From the Society for Vascular Surgery

Pediatric nonaortic arterial aneurysms Frank M. Davis, MD,a Jonathan L. Eliason, MD,a Santhi K. Ganesh, MD,b Neal B. Blatt, MD, PhD,c James C. Stanley, MD,a and Dawn M. Coleman, MD,a Ann Arbor, Mich Objective: Pediatric arterial aneurysms are extremely uncommon. Indications for intervention remain poorly defined and treatments vary. The impetus for this study was to better define the contemporary surgical management of pediatric nonaortic arterial aneurysms. Methods: A retrospective analysis was conducted of 41 children with 61 aneurysms who underwent surgical treatment from 1983 to 2015 at the University of Michigan. Arteries affected included: renal (n [ 26), femoral (n [ 7), iliac (n [ 7), superior mesenteric (n [ 4), brachial (n [ 3), carotid (n [ 3), popliteal (n [ 3), axillary (n [ 2), celiac (n [ 2), ulnar (n [ 2), common hepatic (n [ 1), and temporal (n [ 1). Intracranial aneurysms and aortic aneurysms treated during the same time period were not included in this study. Primary outcomes analyzed were postoperative complications, mortality, and freedom from reintervention. Results: The study included 27 boys and 14 girls, with a median age of 9.8 years (range, 2 months-18 years) and a weight of 31.0 kg (range, 3.8-71 kg). Multiple aneurysms existed in 14 children. Obvious factors that contributed to aneurysmal formation included: proximal juxta-aneurysmal stenoses (n [ 14), trauma (n [ 12), Kawasaki disease (n [ 4), Ehlers-Danlos type IV syndrome (n [ 1), and infection (n [ 1). Preoperative diagnoses were established using arteriography (n [ 23), magnetic resonance angiography (n [ 6), computed tomographic arteriography (n [ 5), or ultrasonography (n [ 7), and confirmed during surgery. Indications for surgery included risk of expansion and rupture, potential thrombosis or embolization of aneurysmal thrombus, local soft tissue and nerve compression, and secondary hypertension in the case of renal artery aneurysms. Primary surgical techniques included: aneurysm resection with reanastomsis, reimplantation, or angioplastic closure (n [ 16), interposition (n [ 10) or bypass grafts (n [ 2), ligation (n [ 9), plication (n [ 8), endovascular occlusion (n [ 3), and nephrectomy (n [ 4) in cases of unreconstructable renal aneurysmal disease. Later secondary operations were required to treat stenoses at the site of the original aneurysm repairs (n [ 2) and new aneurysmal development (n [ 1). Postoperative follow-up averaged 47 months (range, 1-349 months). No major perioperative morbidity and no mortality was encountered in this experience. Conclusions: Pediatric arterial aneurysms represent a complex disease that affects multiple vascular territories. Results of the current series suggest that individualized surgical treatment, ranging from simple ligations to major arterial reconstructions, was durable and can be undertaken with minimal risk. (J Vasc Surg 2016;63:466-76.)

Pediatric arterial aneurysms are extremely uncommon. Underlying processes often contribute to the development of these aneurysms, including infection, trauma, connective tissue diseases, noninfectious arteritides, or congenital vascular malformations.1-13 Previous reports From the Section of Vascular Surgery, Department of Surgery,a Department of Cardiovascular Medicine, Department of Internal Medicine and Department of Human Genetics,b and Division of Pediatric Nephrology, Department of Pediatrics and Communicable Diseases,c University of Michigan. Funding provided by Robson Research Fund and Zangara Research Fund granted to J.C.S. and D.M.C. Author conflict of interest: none. Presented at the 2015 Vascular Annual Meeting of the Society for Vascular Surgery, Chicago, Ill, June 17-20, 2015. Additional material for this article may be found online at www.jvascsurg.org. Correspondence: Dawn M. Coleman, MD, Department of Vascular Surgery, University of Michigan, 5364 Cardiovascular Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5867 (e-mail: dawnbarn@umich. edu). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2016 by the Society for Vascular Surgery. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jvs.2015.08.099

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usually described solitary cases or limited series rarely exceeding three or four children. As such, the optimal surgical treatment of nonaortic pediatric arterial aneurysms remains poorly defined. In the current study we investigated the indications, options for surgical interventions, and outcomes after treatment of these unusual aneurysms. METHODS A retrospective study was conducted of the surgical therapy of pediatric nonaortic arterial aneurysms that affected 41 consecutive children with 61 aneurysms treated at the University of Michigan Medical Center between 1983 and 2015. Intracranial and aortic aneurysms treated during this period were not included in this analysis because their management was markedly different from that of peripheral aneurysms reported in this current series. It is of note that only one of this study’s 41 children had an abdominal aortic aneurysm. Nine additional children with an abdominal aortic aneurysm encountered during the same time period exhibited no nonaortic aneurysms and were thereby not included in this study. This research was approved by the University of Michigan Medical School institutional review board (HUM00080240) and a waiver of informed consent was granted. Patients and

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family members within this series were contacted for those who could be reached. Medical records and direct communications with the patients and referring physicians were reviewed for patient demographic characteristics, risk factors, surgical details, and postoperative outcomes. An earlier publication from this institution included eight of the current series’ patients.11 Diagnostic assessment. Preoperative imaging during the earlier years of this experience involved catheter-based digital subtraction arteriography. Magnetic resonance angiography (MRA) and ultrasonography subsequently became common diagnostic tests. Thin-cut computed tomographic arteriography has improved the anatomic characterization of many complex lesions, but was pursued cautiously because of a concern of cumulative radiation exposure in childhood and subsequent oncologic risk. In total, diagnoses were made preoperatively using catheter-based arteriographic studies (n ¼ 23), MRA (n ¼ 6), computed tomographic arteriography (n ¼ 5), or ultrasonography (n ¼ 7). Analysis. Aneurysms were classified in a manner as originally proposed by Sarkar et al: (I) arterial infection, (II) aortoarteritis, (III) autoimmune connective tissue disease, (IV) Kawasaki’s disease, (V) Ehler-Danlos or Marfan syndrome, (VI) other noninflammatory medial degeneration, (VII) arterial dysplasia, (VIII) congenital-idiopathic, and (IX) false aneurysms due to vessel injury.11 In the present study, aneurysms were combined into groups of either visceral artery aneurysms (including renal and splanchnic artery aneurysms) or extremity artery aneurysms (including upper and lower extremity aneurysms) for outcome analysis. Primary outcomes included complications, mortality, and freedom from reintervention determined using Kaplan-Meier analysis. RESULTS General characteristics of the study population. The series included 27 boys and 14 girls, whose median ages were 10.3 and 9.7 years, respectively. The median patient weight was 31.0 kg (range, 3.8-71 kg). Aneurysms affected the renal (n ¼ 26), femoral (n ¼ 7), iliac (n ¼ 7), superior mesenteric (n ¼ 4), brachial (n ¼ 3), carotid (n ¼ 3), popliteal (n ¼ 3), axillary (n ¼ 2), celiac (n ¼ 2), ulnar (n ¼ 2), common hepatic (n ¼ 1), and temporal (n ¼ 1) arteries (Fig 1). Multiple arterial aneurysms affected 14 children including: six with multiple unilateral renal artery aneurysms, one with bilateral renal artery aneurysms, one with multiple femoral artery aneurysms, and six with concurrent aneurysmal disease involving multiple vascular beds. Of the 14 children with multiple aneurysms a potential genetic explanation was found in only three patients; two of whom had neurofibromatosis 1 (NF1) and one had Klippel-Trenaunay syndrome. There were no diagnoses of classical connective tissue disorders in this subset of children with multiple aneurysms. Slightly less than half of the patients (n ¼ 18) appeared to have idiopathic aneurysms. An etiologic factor extrinsic to the artery itself was considered responsible for pseudoaneurysms in 12 patients that were caused by renal artery angioplasty (n ¼ 3), blunt or penetrating trauma (n ¼ 5),

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femoral artery catheterization (n ¼ 2), infection (n ¼ 1), and malignancy (n ¼ 1). Over the 32-year experience of this study, advances in molecular testing allowed for extensive genetic preoperative evaluation, if deemed clinically appropriate, especially in patients suspected to have connective tissue diseases (such as Ehlers-Danlos type IV) and inherited cardiovascular disorders with genetic mutations involving: ACTA2, CBS, COL3A1, FBN1, FBN2, FLNA, MYH11, MYLK, SKI, SLC2A10, SMAD3, TGFB2, TGFBR1, and TGFBR2. Within this cohort, a genetic etiology received support with a confirmed coexistence of NF1 in four patients, Ehlers-Danlos type IV in one patient, and Klippel-Trenaunay syndrome in one patient. Finally, a history of Kawasaki disease was present in four patients. Among the series’ 27 patients with extrarenal aneurysms, a pulsatile mass was present in 16 patients. Stenotic disease and refractory hypertension was evident in all 15 patients with renal artery aneurysms. Aneurysms affecting the series’ remaining 10 patients were incidental findings during evaluations of abdominal discomfort, hydronephrosis, jaundice, a rash, and fever with history of inflammatory disease, or a genetic disease predisposed to arterial degeneration. Arterial reconstructions and ablative procedures undertaken in treating pediatric aneurysms remained constant over the decades of this study. However, specific interventions were dependent on the artery involved, the etiology of the aneurysm, and the age of the patient. Accordingly, the treatment of these aneurysms was best reported for each of the involved vascular territories. Extracranial cerebrovascular artery aneurysms. All three patients in this category experienced nonpenetrating head or neck trauma from athletic competition or a history of parental abuse (Fig 2). The average aneurysm size was 18 mm (range, 9-30 mm; Table I). Each presented with a pulsatile mass and only one patient exhibited neurological complications. That child experienced symptoms of dizziness and transient lower extremity paresthesias with computed tomography imaging that showed a small lacunar infarct. Internal carotid artery aneurysms were excised and the artery reconstructed with an interposition graft using the internal hypogastric artery. This conduit was preferred over an autologous vein graft because of its lesser risk of late aneurysmal change in the low resistant and high diastolic flow present in the extracranial carotid circulation. There were no perioperative complications. The external carotid artery aneurysm was repaired with a simple closed plication. The temporal artery aneurysm was excised with entering and exiting vessels simply ligated. At the time of discharge, all patients were asymptomatic without neurological sequelae including the patient with a previous lacunar infarct. Duplex ultrasonography surveillance showed excellent graft appearance and function with an average postoperative follow-up of 18 months (range, 13-24 months). Splanchnic artery aneurysms. Among the six patients with aneurysms involving the intestinal arteries, two of the three superior mesenteric artery aneurysms were associated with abdominal pain, and the hepatic artery aneurysm with

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Fig 1. The pediatric nonaortic arterial aneurysm cohort. Arterial territories of 61 aneurysms subjected to surgery in 41 pediatric patients treated at the University of Michigan from 1983 to 2015.

jaundice. The remaining aneurysms were asymptomatic. The average aneurysm size was 21 mm (range, 4-46 mm; Table II). Surgical treatment most often involved arterial ligation in the presence of adequate intestinal collateral circulation. Resection of the largest celiac artery aneurysm was followed by an end to end reanastomosis of the common hepatic artery to the splenic artery to facilitate excellent collateral flow from the superior mesenteric to the celiac circulation (Fig 3). No reinterventions were needed during a postoperative follow-up that averaged 13 months (range, 1 month-2 years). Renal artery aneurysms. Fifteen patients presented with renal artery aneurysms with an average of 9 mm

(range, 3-25 mm) in size (Table III). The location of renal artery aneurysms affected the main renal artery at its bifurcation (n ¼ 14) and segmental renal arteries (n ¼ 12), with more than half appearing as poststenotic lesions. Balloon angioplasty of renal artery stenoses performed elsewhere complicated by pseudoaneurysm formation accounted for the remaining renal artery aneurysms. Treatment of renal artery aneurysms included: resection with primary anastomosis, angioplastic closure, or reimplantation. Most reimplantations were into a normal segment of the infrarenal aorta or nondiseased adjacent segmental renal artery (Fig 4, A and B). In these circumstances, the renal artery to be implanted or reanastomosed was transected obliquely to create a generous ovoid orifice

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Fig 2. Carotid artery aneurysm. Preoperative arteriogram showing a 30-mm saccular internal carotid artery aneurysm (small arrow) and an 11-mm fusiform external carotid artery aneurysm (large arrow).

with a circumference exceeding that of the adjacent artery. Similarly, the aorta or artery to which the renal artery was to be anastomosed had creation of a generous opening also exceeding the renal artery diameter. Such anastomoses with large circumferences were less likely to develop late strictures and were completed with interrupted sutures in very young children to accommodate vessel growth. Aneurysm excision and a primary angioplastic closure was undertaken with larger aneurysms occurring at the first order branching of the main renal artery (Fig 4, C and D). Renal artery plication, using imbrication of the aneurysm with a continuous suture, was considered optimal treatment of small renal artery aneurysms located at bifurcations of diminutive arteries that prevented their simple resection and reconstruction. The adequacy of the renal artery reconstructions were confirmed using intraoperative ultrasonography or Doppler insonation. Primary nephrectomy or endovascular embolization were undertaken for irreparable renal disease including multiple aneurysms not amenable to any form of

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reconstruction. Extrarenal procedures performed at the time of renal artery surgeries included two aortic and two splanchnic arterial reconstructions. The specifics of the aortic operations have been described in an earlier report.14 Upper extremity artery aneurysms. Seven patients presented with a variety of aneurysms involving the upper extremities (Fig 5). All patients exhibited a mass over the involved artery and one patient experienced distal hand paresthesias. The average aneurysm size was 15 mm (range, 5-30 mm; Table IV). Surgical interventions usually involved aneurysm resection with arterial reconstruction using reversed saphenous vein interposition grafts. Spatulation of both vessels increased the anastomotic circumference and lessened the likelihood of late strictures. There were no perioperative complications with the postoperative follow-up averaging 31 months (range, 1 month-11 years). Lower extremity artery aneurysms. Twelve patients presented with a total of 17 arterial aneurysms that affected the lower extremities (Fig 6, A-C). A diverse etiology of iliac artery aneurysms were noted. In contrast, most femoral and popliteal artery aneurysms resulted from blunt or penetrating trauma including iatrogenic cannulation injury. Iliac, femoral, and popliteal aneurysm diameters averaged 35 mm (range, 4-65 mm), 20 mm (range, 10-34 mm), and 43 mm (range, 45-60 mm), respectively (Table V). Repair of the iliac artery aneurysms involved two aortoiliac bypasses and resection with a primary reanastomosis or plication of the remaining aneurysms. The internal iliac artery aneurysms were treated with excision and arterial ligation. Of note, one internal iliac repair was considered in a 2-month-old child who presented with a 3.8-cm internal iliac artery aneurysm. Vascular intervention in pediatric patients younger than 1 year of age is uncommon. However, because of the marked size of the aneurysm and risk of rupture, surgical intervention was deemed necessary. Simple arterial ligation was performed because an inadequate conduit for a patient this age precluded a formal arterial reconstruction. All iliac aneurysm repairs were durable without a need for reintervention during an average follow-up of 14 months (range, 1 month-3 years). Most femoral and popliteal artery aneurysms were resected followed by a primary reanastomosis. A minority of aneurysms were repaired with an interposition vein graft. All of the femoral and popliteal interventions were uncomplicated with follow-up averaging 3 years (range, 1.55.3 years). There appeared to be long-term differences in outcomes between the various arterial territories involved. Mean postoperative follow-up for visceral artery aneurysms (renal and splanchnic artery aneurysms) was 54.4 months (range, 1-349 months) and for extremity artery aneurysms was 31.6 months (range, 1-132 months). Analysis of visceral artery aneurysm repairs showed a freedom from reintervention of 83.3% and 69.4% at 1 and 3 years, respectively (Supplementary Fig and Supplementary Table, online only). Three of these patients (15%) required secondary surgical interventions; two who

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Table I. Extracranial cerebrovascular arterial aneurysms Size (mm)-morphological features; histological features

Patient

Age (years)/ sex

1

11 Female

Temporal

9 - Fusiform; fibrosis

2

14 Female

Internal carotid and external carotid

30 - Saccular and 11 - Fusiform

3

14 Female

Internal carotid

22 - Fusiform; extensive loss of media and diffuse myxoid change

Affected artery

Associated diagnosis Pseudoaneurysm, trauma Pseudoaneurysms, trauma

Pseudoaneurysm, trauma

Treatment, follow-up

Classa

Ligation, 13 months

IX

Resection, hypogastric interposition graft (internal carotid) and plication (external carotid), 19 years Resection, hypogastric interposition graft, 2 years

IX

IX

a

Pediatric Aneurysm Classification System defined according to Sarkar et al.11

Table II. Splanchnic artery aneurysms Patient

Age (years)/ sex

4

13 M

5

6M

6

4M

7

10 M

8

14 M

9

15 F

Affected artery

Size (mm)-morphological features; histological features

Celiac

10 - Saccular

Celiac, superior mesenteric Common hepatic

4 and 4 - Saccular

40 - Saccular; medial derangement Superior mesenteric 40 - Fusiform; medial degeneration Superior mesenteric 46 - Saccular; suppurative inflammation with microorganisms Mesenteric branch 8 - Fusiform

Associated diagnosis

Treatment, follow-up

Classa

Superior mesenteric artery stenosis AAA, bilateral renal artery stenosis, heterotaxy Kawasaki disease

Resection with reanastomosis, 1 month Plication twice, 2 years

VI

Ligation, 1 month

IV

Ehler-Danlos

Ligation, 2 years

V

Endocarditis, (bicuspid aortic valve)

Ligation, 1 years

I

Ligation, 1 month

VII

e

VII

AAA, Abdominal aortic aneurysm; F, female; M, male. a Pediatric Aneurysm Classification System defined according to Sarkar et al.11

Fig 3. Celiac artery aneurysm. Preoperative selective arteriogram of (A) a poststenotic celiac artery aneurysm and (B) a postoperative computed tomographic arteriography image after resection and primary end to end anastomosis of the proximal hepatic to proximal splenic artery (arrows).

developed renovascular hypertension at 3 and 9 months after their initial surgery due to stenosis at the site of renal artery reimplantation and one patient who developed a recurrent aneurysm at the site of repair 32 months after

the index operation. The two patients with renovascular hypertension were treated with either an endovascular embolization or angioplasty of the involved artery. The recurrent aneurysm underwent resection with reanastomosis

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Table III. Renal artery aneurysms

Patient

Age (years)/ sex

Affected artery

Size (mm)-morphological features; histological features

Associated diagnosis

10

3F

Renal (L)

25 - Fusiform

e

11

3F

3 Renal (R)

15, 4, and 6 - Saccular

e

12

4F

Renal (L) and common iliac (R)

13

4M

Renal (L)

14

7M

2 Renal (R)

15

8M

2 Renal (R)

8 - Saccular (see Table V, common iliac aneurysm) 7 - Fusiform; medial derangement and intimal fibroplasia 3 and 10 - Saccular; intimal hyperplasia and elastin fragmentation 8 and 9 - Saccular

16

8M

Renal (R)

10 - Saccular; intimal and medial fibroplasia

17

10 M

2 Renal (R), renal (L), and common iliac (R)

18

11 M

Renal (R)

4 and 12 - Saccular (R) and 9 - Saccular (L); intimal fibroplasia (See Table V: common iliac aneurysm) 15 - Fusiform

19

14 F

2 Renal (L)

4 and 4 - Saccular; fibrodysplasia

e

20 21

15 F 15 M

Renal (R) 3 Renal (L)

e e

22

16 M

2 Renal (R, L)

7 - Fusiform 10, 3, and 3 - Saccular; medical thinning 5 and 5 - Saccular at origins

23

16 M

Renal (R)

24

17 M

2 Renal (L)

25 - Fusiform; fibromuscular dysplasia 4 and 8 - Fusiform

Klippel-Trenaunay e NF1, abdominal aortic coarctation

Treatment, follow-up Resection with reimplantation, 29 years Nephrectomy, 2 months Nephrectomy, 8 months Resection with reimplantation, 4 years Plication and ligation once each, 7 years

Classa VII VII VIII VII VII

NF1, celiac and superior mesenteric artery stenosis Pseudoaneurysm prior angioplasty, NF1, Noonan syndrome e

Plication twice, 5 years

VII

Nephrectomy, 2 years

IX

Resection with reanastomoses once, endovascular embolization once, 2 years

VIII

e

Resection with reimplantation, 1 month Resection with reanastomoses twice, 1 month Plication, 4 years Nephrectomy, 1 month

VII

Pseudoaneurysm, abdominal aortic narrowing, celiac and superior mesenteric artery stenosis e e

VII VII VII

Resection with reimplantations twice, 1 month

IX

Resection with angioplastic closure, 2.5 years Endovascular embolization, 15 years

VII VII

F, Female; L, left; M, male; NF1, neurofibromatosis 1; R, right. a Pediatric Aneurysm Classification System defined according to Sarkar et al.11

but was complicated by a pseudoaneurysm, which was successfully treated with a subsequent aortorenal bypass. No treated extracranial carotid or extremity artery aneurysm required a secondary reintervention after the index surgery. There were no aneurysm ruptures before surgery or perioperative deaths after either the primary or secondary surgical intervention. DISCUSSION Pediatric nonaortic arterial aneurysms are a rare topic of isolated case reports and small series of affected

children.1-13 The current series to our knowledge represents the largest reported cohort of pediatric nonaortic aneurysms and their surgical treatment. A clinicopathologic classification system has previously been proposed to categorize pediatric aneurysmal disease.11 Within the current series, traumatic, dysplastic, and congenital idiopathic aneurysms represent the three dominate types (Tables I-V). In some patients, NF1, Ehlers-Danlos type IV syndrome, or Klippel-Trenaunay syndrome likely contributed to these unusual aneurysms.15-20 Poststenotic aneurysms were present in 35% of this series’ patients. Most occurred

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Fig 4. Renal artery aneurysms. Preoperative angiogram, oblique view, (A) showing renal artery aneurysm in the region of critical stenosis (arrow) and postoperative angiogram (B) after resection with reimplantation of the primary segmental branch to the main renal artery (arrow). A second child with preoperative (C) and postoperative (D) angiograms that show, respectively, a large renal artery aneurysm at the main renal artery bifurcation and the postoperative appearance after resection of the aneurysm and angioplastic closure.

Fig 5. Upper extremity artery aneurysms. A, Preoperative magnetic resonance angiography (MRA) in a child with a history of Kawasaki disease with a proximal brachial artery aneurysm. B, Preoperative arteriogram in a second child with an ulnar artery aneurysm.

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Table IV. Upper extremity artery aneurysms

Patient

Age (years)/ sex

Affected artery

25

2M

Axillary (L)

26

18 M

Axillary (R)

27

4M

Brachial (R)

28

6M

Brachial (R)

29

10 F

Brachial (L)

30

2M

Ulnar (R)

31

18 M

Ulnar (R)

Size (mm)-morphological features; histological features 17 - Fusiform; fibromyxoid changes, and calcifications 30 - Fusiform 18 - Saccular; medial thinning and minimal fibrosis 16 - Fusiform; medial degeneration

16 - Saccular; fibrointimal thickening and myxoid degeneration 5 - Saccular; fibrosis 6 - Saccular; medial and intimal fibrosis

Associated diagnosis e Pseudoaneurysm, stab wound Kawasaki disease Kawasaki disease (no treatment of aneurysms of R common iliac, L femoral, and R popliteal arteries) e Pseudoaneurysm, trauma Pseudoaneurysm, trauma

Treatment, follow-up

Classa

Interposition SV graft, 3 months

VIII

Interposition SV graft, 7 months Excision with interposition graft, 11 years Interposition SV graft, 6 years

IX IV IV

Interposition SV graft, 2.5 years

VIII

Resection with reanastomosis, 1 month Interposition vein graft, 2 months

IX IX

F, Female; L, left; M, male; R, right; SV, saphenous vein. a Pediatric Aneurysm Classification System defined according to Sarkar et al.11

Fig 6. Lower extremity artery aneurysms. A, Preoperative arteriogram in a child with a right common iliac artery fusiform aneurysm, (B) treated with an aortoiliac bypass with a 7-mm polytetrafluoroethylene prosthesis. C, A second child with computed tomographic arteriography documentation of an iatrogenic, cannula-induced aneurysm of the common femoral artery.

immediately distal to renal artery narrowings in children, all of whom were hypertensive. However, certain renal artery aneurysms have been reported in children without hypertension, which suggests that hypertension is not always a prerequisite for their development.3 The natural history of pediatric nonaortic aneurysms remains ill-defined. Within the current study, none of the patients underwent surveillance and instead early intervention was preferred. Indications for operation in the current series included risk of expansion and rupture, potential

thrombosis or embolization of aneurysmal thrombus, local soft tissue and nerve compression, and secondary hypertension in the case of renal artery aneurysms. Treatment options were complicated by issues related to patient size, future growth, whether the involved artery was critical to organ function, and availability of suitable conduits for repair. Carotid artery aneurysms in children might arise from congenital arterial dysplasias,21 inflammatory diseases,9 and blunt or penetrating trauma,22,23 the latter being the

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474 Davis et al

Table V. Lower extremity artery aneurysms Age (years)/ Patient sex

Affected artery

Size (mm)-morphological features; histological features

Associated diagnosis

32

0.2 F

33

2M

34

4F

12b

4F

17b

10 M

35

2M

36

15 M

Common iliac (R) and 2 5 - Fusiform; common e internal iliac (L and R) iliac, 38 - L fusiform and 4 - R fusiform internal iliacs; inflammation and fibrosis of arterial wall Common iliac (L) 25 - Fusiform; mural Kawasaki disease fibrosis, dystrophic calcification and chronic inflammation Common iliac (R) 40 - Saccular; medial e thinning and intimal fibroplasia Common iliac (R) and 65 - Fusiform; medial Klippel-Trenaunay renal (L) calcification (see syndrome Table III: renal aneurysm) 2 Renal (R), renal (L), 30 - Fusiform; intimal e and common iliac (R) fibroplasia (see Table III: renal artery aneurysm) 4 Femoral (R) 10, 10, 15, and e 20 - Fusiform; intimal thickening with absent internal elastic lamina Femoral (R) 34 - Saccular Pseudoaneurysm, trauma

37

15 M

Femoral (R)

40 - Fusiform

38

17 F

Femoral (R)

34 - Saccular

39

5F

Popliteal (R)

45 - Fusiform

40

16 M

Popliteal (R)

60 - Fusiform

41

17 M

Popliteal (L)

54 - Fusiform

Treatment, follow-up

Classa

Plication once common VIII iliac, and ligation twice internal iliacs, 1 month

Resection with reanastomosis, 2 months

IV

Resection with R VIII external and L internal anastomosis, 3 years Aortoiliac bypass with VIII 7-mm PTFE graft, 8 months Aortoiliac bypass with 7-mm PTFE graft, 2 years

VIII

Interposition SV graft, 18 months

VI

Resection with reanastomosis, 19 months Ligation, 19 months

IX

Pseudoaneurysm, liver transplant, femoral artery cannulation Pseudoaneurysm, Resection with autoimmune hepatitis reanastomosis, 4 years Pseudoaneurysm, trauma Endovascular embolization, 8 years Pseudoaneurysm, Interposition SV graft, 4 months erosion by osteochondroma Pseudoaneurysm, open Resection with reduction femur reanastomosis, 5 years fracture, NF1

IX IX IX IX IX

F, Female; L, left; M, male; NF1, neurofibromatosis 1; R, right; PTFE, polytetrafluoroethylene; SV, saphenous vein. a Pediatric Aneurysm Classification System defined according to Sarkar et al.11 b Patient noted in Table III had iliac and renal aneurysm repairs.

etiology in all of our patients. The indications for intervention for pediatric extracranial carotid artery aneurysms are not clearly defined but because of the risk of central nervous system complications, early surgical treatment is usually pursued. The most common reported procedures have been aneurysmectomy with saphenous vein24 or prosthetic interposition bypasses,21 and simple ligation.25,26 Although ligation might be undertaken in children with an intact Circle of Willis, such carries a small risk of acute stroke and predisposes these individuals to an increased risk of later stroke and possible death if the collateral circulation becomes compromised. In our patients, the hypogastric artery was chosen as the preferred conduit because our prior experience has shown it to be a durable graft, and

that autogenous vein grafts, even when carefully prepared and handled, might undergo late aneurysmal deterioration when placed in low-resistance arterial beds with high diastolic flow.27 Furthermore, the hypogastric artery has been previously used as a conduit for diverse pediatric arterial repairs with an excellent long-term patency.28 The most common site of arterial aneurysm reported in this study was the renal artery. Such is likely a reflection of an active renovascular hypertension referral practice at the authors’ institution. The surgical options for treating these aneurysms are complex, including angioplastic closure, bypass, or reimplantation of the affected vessels after resection of the aneurysm. Ethanol ablation and coil embolization for treatment of renal artery

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aneurysms have also been described in the literature, but within the current series these treatment modalities were rarely used.29,30 Follow-up in most series on endovascular repair for treatment of renal artery aneurysm is much shorter than that after open surgical procedures, and comparisons of long-term success rates of embolization with conventional surgery do not exist at this time. Splanchnic artery aneurysms were uncommon in this series. Consistent with previous case reports in the literature these pediatric aneurysms might have a mycotic, noninfectious inflammatory, or connective tissue disease origin.10,31 Surgical intervention to exclude the aneurysm and re-establish arterial continuity might be ideal. However, in the case of mycotic or connective tissue disorders, like Ehlers-Danlos type IV disease, this is hazardous because of vessel friability. In such cases, ligation of the aneurysm with reliance on collateral flow seems preferable.10,32 Endovascular treatment options have been described in adult patients with splanchnic aneurysms, but these treatment modalities remain unproven in children. Upper extremity peripheral artery aneurysms often present with an asymptomatic mass.6,33,34 The causes are most often trauma6 or Kawasaki disease.35 However, two of our patients manifested idiopathic axillary artery aneurysms. An earlier study of 19 patients with peripheral artery aneurysms distal to the axillary artery showed that either aneurysm resection or arterial ligation and aneurysm resection and concomitant arterial reconstruction could be conducted with minimal morbidity or mortality.33 In our series, all seven patients underwent aneurysm resection with primary reanastomosis or reconstruction using a reversed saphenous vein interposition graft. Overall, iliac artery aneurysms are rare, with limited case reports in the literature.4,36,37 With adequate collateral circulation, internal iliac artery aneurysms may be treated with excision and simple ligation. However, resection of common iliac artery aneurysms requires restoration of pelvic and lower extremity blood flow by reanastomosis, plication, or an aortoiliac bypass. Native vessel aneurysm repair was preferred, as this would thereby avoid the possibility of replacement at a later period. However, use of a prosthetic graft is an important option if the conduit diameter is chosen to be as large as possible, short of being so large that excessive luminal thrombus accumulates. The intent is always to oversize prosthetic grafts compared with the native vessel, with anticipated growth otherwise resulting in a graft too small to maintain normal distal flow as the child grows into maturity. All of the current series’ children underwent completion angiography or ultrasonography after their visceral or extremity artery repairs. We recommend that children who undergo an arterial reconstruction receive aspirin for a minimum of 6 months after surgery to lessen the risk of platelet accumulation and thrombus formation at anastomotic sites of these small arteries. We are cognizant of such increasing risk of Reyes syndrome but believe the risks of arterial thrombosis exceed such an occurrence. Although no reinterventions were necessary after treatment

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of extracranial cerebrovascular or extremity artery aneurysms, repeated surgery was required in 15% of children who underwent treatment for visceral aneurysms. Repeated surgeries occurred as late as 3 years after the primary surgery. Life-long follow-up is important because of a child’s lifespan, and the cumulative risks of aneurysm recurrence or de novo aneurysm formation that would require further treatment. Annual noninvasive assessments of blood flow after extremity arterial reconstructions are recommended with the use of duplex ultrasound or exercise anklebrachial indices. Visceral arterial repairs are best followed by MRA at 12 and 24 months after surgery with additional imaging if blood pressure increases occur in patients who have undergone renal artery reconstructions. Limitations of the current study are those inherent to a retrospective analysis of a rare anomaly. In addition, the University of Michigan receives numerous national and international referrals for the treatment of pediatric vascular disease, including pediatric arterial aneurysms. As such, long-term postoperative follow-up is often dependent on the child’s local physician with detailed instructions from the authors regarding suggested monitoring. In some, though not all of the patients within this cohort, detailed follow-up of their clinical status is limited. CONCLUSIONS Pediatric arterial aneurysms represent complex diseases that affect multiple arterial beds. Individualized surgical treatment on the basis of patient age and anatomical factors can be undertaken with minimal perioperative risk and sustained durability. Long-term follow-up with noninvasive studies and imaging is recommended in light of the pediatric patient’s overall health and predicted long life expectancy. AUTHOR CONTRIBUTIONS Conception and design: FD, JS, DC Analysis and interpretation: FD, JS, DC Data collection: FD, JS, DC Writing the article: FD, JS, DC Critical revision of the article: FD, JE, SG, NB, JS, DC Final approval of the article: FD, JE, SG, NB, JS, DC Statistical analysis: FD, DC Obtained funding: JE, JS, DC Overall responsibility: DC REFERENCES 1. Bahcivan M, Yuksel A. Idiopathic true brachial artery aneurysm in a nine-month infant. Interact Cardiovasc Thorac Surg 2009;8:162-3. 2. Callicutt CS, Rush B, Eubanks T, Abul-Khoudoud OR. Idiopathic renal artery and infrarenal aortic aneurysms in a 6-year-old child: case report and literature review. J Vasc Surg 2005;41:893-6. 3. Checinski P, Henschke J, Pawlak B, Karwowski A, Samolewska E. Multiple aneurysms in childhood - case report and review of the literature. J Vasc Endovasc Surg 2000;20:108-10. 4. Chithra R, Sundar RA, Velladuraichi B, Sritharan N, Amalorpavanathan J, Vidyasagaran T. Pediatric isolated bilateral iliac aneurysm. J Vasc Surg 2013;58:215-6.

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5. English WP, Edwards MS, Pearce JD, Mondi MM, Hundley JC, Hansen KJ. Multiple aneurysms in childhood. J Vasc Surg 2004;39: 254-9. 6. Got C, Tan TW, Thakur N, Marcaccio EJ Jr, Eberson C, Madom I. Delayed presentation of a brachial artery pseudoaneurysm after a supracondylar humerus fracture in a 6-year-old boy: a case report. J Pediatr Orthop 2010;30:57-9. 7. Kaye AJ, Slemp AE, Chang B, Mattei P, Fairman R, Velazquez OC. Complex vascular reconstruction of abdominal aorta and its branches in the pediatric population. J Pediatr Surg 2008;43:1082-8. 8. Lopez D, Sarac T, Lorenz R. Primary internal carotid artery aneurysm in a 15-year-old male: case report and review of the literature. Ann Vasc Surg 2015;29:126.e1-4. 9. Pourhassan S, Grotemeyer D, Fokou M, Heinen W, Balzer K, Ramp U, et al. Extracranial carotid arteries aneurysms in children: single-center experiences in 4 patients and review of the literature. J Pediatr Surg 2007;42:1961-8. 10. Ruddy JM, Dodson TF, Duwayri Y. Open repair of superior mesenteric artery mycotic aneurysm in an adolescent girl. Ann Vasc Surg 2014;28: 1032.e21-4. 11. Sarkar R, Coran AG, Cilley RE, Lindenauer SM, Stanley JC. Arterial aneurysms in children: clinicopathologic classification. J Vasc Surg 1991;13:47-56; discussion: 57. 12. Sheppard DG, Wilkinson AG. Syndrome of idiopathic childhood aneurysms: a case report and review of the literature. J Vasc Interv Radiol 2000;11:997-1004. 13. Short DW. Multiple congenital aneurysms in childhood: report of a case. Br J Surg 1978;65:509-12. 14. Stanley JC, Criado E, Eliason JL, Upchurch GR Jr, Berguer R, Rectenwald JE. Abdominal aortic coarctation: surgical treatment of 53 patients with a thoracoabdominal bypass, patch aortoplasty, or interposition aortoaortic graft. J Vasc Surg 2008;48:1073-82. 15. Friedman JM, Arbiser J, Epstein JA, Gutmann DH, Huot SJ, Lin AE, et al. Cardiovascular disease in neurofibromatosis 1: report of the neurofibromatosis 1 Cardiovascular Task Force. Genet Med 2002;4: 105-11. 16. Lehrnbecher T, Gassel AM, Rauh V, Kirchner T, Huppertz HI. Neurofibromatosis presenting as a severe systemic vasculopathy. Eur J Pediatr 1994;153:107-9. 17. Gao J, Fisher A, Chung J. Color duplex ultrasonography in detecting renal artery abnormalities in a patient with neurofibromatosis 1: a case report. Clin Imaging 2006;30:140-2. 18. Greene JF Jr, Fitzwater JE, Burgess J. Arterial lesions associated with neurofibromatosis. Am J Clin Pathol 1974;62:481-7. 19. Stansfield BK, Bessler WK, Mali R, Mund JA, Downing BD, Kapur R, et al. Ras-Mek-Erk signaling regulates Nf1 heterozygous neointima formation. Am J Pathol 2014;184:79-85. 20. Akagi D, Ishii S, Kitagawa T, Nagawa H, Miyata T. Popliteal arterial aneurysm associated with Klippel-Trenaunay syndrome: case report and literature review. J Vasc Surg 2006;43:1287-9. 21. Cinar B, Fazliogullari O, Goksel O. True aneurysm of extracranial internal carotid artery in a 10-year-old. Eur J Vasc Endovasc Surg 2006;32:386-8.

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22. Chambers N, Hampson-Evans D, Patwardhan K, Murdoch L. Traumatic aneurysm of the internal carotid artery in an infant: a surprise diagnosis. Paediatr Anaesth 2002;12:356-61. 23. Henriksen SD, Kindt MW, Pedersen CB, Nepper-Rasmussen HJ. Pseudoaneurysm of a lateral internal carotid artery in the middle ear. Int J Pediatr Otorhinolaryngol 2000;52:163-7. 24. El-Sabrout R, Cooley DA. Extracranial carotid artery aneurysms: Texas Heart Institute experience. J Vasc Surg 2000;31:702-12. 25. Unal OF, Hepgul KT, Turantan MI, Bozboga M, Yazicioglu E. Extracranial carotid artery aneurysm in a child misdiagnosed as a parapharyngeal abscess: a case report. J Otorhinolaryngol 1992;21: 108-11. 26. Windfuhr JP. Aneurysm of the internal carotid artery following soft tissue penetration injury. Int J Pediatr Otorhinolaryngol 2001;61: 155-9. 27. Stanley JC, Criado E, Upchurch GR Jr, Brophy PD, Cho KJ, Rectenwald JE. Pediatric renovascular hypertension: 132 primary and 30 secondary operations in 97 children. J Vasc Surg 2006;44:1219-29. 28. Milas ZL, Dodson TF, Ricketts RR. Pediatric blunt trauma resulting in major arterial injuries. Am Surg 2004;70:443-7. 29. Hobbs DJ, Barletta GM, Mowry JA, Bunchman TE. Renovascular hypertension and intrarenal artery aneurysms in a preschool child. Pediatr Radiol 2009;39:988-90. 30. Gumustas S, Ciftci E, Bircan Z. Renal artery aneurysm in a hypertensive child treated by percutaneous coil embolization. Pediatr Radiol 2010;40:1285-7. 31. de Leeuw K, Goorhuis JF, Tielliu IF, Symoens S, Malfait F, de Paepe A, et al. Superior mesenteric artery aneurysm in a 9-year-old boy with classical Ehlers-Danlos syndrome. Am J Med Genet A 2012;158A: 626-9. 32. Oderich GS, Panneton JM, Bower TC, Lindor NM, Cherry KJ, Noel AA, et al. The spectrum, management and clinical outcome of Ehlers-Danlos syndrome type IV: a 30-year experience. J Vasc Surg 2005;42:98-106. 33. Gray RJ, Stone WM, Fowl RJ, Cherry KJ, Bower TC. Management of true aneurysms distal to the axillary artery. J Vasc Surg 1998;28:606-10. 34. Godwin SC, Shawker T, Chang B, Kaler SG. Brachial artery aneurysms in Menkes disease. J Pediatr 2006;149:412-5. 35. Cabrera ND, Sridhar A, Chessa M, Carminati M. Giant coronary and systemic aneurysms of Kawasaki disease in an infant. Pediatr Cardiol 2010;31:915-6. 36. Zimmermann A, Kuehnl A, Seidl S, Eckstein HH. Idiopathic aneurysm of the common iliac artery in an 11-year-old child. J Vasc Surg 2009;50:663-6. 37. Taketani S, Imagawa H, Kadoba K, Sawa Y, Sirakura R, Matsuda H. Idiopathic iliac arterial aneurysms in a child. J Pediatr Surg 1997;32: 1519-21.

Submitted Jun 24, 2015; accepted Aug 21, 2015.

Additional material for this article may be found online at www.jvascsurg.org.

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Davis et al 476.e1

Supplementary Fig (online only). Visceral artery aneurysm repair; freedom from reintervention. The Kaplan-Meier survival curve solid line reflects the freedom from reintervention after splanchnic and renal interventions. Dotted lines represent standard error of the mean.

Supplementary Table (online only). Life table analysis of visceral aneurysm repair over time Time interval, months 0-12 12-24 24-36 36-48 48-60 60-72 72-84 84-96 96-108 108-120 120-132 132-144 144-156 156-168 264-276 276-288 336-348

Repairs at risk

Repairs that required reintervention

Repairs with incomplete follow-up for interval

Overall freedom from reintervention

Standard error

21 11 9 6 6 5 5 5 4 4 4 4 4 3 2 2 1

2 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0

7 1 1 0 1 0 0 1 0 0 0 0 1 0 0 1 0

0.846 0.846 0.705 0.705 0.705 0.705 0.705 0.705 0.705 0.705 0.705 0.705 0.705 0.705 0.705 0.705 0.705

0.1000 0.1000 0.1533 0.1533 0.1533 0.1533 0.1533 0.1533 0.1533 0.1533 0.1533 0.1533 0.1533 0.1533 0.1533 0.1533 0.1533