Dawn M. Coleman

Midterm outcomes after treatment of type II endoleaks associated with aneurysm sac expansion

Purpose To examine the outcomes following interventions for type II endoleaks in patients with aneurysm sac expansion after endovascular aneurysm repair (EVAR). Methods A retrospective review was conducted of all patients who underwent treatment for type II endoleak from July 2001 to September 2010 in a single center. In this time period, 29 (4.7%) patients (22 men; mean age 78.6 years, range 54–87) were identified as having a type II endoleak and enlargement of the aneurysm sac, meeting the criterion for treatment. All patients had at least one attempted percutaneous intervention. Patients were followed both clinically and radiographically, with computed tomographic angiography every 3 to 12 months, over a follow-up period that ranged from 1 to 10 years (mean 3.5). Results Forty-eight interventions were performed on the 29 patients. Of these, 15 (56%) patients underwent multiple (2–4) procedures. Of the 11 endoleaks with an isolated inferior mesenteric artery identified as the source, initial success for transarterial embolization at 2 years was 72%, with 2 of the failures having successful secondary interventions. For the 18 endoleaks with a lumbar source, the success of the initial intervention was 17% at 2 years; repeated embolization attempts produced a 40% secondary success rate. Seven (24%) patients had continued endoleak despite multiple treatment attempts; 3 ultimately required elective aortic graft explantation. There were no ruptures or deaths during the study period. In a comparison of type II endoleak patients who had stable aneurysm sacs and those who had persistent sac expansion, the only significant differences in preoperative anatomical characteristics were a lower prevalence of mural thrombus (p=0.036) and longer right iliac arteries (p=0.012) in the group with sac expansion. Independent predictors of type II endoleak were mural thrombus (p<0.001), patent lumbar arteries (p=0.004), aneurysm length (p=0.011), and iliac artery length (p=0.004) Conclusion This study demonstrates that most patients require multiple reinterventions to treat type II endoleaks; specifically, lumbar artery embolization carries a low midterm success rate.

Endovascular aortic aneurysm repair with carbon dioxide-guided angiography in patients with renal insufficiency.

OBJECTIVE Renal dysfunction following endovascular abdominal aortic aneurysm repair (EVAR) remains a significant source of morbidity and mortality. We studied the use of carbon dioxide (CO(2)) as a non-nephrotoxic contrast agent for EVAR. METHODS Recorded data from 114 consecutive patients who underwent EVAR with CO(2) as the contrast agent over 44 months were retrospectively analyzed. CO(2) was used exclusively in 72 patients and in an additional 42 patients iodinated contrast (IC) was given (mean, 37 mL). Renal and hypogastric artery localization and completion angiography were done with CO(2) in all patients, including additional arterial embolization in 16 cases. Preoperative National Kidney Foundation glomerular filtration rate (GFR) classification was normal in 16 patients, mildly decreased in 52, moderate to severely decreased in 44, and two patients were on dialysis. RESULTS All graft deployments were successful with no surgical conversions. CO(2) angiography identified 20 endoleaks (two type 1, 16 type 2, and two type 4) and three unintentionally covered arteries. Additional use of IC in 42 patients did not modify the procedure in any case. When compared with a cohort of patients who underwent EVAR using exclusively IC, the operative time was shorter with CO(2) (177 vs 194 minutes; P = .01); fluoroscopy time was less (21 vs 28 minutes; P = .002), and volume of IC was lower (37 vs 106 mL; P < .001). Postoperatively, there were two deaths, two instances of renal failure requiring dialysis, and no complications related to CO(2) use. Among patients with moderate to severely decreased GFR, those undergoing EVAR with IC had a 12.7% greater decrease in GFR compared with the CO(2) EVAR group (P = .004). At 1, 6, and 12-month follow-up, computed tomography angiography showed well-positioned endografts with the expected patent renal and hypogastric arteries in all patients and no difference in endoleak detection compared with the IC EVAR group. During follow-up, eight transluminal interventions and one open conversion were required, and no aneurysm-related deaths occurred. CONCLUSIONS CO(2)-guided EVAR is technically feasible and safe; it eliminates or reduces the need for IC use, may expedite the procedure, and avoids deterioration in renal function in patients with pre-existing renal insufficiency. A prospective trial comparing CO(2) with IC during EVAR is warranted.

The contemporary management of renal artery aneurysms

BACKGROUND Renal artery aneurysms (RAAs) are rare, with little known about their natural history and growth rate or their optimal management. The specific objectives of this study were to (1) define the clinical features of RAAs, including the precise growth rate and risk of rupture, (2) examine the current management and outcomes of RAA treatment using existing guidelines, and (3) examine the appropriateness of current criteria for repair of asymptomatic RAAs. METHODS A standardized, multi-institutional approach was used to evaluate patients with RAAs at institutions from all regions of the United States. Patient demographics, aneurysm characteristics, aneurysm imaging, conservative and operative management, postoperative complications, and follow-up data were collected. RESULTS A total of 865 RAAs in 760 patients were identified at 16 institutions. Of these, 75% were asymptomatic; symptomatic patients had difficult-to-control hypertension (10%), flank pain (6%), hematuria (4%), and abdominal pain (2%). The RAAs had a mean maximum diameter of 1.5 ± 0.1 cm. Most were unilateral (96%), on the right side (61%), saccular (87%), and calcified (56%). Elective repair was performed in 213 patients with 241 RAAs, usually for symptoms or size >2 cm; the remaining 547 patients with 624 RAAs were observed. Major operative complications occurred in 10%, including multisystem organ failure, myocardial infarction, and renal failure requiring dialysis. RAA repair for difficult-to-control hypertension cured 32% of patients and improved it in 26%. Three patients had ruptured RAA; all were transferred from other hospitals and underwent emergency repair, with no deaths. Conservatively treated patients were monitored for a mean of 49 months, with no acute complications. Aneurysm growth rate was 0.086 cm/y, with no difference between calcified and noncalcified aneurysms. CONCLUSIONS This large, contemporary, multi-institutional study demonstrated that asymptomatic RAAs rarely rupture (even when >2 cm), growth rate is 0.086 ± 0.08 cm/y, and calcification does not protect against enlargement. RAA open repair is associated with significant minor morbidity, but rarely a major morbidity or mortality. Aneurysm repair cured or improved hypertension in >50% of patients whose RAA was identified during the workup for difficult-to-control hypertension.

ATDC/TRIM29 phosphorylation by ATM/ MAPKAP kinase 2 mediates radioresistance in pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) is characterized by therapeutic resistance for which the basis is poorly understood. Here, we report that the DNA and p53-binding protein ATDC/TRIM29, which is highly expressed in PDAC, plays a critical role in DNA damage signaling and radioresistance in pancreatic cancer cells. Ataxia-telangiectasia group D-associated gene (ATDC) mediated resistance to ionizing radiation in vitro and in vivo in mouse xenograft assays. ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC. Our results identify a DNA repair pathway leading from MK2 and ATM to ATDC, suggesting its candidacy as a therapeutic target to radiosensitize PDAC and improve the efficacy of DNA-damaging treatment.

Renal artery aneurysms

Renal artery aneurysms are rare in the general population, although the true incidence and natural history remain elusive. Controversy over criteria for repair persists across decades. Indications for repair presently include aneurysm size >2 cm, female gender within childbearing age, symptoms like pain and hematuria, medically refractory hypertension including that associated with functionally important renal artery stenosis, thromboembolism, dissection, and rupture. Conventional surgical reconstruction options are variable and continue to offer technically sound and durable results. Endovascular therapies with novel devices also offer technical success with few major adverse events, and are increasingly employed as indications for intervention broaden. This review summarizes the accumulated evidence on true renal artery aneurysms with a particular focus on contemporary treatment criteria, natural history, options for repair and outcomes following such.

Outcomes after late explantation of aortic endografts depend on indication for explantation.

BACKGROUND With the growing prevalence of endovascular repair for abdominal aortic aneurysm (AAA), the number of patients requiring graft explantation is increasing. Therefore, knowledge related to outcomes after explantation may lead to improvement in surgical options. In this study we compare our experience with explantation of aortic endografts, based on indication. METHODS The medical records of all aortic procedures performed at our center were queried during the period from 2002 to 2012. Relevant data from patients needing explantation of aortic endografts were analyzed using Fishers exact test, t-test, and Kaplan-Meier analysis. RESULTS Thirty-nine patients underwent aortic endograft explantation (64.1% men). Mean age was 71.9 years with a mean aneurysm size of 6.8 cm (range 3.5-10.7 cm). Hypertension (97.4%), hyperlipidemia (76.9%), and history of smoking (82%) were the most prevalent risk factors. Mean time to explant was 41.7 months (range 2.2-118.4 months). The primary explant indication was endoleak in 27 (69.2%) and infection in 12 (30.8%) patients. The endoleak group consisted of 13 type I, 8 type II, 1 type III, 4 endotension, 1 rupture, and 4 patients with multiple endoleaks. Seven patients were symptomatic, whereas 2 had ruptured aneurysms. Half of the patients in the infection group required supraceliac clamping for explantation. Operative blood loss (P = 0.08) and need for transfusion (P = 0.005) were significantly higher in the infection group. Thirty-day morbidity was 51.8% for the endoleak group and 83% for the infection group (P = 0.08). There were only 2 deaths in the cohort within 30 days, both in the infection group. Twenty-seven patients were alive at a mean follow-up of 1.9 years (range 0.1-8.4 years). CONCLUSIONS Endograft explantation is a challenging operation with high morbidity and mortality. Furthermore, patients with an infectious etiology have significantly worse outcomes than those requiring explantation for endoleaks.

Aneurysms in abdominal organ transplant recipients

OBJECTIVE The purpose of this study was to characterize the prevalence and natural history of aneurysms among abdominal transplant recipients. METHODS This article is a retrospective review of adult patients who underwent a kidney or liver transplant at a single center between February 23, 2000, and October 6, 2011. Data were obtained by searching electronic medical records for documentation of arterial aneurysm. Abdominal aortic aneurysms (AAAs) were included if they were ≥3.0 cm in diameter, and thoracic aortic aneurysms were included if they had a diameter ≥3.75 cm. Additional data collected included recipient demographics, transplant-specific data, and characteristics of the aneurysms. RESULTS There were 927 liver transplant recipients, 2133 kidney transplant recipients, 23 liver-kidney transplant recipients, and 133 kidney-pancreas transplant recipients included in our study; 127 of these patients were identified to have aneurysms (40 liver, 83 kidney, 3 liver-kidney, 1 kidney-pancreas). The overall prevalence of any aneurysm was similar for liver and kidney recipients, but the distribution of aneurysm types was different for the two groups. AAAs made up 29.6% of aneurysms in kidney transplant recipients and 11.4% of aneurysms in liver transplant recipients (P = .02). Visceral aneurysms were 10-fold as common in liver transplant recipients compared with kidney transplant recipients (47.7% of aneurysms vs 5.1% of aneurysms; P < .01). The majority of visceral artery aneurysms involved the hepatic and splenic artery. For both liver and kidney transplant recipients, most aneurysms occurred post-transplantation. All known aortic aneurysm ruptures occurred post-transplantation (25% of AAAs in liver transplant patients and 22.2% of thoracic aortic aneurysms in kidney transplant patients). There was a trend toward higher AAA expansion rates after transplantation (0.58 ± 0.48 cm/y compared with 0.41 ± 0.16 cm/y). CONCLUSIONS Compared with the general population, aneurysms may be more common and may have an aggressive natural history in abdominal transplant recipients. Furthermore, the types of aneurysms that affect liver and kidney transplant recipients differ. Care teams should be aware of these risks and surveillance programs should be tailored appropriately.

Rifampin Soaking Dacron-Based Endografts for Implantation in Infected Aortic Aneurysms—New Application of a Time-Tested Principle

Infections involving the aorta are associated with high rates of morbidity and mortality, and their management is complex. Saturating Dacron grafts in rifampin (60 mg/mL) inhibits the growth of organisms commonly found to be involved in both primary aortic infections and aortoenteric fistulas. Open repair and replacement of the aorta with rifampin-soaked Dacron grafts is frequently used in clinical practice and is considered a viable option for open repair with a low recurrence of infection; however, the morbidity and mortality of the procedure is significant. More recently, patients who are high risk for open surgery have been managed with endografts to treat infected aortas and aortoenteric fistulas with limited success, a high recurrence rate, and elevated mortality. We describe a technique to expose Dacron endografts with rifampin delivered via injection port or into the sheath before deployment in selected patients with aortic infections. We used this novel technique in 2 patients who were high risk for open repair: 1 with a bleeding aortoenteric fistula and 1 with mycotic abdominal aortic aneurysm. The first patient tolerated 1.5 years without surgical correction of the duodenal defect after placement of a rifampin-treated endograft. This allowed her to recover and ultimately undergo definitive repair under elective circumstances. Our second patient remains without evidence of recurrence 1 year after implantation for a mycotic abdominal aortic aneurysm. Following the principles of rifampin use in open vascular repairs, treating Dacron endografts with rifampin may add similar antimicrobial resistance when used to treat selected aortic infections.

Cigarette smoke–induced MMP2 and MMP9 secretion from aortic vascular smooth cells is mediated via the Jak/Stat pathway

It is hypothesized that cigarette smoke may increase MMP2 and MMP9 secretion through Jak/Stat pathway in the aorta, thereby facilitating abdominal aortic aneurysm (AAA) formation/progression in smokers. We observed through zymograms that treatment of male rat aortic vascular smooth muscle cells (RASMC) with an aqueous extract of cigarette smoke (CSE) for 24 hours resulted in a significant increase in pro-MMP9 (P = .005) and a modest increase in pro-MMP2 (P = .055) production. Western blot with protein extracts from CSE-treated RASMC showed up-regulation of pStat3, pJak2, and T-Jak2 and unchanged levels of T-Stat3. Transfection of RASMC with small interfering RNAs for Jak2, Stat3, or both Jak2 and Stat3 significantly reduced pro-MMP9 (P < .005) and pro-MMP2 (P < .05) in medium of CSE-treated RASMC compared with control small interfering RNA-transfected cells. Immunoprecipitation with total Jak2 antibody showed increased pStat3 and T-Stat3 in the cytoplasm and nucleus of CSE-treated RASMC. Immunofluorescence revealed increased presence of pJak2, T-Jak2, pStat3, and T-Stat3 in the cytoplasm and nucleus of the CSE-treated cells. Treatment of control human tissues with CSE resulted in pro-MMP9 secretion and up-regulation of the Jak/Stat proteins. In addition, AAA tissues showed more pJak2 and pStat3 than control human tissues. Therefore, inhibiting the Jak/Stat pathway could be a potential therapeutic approach in the treatment of AAA.

Biomarkers for the diagnosis of deep vein thrombosis

Venous thromboembolic disease (VTE) remains a significant source of morbidity and mortality. As non-specific subjective complaints and a paucity of objective clinical examination findings complicate the diagnosis of both deep venous thrombosis (DVT) and pulmonary embolism, diagnostic modalities remain essential. Compression ultrasound remains the gold standard for DVT diagnosis. Reliable imaging is not always available making a serologic diagnosis, or biomarker, highly desirable. While D-dimer, a highly sensitive biomarker, is useful for excluding acute VTE, it lacks the specificity necessary for diagnostic confirmation. As such, ongoing research efforts target and support the utility of alternative plasma biomarkers to aid in the diagnosis of VTE including selectins, microparticles, IL-10 and other inflammatory markers. These molecular markers may also predict recurrence risk, guide length and modality of treatment, and predict which thrombi will resolve spontaneously or recanalize, thus potentially identifying patients who would benefit from more aggressive therapies than standard anticoagulation.