Juvenile Nasopharyngeal Angiofibroma Treatment & Management

Hormonal therapy

The testosterone receptor blocker flutamide was reported to reduce stage I and II tumors to 44%. Despite tumor reduction with hormones, this approach is not routinely used. Schuon et al reported on the immunohistochemical analysis of growth mechanisms in juvenile nasopharyngeal angiofibroma. ^[6] They concluded that juvenile angiofibroma (JNA) growth and vascularization are driven by factors released from stromal fibroblasts. Therefore, inhibition of these factors might be beneficial for the therapy of inoperable juvenile nasopharyngeal angiofibroma (JNA).

Radiotherapy

Some centers have reported 80% cure rates with radiation therapy. However, concerns regarding potential effects of radiation make radiation therapy a nonuseful modality in most cases.

Stereotactic radiotherapy (ie, Gamma Knife) delivers a lower dose of radiation to surrounding tissues. However, most authorities reserve radiotherapy for intracranial disease or recurrent cases.

Conformal radiotherapy in extensive juvenile nasopharyngeal angiofibroma (JNA) or intracranial extension provides a good alternative to conventional radiotherapy regarding disease control and radiation morbidity, even with advanced disease. ^{[7, 8]}

Owing to the possibility of massive bleeding, biopsying suspected JNA is contraindicated.

Surgically, a lateral rhinotomy, transpalatal, transmaxillary, or sphenoethmoidal route is used for small tumors (Fisch stage I or II).

The infratemporal fossa approach is used when the tumor has a large lateral extension.

The midfacial degloving approach, with or without a Le Fort osteotomy, improves posterior access to the tumor. (A study by de Mello-Filho et al of 40 patients indicated that JNA can be successfully treated with resection by Le Fort I osteotomy, with the surgery being effective even when the tumor has invaded the central nervous system. ^[9] )

The facial translocation approach is combined with Weber-Ferguson incision and coronal extension for a frontotemporal craniotomy with midface osteotomies for access.

An extended anterior subcranial approach facilitates en bloc tumor removal, optic nerve decompression, and exposure of the cavernous sinus.

Some authors advocate the use of intranasal endoscopic surgery for lesions with limited extension to the infratemporal fossa. Image-guided, endoscopic, laser-assisted removal has also been used. Hackman et al (2009) reviewed 31 cases of JNA at the University of Pittsburgh Medical Center from 1995 to 2006. ^[10] Most tumors were completely excised using the expanded endonasal approach (EEA) alone or in combination with minor sublabial incisions, avoiding the morbidity associated with larger open approaches or postoperative radiation therapy.

Radical removal of a large JNA may be difficult because of its extreme vascularity and extension to the cavernous sinus, orbit, middle fossa, and anterior fossa. Nevertheless, most JNAs with intracranial extension can be resected in the first operation with minimal morbidity through a facial degloving and further combination of expanded endoscopic endonasal approaches. ^[11]

In a retrospective review, Battaglia et al (2014) evaluated the use of endoscopic endonasal surgery in the radical resection of benign or nonmetastatic malignant tumors that have either developed in or extended to the infratemporal fossa or upper parapharyngeal space. ^[12] According to the investigators, the results, derived from 37 patients, including 20 with JNA, suggested that purely endoscopic endonasal radical resection can be safely used to treat selected tumors involving these spaces.

In a review article, Cloutier et al (2012) reported on 72 patients operated on over a 10-year period. ^[13] They concluded that the progress in skull-base surgery allowed for expansion of the indications for endoscopic removal of JNA. This approach has a better outcome in terms of blood loss, hospital stay, and complications. Of course, an external approach should be considered only for selected cases due to massive intracranial extension or optic nerve or internal carotid artery entrapment by the tumor.

In a meta-analysis of the endoscopic surgical outcomes of JNA, covering 92 studies and a total of 821 patients, Khoueir et al (2014) calculated that the mean operative blood loss from endoscopic JNA surgery was 564.21 mL. Random effect estimates for recurrence, complications, and residual tumor were 10%, 9.3%, and 7.7%, respectively. The authors stated that endoscopic treatment is currently considered the treatment of choice for JNA but also commented that they could find no randomized, controlled studies for their analysis. They advised that future studies propose a new, endoscopic approach – based classification system. ^[14]

A study by Overdevest indicated that surgical blood loss in JNAs tends to be greater when the lesions are supplied by the internal carotid artery or have a bilateral arterial supply. ^[15]

Yi et al (2013) described a simplified classification system and management option for juvenile nasopharyngeal angiofibroma, as follows ^[16] :

• Type I includes tumor localized in the nasal cavity, paranasal sinus, nasopharynx, or pterygopalatine fossa. The transnasal cavity approach with endoscopic guidance is suitable for this type.

• Type II is if the lesion extends into the infratemporal fossa, cheek region, or orbital cavity, with anterior and/or minimal middle cranial fossa extension but intact dura mater. The transantral-infratemporal fossa-nasal cavity combined approach is reliable for type II.

• Type III is a calabashlike, massive tumor lobe in the middle cranial fossa. For type III tumors, the complete removal is challenging. A combined extracranial and intracranial approach is often needed. Radiotherapy is useful for treating the residual intracranial part.

Preoperative embolization has typically been performed via a transarterial route using a variety of embolic materials. It is accomplished using reabsorbable microparticulate substances (eg, Gelfoam, polyvinyl alcohol, dextran microspheres) or nonabsorbable microparticulates (eg, Ivalon, Terbal). Limiting blood loss during surgery is essential. Endoscopic assistance has been used for direct transnasal tumor puncture and intratumoral embolization using the liquid embolic agent Onyx. ^[17]

Preoperative angiography and embolization minimize intraoperative blood loss, and the current shift in the treatment to endoscopic excision in selected cases reduces perioperative morbidity. ^[18] Low-grade consumption coagulopathy may complicate small juvenile nasopharyngeal angiofibroma (JNA) and implies that preoperative coagulation screening may have a role in perioperative hemostasis.

Malignant transformation has been reported in 6 cases; 5 of these patients were treated with radiotherapy, according to a study by Makek et al. ^[19]

Transient blindness has been reported as a result of embolization, but it is a rare occurrence. Osteoradionecrosis and/or blindness due to optic nerve damage may occur with radiotherapy.

Fistula of the palate at the junction of the soft and hard palate may occur with the transpalatal approach but is prevented by preservation of the greater palatine vessels during flap elevation.

Anesthesia of the cheek is a frequent occurrence with the Weber-Ferguson incision.

A rare case of massive epistaxis from spontaneous rupture of the intracavernous tract of the internal carotid artery 20 days after resection of a giant JNA by midface degloving was recently reported. ^[20] Coils were selectively used to occlude the vessel and to stop the hemorrhage.

The presence of tumor in the pterygoid fossa and basisphenoid, erosion of the clivus, intracranial extension, feeders from the internal carotid artery, a young age, and a residual tumour are risk factors associated with the recurrence of juvenile nasopharyngeal angiofibroma (JNA).

A retrospective study by Song et al indicated that in patients treated for juvenile nasopharyngeal angiofibroma (JNA), time to recurrence tends to be longer when levels of hypoxia-inducible factor 1-alpha in the endothelial cells are low. ^[21]

A literature review by Reyes et al indicated that in patients without intracranial compromise, the rate of recurrence after endoscopic surgery for juvenile nasopharyngeal angiofibroma (JNA) is significantly less than that following the open surgical approach (13% vs 28%, respectively). In patients with intracranial compromise, the recurrence rates did not statistically differ. ^[22]