because of failure of log-rank test assumptions). Composite freedom from migration, type IA endoleak, or aneurysm expansion was 95.9% among the on-IFU cohort vs 85.1% in the off-IFU cohort (P = .0017). CONCLUSIONS: Consistent with the introduction of a novel therapy, the presentation of failure modes of EVAS over time was inevitable. Using detailed imaging as well as engineering and statistical analysis, we were able to understand risk factors for adverse events specific to EVAS and defined those patients best suited for Nellix. With this EVAS-specific approach to defining IFU, on-IFU patients were identified as those with large aneurysms with little thrombus that would be prone to type II endoleaks and sac expansion with traditional devices. When treated with Nellix, these patients were predicted to experience exceptional results, especially with regard to a low composite endoleak rate and low all-cause mortality.

Extreme anemia (hemoglobin 1.8 g/dL) secondary to colon cancer.

We present the case of a 34-year-old man who presented to the emergency department with complaints of generalized fatigue and palpitations, with a heart rate of approximately 100 beats per minute and an orthostatic blood pressure of 80/30 mm Hg upon standing. A hemoglobin of 1.8 g/dL was discovered. A positive fecal occult blood test led to the diagnosis of colon cancer. Once the cancer was resected, the patient's anemia resolved.

Mortality After Nontraumatic Major Amputation Among Patients With Diabetes and Peripheral Vascular Disease: A Systematic Review.

High mortality rates have been reported after major amputations of a lower limb secondary to diabetes and peripheral vascular disease. However, the mortality rates have varied across studies. A systematic review of the 5-year mortality after nontraumatic major amputations of the lower extremity was conducted. A data search was performed of Medline using OVID, CINHAL, and Cochrane, 365 abstracts were screened, and 79 full text articles were assessed for eligibility. After review, 31 studies met the inclusion and exclusion criteria. Overall, the 5-year mortality rate was very high among patients with any amputation (major and minor combined), ranging from 53% to 100%, and in patients with major amputations, ranging from 52% to 80%. Mortality after below-the-knee amputation ranged from 40% to 82% and after above-the-knee amputation from 40% to 90%. The risk factors for increased mortality included age, renal disease, proximal amputation, and peripheral vascular disease. Although our previous systematic review of the 5-year mortality after ulceration had much lower rates of death, additional studies are warranted to determine whether amputation hastens death or is a marker for underlying disease severity.

Surgical management of carotid body tumors: a 15-year single institution experience employing an interdisciplinary approach.

Cervical paragangliomas are rare neoplasms that arise from extraadrenal paraganglia in close association with the cranial nerves and extracranial arterial system of the head and neck, and therefore surgical extirpation can be challenging. A retrospective study was conducted of all patients undergoing surgical excision of a cervical paraganglioma between 2000 and 2015. The demographic characteristics, clinical features, surgical approach, and outcomes were reviewed. A total of 20 cervical paragangliomas were excised in 17 patients. There were 14 female and 3 male patients with a mean age of 56.6 ± 17.0 at the time of operation. Twelve patients had unilateral tumors and 5 patients had bilateral tumors. Familial involvement was confirmed by history or direct genetic analysis in 8 (47%) of the 17 patients. There were no malignant paragangliomas, and only 3 patients had tumors that were determined to be functional. Tumor size ranged from 1.3 to 6.0 cm. Two patients required combined arterial resection as part of complete excision of the tumor. There were no permanent operative cranial nerve injuries, no recurrences, minimal morbidity, and no mortality. In conclusion, optimal management of cervical paragangliomas should include a thorough preoperative evaluation, accurate definition of the surgical anatomy, and exclusion of synchronous paragangliomas. A combined therapeutic approach by a multidisciplinary team including surgeons and interventional radiologists provides safe and effective management of cervical paragangliomas with very low morbidity and excellent outcomes.

The impact of foot ulceration and amputation on mortality in diabetic patients. I: From ulceration to death, a systematic review.

A great deal of emphasis, clinical and financial, is placed on limb salvage efforts in diabetic patients suffering from lower extremity ulceration. This is because of the impression that amputation in such patients may be a proximal cause of death. While amputation is certainly a negative clinical outcome, it is not entirely clear that it causes death. In this systematic review, we examine the available literature to attempt to understand the role that the ulceration itself may play in mortality. In brief, we searched for human studies in OVID, CINAHL and the COCHRANE CENTRAL DATABASE from 1980 to 2013, looking for articles related to ulcer or wound of the foot, in patients with diabetes or peripheral vascular disease, and death. We looked for articles with 5 years of follow-up, or Kaplan-Meier estimates of 5-year mortality, and excluded reviews and letters. Articles were assessed for quality and potential bias using the Newcastle-Ottawa scale. We find that while the patient populations studied varied widely in terms of demographics and comorbidities, limiting generalisability, 5-year mortality rates after ulceration were around 40%. Risk factors for death commonly identified were increased age, male gender, peripheral vascular disease and renal disease.

Endovascular aortoiliac aneurysm repair: surgical progress through new treatment paradigms and innovative endograft design.

Effective treatment for patients with an abdominal aortic aneurysm (AAA) began more than 50 years ago through the development of prosthetic grafts, which were used to replace aneurysmal segments of diseased arteries. Open surgical repair of AAAs became the gold standard for treating this disease. In 1999, two device manufacturers received US Food and Drug Administration approval for their endovascular aneurysm repair (EVAR) devices to treat selected patients with AAA. During the next 10 years, multiple other EVAR devices received US Food and Drug Administration approval, and, now, EVAR rivals open surgical repair as the standard for treating aortoiliac aneurysm disease. The purpose of this article is to outline advances in the device technology used for EVAR procedures, identify historical progress of treatment options, recognize complications after EVAR, describe improvements in device design, and specify related nursing implications.

The management of chronic venous insufficiency with ulceration: the role of minimally invasive perforator interruption.

BACKGROUND: The purpose of this study was to analyze the long-term outcomes associated with interruption of incompetent perforator veins (IPV) using minimally invasive techniques as adjunctive therapies in the management of patients with chronic venous insufficiency (CVI). METHODS: This is a retrospective review of a prospectively maintained venous database collected over 6 years (2005-2011). The study cohort included 64 patients with CVI stage C5 or C6 who underwent minimally invasive perforator interruption with subfascial endoscopic perforator surgery (SEPS) or radiofrequency ablation of IPV (RFA-IPV) as part of the management of their CVI. All patients were referred for evaluation after having failed conservative treatment with compression dressings. Relevant patient characteristics and comorbidities were recorded along with symptom resolution, venous ulcer healing, recurrence, and surgical complications. In addition to clinic follow-up examination by a surgical provider, chart notes from other subspecialties were also reviewed. We also conducted telephone assessments in patients who had been lost to clinic follow-up in order to provide complete outcome data. RESULTS: In this subset (n = 64) of patients with CVI who had adjunctive IPV treatment, 41 (64%) underwent SEPS and 23 (36%) patients underwent RFA-IPV along with ablation of the greater saphenous vein for C5 or C6 disease. The mean patient follow-up was 37 months. There were no differences in patient demographics or risk factors. Twenty-three (88%) SEPS and 12 (100%) RFA-IPV patients (P = NS) with C6 disease went on to completely heal their venous ulcers after the procedure with an average healing time of 5.2 (SEPS) and 4.4 (RFA-IPV) months (P = NS). Overall, 7 (17%) SEPS and 6 (23%) RFA-IPV patients (P = NS) developed a recurrent ulcer after surgical treatment. Procedural complications were seen in 14 (34%) SEPS and 2 (9%) RFA-IPV patients (P = NS), mostly minor. Major complications only occurred in the SEPS group consisting of 2 major amputations caused by pain from nonhealing ulcers and 1 deep venous thrombosis. CONCLUSIONS: This study supports the premise that in patients with advanced venous disease, there may be a demonstrable benefit directly attributable to perforator interruption. Our recurrent ulceration rates are acceptable, with low complication rates in patients undergoing RFA-IPV, thereby making this procedure more attractive in patients with multiple comorbidities. We support an aggressive approach to patients with C5/C6 disease that includes perforator elimination when appropriate.

Limitations of current EVAR endografts and potential solutions for their deficiencies.

All current endovascular aneurysm repair (EVAR) devices have defined limitations that prevent the endovascular therapist from using them to treat all forms of aortoiliac aneurysm disease. Short, angulated infrarenal aortic neck pathology, occlusive disease in iliac access arteries, need for preservation of important branch vessel arterial flow, endograft migration, and endoleak all represent major impediments for successful EVAR. Need for secondary intervention after EVAR in a significant number of patients has detracted from universal acceptance for this therapy. New devices in manufacturers' pipelines may provide solutions for many of the current EVAR device deficiencies. As these new devices become more complex, meticulous patient follow-up to verify anticipated outcomes and new training paradigms for the future endovascular therapist will be required.

Influence and critique of the PIVOTAL and the EVAR 2 Trials.

Management of a condition that has potentially life-threatening consequences may not lend itself effectively to the scrutiny of a randomized clinical trial when an observation or no treatment option is offered as part of the trial. This type of trial often experiences a significant rate of crossover of subjects from no treatment to treatment, and when results are analyzed on an intent-to-treat basis, they may fail to resolve the issue under study. These trials are frequently used as Level 1 medical evidence and the potential impact on clinical decision-making and reimbursement can be quite significant and long-lasting. The authors observed this phenomenon during participation in the Positive Impact of Endovascular Options for Treating Aneurysms Early (PIVOTAL) trial and have observed it in an analysis of the Endovascular Aneurysm Repair 2 (EVAR 2) trial. Possible solutions to mitigate the high crossover effect are offered for consideration. Some clinical conditions dealing with potentially life-threatening problems probably do not lend themselves to be studied in randomized prospective clinical trials containing an observation or no treatment arm.

Economic and outcomes-based analysis of the care of symptomatic varicose veins.

OBJECTIVE: Endoluminal treatment of symptomatic varicose veins (VV) reduces or eliminates inpatient hospital stays, lowers complication rates, and increases revenue for vein care centers adopting the technique. This study compares the outcomes and economics of two treatments for VV. METHODS: Since May 2007, endovenous radiofrequency ablation (RFA) of symptomatic VV has been performed at our institution. For outcome measurements, a cohort of 100 RFA procedures (26% CEAP class C5 and C6) was compared with 100 open greater or lesser saphenous stripping and ligation procedures (SL, 18% C5 and C6). Procedures were performed between August 2002 and October 2007. The time frame was chosen to allow for a 6-mo follow-up. Patients who had adjunctive removal of secondary varicosities were included in both cohorts. Cost estimates are based on the actual total direct costs derived from the hospital's charge sheets for 20 of the 100 patients in each of the cohorts (n = 40). The actual direct costs are based on 2009-dollar values and do not include the surgeons' professional fees. RESULTS: Seventy-nine percent of the RFA therapies were performed in an outpatient clinic treatment room with the remaining 21% performed in an operating room (OR). For the SL group, all procedures were performed in the OR with 68% of patients requiring at least one night of hospital stay (average length of stay 1.2 d). The estimated direct cost of performing RFA in the treatment room was $906. This was considerably less than the estimated $4241 total direct cost for open SL followed by in-hospital observation. Outpatient open SL cost $2622, which is only slightly more than the $2533 cost for outpatient RFA performed in the OR. The use of RFA was associated with an earlier return to normal leisure activities (3.3 d versus 26 d, P < 0.05), fewer total hospital nights (3 d versus 82 d, P < 0.05), and less use of general anesthesia (16% versus 95%, P < 0.05). There were no major complications in the RFA group compared with three major complications in the SL group. CONCLUSIONS: With the introduction of endovenous techniques at our institution, there has been a significant increase in the volume of patients seeking this less invasive treatment modality. This is due largely to the ease and comfort with which patients can now be treated as well as the reduced length of stay, reduction of general anesthetic use, and the speed at which they can return to normal activities. We recommend endovenous ablation techniques as both cost-saving and patient-preferred.

Inherent problems with randomized clinical trials with observational/no treatment arms.

Randomized clinical trials (RCTs) offering an observation/no treatment (OBS/NoRx) arm as control and which are focused on the management of a condition with potentially life-threatening consequences, however small the risk, often experience a significant rate of crossover to treatment by those randomized to the OBS/NoRx arm. Results of these trials when analyzed on intent-to-treat basis often fail to resolve the issue at which they were directed. The authors have observed this in trials of abdominal aortic aneurysms with this design and use these to exemplify the dilemmas RCTs of such design create, with crossovers ranging from 27% to over 60% (EVAR II, UKSAT, ADAM, PIVOTAL). Results of these trials are frequently used as level I medical evidence and their potential impact on clinical decision making and reimbursement can be quite significant and long-lasting. Recommendations regarding trial end points and suggestions to mitigate the high crossover effect are offered. It may be that some clinical conditions dealing with potentially life-threatening problems should not be studied in randomized prospective clinical trials containing an OBS/NoRx arm.

Endovenous ablation for the treatment of chronic venous insufficiency and venous ulcerations.

OBJECTIVE: Conventional treatment of chronic venous disease with ulceration is layered compression dressings. Saphenous vein stripping is reserved for recurrent or nonhealing ulcers. This study examines outcomes of aggressive endovenous therapy in promoting ulcer healing and/or preventing ulcer recurrence. The role of additional perforator vein ablation also is analyzed. METHODS: This retrospective chart review occurred during a 2.5-year time frame during which 356 patients with venous insufficiency were seen in our vein center and underwent 412 venous operations (56 with bilateral disease treated on separate dates). A cohort of 75 (21.1%) patients with severe chronic venous disease underwent 83 (20.1%) procedures (C5: n = 52, 63%; C6: n = 31, 37%); 8 patients had bilateral procedures. Data analysis included body-mass index (BMI), history of deep vein thrombosis (DVT) or previous vein surgery, and type of procedure (radiofrequency ablation (RFA) of greater saphenous vein (GSV) alone or GSV and perforator ablation (GSVP)). Complications, ulcer healing rates, and recurrent ulcerations were examined. Descriptive statistics are reported and contingency tables used when appropriate. RESULTS: Overall, the patients were 63.5 +/- 13.4 years of age (men: n = 36, women: n = 39) with a BMI of 32.4 (range, 20.8-53.4). All of the patients had GSV insufficiency and 30 (44%) patients had deep vein incompetence. Only 19 (28%) patients had a history of a DVT and 13 (19%) had previous vein procedures. The 31 extremities with C6 disease had been treated conservatively with compression for an average of 7.6 +/- 4.2 (range, 1-156) months before undergoing ablation. Ablation site was GSV in 49 (72%) and GSVP in 19 (28%). Only two (2.9%) complications occurred: excessive hemosiderin staining and paresthesias each occurred in one patient. Of the C5 patients treated, two (4.7%) developed recurrent ulcerations and five (20%) C6 patients did not heal completely or developed a recurrent ulcer. There was no statistically significant difference in ulcer healing or recurrence rates between C5 and C6 patients treated with and without the addition of perforator interruption. CONCLUSIONS: Chronic venous insufficiency with active or healed ulceration is commonly seen in our academic vein center. In this series, endovenous ablation allowed for excellent healing rates and acceptable recurrent ulcer rates. It is unclear from this small cohort whether the addition of perforator ablation was of benefit in improving venous hemodynamics.

Technical tips for endovascular repair of common iliac artery aneurysms.

Isolated common iliac artery aneurysms are rare, comprising <2% of all aneurysm disease. These aneurysms present as either isolated disease, .03% of the population, or, in conjunction with abdominal aortic aneurysm, in approximately 20% to 25% of such cases. Common iliac artery aneurysms are defined as any localized dilatation of the common iliac artery >1.5 cm in diameter. Elective repair for isolated common iliac artery aneurysms is generally not undertaken for aneurysms <3 cm in diameter unless they are part of an abdominal aortic aneurysm repair. Most common iliac artery aneurysms are found incidentally during abdominal/pelvic diagnostic imaging studies or at the time of pelvic or abdominal surgery. As with abdominal aortic aneurysms, endovascular repair of common iliac artery aneurysms follows techniques similar to those used for endovascular repair of abdominal aortic aneurysm. Management includes aneurysm exclusion with an endograft, which seals at sites within the proximal and distal common iliac artery and may involve coil occlusion of the hypogastric artery with extension of the reconstruction into the proximal external iliac artery, or use a "bell-bottom" endograft limb placed at the common iliac bifurcation. Technical tips for successful outcome are described here, and all US Food and Drug Administration approved endografts have been used for repair. There were no statistically significant differences in outcomes that correlated with device or repair techniques used for management of common iliac artery aneurysms. Mid-term 54-month outcome has been excellent, with no common iliac artery ruptures or aneurysm-related deaths and the need for secondary interventions was gratifyingly small.

Device-specific aneurysm sac morphology after endovascular aneurysm repair: evaluation of contemporary graft materials.

OBJECTIVE: This study analyzed device-specific aneurysm sac morphology after endovascular aneurysm repair (EVAR) with low-permeability devices. METHODS: Between September 2004 and May 2006, 122 patients were treated with EVAR. Three different devices were implanted: 47 Zenith (Cook, Indianapolis, Ind), 46 AneuRx (Medtronic, Santa Rosa, Calif) with Resilient Dacron Graft Material, and 29 Excluder (W. L. Gore & Associates, Flagstaff, Ariz) with low-porosity polytetrafluoroethylene (PTFE). Patients were followed up at 1, 6, and 12 months and then biannually with computed tomography (CT) angiography. Standard axial two-dimensional CT measurements were obtained and compared with preoperative imaging. The preoperative scan served as a baseline, and the minor axis diameter, measured at the largest axial cut of the abdominal aortic aneurysm, was compared with the same measurement at follow-up. RESULTS: Patient age, sex, and preoperative aneurysm morphology were similar among groups. Patients receiving the Zenith endograft had a significantly larger neck diameter; however, there was no difference in the neck length between groups. The rate of type II endoleaks was similar for the Zenith (17%), AneuRx (17%), and Excluder (14%). At 1, 6, 12, and 18 months, all three grafts were associated with sac shrinkage. The resulting decreases in mean aneurysm size at 18 months and corresponding shrinkage were Zenith, 11%, 6.4 +/- 1.8 mm; AneuRx, 18.9%, 12.7 +/- 2.7 mm; and the Excluder, 5.5%, 3.3 +/- 0.9 (P < .05). The sac size in the 19 patients with a type II endoleak decreased 8.06% compared with a 15.43% decrease in sac size in patients without endoleak at 6 months. No significant sac expansion > or =5 mm has been observed among any of the groups to date. CONCLUSIONS: Sac regression with all devices appears to have been favorably influenced by the new generation of graft materials and is improved compared with published reports of older generation graft materials for the AneuRx and Excluder. However, there is a trend toward greater sac regression with devices using Dacron vs PTFE. The relationship of aneurysm morphology and long-term effects on aortic stent grafts is yet to be determined.

Use of the internal mammary vein for access outflow in a hemodialysis fistula.

A patient with occlusion of multiple central veins from both dialysis and nondialysis catheters required permanent access for hemodialysis. Magnetic resonance imaging showed a patent left innominate vein. He underwent creation of a left axillary artery to internal mammary vein transposition fistula using the basilic vein from his right arm. The fistula has required one revision for outflow stenosis and one for aneurysmal degeneration. It continues to function well 3 years after placement. The internal mammary vein is an option for outflow when permanent hemodialysis access has failed in the presence of a patent innominate vein with occluded or severely stenotic ipsilateral subclavian and jugular veins.