Keywords skull base - osteoradionecrosis - free flap
Introduction
The use of radiotherapy (RT) is common in the multimodal management of head and neck
cancers.[1 ] While having oncologic efficacy, head and neck RT can carry long-term complications
including osteoradionecrosis (ORN),[2 ] a potentially devastating complication that causes pain, diminished quality of life,
as well as possible cerebrospinal fluid (CSF) leak, or carotid artery hemorrhage.[2 ]
[3 ]
[4 ]
ORN of the skull base is rare with a reported incidence of 1.04% ORN development in
the anterior skull base for nasopharyngeal cancer patients treated with RT.[5 ] The time of onset of ORN after RT varies with studies reporting latency times between
17 and 116 months.[5 ]
[6 ]
[7 ] The management of ORN requires aggressive multidisciplinary surgical and medical
treatment, including debridement, intravenous antibiotics, and hyperbaric oxygen (HBO)
therapy.[8 ]
[9 ]
Following debridement of necrotic tissue various reconstructive options can be utilized.
While microvascular free flaps are effective in the primary reconstruction of oncologic
defects, their use in the treatment of anterior skull base ORN is still less commonly
implored.[7 ]
[10 ]
[11 ]
[12 ]
[13 ]
[14 ]
[15 ]
Here we describe the use of an anterolateral thigh (ALT) free flap to successfully
treat delayed onset ORN following basaloid squamous cell carcinoma of the sinonasal
cavity. With eight reported cases in the English medical literature of extensive anterior
skull base reconstruction by a microvascular free flap for ORN, we present an important
experience herein.[16 ]
Case Report
A 59-year-old woman with a remote history of treated breast cancer underwent an initial
endoscopic resection of basaloid squamous cell carcinoma of the sinonasal cavity 12
years prior to presentation. One year after the initial oncologic resection, she underwent
an anterior craniofacial resection with left maxillectomy and skull base reconstruction
followed by adjuvant chemoradiotherapy for residual basaloid squamous cell carcinoma
with intracranial extension through the anterior skull base. Reconstruction by the
neurosurgical serve was performed with a pericranial galeal flap for the anterior
skull base repair. She had a radiologic gross total resection with microscopic residual
disease at the histologic margins prompting adjuvant chemoradiotherapy to target volume
doses of 66 to 70Gy with concurrent cisplatin chemotherapy. She tolerated two out
of four intended chemotherapeutic cycles and the full intended radiation treatment
course. In the interim period, she had no signs of recurrence on close clinical and
radiographic surveillance. At 9 years post-treatment, she developed a complicated
sinusitis with a left frontal lobe abscess that required a combined open craniotomy
with drainage and endoscopic debridement of the sinonasal cavity and anterior skull
base. She was treated with intravenous antibiotics at that time.
Most recently at 11 years post-treatment she presented with headache and left visual
disturbances with retroorbital pain, magnetic resonance imaging) was completed showing
progressive edema with T2 enhancement involving the left frontal lobe with extension
through the cribriform plate into the paranasal sinuses (
[Fig. 1 ]). Despite aggressive surgical and medical therapy, her symptoms persisted with objective
evidence of chronic sinusitis, frontal cerebritis, and skull base ORN.
Fig. 1 Axial brain magnetic resonance imaging demonstrating edema with T2 enhancement in
the left frontal lobe, and enhancement extension to the paranasal sinuses and through
the cribriform plate.
She then underwent a combined open bifrontal craniotomy with debridement of frontal
lobe abscess and cerebritis, along with endoscopic resection of the anterior skull
base ORN with an ALT free flap reconstruction and titanium mesh cranioplasty, as shown
in [Fig. 2 ]. An ALT flap appeared to be the best and least morbid option given the patient's
status. Phlegmonous changes involving the epidural and dural tissues extending through
the frontal sinus, anterior skull base, and left maxillary sinus were debrided until
normal dura, sinonasal mucosa, and anterior skull base bone were encountered, as shown
in [Fig. 3 ]. Remaining portions of supraorbital ethmoid air cells, the posterior table of the
frontal sinus, and intersinus septum were removed with ablation of mucosal remnants
to create a marsupialized and cranialized frontal sinus. The 5 × 5 cm dural defect
was reconstructed with DuraGen inlay (Integra Life Sciences, Plainsboro, New Jersey,
United States), and the 5 × 4cm bony anterior skull base defect was repaired by a
fasciocutaneous ALT extradural free flap reconstruction ([Figs. 4 ] and [5 ]). A parachute inset was performed between the tensor fascia of the free flap and
the dural margin at the posterior cribriform with tacking sutures placed around the
margins of the craniotomy to create broad cranial and dural coverage for the vascularized
anterior skull base repair. The free flap pedicle was then anastomosed to the recipient
left superficial temporal artery and vein ([Fig. 5 ]).
Fig. 2 A bicoronal approach was used to gain access to the frontal sinus and areas of cerebritis
involving the frontal lobe. Shown here is the hardware from the previous craniotomy
sites after the bicoronal approach was performed.
Fig. 3 After the 8 × 6.5 cm frontal and temporal craniotomy, a view of the frontal lobe
and cranialization of the frontal sinus is visible with the left frontal area of DuraGen
dural repair.
Fig. 4 The anterolateral thigh musculofascial free flap with the lateral circumflex vessels
in situ.
Fig. 5 The anterolateral thigh free flap extradural onlay reconstruction (star), flap pedicle
(arrow) by superior external view.
The cranioplasty was performed for the coverage of the bifrontal craniectomy defect
utilizing a Synthes preformed MatrixNeuro 8 to 10 CM frontal titanium mesh implant
(Johnson and Johnson, West Chester, Pennsylvania, United States). The free flap pedicle
exited the left side where it was anastomosed to the left superficial temporal artery
and vein, as shown in [Fig. 6 ]. The bicoronal incision was then closed with a combination of deep dermal sutures
and staples for skin closure. After the bicoronal incision was closed, the anterior
skull base reconstruction was examined endoscopically ([Fig. 7 ]), revealing a low-flow CSF leak along the cribriform plate that was plugged with
Gelfoam (Pfizer, New York, NY, United States) and Adherus dural sealant (Stryker,
Chicago, Illinois, United States).
Fig. 6 After placement of the free flap, a titanium mesh cranioplasty was placed over the
cranial defect with the free flap pedicle exiting the left side where it was anastomosed
to the left superficial temporal artery.
Fig. 7 An endoscopic view of the anterolateral thigh free flap reconstruction along the
anterior skull base extending from the anterior table of the frontal sinuses, posteriorly
to the cribriform fossa, and laterally to the lamina papyracea bilaterally.
Postoperatively, the patient was monitored in the intensive care unit with a lumbar
drain in place and she had an uncomplicated postoperative course. The lumbar drain
remained in place for 6 days postoperatively, following a 48-hour clamping trial without
signs of CSF leak. Final pathology revealed fibrous tissue with extensive inflammation
and necrosis, numerous fungal elements, and osteonecrosis. She received inpatient
antimicrobials and had an uncomplicated hospital course without concern for CSF leak
or viability of the free flap, as assessed by doppler flow monitoring. She was discharged
to home on a long-term course of voriconazole and nafcillin, for positive intraoperative
cultures of Aspergillus fumigatus and Staphylococcus hominis . At 3 months follow-up, she had healed appropriately with no evidence of recurrence
or complications ([Fig. 8 ]). She remains on long-term antifungal therapy with involvement by infectious disease
colleagues for chronic fungal frontal cerebritis.
Fig. 8 Three-month postoperation. Well-healing external excision and endoscopic view of
well-healing anterolateral thigh free flap repair of skull base defect.
Discussion
Skull base ORN is associated with significant morbidity, and treatment can be challenging,
with patients often failing conservative measures. Here, we expound upon limited previous
reports of free tissue transfer as an effective option for delayed ORN in the setting
of concurrent active infection.
In our patient, ORN was complicated by a chronic fungal infection, for which she received
antifungals and antibiotics. For patients presenting with ORN in its early stages,
a trial of medical management can be prudent. When therapies such as antimicrobials
or HBO fail, early and aggressive surgical management is essential to mitigate the
development of more serious neurological and intracranial complications. In our case,
the latency from radiation to ORN was approximately 9 years, which is delayed compared
with the average 2 to 4 years length reported in the literature for most head and
neck cancers.[17 ] Our patient's initial complications 9 years post-treatment had been identified and
managed as sinusitis; however, they were most likely the early stages of developing
ORN. At the time of the initial anterior craniofacial resection, there was notably
a near-total cranialization of the frontal sinus. However, residual cells in the supraorbital
areas may have served as a potential nidus for this delayed infectious presentation.
For this reason, a thorough debridement and revision cranialization were undertaken
at the time of the debridement and microvascular reconstruction for source control.
Imaging findings as shown in [Fig. 1 ], including enhancement in the frontal lobes and paranasal sinuses, can aid in the
recognition of ORN, although clinical worsening and symptoms prompted further evaluation.
Early identification and treatment with free flap can avoid prolonged “stop-gap” solutions
and address the source pathology by facilitating more complete surgical debridement
with this advanced reconstructive option.
Initial surgical treatment strategies for skull base ORN include serial debridement
with healing by secondary intention where feasible.[10 ] Our decision to pursue aggressive debridement and free flap reconstruction was based
on the disease extent and the anticipated large-area skull base defect necessary to
gain adequate surgical debridement of the extracranial and intracranial extent of
necrosis.
The traditional mainstay of surgical therapy for ORN consists of complete debridement,
optimally with resection to viable unaffected tissues.[18 ] Following debridement of necrotic tissue, vascularized reconstructions can aid in
healing and preventing additional complications. In reconstructive surgery, the principle
of a reconstructive ladder regards microvascular free tissue transfer as the near-final
step after other options have been exhausted.[19 ] In our case, the extent of ORN of the skull base dictated a need for free tissue
reconstruction.
For head and neck oncologic reconstructions, free tissue transfer has been associated
with improved functional and aesthetic outcomes across various pathologic process
and anatomic subsites.[20 ] Moreover, microvascular free flaps can be particularly suited to ORN given the underlying
pathology of compromised blood supply to the region.[21 ] In cases of ORN for the mandible, free flap reconstruction is considered part of
the gold standard after adequate surgical debridment.[17 ] A gold standard for the management of skull base ORN has not similarly been established,
although other groups have also reported successful outcomes for skull base ORN definitively
treated with microvascular free flaps.[7 ]
[21 ] Notably, in these reports ample time was provided for the failure of conservative
treatment options. However, in a systematic review of central skull base ORN, the
success rate following primary medical therapy was approximately 41%, whereas for
patients who were treated with primary surgical therapy, treatment success rates were
approximately 88%.[22 ] In light of a successful outcome with our patient, we advocate considering vascularized
free tissue transfer early in the treatment paradigm for skull base ORN with careful
patient selection. The multidisciplinary approach of endoscopic and open skull base
surgery alongside free tissue transfer techniques can be taken to manage complex skull
base and intracranial cases of ORN as shown herein. At 3 months follow-up, our patient
has shown baseline neurologic and functional outcomes while remaining on prolonged
medical therapy with antifungal therapy for cerebritis not amenable to further resection.
In conclusion, we affirm this unique treatment modality as a viable option in the
reconstruction of skull base defects following ORN, even in cases with numerous complicating
factors. As advancements in the primary treatment of head and neck cancers continue
resulting in improved patient survival, so too should the management of late-treatment
complications. In areas where access can be limited such as the skull base, a multiteam
approach such as endoscopic-assisted skull base resection with free tissue transfer
reconstruction may offer definitive solutions for ORN in select patients.
