Multidisciplinary management of juvenile nasopharyngeal angiofibroma

Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign, but the locally aggressive, vascular tumor that occurs almost exclusively in young men. Although this tumor accounts for only about 0.5% of head and neck tumors, it is by far the most common benign nasopharyngeal neoplasm. It is presented typically with epistaxis, obstructive symptoms, and chronic otomastoiditis. The examination of this tumor reveals pale reddish-blue mass. The tumor is seen on imaging as vividly augmenting soft-tissue mass centered on the sphenopalatine foramen. The treatment of choice is usually surgical resection; either open or endoscopic. Pre-operative embolization is usually done to help with hemostasis. We aim to address the efficiency and the safety of endovascular modality in JNA. In the period between January 2012 to December 2017, 20 male patients with age ranging from 6 to 20 years were referred to the Endovascular Unit, at Departments of Neurosurgery in Sohag, Alexandria, and Tanta University Hospitals with JNF. Preoperative trans-arterial embolization was done, followed by endoscopic surgical resection by our ENT surgeons. All patients were subjected to clinical and radiological Imaging evaluation pre embolization, post embolization, and post endoscopic resection. All patients had clinical and radiological follow-ups for at least 1 year. 20 male patients with JNA underwent preoperative super-selective trans-arterial embolization. The average age at presentation was 13 years. All patients underwent successful embolization with total obliteration of vascular blush of the tumor in 15 patients, and near-total obliteration of blush in 5 patients. The dramatic effect of preoperative embolization was observed on limiting intraoperative blood loss (average 200 ml) and decreasing the time of surgery (average 2.5 h). There was no permanent morbidity or mortality related to either embolization or endoscopic resection in all patients. Trans-arterial embolization is strongly recommended in patients with JNA, it offers a good assist to the surgeon, reduces blood loss, decreases the amount of transfusion, improves the degree of resection, reduces operative time, and decreases the incidence of recurrence.


Introduction
Juvenile nasopharyngeal angiofibroma (JNA) is a quite rare benign tumor in children; that accounts for around 0.05% of all head and neck tumors [1]. JNA is nearly and exclusively a disease of males of adolescent age, but the age range is very wide actually, it is from 7 to 29 years [2].
The disease is typically presented initially with recurrent unilateral epistaxis, nasal obstruction and/or nasopharyngeal mass. Despite of being benign, it may be aggressive and erode the surrounding bone and soft tissues, as it evolves from its usual site in the lateral nasopharynx in the vicinity of the superior border of the sphenopalatine foramen [3].
Histopathologically, JNA is composed of randomly arranged vascular channels surrounded by dense fibroblastic stroma, with myofibroblasts composing the main cell [2]. The bleeding tendency of JNA is because the small blood vessels in the center of the lesion tend to lack muscular elastic lamina, predisposing these vessels to uncontrolled bleeding [3].
Diagnosis of JNA is done mainly by CT or MRI. CT can reveal the detailed bony involvement of the tumor. However, the definitive diagnosis is established by MRI imaging. The optimal method, to identify the extent of intracranial extension of JNA, is based on T1 weighted imaging (T1WI) with gadolinium contrast, using fat suppression. An MRA can add the delineation of the arterial supply to JNA which is very important for pre-embolization planning. Owing to the highly vascular nature of JNA, a biopsy is contraindicated [4]. Besides, attention must be paid to the surrounding vascular structures during resection for the fear of potentially fatal bleeding from this highly vascular area; especially the internal carotid artery, as well as any arterial supply from the contralateral external carotid artery [2].
Surgical resection is still the definite treatment for JNA. However, pre-operative angioembolization is increasingly recommended to limit the risk of uncontrolled intraoperative bleeding. Other treatment lines, including radiation, cryotherapy, electrocoagulation, or hormonal therapy, have been proved to be less effective with increased incidence of recurrence and side effects [5].

Methods
In the period between January 2012 and December 2017, 20 male patients with age ranging from 6 to 20 years were referred to Endovascular Unit, at the Departments of Neurosurgery in Sohag, Alexandria, and Tanta University Hospitals with JNA. All patients were subjected to detailed history, and took complete clinical and neurological examination, audiometric evaluation, full laboratory investigations, and finally full radiological evaluation including CT and MRI scans.
CT is especially helpful for defining bony changes. Usually, CT is seen as a lobulated non-encapsulated soft tissue mass centered on the typically widened sphenopalatine foramen. Following contrast administration, there is usually marked contrast enhancement. Massive bony destruction is not usual, but an intracranial extension could occur.
MRI is excellent for the evaluation of intra-orbital and intracranial tumor extension. The tumor is usually so intense in T1, heterogeneous signal in T2 with flow voids and prominent enhancement with gadolinium. Flow voids are present in most sequences giving characteristic salt and pepper appearance.
Extensive bony destruction is not usual with JNA, but an intracranial extension could occur. Intracranial extension may be extradural or intradural. Extension may occur from the Pterygo-palatine fossa through the pterygoid canal and foramen rotundum to the middle cranial fossa, through the pterygo-maxillary fissure to the infra-temporal fossa or through the inferior orbital fissure to the orbit. Extension to the cavernous sinus is also reported. The superior orbital fissure is the most frequent route of intracranial spread in patients with extensive involvement of the infratemporal fossa.
Under general anesthesia, standard trans-femoral approach was applied in all cases using 5F and sometimes 6F femoral sheath. Using 5F multipurpose diagnostic catheter, angiography was done in all cases to check tumor feeders and to define dangerous anastomosis with intracranial circulation if present. Replacement with 5F, and sometimes 6F guiding catheter, was done in all cases. The available guiding catheters in Egypt include: Chapron (Microvention, TERUMO), and Guider Softip XF (Stryker, USA). Super elective navigation of the main feeding arteries was done using flow directed microtheters, such as Marathon (Stryker, USA) or non-flow directed microcatheters, such as Echelon ™ (Medtronic). The size of polyvinyl alcohol (PVA) particles (Contour particles (Boston Scientific, USA)), intended for injection, was 45-150, 150-250, and 250-355 depending on the size of the tumor vessels. Pulsed injection is implemented targeting the tumor bed until the disappearance of the tumor blush with repeated control DSA. In the end, Control DSA evaluated embolization success, after wards, started the referral to ENT department at the second morning for endoscopic excision of the tumor. Surgical excision is preferred in the first 48 h post embolization. Assessment of the amount of blood loss needed amount of blood transfusion; degree of resection and time of surgery was addressed. Post excision CT was done for assessment of the degree of resection. Clinical and Radiological follow-ups were made for at least 1 year in all cases.

Results
20 male patients with JNA underwent preoperative super-selective trans-arterial embolization. The average age at presentation was 13 ± 4.1 years (6-20 years). The presentations included epistaxis, obstructive symptoms and chronic otomastoiditis due to Eustachian tube obstruction. According to the Radkowski grading system for JNA (Table1).
[6]; 2 patients had grade IA, 6 patients had grade IB, 4 patients had grade IIA, 4 patients had grade IIB, and 2 patients had grade IIIA, and 2 patients had grade IIIB ( Table 2). Feeding arteries included most commonly internal maxillary artery through sphenopalatine and descending palatine arteries (branches of the internal maxillary artery), a superior pharyngeal artery from pharyngeal trunk (branch of ascending pharyngeal artery, ascending palatine artery (branch of the facial artery), and petrous branches from the internal carotid artery. In one case with grade IIIA; feeders were shown from both sides ( Table 3).
All patients underwent successful super-selective trans-arterial embolization with total obliteration of vascular blush of the tumor in 15 patients, and near-total obliteration of blush in 5 patients. These 5 patients had supplementary feeders from the internal carotid artery or external carotid artery with dangerous anastomosis to the internal carotid artery. The embolization of these small feeders is technically difficult and carries risk for dangerous complications. ENT surgeons reported no significant bleeding in these cases with near-total embolization. Necrosis was evaluated by absent enhancement or a decrease of contrast uptake in post embolization contrasted CT and MRI. No permanent morbidity or mortality, related to embolization techniques in our series, was shown.
Surgical reports from our ENT surgeons showed a dramatic effect of preoperative embolization on limiting the amount of intraoperative blood loss and decreasing the time of surgery. Two patients required combined endoscopic and transcranial approaches and another two patients required pure transcranial approach for complete excision of the lesions. The average intraoperative blood loss was 225 ± 82 ml (range 100-400 ml), no transfusion was needed in 14 patients (70%), and the average operative time was 2.53 ± 0.57 h (range 2-4 h). No permanent morbidity or mortality, related to surgical techniques in our series, was shown other than one patient revealed CSF leak that treated medically. The mean hospital stay was 5.2 ± 1.1 days (4-7 days) for both embolization and surgery.
The mean follow-up period was 2.1 ± 1.6 years (1-4 years). Only one patient had recurrence after 1.5 years and was treated by trans-arterial embolization followed by surgical resection. Another patient had a small residual after endoscopic removal and remained stable under follow-up.

Discussion
JNA are a group of highly vascular benign tumors seen exclusively in pediatric to adolescent males, and in most cases manifested with recurrent epistaxis. They are centered on the sphenopalatine foramen and extend into the neighboring structures causing bone erosive changes [7,8].
The current study included 20 male patients with JNA who underwent preoperative super-selective trans-arterial embolization. In addition, all of the cases studied by   Amran et al. [9], Lv et al. [10], Banjara et al. [11], Kasem et al. [12], Gemmete et al. [13], Punj et al. [14] and Rosenbaum-Halevi et al. [15] were males. The mean age at presentation was 13 ± 4.1 years. This was similar to the age average of Rosenbaum-Halevi et al. [15] and Kasem et al. [12] studies which showed a mean age of 14.1 years in both studies, and that of Banjara et al. [11] study which had a mean age of 14.5 years. This mean age was slightly lower than that of Gemmete et al. [13], which was 15 years, and that of Lv et al. [10] and Punj et al. [14] cases, which was around 16 years. 4 out of the 5 cases studied by Amran et al. [9] had an age range from 11 to 16 years, but the fifth case was much older; 61 years. According to the Radkowski grading system for NPA; 2 patients had grade IA, 6 patients had grade IB, 6 patients had grade IIA, 4 patients had grade IIB, 2 patients had grade IIIA. This distribution was somewhat different from that of Lv et al. [10] cases, where most of the cases had grade IIIA, IIIB or IIC. In the study of Rosenbaum-Halevi et al. [15], all cases were in grade II, IIA, IIB or IIC. All of the cases of Banjara et al. [11] were either stage II or III. In the study of Gemmete et al. [13],