Management of Seat Belt-type Blunt Abdominal Aortic Trauma and Associated Injuries in Pediatric Patients.

BACKGROUND: "Seat belt-type" pediatric abdominal aortic trauma is uncommon but potentially lethal. During high speed motor vehicle collisions (MVCs), seat or lap belt restraints may concentrate forces in a band-like pattern across the abdomen, resulting in the triad of hollow viscus perforation, spine fracture, and aortoiliac injury. We report 4 cases of pediatric seat belt-type aortic trauma and review management strategies for the aortic disruption and the associated constellation of injuries. METHODS: -approved, retrospective review of all pediatric patients requiring surgical intervention for seat belt-type constellation of abdominal aortic/iliac and associated injuries over a 5-year period. Blunt thoracic aortic injuries were excluded. RESULTS: We identified 4 patients, ranging from 2 to 17 years of age, who required surgical correction of seat belt-type aortoiliac trauma and associated injuries: 3 abdominal aortas and 1 left common iliac artery. The majority (3/4 patients) were hemodynamically unstable at emergency room presentation, and all underwent computed tomography angiography of the chest/abdomen/pelvis during initial resuscitation. Injuries of the suprarenal and proximal infrarenal aorta were accompanied by unilateral renal artery avulsion requiring nephrectomy. Presumed or proven spinal instability mandated supine positioning and midline laparotomy, with medial visceral rotation utilized for proximal injuries. Aortoiliac injuries requiring repair were accompanied by significant distal intraluminal prolapse of dissected intima, with varying degrees of obstruction. Conduit selection was dictated by the presence of enteric contamination and the rapid availability of an autologous conduit. The sole neurologic deficit was irreparable at presentation. CONCLUSIONS: Seat belt aortoiliac injuries in pediatric patients require prompt multidisciplinary evaluation. Evidence of contained aortoiliac transection, major branch vessel avulsion, and bowel perforation mandates immediate exploration, which generally precedes spinal interventions. Lesser degrees of aortoiliac injuries have been managed with surveillance, but long-term follow-up is needed to fully validate this approach.

Penetrating Aortic Ulcer and Intramural Hematoma.

Acute aortic syndromes include a variety of overlapping clinical and anatomic diseases. Penetrating aortic ulcer (PAU), intramural hematoma (IMH) and aortic dissection can occur as isolated processes or can be found in association. All these entities are potentially life threatening, so prompt diagnosis and treatment is of paramount importance. PAU and IMH lesions in the Stanford Type A distribution often require urgent open surgical repair. Lesions in the Stanford Type B distribution may be managed medically in the absence of symptoms or progression; however, a low threshold for endovascular or surgical treatment should be maintained. This review summarizes the clinical presentation, epidemiology, diagnosis, indications for treatment and endovascular strategies in patients with PAU or IMH.

Feasibility of endovascular repair of splenic artery aneurysms using stent grafts.

OBJECTIVE: Percutaneous transcatheter embolization of splenic artery aneurysms (SAAs) has been widely accepted as the first line of treatment in patients with symptoms, rupture, or large aneurysm size. Although embolization can usually be performed safely, ischemic complications, such as splenic infarct or abscess, occur in some patients. This study evaluated the feasibility and outcomes of endovascular SAA repair (ESAAR) using stent grafts, which may allow treatment while preserving flow to the spleen. METHODS: We reviewed the clinical data of all consecutive patients who underwent ESAAR using stent grafts. Brachial access was used except for patients with favorable angle of origin from the aorta. To overcome tortuosity and provide support, a coaxial system with a hydrophilic sheath was used. Low-profile 0.018-inch stent grafts were used for distal SAAs with a 10-mm to 15-mm length of proximal and distal segment of splenic artery measuring 4 to 11 mm in diameter. Follow-up included clinical examination and computed tomography imaging within 4 to 6 months after the procedure and yearly thereafter. End points were morbidity, stent graft patency, and freedom from endoleaks and reinterventions. RESULTS: ESAAR was attempted in 10 patients, four males and six females, with median age of 64 years (range, 48-77 years). Median SAA size was 2.8 cm (range, 2-5.7 cm). Nine patients were asymptomatic, and one had pancreatitis and gastrointestinal bleeding. The arterial access site was the brachial artery in six patients and the femoral artery in four. Two patients had brachial and femoral access to facilitate splenic artery stenting. Technical success of ESAAR using stent grafts was 80% (8 of 10). In two patients with distal SAAs, stent graft placement was not possible due to excessive vessel tortuosity, and treatment was by coil embolization. One patient developed brachial artery thrombosis, which was treated surgically. There were no ischemic complications in patients treated by ESAAR with stent grafts. Median length of stay was 1 day. One patient treated by coil embolization developed splenic infarct, which required readmission for pain control. Median follow-up was 9 months. Follow-up imaging in all successfully stented patients revealed patent stent grafts, no endoleak, and no aneurysm sac enlargement. No reinterventions were required. CONCLUSIONS: ESAAR using self-expandable stent grafts offers a viable alternative to coil embolization in selected patients with SAAs. Distal SAAs with excessive vessel tortuosity may result in technical failure requiring embolization. Among patients who underwent successful ESAAR, there were no ischemic complications, stent graft occlusions, endoleaks, or sac enlargement.

False Lumen Embolization to Treat Disseminated Intravascular Coagulation After Thoracic Endovascular Aortic Repair of Type B Aortic Dissection.

PURPOSE: To present a rare case of disseminated intravascular coagulation (DIC) after thoracic endovascular aortic repair (TEVAR) and its novel treatment. CASE REPORT: A 55-year-old man presented with DIC 10 months after TEVAR for chronic type B aortic dissection and descending thoracic aortic aneurysm. He had persistent retrograde flow in the false lumen with a stable aneurysm diameter. The false lumen was embolized with multiple Amplatzer plugs, which promoted false lumen thrombosis. Laboratory evaluation on postoperative day 7 demonstrated resolution of the coagulopathy. Follow-up at 18 months revealed no recurrent DIC; computed tomography angiography showed a stable aortic diameter and excluded thoracic aneurysm sac. CONCLUSION: This case demonstrates an unusual, potentially fatal postoperative complication of endovascular treatment of type B aortic dissections successfully treated with an innovative endovascular solution.

Treatment of nutcracker syndrome with open and endovascular interventions.

OBJECTIVE: Nutcracker syndrome (NS) is a rare cause of hematuria, flank pain, and renal venous hypertension due to compression of the left renal vein (LRV) between the aorta and the superior mesenteric artery. To evaluate outcomes of open surgery and endovascular interventions, we reviewed our experience. METHODS: A retrospective review of clinical data of all patients treated at our institution with an intervention for NS between January 1, 1994, and February 28, 2014, was performed. Primary outcomes were morbidity and mortality. Secondary outcomes included late complications, patency, freedom from reintervention, and resolution of symptoms. RESULTS: Thirty-seven patients (30 female, seven male) with a mean age of 27 years (range, 14-62 years) were treated. The most frequent symptom was flank pain (97%); the most frequent sign was hematuria (68%). NS was diagnosed with duplex ultrasound scanning with measurement of LRV diameters and flow velocities (87%), with computed tomography or magnetic resonance venography (94%), and with contrast venography with measurement of pressure gradients (93%). Initial treatment was open surgery in 36 patients, endovascular in 1. Distal transposition of the LRV into the inferior vena cava (IVC) was performed in 31 patients. Adjunctive procedures to optimize venous outflow included great saphenous vein cuff in six patients, great saphenous vein patch in four, and both cuff and patch in four. Three patients had patch alone; two had transposition of the left gonadal vein into the IVC. Two patients had anterior reimplantation of retroaortic LRV into the IVC. There were no major early complications, renal failure, or mortality. Three patients underwent early reinterventions within 30 days (stent, two; open revision, one). All LRVs and left gonadal veins were patent at discharge. Follow-up was 36.8 ± 52.6 months (range, 1-216 months). Reinterventions after 30 days were performed in eight patients because of LRV stenosis (n = 7) or LRV occlusion (n = 1). One stent migrated into the IVC and required endovascular removal with repeated stenting. Six patients required stenting. Primary, primary assisted, and secondary patencies at 24 months were 74%, 97%, and 100%, respectively. Freedom from reintervention at 12 and 24 months was 76% and 68%, respectively. Resolution of symptoms occurred in 33 patients (87%). CONCLUSIONS: Open surgery, mostly LRV transposition, remains a safe and effective treatment of patients with NS. However, one of three patients after open repair required reintervention, most frequently LRV stenting. Open reconstruction should be tailored to the patient's anatomy, and placement of vein cuff or patch may reduce restenosis. Although renal vein stents improved patency, the safety and durability of currently available stents need to be established.

Open surgical removal of a tilted and dislodged inferior vena cava filter through a lumbar branch without cavotomy.

Retrievable inferior vena cava (IVC) filters decrease the risk of pulmonary embolism. Retrieval is recommended but device migration, tilting, or perforation of the IVC by the filter may prevent successful removal. We present a case of a tilted IVC filter with the retrieval hook lodged in a lumbar vein preventing endovascular removal. A subcostal incision was used for open removal. The thrombosed lumbar vein was encircled with vessel loops, facilitating collapse of the filter. No cavotomy was made. This technique, with minimal variation, can be used to remove most nonthrombosed retrievable filters from the IVC, without the need for venotomy.

Efficacy of combined renal and mesenteric revascularization.

OBJECTIVE: Small numbers of patients have advanced renal and mesenteric vascular disease requiring treatment. Open surgical treatment has been considered high risk, and the advent of endovascular intervention has affected management. This study evaluated the safety and long-term efficacy of concomitant mesenteric and renal revascularization with open techniques. METHODS: Data from 90 consecutive patients who underwent mesenteric and renal revascularization during a 30-year period were analyzed. Early and late outcomes were evaluated over two intervals: 48 in period A (1978 to 1995), concomitant open renal and mesenteric revascularization (COR; n = 46) and sequential open renal and mesenteric revascularization (SOR; n = 2); 42 in period B (1996 to 2009), 22 COR, 4 SOR, 13 sequential hybrid open/endovascular repairs (SOER), and 3 sequential endovascular repairs (SER). RESULTS: There were 26 men and 64 women (median age, 67 years). Renal insufficiency was present in 24% and coronary artery disease (CAD) in 53%. Open surgical reconstruction was performed in 126 renal and 149 mesenteric arteries, with angioplasty/stenting in 15 and 8, respectively; 58 patients had concomitant aortic reconstruction (AR), and 9 had prior AR (8 in period A, 1 in period B). Hospital mortality was 8.8% overall; seven (14.5%) in period A and one (2.3%) in period B. Causes of early death were hemorrhage in three and multisystem organ failure in five. During a median follow-up of 4.5 years (range, 6 days-26.5 years), 11 patients progressed to hemodialysis (7 COR, 4 SOER), and 6 had recurrent mesenteric ischemia (4 COR, 1 SOER, 1 SER). Eight patients in period A and seven in period B required further procedures (9 renal, 9 mesenteric; 11 COR, 2 SOER, 1 SOR, 1 SER). Univariate analysis of COR patients showed CAD (P = .017) and prior AR (P = .035), but not concomitant AR (P = .366), predicted early death. Five-year survival for COR patients was 65% overall, but 74% in patients who survived the operation, with no difference between time periods (P = .55). CONCLUSIONS: Concomitant open mesenteric and renal revascularization is associated with low early mortality and good long-term durability in appropriately selected patients. It remains a viable procedure, especially in patients requiring concomitant aortic reconstruction. High-risk patients with CAD or prior aortic surgery should be considered for endovascular treatment, when anatomically feasible.

Left renal vein transposition for nutcracker syndrome.

OBJECTIVE: Nutcracker syndrome, caused by compression of the left renal vein (LRV) between the superior mesenteric artery and the aorta, results in left renal and gonadal venous hypertension. Several treatment options have been described to relieve associated symptoms. The purpose of this study was to evaluate late results of LRV transposition and identify risk factors affecting outcomes. METHODS: Clinical data from 23 consecutive patients diagnosed with nutcracker syndrome from January 1996 to October 2007 were retrospectively reviewed. RESULTS: There were 10 males and 13 females (median age 22 years; range, 14-67) with radiologic evidence of LRV compression. On ultrasound evaluation (15/23 patients), the mean ratio of LRV peak systolic velocity measured at the site of compression and the renal hilum was 7.3 (range, 2.5-12). On venography (14/23 patients), the mean renocaval pressure gradient was 4 mm Hg (range, 2-6 mm Hg). Twelve patients with atypical abdominal pain (n = 4), hematuria (n = 5), and varicocele (n = 6) were managed expectantly. Eleven patients underwent LRV transposition through a transperitoneal exposure. Symptoms in these patients included left flank pain (n = 10), hematuria (n = 7), and varicocele (n = 3). In 2/11 patients, the LRV was found to be occluded at operation. There were no early postoperative complications. Most conservatively managed patients remained stable or improved over a mean follow-up period of 26 months (range, 0.2-59 months). Two patients were lost to follow-up at our institution and ultimately underwent intervention with LRV stenting and autotransplantation elsewhere. One patient was diagnosed with thin basement membrane disease on renal biopsy. Five patients with varicocele remained asymptomatic; 1 underwent local repair. Over a mean follow-up of 39 months (range, 0.13-144 months) in surgically managed patients, symptoms of flank pain and hematuria resolved or improved in 8/10 and 7/7, respectively. Varicoceles recurred in 2/3 patients in spite of resolution of flank pain. Both preoperatively occluded LRVs rethrombosed; one underwent thrombolysis with stenting, the other reimplantation of the left gonadal vein into the IVC. CONCLUSION: Evaluation of the clinical significance of radiologic LRV compression remains challenging, as does selection of patients for intervention. LRV transposition is a safe, effective procedure in selected patients with persistent, severe symptoms. Patients with progression to occlusion of the LRV should be considered for alternative therapeutic procedures. Varicoceles, in the setting of nutcracker syndrome, may need independent repair.

Effect of disrupting seven-in-absentia homolog 2 function on lung cancer cell growth.

BACKGROUND: Hyperactivated epidermal growth factor receptor (EGFR) and/or RAS signaling drives cellular transformation and tumorigenesis in human lung cancers, but agents that block activated EGFR and RAS signaling have not yet been demonstrated to substantially extend patients' lives. The human homolog of Drosophila seven-in-absentia--SIAH-1 and SIAH-2--are ubiquitin E3 ligases and conserved downstream components of the RAS pathway that are required for mammalian RAS signal transduction. We examined whether inhibiting SIAH-2 function blocks lung cancer growth. METHODS: The antiproliferative and antitumorigenic effects of lentiviral expression of anti-SIAH-2 molecules (ie, a dominant-negative protease-deficient mutant of SIAH-2 [SIAH-2(PD)] and short hairpin RNA [shRNA]-mediated gene knockdown against SIAH-2) were assayed in normal human lung epithelial BEAS-2B cells and in human lung cancer BZR, A549, H727, and UMC11 cells by measuring cell proliferation rates, by assessing MAPK and other activated downstream components of the RAS pathway by immunoblotting, assessing apoptosis by terminal deoxynucleotidyltransferase-mediated UTP end-labeling (TUNEL) assay, quantifying anchorage-independent cell growth in soft agar, and assessing A549 cell-derived tumor growth in athymic nude mice (groups of 10 mice, with two injections of 1 x 10(6) cells each at the dorsal left and right scapular areas). All statistical tests were two-sided. RESULTS: SIAH-2 deficiency in human lung cancer cell lines reduced MAPK signaling and statistically significantly inhibited cell proliferation compared with those in SIAH-proficient cells (P < .001) and increased apoptosis (TUNEL-positive A549 cells 3 days after lentivirus infection: SIAH-2(PD) vs control, 30.1% vs 0.0%, difference = 30.1%, 95% confidence interval [CI] = 23.1% to 37.0%, P < .001; SIAH-2-shRNA#6 vs control shRNA, 27.9% vs 0.0%, difference = 27.9%, 95% CI = 23.1% to 32.6%, P < .001). SIAH-2 deficiency also reduced anchorage-independent growth of A549 cells in soft agar (mean number of colonies: SIAH-2(PD) vs control, 124.7 vs 57.3, difference = 67.3, 95% CI = 49.4 to 85.3, P < .001; shRNA-SIAH-2#6 vs shRNA control: 27.0 vs 119.7, difference = 92.7, 95% CI = 69.8 to 115.5, P < .001), and blocked the growth of A549 cell-derived tumors in nude mice (mean tumor volume on day 36 after A549 cell injection: SIAH-2(PD) infected vs uninfected, 191.0 vs 558.5 mm(3), difference = 367.5 mm(3), 95% CI = 237.6 to 497.4 mm(3), P < .001; SIAH-2(PD) infected vs control infected, 191.0 vs 418.3 mm(3), difference = 227.5 mm(3), 95% CI = 87.4 to 367.1 mm(3), P = .003; mean resected tumor weight: SIAH-2(PD) infected vs uninfected, 0.12 vs 0.48 g, difference = 0.36 g, 95% CI = 0.23 to 0.50 g, P < .001; SIAH-2(PD) infected vs control infected, 0.12 vs 0.29 g, difference = 0.17 g, 95% CI = 0.04 to 0.31 g, P = .016). CONCLUSIONS: SIAH-2 may be a viable target for novel anti-RAS and anticancer agents aimed at inhibiting EGFR and/or RAS-mediated tumorigenesis.

Open repair of juxtarenal aortic aneurysms (JAA) remains a safe option in the era of fenestrated endografts.

OBJECTIVES: Widespread application of infrarenal endovascular aneurysm repair (EVAR) has resulted in a proportionate increase in open juxtarenal aortic aneurysm (JAA) repairs. Fenestrated endograft technology for JAA is developing rapidly, but only limited outcomes are known. The aim of this study was to review our open JAA experience in an era of fenestrated endograft technology, identify factors associated with increased surgical risk, determine early and midterm outcome, and provide a basis for comparison for future endovascular procedures. METHODS: Data from 126 consecutive patients who underwent elective JAA repair requiring suprarenal aortic clamping from 2001 to 2006 were analyzed retrospectively. Electronic medical chart reviews were used to record 30-day complication rates. Multivariate analyses were performed to identify risk factors associated with surgical morbidity. Mail-out questionnaires and telephone surveys were conducted to determine long-term follow-up. RESULTS: Ninety-eight males and 28 females (median age 74 years; range 55 to 93) were included in the study. Preoperative risk factors included: coronary artery disease (CAD) 58%, pulmonary disease 41%, renal insufficiency (serum creatinine [Cr] > 1.5mg/dL) 17%, and diabetes 9%. Fifteen patients underwent concomitant renal artery revascularization. Mean operative time was 319 minutes (range 91 to 648). Thirty-day mortality was 1/126 (0.8%). Median hospital length of stay was 7 days (range 3 to 85); median intensive care unit length of stay was 2 days (1 to 64). Complications included renal insufficiency (Cr increase > 0.5 mg/dL) in 22 (18%), cardiac in 17 (13%), and pulmonary in 14 (11%). Five patients required temporary hemodialysis; only one after hospital dismissal. Mean follow-up was 48 months (range 9-80). On multivariate analysis, age > or = 78 years (P = .001), male gender (P = .04), hypertension (P =.01), previous myocardial infarction (P = .047), and diabetes (P =.009) were predictive of cardiac complications. Renal artery revascularization (P = .01) and prior MI (P = .04) were multivariate predictors of pulmonary complications. Both prolonged operative (> or =351 minutes, P = .02) and renal ischemia (> or =23 minutes, P =.004) times predicted postoperative renal insufficiency. One, 3, and 5-year cumulative survival rates were 93.9%, 78.3%, and 63.8%, respectively and were not significantly different than an age- and gender-matched sample of the US population (P = .16). Mortality was not predicted by any specific risk factors. CONCLUSIONS: Open surgical repair of JAA is associated with low mortality and remains the gold standard. Although 18% had renal complications, only one patient had permanent renal failure. Patients with a combination of physiologic and anatomic risk factors identified on multivariate analysis may benefit from fenestrated endograft repair.

Inhibition of RAS-mediated transformation and tumorigenesis by targeting the downstream E3 ubiquitin ligase seven in absentia homologue.

Constitutively active RAS small GTPases promote the genesis of human cancers. An important goal in cancer biology is to identify means of countervailing activated RAS signaling to reverse malignant transformation. Oncogenic K-RAS mutations are found in virtually all pancreatic adenocarcinomas, making the RAS pathway an ideal target for therapeutic intervention. How to best contravene hyperactivated RAS signaling has remained elusive in human pancreatic cancers. Guided by the Drosophila studies, we reasoned that a downstream mediator of RAS signals might be a suitable anti-RAS target. The E3 ubiquitin ligase seven in absentia (SINA) is an essential downstream component of the Drosophila RAS signal transduction pathway. Thus, we determined the roles of the conserved human homologues of SINA, SIAHs, in mammalian RAS signaling and RAS-mediated tumorigenesis. We report that similar to its Drosophila counterpart, human SIAH is also required for oncogenic RAS signaling in pancreatic cancer. Inhibiting SIAH-dependent proteolysis blocked RAS-mediated focus formation in fibroblasts and abolished the tumor growth of human pancreatic cancer cells in soft agar as well as in athymic nude mice. Given the high level of conservation of RAS and SIAH function, our study provides useful insights into altered proteolysis in the RAS pathway in tumor initiation, progression, and oncogenesis. By targeting SIAH, we have found a novel means to contravene oncogenic RAS signaling and block RAS-mediated transformation/tumorigenesis. Thus, SIAH may offer a novel therapeutic target to halt tumor growth and ameliorate RAS-mediated pancreatic cancer.